07> Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/practicaltreatis01robe / I PRACTICAL TIIEATJSE URINARY AND RENAL DISEASES, INCLUDING URINARY DEPOSITS. ILLUSTRATED BY NUMEROUS CASES AND ENGRAVINGS. BY WILLIAM ROBERTS, M.D., F.R.S., FELLOW OF THE ROYAL COLLEGE OF PHYSICIANS, LONDON ; PROFESSOR OF MEDICINE AT THE VICTORIA UNIVERSITY ; CONSULTING PHYSICIAN TO THE MANCHESTER ROYAL INFIRMARY. ASSISTED BY ROBERT MAGUIRE, M.D. Lond., MEMBER OP THE ROYAL COLLEGE OF PHYSICIANS, LONDON ; PHYSICIAN TO OUT-PATIENTS, ST. MARY's HOSPITAL, LONDON : LATE PATHOLOGIST TO THE MANCHESTER ROYAL INFIRMARY. FOURTH EDITION. PHILADELPHIA: LEA BROTHERS & CO. 1885. DORNAN, PRIKTEE. PREFACE. The design of the present work is to give an account of the organic diseases of the kidney, and of those diseases and disorders of which the chief characteristic is some alteration of the urine. The work naturally falls into three parts. The first part, which may be regarded as introductory to the other two, is devoted to the physical and chemical properties of the urine, and to the various alterations which it undergoes under different cir- cumstances of health and disease, in so far, and only in so far, as they seem to have a practical bearing. The methods of examining the urine for clinical purposes are explained; and the significance of the diverse changes experienced by it pointed out. The naked-eye and micro- scopical appearances of urinary deposits are described and figured, together with those of the extraneous matters which accidentally find their way into the urine. Of the vast array of researches on the composition of the urine, and the rate of excretion of its several ingredients, accumulated in recent times, it has been found impracticable to give even an abstract without greatly exceeding the limits of practical utility. It has seemed to the author more convenient to consign these purely chemical and physiological materials to separate treatises, in the manner adopted by Neubauer and Vogel and Dr. Parkes, at least provisionally, that is, until such time as they can be shown to possess some clinical value. Further, these subjects are treated so amply in the works (in addition to those of the authors just mentioned) of Beale, Thudichum, Hassall, IV PEEFACE. and others, that the omission of them has caused the author little regret. It is hoped, however, that nothing has been omitted a knowledge of which possesses any interest for the actual practice of medicine. The second part treats of a group of affections which may be desig- nated briefly as "urinary diseases," viz., diabetes insipidus, diabetes mellitus, gravel and calculus, and chylous urine. In his description of .these diseases (with the exception of gravel and calculus), the author has endeavored to present an analysis of all the facts hitherto published in relation to them, together with those which have fallen under his own notice. In the chapter on gravel and calculus, prominence has .been given to the medical treatment, and especially to the author's own researches in this direction. The organic diseases of the kidney form the subject of the third and largest part of the work. The most important of these, Bright's dis- ,ease and its allies, are treated with a fulness commensurate with their gravity and frequency, and mainly from a clinical point of view. The less frequent affections of the kidney — hydronephrosis, cystic degeneration, cancer, tubercle, parasites, malpositions and malforma- tions are treated analytically, and at considerable length. The extreme poverty of the older English systematic works on these subjects seemed to demand this compensation. The third edition of this work has been exhausted for some years, but I have been hitherto unable, for want of leisure, to undertake the pre- paration of a fourth edition. Having, however, obtained the valuable assistance of Dr. Robert Maguire, this object has been accomplished. Dr. Maguire has carefully revised the entire work ; and has brought up the several articles to the level of our existing knowledge. PREFACE V I have almost entirely rewritten tlic articles on albuminuria and on microorganisms in the urine. Much new matter has been introduced into the chapters relating to Bright's disease. The observations of Bancroft, Manson, and Dr. Stephen Mackenzie on the filaria sanguinis hominis in relation to the causation of chyluria will be found incor- porated in the chapter on entozoa in the kidneys. The practical aim of the work has been steadily kept in view ; and no alterations or additions have been introduced which are not desirmed to enhance the clinical value of the book. Nevertheless an endeavor has been made to give full references to pathological researches, with a view of facilitating the labors of special workers. W. E. Manchester, 89 Mosley Street, January, 1885. CONTENTS. PART I. The Physical and Chemical Properties of the Urine in Health and Disease — Urinary Deposits. CHAPTER I. INTRODUCTORY, I. Summary of the properties and composition of the urine ; its physio- logical and pathological variations . . . .33 Physiological alterations . . . . . .34 Pathological alterations . . . . . .35 II. Methods of examining the urine — Apparatus requned . . .35 Scheme for the examination of the urine . . . .36 Apparatus . . . . . . . .37 III. Extraneous matter in urine . . . . . .37 lY. Changes in the urine on keeping . . . . . .39 Acid urinary fermentation . . . . . .40 Ammoniacal decomposition . . . . . .40 CHAPTER II PHYSICAL PROPERTIES OF I. Odor ......... 42 II. Color 42 Normal pigments of healthy urine . . . . .43 Pathological pigments . . . . . .44 Derived pigments . . . . . . .46 Adventitious pigments . . . . . .47 III. Density or specific gravity . . . . . .49 Range in health . . . . . . .49 Clinical significance of variations in the density of the urine . 49 Estimation of the solids of the urine from the density . . 50 IV. Quantity of the urine . . . . . . .50 Variations in health . . . . . .51 Solid urine . . • . . . . .52 Clinical significance of variations in the quantity' of the urine . 53 THE URINE. Vlll 11 CONTENTS. PAGE V. Suppression of urine (anuria) . ' . . . . .54 Non-obstructive suppression 54 Obstructive suppression 57 Causes 57 Symptoms 59 Illustrative cases 60 Duration of life . 74 Treatment 75 VI. Reaction of the urine Effects of food and fasting . EflFects of medicine . Effects of the cold bath Effects of disease 76 77 . 80 81 . 81 Ammoniacal urine — Decomposition of urea . 82 CHAPTER III. CHEMICAL CONSTITUENTS OF THE URINE AND THEIR VARIATIONS — INORGANIC DEPOSITS. I. Preliminary remarks on urinary deposits and their classification II. Uric acid ... Naked-eye characters Micro-chemical characters Quantitative determination Origin and occurrence Clinical significance III. Amorphous urates Naked-eye characters Micro-chemical characters Clinical significance Treatment . IV. Crystalline urates Urate of soda Urate of ammonia V. Oxalate of lime . Naked-eye characters Micro-chemical characters Production and occurrence Clinical significance Oxaluria Treatment . VI. Cystine . VII. Xanthine VIII. Leucine and tyrosine IX. Phosphoric acid and the phosphate: Excretion of phosphoric acid in health and disease 87 87 87 90 91 92 94 94 94 '96 97 97 97 98 99 99 100 101 102 103 105 106 111 114 115 116 C O N T K N 'I' a . IX Deposits of earthy phosphates ..... Amorphous phosphate of lime, or bonc-oarlh Crystallized phosphate of lime, or stellar phosphates Phosphate of ammonia and magnesia, or triple phosphate X. Carbonate of lime XL Sulphuric acid and the sulphates XII. Chlorine and the chlorides Supplementary remarks on the excretion of phc chlorine .... XIII. Urea ..... Excretion of urea in health Methods of estimating urea in urine Pathological relations of urea Azoturia .... osphorus, sulphur, and 117 118 110 121 123 123 124 124 125 120 126 130 131 CHAPTER IV. ABNORMAL SUBSTANCES IN THE URINE: ORGANIC DEPOSITS. I. Extra-renal epithelium ...... II. Eenal epithelium and casts of tubes; the deposits associated with al 134 buminuria 137 Epithelial casts 138 Opaque granular casts 138 Transparent or waxy casts . 138 Patty casts . 139 Blood casts . 139 Pus casts 139 Clinical significance of renal epithelium and tube -casts 141 Tube-casts without appreciable albuminuria 142 III. Patty matter in urine . ■ . 143 Cholesterine 144 Kiesteine 146 IV. Pus in urine 146 Micro-chemical characters . 146 Clinical significance 147 V. Blood in urine — Hsematuria 148 Microscopic characters 149 Causes of haamaturia 150 Hismaturia from local lesions 150 Endemic hasmaturia 153 Symptomatic ha3maturia . 154 Supplementary hematuria . 155 Treatment of hsematuria 155 VI. Hemoglobinuria — Paroxysmal htemog] obinuria 157 Symptoms . 158 Characters of the urine 159 Illustrative cases 162 Etiology 166 Pathology . 167 Treatment . 169 CONTENTS. VII. Cancerous and tuberculous matter in urine VIII. Spermatozoa in urine — Spermatorrhoea Treatment .... IX. Microorganisms in the urine Torulaceous vegetations (saccharomyces) Sarcina .... Bacteria — Bacteruria Bacteruria associated with incipient putrefractive urine Bacteruria with ammoniacal fermentation of the Bacteruria without decomposition of the urine X. Albumen in the urine Albuminoid substances Tests for albumen . Quantitative determination New process of the author Clinical significance Saturnine albuminuria Punctional albuminuria Neurotic albuminuria Pathology of albuminuria XI. Sugar in urine Tests for sugar (qualitative (quantitative) Clinical significance chansre in the PAGE 170 171 173 175 175 176 177 178 178 179 185 185 186 190 191 194 195 196 197 199 204 205 213 221 PART II. Urinary Diseases — Diseases of which the Chief Charac- teristic IS AN Alteration of the Urine. CHAPTEK I. DIABETES INSIPIDUS. Synonyms — Classification Etiology Course and symptoms Duration . Morbid anatomy . Illustrative cases . Nature Diagnosis and prognosis Treatment . Appendix. — Cases character: in the urine zed by diuresis, with slight traces of sugar 228 224 226 229 230 280 236 239 289 241 CONTENTS. XI CIIArTElt II. I'AOB . 248 . 244 . 248 . 253 . 254 , . 260 ) diabetes . 264 . 270 , . 272 . 286 DIAUKTKH MKLLITUK. Classification of cases of saccharine urine Etiology of diabetes mellitus . • . Symptoms ...... Course, duration, termination Complications ..... Morbid anatomy ..... Physiological and theoretical considerations relating to Diagnosis and prognosis .... Treatment ..... Appendix. — Milder types of diabetes CHAPTEE III. GRAVEL AND CALCULUS. General etiology .... Classification of urinary calculi; their chemical characters, origin, groAvth, and general clinical history Of the particular varieties of urinary calculi 1. Uric acid calculi . 2. Urate concretions 3. Oxalate of lime . 4. Cystine .... 5. Xanthine 6. Patty or saponaceous — TJrostealith 7. Carbonate of lime 8. Basic phosphate of lime . 9. Mixed or secondarj^ phosphates . 10. Fibrine and blood-concretions . 11. Indigo .... 12. Prostatic calculi . On the diagnosis of the species of urinary calculi within the bla kidneys ..... Medical treatment of gravel and calculi . A. — Preventive treatment . B. — Solvent treatment Preliminary remarks Solvent treatment of uric acid calculi Experimental inquiries: Comparison of potash and soda Effects of strength of solution Effects of quantity of solution Absolute rate of dissolution . Best method of alkalizing the urine Experiments with alkalized urine Illustrative cases Discrimination of the cases to which the solvent treatment is suitable ...•.•■■ dder or 292 294 297 297 298 299 300 301 301 308 306 306 307 309 309 309 311 811 315 315 817 317 317 318 319 319 320 320 327 XI 1 CONTENTS. Rules for carrying out the solvent treatment Objections answered . . Experiments on the solvent treatment of uric acid by injections bladder ....... Experiments on the solvent treatment of cystine calculi Experiments on the solvent treatment of oxalate of lime calculi Solvent treatment of phosphatic calculi into the Characters of the urine . Course and symptoms Illustrative cases . Duration and termination Etiology . Pathology . Treatment CHAPTER IV. CHYLOUS URINE. PAGE 329 330 332 333 333 334 385 337 338 344 344 344 355 PART III. Organic Diseases of the Kidneys. CHAPTER I. CONGESTION OF THE KIDNEYS. Preliminary observations — Experimental researches .... Active congestion ........ Passive congestion ........ Appendix. — On the connection of renal congestion, albuminuria, and Bright's disease, with pregnancy and eclampsia .... CHAPTER II. bright's disease. Preliminary remarks . . ■. . . . . General etiology of Bright's disease ...... CHAPTER III. acute bright's disease. Anatomical characters Course and symptoms Diagnosis . Prognosis . Etiology . Treatment . 357 360 365 371 376 379 383 386 391 392 392 393 CONTENTS, CHAPTEK IV. CHKONIO hkight'h bisjcase Anatomical changes in the kidneys 1. Smooth white kidney Synopsis of symptoms and conditions of origin 2. Granular contracting kidney Synopsis of symptoms and conditions of origin Oneness or multiformity of Bright's disease 3. Lardaceous or waxy kidney Synopsis of symptoms and conditions of origin General course and symptoms Illustrative cases .... Particulars of symptoms, and complications Urine Blood Dropsy Skin . Pulse . Ketina Complications, and connection with other diseases Bright's disease and phthisis Bright's disease and cardio-muscular changes Uraemia ...... General features .... Uremic amblyopia .... Convulsions and coma Distinction of uremic coma from narcotic poisoning and apoplexy Urseraic vomiting and diarrhoea Ura3mic dyspnoea Theories of ureemia Diagnosis . Prognosis . Treatment . I'AOK 396 .396 898 399 402 403 404 406 407 409 414 414 417 417 418 418 418 419 420 424 428 429 429 430 433 433 433 434 437 439 441 CHAPTER V. SUPPURATION IN THE KIDNEY : RENAL EMBOLISM. Phlegmonoid abscess Multiple or metastatic abscesses Eenal embolisni . 449. 451 453 Morhid anatomy JEtiology CHAPTER VI. PYELITIS AND PYONEPHROSIS. 455, 456 XIV CONTENTS. PAGE Symptoms . . 459 Illustrative cases . . 461 Diagnosis . . 467 Prognosis . . 469 Treatment . 470 Precipitation of uric acid and ur Symptoms of renal calculi Diagnosis . Treatment . . . , Extirpation of the kidney CHAPTER VII. CONCRETIONS IN THE KIDNEYS. (.es in the kidneys of infants CHAPTER YIII. HYDRONEPHROSIS. Morbid anatomy Etiology . Symptoms . Terminations Diagnosis . Prognosis , Treatment CHAPTEPv IX. CYSTS AND CYSTIC DEGENERATION OF THE KIDNEY. Scattered cysts in kidneys otherwise healthy Disseminated cysts in the atrophic form of B right's kidney Congenital cystic degeneration of the kidneys . General cystic degeneration of the kidneys in adults 474 475 476 477 478 479 484 492 494 494 496 496 501 502 502 504 CHAPTER X. CANCER or THE KIDNEY. A. — Primary cancer of the kidney Morbid anatomy Etiology Symptoms and physical signs Duration Illustrative cases Diagnosis Prognosis Treatment B. — Secondary cancer of the kidney Appendix. — Sarcoma of the kidney 514 514 518 519 522 523 538 535 536 536 539 CONTENTS. XV CIIAPTEli XI. BENIGN GROWTHS IN THIS KIDNEY. Osseous growths ...... Pibrous and flbro-fatty growths .... . .041 . G41 Lymphatic growths .... Syphilitic deposits ..... Mixed growths ..... . .542 . .542 . .543 CHAPTEK XII. TUBERCLE Or THE KIDNEY Comparative frequency of tubercle in the kidneys A. — Primary tubercle of the kidney Morbid anatomy Etiology Symptoms . Illustrative cases Duration Diagnosis Prognosis Treatment . B. — Secondary tubercle of the kidneys CHAPTER XIII. ENTOZOA IN THE KIDNEYS. .544 .544 .544 .546 .540 548 554 554 555 555 556 I. Hydatids in the kidney . Natural history Morbid anatomy Symptoms . Illustrative cases . 558 . 5.58 . 561 . 566 . 568 Duration . 571 Termination . 571 Etiology . 572 Diagnosis Prognosis Treatment . II. Bilharzia hsematobia . 572 . .S73 . 574 . 575 Natural history Morbid anatomy Symptoms . Treatment . . 575 . 576 . -577 . 580 III. Filaria sanguinis hominis . 581 IV. Strongyliis gigas V. Pentastoma denticulatum . 584 . 583 VI. Erratic worms . . 585 VII. Spurious worms . . 586 XVI CONTENTS. CHAPTEK XIV. ANOMALIES OF POSITION, FORM, AND NUMBER OF THE KIBNEYS. PACE I. Anomalies of position ....... 587 A. Fixed malpositions of the kidneys .... 587 B. Movable kidneys ...... 591 Physical signs and symptoms .... 591 Illustrative cases . . . . . . 593 Etiology , . . . . . .599 Diagnosis ... . . . . 602 Treatment . . . . . . .602 II. Anomalies of form ....... 604 Horseshoe kidney . . . . . . . 604 III. Anomalies of number ....... 605 Solitary kidney ....... 605 Bibliography Index or Subjects Index of Authors 607 619 623 PART I. THE PHYSICAL AND CHEMICAL PROPERTIES OF THE URINE m HEALTH AND DISEASE-URINARY DEPOSITS. CHAPTEE I. INTRODUCTORY. I.— SUMMARY OF THE PEOPERTIES AND COMPOSITION OF THE UEINE; ITS PHYSIOLOGICAL AND PATHOLOGICAL VARIATIONS. Healthy urine is a clear, watery, amber-colored, saline solu- tion, generally acid, with a specific gravity of about 1020. It con- tains a large quantity of urea; and smaller quantities of uric acid, hippuric acid, creatine, and creatinine. In addition to these, which are its characteristic constituents, the urine contains certain saline substances, namely, chlorides, phosphates, and sulphates, of which the bases are soda, potash, lime, and magnesia ; also minute quantities of oxalic and lactic acids, aynmonia, pigment, diastase^ and other substances which are classed under the head of extrac- tive matters. All these substances preexist in the blood, and are simply separated therefrom by the secerning action of the kidneys. The average proportions of the chief constituents of the urine ^ It has been stated that traces of pepsin have been found in the urine. (Briicke, Sitzimgsb. d. Wien. Akad., Bd. 43.) I have tested several specimens of urine with regard to this point, but have invariably obtained negative results. With regard to diastase the case is different. Healthy urines have a considerable power of changing starch mucilage into dextrine and sugar. This power is de- stroj'ed by heating the urine to boiling. I found the diastatic power of healthy urine to vary from 0.03 to 0.13, compared with healthy saliva as 10 to 17. That is to say, speaking roughly, urine has a diastatic value one hundred times less than that of saliva. {See the author's paper on " The Estimation of the Amylo- lytic and Proteolytic Activity of Pancreatic Extracts." Proc. Roy. Soc, 18'81.) Griitzner states that urine also contains rennet ferment and peptones, together with pepsin and trypsin, the last in the form of a zymogen. (Bresl. artz. Zeit- schrift. No. 17.) 3 34 INTEODUCTORY. may be judged of by the following table, whicli has been con- structed from a large number of the best analyses : Water ■ 954.81 Solid matters 45.19 Urea Uric acid Extractives ^ i Chlorine Sulphuric acid Phosphoric acid Potash . Soda Lime Magnesia Creatine, creatinine Ammonia, hippuric acid Xanthine, hypoxanthine Sarcine, pigment, unoxidized sulphur and phosphorus, mucus, etc. 21.57 0.36 6.53 4.57 1.81 2.09 1.40 7.19 0.11 0.12 The composition and physical properties of the urine may undergo alterations from physiological and from pathological causes. Physiological Alterations. — The physical properties of the urine, and the relative proportion of its ingredients, vary greatly under the different conditions of healthy existence. Exercise, rest, the quantity and quality of the food and drink, digestion, fasting, sleep, the quantity of the cutaneous transpiration, atmos- pheric states, etc., react on the urine; and are, so to speak, reflected in its composition. Some of the urinary constituents are derived, wholly or in part, directly from the food. This is especially the case with the saline or mineral matters, and the water. When the diet is especially rich, or especially poor, in any of these, their relative proportions in the urine rise or fall correspondingly. Again, certain constituents (especially water) have other ways of passing out of the body than the kidneys, namely, by the skin, the lungs, the intestines; and if these show any unusual activity, the composition of the urine is necessarily affected. The greatest constancy of proportion is exhibited by the organic (nitrogenized) constituents — urea and uric acid, etc. — which are derived from the disintegration of the tissues ; but even these oscillate not a little with the quantity and quality of the food, and with exercise or rest of the body. The reaction, which influences so importantly the physical properties of the urine, and its capacity for holding in solution certain ingredients which otherwise tend to be precipitated, is greatly affected by the digestion of food, and may be changed thereby from acid to alkaline during several hours in the day. METHODS OF EXAMINING THE UKINE. dO Pathological Alterations may be distinguished mio general and special. It is desirable to indicate these separately; though practically they frequently merge into each other. General pathological alterations are those which depend on some general bodily disorder, such as fever, rapid waste of the tissues, anEemia, etc. Alterations of this class, although of great interest for the elucidation of general pathological doctrines, have very little symptomatic value; and it has not been shown that a particular knowledge of them in an individual case of disease, is capable of furnishing any information on diagnosis, prognosis, or treatment, which may not be obtained more easily and accurately by other means, namely, by physical examina- tion of the organs, temperature measurements, weighing the patient, etc. Special 'pathological changes are : {a) those in which some new and unnatural ingredient is mixed with the urine — such as albu- men, sugar, fat, cystine, blood, pus, fibrine, epithelial cells, spermatozoa, etc. : (h) those in which some constituent is present in such unnatural proportion that the circumstance forms a lead- ing feature of some particular disease — as the excessive quantity of\vater in diabetes, the excessive diminution of urea in Bright's disease, etc.; (c) those in which some constituent is in an un- natural physical condition — thereb}^ producing or indicating a particular morbid state — as in the occurrence of uric acid, oxalate of lime, and earthy phosphates as urinary deposits or calculous concretions. In the present work, physiological and general pathological changes of the urine are only considered in so far as they pos- sess some practical interest. The special pathological changes, on the other hand, are considered at length. 11.— METHODS OF EXAMINING THE URIISrE— APPAEATUS REQUIEED. An examination or analysis of the urine for clinical purposes is much more restricted in its objects than one which is designed for original investigations. The object of the former is to ascertain those points, a knowl- edge of which, in a particular case, is found from previous experience to throw a light on the nature, course, diagnosis, • prognosis, or treatment of the disease. The object of the latter is to obtain new and additional indications in the same directions ; it embraces every conceivable information, and is consequently indefinitely elaborate. The subjoined scheme is of the former kind, and is sufficiently simple to be within reach of every practitioner. It requires- only 36 INTRODUCTORY. an elementary knowledge of chemistry, and answers nearly all the requirements of actual practice. The points requiring to be noted in an examination of the urine are — 1. The general appearance and color; clearness or turbidity; presence or absence of deposit, and of extraneous impurities. 2. Odor. 3. Reaction. 4. Specific gravity. 5. Presence or absence of albumen : if present, an approxi- mate estimate of its quantity. 6. Presence or absence of sugar : if present, an estimate of its quantity. Fig. 1. Apparatus for urine-testing. A. Urine-glass — depth, 53^2 inches ; diameter, l)^ inch. , B. Urinometer. C. Burette. D. 200 grain measure. E. Stand of urine-tests. 7. An estimate of the total quantity of urine in twenty-four hours. If there be a deposit, it is necessary to note — 8. Its aggregation and color : whether it be amorphous or crystalline, light or heavy; the manner of its subsidence or precipitation. 9. Its solubility or insolubility by heat; solubility in nitric acid, in acetic acid, in liquor potassse; insolubility in both acids and alkalies. 10. By the microscope : absence or presence of crystals, their EXTRANEOUS MATTERS IX URINE. .'iT appearance and form; of epithelial cells — renal or extrarenal; of blood disks; pus globules; spermatozoa: librinous cylinders; bacteria, etc. The apparatus required consists of — 1. Three or four urine-glasses. Fig. 1, A. 2. Litmus paper. 3. Urinometer. B. 4. Ilalf-a-dozen test-tubes. 5. Spirit-lamp. 6. I^itric acid. 7. Acetic acid. 8. Liquor potassse. 9. Liq. ammon. fort. 10. Drop-tubes and stirring rods. For sugar testing — 11. Prepared copper solution. 12. Graduated burette. C. 13. Two-hundred-grain measure. D. 14. Six-ounce graduated measure. 15. Small flask. These may be conveniently arranged together for use on a circular stand of two tiers, as represented at E,^ A microscope is, of course, essentially necessary. It should be provided with a first-class :^-inch object-glass, and an eye- piece to magnify not less than 240 diameters. III.— EXTEANEOUS MATTERS IN UEINE. It is important that the student should be familiar with the appearance of certain extraneous matters which are apt to find their way into the urine after emission, and to be mistaken for urinary deposits. Cotton fibres {see Fig. 2, a) have a flat limp appearance, are often folded on themselves, usually with a dark-looking medullary part ; sometimes they present the appearance of narrow glassy cylinders. They vary in breadth from 3 q\^ q to YTunr ^^ ^^^ inch. Flax fibres (b) are jointed at intervals, and have a round, solid appearance. Their broken ends are usually torn into a brush of fibrillse. When sharply bent they break with a " green-stick", fracture, WooUe7i hairs (c) present the appearance of hard cylin- ders, with fine transverse markings and slight serrations along their margins. From their elongated form and somewhat simi- 1 This stand was constructed for me by Mr. Payne, of the firm of Mottorshead & Co., Market Place, Manchester, from whom similar ones may he obtained, com- pletely furnished, for the price of £2 2s. With the stand is supplied a printed card, containing directions for urine testins;. 38 INTEODUCTORY. lar diameters these three objects are liable to be mistaken tor casts of the uriniferous tubes. The latter, however, are distinguished by their softer aspect and less defined outline, and they are never fibrillated at their extremities. A few air-bubbles [d) are generally retained beneath the cover- ing-glass of the microscopic slide, and are apt to puzzle students. Fig. 2. Extraneous matters found in urine : a. Cotton libres ; b. I'lax fibres ; c. Hairs ; d. Air-bubbles ; e. Oil globules ; /. Wheat starch ; g. Potato starch ; h. Kice-starch granules ; Hi. Vegetable tissue ; Ic. Muscular fibres : I. Feathers. If small, they are spherical; if large, irregularly flattened. They are identified by their strong refraction, deeply colored thick borders and clear centres. Oil globules [e) are sometimes pres- ent in urine as a morbid product, in which case they are always very minute. More often they occur as accidental impurities ; CHANGES IN THE URINE ON KEEPING. 89 they may be derived from the use of uii oiled catheter; from milk, butter, l)roths, and other articles of food ; from oily sul^- stances previously contained in the insufficiently cleansed bottle in which the urine has been conveyed for examination. Oil globules have a less strongly marked outline than air-bubbles; they appear Hatter, and have generally a distinctly yellowish tint. Confervoid vegetations or torultc and various forms of bacte- ria are frequently encountered in the examination of the urine. The former are invariably derived from an extraneous source. The latter (bacteria) are sometimes of extraneous origin and sometimes are generated within the urinary passages. These will be more fully noticed hereafter. [See Microorganisms in the Urine.) From the sputa may be introduced portions of bread, meat, fresh vegetables, as well as the epithelial debris of the oral cavity and air-passages. Starch granules find their way into the urine from certain articles of food, or the use of tooth and cosmetic powders. Wheat and potato starch granules are recognized by their concentric lines and hilus {fg). Rice granules are very minute cubical bodies (A). If the granules are ruptured by the operations of cookery (as in bread, puddings, gruel, etc.), they can no longer be identified by their forms, but a drop of iodine- water insinuated beneath the covering-glass instantly strikes a deep blue color with them. Fecal matters may mingle with the urine by inadvertence, or they may find their way into the blad- der through a fistulous communication with the intestines. Their presence is recognized by the food remnants which they contain. At ii) and [k) are represented vegetable tissues and muscular fibres which were detected in the urine of a patient whom I saw with Mr. Jameson, of Hey wood. The urine was not sensibly fecal to the smell ; but the discovery of these structures in it proved decisively the existence of a narrow communication between the bowels and the urinary tract, and threw a strong light on an otherwise very obscure case. Particles of soot and sand, and other matters which may be designated as dirt, are of frequent occurrence. They are dark shapeless masses of various sizes, and all dissimilar. Any object of undefined shape, of which there are none similar to itself in the field, may almost with certainty be set down as dirt. IV.— CHANGES IIS THE UEIjSTE ON KEEPING. The changes which take place in urine after emission are a frequent source of misapprehension. These changes differ in degree and direction according to the reaction and concentra- tion of the urine. 40 INTRODUCTORY. A healthy acid urine generally undergoes the following series of changes. There occurs first a precipitation of the amorphous urates, then of uric acid and often of oxalate of lime. After a while confervoid vegetations or torulse make their appearance. In the course of four or five days or longer the acidity begins to decline, and the urine passes into a state of ammoniacal putrefaction. It then becomes opaque from the development of myriads of bacteria; the odor and reaction of ammonia, together with an offensive efiluvium of putrefaction, become perceptible. The amorphous urate deposit will now be found changed into dark round masses of urate of ammonia ; uric acid crystals give place to bright prisms of triple phosphate and an abundant sediment of amorphous phosphate of lime sinks to the bottom of the vessel. The confervoid vegetations cease to grow with the change of reaction, and finally perish as the secretion becomes fairly putrid. Urines of low density or of feeble acidity do not deposit urates on standing, and pass rapidly — in a day or two or even in a few hours — into a state of ammoniacal decomposition. Under the name of the add urinary fermentation Scherer^ de- scribed a series of changes in healthy urine chiefly characterized by a progressive increase of its acidity, due to the production of lactic acid and partly of acetic acid. He attributed these changes to a fermentation in which the mucus of the bladder acted as a ferment on the urinary pigment, transforming it into lactic acid. Later researches by Rohmann^ have thrown great doubt on the correctness of Scherer's account of the occurrence of a normal acid urinary fermentation. Rohmann found that in fourteen out of sixteen specimens of healthy urine no increase of the acidity took place. In the remaining two specimens a slight increase of acidity was observed; this he attributed to the presence of traces of sugar or of alcohol in the urine, both of them substances which readily yield acid (lactic or acetic) under the action of organized ferments. The changes which take place in an opposite direction — that is, towards alkalescence — are much more prOne to mislead than those just described. The transformation of urea into carbonate of ammonia {see Reaction) is a frequent source of confusion in the examination of the urine. This transformation is brought about with great rapidity by bacterial fermentation. The physical and chemical characters of the urine are then so altered, that it is unfit for clinical examination, and should invariably be rejected, except in cases where the transformation takes place 1 Annalen d. Chemie u. Pharm., Bd. 42, p. 171. * Maly's Jahresbericht f. Thiex-chemie, 1881, p. 454. CHANGES IN THE URINE ON KEEPING. 41 within the urinary passages and a more natural specimen is therefore not procurable. In consequence of these changes it is desirable to examine the urine within a few hours of the time of emission. Certain organic deposits are liable to be greatly altered, or altogether destroyed, by an exposure of twelve or twenty-four hours, even when the more obvious characters of the secretion have not undergone a perceptible change. Blood corpuscles, renal epi- thelium, andSrenal casts, are very rapidly disintegrated, especi- ally if the urine be of low specific gravity. On the other hand, pus, pavement epithelium, and spermatozoa resist mucli longer without efFacement of their microscopical characters; and they may generally be recognized without difficulty in urine far ad- vanced in putrefaction. CHAPTER II. PHYSICAL PROPERTIES OF THE URINE. I.— ODOE. The natural odor of healthy urine is faint and peculiar; it may be described as urinous; it is due to the presence of certain volatile organic acids. The addition of a mineral acid greatly intensities, and to a certain extent modifies, the urinous odor. The sense of smell is a rough test of the presence of ammonia, and of the freshness of the secretion, or the advent of putre- faction. When urine is alkaline from fixed alkali, it has a sweetish aromatic odor like that of the fresh urine of the horse or ox. In this way the smell of the urine comes to be a ready index of its reaction. Certain drugs (turpentine, copaiba, cubebs), and certain articles of food (asparagus, garlic), communicate peculiar odors to the urine which lead to their immediate detection. Diabetic urine when fresh has a faint whey-like fragrance, and sometimes an odor resembling chloroform {see Diabetic Coma). When fer- menting, diabetic urine smells like sour milk. Urine containing blood or sanious discharges from the genital passages emits a stale, offensive smell, like the washings of slightly tainted flesh. II.— COLOK. The color of the urine in health is a yellowish-brown. It varies in intensity from the palest straw to a full amber. The study of urinary pigments is one of great inherent difficulty; and it has been rendered truly intricate by the multiplication of new terms by successive investigators, and the confounding of pigments produced by decomposition with those really preexist- ing in the urine. The coloring matters encountered in the urine may be divided into four categories, viz. : 1. I^^ormal pigments of healthy urine. 2. Pathological pigments due to disease. 3. Derived pigments due to decomposition of the normal pig- ments, or of certain color-yielding extractives of the urine, espe- cially in disease. 4. Adventitious pigments due to admixtures of bile, blood, COLOR. 43 hsematin, pus, etc., with the urine, or to the adrniiiiKtriitiori of certain drugs — logwood, rhul)ar}), senna, santonin, etc. 1. Normal Pigments of Healthy Ukine. — Dr. Schunck's in- vestigations^ have led him to the conclusion that the ordinary color of normal urine is due to the presence of two substances having the properties of extractive matters. He has succeeded in separating these from one another, and from the other con- stituents of the urine. They have then the appearance of dark yellow syrups, being quite amorphous and deliquescent, with a peculiar, rather pleasant (not urinous) odor and a strong acid reaction, which proceeds from the presence of organic acids resulting from their spontaneous decomposition. Tlie dilute watery solutions of these extractives have exactly the same color as urine itself. The iirst of these extractives — which Dr. Schunck has named Urian — is soluble in alcohol and ether as well as water. Its com- position is expressed by the formula CggHg^NOgg, and does not vary. In a long series of experiments made with urine obtained at diiferent times and from different places. Dr. Schunck always found its composition the same. It is decomposed at a boiling temperature, yielding a large quantity of a brown resin and volatile organic acids. Its watery solution becomes several degrees darker on the addition of sulphuric or hydrochloric acid, and a brown resinous substance is gradually deposited. The second extractive he has named TJrianine. Its formula is C38H27NO28. This extractive is soluble in alcohol, but not in ether ; it seems to have a great tendency to absorb four addi- tional equivalents of oxygen (C38II27NO32 = oxurianine), but without suffering anj^ change in its physical properties. Uri- anine is probably a glucoside, for by the action of acids it yields a brown pow^der, insoluble in water (uromelanine), and the filtered liquid reduces the cupro-potassic test like grape sugar. Urian and urianine are both decomposed when heated for some time in the water-bath, giving products which are in- soluble in water. Watery solutions of both become several shades darker when mixed with dilute sulphuric or muriatic acid. Jaffe has distinguished another pigment in the urine to which he has given the name of Urobilin.'^ Maly has shown that it can be formed from Bilirubin by reducing agents, and that it is identical with Hydrobilirubin. It is a red amorphous substance and soluble in alcohol, ether, and chloroform, partially soluble in water, having a characteristic spectrum, and giving in solu- tion a green fluorescence. 1 Proceedings Eoy. Soc, 1867. 2 Vircli. Arch., Bd. 47. See also a paper by McMunn in Proc. Eoy. Soc, 1880, in which is given a process for the isolation of bilirubin. 44 PHYSICAL PROPERTIES OF THE URINE. Variations in the depth of the normal color of the urine cor- respond generally with its degree of dilution (or wateriness), and concentration. Very pale urines are voided by patients suiFering from diabetes, from aneemia and chlorosis, and during convalescence from acute diseases — also by healthy persons after profuse drinking. Hysterical and nervous individuals, after paroxysmal attacks, void a very pale urine. As a rule, pale urines indicate the absence of pyrexia. High-colored urines, on the other hand, accompany the febrile state, and any other morbid condition associated with rapid wasting of the tissues. Healthy persons void a similar urine after violent and prolonged muscular exercise and severe sweating. The varying degrees of coloration of the urine have not as yet been made to yield much information of a practical value. Possibly this has been due to the want of an exact method of estimating and describing these variations. A first step towards this desirable object has been taken by J. Vogel, who has pub- lished a standard scale of colored plates, with which the color of any particular urine can be compared. Vogel divides the tints exhibited by urines into three groups, each consisting of three members. {See Plate I.) The first group consists oi yellow urines, embracing : (1) pale yellow ; (2) bright yellow ; (3) yellow. The second group consists of reddish urines, and in- cludes : (4) reddish-yellow; (5) yellowish-red; (6) red urines. The third group consists of brown or dark urines. These are subdivided into : (7) browmish-red ; (8) reddish-brown ; and (9) brownish-black. In comparing the color of a urine with the tints of the scale, the two following precautions must be observed, in order to obtain uniform results. If the urine be not absolutely clear, it must be filtered. Secondly, the urine must be examined by transmitted light, in a glass which is four or five inches in di- ameter. Lastly, it must be remembered that the scale is not adapted for the estimation of the adventitious pigments some- times found in urine, such as blood or bile ; nor does it exactly reproduce some of the pathological tints observed in disease.^ 2. Pathological Pigments. — The most familiar of these is a reddish-pink pigment (purpurine of Bird, and uro-erythrine of Heller), which makes its appearance in various febrile and other complaints. Purpurine has an intense affinity for uric acid and 1 The use of Vogel's scale for the purpose of estimating the quantity of pig- ment in the urine is, I believe, impracticable; and the statement made by him that all the nine varieties of color form one continuous series, and that they " may be considered as merely different degrees of dilution of one and the same pigment matter," is certainly, according to my experiments, inexact. The real usefulness of the scale consists in the aid it gives to accurate description. COLOR. 45 the urates, und when the latter are thrown down aH a deposit it communicates to them a beautiful j)iiik color. Purpurine abounds in the urine of persons suffering from severe organic diseases, and especially organic diseases of the liver; it is like- wise present in all febrile and inilammatory urines. It is said to be abundant in poisoning by lead and other metals. A black pigment, melanin, is excreted in the urine of patients suffering from melanotic tumors, especially when the disease attacks the liver or the skin. The fact was pointed out as early as 1820 by Norris, and afterwards, in 1826, by Faw- dington, a Manchester surgeon. Occasionally the urine is pale when passed, but becomes darker and deposits a black or brown precipitate on exposure for some time to the air, or immediately on the addition of a strong acid. Thus in the fresh urine there is present a colorless substance, melanogen, which on oxidation yields the dark pigment. Zeller^ has lately reported a very in- teresting case of melanotic tumors of various organs, in which the quantity of melanin in the urine varied, in inverse propor- tion to that of urobilin. He argues, therefore, that the two coloring matters must belong to the same group of bodies. In certain other conditions the urine shows the peculiarity of being pale when passed, but becoming dark in color on expo- sure to the air. (See p. 48.) Pyrocatechin, which is always present in the urine of the horse, has been found by Ebstein and Miiller and other observers in human urine in rare cases. The urine may then show the above reaction, but the dark color appears immediately if caustic alkali is added. Bodecker de- scribed, under the name of alkapton, a bodj^ in the urine, which other researches seem to show to be identical with Pyrocatechin. The so-called alkapton urine reduces Fehling's solution, almost like diabetic urine, but differs from it in not fermenting with yeast. In a case described by Dr. Armstrong [Dublin Journal of Med. Sci, 1882), Dr. Smith found that the urine, while pre- senting the above characters, contained not pyrocatechin but protocatechuic acid, [A specimen of urine sent to me lately by Dr. Gray, of Armagh, also contained protocatechuic acid. The patient -was a young lady, under the care of Dr. Gray and Dr. Whitla, of Belfast, and had suffered from symptoms of ulcer of the stomach, with apparently perforation and consequent attacks of localized peritonitis. At intervals she passed urine which, while of ordi- nary color at the time of leaving the bladder, became of a deep brown, almost black color, after standing for a short time. The urine as I received it, that is, after being corked up for some time, was of a pale brown color and of an alkaline reaction, and. 1 Arch. f. klin. Chirurg., Bd. XXIX. p. 245. 46 PHYSICAL PROPERTIES OF THE URINE. contained a deposit of triple and stellar phosphates. There was a somewhat more than normal amount of indican present. If the urine were exposed to the air for a short time, or if a little liq. potassse were added, a deep dark brown color was produced. When, however, the urine was acidified, it might be exposed for some days without any alteration in color occurring, and the dark urine became considerably lighter on the addition of acetic acid. The urine showed only a slight reducing action on Fehling's solution, but immediately reduced an ammoniacal solution of nitrate of silver. A weak solution of ferric chloride, when added to the urine, caused the appearance of a bluish- green coloration, which, on the addition of a little liquor am- monise, changed to reddish-violet. These reactions showed the presence of either pyrocatechin or protocatechuic acid. The peculiar coloring agent was, however, not distilled over on heating, nor removed by shaking with ether, and hence, ac- cording to Dr. Smith, it must consist of protocatechuic acid and not pyrocatechin. The patient passed the dark urine only at intervals, but it was found that between these periods the urine was acid, and occasionally, at least, if alkalized, it showed again the change in color. It is evident from the above reactions that this dark coloring matter was a product of oxidation, but that it could only be formed in an alkaline solution. — R. M.] 3. Derived Pigments. — Schunck has shown that the normal pigments of the urine are extremely susceptible of decomposi- tion. All strong alkaline or acid reagents, and even simple boiling, are sufficient to change them ; and there is little doubt that a considerable number of the substances described by pre- vious writers as pigments preexisting in the urine, were, either partly or wholly, products of such decompositions. Among these may be enumerated the various brown and blackish resins of authors, the melanic acid of Prout, the urcemaiin of Harley, and probably the urochrome of Thudichum. The discovery of indican (or a substance closely resembling it) as a normal constituent of the urine by Schunck, afterwards confirmed by Carter, has thrown a strong light on the nature of some of the pigments found in the urine. This substance, which appears to be identical with the uroxanthine of Heller, imparts a yellow color to the urine, and yields, by decomposition, two colors well known in the arts, viz., indigo-blue and indigo-red (uro- glaucine and urrhodin of Heller). Indigo-blue is frequently seen in putrescent urines, forming glistening blue shreds and films on the sides of the glass and the surface of the urine. Occasionally it is observed clinically. It was so noticed by Prout, who clearly indicated its nature and composition. It is also probably identical with the cyanourine of Braconnot. In the highly ammoniacal urine of cystitis I have seen on two oc- COLOR. 47 casions the precipitated urate of ammonia tinted of a beautiful violet by indigo-l)lue. The quantity of indican in urine varies from a mere trace to a considerable proportion. For its detec- tion an equal part of hydrochloric acid is mixed Avith the urine, and afterwards a concenti^ated solution of chloride of lime is added drop by drop, and the mixture well shaken. The in- dican is then decomposed, forming indigo-blue, which imparts a greenish or blue color to the mixture (Jaffe). According to Senator, if a little chloroform or ether be now shaken up with the solution, this will take up the indigo, and on standing will form a separate layer. The depth of color in this layer will then give an approximate estimate of the amount of indican present. Normal urine treated in the above manner is usually colored reddish-violet.. The quantity of indican in the urine is increased in various affections, the more important of which are obstructions in the intestines, peritonitis, and cancer of tVie stomach. The subject has been studied, experimentally and clinically, by Jaffe, who has found that obstruction in the small intestine and diffuse peritonitis are accompanied by great in- crease in the amount of indican, while obstructions in the large intestine and circumscribed peritonitis cause only a slight in- crease. Senator has observed increase of indican in the urine in many chronic affections, accompanied by changes of nutri- tion. He has also found a similar increase in cases of granular kidney, but not in other forms of Bright's Disease.-^ 4. Adventitious Pigments. — In jaundice the coloring matter of the bile is freely excreted by the kidneys, and communicates to the urine a color varying from a saffron-yellow to a dark olive-green. Bile-pigment m urine may be discovered by placing a few drops of the secretion on a white porcelain plate, with a few drops of nitric acid in juxtaposition. The two fluids are brought into contact by inclining the plate : if bile be present, a beautiful play of colors — violet, green, and red — is observed, which passes rapidly away. Bile-pigment appears in the urine before the skin is perceptibly discolored; it also continues after the skin has attained its natural tint; so that its recognition is sometimes a useful warning of impending jaundice or a verification of a preexisting jaundice. When a urine con- taining bile is kept for some days, it sometimes changes to a grass-green color from oxidation of the biliary pigment.- Dr. Harley considers that the presence of the biliary acids in the urine is characteristic of jaundice from retention of bile, as distinguished from jaundice arising from suppression of bile. ^ Salkowsky has described a great increase of carbolic acid in the urine in cases of obstruction in the small intestine. Normal urine contains only a trace. ^ Marechal has recommended tincture of iodine as a test for bile-pigment in the urine. It gives a green color, passing to rose and yellow. 48 PHYSICAL PROPERTIES OF THE URINE. For the detection of the biliary acids he recommends that a couple of drachms of the urine be poured into a test-tube with a small fragment of loaf sugar. Then about half a drachm of strong sulphuric acid should be slowly added, in such a manner that the two fluids shall not mix. If biliary acids be present, there will be observed at the line of contact of the acid and urine — after standing a few minutes — a deep 'purple hue} In a case of long-standing retention of bile from compression of the common duct by a cancerous growth of the head of the pancreas, which I saw with Dr. Henry Simpson, only a brandy-red colora- tion of the urine was produced by the application of this test. Blood and pus mixed with the urine communicate to it their appropriate colors. {See Hsematuria, Hsemoglobinuria, and Pus in Urine.) Certain medicinal and poisonous substances administered in- ternally produce peculiar alterations of color in the urine. Creasote, and the external application of tar ointment, have been known to produce a very dark, almost hlack urine. In some cases of this kind which occurred in Guy's Hospital, Dr. Odling identified the dark coloring matter with indigo-blue, and he pointed out the close chemical relations between indigo and creiisote.^ The application of carbolic acid solutions to the surface of wounds also causes the urine to become very dark, and occasionally, although the urine is light when passed, it becomes darker on exposure to the air. Baumann and Preusse* have shown that this is due to the presence in the urine of hy- drochinon, a further oxidation product of carbolic acid. It is excreted as a sulphate which is colorless, and very easily de- composed. The free hydrochinon then absorbs oxygen from the air, and forms a dark pigment which gives the peculiar color to the urine. Marcet, Prout, and Dulk have also de- scribed cases in which a black coloring matter existed in the urine. In patients taking gallic acid a dusky hue is communi- cated to the urine. Yogel records an instance of black dis- coloration of the urine after poisoning by arseniuretted hy- drogen. (See Hsemoglobinuria.) Rhubarb given internally colors the urine a deep gamboge- yellow, which is changed to red by the addition of ammonia. Senna communicates a brownish, and logwood a reddish tinge to the urine when administered as infusions. Santonin imparts a conspicuous orange-red color to the urine if it be alkaline, and a rich golden-yellow if it be acid. ^ Harley on Jaundice, p. 61. 2 Bird's Urinary Deposits, 5th ed., n. 336. 3 Zeitschrift f. Phys. Chemie, III. p. 156. SPECIFIC GRAVITY. 49 III.— DENSITY OR SPECIFIC GRAVITY. The specific gravity of the urine is estimated ]>y rneaii.s of the iirinoraeter. The instrument indicates whether the urine is concentrated or dilute : and as the range of health is very great, the density does not yield direct indications of disease; nevertheless the information thus furnished is in some cases of great importance, and indicates at once the path of further research. The usual range of density in healthy urine extends from 1015 to 1025 ; but it frequently mounts above or sinks below these limits. After abundant potation on an empty stomach the urine is profuse in quantity, clear, and dilute as water. Under such circumstances the density may fall as low as 1000.6, and numbers varying from 1002 to 1008 are common. Copious drinking on a full stomach has comparatively little immediate efl'ect on the flow of urine. Prolonged fasting ren- ders the urine concentrated. How high it is possible for the density to mount in healthy individuals it is diflicult to say; but I have known it as high as 1036. With this very considerable range in health, caution must be exercised in drawing inferences from any unusual depression or elevation of the density in dis- ease. If, however, the urine exhibit habitually, and especially in the morning before breakfast when the urine is naturally concentrated, a density below 1015, the presence of albumen in it may be suspected; if the density persist at a still lower point — 1005 to 1008 — the existence of insipid diabetes is to be appre- hended. After hysterical paroxysms in women, after similar attacks in men, and sometimes in the apoplectic state, the urine is discharged in large quantity and of exceedingly low density. In cases of suppression of urine from mechanical obstruction, the urine — if any escape past the obstacle — is of remarkably low density. This peculiarity will be treated of more fully in a future chapter. {See Suppression of Urine.) On the other hand, a density above 1025, especially in a pale, apparently dilute urine, is strongly suspicious of the presence of sugar ; and the higher densities, from 1035 to 1050, belong almost entirely to saccharine diabetes. Yet, not exclusively so; the heaviest urine ever submitted to my examination, which had a density of 1065, did not contain a particle of sugar, but a very large quantity of albumen. A high density in a urine free from sugar indicates concentra- tion, and more particularly a large percentage of urea. In the febrile state there is an absolute increase of urea, uric acid, and the sulphates in the urine, with a diminished elimination of water, consequently the specific gravit}- ranges high. The urine 4 50 PHYSICAL PROPERTIES OF THE URINE. has also a high density when there is rapid wasting of the tissues, especially if there he concurrent sweating or diarrhoea, in simple abstinence after profuse perspiration from any cause, and after excessive ingestion of nitrogenized food without a corresponding use of aqueous fluids. From the density of the urine, a rough estimate may be formed of the percentage of solid constituents contained in it; and if the quantity voided in twenty-four hours be known, the daily excretion of what may be called "solid urine" can be approxi- mately ascertained. Tables have been constructed on an experi- mental basis, exhibiting the quantity of solid matters per 1000 parts in urines of different spe-cific gravities ; and formulae have been proposed by means of which the same result can be obtained by a simple calculation. Probably the most accurate, as well as the simplest formula, is that proposed by Trapp. According to this, if the last two figures of the specific gravity are doubled, the quotient represents the amount of solid matters per 1000. A thousand grains of urine, sp. gr. 1020, would therefore contain 40 grains of solids. This method yields but rough approximations. If the urine were a solution of a single substance, or of a number of different substances in a fixed proportion to each other, the rising and falling density would indicate accurately the varying strength of the solution ; but the urine is a fluid of complex composition, and its numerous constituents vary every hour in their mutual proportions, so that the results obtained in this wa}^ cannot be regarded as exact estimates. Vogel took the trouble to inquire what are the precise limits of error in this method; and he assigns them as follows : In healthy urines there is a liability to error of -^o^^ even i ; but in morbid urines, and especially those of high density, the range of error may reach i or even ^. With very multiplied observations this method certainly yields results of practical value ; and it is the only one which can be used by practitioners generally. When more accurate results are required, resort must be had to the tedious but more exact method of evaporation to dryness, and weighing the residue. From a large number of observations by different physiolo- gists. Dr. Parkes estimates the mean discharge of solid urine in healthy men, between twenty and forty years of age, living on good diet, at 945 grains per day. IV.— QUANTITY OF THE UKINE. Closely connected with the specific gravity, and holding an inverse relation to it, is the quantity of the urine. The mean daily discharge ranges, in health, between 40 and 50 fluid- ounces. There are, however, considerable differences between QUANTITY. 51 individuals. The average for some persons is only 35 ounces a day; for others as much as 07 ounces. Oscillations in the same individual on different days are also very considerable. The urine may mount to 70 or 80 ounces, or sink to 25 ounces within the limits of health. The flow of urine is essentially regulated by the quantity of fluid drunk: controlled, however, in a most important degree by the pulmonary and cutaneous exhalation, and by the call of the system for water at the time. When the blood and tissues contain their full complement of water, any further potation results in immediate diuresis, whereby the superabundance is carried oflf. But when the organs and tissues of the body are craving for more water, a large quantity may be drunk without causing diuresis. The kidneys eliminate water in strict accord- ance with these conditions — it being an essential and important part of their function to regulate the aqueousness of the blood. ^ There is very great irregularity in the flow of urine from hour to hour as the conditions of its separation vary. After prolonged fasting the urine may sink to 2 J drachms per hour; during sleep, likewise, the urine flows slowly — at the rate of about half an ounce per hour; but after meals it rises to two or three ounces; and after drinking abundantly on an empty stomach I have seen 26-| ounces secreted in an hour; so that the stream of urine may run 85 times stronger at one time than another. It would seem, indeed, as if the kidneys (in health) supplied conditions of an almost mechanical nature, by which they were enabled to separate water at an almost unlimited rate — equal, at least, to the capacity of the gastric vessels to absorb water. When the mode of life is equable, and the meals are taken at regular intervals, the quantity of urine secreted at different periods of the day and night follows certain tolerably regular oscillations, as is shown in the following table, which is a fair sample of a very large number of observations : Breakfast at 8 ; dinne • a t2. SLeepfrom 11 P.M. to 7 A.M. Time of duy. 7-8 A.M. 8-9 oz. dr. 1 9-10 (iz. dr. 2 10-11 11-12 12-2 P.M. Hourlj' rate. oz dr. 6 oz. dr. oz. dr. 14 17 oz. dr. 1 3 Time of day. 2-3 F.Ji. 3-i 4-5 5-6 6-7 7-9 9-11 11-7 A.M. Hourly rate. oz. dr. 1 2 oz. dr. 10 oz. dr. 2 3 oz. dr. 2 8 oz. dr. 2 9 oz. dr. !oz. dr. 14 10 OZ. dr. 4 ^ The experiments on which these and the remarks which follow are based, are fully detailed in two papers by the author — one in the memoirs of the Manch. Lit. and Phil. Soc, 1858-9; and the other in the Edinb. Med. Journ., March and April, 1860. 52 PHYSICAL PROPEKTIES OF THE URINE. A much closer insight into the varying activity of the kidney is obtained by comparing the quantity of solid urine excreted at difierent periods of the day. The solid matters are much more constant in their quantity than the volume of the urine, which is liable to be greatly aifected by potation, perspiration, etc. The annexed table contains the average results of observations made during seven days, all consecutive except one. The solid urine was calculated from the specific gravity in the manner ex- plained in the preceding section : Time of clay. Solid urine discharged per hour, in grains. Diet, etc. 8- 9 A.M. 9-10 " 10-11 " 11-12 " 12- 2 P.M. 29 27 39.22 44.34 45.24 41,48 Breakfast at eight; coffee or tea, with meat and bread and butter. 2- 3 P.M. 3- 4 " 4- 5 " 5- 6 " 6- 7 " 7- 9 " 9-11 " 11- 1 A.M. 38.69 38.79 41.21 41.09 49.01 47.44 37.66 28.53 Dinner at two ; meat, potatoes, bread, cheese, water. (No solid food of any sort taken after dinner.) 1- 7 A.M. 15.53 Hours of sleep. 7- 8 A.M. 17.75 Prolonged fasting in the waking state. The table shows in an interesting manner the increase of the renal excretion after meals, and its diminution during fasting and sleep. The increase began within the first hour after breakfast, and continued during the succeeding two or three hours ; then a diminution set in, and continued until an hour or two after dinner. The effect of dinner did not appear until two or three hours after the meal; and it reached its maximum about the fourth hour. From this period the excretion steadily decreased until bed-time. During sleep it sank still lower, and reached its minimum — being not more than one-third of the quantity excreted during the hours of digestion. All the urinary ingredients appeared to partake in the in- crease after meals. The urea was found more than doubled ; the uric acid more than trebled; the earthy and alkaline phos- phates nearly doubled. The table shows that the vegetative functions share to some extent with the animal in the repose of sleep. The mean hourly discharge of solid urine during the waking hours, on the seven days of the table, was 33.14 grains; while the average of the QUANTITY. 53 hours of sleep was 15.5'j grains, or less tliari one-half. This ditference is not, of course, to be wholly attributed to tJie effect of sleep, inasmuch as, under the arrangement of meals, during this scries of observations, the period of sleep was also a time of fasting. A more exact estimate of the effect of sleep alone is obtained by comparing the urine secreted during the hours of sleep with that secreted during hours of combined waking and fasting. If we take the last two hours before sleeping (from 11 to 1), and the first hour after waking (from 7 to 8), we shall find that the mean discharge of solid urine in these three hours was 23.59 grains per hour, which is one-third more than the average ot the sleeping hours. In drawing practical conclusions concerning any deviation from the usual volume and quantity of the urine, the following points should be borne in mind. When the urine is unusually scanty, it should be ascertained, before pronouncing it a morbid phenomenon, whether the patient has abstained from liquids above his habit, whether water has been eliminated in excess by some other channel, as the skin or bowels. The urine is always scanty in cirrhosis of the liver; in some forms of Bright's disease through their entire course; and in the last stage of all forms; in any condition of the heart which directly or indirectly causes passive conges- tion of the renal veins whereby the circulation through the kidneys is impeded. In the early stage of acute Bright's Dis- ease, the urine is very scanty, sometimes approaching or reach- ing total suppression. The same occurs in the collapse period of cholera. Partial or total suppression also occurs in the later stages of all organic diseases of the kidneys ; and when any mechanical obstacle obstructs the flow of urine. A diminution of the urinary secretion which at all approaches suppression is of most serious consequence, and is soon followed b}- a formid- able train of symptoms, which bring life to a termination unless speedily relieved. [See Ilrsemia.) The flow of urine is abundant when the surface of the body is cool; also as a direct and invariable consequence of potation, unless some of the conditions already mentioned intervene. In disease, the urine is discharged in excessive quantity in two special maladies — diabetes insipidus and diabetes mellitus, which w^ill be described in future sections ; also in the middle stages of atrophic degeneration of the kidneys. Temporary excess of urine occurs after hysterical paroxysms, and certain other convulsive attacks in males and females. An increased tension in the arterial system, as in some cases of hypertrophy of the left ventricle, is associated with increased secretion of urine. It is a curious circumstance, that in several organic diseases of the kidneys in which the renal substance is gradually- 54 PHYSICAL PROPERTIES OF THE URINE. destroyed (atrophic Bright's Disease, cystic degeneration, double hydronephrosis), the volume of the urine is sometimes increased though the solid matters are diminished. This appears to be an attempt on the part of IsTature of a compensating character, to maintain, by excessive transudation of water, the depurating function of the kidneys under failing anatomical conditions. When at length the destruction has gone so far that this kind of compensation can no longer suffice, symptoms of fatal sup- pression of urine rapidly supervene. v.— SUPPEESSION OF UEINE (ANUKIA). Suspension of the secretion of urine arises under two distinct classes of circumstances. (1) It may arise from organic disease of the secreting tissue or from some disturbance in the innerva- tion or vascular supply of the kidneys. These cases are not dependent on any impediment to the outflow of the urine by its excretory channels, and I would propose to classify them under the designation of non- obstructive suppression. (2) The secretion of urine may be suspended by the establishment of a mechanical obstruction in the ureter or in the pelvis of the kidney. In these cases the organs themselves are not primarily at fault, but their function is arrested by the blocking up of their excretory channels. These may be designated as cases of obstructive sup- pression. The two classes of cases contrast with each other, not only in their determining cause, but also, most markedly, in their symptoms and course. ISTon-obstructive suppression rarely, if ever, proves fatal as a direct consequence of the suspension of the secretion of urine, but through the general effect of the shock and collapse which have produced that suspension. The cases usually run a very rapid course, ending in death or in recovery in a few hours or a day or two. Suppression from obstruction produces its effects more slowly; if it result fatally, the termination is delayed for eight or ten days or more. In both classes of cases the suppression is frequently not absolute ; some small quantity of urine is generally voided, and the char- acter of this urine is distinctive. In non-obstructive cases the urine is either high-colored and concentrated, or it contains albumen and casts, which plainly indicate disease of the renal tissue. In obstructive cases, on the other hand, the urine which escapes past the obstacle is pale and watery, and devoid of albumen and casts. 1 . — Non-obstructive Suppression. There is comparatively little known about this subject, and it merits a more extended study. SUPIVRESSION OF URINE, 55 In the terminal stage of chronic .Briglit's DiseaHC, the urine is often suppressed for ten or twenty liours before death, probably from the destructive process in the kidney having reached an extreme degree. In the earliest stages also of acute Bright's Disease, especially in the scarlatinal form, the urine is sometimes sup[)ressed for many hours or for a day or two. The return of the urinary flow is sometimes sudden and very copious, more frequently it is gradual. A similar suppression may occur in scarlatinal dropsy, which is unaccompanied by albuminuria. The following is a characteristic example : A child of seven had sickened with scarlet fever about a fortnight before my visit. The attack was mild ; and the patient entered on con- valescence five days ago. Two days ago general anasarca set in, with vomiting and purging. The urine became scanty, almost to suppression. When I saw the child only two drachms of urine had been voided in the previous twenty-four hours. It was of a deep saflTron color, and highly concentrated ; it contained casts, but not a trace of albumen. The pupils were strongly contracted, and the tongue and skin were dry. There were vomiting and purging. Under the influence of blanket baths, a considerable amelioration in the general symptoms was produced ; but in the two following days only three ounces of a deep yellow urine were voided. On the fourth day violent vomiting came on again, and loud pericardial friction was heard. Death took place next day — preceded by great restlessness, but without coma or convulsions. The total quan- tity of urine voided in the last seven days of life amounted to between six and seven ounces. No autopsy was permitted. The most remarkable examples of this form of suppression occur in that state of system which is called shock or collapse. In the algide stage of cholera and yellow fever the urine is fre- quently suppressed for twenty or thirty-six hours. The return of the flow is generally gradual; the first portions of urine being scanty, high-colored, and containing blood and albumen. All types of violent fever and inflammation are liable to be comp)licated with suppression of urine. And a similar efi^ect may attend an overdose of turpentine or poisoning by the min- eral acids and other irritants. liiegel has described diminution in the quantity of urine during paroxysms of lead colic. ^ Suppression also is a common attendant on the shock an'd collapse following serious internal injuries, such as rupture of the bowels or of the liver, spleen, or uterus. The kidneys appear peculiarly sensitive to injuries or violence applied to the urethra, and rapidly fatal collapse with suppres- sion of urine has been known to follow slight operations on the 1 Deutsches Arch. f. klin. Med., Bd. 21, pp. 175, 193. 66 PHYSICAL PROPERTIES OF THE URINE. urethra, or even the passing of a catheter. I remember an in- stance in which death in twenty hours — with total suppression — followed catheterism in an old case of stricture where instru- ments had been repeatedly used before without any ill-eifects. The only post-mortem appearance of consequence was intense congestion of the kidneys. Sir H. Thompson mentions a case in which a man with old-standing narrow stricture died fifty- four hours after the passing of an instrument which had been used at least a hundred times before. ISTo damage whatsoever was found to have been inflicted on the urethra. Rigors and vomiting commenced about an hour after catheterization, and not another ounce of urine was secreted from that time until death. In this case the kidneys were found congested to an extraordi- nary degree, but no sign of inflammation existed in any part of the excretory urinary apparatus. Similar consequences have been known to follow Holt's operation for stricture. In Mr. Fayrer's case rigors and vomiting ushered in collapse, with total suppression of urine, and death in thirty-six hours.^ Renewed attention has recently been called to this group of cases by Sir A. Clark in a paper read before the Medical Society of London, entitled "Catheter Fever." {See Brit. Med. Journ.., Dec. 1883.) A number of additional examples were cited in the paper, and in the course of the discussion which followed, but no fresh light was throw^n on their nature or causation. The pathology of these cases is very obscure. The imme- diate cause 'of the suppression would appear to be intense con- gestion of the kidneys. Disturbance of the innervation of the organs is probably the primary cause and possibly, also, in many cases, the direct cause of the suspension of the secretion. Death is too rapid to be due to the non-elimination of the urinary excreta. The suppression, in fact, is only one among the many phenomena of fatal collapse. In the way of treatment there is nothing equal to the hot bath. In many cases the relief is both striking and prompt; the flow of urine being sometimes restored while the patient is actually immersed. The efi'eet may be kept up by hot mustard and meal poultices to the loins. Hot gruel enemata are also useful. Medicines by the mouth can rarely be administered on account of the incessant vomiting. Amongst hysterical patients there is sometimes observed, not merely the common symptom of retention of urine, but true suppression of urine. In many of the cases reported as such, especially of old date, this condition was undoubtedly simulated. Laycock,^ however, was amongst, the first to point out that the ^ See a paper, by W. M. Banks, on Urethral Fever, in Edin. Med. Journ. for June, 1871. ''■ Nervous Diseases of Women. SUPPRESSION OF URINP:, 57 suppression may be real. In rnore recent times Cliarcot' has called particular attention to this fact, and has described a case in which no urine whatever was secreted for as long as eleven days. The utmost ])recautions were taken to i)revent deception. The patient sufiercd during this time from excessive vomiting, and the vomited matters were found to contain a quantity of urea. N^o other ill-effects were observed, and the urinary flow was afterwards spontaneously reestablished. 2. Obstructive Suppression. The most common case ot obstructive suppression is due to the impaction of a stone in the ureter of a person who has only one kidney, or, at least, only one capable of secreting urine. Sometimes one of the kidneys is congenitally absent; or one kidney has been permanently disabled at some preceding period of life by the lodgement of a stone in its ureter, or by some other accident or disease. In such a case the passage of a stone into the ureter of the surviving kidney would, of necessity, produce complete suppression of urine. The next most common case is due to the blocking up of the terminal portions of the ureters by the progress of a morbid growth, involving the base of the bladder. The less frequent cases depend on some congenital malformation of the ureters, or of the renal arteries, whereby an impediment is constituted to the outflow of urine. This may be slight at first, but in process of time it becomes progressively greater, until at length it arrests the secretion of urine. Ex- amples of these three modes of obstruction will be found among the following cases.^ A case of suppression from obstruction seldom reaches a fatal climax without some urine having been voided during its course — it may be a few ounces, or it may be a few pints. The char- acter of this urine is very remarkable. Instead of being high- colored and concentrated — as one would expect under such circumstances — it is pale and watery, and of very low specific ^ Diseases of the Nervous System, New Syd. Society, vol. i. ^ [An unusual cause of obstructive suppression of urine recently came under my notice in the Post-mortem Theatre of the Manchester Koyal Infirmary. The right kidney was transformed into a large sac of cheesy matter, and similar material filled and completely blocked the right ureter. The left kidney was enlarged, somewhat congested, and contained numerous small masses of tuber- culous material, situated for the most part in the cortical portion. The left ureter was slightly distended bj' clear urine as far as its entrance into the walls of the bladder. The bladder itself was congenitally small, and measured only IJ- inch in length. Its mucous membrane was greatly swollen and congested, and con- tained numerous tubercular masses. The orifice of the left ureter was surrounded by thick fibrous tissue, and its lumen completely closed by the swollen mucous membrane of the bladder. The suppression of urine had lasted for five days- before death. E. M.] 58 PHYSICAL PROPERTIES OF THE URINE. gravity. It may accidentally be colored by blood, but it is defective in the proper urinary pigment, and, as a rule, is free from albun,ien. This peculiarity depends on the physical conditions under which the urine in these circumstances is secreted. In order to understand the matter clearly, it v^nll be necessary to call to mind the mutual relations in health of the blood circulating in the renal arteries arid the urine newly secreted from it, and flowing down the nriniferous canals. In the normal state, the limiting membrane intervening between the blood circulating in the Malpighian tufts and around the convoluted tubes on the one hand, and the urine in the uriniferous canals on the other, is subject on the side of the blood to a considerable pressure, namely, the lateral pressure within the arterial system; while on the other side there is no counter-pressure at all so long as the escape of urine is free. This inequality of pressure, as was first suggested by Ludwig, and afterwards experimentally proved by Hermann,^ is a capital factor in the production of the urine. Hermann (operating on animals) found that when the pressure w^ithin the renal artery was lowered, the flow of urine was proportionately diminished. He tested this point in two ways. In the first set of experiments he lowered the blood-pressure in the kidney by contracting (by a clamp) the calibre of the renal artery. In the second set he created a counter-pressure in the uriniferous canals by impeding the flow of urine by means of a column of mercury communi- cating with the ureter. By this latter method he exactly imi- tated the condition produced when the ureter is blocked up by a stone, or some other mechanical obstruction. Hermann found that a pressure in the ureter of 10 millimetres of mercury (0.4 inch) caused a sensible diminution in the flow of urine ; this diminution went on increasing up to a pressure of 50 millimetres; and with a pressure of 60 millimetres of mercury (2.4 inches) the secretion of urine was altogether arrested. In these experi- ments the specific gravity and coloration of the urine are not alluded to, but it was uniformly found that the percentage of urea progressively diminished as the pressure in the ureter increased. Basing our deductions on the clinical facts to be presently adduced, and on the results obtained experimentally by Her- mann, we may assume that a mechanical obstruction in the ureter will inevitably produce the following series of events : As soon as the obstruction is established the urine begins to accumulate above it; the accumulating urine determines an upward pressure first in the ureter, then in the pelvis of the 1 Henle and Pfeufer's " Zeitschrift," 1862, p. 1. SUPPRESSION OP^ UKINE. ^}9 kidney, and ultimately in the ui-iiiiierouK tuboH, Ah the urino goes on accumulating, the pressure within these channels neces- sarily increases, until at length the pressure so created is suffi- ciently great in the uriniferous canals to counterpoise the pressure within tlie renal bloodvessels. When this point is reached the secretion of urine is arrested and total sufipression ensues.^ If, again, the obstruction be not altogether complete, and there be room for some urine to escape past the obstacle, the urine so escaping will have been secreted under a high pressure within the uriniferous canals, and its constitution will be found thereby materially altered; it will be very pale, watery, devoid of its proper coloring matter, poor in urea, and of low specific gravity. It may, indeed, be tinged with blood, but this is an accidental circumstance. Another point with regard to the urine in obstructive sup- pression is the irregularity of its times of emission. In nearly all the cases observed this is a marked peculiarity. One day there will be a discharge of urine, the next day none, or perhaps none for two or more days, and then again a return of the flow^, and again an arrest. This point will be again adverted to. The long delay of characteristic symptoms is also a striking circumstance. When even the suppression is absolute, seven or eight days elapse before the special symptoms of ursemic poisoning make their appearance, but when these do appear the end approaches rapidly, and death is not delayed beyond two or three days. Up to the rise of the proper ursemic symp- toms the condition of the patient is, as a rule, Avonderfully calm and free from distress. There may be more or less gastric dis- turbance and insomnia, and declension of the muscular strength, but the functions generally proceed tranquilly, and the intelli- gence is undisturbed. The most distinctive and invariable of the special urtemic signs are muscular twitchings. I believe that these are never wanting. Contraction of the pupils is also a constant sign, but later in its development than muscular twitches. Eapidly in- creasing muscular weakness is also constantly- wntnessed, and as this invades the respiratory muscles the breathing becomes markedly slow, panting, and laborious. The tongue and palate become quite dry in the last tw-o or three days. The cerebral, functions are much less involved than might be expected. ^ In retention, of urine the obstruction is situated below the bladder — in the urethra; and the physical conditions are essentially ditJ'erent from those of an obstruction in the ureter — on account of the enormous distensibility of the bladder which permits the urine to accumulate in that viscus, and thus prevents the pressure extending immediately up the ureters. But this distensibility is not, of course, unlimited, and a time must arrive — if life continue and the obstruction be not oveicome — when the eft'ects of the block are felt in the ureters, and then suppression of urine is superadded to retention. 60 PHYSICAL PROPERTIES OF THE URINE, There is increasing drowsiness, with short, fitful snatches of sleep-, and a little rambling delirium, but absolute coma rarely supervenes, and convulsions are quite exceptional. The in- tellect is more commonly preserved to the last, and in more than one instance the patient has spoken sensibly the instant before death. Diarrhoea (unless produced artificially) is quite exceptional, so likewise is excessive vomiting. There is not any dropsical symptom.^ The skin is commonly moist, often sweating profusely. There is never any ammoniacal or urinous odor from the breath or skin, nor from the body after death. ^ The power of taking food varies : as a rule, it is moderate up to an advanced stage, but complete anorexia comes on a day or two before death. There are some other points relating to the morbid anatomy, the survivorship, and the treatment, which will be more con- veniently noticed in the way of comment on the particular cases to be now described, or in the concluding part of the section. Case 1. — A man, set. 67, who twelve years before had suffered from symptoms of renal colic, but had not passed any stone, was attacked about six weeks before his death with symptoms of left renal calculus, with frequent micturition and pains in the left loin, etc. A fortnight- before his death, after a long walk, he felt a sudden access of intense pain in the left loin. This continued in great severity for four days, and was accompanied with very frequent and scanty micturition. At the end of these four days the urine became altogether suppressed, and the pain ceased a few hours after. On the third day of complete suppres- sion, I saw the patient. He had absolutely no symptoms referrible to the suspended urinary function ; he was calm, free from pain, also from nausea and vomiting, without desire to void urine ; pulse 80 ; tongue clean ; skin dry ; he had had no sleep for two nights. He was ordered a warm bath, a saline mixture, and to have the course of the left ureter well kneaded with the aid of a liniment. Next day (fourth day of sup- pression) he passed a pint of pale, limpid urine; he had perspired freely and slept some hours. On palpating the renal regions, the right was felt to be flat and empty, contrasting with the left, which presented its natural roundness and sense of resistance. On the next day (fifth) twelve ounces of urine were voided. It was clear, almost colorless, sp. gr. 1010, not albuminous, and contained 1.92 grain of urea per ounce. There were anorexia, thirst, nausea, and occa- sional vomiting, a slight sense of mental confusion, but no actual deli- rium ; pulse 80 ; respiration 24. On the following day (sixth) the same symptoms continued, with intense restlessness and insomnia. Sixteen ounces of colorless urine were passed, sp. gr. 1011, containing 2.08 grains of urea per ounce. The fol- lowing new symptoms also showed themselves — dryness of tongue at tip, ^ For an exception to this rule, see Case 10, further on, and Dr. Eussel's Case in Med. Times and Gaz., 1879, I. p. 474. 2 This seems a point of distinction from rete)itio7i of urine. SUPPRESSION OF UKINK. fjl contraction of pupils, and occasional hiccough. In the evening of" this day, six more ounces of limpid urine were voided ; sp. gr. 1011 ; tem- perature in axilla 08.6°. On the afternoon of the next day (seventh) a great change for the worse was observed. Pulse 80, irregular ; respiration 20, labored, long- drawn, interrupted ; tongue dry and brown ; frequent muscular twitches all over body ; patient indifferent and drowsy, but answering questions intelligently ; no urine for the last eighteen hours. Death took place thirty-six hours after the last visit — exactly nine and a half days from the commencement of the suppression. The symptoms during this last period, as observed by the late Mr. Mellor, with whom I saw the case, were — increased laboriousness and slowness of the respiration, which assumed a panting character; deepening in- difference, but still he answered "yes" and "no" to questions addressed to him, though slowly and unwillingly ; pupils contracted to pin's points ; finally complete coma. There was a doubtful convulsive seizure immediately before death. Autopsy. — Strong rigor mortis; body well nourished, and quite free from urinous or ammoniacal odor. All the organs healthy except the kidneys and ureters. The right kidney was wholly converted into a fibrous mass, studded with cysts, and weighed two and a half ounces. The corresponding ureter was impervious throughout, and changed into a fibrous cord, which was thickened about the middle to double its width. This thickened part was solid and fibrous like the rest. No stone existed in any part of the ureter or kidney, but it was conjectured that the thickened part of the ureter had been the seat of an obstruction, and that the stone, or whatever object had constituted the obstruction, had been subsequently removed by absorption. The left kidney was much enlarged, it weighed ten ounces, and, on section, appeared dark and intensely congested. The ureter was as thick as a goose-quill, and distended with urine. .At its lower part were found three little oxalate of lime calculi about the size of hemp-seeds, and weighing altogether a grain and a half. One of these was tightly impacted in the terminal part of the ureter, where it passes through the coats of the bladder ; this was the cause of the obstruction. The fluid imprisoned in the ureter amounted to three drachms, and consisted of grumous bloody urine. The pelvis of the kidney was only slightly dilated, and contained about two drachms of bloody urine. The bladder contained about six ounces of pale dilute urine ; its coats were healthy. The course of events in this man appears to have been the following : About a month before the patient came under ob- servation, three small calculi, which had been previous!}- lying harmlessly in one of the infundibula, w^ere dislodged, and fell into the pelvis of the kidney. Here they sojourned some four wrecks, causing pains in the left loin and frequent micturition. At the end of this period they suddenly entered the ureter, and for four days, amid great suffering, continued their descent to its lower part. Here the foremost calculus became impacted, ■ 62 PHYSICAL PROPERTIES OP THE URINE. the pain ceased suddenly, the passage of urine was blocked up, and suppression ensued. Had the opposite kidney been intact, no serious consequences would have followed. The healthy kidney would have become proportionately hypertrophied and performed double duty. But the right kidney was, by an unto- ward coincidence, practically non-existent. It had itself, as may be conjectured, many years before passed through a train of events similar to that which had now extinguished the activity of its fellow. The suppression of urine in this case lasted nine days and a half. During the first three days the suppression was complete. Then followed a period of four days, during which an aggregate quantity of fifty-four ounces of urine was voided. Finally, in the last two and a half days no urine was passed, but six ounces were found in the bladder after death, making a total of sixty ounces of urine secreted in nine days and a half. This seems at first sight a not inconsiderable quantity, and causes surprise that, suppression being so incomplete, life was not longer main- tained. But on closer inquiry the suppression proves to have been more complete than at first appeared. The urine dis- charged was exceedingly dilute, its sp. gr. ranged from 1010 to 1011, and its proportion of urea was only about two grains per ounce ; this gives a total weight of urea excreted in nine and a half days of only 120 grains, which is less than one-fourth of the normal amount for a single day. Case 2. — A very stout, tall man, set. 59, suffered four years before from symptoms of the passage of calculi from the left kidney. Two small uric acid stones were passed after several weeks of suffering, and then the symptoms subsided. After four years of good health, the patient was seized one morning, without assignable cause, with sudden pain in the right loin and urgent desire to pass water. The pain and urgency of micturition continued until the afternoon, and small quantities of bloody urine, amounting altogether to about half a pint, were voided at short intervals during the day. The stomach was irritable throughout the day. Toward even- ing the flow of urine ceased entirely, and the pain diminished. I saw the patient for the first time about fifty hours after the com- mencement of the suppression, with Mr. Grindrod, of New Mills; and I visited him daily until his death, which took place nine days and a few hours after the arrest of the urinary flow. During this period he only voided urine once, namely, two ounces on the fourth day, and none was found in the bladder after death. This specimen of urine was quite characteristic of obstructive suppression. Its sp. gr. was 1010 ; it con- tained a little blood, and a slight corresponding trace of albumen. When the blood-corpuscles had subsided, the urine had a pale straw color, and the deposit contained, besides blood-disks, a large number of epithelial cells of a transitional character, resembling those of the pelvis of the kidnev. SUPPRESSION OP UlilNE. 63 The case, which was closely watched throughout its course, presented a typical example of death from pure anuria. Dr. Garrod was tele- graphed for from London, and joined our consultation on the fifth day of suppression. For the first six days the symptoms were marvellously slight, and yielded but faint indications that one of the capital functions of the body was in absolute abeyance. The muscular strength had indeed de- clined, and the sleep was bad, but the patient was calm ; his tongue, skin, and pupils were natural ; there was little nausea, and no vomiting after the fourth day ; the intellect was unclouded ; there was not the least urinous or ammoniacal odor about the breath or sweat; the pulse was steady, at about 72, the respirations 24, and the temperature scarcely varied from the normal limits. There was no desire to make water, scarcely any pain or tenderness in the right loin, and he continued to take a fair amount of nourishment. On the seventh day the character- istic symptoms of suppression began to show themselves. On this day occasional slight twitchings or pluckings of the muscles were observed on the trunk and limbs, and the tongue began to be dry. The insomnia, which had been a marked symptom from the first, became very distres- sing ; he dozed frequently for short periods, and started on falling asleep and awaking. He took nourishment fairly, and had no vomiting or thirst, and only very slight and transient nausea. On the eighth day the patient was still calm, and quite free from mental confusion or indifference when fairly awake, but when left alone he was constantly falling off in a fitful doze, and awaking with a start. The muscular twitchings were more marked than yesterday, and the muscular weakness had increased greatly ; nevertheless, he was up and dressed in his bedroom for an hour and a half. The pupils were natural, and he took his food pretty well — a quart of milk, some cocoa, bread and butter, and rice pudding. The skin had acted profusely from the beginning in response to warm baths. No nausea or vomiting. A pecu- liar panting character of the respiration was noticed to-day, which became more and more pronounced until his death. The temperature also began to fall. On the ninth day the patient's condition changed greatly for the worse. The insomnia and restlessness were most distressing ; the twitchings of the muscles very frequent and severe ; the tongue and mouth were per- fectly dry ; the pupils were decidedly contracted, though still sluggishly responsive to light ; thirst was troublesome, and the appetite quite gone ; the weakness was so great that he could not walk without the help of two assistants ; his legs had to be lifted into the bath. There was no persistent nausea, but he vomited after a compound jalap jDowder. Although his intellect was clear when he was roused (he transacted- some business with his lawyer"), there was marked indifference when he was left undisturbed, and he lapsed at once into a dozy state, lying with his mouth open and jaw half dropped, breathing pantingly with long pause between expiration and inspiration. On the tenth day, at 1 p.m., the patient died, having lived for a little more than nine whole days from the onset of the suppression, and having voided in this interval only two ounces of a very dilute urine. The incidents of the closing scene were very distressing. The weak- 64 PHYSICAL PROPERTIES OF THE URINE. ness increased rapidly ; the night was most restless ; the patient was con- stantly getting up to have a stool, but voided nothing except a little mucus; The thirst, dryness of the mouth, and the muscular twitchings went on increasing. At 6 a.m. the breathing became very embarrassed, threatening suffocation. He asked to be instantly raised on the side of the bed into a sitting posture. He then belched up a large quantity of flatus, and was thereby much relieved in his breathing. After a couple of hours he lay down agaip, but with his head raised. The power of his legs was now quite gone; he said he could- not feel them. At nine o'clock the pulse was 80, respirations 15, very labored and interrupted. The pupils were strongly contracted. The twitchings were incessant all over the body and limbs. The breathing becoming again more embar- rassed, he was lifted on the side of the bed, and finally into his arm- chair. His strength failed now more and more, and the breathing became more and more difficult, and the uneasiness and distress in- creased, dozing and starting incessantly. He remained in his chair until one o'clock, when he began to slide off, and, while about to be assisted up again, he asked to have his hands rubbed, and suddenly fell back dead. There was neither coma nor convulsions throughout. He ap- peared to wander at times through the night, but when his attention was roused, he showed unshaken consciousness and intelligence to the end. The character of his breathing in the last few days was peculiar, and became increasingly so as death approached. The inspiration became more and more prolonged and laborious, and expiration shorter and more panting, with a lengthening pause between. The respiratory diffi- culty, which appeared to be the immediate cause of death, evidently arose from the diminishing power of the inspiratory muscles. The post-mortem examination was confined to the abdomen. All the organs were healthy, except the kidneys and ureters. The right kidney was enlarged, and weighed 11* ounces. Its surface was dotted here and there with numerous black blood-spots ; but the general appearance,, both on the surface and on section, was pale mottled, decidedly anaemic- looking. It contrasted strongly with the dark, almost black congested kidney found in Case 1. The pelvis and ureter were not in the least dilated. They contained about two teaspoonfuls of blood-stained urine. A small uric acid calculus was found tightly impacted in the lower part of the ureter, just above its entrance into the bladder. It was about the size and shape of a hemp-seed, and weighed Ih grain. The left kidney was found completely destroyed. It was hollowed out into a lobulated sac, about as large as the healthy kidney. On cut- ting it open, there escaped about five ounces of an opaque white fluid, exactly resembling new milk. This singular-looking fluid retained its milky appearance, even on long standing ; it was found to consist of myriads of needles of urate of soda floating in a highly albuminous serum. The sac wall consisted of a tough leathery tissue, from one ta two lines in thickness, quite devoid of any recognizable renal structure. The cause of this mischief was found at the entrance into the ureter, Avhere the channel was completely blocked up by a uric acid stone, weighing 52 grains. The rest of the ureter was pervious and normal. The bladder was empty and healthy. The body generally was per- fectly sweet and free from any urinous or ammoniacal odor. SUI'TRESSION OF URINE. 65 The pathological story of this man's case was easily read even during life, and only a few details were left to be filled in at the autopsy. The left kidney was destroyed four years before by the impaction of a calculus in its ureter. The right kidney then became hypertrophied, and performed double duty in a perfect manner until another calculus blocked up the right ureter. Then the secretion of urine was suddenly and permanently ar- rested, and the patient destroyed in less than ten days. In reviewing the symptoms in this case, it may be observed that insomnia and progressive failure of the muscular strength marked the entire course of the case. A certain disturbance of the stomach and slight febrile movement set in when the stone was impacted in the ureter; but these passed away after the fourth day. A fair amount of nourishment was taken up to the eighth day, after which the power of taking food almost wholly failed. The movements of the pulse, respiration, and temperature may be seen by a glance at the following table : Pulse. Respiration. Temperature. Third day . . Fourth day .... 72 — 72 24 100.0° 72 24 99.7 72 24 99.7 76 20 98.6 76 22 98.2 76 20 97.4 80 15 — Fifth day Sixth day Seventh day Eighth day Ninth dajr Tenth day The pulse remained almost stationary, but with a slight ten- dency to increased frequency. The respiration showed a ten- dency to diminished frequency, especially toward the last. The temperature manifested a steady tendency to diminution, espe- cially as death approached. This, I believe, will be found to be the general rule in fatal anuria. Muscular twitches were first noticed on the seventh day. At first they were slight and in- frequent, but they became more and more frequent and severe as the case approached its termination. The faculties were clear to the last gasp ; there existed, however, in the last three days a constant tendency to lapse into indifference, with fitful dozing and starting, when the patient was left undisturbed. The pupils did not show decided contraction until the ninth day, and dry- . ness of the tongue and mouth became a marked feature on the same day. This case and Case 1 illustrate a noteworthy point in the morbid anatomy of obstructive suppression. In both of them it is noted that the ureter above the obstruction, and the pelvis of the kidney, although moderately filled with stagnant urine, were not materially dilated or enlarged. Those examples of monstrously enlarged ureter and pelvis (sacculated kidney or 66 PHYSICAL PROPERTIES OF THE URINE. hydronephrosis), which are often witnessed as the effects of obstruction in the ureter, are produced by slow degrees, and must be r^egarded as a growth rather than a simple dilatation. Indeed, the ureter and renal pelvis appear incapable of that rapid dilatation which we are familiar with in the bladder. This consideration enables us to explain how two different results may follow one and the same cause, namely, obstruction in the ureter. When the obstruction is suddenly established and is at once complete, the consequence is not enlargement and sacculation, but atrophy of the kidney and ureter. When, on the other hand, it is slowly established and is incomplete, it produces hypertrophic dilatation of the ureter and pelvis, and eventually sacculation of the kidney or hydronephrosis. Case 3. — A man, set. 40, had suffered three months before from symp- toms of renal colic on the right side, and voided some small calculi. He soon recovered from this attack, and went about his business in his usual health, until three weeks before his death. He then began to suffer from pain in his left loin, which continued for a fortnight. During this period the urine was voided in apparently the usual quantity, but his wife noted that it had entirely changed its character. Before it had been high-colored, but now it became " clear as water." At the end of the fortnight complete suppression of urine came on, and death ensued in five days. I only saw this man once, on the day before his death, in consultation with Mr. Edwards, of this town. He was then in a state of full uraemic intoxication — pupils contracted to pins' points — muscular twitchings universal over the whole body — breathing panting, slow, and inter- rupted — tongue and mouth quite dry. He was very restless, and almost indifferent, yet he answered questions sensibly when roused. He died next day without coma or convulsions ; he spoke sensibly half an hour before his death. Autopsy next day. The body was quite free from urinous or ammo- niacal odor, and healthy in every part except the urinary organs. The right kidney, which was about the normal size, was hollowed, and in process of atrophy ; the cortical substance alone partially remained, and this was pale and wasted. The infundibula were moderately dis- tended, and contained about an ounce of pale fluid, which was lost. The right ureter was plugged up at its commencement by an elongated uric acid stone, weighing twenty-two and a half grains. Another little stone, as big as a hemp-seed, lay in one of the infundibula. The ureter below the plug was normal. The left kidney was much enlarged, but healthy. It had the mottled appearance of the right kidney in Case 2. Three little uric acid calculi, like flattened mustard seeds, lay free in the infundibula. The ureter and pelvis were moderately distended with fluid ; the ureter appearing about the size of a crow-quill. On slitting it open, superficial abrasions were seen along its entire track, showing the footsteps of a descending calculus. Near the bladder this calculus was found, at the termination of the ureter. It slipped into the bladder during the manipulations. It SUPPRESSION OF URINE. 67 was a round uric acid stone as large as a small pea, and weighed a grain and a half. The bladder was empty and healthy. Though this case was seen but once, the diagnosiH presented no dithculties. The course of events was evidently as follows : Three months before the fatal attack the right ureter was plugged by a calculus, the function of the right kidney was thereby permanently extinguished, and the organ at once passed on to a state of atrophy, which was nearly complete at the time of death. The left kidney then took up the double duty, and became proportionately hypertrophied. The calculous ten- dency, however, was not arrested, and about three weeks before death a small calculus passed into the left ureter. It con- tinued to descend amid much suffering, for about a fortnight, causing partial suppression of urii]fe. The urine voided during this period had the special characteristic of urine secreted under pressure from below — i. e., it was pale and watery. At the end of the fortnight the calculus had reached the terminal portion of the ureter; there it became immovably impacted, complete suppression ensued, and death followed in five days. It must be assumed m this case that during the fortnight of partial suppression a certain degree of blood-poisoning took place from the accumulation in the blood of the eifete ingredients which should have been removed by the kidneys, so that when the suppression became complete it only required five days (instead of nine or ten) to render the blood poisoned to such a degree as to be incompatible w4th the maintenance of life. Case 4. — A man, set. 65, had been subject for some years to attacks of renal colic, and had from time to time voided uric acid calculi. Some fourteen days before my visit, symptoms of left renal colic had set in, with pain in the loin and frequent micturition. I Avas informed that during these fourteen days a considerable quantity of pale, clear urine had been voided, averaging altogether about two pints a day, but dis- charged irregularly. On some days none had been discharged, while on other days it had flowed copiously at two or three separate micturitions. AVhen I saw the patient he was in the last phase of uraemia ; the pupils were strongly contracted; there were frequent and universal muscular twitchings : pulse 100; respirations 16, markedly panting, but • consciousness was intact when the attention was roused. The hypogastrium being protuberant and dull, a catheter was intro- duced, and two pints of urine were withdrawn. This presented the usual characteristics of obstructive suppression, it was very pale, and its sp. gr. 1006. Death took place on the fifteenth day of suppression, which, however, had only been partial throughout. A post-mortem examination was not permitted, but it was not difficult to divine what had occurred. The right kidney had doubtless been destroyed at some previous period by 68 PHYSICAL PROPERTIES OF THE URINE. the impaction of a calculus in its ureter. The left kidney, which had then become the sole organ of the urinary function, was in its turn sub- jected to a similar accident; a calculus entered its ureter and failed to clear the passage into the bladder, incomplete suppression ensued, and death in fifteen days. This case is instructive in one respect, and suggestive of a caution in judging of the amount of urinary secretion. This man voided on an average about two pints of urine daily. Had this amount been of normal density and appearance, it would have indicated a degree of renal activity certainly equal to the prevention of ursemic poisoning. Patients may live for months without voiding more than lifteen or twenty ounces of urine a day, as is frequently witnessed in cases of cirrhosis of the liver and in regurgitant heart disease. But in these cases the urine is always of high, density, deeply colored, and fully charged with urinary ingredients. Here, on the contrary, the urine was pale and dilute, and the density of the specimen examined was only 1006. What amount of normal urine this represented cannot be accurately determined, but judging by the result of my analysis of the urine passed under similar cir- cumstances in Case 1, the urea would not amount to more than about one grain to the ounce. Calculating on this basis, this man excreted only forty grains of urea per da}^, which is not more than one-tenth of the normal amount. Another point in the case deserves notice as being more or less constantly charac- teristic of the mode of emission of urine in obstructive suppres- sion ; this was the irregularity of the times of discharge. Although the patient in this case discharged an average quantity of two pints a day, this was not voided with that approach to regularity which marks the normal .state, but most irregu- larly; one day no urine at all would be voided, the next day it would be voided copiously two or three times, then again none at all for two or three days, and so forth. I have noticed this paroxysmal character of the urine-discharge in all my cases of obstructive suppression, and I believe it to be a point of con- siderable diagnostic value. The two following remarkable cases show that recovery is possible even after very protracted suppression of urine, pro- vided the flow of urine can be reestablished. The notes of the two cases were furnished to me by Dr. Cliftbrd Allbutt, of Leeds, and Dr. Duigan, of Gainsborough, respectively. In the first case the suppression continued for nearly ten days, and in the second for nine days. In neither case were twitchings of the muscles noted, but the pupils had become contracted in Dr. Allbutt's case, and there was some mental confusion. From my own experience I should regard muscular twitchings as the first SUPPRESSION OF URINK. 69 really undoubted and characteristic symptom of urtemic [joison- ing; it cannot, therefore, be said that recovery followed in either case after the full declaration of ursemic symptoms. Another appai'ently well-authenticated case of recovery after nearly ten days' total suppression, of obscure nature, is record(id in the tenth volume of the Edinburgh Medical and Surgical Journal, p. 409. Case 5. (From the notes of Dr. AUbutt.) — Mr. W., a healthy vigor- ous man of about 56, was first seen by Mr. Wheelhouse, on Wednesday, September 11, 1867. He complained of great lumbar pain, weight, sense of fulness, sickness, and febrile disturbance. Monday, 16th. — Symptoms of descent of calculus along ureter com- menced. Saturday, 21st. — During this time stone apparently traced along u reter. October 2d. — ^Stone from last date till now seemed to be impacted at entrance into bladder, constant pain augmented in paroxysms till 3 a.m. this morning, when sudden and entire relief was felt, and the patient was told how to look for symptoms of stone in the bladder. At 6 a.m. he passed the last quantity of urine, about 5ij. Up to this time the flow had been free and the fluid normal. 3d, 9 A.M. — No urine passed. Catheter used, but no obstruction found. Bladder quite empty. 3 p.m. — Same state. Perfect freedom from pain, no urine. No symptoms of ursemia. 10 p.m. — Consultation with Dr. AUbutt. Same state. Temperature 100°. Hot bath and fomentations ordered. 4th (Friday), 9.30 a.m. — Same state. No urine. No uraemia. Much local uneasiness and restlessness. Temperature 98.2°. Fomentations, saline purgatives and diluents. Bromide of potassium with a little iodide given as a sedative, opium being inappropriate. 9 p.m. — Same state. A drop or two of urine had been coaxed out, just enough to make a stain at the bottom of a small vessel. No symptoms of poisoning. Patient quite clear and much more comfortable. 5th.— Mr. W. summoned at 5 a.m. Much pain at the old point; cramped limb of same side; not a drop of urine, though frequent solici- tations; firm pressure on part gives relief. Sp. ^th. sulph. ordered every half hour. 8.30. — Seen with Dr. AUbutt. Pain subsided after a few doses of ether; no urine; breath sweet; perspiration normal. On examination whole left side of belly from middle line dull ; left rectus tense; dulness varies a little with position. Patient clear and intelligent; no drowsiness. Ether and bromide omitted. 3. p.m. — " Same condition; pain returning; no urine; no uraemia. 9.30. — Seen with Dr. AUbutt. Physical examination : Dulness over whole of hypo- gastrium below a cross line drawn through the navel; dulness little affected by position. Examination per rectum showed only a tender spot behind the prostate ; no bulging ; catheter passes freely, and is moistened with a few drops of urine, perhaps twenty or thirty drops ; upon the end of it is a little bloody mucus. Breath decidedly urinous; 70 PHYSICAL PROPERTIES OF THE URINE. mind clear ; no headache. Pulse weaker and quickening a little. Pulse and temperature have been normal. 6th, 9.30. — Pulse 96, better ; temperature 98.2°. Had passed a fair night ; no urine. Dulness of belly extends a little above navel on left side, but not extending so far to the right as yesterday. Breath not urinous. Bowels have been kept open by salts until to-day, when no motion was reported. 9.30 p.m. — Singularly clear in head ; placid sleep for five hours. Two watery stools. No urine, unless it be a very few drops passed after repeated efforts ; is cheerful, and walks about the room easily, and is well able to sit down and rise. A little cough which he has seems to shake and hurt the lower belly. Tongue coated, but food taken fairly in small quantities. Has had, for instance, a little partridge to-day. Pulse and temperature normal. Breath sweet. Ankles not puffy. Dulness all over hypogastrium. 7th, 9.30 A.M. — Good night. Pulse natural. Temperature 97°. No stupor or headache. Sense of a movable tumor in lower abdomen. A few drops of urine, perhaps a teaspoonful, accumulated after repeated efforts. 10 P.M. — Complains of weight at lower belly on left side, and pain there on coughing. Sickly during the day. Pulse and tempera- ture normal. No ursemic symptoms. 8th, 9th, and 10th. — Same report, unless there be a little drowsiness and tendency to be a little "lost" at times. 11th. — This morning a little urine was passed, quantity not recorded. There is a good deal of mental oppression, especially after awaking. Aspect dull and heavy. Pupils contracted. Dulness of abdomen about the same ; it is a little increased on left side, but diminished a little to the right. He has been purged to-day without medicine. 12th. — Has passed ^ivss of water, and there is a little less mental ob- fuscation. Has had a warm bath, which relieved him in every way. Is still purged also, an action which is not prevented. Tongue loaded, appetite nil. Temperature normal. 13th. — Marked improvement; a copious flow of urine last night. The head clear; a refreshing night. Some return of appetite. Ab- normal dulness much diminished. 14th and 15th. — A good deal of pain, dragging and paroxysmal; chiefly in the old place, above and to left of pubis ; is irritable and rest- less; expression worn and anxious. There is no pain at the end of the penis. Pulse 100, weak. Temperature 100°. As the water is now very abundant, we are able to give him champagne and morphia injections, which with warm water baths relieve him. Is still purged. 16th and 17th. — Pains cease. No stone is discovered. Convalescence. 21st. — May be considered well. Functions normal. Appetite good. No dulness in abdomen. I strongly suspect that the. suppression in this man was not due to the impaction of a calculus in the ureter, as seems to have been the impression of Mr. Wheelhouse and Dr. Allbutt, but to the existence of a double hj^dronephrosis, and that the case was similar, pathologically, to one which fell under my notice some three years ago, and which will be related hereafter (see hydro- SUPI'UKSSIOISr OF UKJNK. 71 iie[)lii'08is, case of J. S.). Tcriiporiiry .suppression of urine, exteiidini!; over some days, followed by copious flow of urine, is a distinctive feature of cases of hydronephrosis; and the exten- sive dulncss in the abdomen, which disappeared after the urine began to How, can (the bladder being emptied) scarcely be otherwise explained. In the next case, however, the suppression was undouijtedly due to the impaction of calculi in the ureter, and ceased when these were voided. Case 6. (From the notes of Dr. Duigan.) — The patient was a strong, stout, middle-aged cattle-jobber, living in the country. He had often suffered from renal colic, and had frequently passed uric acid calculi. The attack began with pain in both loins, and the patient had had com- plete suppression for three or four days when first seen by Dr. Duigan, in consultation with Dr. Smallman, of Willingham. The pain had then completely subsided, and except for loss of appetite and the suppres- sion, the man presented no marked symptoms. The introduction of a catheter showed that the bladder was empty. For nine days he con- tinued in this state, never passing any urine all that time, and not suffer- ing from any bad symptoms, sickness, or other indications of ureeraic poisoning. At the end of this period the kidneys began to act, and he j)assed a quantity of clear urine of low specific gravity, containing nothing abnormal. With this urine he voided three or four uric acid calculi, and shortly after got quite well. In this case it is probable that one kidney had been destroyed at some former period by the impaction of a calculus in its ureter; at the same time it is not absolutely impossible, as Dr. Duigan suggests, though, I think, highly improbable, that both kidneys may have been sound, and that both ureters were obstructed by calculi at the same moment. Case 7. — A man, set. 59, was visited by me with Dr. Herbert Een- shaw, of Sale, on July 10, 1871. Six months before he began to suffer from pain in his back, loss of appetite, failure of strength, and consti- pated bowels. The pain in the back was of a constant and severe ach- ing character, requiring endermic injection of morphia for its relief. The urine was pale and abundant, but discharged irregularly. It did not at any time up to my visit contain blood or albumen. A month before, the patient had total suppression of urine for four days. This was overcome by compulsorily walking him about between* two assistants. The urine returned and the pain subsided. After this, however, the discharge of urine was extremely irregular, and it was noticed that when the urine flowed freely the pain in the back was re- lieved, and that the pain became aggravated when the urine was for a time suppressed. After the above-mentioned four days' suppression, he recovered a good deal, and went to Southport. There he was attacked with diar- rhoea, and had to return home in consequence. 72 PHYSICAL PROPERTIES OF THE URINE. At the date of my visit he was suffering severely from the pain in the back; he was very weak, and his legs were slightly oedematous. He was then passing from one to two pints of a dilute urine daily; this con- tained a trace of albumen. I requested that all the urine which the patient voided should be collected and brought to me day by day for the next three days. The first day he voided two pints, the second day one pint, and the third day eight ounces. For the next three days the urine was totally suppressed, and he died. The specimens of urine were all alike ; they vv'ere pale and watery, the specific gravity ranged from 1009 to 1010; they were acid, and contained a trace of albumen. The symptoms during the last three days of life were as follows, according to the statements of Dr. Renshaw and the patient's wife, for I saw him only once myself: Increased weakness, marked panting breathing ; diarrhoea for the last two days ; twitchings of the muscles ; rambling delirium when left to himself, but perfect consciousness to the last when his attention was roused ; no coma, no convulsions. Autopsy. — Body quite free from urinous or ammoniacal odor. All the organs were healthy except the urinary apparatus. The source of mis- chief was found to be a hard scirrhous mass, as large as an orange, which half filled the pelvis. This growth involved the base of the bladder and the prostate gland. The rectum was adherent to it and constricted for the space of an inch ; but I could get two fingers through the nar- rowest part. The seat of the scirrhous growth in the bladder was the submucous tissue. Neither the mucous nor peritoneal coats were impli- cated, though much puckered and folded, owing to the contraction of the thickened wall of the bladder. The whole trigone was involved, and the disease extended for a full inch above the trigone, terminating in a thick, abrupt rim or border. The walls of the bladder in the implicated region measured from half to three-quarters of an inch in thickness. The fundus of the bladder was quite healthy, and the organ was capable of containing about half a pint of urine. The urethra for the length of an inch passed through the dense mass of the prostate, which was fully an inch and a half thick. The channel was quite free, a catheter had been repeatedly passed during life without any difiiculty. The terminal portions of both ureters passed for the length of an inch through the scirrhous mass; their course in this part was tortuous, and their channel compressed by the surrounding growth, but a probe could be insinuated through both of them, showing that neither w^as completely occluded. Above the bladder both ureters were dilated to the size of the little finger (the left more than the right), and distended with urine. The left kidney was greatly atrophied, and weighed only 2} oz. ; the inte- rior was hollowed, without trace of pyramids, and the cortical substance was reduced to a fleshy rim of tissue of homogeneous appearance. The right kidney was enlarged, and weighed 7 oz. ; it was hollowed, but not so completely as its fellow. The pyramids were gone, and the cortical substance was undergoing absorption. The pelvis was enlarged to the size of an egg, and distended with urine. It was evident that the left kidney had not done any duty for some months, and that life had been sustained by the hypertrophied right kidney until its ureter also was blocked up by the progress of the growth in the bladder. SUPPRESSION OF URINE. Y--) The tumor had contracted adhesions to, and made extensions into, the adjacent parts in the pelvis. The iliac vessels passed through a dense scirrhous mass, whereby they must have been more or less compressed ; this was evidently the cause of the oedema of the legs. My notes of the next two cases are imperfect, but as oacli of them illustrates some point in the historj' of obstructive suppres- sion, I will add them to the series. Case 8. — This was an old lady of about 60, whom I saw with Dr. Gardiner, of Ashton. She was afflicted with cancerous disease of the uterus and vagina, involving the base of the bladder and (presumably) implicating the terminal portions of the ureters. When I visited her no urine had been passed for four days, and the suppression continued without interruption for three days longer, altogether a total of seven days. After this the urine returned, and flowed normally for the re- maining four weeks during which she lived. During the time of sup- pression there were great restlessness and insomnia, with a flushed and anxious expression of countenance, but no twitchiugs of the muscles, a,nd no convulsions nor coma. There was no autopsy. Seven days of suppression of urine, without the development of urse-.mic symptoms, and issuing in recovery so far as the sup- pression was concerned, is, as we have seen, not an unprecedented occurrence. It may be conjectured that in this case one ureter was permanently occluded by the morbid growth ; and that during the epoch of suppression the opposite ureter had become blocked up, probably by a fungous excrescence projecting into its calibre, and that an ulcerative process at the end of seven days again cleared the passage. This is a process analogous to that which sometimes occurs in scirrhus of the pylorus, when the strictured state prevailing in the earlier periods is after- wards removed by the softening and ulcei-ation of a portion of the cancerous mass. Case 9. — A man of about 35, greatly given to alcoholic excesses, was seen by me on January 15, 1869. He had then passed no urine for four days. He was somewhat stout, and both loins weie doubtfully thought to be the seat of bulging, of an elastic, quasi-fluctuating character. The previous history threw no light w^hatever on the nature of the case. There were no ursemic symptoms, but a great sense of tension of the abdomen. I saw this man on three successive days, and introduced a tubular needle to the depth of three inches into one of the lateral bulg- ings, but without reaching any collection of fluid. The notion I enter- tained was that a double hydronephrosis existed, and that the swellings in the loins were the sacculated kidneys distended with urine. He died two days after my last visit. No post-mortem examination was per- mitted. The suppression lasted nine days, and during that jieriod only about an ounce of urine was voided, which was said to be pale. Up to 74 PHYSICAL PROPERTIES OF THE UPINE. the seventh clay of suppression there were no twitchings of the muscles nor marked contraction of the pupils. The information respecting the final symptoms is defective. There were great restlessness and insomnia. Consciousness was maintained to the last, and the patient asked to be prayed with just before his death. The foUowina^ case is remarkable in two respects — namely, the long survival of the patient (15 days) and the occurrence of transient anasarca. Case 10. — Mrs. P., set. 56, had been suffering for 18 months from occasional uterine hemorrhage, due to scirrhus of the os and cervix uteri. On January 15, 1876, the urine became very scanty, and next day it altogether ceased. From this date to the day of her death, on January 30th, not a drop of urine was secreted. I saw her on the tenth day of suppression, with my friend Dr. Lloyd-Roberts, to whom I am indebted for the notes of her case. Her condition was singularly calm. She took her food, and slept well ; the tongue was moist and the pupils natural. Pulse 84 ; temperature 99°. There was no pain anywhere. Dr. Roberts informed me that on the first two days of suppression there was slight general anasarca — most marked in the face. This symptom entirely passed off on the third day; but there was a slight recurrence of oedema in the feet on the day before death. On making a digital examination, an extensive scirrhous growth was found, involving the cervix uteri and the adjoining part of the vagina corresponding to the base of the bladder. This explained the suppres- sion ; the ureters, as they passed through the trigone, were doubtless involved in the cancerous growth, and thereby occluded. The bladder was found empty. The symptoms continued almost unchanged until January 29th. On that day she became worse. The pupils became contracted ; and mus- cular twitches were observed in the face. The muscular power failed rapidly, first in the arms and legs, and lastly in the trunk. She died quietly on the morning of January 30th, apparently from paralysis of the respiratory muscles. The temperature on the 29th sank one degree below the normal. No autopsy was permitted. The duration of life in complete obstructive suppression appears to range, as a rule, from nine to eleven days, and the passage of a few ounces, or even two or three pints, of a dilute urine does not seem to extend the time of survival beyond a few hours. I have not discovered more than four well-authenticated cases (in addition to the one just related — Case 10) in which suppres- sion of urine was complete, or approached completeness, where the patient survived beyond the eleventh day. The first of these is recorded by Rayer {Mai. des Reins, t. iii. p. 490). The patient was a man of 64 years of age, who had hydronephrosis of the right kidney of many years' standing. The ureter of the left kidney was blocked up by a calculus, and suppression of urine SUrPKESSlON OF URINE. 75 ensued. TIj'ih proved fatal in twenty-five days, and in tliat in- terval oidy two oun(;es of urine were voided. The necond case is described by Sir J. Paget in the second volume of the Trans- actions of the' Clinical Society. The patient was seventy-three years of age. The right kidney was atrophied and apparently incapable of secreting any normal urine. The left kidney was hypertrophied and the ureter blocked by a stone. Complete suppression ensued for thirteen days. ISTo symptoms of urfcmic poisoning appeared until the last of these thirteen days, when a slight attack of convulsions occurred. Then, on the fourteenth day, he passed an uncertain but " considerable " quantity of urine, and again six ounces on the same day; some slight con- vulsive movements which had been observed during the day then ceased. From this period until his death, seven days after- wards, the suppression was complete, and no urine was found in the bladder after death. So that there was total suppression for twenty-one days, only interrupted by one day's emission of urine. Muscular twitchings made their appearance on the six- teenth day. Sir J. Paget attributed the extraordinary protraction of life in this case mainly to the patient's advanced age ; but this view is scarcely borne out by other experience. My first patient was sixty-seven — only six years younger than Sir J. Paget's case, yet he only survived nine and a half days, though he secreted sixty ounces of urine in that period. A third case is reported by Dr. Eussell in the 31ed. Times and Gazette, 1879, i. p. 474, where the patient, after complete obstruc- tive suppression lasting twenty days, recovered for a time, but died afterwards. There was excessive vomiting and also gen- eral oedema. A post-mortem examination show^ed the presence of calculi in the pelvis of each kidney, blocking the ureter. Tenneson {Gfaz. Hebdomad., 1879) reports a case in which the suppression of urine lasted fifteen days before death ensued. OEdema was also present in this case. There are, indeed, other cases on record, in the more ancient literature of medicine, in which patients are alleged to have survived many months of total suppression of urine; but it may be safely affirmed that imposition of some sort or other was practised in these cases. Treatment. — Our notions of the treatment must vary accord- ing to the nature of the obstruction. Taking first those cases which are due to impaction of a stone in the ureter, it must appear that the use of ordinary diuretics cannot avail against a physical obstacle. Eeliquet^ has recorded a successful case in which he applied gutta-percha bands to the limbs, with a view of increasing the blood pressure in the kidneys. There is some- 1 Union Medicale, Xos. 69 and 70. 76 PHYSICAL PROPEETIES OF THE URINE. thing to be said in favor of means directed to excite the con- tractile power of the ureter. In my second case Dr. Garrod suggested, with this view, the use of turpentine, but it provoked vomiting and could not be persevered with. In a case reported by Carrere {Gaz. Hehd., 1879) ergot was given, recovery follow- ing shortly afterwards. Or remedies of an opposite class might be alternately tried with the purpose of relaxing the spasm of the ureter, such as opium, chloroform, belladonna, venesection, and warm baths. My own impression, however, is more in favor of mechanical means; and in reviewing the cases which have fallen under my notice, I cannot help thinking that some- thing further might have been attempted in this way with a prospect of advantage. One such means, namely, kneading and shampooing the renal region and the course of the ureter, was in two of my cases followed by a so immediate, though only transient, flow of urine, that I could scarcely doubt that it was due to the means employed.^ But in a large number, if not the majority of cases the impaction takes place near the bladder, where no direct force can be applied. Indirect means may, however, be tried. The physical condition is generally this : Above the calculus the ureter is open and distended with stag- nant urine ; at the seat of the lodgement, and below it, the ureter is contracted. A displacement either upwards or downwards would be likely to be followed by relief. To provoke such dis- placement, succussion of the body and various changes of posture might be tried. The patient should be directed to support him- self from time to time on his knees, with the upper half of the body depressed, and the sacrum might be repeatedly struck with the fist. The force of gravity would thus be brought in aid to coax the obstacle back toward the kidney. Or walking the patient between two assistants up and down stairs and about the room might be practised in the earlier periods of the case, with the object of facilitating the descent of the calculus into the bladder. Means of this class should be persevered in to the end, for experience is warrant that hopes may be entertained, even almost to the last, that the obstruction may be yet over- come. VI.— EEACTION OF THE UEINE. There is no property of the urine of more varied and im- portant significance than its reaction. Therewith is intimately connected the occurrence of several kinds of urinary deposits, together with the origin, growth, and medical treatment of gravel and urinary calculi. ^ Lately it has been recommended to open the ureter or the pelvis of the kidney above the obstruction, and so establish a permanent urinary fistula. [See Brit. Med. Journ., Dec. 1883.) REACTION OF THE URINE 77 The reaction of the urine is liable to be affected by : /oo<-/, the cold hath, medicinal suhstances, general dJse.ase, and drcdnipofiiiioii of the secretion. It is also important not only to distinguish acid from alkaline urine, but it is at least equally so to distinguish between alkalescence from fixed alkali (potash and soda) and alkalescence from the volatile alkali (ammonia). The most convenient method of ascertaining the reaction of the urine is by means of blue and red litmus paper. For deli- cate operations the violet-tinted papers are the best; and they answer both for acid and alkaline fluids — being turned red by the former and blue by the latter. To distinguish between the volatile and fixed alkali, the paper, aftej being rendered blue, should be allowed to dry in the open air. If the blue color persist after complete desiccation, the alkali is fixed ; if it dis- appear, and the original color be restored, the alkalescence is due to ammonia. The smell of the urine is also a useful indi- cation in such cases. Healthy urine is generally acid. This arises chiefly from the presence of a number of acid salts — phosphates and urates; partly also from free acids — lactic, oxalic, acetic, etc. In a number of observations by the present writer, it was found, on an average of nineteen days, that in a healthy man it required 14.10 grains of dried carbonate of soda to saturate the total daily acidity of the urine. Some days were found throughout to exhibit a feeble acidity; on one of these only 5.9 grains of dried carbonate of soda were necessary to neutralize the whole acidity. On other days the acidity ruled high ; one day the acidity equalled 22.34 grains of carbonate of soda. The circumstances which modify the reaction of the urine may be considered under the following headings : 1. Food and Fasting. — Dr. Bence Jones was the first to point out that the reaction of the urine holds a close relation to the digestion of food. He found, by examining the urine at short intervals, that a notable falling off in its acidity took place after a meal ; and that in numbers of healthy persons the urine became neutral or alkaline for two or three hours after breakfast and dinner. Doubts have been thrown on the conclusions of Dr. Bence Jones bj' Vogel, Beneke, Sellers, and Delavaud. Some years ago I undertook a series of experiments with a view of submitting this question to a fresh examination.^ The urine of a healthy person w^as examined at hourly periods after a meal, and its acidity or alkalescence carefully determined by volu- metrical analysis. My results confirmed, in the fullest manner, the observations of Dr. B. Jones. A meal, whether of animal, 1 See a paper by the author, entitled "A Contribution to Urology," in the Memoirs of the Manchester Lit. and Phil. Soc, 1859. 78 PHYSICAL PROPERTIES OF THE URINE. vegetable, or mixed food, was found invariably to depress the acidity of the urine, and in most instances to render it actually alkaline. To this movement the name of alkaline tide maj^, for the sake of brevity, be applied. After breakfast the alkaline tide was found to set in earlier than after dinner, and its dura- tion was more brief. In forty minutes after breakfast there appeared, nearly always, a sensible declension of ac^dit^^ The urine, however, never became actually alkaline, or even neutral, so soon. During the second hour after breakfast, the alkaline tide usually culminated ; but in about a third of the observa- tions the point of least acidity was not reached until the third hour. Then the tide turned ; during the fourth hour the urine was found to be rapidly recovering its lost reaction, and toward the end of that time it had usually regained its original acidit3^ Thus for about four hours breakfast exercised a depressing effect on the acidity of the urine; but the secretion was not actually alkaline usually for more than an hour, sometimes for two, and very rarely for three hours. The effect of dinner was not perceptible until the second hour after the meal. During the succeeding three hours (third, fourth, and fifth hours) the alkaline tide ran in its greatest strength. In the third and fourth hours the urine was always (with two exceptions) alkaline, when the meal had been of naixed food or animal diet. At the end of the sixth hour the tide had generally turned, and the acid reaction been restored. Three hours was the usual duration of the alkalescent state after dinner ; sometimes two hours ; more rarely four hours ; and on one occasion five hours. The amount of free alkali discharged after dinner was generally nearly double the quantity after breakfast. This was due, probably, to the fact that dinner was usually a much heavier meal than breakfast, and its impression on the system consequently more intense. The alkaline urine voided after food owed its reaction to fixed alkali, and not to ammonia. It was rich in earthy and alkaline phosphates. Sometimes it was clear when voided, but more commonly turbid, from the precipitation of earthy phosphates. Although the immediate effect of a meal was thus to depress the acidity of th6 urine, the more remote consequence was to main- tain and even increase the acidity. This was seen most dis- tinctly when comparison was made of the acidity of the morning urine, when supper had been taken the night before, with that of the morning urine when no supper had been taken. In the former case the free acid discharged in the hour preceding break- fast was enough to saturate 0.88 grain of dried carbonate of soda : whereas on the mornings after supperless nights the dis- charge of acid was only equal to 0.51 grain. The remote effect of animal food appeared considerably REACTION OF THE URINE. 79 greater than that of vegetable food : 80 that a highly animalized diet would tend in the long run to intenHify the acidity of the urine — a conclusion quite in harmony with ancient opinion. Clinically, the urine is rarely observed to be alkaline after food. For, although it may be alkaline as it leaves the kidneys during several hours a day, after the two principal meals, it is mixed in the bladder with acid urine secreted before and after the alkaline tide, and the whole product ejected by micturition is acid. It is necessary, therefore, in order to test the effect of a meal, to analyze the secretion, as it were, by examining it at hourly intervals. It happens occasionally, however, that the urine of an ordinary micturition is the isolated product of the alkaline tide. I have known even a calculous patient, whose urine habitually deposited large quantities of uric acid, to void an alkaline urine in the forenoon from the effect of breakfast. Dr. B. Jones considered the depression of the acidity of the urine after a meal to depend on the withdrawal of acid from the blood into the stomach for the purposes of digestion : whereby the blood became for the time less capable of yielding acid to the kidneys. On the completion of digestion the gastric juice was re-absorbed with the chyle and presently communicated its acid to the urine. An antagonism was thus supposed to exist between the stomach and kidneys ; when the stomach was empty its mucous membrane was neutral, while the urine on the con- trary was highly acid; but when the stomach was full, acid gastric juice was abundantly poured out on its mucous surface for the purposes of digestion, and at the same time the urine tended towards neutrality or alkalescence. While admitting the strong probability of some such corre- spondence, I am disposed to attribute the occurrence of the alka- line tide after meals mainly at least to a different cause — namely, to the entrance of the newly digested food into the blood. If, as is believed, the normal alkalescence of the blood is due to the preponderance of alkaline bases in all our ordinary articles of food, a meal is pro tanto a dose of alkali, and must necessarily, for a time, add to the alkalescence of the blood ; and as the kidneys have delegated to them the function of regulating the reaction of the blood, the urine immediately reflects any undue addition to, or subtraction from, the blood's proper alkalescence. This hypothesis is mainly supported by the coincidence of titHe w^hich exists between the j)assage of the digested food into the blood and the occurrence of the alkaline tide. The gastric juice is poured into the stomach immediately after a meal, but the acidity of the urine does not suffer depression for an hour or two afterwards — not in fact until the meal has been in great part absorbed. After the primary effect of a meal has passed off", the acidity 80 PHYSICAL PEOPERTIES OF THE URINE. of the urine slowly increases until food is taken again. The highest acidity is, therefore, always found after the longest fast- ing, or just before meals. In the early morning before break- fast, the urine was always found excessively acid, and deposited abundance of urates on cooling. There seems, however, a limit to the increase of the acidity after prolonged fasting; Dr. Bence Jones found that continuing to fast for twelve hours beyond the usual time of taking food did not intensify the acidity of the urine. 2. Eppects of Medicines. — Both mineral and vegetable adds, when administered in large quantities, tend to raise the acidity of the urine; but their effect is inconsiderable. Urine that is habitually alkaline can certainly not be rendered acid by the internal administration of acids even in very large quantities.^ The most powerful acidifiers of the urine are probably free car- bonic acid (Heller) and benzoic acid; the latter appears in the urine as hippuric acid. Alkaline substances have a much more powerful influence; and it is an easy matter to deprive the urine of its acid reaction and to render it strongly alkaline at pleasure. This effect may be attained by the caustic and carbonated alkalies, or by the alka- line salts of a certain group of vegetable acids — acetic, tartaric, citric, malic, and lactic acids. The most convenient for the purpose, as well as the least disturbing to the digestive organs, are the bicarbonates of potash and soda, and the acetates and citrates of the same bases. By the administration of these salts the urine may be kept persistently alkaline for weeks and months without detriment to the general health. It requires from 300 to 400 grains of the bicarbonate of potash, and about as much of the acetate and citrate, given in divided doses during the twenty-four hours, to keep the urine steadily alkaline in the adult. From numerous observations on different individuals, I found that, given in these large doses, about two-thirds of the alkali appeared in the urine as free carbonate; while the remain- ing third was expended in neutralizing the acidity of the urine and otherwise disposed of. The conversion of the acetates, citrates, etc., into carbonates, which was shown long since to occur by Wohler, takes place, according to Buchheim and Magawley, in the intestinal canal, and the salts in question are therefore absorbed into the blood as carbonates. The bicarbo- nates, acetates, and citrates, if moderately diluted, were not found to have any tendency to cause diarrhoea; the tartrates,, on the other hand, were always found to occasion more or less purging. 1 For further information on the action of acids on the urine, see Parkes, "On the Composition of the Urine," p. 145 et seq. See also a paper by Dr. Benoe Jones, St. George's Hosp. Keports, 1869. REACTION OF THHJ UIUNE, 81 The basic phosphate of soda, the eorrmioii pliospliate of soda, and borax, likewise possess the power of alkalizing the urine; but their eft'ect is very feeble, compared with that of the salts before mentioned. The common phosphate of soda, in the quantity of 640 grains in the twenty-four hours, in divided doses, produced a total alkalescence of the urine, only equal to 22 grains of carbonate of soda; whereas half the quantity of the acetate of potash produced an all<:alescence equal to 120 grains of carbonate of soda; 640 grains of the basic phosphate of soda produced an alkalescence equal to 37 grains of carbonate of soda; 320 grains of borax gave an alkalescence of 9 grains of carbonate of soda; this last salt proved difficult of toleration by the stomach. The power of alkalizing the urine is especially valuable in the treatment of urinary gravel and calculi; and to the chapter on the solvent treatment of urinary concretions I must refer the reader for further details on the subject. 3. The Cold Bath. — Duriau^ found that the urine became invariably alkaline after prolonged immersion of the body in a bath at a colder temperature than that of the body. Even the addition of nitric acid to the bath did not in the least alter the result; nor did the addition of carbonate of potash cause an increased alkalescence. 4. General Disease. — Frequent or persistent alkalescence of the urine, from fixed alkali, is an uncommon condition in any class of complaints; but a series of such cases have been recorded by Dr. Bence Jones,^ and I have observed a considerable number myself. In persons of debilitated constitutions, in the anaemic state which sometimes follows subacute rheumatism and gout, in chlorosis, atonic dyspepsia, chronic vomiting, and even in chronic phthisis, I have seen the urine present this character. Generally, the alkalescence came and went capriciously ; con- tinuing for two or three days, and then disappearing; but pres- ently returning again. Sometimes, however, the urine remained steadily alkaline for many weeks without intermission. In one case of this kind — a phthisical patient — the urine became acid on the occurrence of an attack of erysipelas of the head and face: it remained acid during the attack, and after its subsidence became again alkaline. The clinical significance of alkaline urine from fixed alkali is by no means serious; it is not associated with any special morbid state, but is an occasional accompaniment of debility and span^emia, from whatever cause arising. It is to be remem- bered, however, that there is a rare variety of urinary calculus 1 Archives Generales, 1856, I. 167. " - Med. Chir. Trans., vol. xxxv. 82 PHYSICAL PROPERTIES OF THE URINE. composed of phosphate of lime, which must be caused by some such condition of urine as this. Individuals passing an alkaline urine are generally suitable subjects for a tonic and stimulat- ing treatnient: and, if otherwise permissible, exercise in the open air. 5. Ammoniacal Urine. Decomposition of Urea — The impor- tance of distinguishing between urine which is alkaline from fixed alkali, and that which is alkaline from ammonia, has already been insisted on. The two conditions are contrasted, not only chemically, but equally so pathologically and clinically. Urine which is alkaline from fixed alkali is always secreted alkaline by the kidneys ; it deposits, if at all, simple amorphous phosphate of lime, of which the particles have no tendency to accrete into gravel or calculi; it has a sweet aromatic odor; it is perfectly bland and innocuous to the mucous membranes, and is not associated with inflammation of the urinary passages. Ammoniacal urine, on the other hand, is only in the rarest instances, and in the gravest circumstances, secreted ammo- niacal by the kidneys, but usually becomes so by an after- FiG. 3. The normal deposit from ammoniacal urine, showing crystals of ammoniaco-magnesian phosiihate, amorphous phosphate of lime, and spheres of urate of ammonia. change occurring in the lower urinary passages, or after it has been voided. Ammoniacal urine is always sedimentary; it deposits a mixture of the amorphous phosphate of lime and crystals of the ammoniaco-magnesian phosphate — sometimes, if the urine be concentrated, with the addition of lumpy spheres and rude dumb-bells of urate of ammonia (see Fig. 3). This deposit has a strong tendency to aggregate into masses or con- cretions; the urine has an ammoniacal and often an offensive REACTION OF THE UK7NK. 83 putrescent odor; it is highly irritating to tli<; uiucou.s rnoni- branes, and excites inilammation of them if the conlact ix; lony; continued. A urine alkaline from fixed alkali ([)otaHh or sodaj reflects a state of the blood; a urine alkaline from ammonia (if alkaline when voided) points to a local affection of some part of the lower urinary passages. This latter statement is, however, not to be taken altogether without ({ualification. In two instances (both cases of advanced Bright's disease) I have observed the urine to be ammoniacal as it flowed from the l)ladder without any clinical or post-mortem sign of inflammation of any part of the urinary passages, or any evidence of such delay in the evacuation of the urine as might determine decomposition of it in the bladder. One of these cases is referred to hereafter {see Bright's Disease). Dr. Graves {Clin. Leds., 1, p. 272) gives also two cases, one of continued fever, and the other of anasarca and ascites, in which the fresh urine contained large quantities of carbonate of ammonia without the least evidence of decomposi- tion after secretion. The transformation of urea into carbonate of ammonia is easily explained. One molecule of urea combines with two molecules of water to form one molecule of carbonate of ammonia: CO(NH,), + 2H,0 = (NHJ,C03 or C0^g^ + 2H,0=.C0.gg;g It is now well established that the production of ammoniacal urine is an example of bacterial fermentation. Pasteur showed that urea was changed into carbonate of ammonia by the action of a minute micrococcus — to which Cohn subsequently gave the name of Micrococcus urece. The power of decomposed organic matter and of stale urine to bring about this change with celerity is simply due to the fact that these decomposing materials are highly charged with bacteria of various kinds. It is not at all probable that Pasteur's micrococcus is the only organism which acts as a urea-ferment. There are, in all likelihood, other bac- teria capable of breaking up urea into carbonate of ammonia — though not, perhaps, with the same rapidity as the M. urese. This subject will come under notice again in the section on Microorganisms in the Urine (Chapt. iv. Sect. ix.). If the urine be ammoniacal lolwi voided, this is nearly always associated with inflammation of some part of the urinary mucous membrane — generally that of the bladder. Any condition which interferes with the complete emptying of the bladder in mictu- rition favors the production of ammoniacal urine. Consequently, 84 PHYSICAL PROPERTIES OF THE URINE, injuries to the spine determining paraplegia with paralysis of the bladder, obstinate urethral stricture, enlarged prostate, calculous concretions, morbid growths of foreign bodies in the bladder, are sooner or later complicated with ammoniacal urine. A very dis- tressing and intractable state of things is thus brought about. The ammoniacal urine irritates the mucous membrane and in- duces cystitis; and the purulent secretion thus engendered reacts on the urine and favors its decomposition. The two con- ditions naturally aggravate each other and perpetuate each other's existence after the original cause has passed away. Cystitis may, in this way, persist for years after the removal of a stone, or the cure of a stricture, which was its original cause. Dr. Owen Rees believes that the urine is sometimes alkaline from the secretion of an alkaline mucus by the mucous mem- brane of the bladder. When the membrane is irritated or in- flamed, as in paraplegia from spinal injuries, extroversion of the bladder, etc., the irritated membrane pours out, as he be- lieves, so much alkaline mucus that the reaction of the urine is changed thereby. Dr. Rees fortifies this hypothesis by an observation which he made on a case of extroverted bladder. He says : "As is usually the case in such persons, the anterior portion of the bladder was wanting ; so that the fundus of that viscus covered by mucous membrane was projected forward where the abdominal walls were deficient. The openings of the ureters were thus presented to view. The mucous membrane was red and inflamed from exposure, and an alkaline fluid was constantly discharging from its surface. To what this alkaline flux amounted during the day it was, of course, impossible to ascertain ; but it was more than suflicient to destroy the acidity of the urine, which was quite alkaline after flowing over the membrane. Thus a piece of blue litmus was applied to the openings of the ureters, so as to test the urine immediately it flowed from them : the paper was reddened, indicating that the urine was secreted of its natural character, and with its full amount of acidity. When, however, the litmus paper was applied about a quarter of an inch below the opening, so as to test the urine after it had passed over that short distance of mucous surface, its character was quite changed: it no longer reddened the blue litmus paper, but on the contrary was suf- ficiently alkaline to restore the blue color to those parts of the paper which had been previously reddened by exposure to the urine as it escaped fresh from the ureters."^ An opportunity occurred to me of repeating this observation on a patient with extroversion of the bladder; but I was not able to satisfy myself that the alkalinity of the exposed mucous 1 Lettsomain Lectures, Med. Times and Gaz., 1851. REACTION OF THE URINE. 85 membrane was not owing to blood-serum or lymph wliicb oozod from the raw excoriated surface, rather than to any mucous secretion such as might be yielded by a merely inflamed mucous membrane. The therapeutical indications in cases of ammoniacal urine from decomposition within the bladder, are clear enough. The first object is to remove, if possible, the impediment to the com- plete emptying of the viscus. In the case of a stone or foreign body in the bladder, and in stricture, this is within reach of surgical operation. If the cause be irremovable, or if the am- moniacal urine and cystitis persist after the removal of the original cause, all our efforts must be directed to prevent the sojourn in the bladder of the stale remnants of urine after micturition; this can be best effected by completely emptying the bladder two, three, or four times daily with an elastic catheter, which the patient may be taught to introduce for him- self. The bladder should also be washed out once or twice a day with an antiseptic solution — such as a saturated solution of boracic acid, or a weak dilution of carbolic acid. There is, however, another mode of washing out the bladder, which I have several times resorted to with advantage in a certain class of cases, more particularly in those in which chronic cystitis is kept up by the ammoniacal state of the urine, after the original cause has been removed. In these cases the patients are made to drink large quantities of water at regulated intervals. An abundant flow of very dilute urine is thereby kept up which effectually washes out the bladder and gradually restores the urine to its natural state. CHAPTEE III. CHEMICAL CONSTITUENTS OF THE URINE AND THEIR VARIATIONS— INORGANIC DEPOSITS. I.— PKELIMINAEY EEMAEKS ON UKINARY DEPOSITS AND THEIK CLASSIFICATION. A VERY scanty, light, cloudy deposit is natural even to the healthy urine after standing some hours. This usually sinks to the bottom ; but occasionally it floats like a cloud about the middle or near the surface. It is composed of epithelial scales (or remnants of them) from the* mucous surfaces of the bladder and urethra, and pelvis of the kidney. Of mucus, having the usual glairy character, there is no visible trace in perfectly healthy urine. Under a variety of unnatural circumstances more abundant deposits or sediments occur in urine; and a knowledge of their nature sometimes yields most important practical information. Urinary deposits are arranged in two divisions — Inorganic and Organic. Inorganic deposits include substances which, for the most part, exist naturally in the urine in a soluble state; but which, owing to their excessive quantity, or a change of reaction in the urine, or some other circumstance, are rendered insoluble, and thereby precipitated in a crystalline or amorphous condition. This division contains: Uric acid, the amorphous urates, urates of ammonia and soda, oxalate of lime, ammoniacal and earthy phosphates, carbonate of lime, cystine, leucine, and tyrosine. All these are soluble in mineral acids or in alkalies, and one of them (the amorphous urate) by simply warming the urine. Organic deposits embrace all those organic forms, of which the presence alone in urine is suificient, from their insolubility, to determine their subsidence. They do not belong in any pro- portion to the healthy secretion; and whenever present, they are merely suspended in it; so that when the urine is left at rest, they gravitate to the bottom and form a sediment. This group includes epithelial cells from the uriniferous tubes or from any part of the genito-urinary passages, casts or moulds (composed of a fibrinous matter) of the uriniferous tubes, oily particles, pus, blood, cancerous and tuberculous debris, sperma- URIO ACID. 87 tozoa, and bacteria. All these are insolublem acid.s and alkalies as applied in the ordinary examination of the urine. II.— URIC ACID, CjIIiN/V {Synonym — Litldc acid. ) Uric acid exists in normal urine in combination with alkaline bases; but under certain conditions it is precipitated in the free state, and forms a deposit of orange-red crystals. Naked-eye Characteks. — The crystalline nature of the deposit can nearly always be recognized by the naked eye ; but in rare instances the crystals are so small that they require the micro- scope for their detection. Uric acid crystals may form a lilm on the surface, or lie scattered as brilliant brown specks on the sides of the glass, or subside into a dense red deposit like cayenne pepper. The naked eye is nearly always sufficient to identify uric acid with, certainty, because no other brown crystals occur in urine as a spontaneous deposit. When the crystals are very minute, the deposit resembles the amorphous urate, but is denser, and sinks more rapidly. Urine depositing uric acid has com- monly a rich yellow or orange color, and is invariably acid. Micro-chemical Characters. — The primary form of uric acid is a rhombic prism or lozenge, and to some modification of Fig. 4. The simpler forms of uric acid crj'stals — quadrangular and oval tablets, cubes, six-sided tablets, lozenge and barrel-shaped figures. this figure the protean diversities of uric acid crystals mar all be referred. The angles of the crystals are sometimes almost 88 CHEMICAL CONSTITUENTS OF THE URINE, equal, and then quadrangular tables or almost perfect cubes are obtained (Fig. 4, a b). More frequently the angles are rounded oif (c d) so as^ to pro- duce ovoid s and barrel shapes. A still greater elongation pro- duces a rod, and when a number of these are joined together in a common centre, stars are produced. The beauty and end- FiG. 5. stars of uric acid. less variety of these stars are marvellous, and render them seductive microscopic objects (Figs. 5 and 6). Sometimes the rays extend only in one direction, and a fan- shaped figure is produced, or two fans are joined in a common centre (Fig. 6). Among the less common varieties may be mentioned pointed, solid-looking crystals, with a dark shading at either end (Fig. 7, a). When these lie flat, they have a totally different appearance, and resemble prisms of the triple phosphate {h b). Other forms are halbert-shaped (c), six-sided tablets (Fig. 4, e), etc. The most curious and varied forms of uric acid are gen- erally found in albuminous urines.^ Uric acid is excessively insoluble. It requires 1800 parts of boiling water and 15,000 parts of cold water for solution. It is ^ Some interesting details on the varying forms of uric acid crystals and the conditions under which they appear may be found in a paper by Dr. Wm. Ord, St. Thos. Hosp. Kep., 1870, p. 335. Dr. Ord returns to this subject, and gives some additional information in a paper in the Med. Chir. Trans., 1875. See also his work, "On the Influence of Colloids upon Crystalline Form and Cohesion." Lond., 1879. URIC ACID. 89 insoluble in all dilute acids, hut is decomposed with efferves- cence by strong nitric acid. Caustic alkalies dissolve it readily, Fig. 6. Stars aud spikes of uric acid. especially with the aid of heat. It dissolves also freely in weak solutions of the carbonates of lithia, potash, and soda, and in EiG. 7. Karer forms of uric acid crystals. solutions of borax and common phosphate of soda. It is in- soluble in alcohol and ether. It is entirely dissipated by a red 90 CHEMICAL CONSTITUENTS OF THE UEINE. heat. The most delicate mode of recognizing uric acid is by the murexid test. This is performed by taking a small quantity of the suspected substance and placing it on a porcelain dish or a slip of glass; a couple of drops of strong nitric acid are then added, and the heat of the spirit-lamp applied; the uric acid dissolves with eifervescence; the heat is continued until the liquid dries into a yellowish-red residue. If the residue, when cool, is touched with a rod dipped in caustic ammonia, a bright violet-blue (murexid) is instantly developed, which is perfectly characteristic. Quantitative determinations of uric acid in urine are generally made by adding excess of acetic or muriatic acid to a known quantity of the urine, and allowing it to stand for twenty-four hours to precipitate. The acid is thrown down in a crystalline form, and may be collected either by decantation and levigation, or on a weighed filter ; it is then dried and weighed. The Rev. W. Yernon Harcourt, in a long series of observations, has shown that the above process is liable to very great errors, even when the urine has been previously concentrated by evaporation. He obtained much more accurate results by the following method : ISTeutralize a third or fourth part of the urine of twenty-four hours, if alkaline with hydrochloric acid, or if acid with car- bonate of potash ; reduce this to IJ fluidounce by evaporation ; treat this with 3 drachms of hydrochloric acid combined with 1 J ounce of alcohol ; decant when the uric acid has been pre- cipitated and the liquid is clear; wash the deposit on a weighed filter first with alcohol, and when that dissolves no more, with equal parts of acetic acid and water; lastly, dry the filter and weigh. ^ Dr. Pavy^ estimates uric acid by making use of its reducing action on ammoniated solution of sulphate of copper (see Sugar). The total reducing power of the urine is first determined, and then the uric acid is precipitated by acetate of lead. The re- ducing power is then again determined, and the difierence of the two determinations gives the reducing power of the uric acid present. Mr. Cook finds it difficult to decide the determining point in the above method. He recommends the following process : To the alkalized urine, add a solution of sulphate of zinc, and col- lect the precipitate of urate of zinc which forms. Thoroughly wash the precipitate with saturated solution of urate of zinc, in order to remove urea and ammonia. The filter paper contain- ing the precipitate may then be placed in a urea-estimation ap- paratus, and treated with hypobromite of sodium. The urate 1 Med. Times and Gaz., 1869, vol. ii. p. 482. ^ Med. Chip. Trans., vol. Ixiii. URIC AC J D. 91 of zinc is decomposed, and the uric acid may he estimated hy the amount of nitrogen given off. (For details, see Brit. Med. Journ., April, 1882.) Origin and Occurrence. — The quantity of uric acid in the urine is very minute; and were it not for its sparing solubility and liability to he precipitated both before and after emission, its clinical significance would be very slight. The daily excretion of uric acid amounts to no more than 8 or 10 grains. Indi- viduals vary a good deal in the amounts which they habitually separate. In three healthy young students living on a similar diet and under similar circumstances, I found the following numbers: No. I (mean of 47 clays) 8.051 grains. " 2 (mean of 5 days) ....... 3.462 " " 3 (mean of 3 days) G.071 " Dr. Hammond found in his own case the daily average as high as 14.14 grains. The excretion of uric acid also presents considerable varia- tions in the same individual from day to day. The greatest oscillation of this sort observed by myself amounted to a difler- ence of more than one-half on two successive days: on the first day 5.45 grains were separated, and on the following day 11.7 grains. It was found that when the mode of life was tolerably uniform, the amounts separated in periods of five consecutive days varied only slightly from each other in the same individual. The occurrence of a spontaneous deposit of uric acid is by no means a sure indication of an increased excretion ; and I fre- quently found that those days on which a spontaneous deposit occurred, showed less uric acid tha^n those days on which no uric acid was spontaneously deposited. The mean daily quan- tity of uric acid separated in twelve days on which there was a deposit was 7.7 grains; and the mean of twenty-five other days on which no uric acid was spontaneously deposited was 7.3 grains. The digestion of food has a marked effect on the excretion of uric acid. I found it increased after eating, not only absolutely, but also relatively to the other solid matters of the urine. In the following table the results of seven days' ohservations on the effect of dinner are exhibited. Three periods are chosen for comparison, namely: 1, during the prevalence of the alka- line tide which corresponds with the passage of the digested food into the blood; 2, during the subsequent period in Avhich the acid of the urine is restored, but the effect of the meal still continues to be perceptible in the considerable quantity of solid 92 CHEMICAL CONSTITUENTS OF THE URINE, matters separated by the kidneys;^ and, 3, during sleep, which is also a time of fasting. Time of day. (Dinner at 2 p.m.) 4- 7 P.M., alkaline tide. 9-11 " acidity restored. 1— 7 a.m., urine of sleep. Uric acid, per 1000 grains of liquid urine. 0.40 grain. 0.18 " 0.39 " Uric acid per hour. 0.36 grain. 0.13 " 0.10 " Uric acid, per lou grains of solid urine. 0.83 grain. 0.34 " 0.60 " It is seen that the absolute quantity hourly secreted is three times greater during the period of the alkaline tide than during the other periods ; its proportion to the total solids is also very sensibly greater. Even its proportion to the water of the urine is greater than at any other period, though the urine of sleep generally (under the mode of life then followed) deposited amor- phous urates very copiously after standing a few hours, whereas the urine of the alkaline tide never deposited urates.^ It is further seen from the table that the amount of uric acid has no relation to the degree of acidity of the urine. Professor Ranke has shown that neither sex nor age, nor the height and weight of the body, have an^^ decided relation to the daily excretion of uric acid.^ The season of the year, and the animal or vegetable nature of the food, have little influence, provided the articles of diet are equally rich in nitrogen. The effect of exercise is uncertain; sometimes it increases, sometimes it diminishes the uric acid.* Pathologically, it is found that the daily excretion of uric acid is markedl}^ increased in the febrile state, in certain diseases of the liver, in strumous and tubercular subjects, in rickets, scurvy, and leukaemia, and after an attack of gout. On the other hand, it is diminished during the paroxysm of gout, and, according to Ranke, after large doses of quinine. Uric acid is nearly related, both chemically and physiologi- cally, to urea. Uric acid yields urea as one of the products of its decomposition, both by artificial means in the laboratory and within the animal body. ISTevertheless, the most exact observa- tions have failed to show that there is any inverse correspond- ence between the excretion of the two substances; usually urea and uric acid increase and diminish together. Clinical Significance of Ukic Acid. — From what has been already stated, it will be readily conceived that the clinical in- 1 See Table, p. 52. ^ The seven days' experiments here spoken of are the same seven days which are tabulated at p. 52. ^ Kanke, Ausscheidung d. Harnsaure beim Menschen, Munich, 1858. * See Parkes, on the Composition of the Urine,"'p. 88. URIC AG11>. 03 terest of uric acid in the uriiio lia.s not ko much to do witli the variations of its quantity, wliother absolute or rehitivo, as witli its precipitation in the free state, and the time and place of that precipitation. The circumstances favoral^le to the preci[)itation of free uric acid are, an acid reaction of the urine, and abeyance of the conditions which determine the precipitation of uric acid in combination (amorphous urates); these latter are considered in the next section. A deposit of uric acid occurring some twelve or twenty hours after emission has no pathological signification. IlealtJjy acid urines usually deposit uric acid as a normal event on long stand- ing. If the deposit take place within three or four hours after emission, the circumstance is certainly not natural; but it is not one requiring special therapeutical attention; it is frequently observed in convalescence from febrile complaints, especially articular rheumatism; also in the middle periods of chronic Bright's disease, in chorea, in certain types of diabetes, and in enlargements of the spleen. But if uric acid be precipitated before the urine cools, or im- mediately after, it cannot fail to awaken apprehensions that a similar event may take place within some part of the urinary passages, and give rise to the formation of gravel and calculi, with all their train of painful and dangerous consequences. A prophylactic treatment is urgently called for under such circum- stances, by which this danger may be warded ofi". But it will be more convenient to postpone the further consideration of this important subject to the sections which are specially devoted to the pathology and treatment of calculous disorders. The relation of uric acid to the pathology of gout has been studied with great success by Dr. Garrod. He has proved that the blood of a gouty patient is permanently surcharged with uric acid, and that the acid is deposited in combination with soda in the cartilaginous and fibrous tissues of the joints, and becomes the cause of the articular inflammations which are characteristic of gout. This unnatural accumulation appears to be due to a defective power of eliminating uric acid in the kid- neys. The kidneys themselves also suffer — their secreting tubules and the intertubular substance are clogged with urate deposits, and the foundation is laid of those atrophic changes which constitute one of the most fatal forms of chronic Bright's Disease. It maj^ be regarded as probable that the defective power of the kiclneys to eliminate uric acid in gout arises from a diminished alkalescence of the blood, and that the rational correction of this defect is, in addition to a revision of the diet- ary, a steady exhibition of the carbonates of lithia or potash in the intervals of the articular paroxysms. 94 CHEMICAL CONSTITUENTS OF THE URINE, III.— AMOKPHOUS URATES. [Synonyms^^amorphous lithates ; urate of ammonia of Prout and Bird ; urate of soda of Heintz and Lehmarin; lateritious deposit.) ]S"aked-eye Characters. — The " amorphous urate "'' usually occurs as a loose, reddish, pulverulent deposit wholly devoid of crystallization. Its color is always deeper than the urine from which it falls ; but the color varies extremely both in intensity and tint. It may be fawn, orange, brick-red, pink, or purplish. It commonly sinks soon and completely ; more rarely, especially in albuminous urines, the precipitate continues a long while diffused in the urine, giving it a milky appearance. If the pre- cipitation take place after the urine has been at rest in the urine glass, a film or bloom forms on the surface and sides, which is readily seen by inclining the glass to one side. By this pecu- liarity the amorphous urates may be distinguished from all other urinary deposits by the unaided senses. MiCRO-CHEMiCAL CHARACTERS. — Under the microscope the de- posit is found to be composed of minute particles or granules, coarser or finer, and more or less opaque, according to the close- ness of its aggregation (see Fig. 8). Fig. 8. Amorphous urate deposit. By warming the urine, the amorphous urate dissolves ; the light-colored and looser deposits disappear with a slight heat, but the deeper colored and denser ones require a more elevated temperature. As no other urinary deposit disappears with simple heat, this circumstance offers an easy means of recog- nition. The amorphous urate answers to the murexid test for uric acid. It is decomposed by the vegetable and mineral acids A M O R r H O U H U li A T E S . 95 (though only slowly in the cold by the former), and uric acid crystals are deposited, which iriay be recognized under the riiicro- scope. The urates dissolve in the caustic alkalies, and in solu- tions of the alkaline carbonates. They possess an intense afKnity for the brown and pink pigments of the urine, which they carry down with them when precipitated ; and the varied tints which they present as deposits depend on this circumstance. The chemical composition of this de])Osit has been a sul)ject of much dispute. Prout and Bird believed it to be com[)Osed of urate of ammonia, and it usually passes under that name in this country. In Germany it is commonly considered to be mainly composed of urate of soda. More recent observations indicate that neither of these views is correct ; it would appear rather that the amorphous urates have not a fixed and constant composition, but vary considerably in dififerent samples. In all, however, uric acid is combined with several bases — potash, soda, ammonia, and lime ; and this is the special chemical character- istic of the deposit, that it is composed of mixed urates. Some- times one base and sometimes another preponderates. The proportion of uric acid in the deposit is very large, but not con- stant. Scherer found a little over 80 per cent. ; Dr. Bence Jones over 90 per cent. This proportion is about twice as much as is necessary to form acid urates (biurates) with the bases present: so that about one-half of the uric acid is loosely united Avith the biurates to form the deposit, which, therefore, resembles in its chemical constitution the quadroxalate of potash. The loosely combined uric acid can be separated from the associated biurates by simply treating the deposit with warm water, or by repeatedly washing it on a filter with cold water. Dr. B. Jones found potash the most abundant base, next ammonia, and last soda, as the following table of his analyses shows : ' First analysis. Second analysis. Uric acid 94.36 91.06 Potassium 3.15 3.78 Ammonium . . . . . . .1.36 3.36 Sodium 1.11 1.87 Hassall and Scherer always found lime in not inconsiderable quantity. Dr. Bence Jones succeeded in producing artificiallv exact counterparts of the amorphous urates both with potash and soda. The precipitation of the amorphous urates depends on a con- junction of the following conditions : an acid reaction, low temperature, and concentration of tb£ urine. The occurrence ^ See a paper by Dr. Bence Jones in the Journal of the Chemical Society, June, 1862. 96 CHEMICAL CONSTITUENTS OF THE URINE. of this deposit is a sure sign of an acid reaction ; and the more acid the urine, the more liable is it to deposit the amorphous urates: A drop of acetic or nitric acid will frequently deter- mine at once the precipitation of the amorphous urates in a previously clear urine. The effect of temperature is very marked : and on cold winter mornings the urine voided on getting out of bed generally becomes turbid from precipitated urates a few hours after. The amorphous urate deposit is not a sign of excessive secre- tion of uric acid by the kidneys ; it indicates rather, that its proportion to the water of the urine is excessive. Urines of a high density, provided their reaction be acid and the tempera- ture low, usually deposit urates in healthy persons. There is this difference between the conditions favorable to the deposit of free uric acid and of the amorphous urates — that a high density or (concentration) favors the latter, and a low density (or dilution) favors the former. On a comparison of the densi- ties of a large number of urines, depositing respectively amor- phous urates and free uric acid, I found the mean sp. gr. of the former 1027, and of the latter 1021. It is familiarly observed that a urine which throws down urates, will begin to deposit free uric acid a few hours after, when it has become, quoad uric acid, less concentrated. The clinical significance of a urate deposit can be appreciated only after due consideration of the above physical and chemical conditions of its occurrence in the physiological state. I have already stated that no conclusion as to excessive elimination of uric acid can be drawn from the occurrence of the urate deposit. It has also been shown in a previous page, that during the absorption of food, and the flow of the alkaline tide, the excre- tion of uric acid is at its maximum, though the urine at this period very rarely deposits urates, owing to the depression or disappearance of its acidity : and conversely, that after long fasting the urine is very apt to deposit urates, because it is then concentrated and highly acid, though the hourly rate of excre- tion of uric acid is then at its lowest ebb. A deposit of amorphous urates may be regarded as having either a physiological or a pathological signification. Physio- logically, a urate deposit may be expected after profuse sweating, violent exercise, prolonged abstinence from food and drink, and in cold weather. Under these circumstances the deposit is occasional, and its color usually fawn or brownish. Pathologically, the most common determining cause of the precipitation of the amorphous urates is the febrile state. Even a slight degree of pyrexia, as in a common cold, is usually accompanied with a urate deposit. The frequent or constant occurrence of a brownish or red urate deposit without, or with only a feeble degree of pyrexia, C I i Y H T A L L I N K U K A 'J^ E S . 97 18 a circumstance to awaken Hii8])icionH of Honio HeriouB organic disease; but the indication is more general than speciaL Or- ganic disease of the lungs, heart, liver, spleen, or any other part, attended with emaciation and waste of the tissues, is usually accompanied with abundant deei)-colorcd urate deposit. Functional derangements of the digestive organs arc also generally accompanied by pale urate deposits in the urine. Their occurrence depends, in many cases at least, as Dr. B. Jones has indicated, on a connection between the reaction of the mucous membrane of the stomach and that of the urine. Treatment. — From what has been stated of the determining conditions of the amorphous urate deposit, it is evident that it seldom requires direct treatment. Its indications are of more service in diagnosis and prognosis than in therapeutics. Some- times the persistence of a urate deposit occasions such alarm to the patient that it may serve a good purpose to cause it to dis- appear, though no really curative end may be gained thereby. This is easily and harmlessly effected by a few two-scruple doses of citrate of potash. When this direct purpose is not aimed at, the treatment must be directed to the removal of the condition causing the deposit. Fig. 9. iy._CEYSTALLINE UKATES. Urate of soda and urate of ammonia are sometimes deposited separately in urine, in the crystalline form, and under circum- stances wholly different from those which determine the pre- cipitation of the amorphous urates. Urate of Soda. — Urate of soda is familiarly known as a con- stituent of gout}^ concretions. When the point of a lancet is thrust into one of the yellowish-white nodules so common on the ears of gouty persons, a whitish mortar-like matter escapes, which, un- der the microscope, is resolved into myriads of long delicate needles, ar- ranged into bundles or stars, or lying separately (Fig. 9, a «). These acicular forms are never de- posited spontaneously in the urine; but they may be readily produced by adding a little liquor sod?e to the com- mon amorphous urate, in a watch-glass, and allowing the solution so formed to concentrate by evaporation in the air (Fig. 9, b b). Urate of soda is a comparatively rare spontaneous deposit in urine. It 7 Urate of soda. a a. From a gouty concretion ; 6 6. Artificially prepared bj' adding liq. . sodce to the amorphous urate deposit. 98 CHEMICAL CONSTITUENTS OF THE URINE. occurs, however, occasionally in gout, and in the febrile state, especially in children. It forms a whitish or yellow sediment, which" sinks rapidly; it is associated with an acid reaction of the urine, and is frequently, if not generally, deposited in the bladder before the emission of the urine. In this respect it differs from the amorphous urate, which is never deposited until the urine has cooled. Under the microscope the spontaneous deposit of urate of soda exhibits irregular, opaque, globular, and lumpy masses, from which project spiny crystals, sometimes straight, sometimes variously curved [see Fig, 10). The occurrence of this deposit in the febrile complaints of infants and children probably depends on the urine being exces- sively scanty and concentrated and long detained in the bladder. Its appearance in such cases is temporary, and ceases on the reestablishment of the flow of urine. The annexed drawing (Fig. 10) was made from a deposit voided by a little child of three years. The child was suffering from severe infantile re- mittent, and no urine had been passed for two days. While I was examining the abdomen, the child cried, and the urine began to flow. The first portions were turbid and of a gamboge-yell ov7 color, and contained the spiny masses here delineated; after about an ounce of this had come away, several ounces of clear high-colored acid urine followed. Clinically, this deposit derives its chief importance from the circumstance that it is precipitated within the urinary passages. The spiny crystals irritate the mucous Tig. 10. membrane of the bladder Or urethra ; and the latter canal may even be blocked up by impaction of masses of the deposit. It may also form a nucleus around which calculous matter may hereafter aggregate. The great com- parative frequency of vesical calculi in children is not improbably owing to the occurrence of this deposit in the numerous fugitive febrile attacks to which children are subject.'^ Urate of Ammonia. — When urine becomes strongly ammoniacal, it is liable to precipitate urate of ammonia, in addition to the mixed phosphates which are necessarily deposited under those circumstances. The urate of ammonia 1 The correctness of this conjecture is fully borne out by the researches of Dr. Vandyke Carter on the Structure and Formation of Urinary Calculi. He found that urates formed the chief part of the nucleus in the majority of urinary calculi. (On the Microscopic Structure of Urinary Calculi, Lond., 1873.) Hedgehog crystals of urate of soda, spontaneously deposited from the urine of a child. OXALATE OF LIME. 99 has usually a dense w)ntc color; hut, I liave known it j)Osse88 a beautiful violet hue. Two forms are seen under the microscope. The most com- mon are spheres and i^lobular masses, which appear almost black by transmitted light, owing tf) their opacity {see Fig, 11, a). These Fio. n. spheres are easily obtained by leaving a urine containing the amorphous urate to stand in the air until it becomes ammoniacal. The second form [h) oc- curs as very minute slender dumb-bells: these generally lie singly; or two lie '^ _ 'C'y " i^ ^^ athwart each other so as to form a cross ; ^ '■-'4, n )>> ^ or three are united so as to form a ;,„^. / rosette. They become coarser " and '' / larger with long keeping of the urine. -^ This deposit has no special clinical sig- i-''">= "^ ammouia si-uutuntMmsiy niiicance: its occurrence is merely an '^'^p°«"''^i- «• spheres and giobuiar ■ ' • t , ■ ,1 • 11 "^ . masses; h. Bumb-bolls, crosses, incident in the ammoniacal decoraposi- rosettes. tion of the urine. It is a frequent ingredient of the secondary phosphatic crust which invests urinary calculi in the later periods of their growth (see Uro- lithiasis). v.— OXALATE OF LIME. {^Oxaluria ; oxalic acid diathesis.) E"aked-eye Characters. — A deposit of oxalate of lime is usually very scanty, and looks like a slight cloud of mucus. Owing to this, and its colorlessness, it seldom attracts the atten- tion of a patient. If, however, the urine be transferred into a urine-glass immediately after emission, as is usually practised in hospital wards, the following appearances are produced, which are sufficiently characteristic to enable the observer to recognize the deposit with certainty by the unaided eye. The sid'es of the glass are seen to be traversed by very numerous fine lines, running in bands, transverselj' or obliquely, giving an appear- ance as if the glass were finel}^ scratched. This appearance is due to the crystallization of the oxalate 011 the tine lines or inequalities left after cleaning the glass by towelling. The subsided portion is equally peculiar ; it consists of two parts — a soft, pale gray, mucous-looking sediment, occupying the bot- tom of the vessel, and overlying this a snow-white denser layer with an undulating but sharply limited surface. The only other substance which crystallizes in lines on the sides of the glass is uric acid; this is easily discriminated by the greater coarseness of the lines and their more or less brown color. 100 CUEMICAL CONSTITUENTS OF THE URINE, Micro-chemical Characters. — Oxalate of lime occurs in very minute crystals, the largest only appearing to the naked eye as sparkling points. Two forms are met with. The most common are octahedra, greatly shortened, or flattened, in one direction. The crystals present different appearances according to the side on which they lie. Commonly they rest on their short axis, and appear as squares crossed diagonally by a pair of lines (Fig. 12, a). As they roll over in the lield of the micro- Fio. V2. Oxalate of lime, o, h, c. Octahedra in "various positions ; d. Pyramids ; e. Pyramids witli intervening square bases. scope, they assume various forms — lengthened, pointed octa- hedra, crossed parallelograms, etc. (6, c). Sometimes half-crystals are seen — four-sided pyramids on a square base {d); and some- times two such pyramids, instead of being united by their bases to form the ordinary octahedron, are separated by a short square prism (e). The second form of oxalate of lime is that of dumb- bells and minute ovoids and circles (Fig. 13). The different appearances are produced by the diiferent postures assumed by the objects; and, as they roll over in the field of the microscope, the dumb-bell is seen to change to an ovoid or circle, and vice versa. Their real shape is that of an oval or circular disk, with rounded margins, and a depression in the centre on either face. The dumb-bells are probably identical in composition with the octahedra. Dr. Bird, in his later editions, expressed a doubt on this point, on the ground of their different behavior with O X A I. A 'J' E O V L I M E . 101 polarized liglit,' and suii^i^cstod tliat tlicy consisted of oxalurate of lime. Sehiuick has recently shown that oxalurate of ammonia may be found in normal urine.^ If this [)r(>ve to be universally true, it would afford an easy explanation of the frequent occur- rence of oxalate of lime in urine. The precipitation of oxalate ¥w. 13. Dumb-bells and ovoids of oxalate of lime. of lime as dumb-bells depends on some physical condition which interferes with the ordinarj^ crystallization. Yery frequently urine depositing dumb-bells contains little masses of viscid mucus; and it seems probable that a certain viscidity of the urine is essential to this globular precipitation.^ Oxalate of lime is insoluble in alcohol, ether, water, and the vegetable acids; but it dissolves readily in the mineral acids. The urine depositing it is usuall}^ high-colored and acid ; very rarely neutral or faintly alkaline ; and never, so far as I have seen, freely alkaline. Oxalate of lime is often conjoined with uric acid and the amorphous urates ; much more rarely with the stellar phosphate of lime. Production and Occurrence. — The frequent occurrence of oxalic acid in the urine cannot be a matter of surprise when it is remembered that it differs from carbonic acid — one of -the 1 Thudichum states that octahedra of oxalate of lime do polarize light, and that there is no reason to believe that the dumb-bells difter from them in compo- sition. 2 Proceedings of Eoy. Soc, 1867. ^ The precipitation of carbonate of lime in spheres and close dumb-bells in the viscid urine of the horse is an example of the same kind. Mr. Kainey has shown a much wider application of the same principle in the calcifications which take place naturally in the hard tissues of the body. See Med.-Chir. Eev., vol. xx. p. 4-51. 102 CHEMICAL CONSTITUENTS OF THE URINE. chief final products of the disintegration of the tissues — only in possessing half an atom less of oxygen. It constitutes probably one of the penultimate stages in the series of decompositions through which the effete tissues pass preparatory to their final exit from the body. A large number of substances which occur in the body (uric acid, creatin, fats, starch, sugar, etc.) can be made to yield oxalic acid in the laboratory; and it is highly probable that a similar change occurs in the living economy. With regard to uric acid, this has been positively ascertained by Wohler; and Dr. Garrod has succeeded in showing that oxalic acid is present, sometimes at least, in the blood. It is therefore easy to understand how oxalic acid should exist in urine ; also that it may be partly derived from the blood and appear in the urine at the moment of secretion, and partly be produced after the urine is secreted by conversion from uric acid. Dr. Owen Rees has nevertheless expressed his strong disbelief in the existence of oxalate of lime in the blood, appar- ently on the ground of the chemical difiiculty in conceiving that oxalate of lime, from its insolubility, could exist dissolved in the blood ; he contends that all the oxalate of lime found in urine is produced from uric acid after separation from the blood. ^ These theoretical objections, however, do not avail against the positive fact, that oxalic acid and its compounds, even the in- soluble oxalate of lime, pass through the blood into the urine when introduced into the stomach. "Wohler found that oxalic acid given to dogs caused oxalate of lime to appear in the urine. Piotrowsk}^ confirmed these results by experiments on himself. He took, in divided doses, from 80 to 100 grains of oxalic acid in the course of about six hours, and found that from 8 to 14 per cent, appeared in the urine as oxalate of lime, mixed with a little alkaline oxalate. Similar results were obtained with the oxalate of soda. When the insoluble oxalate of lime was taken in the same doses, very much less of it appeared in the urine ; still about 1| per cent, could be recovered.^ Clinical Significance. — Distinction must be made between slight occasional deposits, and large quantities occurring per- sistently. In the former case, it cannot be said positively that there is any departure from the normal state, seeing that oxalic acid is in all probability a natural constituent of urine; at least, it is constantly found in the urine of perfectly healthy individuals. But when the deposit is constant and large, an abnormal state must be recognized to exist; and we are called upon to con- 1 " On Calculous Disease." Croonian Lectures for 1856, pp. 2 et seq. 2 Archiv f. Physiol. Heilk., 1857, p. 122. Dr. Leared and Dr. Dyce Duck- worth have also found that taking ^iij of lime-water or a grain of oxalic acid caused oxalate of lime crystals to appear in the urine of healthy persons. St. Barthol. Hosp. Rep., 1866, p. 160; and Med. Times and Gaz., 1867, I. 219. OXAJ.A'l'K OF LIMK. 103 sider what puth()loii:;iciil sii^niiicai)cc it rruiy liuve, and vvhctlicr it siipi)liuH any iiidicalionw for trcatrnojit. The most obvious inference 18, that there exists in such a case a liability to the formation of an oxalate of lime calculus. 'I'his point, and the preventive treatment to be followed, will be con- sidered in the section on calculous disease. But a much wider significance has been given by some authors to oxalate of lime deposits; and a certain group of symptoms which are alleged to accompany these deposits, has been erected into a distinct pathological state under the name of the oxalic acid diathesis. Dr. Prout was the lirst to promulgate this view; and he has been followed by Dr. Bird and Dr. Begbie. Dr. Bird gives the following account of the symptoms which accompany oxaluria: "They" (the patients) "are generally much emaci- ated, excepting in slight cases, .extremely nervous, painfully susceptible to external impressions, often hypochondriacal to an extreme degree, and in very man}- cases labor under the im- pression that they are about to fall victims to consumption. They complain bitterly of incapability of exerting themselves, the slightest exertion bringing on fatigue. Some feverish excite- ment, with the palms of the hands and soles of the feet dry and parched, especially in the evening, is often present in severe cases. In temper they are irritable and excitable; in men the sexual power is generally deficient and often absent. A severe and constant pain, or sense of weight across the loins, is gen- erally a prominent symptom, with, often, some amount of irri- tabilit}' of the bladder. The mental faculties are generally but slightly affected, loss of memory being sometimes more or less present." ("Urinary Deposits," 5th ed., p. 251.) This train of sj^mptoms is familiar enough to every prac- titioner : and the occurrence of oxaluria in such cases is un- doubtedly common enough ; but these symptoms may be present in typical completeness without oxaluria, and conversely oxaluria may exist in its highest intensity, and even go on to the forma- tion of a mulberry calculus, without evoking any of the above- mentioned symptoms. Every one who has had experience in calculous disorders cannot have failed to observe that the sub- jects of mulberry calculus, especially children, are not unfre- quently in the enjoyment of blooming health so long as no local irritation has been set up by the concretion. It will also not fail to be remarked that the symptoms attributed to oxaluria are almost identical with those attributed to spermatorrhoea. Disturbed equilibrium and loss of tone of the nervous system, with symptoms (more or less intense) of impaired digestion, are unfortunately a too common resultant of the intense activity of mind and body, and the trying wear and tear of modern life : and both physician and patient are naturally anxious to find 104 CHEMICAL CONSTITUENTS OF THE URINE. some material alteration to account for a condition which is sufficiently serious, and which is remarkable for its want of defi- nition. The patient often fixes on some derangement of the sexual function, generally, in these times, on spermatorrhoea, under the inspiration of unscrupulous publications too widely circulated among the curious public ; or on heart disease, con- sumption, or gravel. The physician is able by means of phy- sical examination to set aside these more open delusions, but falls himself into the trap of his own ingenuity, and is only more elaborately wrong than his patient. He finds crystals of oxalate of lime in the urine, and persuades himself that he has discovered the first link in the chain of consequences. It may be much questioned (and I certainly see no necessit}^ for such a supposition) whether there be any morbid condition ante- cedent to the plain symptoms of the case, namely, an overtasked and disturbed nervous system, and a mismanaged and deranged digestion. The facts and considerations which lead to the above reflec- tions are : 1. Intense oxaluria may exist persistently without evoking the group of symptoms attributed to the oxalic diathesis. 2. This group of sj^mptoms ma}^ exist in typical development without the occurrence of deposits of oxalate of lime in the urine. 3. The most varied morbid states are found to coexist with oxaluria. I have been in the habit for many years of noting the symptoms and pathological states of those patients in the Manchester Infirmary who had pronounced oxalate of lime de- posits, rive out of every six exhibited none of the symptoms attributed to oxaluria. Almost every variety of disease was occasionally found associated therewith. The following espe- cially were observed : chronic phthisis, cardiac afi'ections, em- physema with chronic bronchitis, chronic rheumatism, ansemia, hemiplegia, malignant disease of the liver and stomach, chronic vomiting, and cirrhosis. I am strongly convinced, that oxaluria arises from a variety of conditions — many of them not accompanied by appreciable departures from health — in which the assimilation of food or the disintegration of the tissues goes on imperfectly; .and that it is impossible to assign any constant train of symptoms as the cause or the consequence of oxaluria. At the most, oxaluria is only one in a long list of symptoms, and one of the least significant. Beneke, who has subjected this question to an elaborate exami- nation, both in the way of experiment and observation, has formulated the following propositions, which appear to me to be well founded : OXALATE OK LIMK. 105 1. Oxaluria, a condition which accorn[)HnicH the litz;}jlor of severer forms of illness, has its proximate cause in an impeded metamorphosis — that is, in an insufficient activity of that stage of oxidation which changes oxalic acid into carhonic acid. 2. Oxalic acid has, if not its sole, its chief source in the azo- tized constituents of the blood and food; everything, tljerefore, which retards the metamorphosis of these constituents occasions oxaluria, 3. Such a retardation of the metamorphosis of the azotized constituents of the blood may be determined by the following causes : a. Abuse of azotized articles of food (direct retardation). b. Abuse of saccharine and starchy articles of food (indirect retardation). c. Insufficiency of the red blood-corpuscles and (eventually) diminished oxidation. d. Insufficient enjoyment of pure, fresh, ventilated air. e. Organic lesions which in any way impede respiration and the circulation of the blood. /. Conditions of the nervous system which bear a character of depression, wdiether these arise primarily from mental de- rangement or from pathological states of the blood. 4. Excess of alkaline bases in the blood, which, as numerous observations tend to show, plays an important part among the etiological conditions of oxaluria; and it is not improbable that an increased production of lactic and butyric acids in the diges- tive canal, consequent thereupon, impedes the development of the red blood-corpuscles, and thereby generates that chlorotic state which so often occasions and accompanies oxaluria. 5. Catarrhal conditions of the intestinal mucous membrane, in case they are accompanied by oxaluria, have at most only a common source. They may determine oxaluria by causing deranged digestion, but cannot be considered as its proximate cause.'^ Treatment, — After the foregoing reasoning and conclusions, it is scarcely necessary to say that oxaluria does not, in the opinion of the present writer, furnish special indications for treatment ; nevertheless it will be found that, apart from the existence of organic disease, the conditions most frequently found associated with oxaluria, varied as they are, call for a toler- ably uniform therapeutical action. They demand a quickening of the oxidation processes, and a careful regulation of the diet. The skin should be encouraged to activity by systematic use of cold sponging, friction of the skin with flesh-brushes, wearing ^ Zur Entwicklungsgeschichte d. Oxiilarie, bv E. W Beneke. Gottingen, 1852. 106 CHEMICAL COXSTITJENTS OF THE URINE. of flannel vests and drawers, regulated exercise in the open air — if available, horse exercise. Many of the cases yield only to repeated change of air ; the bracing atmosphere of upland and sea-side localities generally suits the best. It will often be found advantageous to withdraw for a time the use of tea and coffee, and to substitute milk; or if this prove heavy, milk mixed with one-fourth of lime-water. The diet should be judiciously com- pounded of due proportions of animal and vegetable substances — diminishing the one or the other group of aliments according to the ascertained idiosyncrasy of the patient. He must be cautioned against heavy meals, and trained to partake more moderately of four meals a day. Digestion may be promoted by the administration of the mineral acids in light bitter infu- sions, or by small doses of the bicarbonate of potash in the same combination. It is not easy to determine beforehand which of these opposite medicaments will prove most grateful to the stomach. The rule of choice is, to administer the acid when the dyspeptic symptoms point to an atonic state of the organ and of the body generally, and the alkali when the signs point to gastric and general irritation. YI.— CYSTINE (CgH^NSO^). [Synonym — -cystic oxide.) Cystine or cystic oxide is a crystalline body of great rarity,, v^hich is found only under certain abnormal conditions in the bodies of animals. Hitherto it has been detected with certainty only in man and the dog. Oloetta asserts that he found it once in the kidneys of an ox. Cystine was discovered by Wollaston in 1805, in a urinary calculus which was mainly composed of it. Since that time a considerable number of cystine calculi have been found in dif- ferent parts of Europe and America; but, as compared with other urinary concretions, this is one of the most rare. As a urinary deposit, cystine has been even less frequently met with than as a calculus ; and as nothing is known touching the organic processes and constitutional states in which cystine is produced, the clinical interest attaching to it is for the most part conflned to its manifestations as gravel and calculus. A number of cases have, however, been observed where cystine existed simply as a urinary deposit, or dissolved in the urine. ^ 1 Niemann (Deutscli. Arch. f. klin. Medicin, Bd. xviii. p. 232) has collected 52 cases of cystinuria. The following additional cases may be referred to : Loebisch, Liebis's Annalen, 182; Southam, Brit. Med. Journ:, II., 1876, and II., 1878; Guyot, Progres Medical, 1878, No, 10; Ebstein, Deutsehes Arch. f. klin. Med., Bd. xxiii. ; Ultzmann, Med. Pr., No. 29, 1878; Wood, Bost. Med. and Surg. Journal, 1878. Y S '1' 1 N K . 107 The followiTiii;' case of cy>stine calculuH witli coiicurront cjKti- niiria occurred in the Matiche.ster Iniirmary : J. M., set. 57, admitted June 15, 1874. There was no history of stone or gravel in any member of his. family. He was quite healthy until January, 1873, when he sulfered from repeated attacks of renal colic. In April, 1873, symptoms of vesical calculus appeared, and these have wmtinued ever since. On sounding, a stone was found in the bladder. The urine contained a good deal of pus, and under the microscope numerous well-formed hexagonal crystals of cystine were detected (Fig. 14). Fig. 14. Crystals of cystine spontaneoiTsly voided with tlie urine of J. M. This man was subjected to one sittins: with the lithotrite by Mr. Southam. Much irritation of the bladder followed, with severe bron- chitis, of which the patient died a fortnight after the operation. After death extensive pyelitis with sacculation of the kidneys was found ; and broken portions of a cystine calculus were discovered in the bladder. Generally, urine depositing cystine is turbid when voided; and on standing, a copious light sediment subsides, much re- sembling (to the naked eye) fawn-colored lithates. The urine from which cystine is deposited has sometimes a peculiar sweet- briar odor, a honey-yellow color, and an oily appearance. It ts usually faintly acid and very liable to spontaneous decomposi- tion, in the course of which it evolves sulphuretted hydrogen, and blackens white glass vessels. Dr. Golding Bird observed that urine containing cystine changed from yellow to green when it became decomposed. A few drops of acetic acid always precipitate an additional quantity of cystine from the supernatant urine; and if a urine 108 CHEMICAL CONSTITUENTS OF THE URINE, containing cystine holds it all in solution, as may happen when the quantit}'' is very small, acetic acid throws it down. A deposit of cystine is not dissolved by heat, nor by the vege- table acids. It is instantly dissolved by caustic ammonia, and if the solution be exposed in a watch-glass to evaporation in the air, beautiful six-sided crystals are obtained as the volatile alkali exhales (Fig. 15). This is the characteristic reaction of cystine, Fig. 15. Cystine. Hexagonal tablets and prisms from an evaporated ammoniacal solution. and leads to its easy identification. Cystine is also soluble in the carbonates of the fixed alkalies ; but not in carbonate of ammonia, which, indeed, is its best precipitant from acid solu- tions. It is soluble also in the mineral acids, but insoluble in acetic and tartaric acids. It is insoluble in water and alcohol. Heated on platina foil, it evolves thick white fumes, having a peculiar offensive odor resembling garlic. Cystine is a body of very weak aflinities, without taste or smell ; it acts as a feeble base, and forms crj^stalline compounds with nitric and hydrochloric acids. According to Pelouze, it may also play the part of an acid; he obtained two compounds with silver, which he denominated cystates.^ A spontaneous deposit of cystine in urine is composed of 1 "Note sur la cystine," 'by Peloiize, appended to Civiale's M^moire sur les calculs de cystine, at p. 441 of Civiale's treatise Du traitement medical de la pierre. Some further consideration respecting the constitution and physiological relations of cystine may be found in a paper, by J. Dewar and A. Gamgee, in the Journ. for Anat. and Physiol., 1870. CYSTINE. 109 hexagonal tablets. Wlieu the aininoniacal solution of cystine is allowed to evaporate in the air, magnificent crystals are obtained, which furnish brilliant o]>jects for the microscope. Cystine is dimorphous, and crystallizes in two forms, namely, as six-sided tablets and square prisms {see Fig. 15). The ammoniacal solution generally deposits hexagonal plates only, or these mixed with a few prisms; sometimes, however, the prisms are more abundant than the plates. The prisms either lie singly or form stars: they refract light strongly, and the facets which lie slantingly out of the direct line of vision appear perfectly black, contrasting with the brilliant lustrous white of the planes through which the light passes vertically. This gives a peculiar striped appearance to the prisms, and causes them to appear deceptively six-sided. The hexagonal tablets have an iridescent mother-of-pearl, lustre; their surfaces are often beautifully chased by lines of secondary crystallization ; they also form thick rosettes of great brilliancy. The production of cystine in the animal body has as yet re- ceived no elucidation. It may, hoAvever, be assumed that it preexists in the blood, and is merely separated by the kidneys. The most remarkable fact respecting the constitution of cystine is the large amount of sulphur (nearly 26 per cent.) v^hich it contains. The close analogy of composition between it and taurine, renders it not improbable that the liver is the origi- nal source of cystine;^ the discovery of cystine in the livers of typhus patients by Scherer^ lends support to this view; and Marowsky^ also found cystinuria accompanying a diminished secretion of bile. Later researches, however,* have thrown doubt on this theory. Ebstein has reported a case in which cystinuria, accompanied by albuminuria, suddenly' occurred in the course of joint rheuma- tism, the joint pains at the same time diminishing. After about a fortnight's duration, the albumen and the cystine suddenly disappeared from the urine. The other constituents of the urine have not been found altered in any constant manner in cystinuria; and the later 1 The close connection between cystine and taurine may be gathered at a glance by a comparison of their composition per cent. : Cystine. Taurine. Carbon 30.00 19.20 Hydrogen 5.00 5.00 NitrogW 11.66 11.20 O^xygen 26.66 38.40 Sulphur 26.66 25.60 2 Arcbiv f. Path. Anat., Bd. x. p. 228. 3 Deutsch. Arch. f. Idin. Medicin, Bd. iv. p. 449. * See Niemann, loc. cit. p. 232. 110 CHEMICAL CONSTITUENTS OF THE URINE. analyses of Beale^ and ToeP tend to support the original opinion of Civiale, that in cystinuria, as in most other calculous states, the composition of the urine, apart from the dominant calculus- forming constituent, is normal. It would be of interest to de- termine the amount of unoxidized sulphur voided with the urine in these cases. When it is remembered that from 3 to 5 grains of unoxidized sulphur are daily discharged with the urine by healthy men,^ it would seem a priori not improbable that cystine is onW the sulphur extractive in a new form. If it be so, one would expect the unoxidized sulphur to be diminished in cys- tinuria. The excretion of sulphuric acid was not found dimin- ished in a case examined by Beale. Loebisch and Memann, however, have observed in their cases, that the total amount of sulphuric acid excreted, calculated absolutely and also in rela- tion to the nitrogen present, was somewhat less than normal. Niemann also found a diminution of the uric acid excreted, but Ebstein came to the conclusion that a diminution of urea, uric acid, or sulphuric acid could not be proved in cystinuria. Deposits of cystine are very bulky; but the quantity, when weighed, is found unexpectedly small. Percentage determina- tions have been made by Prout and Beale. The former found 0.024, and the latter 0.09. Loebisch and ISTiemann have each determined the daily excretion, and have obtained as the daily average 0.393 grain and 0.509 grain respectively. Cystine may persist in the urine for many years ; it may dis- appear for a while, and reappear again after a longer or shorter interval ; or it may disappear permanently. It is sometimes succeeded by deposits of uric acid. The connection of cystine in the urine with deposits of the earthy phosphates, on which Prout and Civiale insist, is probably nothing more than a coin- cidence depending on the strong tendency of urine containing cystine to decompose and become ammoniacal, whereby the phosphates are necessarily precipitated. One of the most curious circumstances in the history of cys- tine is the unquestionable tendency which it shows to run in families. The facts bearing on this point will be referred to in treating of cystine calculus. Cystine has been found more commonly in males than in females, and mostly in children and young adults ; though no age is exempt. Dr. Shearman, of Rotherham, believes that scrofulous children and chlorotic females are especially liable to cystinuria. In a j^oung woman from whom Mr. Jordan ex- ^ Urine and Urinary Calculi, p. 311. 2 Ann. der Cbem. u. Pliarm., Ed. xcvi. p. 24. ^ Konalds : Phil. Trans., 1847, p. 461. The observations of Konalds have^,been since confirmed by Griffith and Parkes. The same has been found in the urine of dogs by Bischoff and Yoit. XANTHINE. Ill tractcd a cystine calculus Borrie years ago, in the; jMancliCKlei- Infirmary, I found considerable tuberculous consolidation of both apicos. The more recent researches of Fabre' do not su])- port the opinions of Dr. Shearman. Fabre examined the urine of a large number of tu])erculous persons and of thirty-six strumous children, but failed to detect a trace of cystine. In fifteen chlorotic females he likewise obtained negative results. It is undoubted that persons niay void cystine for years, with- out any other deviation from health than what is caused by the physical irritation of the concretions, when these form. The brothers Planta, operated on by Civiale for immense cystine calculi, were known to have been excreting cystine in (quantity for six years continuously, without any impairment of health. The sisters observed by Toel looked well, and were perfectly healthy, except that they were liable to nephritic pains from time to time, when they passed small calculi and gravel. The clinical significance of cystine is therefore chiefl}^, if not wholly, the danger of the formation of stone and gravel. The treatment of cystinuria, apart from that which is designed to prevent the formation of concretions, is necessarilj^, so long as the rationale of its production is so obscure, unsatisfactory. Dr. Prout believed he saw benefit from the long-continued use of nitro-muriatic acid. Dr. Bird, on the other hand, found the same remedy useless. If chlorosis or struma coexist with cystinuria, these will of course demand their appropriate treat- ment; but as yet nothing is known which can i:)retend to have any direct influence in checking the formation of cystine. VII.— XANTHINE (CgH^N^OJ. • [Synonyms — xanthic oxide ; U7'ic oxide.) This rare substance was originally discovered by Dr. Marcet, about the year 1817, in a urinary calculus given to him by Dr. Babington. This concretion weighed only 8 grains, and had apparently been passed spontaneously. In 1816 the elder Lang- enbeck removed from a peasant boy, eight years of age, a stone as large as a small egg, which was afterwards identified by Stromeyer with the xanthic oxide or xanthine of Marcet. In 1837 a portion of this stone was analyzed by Liebig and Wohler ;'- in 1846 it was reexamined by Bodo linger^ with identical re- sults. The name Xanthine was originally used by Unger to ' A. Fabre : De la cystine, etc. Paris Tliesis, 1859. Fabre calls attention to the hexagonal appearance of uric acid crystals when precipitated by acetic acid ; and he attributes the conclusions of Shearman to confounding these with cystine crystals. 2 Poggend. Ann. der Physix, 1837, Bd. xli. p. 393. 3 Liebig's Ann. der Chem. und Pharm., Bd. Iviii. p. 17. 112 CHEMICAL CONSTITUENTS OF THE UKINE. designate a substance found by him in guano, which he at first considered identical with Marcet's xanthic oxide, but which he subsequently established as a new substance under the name of guanine; tlie name xanthine then passed permanently to Mar- cet's xanthic oxide. In 1829, Laugier^ described some minute calculi obtained from a patient who had passed several. Three of these were handed over to Laugier; the largest of them weighed less than one-sixth of a grain. Their deep yellow color, their spherical form, their smooth surface, seemed to indicate that they con- sisted of uric acid. They proved, however, to be xanthine, and yielded the characteristic reaction with nitric acid and potash. Professor Dulk, of Konigsberg, removed a xanthine calculus weighing 7 grains from the urethra of a bo}^ (Bird). In 1866, Mr. T. Taylor discovered in the Museum of the London College of Surgeons a calculus composed of nearly pure xanthine. When entire it weighed 90 grains. It was extracted from a Mussulman child, four years old, by Mr. Coles, a surgeon in the employ of the East India Company.^ Xanthine is a substance closely connected with uric acid, differing from it in composition only in possessing one atom less of oxygen. Xanthine has been discovered by Scherer in the blood ; also in the muscles, liver, spleen, and brain. Scherer* further states that a very minute quantity of xanthine is a natu- ral constituent of healthy urine. Heller has been unable to convince himself of the correctness of this statement.'' Xanthine has been met with five times (as above recorded)^ as a urinary calculus : as a urinary deposit it is alleged to have been encountered by Bird, Douglas Maclagan, and Bence Jones. Maclagan found it mixed with earthy phosphates in the urin^ of a hysterical girl.^ Dr. Bence Jones's case was a school-boy between nine and ten years of age. Three years before he had suffered an attack resembling nephritic colic, but without sub- sequent passage of a stone. When first seen, the urine made at night contained a small quantity of albumen, but that of the morning contained none. A month later the urine was found " quite thick and deep colored. A drop was placed under the microscope, and a crystalline deposit was found resembling one form of uric acid. From this form T considered the deposit ^ Journ. de Chim. Med., vol. v. 1st series. 2 Path. Soc. Trans., xix. 275. =* Liebig's Ann. d. Ch. u. Ph., Bd. cvii. Heft 3, 1858. * Heller's Harnconcretionen, p. 131, note. ^ A short mention of two other cases which occurred in America is found in the Brit. Med. Journ , Jany. 1883, p. 148. *• Edin. Med. Journ., 1858, p. 121. Scherer doubts this case; and thinks the reaction mentioned by Maclagan insufficiently characteristic. X AINTIJINE. 113 was uric acid — (the crystals were pointed ovhIh). On oxaniinin_<^ the unfiltered urine for albumen by heat, I was sur[)rised to see the crystalline deposit entirely dissolve. A fresh portion of sediment showed the same crystalline appearance and the same solubility by heat. ... A day or two afterwards another speci- men was brought to me, containing tiie same crystalline deposit soluble by heat. The sediment formed about an eigbth of tlj(; bulk of the fluid. It was collected on a filter, washed with alcohol, and it gave the following reactions : It dissolved in water and hydrochloric acid; when treated with nitric acid it dissolved without effervescence, and when evaporated to dry- ness it left a yellow residue."' Further examination of the urine on subsequent occasions yielded no traces of xanthine. Jackson thought he detected xanthine in diabetic urine; but the tests he relied on were untrustworthy. Lehmann was unable to detect xanthine in several diabetic urines which he examined. Purified xanthine, according to Stadeler (who operated on xanthine obtained from Langenbeck's calculus), shows itself under the microscope as very small irregular granules. When dried it forms brittle crusts, almost chalk-white, with a slight tinge of yellow, which become deeper-colored when powdered. When rubbed, xanthine acquires a waxy lustre. It is soluble in alkalies, also moderately freely in concentrated and warm hydrochloric acid. This solution becomes turbid on cooling, and deposits quadratic octahedra of a combination of xanthine with the acid. It dissolves without effervescence in nitric acid, and the solution on evaporation leaves a bright yellow residue, which becomes violet-red when treated with solution of caustic potash,^ The solubility of xanthine in water is subject to extra- ordinary variations, which are not yet understood. Stadeler found pure xanthine from Langenbeck's calculus to dissolve in 13,333 parts of cold and in 1178 parts of hot water. Strecker found artificial xanthine, prepared by him from guanine, to vary in its solubility according as it was obtained from the evaporated ammoniacal solution or precipitated from its alka- line solutions by acetic acid. In the former case the solubility in hot water was, in round numbers, 1 in 1350; but in the latter, 1 in 396. Prolonged boiling was found by Strecker to lessen the solubility of xanthine in hot water.* 1 Journal of Chemical Societj', Feb. 1862, p. 79. It may he remarked that in no previous account of xanthine have c7-i/stals of that substance been found. It is to be wished that in Dr. B. Jones's case the identification of xanthine had been more perfect. 2 Strecker, Liebig's Ann., May, 1861, Bd. cxviii. p. 158. •^ Ibid., p. 168. See, also, a recent paper " Sur la Xanthine et sa recherche dans les calculs vesicaux." Lebon. Comptes Kendu?, Ixxiii. 47. 114 CHEMICAL CONSTITUENTS OF THE URINE. VIII.— LEUCINE AND TYROSINE. These two substances were found by Stadeler and Frerichs in the urine in tj'phoid fever and acute yellow atrophy of the liver. Tyrosine has even been found to form a natural urinary deposit in the latter disease. This deposit is described by Frerichs as a greenish-yellow crystalline sediment, which in- creases considerably with slight evaporation of the urine. Under the microscope, greenish-yellow globular masses, com- posed of acicular crystals, are seen. In one of Frerichs's cases of acute yellow atrophy, he says of the urine : " After standing in the cold air, a greenish-yellow light sediment was deposited, consisting entirely of acicular crystals of tyrosine aggregated together in globular masses. When a drop of urine was evapo- rated on a watch-glass, it left behind a residuum, which, upon microscopical examination, was found to be almost exclusively composed of the most characteristic possible crystals of leucine and tyrosine, partly saturated with coloring matter."^ Frerichs regards the occurrence of these deposits as of great importance in the diagnosis of acute yellow atrophy of the liver. In May, 1865, my then clinical assistant, Mr. Clements, brought me a specimen of urine passed by a young woman Fig. 16. Tyrosine, spontaneoiisly deposited from the urine of a patient witli acute yellow atrophy of the liver. who was suffering (and died the day atter) from acute yellow atrophy of the liver, in the home district of the Manchester Infirmary. After standing forty-eight hours, it had deposited an abundant sediment of tyrosine, crystallized in sheaf-like bundles of acicular crystals {see Fig. 16). 1 Frerichs on Dis. of Liver, Syd. Soc. Trans., vol. i., Frontispiece, Fig. 5, and p. 220. PHOSPHORIC ACID AND THK PHOSPHATES. 115 Friinkel' found leucine and tyroHine in the urine in caseH of poisoning by phosphorus. Xanthine, hijpoxanthine, guanine, ii/rosijie, leucine, creatine, and creatinine, may be all regarded as intermediate steps in the re- gressive nietamor[>li()si8 of azotized tissues of wliioh the ultimate stages are urea, uric acid, water, and carbonic acid. It is therefore not surprising that they should )>e found in small quantities in the tissues and the blood ; and that a retardation of this metamorphosis in some particular stage should occasion their appearance in the urine. Hitherto their clinical significance has not been made out with sufticient clearness to be of practical service; and the cir- cumstance that (except xanthine and tyrosine) they never form spontaneous urinary deposits, removes them (at present) from the interest and view of the practitioner. But it is not improb- able that the study of these bodies in the urine may hereafter lead to important clinical indications; until then, it is not desirable to load a practical work like the present with details respecting them,^ IX.— rHOSPHOEIC ACID AND THE PHOSPHATES. Phosphorus exists in the animal body in large quantities, Either oxidized into phosphoric acid, and united with bases so as to form phosphates which pervade the fluids and solids — especially the bones ; or unoxidized, and combined wath albu- minous compounds in some manner not yet understood. Phosphoric acid passes out of the body partly with the feces and partly with the urine. The diurnal excretion of phosphoric acid by the kidneys varies from 30 to 90 grains. The mean of twenty-live sets of observations collected by Dr. Parkes, was 48.80 grains a day. Tw^o-thirds or three-fourths of this are combined with potash and soda to form soluble phosphates, which do not come under the notice of the practitioner as uri- nary deposits. The remainder is united with lime and magnesia to form salts, which, though soluble in acid urine, are speedih^ precipitated when the secretion becomes alkaline, and constitute urinary deposits. Phosphoric acid is derived in part directly from the food; in part also from the oxidation within the body of the phosphorus of the albuminoid tissues. The hourly excretion of phosphoric acid rises considerably after meals; and the earthy phosphates undergo a proportionately larger increase than the alkaline ' Berl. klinisch. Wochensch., 1878, p 265. 2 A paper, by K. B. Hoffmann, in Virchow's Arohiv, Bd. 48, p. 358, may be referred to as containing a large amount of information respecting the excretion of creatinine in health and disease. 116 CHEMICAL CONSTITUENTS OF THE URINE. phosphates. In a series of observations extending over six days, I found that the average hourly separation of the earthy phosphates during the two hours preceding dinner, amounted only to one-half the quantity separated during the third and fourth hours after dinner. The alkaline phosphates rose from 3.47 grains per hour before dinner, to 4.90 grains after dinner. The food is, however, not the sole source of the phosphoric acid of the urine; and the separation of it goes on, though in greatly diminished quantity, after prolonged fasting. A very large number of observations has been made on the excretion of phosphoric acid in disease, but with results of slight clinical value. Dr. Bence Jones has formulated the fol- lowing conclusions (founded on determinations per 1000 parts) : " In acute inflammation of the brain, there is_ an excessive amount of phosphates in the urine. When the inflammation becomes chronic, no excess of phosphates can be shown to exist. ... In some functional diseases of the brain, an excessive amount of phosphates is observable ; this ceases with the de- lirium. Delirium tremens shows a remarkable deficiency in the amount of phosphates excreted, provided no food is taken. "When food is taken the diminution is not apparent."^ These observations are substantially borne out by the observations of Tomowitz and Beale. Professor Yogel ascertained the rate of excretion of phos- phoric acid in a very great number of acute and chronic diseases (having made above 1000 observations), but without eliciting any conclusions capable of clinical use.^ Ziilzer^ again has determined the amount of phosphoric acid in the urine in relation to the nitrogen excreted. He finds that in ordinary health the " relative amount" of phosphates is fairly constant although changed somewhat by food, as mentioned above. In depressed states of the system, however, phosphates are excreted in excess, while in excited states they are dimin- ished. In the febrile state again the nitrogen of the urine is increased, but the phosphates are diminished. When defer- vescence sets in, large quantities of both are eliminated, and during convalescence the phosphates predominate. The con- dition of the urine in cholera was found to be peculiar. That passed in the early stages was rich in phosphates, while as the patient recovered the phosphates again diminished. Ziilzer also found an increased excretion of phosphates after injuries to the nervous system. 1 Medico-Chir. Trans., vol. xxxviii. p. 261. * Neubauer and Vogel : Analysis of the Urine, Syd. Soc. Trans, p. 413 — where the reader is referred for fuller information. Dr. Paton found that mental work caused no increase, but rather a diminution, of the phosphates in the urine. Journ. of Anat and Phys., May, 1871. 3 Virch. Arch., Bd. 66, p. 223. FirosrHORic acij) and the phosphates. 117 Salkowski,' however, objects that in Ziilzer's conclusiorm suf- iicient attention was not paid to the facts that : 1. Phosphates are excreted in the feces as well as in the urine. 2. That the character of the food has great influence on the excretion. 3. That the bones are rich in phosplioric acid, and they pos- sibly take some part in the metabolic changes which occur in the body. To the practitioner, therefore, the interest of phosphoric acid and the phosphates in the urine, is confined to the earthy phos- phates which come before him as urinary deposits and urinary concretions. Dr. Prout dignified with the name of "phosphatic diathesis," the tendency to the deposition of the earthy phosphates in the urine. Dr. Bence Jones^ has, however, clearly shown that this designation is wholly inappropriate. There is not the least reason to believe that there is any constitutional state specially characterized by an excessive excretion of phosphates ; the phos- phatic diathesis of Prout is simply ammoniacal urine.^ Deposits or Earthy Phosphates. Phosphoric acid is spontaneously deposited in the urine chiefly, if not exclusively, in one of the three following com- binations : 1. Amorphous phosphate of lime, or bone-earth (Ca3(PO^)2). 2. Crj^stallized phosphate of lime (CaHP0^+2Aq.). 3. Ammoniaco-magnesian phosphate, or triple phosphate (MgNH,P0,+6Aq.). These three compounds are occasionally precipitated together in one deposit; much more frequently the first and third are found together, forming the ordinar}^ sediment of ammoniacal urine. This latter passes under various names, viz.: "'the mixed phosphates," the "secondary phosphates," or "fusible matter." This will come under notice again as the special con- stituent of secondary calculous formations. The earthy phosphates are readily soluble in the natural acid of the urine; but are insoluble in neutral or alkaline fluids. Their precipitation as deposits is, therefore, properly associated with an alkaline state of the urine; it is, nevertheless, a fact 1 Die Lehre vom Harn, p. 186. "^ Animal Chemistiy, p. 85. ^ (Teissier, of Lyons, has described certain cases under the title of " Phosphatic Diabetes," which are characterized bj" polyuria with excessive excretion of phos- phates, and many of the symptoms of ordinary diabetes. Dr. Kalfe (Lancet, Jany. 1881, p. 406) has also called attention to, and described such cases. The affection, however, seems to have great affinities with Diabetes Insipidus. — K. M.) 118 CHEMICAL CONSTITUENTS OF THE URINE. that the second and third forms are occasionally deposited in urines that are neutral or feebly acid. Urines depositing the earthy phosphates, or tending thereto by their neutral or feebly acid reaction, become turbid when heated. This behavior has been variously explained. Some have thought that the heat expelled the carbonic acid v^hich held the earthy phosphates in solution ; others, that the heat caused rapid decomposition of the urea into carbonate of ammonia, and thereby suddenly increased the alkalescence of the urine. Scherer thought the reaction due to the conversion of the neutral phosphates of lime and magnesia into basic salts. I think that a more simple explanation may be offered. Some salts of lime (like the hydrate) are much more soluble in the cold than at higher temperatures. This is probably the case with the lime phosphates. I find that when a urine which exhibits this reaction is heated in a sealed glass tube by immer- sion in hot water, the turbidity speedily makes its appearance ; but it disappears slowly (either wholly or partially) after the tube has cooled. On reheating the turbidity returns, and again slowly disappears after cooling. This experiment may be repeated many times with a similar result. The same succession of events may be obtained by heating the urine in an ordinary test-tube over the open flame, provided the heating be not pushed to ebullition. If such a urine be sharply boiled there is no resolution of the precipitate after cooling, because probably the chemical change suggested by Scherer has been brought about. ^ 1. — Amorphous Phosphate of Lime, or Bone-earth. This compound is invariably precipitated in alkaline urine. When the urine is alkaline iTom fixed alkali, this is the ordinary, and often the sole deposit ; but far more frequently it is accom- panied by the triple phosphate. It forms an amorphous, whitish, light flocculent deposit, indistinguishable by the naked eye from epithelium. It has no affinity for the coloring matter of the urine, and is consequently of a paler color than the supernatant urine, differing in this respect from the amorphous urates. The surface of the urine is generally covered with an iridescent film. The application of heat does not dissolve the deposit, but, on the contrary, increases it. A drop of any acid causes it instantly to disappear. Under the microscope it appears as very pale, minute granules in irregular clumps or patches, much resembling the fawn-colored lithates {see Fig. 3). ^ For another explanation of this reaction, see a paper bv Prof. Smith in the Dublin Journ. of Med. Sci., July, 1883. PHOSPHORIC ACID AND TJIE F II OSP Jf A'I'ES, 119 Its occurrence depends Bimj»ly on the existence of an alkaline reaction, and the presence of lime and [)hosphoric acid in the urine. This is the normal deposit of the alkaline urine after a meal. It is also frequently seen in persons whose urine has heen ren- dered alkaline by remedies (carbonates, acetates, citrates of the alkalies, etc.), and after the excessive use of sweet and subacid fruits. The turbidity caused l>y the amori)hous phosjdjate exists in its greatest intensity at the moment of emission of the urine, and does not increase on cooling. The clinical significance- and treatment of this deposit are entirely involved in those of alkaline urine. Bone-earth alone very rarely constitutes a urinary calculus; but it enters largely into the composition of phosphatic calculi in combination with the ammoniaco-magnesian phosphate. 2. — Crystallized Phosphate of Lime, or Stellar Phosphate. Dr. Hassall first called attention to the existence of a crystal- lized form of phosphate of lime occurring as a urinary deposit. Ftg. 17. a- Stars aud rods of crystallized phosphate of lime, or stellar phosphate. In 1860 he communicated a paper to the Eoyal Society on the composition and pathological importance of the calcareous phosphates occurring in the urine as a spontaneous deposit of 120 CHEMICAL CONSTITUENTS OF THE URINE. stellar crystals. He considered these crystals to consist of bi- phosphate of lime ; he also believed them of far graver signifi- cance than the triple phosphate of ammonia and magnesia. In 1861 I had an opportunity of reexamining this question, and published the results of my observations in the " British Medical Journal" for March 30, 1861. The crystals in question present considerable variety of form (Fig. 17). The prevailing appearance is that of crystalline rods or needles, either lying loose (d), or grouped into stars, rosettes (a a), fans (6), or sheaf-like bundles (c). Some of the crystals are club or bottle-shaped (e e), and abundantly marked with lines of secondary crystallization. In a case of diabetes under my care in the Manchester Infir- mary, these crystals formed a constant deposit. The urine had been brought down by appropriate treatment to fifty ounces a day, and the patient was steadily gaining fiesh and strength. The deposit was often mixed with oxalate of lime, and some- times with uric acid ; but never, except as the result of putrefac- tive decomposition, with the triple phosphate. I managed to collect about two grains of the crystals in a pure state, and subjected them to analysis. The results indicated the following- formula : 2CaO,IIO,P05-f3IIO (old notation). By adding a little chloride of calcium to health}^ urine, and reducing its acidity to near the neutral point with caustic soda, I have often succeeded in obtaining an abundance of crystals closely resembling those occurring spontaneously in urine. The reaction of the urine in which I have found the crystal- lized phosphate of lime has been sometimes faintly acid, more often neutral, or alkaline. The occurrence of a deposit of the stellar phosphate in urine is not common. It is, in fact, a rare deposit, as compared with oxalate of lime, uric acid, or the triple phosphate. The presence of this deposit in quantity is, according to my experience, an accompaniment of some grave disorder. In addition to the case of diabetes already mentioned, I have seen the stellar phos- phates in cancer of the pylorus, once in phthisis, and more than once in patients exhausted by obstinate chronic rheumatism. They may, however, under peculiar conditions, be precipitated in a healthy urine. When the urine is rich in lime, and its acidity is at the same time depressed to near the neutral line, stellse of phosphate of lime may form quite independently of any grave disorder, merely as the result of a coincidence in the chemical composition and reaction of the urine. For example, after a full meal the acidity of the urine becomes greatly reduced, and lime derived from the food is in excessive propor- tion. In such circumstances, I have several times detected PHOSPHORIC ACID AND THE IMl OS 1' II A '1' KS . 121 stellffi of phosphate of liiiio, hut oiil_y in Hcanty nurriherH. A depressed acidity of the urine is an essential contingent to the formation of these crystals ; and if the urine suhsequently to their formation increase in acidity, they may spontaneously disappear. 3. — The Phosphate of Ammonia and Magnesia, or Iriple Phosphate. This is an insoluhle crystalline compound, which occurs very frequently as a urinary deposit — sometimes alone, but much more commonly accompanied with the amorphous phosphate of lime. When unmixed with any other substance, the deposit has a snow-white appearance; and bright, sparkling, colorless crystals are observed studding the sides of the urine-glass and forming a brilliant crystalline film on the top. The ordinary form of the crystals is a triangular prism with bevelled ends. A very great variety of subordinate forms is produced by a planing off of the ridges and angles, and a hollowing out of the sides (Fig. 18). In a highly anamoniacal urine, the magnesian Fig. 18. lliffurent formt! of triple pbosphute fryr>tals. phosphate forms elegant dielytral crystals, which appear to arise from a hollowing of the sides and a deep notching of the extremities of the prisms. The triple phosphate is easily soluble in acids ; yet it may be found in urine that is feebly acid to test paper. Heat does not affect it; and the urine which deposits it commonly becomes turbid on boiling. 122 CHEMICAL CONSTITUENTS OF THE URINE. This deposit is necessarily present in ammoniacal urine, ex- cept in the very rare contingency of the urine not containing any magnesia. When urine is alkaline from fixed alkali, crys- tals of this salt generally appear after a while. This is easily explicable after the demonstration by Neubauer and Heintz that ammoniacal compounds exist in small quantities even in fresh natural urine. In the immense majority of cases the deposition of this salt is only an incident due to the loss of the acid reaction of the urine, and especially of ammoniacal decomposition of the urine. Occasionally, however, it occurs in fresh urine which is neither decomposed nor sensibly (to the smell) ammoniacal. The fol- lowing is the most remarkable instance which I have witnessed : J. P., a gentleman, aged twenty-nine, of a moderately healthy appearance, but irritable temperament, consulted me on account of a sense of weakness in the back and loins, w^ith general de- bility and languor, and a tendency to sudden perspirations and fits of nervousness. There was severe smarting at the close of micturition. He had suifered from gonorrhoea three years previously, but had been completely free from any urethral discharge for some time. The urine was examined on several occasions. It was faintly acid when voided ; and deposited, sometimes before it was cold, and generally within a couple of hours, an abundant precipitate of the unmixed ammoniaco-mag- nesian phosphate. The annexed note was taken of the urine voided at 11.30 a. m. on January 28, 1861. " In half an hour it was found transparent, perfectly sweet {i. e., not putrescent), faintly acid ; and sparkling crystals of the triple phosphate could be seen floating in it. At four p. m. the same day the specimen was quite clear; brilliant crystals of triple phosphate studded the sides of the glass, and at the bottom was collected an abundant snow-white deposit of the same crystals. The urine was not albuminous, neither did it contain pus or epithelium. On the following day the specimen continued unchanged; but on the fourth day the reaction had become faintly alkaline ; the deposit was losing its snow-white character, and reddish flakes, com- posed of spheres of urate of ammonia, had become deposited. From this date the urine began to decompose, and speedily became ammoniacal and offensive. " This condition of the urine, together with the unpleasant symptoms before noted, gradually disappeared in the course of six weeks, under the influence of cold sponging, systematic exercise in the open air, and the administration of dilute nitric acid in a bitter infusion. Stein^ found a deposit of magnesium phosphate, Mg3(P04)2, in the strongly alkaline urine of a patient suffering from dilata- tion of the stomach. 1 Deutsch. Arch. f. klin. Med., Bd. 18, p. 207. CAREONATE OF LIME, 123 X.— CARBONATE OF LIME. When urine becomes alkaline from carbonate of ammonia, a small quantity of carbonate of lime is precipitated in an amor- phous condition v/ith the earthy phosphates. I have only seen it in a crystalline form in human urine when voided as gravel or small calculi; it is said occasionally to occur in globular spheres and cornucopia-like crystals (Bird, Trassall). In the alkaline and viscid urine of the horse, carbonate of lime is fre- quently^ deposited in the form of minute spheres composed of radiating linear crystals which are striking objects under the Fro. 19. Spheres and diiinb-liells of carlioiiate of lime from the nriue of the horse microscope {see Fig. 19). They show a dark cross with polar- ized light. The assumption of this globular form is probably connected with the viscidity of the urine. Carbonate of lime constitutes a variety of urinary calculus which is of extreme rarity in the human subject, but much more common in the herbivora (see Carbonate of Lime Calculi). XL— SULPHURIC ACID AND. THE SULPHATES. About thirty grains of sulphuric acid, in combination with alkaline bases, are daily excreted by the kidneys. A part is derived directly from the food, and a part from the oxidation of the sulphur contained in the albuminous compounds. The sul- phates are highly soluble, and in only two cases have they been known to constitute a spontaneous urinary deposit.^ 1 Valentiner, Ceiitralblat. f. Med. Wissen, 1863, p. 913; Fiirbrinsier, Deutsches Arch. d. klin. Med., Bd. 20, p. 511. 124 CHEMICAL CONSTITUENTS OF THE URINE. In all febrile states sulphuric acid is increased. Dr. Parkes has observed a decided increase after the use of liquor potassse. An increase is also observed after food, and in all conditions associated with an intensilied metamorphosis of tissue. It has not yet been shown that a knowledge of the quantity of sulphuric acid separated by the kidneys in any particular case of disease is capable of subserving any practical purpose.^ XII.— CHLORINE AND THE CHLORIDES. The chlorides never form spontaneous deposits in the urine ; and the variations in their quantities have only an uncertain relation to special states of disease, but depend chiefly on the times of the meals and on the general rate of tissue-changes. A good deal of attention has been called to the falling oft or disappearance of the chlorides in the urine in acute pneu- monia, and their reappearance when resolution is established. It has been asserted that a knowledge of the amount of chlorides excreted by the kidneys in the course of this disease, furnished valuable information for prognosis and treatment. Later obser- vations have, however, shown that the indication is far from being a reliable one, and that the notions entertained in some quarters of its utility are greatly exaggerated. Although it be a rule of very prevalent application, that the chlorides in the increment stage of acute pneumonia are almost completely re- tained within the body, and that their reappearance in the urine is coincident with commencing resolution, yet there are excep- tions to both these statements, especially to the coincidence of the reappearance of the chlorides with commencing defer- vescence (see Parkes). Supplementary Remarks on the Excretion of Phosphorus, Sulphur, AND Chlorine. These three elements enter largely into tjie composition of the body, and they are abundantly present in articles of food. They pass out of the body chiefly with the urine ; but partly also with the feces. Multiplied observations have been made, and continue to be made, on the rate of their excretion both in health and disease; and important ph^'siological and patho- logical deductions have been drawn from these investigations. 1 (In certain rare cases sulphuretted hydrogen may appear in the urine. In most of such cases there has been found either some communication between the intestinal and urinary tracts, or a pericsecal abscess from which the gas was absorbed. Occasionally, however, neither of these conditions seems to have been present, and the origin of the phenomenon was obscure. See a case by Cameron, Lancet, 1880, vol. ii. p. 766. R. M.) U K K A , ] 2o It has been considered tliat the rate of excretion of i)ho8|)lioru.s and sulphur, under proper precautions and corrections, furnished a measure of the exchange of material within the body — that is, of the activity of the molecular life of the tissues: and that in disease, an important insight into obscure phenomena could be thus obtained, capable of being turned to practical uses. In proportion, however, as these researches have been extended, it has become clearer and clearer that these expectations are not likely to be realized, and that the iDractitioner is not likely to draw much help from these recondite sources. The difficulties in the way are manifold. In the iirst place, quantitative deter- minations of sulphur and phosphorus, notwithstanding all the aid of modern volumetrical methods, are still too troublesome and tedious to be within reach of any but a very select body of practitioners. But this is one of the smallest difficulties. In all such determinations it is necessary to do more than ascertain the proportion per cent. To obtain results of any value, the quantity per day must be ascertained. Again, there are physio- logical variations to make allowance for, arising from food, exercise, sleep, etc. ; and thirdly, it has now been ascertained that, all known conditions remaining the same, the rate of ex- cretion of these elements presents oscillations from an unex- plained temporary retention, or partial retention, of the ele- ments within the body, which is succeeded, after a shorter or longer interval, by a compensating increased discharge. These circumstances render it necessary to continue the observations over a number of days — six or eight — in order to cover the inequalities. For these and other reasons which might be men- tioned, these inquiries are surrounded with difficulties. It is little wonderful, therefore, that the results obtained by diflerent experimenters show a marked want of uniformity : and it is simply the fact that, from a clinical point of view, these laborious investigations must at present be regarded as unfruitful, and for that reason they may be passed over with only a slight notice in a practical work. It is highly desirable, however, that researches of this class should be pushed on ; it is impossible to say how soon practical lessons maj^ be culled from these now apparently dormant facts. At any rate, they cannot fail to enlarge our general ideas on physiological and pathological processes. XIII.— UEEA, C0(NH2).,. Looking at the urine from a physiological point of view, urea must be regarded as its most important constituent. It is the chief final product of the metamorphosis of the albuminous tissues, and furnishes the form under which nearly all the nitro- gen finds its way out of the. body. 126 CHEMICAL CONSTITUENTS OF THE URINE. Urea is a bland crystalline substance possessing the properties of a feeble base. Its best known combinations are the nitrate and oxalate, both of which are much less soluble than urea itself. Urea is very soluble both in water and alcohol ; it never forms a spontaneous urinary deposit. Its presence in a urine of high density, or one artificially concentrated, is easily demon- strated. If to such a urine an equal volume of strong nitric acid be added, in a test-tube, and the tube be plunged into cold water, the mixture speedily becomes a shining mass of crystals of nitrate of urea. The daily separation of urea by adult men between the ages of twenty and forty, averages about 500 grains ; but the amount varies considerably from various causes, such as diet, exercise, meteorological conditions, and individual peculiarities. Of the twenty-four series of observations, of not less than six days each, tabulated by Dr. Parkes, the minimum result is 286.1 grains and the maximum 688.4 grains per day. The body-weight has, as might have been expected, a very apparent relation to the daily excretion of urea, but the relation is not simply a direct one, because the weight of individuals is made up differently — some being heavy from bone and muscle, others from an ac- cumulation of fat. It is estimated that a healthy adult man excretes urea at the daily rate of 3J grains per pound of the weight of his body. The excretion of urea is greatly increased after a meal — espe- cially of animal food. Bidder and Schmidt believed that this arose from a direct transformation into urea of a portion of the alimentary materials without their being previously fixed as tis- sues ; but Bischoff and Yoit, with more probability, attribute this increase to an accelerated tissue-metamorphosis induced by the presence of the new supplies in the blood. Copious water-drinking causes an increased separation of urea. Children secrete more in proportion to their weight than adults. The immediate effect of muscular exercise appears to be to restrain (or at least not to increase) the excretion of urea ; but it is increased in the period of rest which follows exercise.^ The quantitative estimation of urea in urine may be made either by the method of Liebig or by that of Davy, as modified by Drs. Russell and "West. Liebig's Volumetrigal Method. — This method is based on the property of urea to form an insoluble precipitate of fixed 1 For further information respecting the excretion of nitrogen (urea) under various conditions, the reader is referred to the important investigations of Dr. Parkes, Med. Time^ and Gaz., 1867, I. 393, and Proc. Roy. Soc, 1871, p. 849; also Grfihaut, J. de I'Anat. et Phys., 1870, 318; Weigelin, Reichert's Archiv, 1868, 207; Paton, Journ. of Anat. and Phys., May, 1871. UREA. 1-7 composition with the nitrate of the protoxide of mercury. But in order that the test may operate, it h necessary to free the urine beforehand from phosphates and sulphates. It is also necessary for complete accuracy to make allowance for the chloride of sodium present. When chloride of sodium coexists in any fluid with urea-, the nitrate of mercury produces no pre- cipitation of urea until the whole of the chloride of sodium is decomposed with formation of bichloride of mercury and nitrate of soda. After this conversion is completed, urea begins to be precipitated, and the test-solution is to be added until no more urea remains in solution. This point is ascertained by a solu- tion of carbonate of soda, which immediately develops a yellow color when — and not before — all the urea has been thrown down with the mercury. Three solutions are therefore required. First. A baryta solution, to precipitate the phosphates and sulphates. This is composed of one volume of a cold saturated sokition of nitrate of baryta mixed with two volumes of satu- rated baryta-water. Second. The mercurial test-solution. Ten cubic centimetres of this solution contain 0.772 gramme of red oxide of mercury dissolved in nitric acid — that is to say, in the form of nitrate of the peroxide of mercury. Third. A solution of carbonate of soda of about the strength of twenty grains to the ounce. As the preparation of the first and second solutions is verj^ troublesome — the latter especially — it is more convenient to purchase them ready made.^ The analysis is performed in the following manner : 1. Forty cubic centimetres (or two volumes) of the urine are mixed in a beaker with tw^enty cubic centimetres (one volume) of the baryta solution. The mixture is thrown on a Alter; fifteen cubic centimetres of the filtered fluid (which, of course, contains two-thirds, or ten cubic centimetres of urine) are care- fully measured oft" and placed in a small beaker. 2. A graduated burette is filled with the mercurial solution, which is then very carefully dropped into the beaker until the mixture begins to become turbid; a few drops generally suffice. A note is taken of the quantity of the solution used to reach this point: it indicates that all the chloride of sodium is decora- posed and that the urea is now beginning to be precipitated. 3. The mercurial solution is now added more freely, and thoroughly mixed by means of a glass rod : a copious white 1 These and other test-solutions for volumetrical analyses of the urine may be had of Griffin, Bunhill Eow, London, and from Mottershead & Co., Chemists, Manchester. 128 CHEMICAL CONSTITUENTS OF THE URINE, precipitate makes its appearance, and the analysis approaches completion. 4. This point is ascertained by pouring some of the carbonate of soda solution into the bottom of a white porcelain plate ; and taking a drop from the turbid mixture in the beaker by means of the stirring-rod, and letting it fall into the solution on the plate. As long as the drop produces only a white curdy circle the mercurial solution is still to be added; but as soon as a yellow tinge appears the analysis is finished. 5. The quantity of mercurial solution used is then read off, and the portion used before the occurrence of turbidity sub- tracted — the remainder is what has been employed to precipitate the urea. Each cubic centimetre of the solution used indicates 0.154 grain (or 0.01 gramme) of urea. From this, by an easy calculation, the amount of urea in ten cubic centimetres of urine may be ascertained ; and if the number of cubic centimetres of urine voided in the twenty-four hours be known, the daily ex- cretion of urea is readily calculated. Davy's Process modified by Russell and West. — The prin- ciple of this method depends on the decomposition of urea by the hypochlorites and hypobromites. The amount of urea is determined by measuring the volume of nitrogen evolved. A solution is prepared by dissolving 100 grammes of solid caustic soda in 250 c.c. of water and adding 25 c.c. of bromine at the time the solution is required.^ The apparatus constructed by Drs. Russell and West for the performance of the analysis is both compact and cheap." But it is not so convenient and accu- rate to work with as that devised by Mr. Apjohn. Mr. Apjohn's apparatus consists of: 1. A glass measuring tube of about a foot in length drawn out at the end which will be uppermost when the tube is used, like a Mohr's burette, and subdivided into 30 parts of equal capacity, the aggregate volume of which is 55 c.c. 2. A small wide-mouthed gas bottle of about 60 c.c. capacity. 8. A short test-tube of about 10 c.c. capacity, and of such height that when introduced into the gas bottle it will stand within it in a slightly inclined position. The following are the arrangements for combining the appa- ratus and working an experiment : The graduated tube, held in a clamp attached to a retort- stand, is depressed into a glass cylinder, nearly tilled with water, until the zero mark, which is near the upper end, exactly coin- cides with the surface of the water. 15 c.c. of the hypobromite solution (100 grammes of ISTaHO, 250 c.c. of water, 25 c.c. of 1 Lancet, February, 1876, p. 241. 2 It may be had from Cetti, Brooke Street, Holborn, London, price 8s. 6d. UREA, 129 bromine) having been poui-ed into the bottle, the test-tube con- taining the urine is introduced by nieariH of a forceps, care being taken that none of its contents shall spill into the liypobromitc. The tiask is now closed with a very accurately fitting India- rubber stopper, perforated with a hole in which is inserted a short piece of glass tubing open at both ends, and is then con- nected with the measuring tube by means of a piece of elastic tubing. It is now inclined so as to allow the urine to mix with Fig. 20. Apjohn's apparatus for the estimation of urea with Kussell and West's sohition. the hypobromite. Effervescence at once commences, and as it proceeds the measuring tube is gradually raised so as to relieve the disengaged nitrogen from the hydrostatic pressure. The flask is shaken a few times, and when the reaction is completely over, the apparatus is left for a few minutes until it has acquired the temperature of the room in which the experiment is per- formed. Another exact levelling of the measuring tube is made, and the number of the division corresponding to the volume of the developed nitrogen is read oif. The tube is so graduated that, when 5 c.c. of urine are oper- ated on, each division corresponds to 0.1 per cent, of urea, or 0.44 grain pier fluidounce of the British Pharmacopoeia. An easy calculation from these data gives the daily discharge of urea. Suppose 45 ounces of urine are voided in the 24 hours, and that 5 c.c. of this evolve 20 measures of nitroo'en with the hypobromite solution, then : 0.44X20X40 = 896. The daily discharge of urea was 396 grains. 9 130 CHEMICAL CONSTITUENTS OF THE URINE. I have carefully tested this method and have found it easy, accurate, and speedy.^ Pathological Relations of Urea. — The excretion of urea in disease has been examined in a large number of cases. In the acute stage of febrile and inflammatory diseases, there is an increased formation and discharge of urea, depending on an accelerated metamorphosis of tissue. When the crisis of the disorder has passed, and defervescence sets in, the excretion of urea falls even below its natural average. This rule, however, is liable to exceptions ; it appears that in not a few instances there is a retention of urea within the body during the pyrexial period, even when no disorder of the kidneys exists, and a com- pensating discharge when convalescence begins. Acute (inflam- matory) Bright's Disease is a constant exception ; the urine in that complaint is poor in urea ; but this arises, not from dimin- ished formation, but from defective separation, owing to the blocked-up condition of the uriniferous tubes. Frerichs found, in one example of acute yellow atrophy of the liver, a total deficiency of urea in the urine ; in a second case there was abundance of urea in the urine discharged during life, but only a trace in that withdrawn from the bladder after death. In chronic diseases not involving the kidneys, the excretion of urea has not usually been found materially aftected. In saccharine diabetes there is an excessive separation of urea, as might have been expected from the accelerated rate of tissue metamorphosis which must accompany the full feeding and rapid emaciation of these patients. In a case of diabetes insipidus (with a daily discharge of 12 or 14 pints of urine), I found the excretion of urea to oscillate between 394 and 505 grains daily, which yielded a mean rate of 4J grains per pound of the body-weight. This is about a fourth above the average for healthy individuals. In both acute and chronic degeneration of the kidneys (Bright's Disease) there is a marked lessening of the excretion of urea, as will be more fully commented on when those diseases come to be described. The proportion of urea is also greatly reduced in the urine voided by persons sufi'ering from an obstruction in the ureters {see Suppression of Urine). One of the most important properties of urea is the great facility with which it is broken up and resolved into new com- pounds. This property comes into important play when urea is unnaturally retained in the blood or in the urinary passages. 1 For a further account of this method, see Eussell and West's paper, Journ. of Chem. Soc, Aug. 1874; and Practitioner, Feb. 1875. Apjohn's paper is in the Chemical News, Jan. 22, 1875. UKJOA. 131 It has been already explained with wliat conHequoDccs tliis bland and innocuous base is converted into punii;ent carbonate of ammonia in the bladder and other parts of the urinary tract. A similar conversion, taking place in the blood, was believed by Frerichs to be the cause of the stormy and dan- gerous phenomena of urfemia. Dr. Prout believed that there existed a peculiar morbid state characterized by an absolute and relative increase of the excre- tion of urea, unaccompanied by pyrexia. To this condition Dr. Willis, who adopted the view of Prout, gave the name of Azoturia. The subjects of this form of disease, according to Prout, had usually a frequent and urgent desire to pass water both by night and day. This seemed principally due to an irri- table sensation referred to the neck of the bladder, occasionally extending along the urethra; but. in some cases it was due, at least in part, to real diuresis. In almost every instance the quantity of urine voided in the twenty-four hours was somewhat above the natural standard. The quantity was also particularly liable to be increased by causes which would scarcely affect a person in perfect health, at least to the same degree ; such as by a chilly state, mental emotion or excitement, etc.^ In addition to the direct urinary symptoms, there was some- times a sense of weight or dull pain in the back, accompanied by disinclination to bodily exertion ; there was no remarkable thirst; nor craving for food; nor emaciation. Moreover, the functions of the skin appear to be little deranged. Such is a summary of the description of Prout. He does not supply any details as to the daily flow of urine nor the daily amount of urea. At the time Prout wrote, very little was known as to the natural (physiological) variations in the excretion of urea; and the opinion he held as to urea being chiefly the final product of the metamorphosis of the gelatinous tissues has since been proved to be erroneous. Looking at the question from the standing-point of the physiological doctrines now in the ascendant, it is difficult to admit the existence of a condition characterized by the incompatible coincidences of .an increased excretion of urea, with absence of thirst, absence of excessive feeding, and absence of emaciation. Precise facts in support of Prout's view are wanting. Willis's description is too loose to give much confidence, and subseque"nt writers have contented themselves with a reference to Prout and Willis.^ 1 Prout: Stomach and Kenal Diseases, 5th edit., p. 97 ^ The six cases recorded by Dr. Handfield Jones, in the Brit. Med. Journ. for Oct. 12, 1861, under the title of " Cases of Baruria," are so deficient in necessary details, that they are of no service to a reader. In only one of them was the urine of the twenty-four hours collected and examined, and in that case only on one occasion. In the remainder " baruria " seems to have been inferred to exist from the high density of a single specimen. 132 CHEMICAL CONSTITUENTS OF THE URINE. Dr. Parkes/ however, records a remarkable case examined by Dr. Kiiiger. The patient was a middle-aged man weighing 109 pounds, who was not feverish, and appeared only feeble. He was fed on the ordinary diet of the hospital (University College), and passed in each twenty-four hours no less than 1130 grains of urea (mean of twelve days), or 10.36 grains to each pound avoirdupois of his body-weight. There was a trace of sugar, but not enough to determine quantitatively. The daily flow of urine in this case amounted to 96 fluidounces, which is fully double the normal average. In my own experience, I have usually found that cases which at first sight appeared to belong to this category — cases exhibiting a dense urine and a train of nervous symptoms — turned out on more exact investigation to want the special feature indicated by Prout as the essential one ; namely, an absolute increase in the daily discharge of urea, l^evertheless, some facts, rarely observed, have left an impression on my mind that Prout's de- scription is not altogether fanciful. The following case, which I saw with the late Mr. Greaves, of this town, seems to have been one of those Prout had in view when he drew up his account. Mr. L., a man about 50, complained of troublesome irritation at the back of the pharynx, debility, want of energy and power of application to business. In the preceding three months he had lost 20 lbs. in weight. The urine was first examined by me on May 23, 1863. It had sp. gr. 1029, and contained a small quantity of sugar, but less than one grain to the jfluidounce. This was the only occasion on which I detected sugar, but Mr. Greaves had found it once or twice previously. It was arranged that the whole of the urine voided in each 24 hours should be separately collected and sent to me for analysis. This was done for three succes- sive days ; and three weeks later it was done again for two successive days. The following table exhibits the result of the examination : Quantity per clay. Sp. gr. Total urea. May 25 . . 27 ounces 1029.5 542 grains "26. . 80i 11 1029.75 559 " ", 27. . 31" 11 1028.25 555 " June 18 . ■ . 29 u 1027.5 565 " "19. . 34 u 1020.5 510 " This patient was not febrile ; his weight was 120 lbs.; there was little appetite, and no thirst, and yet he excreted daily 4.6 grains of urea for each pound of body-weight on these five days, which is fully a quarter beyond the usual average. I saw the patient again towards the end of January, 1863. The urine had then lost its peculiarity; and the health, under a regulated diet and exercise, and a course of vegetable tonics, with citrate of potash, had become completely reestablished. ^ Parkes : On the Composition of the Urine, p. 374. UREA. 133 Prout was of opinion that thcRC cafies were patholoii^ically re- lated to diabetes ; and he conjectured, though he had not wit- nessed the fact, that they often developed subsequently into that disease. That there is some relation between the two con- ditions seems not improbable; in the cases of Dr. Ringer and myself a small quantity of sugar was temporarily present in the urine with the excess of urea.^ In the case just related the cause of the complaint was mental anxiety; and in all the instances which I have been inclined to place in this group, the origin of the disorder could always be traced to some kind of mental emotion. 1 See Demange, These de Parif=, 1878, and London Medical Kecord, 1879, p. 98. CHAPTER lY. ABNORMAL SUBSTANCES IN THE UBINE: OBGANIC DEPOSITS. I.— EXTEA-EENAL EPITHELIUM. Any part of the genito-uriimry passages may shed its epi- thelium into the urine so as to form a sediment. The urine of the two sexes difiers notably in the character and quantity of the epithelial cells found therein. This arises from anatomical differences in the lower genito-urinary passages; and advantage may sometimes be taken of this circumstance to distinguish the sex of the individual whose urine is under examination. In the male sex an epithelial depositof extra-renal source is most commonly derived from the urethra and prostate gland, Fig. 21. Oval and tailed epithelial cells, found in the thready and flaky deposit of the urine of a man who had formerly suffered from gonorrhoea. and is composed of oval, tailed, or rounded cells (Fig. 21), about twice as large as pus cells and usually flattened, A deposit of this sort is always scantj^ and to the naked eye presents the E X T R A - R E N A L E P 1 T H K L 1 U M 135 a|)pearance of a collection of whitish flakes and strings. When taken up by the pipette for examination, these flakes are found to have the viscid glairy character of mucus. A sediment of this character is not uncommon in men; in many cases it may be distinctly traced to an old gonorrlirjca, which has long since passed away leaving no other vestiges behind it. The deposits found in the urine of persons subject to nocturnal emissions have very much the same appearance to the naked eye. It is well to be aware of the nature of this deposit. Youths principally, but older men not unfrequently, observe for them- selves the presence in their urine of the strings and flakes just described; and they are liable to become subject to hypochon- driacal fears and anxiety respecting them. Such individuals are common victims of unprincipled empirics. I was recently Fig. 22. Tugiual epithelium in the urine. consulted by a gentleman who paid very large sums to a quack who had persuaded him that the flaky shreds in his urine — the innocuous vestiges of a gonorrhoea contracted live years pre- viously — were of a dangerous nature, and required active and long-continued treatment. It is not a trifling matter to be able to allay the alarm of such patients, and to convince them that the subject of their anxiety is wholly unimportant. In females, epithelial sediments are both common and abund- ant. From the simple short urethra the urine receives little or nothing ; but the vaginal membrane is throughout invested 136 ABNOEMAL SUBSTANCES IN" THE URINE, with a lining of pavement epithelium, the elements of which are detached with facility and in great quantity, giving rise to an abundant arnorphous-looking, light, cloudy deposit in the urine. "When examined microscopically this deposit is found composed of large flat cells, resembling the epithelia of the mouth (Fig. 22). The cells either lie discrete, or united by their borders into patches of rude mosaic. A deposit of this character is found only in the urine of females, and comparatively few are wholly exempt from it. In the sub- jects of vaginal leucorrhcea it is always abundant; but it is also present frequently, and in quantity, where there is no appreci- able disorder of the genital passages. Even young (female) chil-^ dren may have a sedimentary urine from this cause, especially those of a strumous habit. The epithelium of the bladder, ureter, and pelvis of the kid- ney finds its way into the urine of both sexes in cases of vesical calculus, renal calculus, and pyelitis from any cause. The epi- Fm. 28. Epithelial cells from the bladder, ureter, and pelvis of the kidney. thelium which lines these parts is of a transitional character, and presents a great variety of forms — cylindrical, spindle- shaped, caudate, oval, spheroidal, and irregular (Fig. 23). It cannot fail to be noticed how like some of these cells are to cancer-cells ; so like, indeed, that the recognition of cancer-cells (as such) in the urine becomes a matter of very great uncer- tainty. In cases of suspected pyelitis the existence of cells of this class in the urine greatly fortifies the diagnosis. {See Pyelitis.) RENAL EPITHELIUM AND CASTS OF TUBES, 137 II.— EENAL EPITHELIUM AND CASTS OF TUI5P:S; THE T^EPOSITS ASSOCIATED WITH ALBUMINUIUA. As renal epithelium and casts of the uriniferous tubes are commonly found together, it will be convenient to consider them in conjunction. The uriniferous tubes are liuud with a single layer of e}jithe- lium. The cells of this layer in the cortical part of the kidney consist, in the healthy state, of a round or slightly oval nucleus having a delicate, regular outline, resembling closely, both in size and asj^ect (except in not ])eing biconcave), the red corpuscle of the blood ; around this nucleus is aggregated a quantity of solid, yet friable, faintly granular substance (Fig. 24, a). A Pig. 24. Kenal epitlielium CASTS OF 'J'UJiKS. ]'6'.) tiou of magenta; sometimes faint markings map their surface, or they show a faint molecular composition. They present extreme differences of diameter; the smallest are not more than the breadth of a blood corpuscle {a a) ; the largest are ^.J,-,-, of an inch, or more, in breadth ibhc); others again are mediiirn sized.' Fig. 25. a a. "Epithelial' iby some portion of the material which originally invested them. The coloring matter of the blood in urine ma}^ also be detected by the spectroscope or by the guaiacum test. The latter is conveniently carried out in the following manner : Pour a little urine into a narrow test-tube and add to it one or two drops of tincture of guaiacum and a little ozonic ether. Shake well and allow to stand for a few moments. If blood- coloring matter is present, the ether on rising to the top of the mixture will be colored blue.^ Urine containing blood is of necessity always more or less albuminous. The quantity may be so great that the urine looks like pure blood, ancl coagulates spontaneously, or so small that the microscope is required to detect it. The hemorrhage may arise from a great variety of causes, which may be classified as follows : 1. Local lesions — external injury, violent exercise, calculous concretions, ulcers, abscesses, cancer, tubercle, parasites, active or passive congestion, B right's disease. 2. Symptomatic — in purpura, scurvy, eruptive and continued fevers, intermittent fever, cholera, etc., mental emotion. 3. SwpplemeMary or vicarious — to menstruation, hemorrhoids, asthma. Cases also occur which are not referrible to any of these cate- gories, of which the origin is extremely obscure.^ 1. HEMATURIA FROM LocAL Lesions. — This division includes by far the largest number of cases. A point of great impor- tance is to ascertain the exact source of the blood. This is not, as a rule, difficult. Hemorrhage from the substance of the kidney is recognized by the existence of tube-casts in the deposit. By far the most com- mon cause of this variety of hsematuria is some form of Bright's disease or its allies (congestion, etc.). In falls and blows on the loins, or any injuries supposed to implicate the kidneys, the occurrence of casts in the urine furnishes a valuable diagnostic sign. In the following remarkable case of laceration of the kidney from a fall, the condition of the urine was accurately noted from the time of the accident till death. 1 See a paper by the author, " On the Effects of Magenta and Tannin on the Blood-corpufcles," in the Proceedings of the Eoyal Society for 1863. 2 If the patient is taking iodide of potassium, or if saliva is mixed with the urine, the test is inapplicable. Heller's test for blood in the urine consists in boiling the urine with liq. potassaj. The precipitate of phosphates which is then thrown down is colored brown if blood be present. ^ It may be necessary to remind students that in females the urine is generally bloody during the menstrual flow ; it may also become so at any time if there be uterine and vaginal hemorrhage. BLOOD IN URINE — IITH M AT U R J A . 151 E. Davis, a bricklayer, aged 86, was brought into the Manchester In- firmary at 8 1'. M. ou April 27, 1868, in a state of complete insensibility, with gasping respiration, apparently dying. In the course of two hours he recovered consciousness, and answered questions imperfectly, in a half- drunken manner. It appeared that he went to his work in the afternoop intoxicated, and that he had fallen a height of seven stories. Tiiere was a compound fracture of the skull, and the legs were severely contused and lacerated. From the time that he recovered speech the patient con- tinued to talk in a curiously incoherent manner, as if he were drunk — except that the pronunciation of words was unaffected. No urine was passed on the day of the accident ; but on the day fol- lowing about eight ounces were withdrawn by catheter. The urine was excessively bloody, dark chocolate-colored, and highly albuminous. On the third day (April 29) the patient was in the same state. No urine was passed spontaneously ; at 8 p. M. about an ounce was withdrawn by catheter ; it was of the same character as before, but less bloody, and less albuminous. On the morning of the fourth day I found the patient breathing rapidly, with a quick small pulse; the tongue was moist ; there was great thirst — no appetite ; the bowels had been opened several times by medicine. At 9 p. m. of the same day I again visited the ward. No urine had been voided, and the bladder was not distended. The general condition was evidently worse ; the delirium was constant, and he swore awfully when his legs were touched. At noon on the fifth day the patient was much weaker ; the breathing was interrupted ; he muttered incoherencies unceasingly; and waved his hands as if he saw spectres in the air ; he picked and tore the bedclothes ; he had torn three sheets to ribbons, and had torn the counterpane. He did this quietly, without violence, and without attempting to get out of bed. When asked questions he answered quite at random ; the tongue was dry and red ; pulse almost imperceptible. No urine had been passed spontaneously this day, nor the day before. The house surgeon introduced a catheter, and succeeded, by compressing the abdomen, in withdrawing about two ounces of a yellowish urine, with small, dark, chocolate-colored granules floating in it. About an hour after, the patient died quietly, without coma or convulsions. During the five days that the patient survived no urine was passed spontaneously ; but eleven ounces were withdrawn by catheter at three different times. The first specimen, drawn the day after the accident, was excessively bloody ; the second, drawn on the third day, was much less bloody ; the third, drawn just before death, contained no liquid blood, and had a yellow color, but it deposited a considerable sediment of chocolate-colored granules which consisted of indurated clots of blood. Although this last specimen, consisting of only two ounces, was the pro- duct of forty hours' secretion, its specific gravity was only 1015, and its proportion of albumen only -^. The microscopic examination of the deposits revealed the existence of an immense quantity of casts of the uriniferous tubes, and these changed character as time passed ovei'. In the first specimen the casts were all dark, opaque, and granular (Fig. 31, a, c, e), evidently composed of crushed blood-clot; no free renal epithe- lium, nor any pyelitic cells, were found. In the second specimen, in addition to the dark granular casts, there were numerous deep-brown 152 ABNORMAL SUBSTANCES IN THE URINE. plain casts, with strongly marked outlines and very few markings (d, d) ; a few transparent casts were also found, some of them studded with epi- thelium. In the second and third specimens free renal epithelium (h, i), and epithelium from the pelvis and infundibula (g), appeared in great abundance. The renal epithelium was deeply browned, evidently from hsematine, but was otherwise natural. Many of the casts had dumb- bells embedded in them. ace. Dart granular casts ; 6, d. Yellow plain cjists ; /. Large transparent cast studded with epithe- lium • i h. Free renal epithelium, i, before, and h, after the addition of acetic acid ; g. Cells from the pelvis and infundibula. Autopsy forty-eight hours after death. Left parietal bone fractured, with a slight depression. Dura mater not lacerated ; no free blood on or under the membrane ; but there was an ecchymotic patch on it as large as a florin, corresponding to the fracture. There was no blood in the arachnoid space ; but the pia mater was injected over the space of two square inches in the vicinity of the fracture. No lymph was thrown out on any part, nor was there softening or other abnormal condition of any portion of the brain. Abdomen. There was no external sign of direct violence over the loins ; all the abdominal organs, except the kidneys, were uninjured and healthy. Left kidney -weighed 9d oz. ; it was not lacerated. On section minute granules of indurated blood were found in several of the infundibula; the whole gland was hypersemic. Right kidney weighed di oz., was torn in two places on its posterior aspect. The lacerations ran across, some- what crookedly, from the outer border almost to the hilum ; they were BLOOD IN URINE — HJ<]MATURIA. 153 about an inch apart, and varied in depth from one to three or even four lines. They were completely closed by a wedge-shaped solid clot of blood, which was very firm, and, where in contact with the renal sub- stance, bleached. The renal tissue immediately adjacent to the lacera- tions appeared perfectly natural — neither injected nor softened. The tunica propria was, of course, torn through over the site of the lacera- tions. The lacerations did not penetrate in any part to the infundibula, but two large, firm, blood-concretions — one as large as a horse-bean, and the other as large as a pea — lay loose in the pelvis, and several smaller ones were found in the infundibula. The perirenal adipose tissue was deeply stained with blood on both sides; but it contained neither fluid blood nor clots. The peritoneum was not injured nor inflamed. The heart and lungs were healthy. It was evident that the direct cause of death in this case was suppres- sion of urine — aided, perhaps, by a degree of delirium tremens. The reason, probably, why no signs of inflammation were found in the brain and peritoneum was, that the patient never really rallied from the shock of the accident ; and that reaction never properly took place. The desquamation of the epithelium of the pelvis and infundibula must be attributed to the irritation of the blood-concretions found therein. H?ematuria is rarely serious from its quantity in any form of Bright's Disease, and is generally quite insignificant. Far more serious are the consequences of the coagulation of the effused blood in the uriniferous canals. Unless these plugs are expelled by the pressure of the urine from behind, they permanently block up the tubes and destroy the function of the correspond- ing portions of the gland. Hence, any hemorrhage from the substance of the kidney, however it may arise, is attended with serious hazard that the foundations of a fatal renal degeneration may be laid thereby. Cancer of the kidney is often associated with profuse and repeated hfematuria; the diagnosis rests chiefly on the presence of a tumor in the loins. [See Cancer of the Kidney.) The endemic hsematuria of Mauritius, Brazils, Cape of Good Hope, Egypt, and some other hot countries, which so greatly puzzled pathologists in times past, seems to have found its expla- nation in the presence of a minute parasite wdiich infests the mucous membrane of the pelvis of the kidney and the bladder. The researches of Griesinger, Bilharz, and Dr. John Harley on this subject will be described in the- chapter devoted to parasites of the kidney. {See Bilharzia H^matobia.) In tubercle, abscess, renal embolism, hydatids, tlie liemor- rhage is seldom more than trifling. In active congestion of the kidneys after taking turpentine or cantharides, the bleed- ing is sometimes severe. As these classes of cases are treated separately in subsequent parts of this work, it will not be necessary here to go into further details. 154 ABNORMAL SUBSTANCES IN THE URINE. Sometimes minute calculous concretions are formed within the tubuli uriniferi, and occasion hsematuria, which is apt to recur again and again. In | these cases crystals or microscopic calculi of uric acid, or oxalate of lime, may often be discovered bj a careful examination of the urinary deposit [see Figs. 32 and 33). HEematuria from this cause may be unaccompanied by Fig. 32. Blicroscopic calculi of uric acid, with fibrinous casts dotted witli crystalline molecules of uric acid in a case of recurrent ha^maturia. any pain beyond a slight aching or sense of fatigue in the loins. Transparent fibrinous casts are also visible in these cases, speckled all over with crystalline molecules, and more albumen is present in the urine than corresponds with the amount of blood voided. Hemorrhage from the pelvis of the kidney and ureters is com- monly due to calculous concretions ; much more rarely to cancer, tubercle, cystic disease, or parasites. When the blood has this source the diagnosis turns on the existence of symp- toms of pyelitis, nephritic colic, and the passage of a foreign body down the ureter. Sometimes the blood coagulates in the ureter, and long vermicular clots may be afterwards recognized in the urine. The passage of these clots along the ureter pro- duces precisely the same symptoms as a calculus passing in the same direction. Hemorrhage from the bladder is usually recognized by symp- toms pointing directly to that organ, namely, excessively frequent micturition, pain in the hypogastrium, and at the neck of the bladder, etc. Exploration of the bladder will generally reveal the existence of calculi or fungoid growth. Varicose enlarge- ment of the veins of the mucous membrane and acute cystitis are also occasional causes of vesical hemorrhage. Urethral hemorrhage is known by the escape of blood in the intervals of micturition. Symptomatic HiEMATURiA. — Purpura hemorrhagica is occa- sionally marked by severe hrematuria. In a case under my care some j-ears ago, there occurred first violent epistaxis re- ]'.LOOD IN UlUNE JlyKMATUKIA. 155 quiring plugging' of the narea; then profuse hiernaturia set in ; when this subsided, the patient rapidly succumbed to intra- cranial hemorrhage. Scurvy is more rarely attended with hsematuria. The eruptive and continued fevers, cholera, and yellow fever, are sometimes the occasion of hsematuria, which is generally a very unfavorable symptom. Supplementary IIti^matukia. — Many curious examples have been recorded in which hasmaturia appeared to be swpplementarj.j to some natural function or some diseased condition. Chopart' relates a case in which hsematuria supplemented a hemorrhoidal flux; Latour-^ adds another. The latter mentions a singular case of spasmodic asthma, of such severity and persistence that the patient had not been able to lie in bed for eighteen months, which disappeared suddenly on the occurrence of hsematuria. Chopart and P. Frank relate examples in which the menstrual flux was deviated to the urinary passages, and appeared under the form of a periodical hsematuria.^ Mental emotion seems capable in very rare instances of pro- ducing hfematuria. BashamHells of a shoemaker who was subject to attacks of hsematuria which always recurred on the occasion of his drunken wife's misconduct. Rayer records an instance in which hsematuria followed a flt of passion. Treatment, — As h?ematuria is merely a symptom, and a symptom which attends a great variety of pathological condi- tions, the treatment of the cases in which it occurs is necessarily diverse. Sometimes, however, we are called on to treat haema- turia for itself — in some cases because of our inability to fathom its exciting cause, in others because the loss of blood is so great that it becomes an urgent object to check it, even though the primary disease of which it is a sj^mptora be irremovable. In the hyper{3emia of the kidneys which occurs in acute Bright's disease, after overdoses of turpentine and cantharides, after blows, falls, muscular efforts, and other external injuries, h?ematuria is a positive relief to the loaded vessels, and were it not that the effused blood is prone to coagulate in the uriniferous tubes, and produce a phj^sical obstacle to the excretion of urine of a most dangerous character, the hemorrhage (unless exces- sive) might safely be left to its own course. To relieve the con- gestion in these cases, derivation by the loins (cupping etc.), by the cutaneous surface (baths, diaphoretics), and by the intestines (hydragogue cathartics), must be energetically practised. ^ Traite des Malad. des voies virinaires. Segalas's edition, p. 283. 2 Cited by Rayer, t. ii. p. 25, * Chopart (1. c. p. 282) cites one instance, and Eayer two instances, in -which hasmaturia occurred at reguhir monthly periods in males. One of these was a butcher of Sedan. The circumstance became known, and such was the disgust caused thereby that no one would purchase meat from him. •'Basham on Dropsy, 3d ed , p. 312. 156 ABNORMAL SUBSTANCES IN THE URINE. When haematuria is supplementary to hemorrhoidal dis- charges, leeches may be applied about the anus. It should be remenibered, however, that if the blood be shed from the mucous membrane of the bladder, and not from the substance of the kidney, such a discharge is not to be looked on unfavorably, nor to be rashly suppressed. When moderate hsematuria occurs vicariously with menstruation, it is to be suppressed only on condition that the normal flux be reestablished. Passive hsematuria in the course of zymotic diseases should be carefully distinguished from acute B right's disease, which some- times forms a sequela to these. In the former, the bleeding is probably from the whole or greater portion of the urinary tract, and not solely, if at all, from the kidneys. The internal reme- dies]of most avail in passive hesmaturia, are the mineral acids, especially sulphuric acid, freely administered. When our object is simply to treat the hsematuria for itself — to stay the loss of blood — the first point is to enforce perfect rest, and to apply cold in the most effective manner to the bleed- ing part. If the kidneys be the source of the blood, ice-poultices should be applied to the loins; if the bladder, iced-water injec- tions may be practised into the bladder, and iced-cloths applied to the perineum and epigastrium. The medicinal hsemostatics which have been found of most service, are gallic acid, acetate of lead, alum, ergot of rye,^ tincture of muriate of iron, turpen- tine, and matico. Dr. Golding Bird speaks highly of acetate of lead given frequently and in large doses for short periods. He recommends 3 or 4 grains, with one-fourth of a grain of opium, in a pill every two hours, until six or eight doses have been administered — care being taken to keep the bowels open by saline purgatives. Dr. Prout observes: "When the bladder be- comes distended with blood, and complete retention of urine in consequence takes place, recourse must be had to a large-eyed catheter and an exhausting syringe, by the aid of which, and the occasional injection of cold water, the coagula may be broken up, and removed. If the hemorrhage be so profuse that the bladder becomes again distended with blood in a very short time, the injection of cold water into the rectum or bladder is some- times of great use; and should these means fail, from 20 to 40 grains of alum may be dissolved in each pint of water injected into the bladder, a remedy that seldom fails to check the bleed- ing even when the cause is malignant disease. I have never known any unpleasant consequences follow the use of this expe- dient; and have seen it immediately arrest the most formidable hemorrhage when all other means had failed, and when the ^ The subcutaneous injection of five grains of ergotin seems worthy of trial, judging by the successful results of this method in pulmonary and uterine hemor- rhages. See Dr. Ritchie, Practitioner, 1871. HEMOGLOBINURIA. 157 bladder had repeatedly become again distentcd with blood almost immediately after its removal."^ VI.— HAEMOGLOBIN UlU A— PAROXYSMAL HyKMOGLOBINURIA. HyBMATiNURiA. — Attention hus been called by Vogcl,^ Oppolzer,^ and Mettenheimer,'' to the escape of the coloring matter of the blood (hseraoglobin) with the urine, unaccompanied by rupture of the capillaries and the presence of blood-corpuscles. The urine in such cases assumes a deep red or blackish-red color, very much as if it contained blood; but no blood-disks can be found under the microscope, nor any fibrin. This condition is invariably accompanied by the presence of albumen in the urine. It is caused by the rapid destruction of the blood-disks in the bloodvessels, such as occurs in that state which is known as "a dissolved state of the blood," in septic, pyeemic, and putrid fevers, and in some extreme cases of scurvy and purpura. In such cases hsemoglobin is set free by the disintegration of the red disks, and appears in the urine. Vogel found that inhala- tion of arseniuretted hydrogen produced an intense (but tempo- rary) degree of hsemoglobinuria. He produced the same condi- tion artificially in animals by inhalation of the same gas and of carbonic acid; also by the injection of substances into the veins which are known to dissolve and break up the red disks. Ponfick (Yirch. " Arch.," B. 72, S. 273) has described hemoglo- binuria as occurring after the transfusion into an animal of blood from an animal of a difierent species. He believed that the heemoglobin of the transfused blood-corpuscles was dissolved in the serum of the recipient animal. Hsemoglobinuriahas also been observed after severe burns Q), in typhoid fever (^), and scarlet fever P), after fat embolism (*), and in poisoning by hydrochloric acid (^), sulphuric acid Q, pyrogallic acid C), carbolic acid (^), and chlorate of potash (^).* A case of ha-moglobinuria from chlorate of potash poisoning, in which death occurred, was described by Dr. Dreschfeld and iProut: Stomach and Eenal Diseases, 5th edit., p. 421. ^J. Vogel: Kranlvh. der Harnbereitenden Organe. in Virchow's Handbuch der Speciellen Path. u. Therap., Band vi., 2te Abth. p. 539. ^"Wiener med. "Wochensch., 1860, Nos. 25 and 26. * Wiirzburger Med. Zeitsch. 1862, p. 1. * (') See Lichtheim, Volckmann's Samml. klin. Vortrag., 134. (^) Iiiimer- mann, Deutsch. Arch. f. klin. Med., Bd. 12, S. 502. (3) Heubner, ibid., Bd. 23, S. 282. (*) Scriba, Deutsch. Zeitsclir. f. Chirurg., 1879, Bd. 12, 118; Puedel, ibid., Bd. 12, S. 118, 1880. (») Naunyn, Dubois Arch., 1868, S. 413 C) Bamberger, Centralbl. f. Med. Wissen., 1874, p. 571. (■)Neisser, Zeitschr. f. klin. Medic, Bd. 1, S. 88, 1880. (8) ZurNieden, Berl. klin. Wochensch., 1881, p. 705. [^) Jacobi, New York Med. Record, 1879, xv.. No. 11 ; Marchand, Virch. Arch., 77, p. 455. Catarrhal jaundice may occasionally be accompanied by ha?moglobinuria. This was exemplified by a case I saw a short time ago in consultation with my colleague Dr. Dreschfeld. 158 ABNORMAL SUBSTANCES IN THE URINE. Mr. Stocks, at the International Medical Congress, London, 1881. The patient, a woman, had taken an uncertain quantity of the drug, to relieve a sore throat. Death was preceded by great cyanosis, and the passage of quantities of haemoglobin from the rectum and vagina, and in the urine. The clinical significance of hsemoglobinuria depends entirely on the pathological state which occasions it. Paroxysmal Hemoglobinuria. [Synonym — Intermittent Hceniatinuria.) Attention was first called in this country to this curious dis- order by Dr. George Harley, who published two cases in the ^' Med.-Chir. Trans." for 1865.^ Subsequently cases were re- corded by Dickinson, Greenhow, Gull, and others; and from an analysis of these, and of personal observations, together with cases reported by Continental observers, the following account has been drawn up :^ ^ The disorder is essentially intermitting or paroxysmal in its nature. Each paroxysm begins with a feeHng of cold or shiver- ing, resembling the cold fit of ague, and terminates with the discharge of a very dark bloody-looking urine. The symptoms then subside, and the urine at the next micturition, or the one after, is found to have resumed its natural healthy appearance. The recurrence of the paroxysms in dift'erent cases is most irregular. In some cases the paroxysm recurs once a day, or even twice and thrice a day. More commonly it recurs on alternate days, or twice a week, or once in ten days, or quite irregularly. The paroxysms are sometimes followed by a hot or sweating stage. The onset of a paroxysm is usually sudden. The patient first experiences coldness of the extremities, fol- lowed by general chilliness, which in most cases passes into distinct rigors, accompanied by a feeling of malaise, a disposi- tion to stretch himself, and to yawn. In most cases, a sense of weight, or a dull heavy pain is felt in the loins, sometimes extending to the umbilicus, or passing down the thighs, occa- sionally there has been noted tenderness over the region of the kidnej^s ; and there is frequently pain, or a feeling of stiffness or weakness, in the lower extremities. Retraction of the testicles has been noted in several cases. Retching is a not infrequent 1 Dr. Wickham Le2:g, in his admirable paper on the subject, has directed atten- tion to the fact that Dessler, in 1854, published a complete account of the disorder in Virchow's Archiv for that year. 2 The article on this subject in the preceding edition of this work was the result of an analysis of twenty cases. Subsequently more numerous observations, however, have rendered necessary many alterations and additions. PAROXYHMA li IT yE M OGLOBI N U K I A . ]o9 symptom, and vomiting was a prominent feature in a few cases, wliilc the patient sometimes comjtlains of thirst, headache, and drowsiness. After these symptoms have lasted for a period varying from thirty minutes to two hours, the patient passes a (quantity of dark-colored urine; the pain and general distui-haiu^e tlien suh- side, leaving the patient apparently quite well till the next paroxysm. The appearance of the dark urine resemhles that of porter or of the darkest port wine. It is generally turbid, and deposits, on standing, an abundant chocolate-colored sediment. The sp. gr. varies from 1015 to 1033, usually ranging from 1022 to 1025. The reaction is either acid or faintly alkaline. It is always highly albuminous, and, on boiling, the albumen coagu- lates into brownish masses, which, on subsiding, leave the clear supernatant urine of nearly its original dark-red color. In Ilar- ley's cases, and in one of mine, the percentage of urea was found to be in considerable excess; in some cases, however, it has been found lower than usual. The chocolate-colored sediment consists chiefly ot amorphous granular matter, which is, presumably, disintegrated blood-cor- FiG. 33. Granular matter, casts, and octaliedra, from the deposit in tlie urine uf a man with paroxysmal ha;moglobinuria. puscles. Gull found in it myriads of minute crystals of hsema- tine. Casts of tubes are also present ; these are mostly of dark granular appearance — mixed, however, with a few transparent fibrinous cylinders. Many casts are formed of masses of haemo- globin. Crystals of oxalate of lime are generally seen, and, very rarely, a few stray blood-disks. The urine gives the usual reactions of blood with the guaiacum and Heller's tests. Usually, on spectroscopic examination, there are found the two absorption bauds between Frauenhofer's D 160 ABNORMAL SUBSTANCES IN THE URINE. and E lines, which are characteristic of oxhsemoglobin. An additional band in the red, indicating the presence of methsemo- globiri, has also been observed by many writers. Concerning this band, however, there is some difference of opinion, and no doubt in many cases it is absent. In most cases the albumen and the haemoglobin appear and disappear together. Murri^ and Rosenbach^ observed albumen in the urine before the blood-coloring matter could be per- ceived. This, however, has not been confirmed by others. Dr. Forrest, on the other hand, found that the albumen persisted after the disappearance of the hsemoglobin, while Dr. Saundby, in one of his cases, saw the blood-coloring matter in the urine when no trace of albumen could be detected. During the attack, the extremities, nose, and ears may be cold and cyanotic. A general eruption of urticaria has been noticed in some cases by Mackenzie, Forrest, Lichtheim, and others. In a few cases the liver and spleen increased in size during the attack; and in Boas's case, pains in the region of the liver seemed to be precursors of an attack. Careful examination of the blood during the attacks has been made by recent observers, particularly hy Ehrlich, Boas, and "Wolff. The main changes observed were, absence of the ordi- nary rouleaux of red blood-corpuscles, variations in shape of the red corpuscles, and the presence of Ponfick's so-called " phan- tom" corpuscles, or red corpuscles from which the coloring matter had been dissolved out. Sometimes, however, the hiicro- scopical examinations of the blood have shown no change. The temperature daring the paroxysm is usually raised, in one of Dr. Saundby's cases to as high as 105.2° It may, however, be normal, or in some cases a preliminary fall may precede the rise. {See Charteris, " Lancet," Jan. 1879.) The first onset of the disorder is invariably sudden, and can usually be traced to some distinct exposure to cold or wet. The subsequent paroxysms are generally quite unconnected with any fresh exposure to cold, but in other cases the contrary is the case. The paroxysms recur, in some cases, with the regu- larity of real ague, for weeks together ; in other cases the perio- dicity is quite imperfect. Each paroxysm lasts from three to twelve hours, and it is noteworthy that no paroxysms occur at night, the urine voided before breakfast being invariably natu- ral.^ The change in the characters of the urine may take place with the utmost abruptness; that passed at one micturition being porter-like, and at the next straw-colored; or it may more 1 Kevista clinica di Bologna, 1879. ^ Berlin, klin. Wochen., 1880, p. 132. * See, however, a case reported by Lepine (Revue Mensiielle, 1880, p. 722), in which cold had no influence, and the paroxysms occurred at midnight. PAROXYSMAL II iE MOGLO J{ I N U R I A . ItJl gradually bocoiue pale, resuming its normal a[)[)oarance at the fourth or fifth micturition after the paroxysm. The state of the general health seems to vary somewhat. In one case reported by Dr. Dickinson, the patient had the appear- ance of robust health the day l)efore an attack came on. In most cases, however, the patient has pi-esented a somewhat sal- low and icteric aspect, or has looked ansemic, pale, and sickly. Sometimes there has been hepatic derangement distinctly present at the time the patient has come under observation. In one case, an intercurrent attack of jaundice came on, the urine being deeply colored with bile, and copiously depositing lithates, but containing no blood-coloring matter, and only once a trace of albumen. Occasionall}^, after severe paroxysms, the conjunctivae are of a yellowish color, but no bile pigment is found in the urine. The color is probably due to serum holding haemo- globin in solution, which is transuded during the attack. A rheumatic tendency is a frequent concomitant of this affection, many of the patients having frequently sufi!ered from rheumatism in various forms. In one of my own cases the patient began to suffer from subacute rheumatism, with swell- ing and pain in the joints after the cessation of the paroxysms. A bronchitic and asthmatic tendency has also been observed in one or two instances. FraentzeP is of opinion that there is a decided tendency to chronic lung disease. Of twenty cases collated by me, four had at one time or another suffered from undoubted ague, but in the remainder no evidence or suspicion of ague or malarial poison existed. The course of the disorder is an interrupted one. The parox- ysms may recur with more or less regularity for a period of a few days, or ffve or six weeks, and then cease altogether for a few days or weeks, or months, and recur again for a period as before. In this way it may continue an interrupted course for many months or years ; in one case for so long a term as eleven 3'ears. The prognosis is generally good. Of the twenty cases men- tioned above none died, twelve were reported as having com- pletely recovered, one was convalescent, and seven were still in progress when reported. By complete recovery is understood that there was no recurrence of the paroxysms for a period varying from six weeks to four years. It must, however* be borne in mind, that a relapse may take place after a pause of several months — in one case a recurrence took place after a pause of live months. The following three examples will serve to illustrate the gen- eral course and symptoms of the disease. The first and second 1 Berl. klinisch. Wochenschr., 1881, p 42. 11 162 ABNORMAL SUBSTANCES IN THE URINE. were observed by myself, the third by Dr. Ritchie ; these cases have not been elsewhere published : Case 1. — J. J., an iron moulder from Stockport, set; 23, consulted me in March, 1868. He was thin and weak, with a conspicuously white, pallid countenance. He stated that for a period of twelve months he had been in the habit of passing dark bloody-looking urine from time to time at frequent intervals. His complaint began in the following manner : He was standing in the street one cold afternoon in March of the previous year, when he was seized with chilliness and shivering and pain in the loins. When he got home he voided urine, and was surprised to see it of a dark- red color. From this time up to the date of his visit to me he continued, with only short intervals, to pass every day urine of a similar character. He became so weak that he did not leave his house for ten months; but he never took to his bed, except for a day or two. The discharge of the dark urine was essentially paroxysmal and inter- mittent. He would go on passing bloody urine daily for periods vary- ing from three to six weeks — then the urine would be natural for an interval of three, four, or even ten days, and then become bloody again for a stretch of several weeks. But the urine was never constantly bloody during any whole period of twenty-four hours. During each diurnal circle, three paroxysms occurred with great regularity : one in the morning (after breakfast) between nine and ten, a second between two and three in the afternoon, and a third between six and nine in the evening. Each paroxysm presented the same succession of symptoms. It began with chilliness, which speedily went on to shivering so that his teeth chattered — at the same time there was severe pain in the loins and hips. At the end of twenty or thirty minutes these symptoms wore off, and then he felt a desire to void urine — and the urine then passed was always bloody ; this completed the paroxysm. It was never followed by a hot or sweating stage. If he made water between the paroxysms, the urine was either perfectly clear and natural, or only slightly dark. The urine voided before breakfast was always quite natural. The patient visited me several times, and brought me several speci- mens of the bloody urine. On one occasion he voided some in my pres- ence, and a description of this will answer substantially for all the rest. It was of the color of the darkest port wine — so dark as to be almost opaque, except in thin layers ; it corresponded pretty closely to No. 9 on Vogel's scale. A brownish deposit formed on standing ; sp. gr. 1028 ; it was highly albuminous, and faintly alkaline. On boiling, the albu- men coagulated into a chocolate- colored clot, but the supernatant fluid did not lose its black-red color. The deposit consisted of a granular matter. It contained numerous crystals of oxalate of lime ; but no blood-disks could be recognized. In April I admitted the patient into the Infirmary, with a view of studying his case more fully. But, with the exception of the first morn- ing, the urine was perfectly normal throughout his stay, and he went home in a week. While in the Infirmary his blood was examined under the microscope, but nothing unusual was found. The liver and spleen were thought to be somewhat larger than usual — otherwise all the organs PAROXYSMAL II^<] M OG LO JM N U HI A . 163 were healthy. After leaving the Infirmary, he continued to attend as an out-patient for some months — taking constantly, three times a day, a pill containing three grains of (juinine and one grain of sulphate of iron. Under this treatment, the symptoms gradually suhsided, the paroxysms became slighter and slighter, and at the end of three months ceased alto- gether. The general health also greatly improved. After the cessation of the paroxysms, he began to suffer from subacute rheumatism, with swelling and pain in the joints. He was troubled in this way for more than a twelvemonth, and went to Buxton, where he derived great benefit, and finally recovered. I saw this man a few days ago (March, l-STO) ; there had been no return of the paroxysms, and he looked well and ruddy. The patient stated positively that, except at the first onset of his com- plaint, the paroxysms came on independently of exposure to cold ; he was just as bad in the summer as in the winter. Throughout his illness he ate and slept well. He had never lived in an aguish district, and he still occupies the same house as when his ailment commenced. Case 2. — The notes of this case are imperfect, and my own observa- tions are confined to an examination of the urine. On November 28, 1871, my colleague. Dr. Renaud, sent me two samples of urine which had been voided by the same man at different periods of the same day. The contrast between the two samples was marvellous. One sample was of the usual yellowish-amber color, clear and free from a trace of albu- men — in short, perfectly normal. The other was of the blackest red color, quite opaque, except in the thinnest layers. Its sp. gr. was 1032 ; it was so albuminous that it solidified into a chocolate-colored jelly when boiled in a water-bath. On standing, it deposited a copious dark-brown sediment. Under the microscope (see Fig. 33) this was found to consist of amorphous granular matter, amid which were seen numbers of tube- casts. The casts were mostly of a medium size, and dark granular char- acter. Some were small, and a few almost transparent and approaching the hyaline character. Not a single recognizable red blood-disk could be seen, but a few corpuscles, resembling the white blood-globules, were scattered here and there. The field was full of minute bright specks of oxalate of lime octahedra. The proportion of urea, as ascertained by Liebig's method, was 5.2 per cent. When the urine was boiled in a test-tube, the brown albuminous clots separated, and left a dark amber* transparent supernatant liquor. The history of the case, as far as it was gathered by Dr. Renaud, was as follows : The patient was a man of forty, of a sallow complexion, who felt, nine weeks before, as if he had taken cold. A fortnight since he lost his appetite, and shivered, and afterwards perspired. He kept his bed four days. On November 21st he passed, at noon, urine the color of blood ; and he has done so nearly at the same time (i. e., once in twenty-four hours) till yesterday. At other times of the day he passed urine of the natural color. I have not been able to obtain further par- ticulars of this case. Case 3. (From the notes of Dr. Ritchie.) — T. M., a tailor, married, set. 32, consulted me on December 18, 1869. He was above the medium height, dark-complexioned, and had a sallow appearance. He gave the following account of himself: He had formerly been a soldier, and had 164 ABNORMAL SUBSTANCES IN THE URINE. lived for nine years in the West Indies ; during that time he had suffered from " black fever," and from repeated attacks of ague, the last of which seized him towards the end of 1865. These were the only illnesses he could remember till March, 1869, when he reminded me he had been under my care in the out-patients' room of the Manchester Royal Infir- mary, suffering from pleurisy with limited effusion ; and again, in Sep- tember, 1869, from subacute rheumatism. He now complained of passing bloody-looking urine once or twice a day — that passed in the intervals being apparently quite healthy. He first observed this symptom about two years before, under the following circumstances : He had been engaged in some gymnastic exercise one November evening, and feeling greatly overheated, had imprudently gone to the door of the gymnasium to cool himself, when he was sud- denly seized with chilliness and violent shivering, followed by severe pain across the loins, and a feeling of nausea. About an hour afterwards he voided a small quantity of urine having the color of porter. The urine passed the next morning before breakfast was apparently quite natural, but at night the porter-like color was again present. For about two months the discharge of this dark urine took place once or twice every day, and then spontaneously ceased. He had had two similar attacks since — one in March, 1868, lasting about six weeks, and the other in September of the same year, lasting nearly four months. His present attack, which was the most severe he had yet suffered from, began about a fortnight before he came to see me. It immedi- ately followed exposure to cold and wet, and was ushered in by all the premonitory symptoms which characterized his previous seizures. The phenomena observe the following order : He feels perfectly well on get- ting out of bed in the morning, and usually passes about ten or twelve ounces of straw-colored urine; about ten o'clock he begins to yawn and shiver, and feels " as if he couldn't stretch himself enough ;" he then suffers a dull, heavy pain across the loins, which sometimes extends round to the umbilicus, passing down the thighs ; the testicles become retracted. There is no pain along the course of the ureters. The shiver- ing and lumbar pain increase for about an hour, at the end of which he usually passes from eight to ten ounces of porter-like urine, upon which the symptoms gradually disappear. He usually voids urine again about one or two o'clock, which to all appearance is perfectly healthy. About four, the same succession of phenomena runs its course, to be followed by the discharge of dark urine about five, and again about ten o'clock in the evening. He has thus had three distinct paroxysms every day from the 2d to the 15th of December — remaining perfectly free from them between the night of the 15th and eleven o'clock in the forenoon of the 18th, when he began again to pass the porter-like urine. He stated that he usually went to bed when he felt the paroxysm coming on, and that he had the greatest difficulty in keeping himself warm ; " so different," as he remarked, " from what it used to be, when he would have the ague." It was about 2 p.m. on the 18th when he came to see me, and he was requested to send for me on the occurrence of the next paroxysm. A message was received from him about 9.15 the same night, and half an hour afterwards I was with him. He was in bed, shivering violently, PAROXYSMAL HyK MOGLOBl W URI A . 165 and feeling very cold ;.his temperature in the axilla was i)().(P Fahr. ; he suffered from the lumbar pain and feeling of sickness previously described ; the testicles were closely retracted. lie was ordered a warm drink, and to have an additional pair of blankets on his bed. A few minutes after my arrival, he passed a quantity of urine, which was secured for the purpose of examination. Five minutes afterwards, he said that he was perfectly free from pain and discomfort, and felt quite well. His temperature was then 98.6°. There was slight ten- derness over both kidneys on deep pressure, and also over the eleventh and twelfth dorsal vertebrte. Lungs apparently healthy, with the excep- tion of slight comparative dulness over the right back — no doubt the remnant of the pleurisy from which he had suffered in the preceding March. Heart sounds and rhythm normal. Liver measured five inches vertically in the maramillary line. Spleen nearly three and a half inches; colorless blood-corpuscles slightly, but not markedly, increased. His general health was good ; appetite fair ; bowels had not been relieved for two days. The urine which he was seen to pass measured eight ounces; it was not unlike porter in color, but had a redder tint ; it was almost opaque — neutral or feebly alkaline in reaction ; sp. gr. 1026. It contained a large amount of albumen which, on the application of heat, was thrown down in the form of a chocolate-colored clot, increased on the addition of nitric acid ; the coagulum occupied about half the bulk of the urine examined, the supernatant fluid retaining its intensely dark reddish- brown color. On microscopic examination, it was found to contain abundant octahedral crystals of oxalate of lime, a few granular tube- easts, a large quantity of granular matter of a dark brownish-red color, and a quantity of amorphous urates. No blood-corpuscles could be detected. The urine passed on the morning of the 19th December, before break- fast, possessed the following characters : it measured about 10^ ounces, was of a light amber color, acid, sp. gr. 1018 ; contained no albumen ; on standing, the dense, snow-white, cloud-like deposit, characteristic of the presence of oxalates, was thrown down. Under the microscope, it was seen to contain octahedral crystals, pavement epithelium, and granular-looking cells. The usual course of the paroxysms was observed, viz., that porter-like urine was voided three times a day, preceded by the same succession of symptoms. He was first ordered ten-grain doses of gallic acid three times a day, then tannic acid, and afterwards turpentine, without the slightest change in his symptoms. On the 28th December, he was ordered two pills three times a day, each containing sulphate of quinine 3 grains, sulphate of iron 1 grain, and strychnia gig- grain. Under tljis treatment he gradually improved, the paroxysms coming on less fre- quently, and being milder in their character, till the 17th January, 1870. He remained perfectly free from that date till the 5th of April, w'hen he had another similar attack after a sudden chill. The paroxysms on this occasion were slighter, and only came on twice daily, viz., in the forenoon and at night. The ui-ine presented the essential characteristics described fully above. He was placed on the same treatment which had 166 ABNORMAL SUBSTANCES IN THE URINE, proved successful on the former occasion, and the paroxysms ceased entirely on the 14th of April. I had lost sight of this patient till the 31st March, 1871, when a letter was received from him, stating that he had gone to reside in the north of Ireland, and that he had remained perfectly free from his former attacks from the time I had seen hira last till the beginning of that month. He had then suffered for nearly a fortnight a recurrence of his former complaint, from which he had just recovered under the use of the same treatment that had been previously adopted. Etiology. — The liability to paroxysmal hsemoglobinuria seems to be almost exclusively confined to males, one only of twenty collated cases occurring in a female. The age of the patients at the time of invasion ranged from 2 years of age to 48 ; two cases being under 20, seven between 20 and 30, six between 30 and 40, two between 40 and 50, and three cases in which the date of invasion is not specified. A hereditary tendency has been occasionally noticed. Hsemoglobinuria has been known to occur occasionally in the course of chronic Bright's disease. As to the exciting cause of the disease, in two cases out of the above twenty it was found distinctly connected with malarial poisoning, both patients actually sufiering from ague at the time the hsemoglobinuria was first "observed. In all the other cases (with one exception) the disease was clearly attributable to vicissitudes of temperature or exposure to wet. The effects of exposure to cold are well exemplified in a case of Dr. Johnson, cited by Dr. Dickinson (loc. cit.), in which the patient, so long as he remained in bed, continued free from the paroxysms ; but if he sat up and got chilled, a paroxysm came on. In a case mentioned by Dr. Pavy ("Path. Soc. Trans.," vol. xviii. p. 157), the patient had sometimes averted an attack by going indoors directly he felt it coming on, and sitting before the fire and drinking something warm. Sir W. Gull believes there is' reason for thinking that a blow or injury to the loins may be the cause of this affection ; and cites the case of a young lady who in getting into a railway carriage fell and hurt her back, shortly after which she passed dark bloody-looking urine, in which he found, on careful examination, no blood-corpuscles, but only the granular pigment matter of disintegrated blood-corpuscles. "Whilst admitting the possibility of such injuries causing haema- turia, or even as in this case haemoglobinuria, we should, how- ever, in the absence of further evidence on the point, hesitate to accept them as a cause of 'paroxysmal haemoglobinuria. Fleischer^ has recorded a case in which heat and cold pro- duced no effect, but the paroxysms were always brought on by 1 Berlin, klin. Wochenschr., 1881, No. 47. PAROXYSMAL H y1<] M OG I.O Ji I N U K I A . 167 exercise. In the rare cases wiiicli occur in worneii, Wolf saw the attack brought on under the influence of menstruation alone. Hfenioglobinuria has been noticed in cases of Jiaynaud's sym- metrical gangrene. {See Southey, " (Jlin. Trans.," vol. xvi. p. 167.) Murri asserts that a causal relation exists between syphilis and paroxysmal hiemoglobinuria. He found a history of sypliilis in such cases, and obtained a cure by the use of antisyphilitic remedies. The Pathology of the disorder is very obscure. It very rarely ends fatally, and the few post-mortem examinations w^hich have been obtained have given no clue to the origin of the disease. More important evidence has resulted from a consideration of hsemoglobinuria produced experimentally in animals, and from a close examination of the paroxysm as it occurs in man. Ponfick found that the hsemoglobinuria caused by transfusion (p. 157) was accompanied by symptoms closely resembling those of the paroxj'smal affection in man. In the artificial affection, however, he found that there was a solution of hsemoglobin in the blood-serum, and that the red blood-corpuscles showed pecu- liar changes, which he believed were produced by their partial destruction. Very similar changes have been noticed, in the paroxysmal affection of man. If during the paroxysm the serum obtained from a blister or a cupping-glass be examined, in many cases, at least, it will be found to contain haemoglobin in solu- tion (Kiissner,^ Hayem, and others), and presumably the whole of the serum of the body is in the same condition. The micro- scopic examination of the blood (p. 160) during the paroxysm has also revealed changes similar to those described by Ponfick in the artificial affection. It therefore seems probable that in paroxysmal hiemoglobinuria we have to deal with a condition in which the blood-corpuscles give up their hsemoglobin to the surrounding serum. We know, however, from the researches of Bernard, and Stokvis, that if certain forms of albumen other than serum albumen circulate in the blood, they are usually filtered off" by the kidneys without change, and appear in their natural con- dition in the urine. So then, if a solution of haemoglobin circu- late in the blood, it also will be excreted in the urine.^ Most observers are now agreed that the solution of the hfemoglobin in the serum precedes its appearance in the urine, and that the symptoms of kidney affection, which are sometimes present, are due to the irritation produced by the passage of the hemoglobin 1 Centralbl. f. Med. Wissensch., 1883, p. 820. 2 Deutsch. Med. Wochenschr., No. 37, 1879. 8 If only a small amount of haemoglobin be dissolved in the serum, it may appear in the urine as bile-pigment (Cohnheim). 168 ABNORMAL SUBSTANCES IN THE URINE. through those organs. Adams^ found that the glomeruli of the kidney alone were concerned in the excretion of the haemo- globin. In Dr. Dreschfeld's case of poisoning by chlorate of potash (p. 157), haemoglobin could not be seen in the glomeruli, but only in the convoluted tubes, while Ponfick^ has lately ghown that all the secreting parts of the kidney may be concerned in the process. A few observers, and amongst them Rosenbach and Lepine, still hold that the kidneys are primarily affected, and that in them the blood-corpuscles are destroyed, and their haemoglobin reabsorbed b.efore it can circulate in the blood-serum. Rosen- bach mainly based his opinion on the fact (see p. 160) that he observed albumen to appear in the urine before haemoglobin. There are, however, only few" observations in which such dis- order of the kidney function was found ; while Roux,^ working in Cohnheim's laboratory, has shown that the amount of albu- men found in the urine of an ordinary case is just sufficient to combine with the amount of iron present, in the proportions necessary to produce hsemoglobin, and that hence the albumen present is probably derived entirely from the haemoglobin. The behavior of the blood-corpuscles has been investigated by Ehrlich and Boas, by ligaturing a finger and then placing it in ice-cold water. In a healthy person this produced no change on the blood of the finger, but in a person who was subject to hsemoglobinuria, solution of haemoglobin in the serum was ob- served, and also the changes in the blood-corpuscles described by Pontick were seen. The red blood-corpuscles were, therefore, less resistant to cold than in the normal state. Boas also showed that they were more easily destroyed by the electric current than were healthy corpuscles.* It seems probable that a similar de- struction of the blood-corpuscles may take place in the exposed and chilled parts in the paroxysmal affection, and such a view is supported hj Dr. Southey's cases of symmetrical gangrene already mentioned. The cause of this condition of the blood-corpuscles is, as yet, a matter of pure speculation. According to Murri the cause is to be sought in a diseased condition of the blood-forming organs, which rendered the corpuscles less resistant to cold and to car- bonic acid than normal corpuscles are. Whether primarily or 1 Dissertat., Leipzig, 1880. 2 " Verhandl. des Congresses f. inn. Medic," Wiesbaden, 1883. This papermay also be consulted for information concerning the so-called " Hsemoglobinasmia," which precedes the change in the urine. The author shows that not only the kidneys, but also the spleen and the liver take part in removing the haemoglobin from the circulation. 3 Cohnheim's Allgemeine Pathologic, ii. p. 295. * Only one experiment, however, was successful, and further evidence is desirable. PAROXYSMAL HAEMOGLOBIN U R I A . l<-i9 secondarily, however, the nervous system must be an active agent in producing the plienomena of the [)aroxysm. There seems to be some connection between this affection and ague, but its precise nature is as yet unknown. Though related, they are not identical, as in by far the greater number of cases there has been neither an aguish tendency nor any evidence of exposure to malarial influences. Treatiment. — The remedies appropriate to the ordinary forms of ha3maturia have been found wholly inefficacious in this dis- order. In two of the reported cases the attacks seem to have passed off without any medicinal treatment, simply by avoiding exposure to cold. In one case, recorded by Dr. Dickinson, cup- ping over the loins, vapor baths, gallic acid, quinine, iron in various forms, were tried in succession, but nothing seemed to affect the disorder; "the hemorrhage always ceased on the re- moval of the cold which caused it." This patient had an inter- current attack of pneumonia, after which he passed into a typhoid condition, from which he slowly recovered under the use of stimulants, and afterwards of quinine and iron, and was discharged well. Dr. Harley gave mercurials, and afterwards quinine in his cases, with marked benefit, one patient having re- mained free from the paroxysms for four years, during which he was under observation. Sir "W. Gull gave two drachm doses of compound tincture of cinchona three times a day, with benefit: the patient went out of hospital "convalescent.'" Dr. Hassall found that the hemorrhage was considerably restrained, by giving, night and morning, a powder containing tannic and gallic acids, and burnt alum, with a mixture containing quinine, sulphate of iron, and excess of sulphuric acid during the day. Dr. Habershon found that quinine and arsenic, and Dr. Green- how that quinine and perchloride of iron, and afterwards qui- nine and syrup of the iodide of iron, with iodide of potassium, had the effect of causing the urinary symptoms to subside, and the patients remained free from attacks for several months after- wards, during the time they were under observation. Dr. Beale calls attention to the importance of giving quinine in full doses, not less than six grains, in order to combat the disorder success- fully. Dr. Begbie, in one of his cases, found that the p)aroxysm did not recur when the patient took twenty grains of sal ammo- niac three times daily. During the paroxysm, Dr. Ritchie found the best treatment was to send the patient to bed, apply artifi- cial heat, and administer warm stimulating drinks, such as hot brandy and water. The evidence generally is strongly in favor of quinine and iron as the most effective medicinal agents. In cases where a syphilitic taint is suspected, it would be well, in view of Murri's results, to prescribe an anti-syphilitic treatment. 170 ABNORMAL SUBSTANCES IN THE UEINK, VII.— CANCEEOUS AND TUBERCULOIJS MATTER IN UEINE. When cancer or tubercle of any part of the urinary tract has t^one on to ulceration, the urine carries away with it some of the aisintegratecl elements, giving rise to an amorphous-looking grumous deposit. Sometimes masses of the morbid tissue as large as a horse-bean are discharged with the urine, and more or less blood is always mixed with such deposits. Very great caution is requisite in coming to a conclusion as to the cancerous nature of cells found in urine, on account of the great similarity between the irregular transitional forms of the epithehal cells lining the urinary "passages, and the cells of can- cerous growths. Indeed it would be quite unsafe, in such a case, to rely on the mere form and size of individual cells. In the annexed drawing (Fig. 34) may be seen the diverse shapes dis- FiG. 34. Cell from the urine of a woman with fungus of the bladder, a, Fibro-plastic cells ; 6, b. Cancer cells ; c. Epithelial cells ; d. Pus ; e. Blood. charged with the urine in a case of malignant fungus of the bladder. If the forms be compared with those in Figs. 23 and 31 {g), the similarity of the cells will appear very striking. It is more safe to take the entire character of the deposit into con- sideration. It may be described as a thick, dirty, blood-stained sediment, containing abundance of blood-corpuscles, mixed with spindle-shaped, oval, and irregular cells. Pus-corpuscles may be either wholly or nearly absent. The presence of shreds or pieces of solid tissue appreciable to the naked eye, should be carefully looked for : their occurrence is almost a certain proof of the existence of some morbid growth. The character of the deposit generally, and especially the presence of numerous SPERM ATORRIin-; A. 1 71 spindle-ahaped (libro-plastic) cells, which cannot 1)6 mistaken for epithelial elements, indicate clearly that soine morbid growth or natural tissue is being l)roken up. The collateral s_yrn})toms are then generally sufhcient to decide whether the broken-up tissue is a portion of the natural membrane or an adventitious growth. In cancer of the kidney no help to the diagnosis must be ex- pected from the character of the urinary deposit (see Cancer of Kidney). The discharge associated with tuberculous ulceration differs from that of a cancerous fungus in being largely purulent ; in- deed, pus-corpuscles are usually the chief appreciable formed elements in the urine in cases of tubercle of the kidney and bladder. But in other cases, broken-down cheesy masses may be seen, together with a large quantity of amorphous, or barely morphous granular debris (for the discovery of tubercle bacilli in the urine, see Tubercle of the Kidney). It follows, of course, that cancerous and tuberculous masses may exist in the kidney, or beneath the mucous membrane of the urinary passages, without contributing anything to the stream of urine. It is only when ulcerated that their elements escape with the urine; before this takes place they may, however, give rise to copius and oft-repeated hemorrhage. VIII.— SPEEMATOZOA IN UEINE— SPEKMATOKEHGEA. The admixture of semen with the urine gives rise to a mucous-looking deposit. When in large quantity, white albu- minous flakes and masses are seen; these exhibit a viscid con- sistence when taken up with the pipette. The microscope reveals the existence of spermatic filaments, consisting (Fig. 35) Fig. 35. Spermatozoa. of a minute oval head, not more than -^ ^ ^ ^^ ^ of an inch in breadth, and a long whip-like tail of extreme delicacy. The length of the entire filament is g^ of an inch. 172 ABNORMAL SUBSTANCES IN THE URTNE. When freshly shed, and still living, they exhibit active eel- like movements, strongly suggestive of volition ;^ but as seen in urine they are always motionless. They oifer considerable resistance to disintegration, and may sometimes be recognized in decomposed urine which has been kept for weeks. A certain quantity of seminal fluid necessarily finds its wsij into the urine of both sexes after coitus ; also into the urine of men after involuntary nocturnal emissions. Involuntary nocturnal emissions occurring occasionally in the young and continent, are not to be regarded as within the limits of disease; but when they take place two or three times weekly or oftener, or when the acts of defecation and micturition are frequently followed by a glairy discharge, a diseased state must be acknowledged to exist; and one also, as experience proves, exceedingly difficult to deal with. Whether it be that the mental phenomena observed in these cases are altogether sec- ondary to the genital defect may well be questioned ; but it is an important — indeed the important — fact in relation to involun- tary seminal discharges, that they are associated with a deplor- able state of mind. Much of this is, no doubt, owing to the prurient eagerness with which persons so afflicted seek satisfac- tion to a fatal curiosity, in the publications of unprincipled quacks, who lure their victims with libidinous descriptions, and afterwards terrify them with exaggerated and lying pictures of the fate which awaits them. But there is a danger that the legitimate practitioner may come to look upon cases of this class too lightly, and thus be the indirect occasion of their seeking the help which is their injury. The least serious cases are those in which the emissions are solely nocturnal. As long as the complaint is confined within these limits the general health does not suffer, and the mental state is seldom gravely disturbed. Sometimes, however, indi- viduals of fervid imagination, whose health is from any cause below par, fix upon this incident (nocturnal emissions) with obstinate tenacity, and hinge their ill-health entirely upon it, when in reality it has nothing to do with the matter. Persons go on for years subject to nocturnal pollutions without any harm resulting, but when they chance to become dyspeptic, or their nervous system becomes upset by overwork, then these emissions loom largely to their imaginations, and they connect them with their failing health. When seminal discharges occur daily, and accompany or fol- low defecation and micturition, a greater departure from the ' Students may be reminded that spermatozoa are not really independent ani- mals, but simply the escaped contents of a cell. They are floating cilia, and resemble the oscillating sperm-cells of the antheridse of mosses. SrJiKMATORRIIfEA 173 natural state is betrayed ; and it is seldom that such a state of things continues for any length of time without inducing pallor, weakness, want of zest and energy for work, as well as a fidgety, vacillating, and sometimes very depressed state of mind. Never- theless, these consequences frequently altogether fail. There was recently a patient under my care at the lioyal Infirmary — a ruddy, strong-looking young man of six-and-twenty — who had been in the habit, according to his own account, for the last seven years, of discharging large quantities of seminal fluid almost daily, more especially with micturition. In a specimen of his urine brought to me, there was at least a tablespoonful of glairy matter having the microscopic and other characters of semen. The mental state was certainly shaken, but solely, as it appeared to me, from the diligent study of Mr. Dawson's book on spermatorrhoea. He talked with a sort of gloomy satisfac- tion of being tired of life, but it was with an air as if he were repeating a lesson, and not as one revealing a terrible conviction. The type of mental disturbance usually associated with sper- matorrhoea, is common in this as in other large towns, inde- pendently of seminal losses, among persons — chiefly men of business — whose health has given way from too engrossing ap- plication to exciting pursuits. Such persons become nervous, apprehensive about themselves to a distressing degree, pusil- lanimous, subject to attacks of incomplete syncope; they lose their sleep and sometimes their appetite ; there is some real •emaciation and a great deal of fancied wasting. They pour into the ears of their medical attendants an endless variety of symp- toms, and worry them beyond the most tedious hysterical women. Such patients, although often men of middle age, or ^t least beyond their first youth, and fathers of families, rarely fail to complete the catalogue of their ailments with a refer- ence to what they conceive to be some anomaly of their sexual functions. Involuntary discharges are not confined to youth or middle iige. Men advanced in years are sometimes tormented in the same way, and exactly the same state of mind is observed in them. They imagine their "substance"' to be ebbing from them, and their virility departing. A gentleman over sixty years of age, the father of a family of married daughters, was so concerned about a slight seminal discharge which in no way affected his health, that he forwarded to me for examination over a hundred specimens of his urine. In the Treatment of this class of cases, the first point to establish is whether the trouble of the nervous system is the primary phenomenon, and the disturbance of the sexual func- tions only an insignificant incident, or whether the seminal losses are in such frequency and quantit}' that they may be regarded 174 ABNORMAL SUBSTAXCES IN THE UKINE. as having a hand in evolving the symptoms complained of. The greater majority of cases belong to the former category ; and indications for treatment are to be looked for in the general state of the patient and the circumstances surrounding him, rather than in the condition of the sexual functions. If it appear, after a patient sifting of the actual phenomena and the past history of the case, that the seminal emissions must be regarded as the fundamental ailment, the next point is to inquire into the exist- ence of any local cause for the emissions. The irritation of ascarides or hemorrhoids sometimes occasions involuntary dis- charges : also herpetic eruptions about the prepuce. Lallemand enumerates a long prepuce as contributing to the same, by the lodgement which it affords, in uncleanly persons, to ofiensive se- cretions. Whatever be the local cause discovered, its immediate removal is of course the first step in the treatment. In the absence of a local cause, the evil can usually be traced to venereal excesses, masturbation, and the reading of salacious literature. Some of these cases are very difficult to deal with. An attempt must first be made to put a stop to the practice which is the cause of the complaint. The further treatment should be directed to improving the tone of the muscular system by daily ablutions with cold water or brine, by sea bathing, regu- lated exercise, change of air, etc. The state of the patient's mind often requires that the time, quantity, and material of the meals shall be minutely regulated. The diet should be nourish- ing and bland; spices and condiments should be avoided. Malt liquors and the lighter wines are to be cautiously employed; the quantity must be judged by their efiects. Any quantity which produces flushing of the face is too much. An opiate sometimes renders good service by securing a good night's rest. Astrin- gent and ferruginous tonics offer valuable aid to the hygienic treatment. Tincture of the muriate of iron has appeared tome to produce a better effect than any other preparation, A blister to the perineum has sometimes seemed to diminish the emissions. In cases of inveterate masturbation, Mr, Hilton found that he could invariably put a stop to the practice by applying a strong solution of iodine or blistering fluid to the penis so as to render the organ too sore for manipulation.^ Lallemand recommends the local application of nitrate of silver to the orifices of the ducts of the vesiculse seminales by means of his porte-caustique, I cannot say that I have ever seen cases in which this severe proceeding seemed justifiable. It must be remembered that it is not without danger. Dr. Bird relates an instance in which a dangerous cystitis was produced in a healthy person by the local application of the solid nitrate of 1 Lancet, 1863, II, 123, MICRO-ORGANISMS IN THE URINP:. 175 silver in this manner. l)v. Chambers has communicated another and more untoward example, in which death followed the appli- cation of an irritant ointment \)y means of a catheter in a case of imaginary spermatorrhcjoa.' Dicenta, B. Schulz,^ and Benedikt,''' speak in high terms of the constant galvanic current. Schulz directs the current to be transmitted along the vertebral column for one or two minutes, and repeated three or four times a week. Twenty or thirty Daniel's elements, of medium size, should be used ; the positive pole should be applied to about the fifth dorsal vertebra, and the negative to the sacrum or perineum. My colleague, Dr. Dresch- feki, has published an account of three cases successfully treated by the application of the constant current twice a week to the lumbar region. ("Practitioner," 1874, p. 360.) IX.— MICKOOKGANISMS IN THE UEINE. The microorganisms met with in the examination of the urine may be classed into three categories — namely: Torulaceous Vegetations, Sarcina, and the various forms of Bacteria. I. — Torulaceous Vegetations (Saccharomtces). Torulse appear in the urine after emission only. They have not been detected in the perfectly fresh secretion — but are ex- clusively derived from germs which gain access to the urine and grow in it after it has left the urinary passages. They appear at first as minute oblong cells (sporules), either lying separate, or strung together into short chains. Presently they elongate into transparent hollow threads wdiich divide and interlace into a fleecy cloud (thallus). The most common are the sporules of the blue and brown moulds [Penicilimn glaucum and Aspergillus niger) and of the yeast plant [Saccharomyces Cerevisice). After a few days' growth the two former ascend to the surface and form patches of mould, constituting the aerial fructification of these vegetations, Torulje are, strictly speaking, extraneous impuri- ties in the urine; and they are only of importance from their liability to be confounded with blood-corpuscles or other objects derived from the urinary passages. Torulje are distinguished from blood-disks by the great difl:erence of size among the in- dividual cells (Fig. 36); the presence of a nucleus in the larger sporules, their tendency to assume an elongated or oval form; and the indications of budding and commencing formation of a 1 Lancet, 1861, p. 582. ^ Year Book, 1863, p. 300. Reports on Surgery also. ^ Elektrotherapie, Vienna, 1868, p. 447. 176 ABNORMAL SUBSTANCES IN THE URINE. thallus. Torulse appear in the urine sometimes in a few hours after emission — more commonly after the lapse of a day or two. Fig. 36. Torulse in urint. SB They require an acid reaction for their free growth ; and they cease to multiply, and finally perish, when the urine becomes ammoniacal. 2. — Sarcina. Since Heller and Mackay, in 1848, first discovered sarcinse in urine, they have been observed by Johnson, Beale, Welcker, Munk, Begbie, and myself. The seat Fig. 37.2 of production of this vegetation is proba- bly the bladder; and it is discharged ® with the urine, sometimes in great quan- tities, and forms a grayish-white amor- phous-looking deposit. It consists of the same elements as the sarcina ventriculi o (of Goodsir), and is usually regarded as «- g, o the same species. Both the cubical « o masses and their component particles ^ are, however, smaller than those of the ^ e gastric sarcina, and Rossmann and «■ "* Welcker^ consider these differences suf- saroinas in urine. ficicut to cstablish a spccific distiuctiou. It seems more probable, however, that the differences in the habitat and conditions of growth are suf- ficient to account for the diversity of size. Dr. P. Munk^ has shown that one of the points relied on by Welcker, namely, the absence (in urinary sarcina) of cubes containing more than 64 1 Ueber Sarcina im Urine des Menschen. Henle and Pfeuf. Zeitsch. 3tte K. Bd. V. 199. ^ After Welcker, Henle and Pfeufer's Zeitsch., Bd. V. Taf. x. ^ Ueber Harnsarcine — Archiv f. Path. Anat. 1861, p. 570. MICKO-OKGANISMS IN 'I'llE UlilNii. 177 particles, is not constant. Munk found cuIjcs of fjll [(articles. In some vomited matter sent to me for examination by Dr. Scowcroft, of Southport, 1 detected small-sized sarcinte mixed with those of ordinary dimensions. This curious vegetation is generally associated with some disorder of the urinary organs (renal pains, |)ainful micturition, vesical catarrh, etc.). It grows, or at least exists, both in acid and ammoniacal urine. In Munk's case the fungus grew in great quantities during the summer months, and disappeared almost wholly in the winter months ; and this was the more remarkable as the patient (who was paraplegic) kept his bed continuously from year to year. Dr. Begbie's patient' suffered from lumbar pains and frequent micturition, together with hypochondriacal and dyspeptic symptoms.^ In the case seen by me, the patient — a merchant about sixty years of age — was suf- fering from long-standing chronic cystitis, due to enlarged prostate. No treatment yet tried has had any appreciable effect in checking the growth of sarcinte in urine. 3. — Bacteria (Bacteruria). Urine, like other organic fluids, when exposed to the contact of air-dust or of ordinary water, passes sooner or later into a state of decomposition. It is then found to swarm with bac- teria. The organisms under these circumstances gain access to the urine, and grow in it after it has left the body. But there are also conditions in which the urine contains bacteria at the moment of emission. In these cases the organisms must have grown and multiplied in the urine during its sojourn in the urinary passages. These cases may be conveniently embraced under the general heading of Bacteruria. But inasmuch as the bacteria discharged with the urine are of various kinds or species, and as the different species affect the urine in quite different ways, the resulting symptoms also difiJer greatly both in degree and in kind. Certain kinds of bacteria affect the composition of the urine very slightly, or not at all; others again rapidly break up its chief constituent, urea, into carbonate of ammonia, and thereby introduce into the previously bland secretion a fiery irritant, which is apt to light up a dangerous inflammation of the urinary mucous membrane. For these reasons it is necessar}' to divide cases of bacteruria into a certain number of groups or categories. How many such groups it may be eventually necessary to establish I cannot say — the sub- ject is as yet new, and the field of inquiry only partially ex- 1 Edin. Med. Journ. 1856-7. '^ iSee also a paper by Heller — "Wien. Med. Presse, xi. p. 13. 12 178 ABNORMAL SUBSTANCES IN" THE URINE. plored. The cases which have hitherto fallen under my obser- vation appear to warrant a division into four groups ; namely, (1) eases in which the presence of bacteroid organisms is asso- ciated with ' incipient putrefactive changes in the urine; (2) cases associated with ammoniacal fermentation of the urine ; (3) cases in which some of the common forms of bacteria are present without decomposition of the urine ; (4) cases in which micrococcus chains are voided with the urine. A good many examples of bacteruria are mixed cases — cases in which more than one form of bacteria coexist in the urine — but the above scheme of classification may be provisionally adopted ; and I propose to devote a separate notice to each group. Group I. Bacteruria Associated with Incipient Putre- factive Changes in the Urine. — This form of bacteruria is very common. The urine is more or less opalescent when voided ; it is feebly acid, neutral or feebly alkaline. When examined under the microscope it is found to contain bacteria in active motion. The kinds of bacteria present in these cases are the common forms found in decomposing organic fluids, of which the least known is the Bacterium termo (Fig, 38). The urine on standing does not recover its transparency ; on the contrary, the turbidity tends to increase, and the urine passes on pretty quickly to decomposition. This condition is accom- panied by few or no symptoms ; there may be a little heat about the genitals, or a slight undue frequency of micturition — but for the most part no complaint is made. This condition is not unfrequent in women of weak health suffering from leucorrhcea, and is common among men who have sufi:'ered from stricture, and who have frequently used catheters or bougies. The aiFec- tion is in itself of no importance, and may persist for years without requiring attention; but it assumes a graver significance if, as I have reason to believe, it renders the subjects of it liable to the next form of bacteruria which is associated with ammo- niacal urine. GrROUP II. Bacteruria with Ammoniacal Fermentation of THE Urine. — This condition always involves the patient in serious suffering and danger. The change which occurs in the urine in these cases is the transformation of urea into carbonate of ammonia. The chemical nature of this change has been already explained [see p. 83). One molecule of urea with two molecules of water become two molecules of carbonate of am- monia, COiNH^)^ + 2H2O = (NHJ2CO3. The transformation is an example of bacterial fermentation. Pasteur believes that the change is due to the action of a minute spherical bacterium to which Cohn has given the name of micrococcus urecB. This organism consists of excessively minute round particles, lying MIGKO-ORG-ANTSMS IN THE URINE. 179 free and in active movement, or strung together into short chains of two, three, or four elements each {see Fig, 88, h). Ammoniacal bacteruria is apt to arise in old stricture cases, in cases of stone in the bladder, after operative procedures, whether lithotomy or lithotrity, in cases of enlarged prostate, paraplegia, morbid, growths in the bladder, and in all conditions in which the organ is unable to empty itself completely, or which require the frequent use of instruments. In these two groups of cases the offending organism gains access to the bladder by the urethra — at least in the over- whelming majority of cases. In the female the short and com- paratively wide urethra oiFers obvious facilities to wandering bacteria to penetrate into the viscus from the external genitals. In the male the long and narrow urethra forbids this mode of entrance in the normal state. But in cases of gonorrhoea, or other type of urethritis, in which the passage is lined with a continuous layer of purulent discharge, it is quite easy to under- stand that along this purulent tract bacteria may breed their way up into the bladder. In a good many cases the infective organisms steal in with the instruments, which always come into use, sooner or later, in all kinds of vesical trouble. A dirty catheter is a most efficient infective agent. It must not, how- ever, be overlooked that, in states of depressed vitality, septic germs may, occasionally at least, find their way into an ailing organ or tissue by the channels of the circulation. Such a mode of intrusion of bacteria-germs into the bladder in cases of para- plegia seems highly probable. G-Roup III. Bacteruria avithout Decomposition of the Urine. — Judging by my own experience, this is a condition far from infrequent. The organisms which are present in the urine in these cases are short moving rods and micrococci. I am not sure that the organisms are always of the same species, but they are evidently neither the bacterium termo nor the micrococcus urese, inasmuch as they produce no change in the chemical con- stitution of the urine. In some examples the organisms resemble the Bacillus suhtilis (of Cohn), and the short rods are found accompanied with long slender threads {see Fig. 38, c and d). The character of the urine in this group ditfers widely from that in the two previous groups. In decomposing urine (Groups I. and II.) the turbidity is persistent, and the organisms go on multiplying in it after it has left the bod}'. But in the group now under consideration, the urine, although opalescent when voided, becomes clear on standing, and the organisms, together with the other formed elements (pus, etc.), subside to the bottom of the vessel. The supernatant urine continues transparent and acid for many days, and the organisms show no signs of multi- plying. Indeed, the urine exhibits less tendency to decomposi- 180 ABNORMAL SUBSTANCES IN THE URINE. tion than ordinarily healthy urine, and remains clear and acid for seven or ten days. Even when the urine is kept in the warm chamber at blood-heat the organisms do not multiply. All this leads to the' inference that in this kind of bacteruria, the seat of growth of the organisms is not the urine itself, but some portion of the surface of the urinarj- mucous membrane. Fig. 38. •! \> a Various kinds of bacteroid organisms found in the freshly voided urine, a. Bacterium termo ; h. Micrococcus urea3 ; c and rf, other bacterial forms — not identified \vith certainty as belonging to any of the known species of bacteria. The symptoms which are associated with this form of bac- teruria are frequent and painful micturition, and pains about the neck of the bladder. They vary greatly in intensity — rising and falling apparently in unison with the increasing or lessening swarms of bacteria discharged in the urine. This form of bacteruria seems to be controlled in an important degree by the internal administration of full doses (30 grains twice a day) of salicylate of soda. In the last four years I have met with a considerable number of cases belonging to this group. The two following may serve as typical examples : Case 1. — -A retired professional man about fifty years of age fell on his hip in February, 1881. As the hip continued painful, a strong solu- tion of iodine was applied to it, which produced vesication. Four or five days afterwards there arose a violent irritation of the bladder. It was conjectured that this might be due to a congested state of the pros- tate, and on that view blistering fluid was applied freely to the perineum. This was immediately followed by an aggravation of the bladder symp- toms. Micurition became excessively frequent and painful. These symptoms persisted with severity for a period of two months, and then MICRO-ORGANISMS IN THE U R 1 N K . 181 began to abate under the use of warm baths. Neither bl(jofl nor alhu- men appeared in the urine during all this time, and the reaction of the secretion was always acid. When he consulted nie, three months after the accident, the same symp- toms continued in a mitigated degree. He voided urine in my presence. It was opalescent, and swarmed with bacteria, but it was sharply acid. A j)ortion set aside in a urine-glass became quite transj)arent in twenty-four hours and let fall a deposit consisting of bacteria rods mixed with pus- corpuscles. This urine remained transparent and acid for seven days in a warm room. Three other specimens subsequently examined behaved exactly in the same way. Thirty grains of salicylate of soda were pre- scribed to be taken twice a day. In less than a week the symptoms subsided, and the bacteria disappeared from the urine. In the subse- quent year the symptoms returned, and continued with considerable violence for some weeks. The urine was again found to swarm with bacteria and to present the same characters as before. This second attack was also cut short in a few days by the salicylate of soda. Case 2. — A merchant, then aged 40, consulted me in 1881, suffering from severe vesical catarrh. The urine passed in my presence was found to be laden with actively moving bacteria, together with pus-corpuscles and a few blood-disks. (This man had suffered from cystitis ten years before, but in the interval had maintained fair health, although he had never been quite free from urinary trouble.) The reaction of the urine was acid ; and it showed the same remarkable indisposition to pass into decomposition as in the preceding case. This man has visited me from time to time until the present year (1884). He has suffered from several recurrences of the bladder trouble — the urine on these occasions is always of the same character and the attacks are always relieved by the use of thirty-grain doses of the salicylate of soda. But the urine never becomes absolutely free from bacteria — and exposure to cold, worry, or excessive fatigue invariably brings on a recrudescence of the symptoms. Ill neither of these cases had an instrument ever been passed into the bladder, and it must be regarded as probable that the organisms had originall}^ obtained access into the bladder by the circulation. In the majority of cases of this group which I have encountered, instruments had been used at some time or other, and it was therefore impossible to be sure whether the organisms had not been introduced by their means. A longer acquaintance with cases belonging to this group — that is, cases where bacteria-forms are discharged with the urine without there being any decomposition of the secretion — has convinced me that the organisms present in diiferent cases are not of one uniform type, and that in some examples two or more distinct species are growing side by side in the bladder. The different microscopic character of the organisms is sufficient to substantiate this in some instances ; but the microscope is a very imperfect guide in the study of specific differences among bac- teria. More light will be thrown on the subject when the 182 ABNORMAL SUBSTANCES IN THE URINE. several kinds encountered in urine have been sifted by the method of artificial cultivation. In this branch of the inquiry I have made but little progress, and I should like to invite observers with more leisure than myself to enter the field. Group IY. Micrococcus Chains in the Urine without De- composition. — Although I have met with but one example of this group, the organism found in the urine was so distinctive that it warrants me in separating this form of bacteruria from the remainder. I have also succeeded in cultivating the organism artificially in a state of absolute isolation from all other organ- isms. The patient was a retired merchant, 68 years old. At the age of sixteen he went to Rio Janeiro and stayed there fifteen years. He then went to India for one year. For the last twenty-eight years of his life he resided in England. With the exception of a few slight attacks of gout he enjoyed good health until within three years of his death. At this period he began to suffer from recurrent attacks of hseraaturia. These attacks, at first slight and occurring at long intervals, became gradually more severe and more frequent. At length the bleeding became continuous; violent cystitis intervened and finally the patient died exhausted. After death three soft bleeding polypoid growths were found in the bladder. It is not necessary for the present purpose to enter more fully on the clinical history of the case nor to recount the various plans of treatment adopted. I first saw the case Avith my friend Dr. Ransome, of Bowden, in the spring of 1881, and we watched it closely until its termin- ation in April, 1882. During the progress of the illness the urine had been repeatedly examined, with no other result than the finding of blood-corpuscles and leucocytes; but in the mid- dle of July I detected something I had not observed before. I saw in the deposit a number of long delicate beaded threads. In all my experience of urinary examinations I had not seen anything like them in the fresh urine. After this date the urine was examined many scores of times, and the same beaded threads were invariably found in large numbers in every specimen. The urine was generallj^ acid; and it showed no unusual tendency to decomposition. It contained no other organisms except the beaded threads until a late period of the case, when, as a sequence to the use of injections into the bladder, bacterium termo and the micrococcus ureae made their appearance. This conjunction evidently hampered the growth of the beaded threads, and they nearly vanished from the urine before the termination of the case. The following account of these fila- ments was gathered from repeated examinations of different samples of the urine, and of the cultivated organism. To the naked eye the fresh urine looked very much like that from an ordinary case of acute Bright's disease. It had a smoky appear- MIGKO-ORG ANISMS IN THE UKTNE, 183 auce, and deposited on standing a loose reddish-brown sediment. The sediment consisted of little soft brownish masses or flakes mixed with blood. Under the microsco})e these flakes were found to be composed of leucocytes or pus-like corpuscles inter- mixed with blood-disks. In these flakes the beaded threads were seen, twisted and turned in every direction, and forming an inextricable tangle of threads running in and out among the corpuscles. In perfectly fresh samples the filaments were found exclusively in these leucocyte-flakes; but after the urine had been kept awliile the flakes broke up more or less, and then detached fragments of the threads were seen scattered about in the field of the microscope. With a magnifying power of .500 diameters the threads were seen to consist of moniliform fila- ments of extreme delicacy and regularity of structure (see Fig. 39). Their width measured from a tenth to a fifteenth part of Fig. 39. Beaded threads — or mici-ococcvis chains— from the freshly-voided urine of the case described in the text — mixed with leucocytes and Wood-disks. the diameter of a blood-disk. Their length varied greatly. Some were so long that they stretched right across and -far beyond the field of microscopic vision ; but they were for the most part so twisted and turned on themselves that it was impossible to gain a precise idea of their length. Under an immersion lens and with good illumination the filaments were resolved into a row of minute spheres appiosed end to end like a string of beads. The organism was found to be easily susceptible of artificial 184 ABNORMAL SUBSTANCES IN THE URINE. cultivation, in either highly diluted albuminous urine or in filtered beef-tea. When a drop of the fresh urine was intro- duced into a sterilized flask containing beef-tea — and the flask was placed in the warm chamber at blood-heat — the new growth soon made its appearance. In from three to six hours light fleecy specks were seen scattered through the transparent me- dium. In the course of another hour or two these gathered themselves together into a voluminous soft cloud. After this no further change occurred — the process of growth seemed ended. From the first cultivation a second, a third, and so forth, up to a sixth cultivation were easily obtained in a state of perfect purity, and without exhibiting the slightest modifica- tion of form. "When a portion of the cloudy mass was placed on a glass slide the patch had a curious white, shiny, satiny appearance — and it resolved itself under the microscope into a close felt or tangle of most delicate beaded filaments of endless length, exactly resembling those found in the fresh urine. The newly grown terminal portions of a filament were a little slenderer than the older portions, and the component molecules were more perfectly spherical. In the voider portions the molecules had a squarer contour — as if from mutual compression. The filaments did not appear to divide or branch in any degree. They appeared to multiply by throwing oft' single molecules or short pieces from their growing ends, which lengthened into new chains. . I could detect no signs of an enveloping sheath. The separate molecules were evidently tightly hung together on their filaments — and the younger threads could be seen to move and twist with a curious uneasy springy motion as they adjusted themselves under the pressure of the covering-glass. There was, however, no real motility of the filaments. The filaments took the aniline dyes readily and yielded beautiful microscopical objects when mounted in Canada balsam. This organism must be very rare. Though constantly on the watch for it during the past three years I have not encountered a second example. I scarcely think that the organism had any thing to do with the disease of which the patient died. At any rate I have failed to find it in the urine of other patients suffer- ing from undoubted polypoid growths in the bladder. How did the organism gain access to the bladder? As the patient had been more than once sounded for stone before the organism was detected in the urine, the germs of it might be supposed to have been introduced with the instruments — but it is difficult to reconcile this view with the extraordinary rarit}- of the organism. Bacteruria after the use of instruments, is an every-day occur- rence — the urine in such cases is being constantly subjected to ALBUMEN IN THE U K ] N E . 385 minute microscopic examination ]>y competent oljKcrverH— -and yet this very distinctive organism has only l)een seen iji a single case.^ X.— ALBUMEN IN THE UEINE. Albumen is not discoverable, even by the most delicate direct testing, in the perfectly normal urine; but it constitutes the most common and most important of the abnormal ingredients found in disease. Its presence in the urine is due to several difterent conditions, so that the fact itself yields only a vague information; but when correctly interpreted it furnishes^ key to certain grave pathological states which would otherwise re- main in great obscurity." The kind of albumen found in morbid urines is serum.- album ev, and in clinical testing our main oljject is to determine the absence or presence of this variety of albumen in the urine. Albumen is sometimes associated with globulin in certain forms of advanced Bright's disease. Globulin is a con- gener of albumen, and coexists with it in the serum of the blood. Its presence in quantity in the urine is detected by sim- ply diluting the urine with a large amount of water — if globulin iDe present, the urine thereupon becomes more or less milky in appearance. This globulin reaction depends on the fact that globulin is insoluble in pure water, but is soluble in saline solutions; and when urine containing it is largely diluted with water, the salts which keep this substance in solution are reduced to so attenuated a proportion that they no longer suffice for this purpose, and the globulin is thrown out of solution. An albu- minous urine, which becomes milky on dilution with water, has its transparency instantly restored by the addition of a few drops of liquor potassse or of a mineral acid. In all other respects globulin answers to the same tests as albumen, and its presence in the urine does not interfere with the ordinary processes for albumen testing.^ In addition to albumen and globulin, the presence of which, in quan- tities appreciable by direct testing, must always be regarded as abnormal, the urine also contains, both in health and in disease, not unfrequently, certain other albuminoid substances of which it is necessary to take cognizance. These are peptone, heniialbtanose, mucin, and the coloring- matters of the blood — hcemoglobin and viefhcemoglobin. Peptone and Hemialbvmose. — Minute quantities of peptone appear occasionally in the urine of healthy persons, and cannot be said to have 1 I sometimes think it possible that the parasite is of exotic origin, and that the patient brought it home with him from South America or India. If so, simihir cases must be loolied for, not in Europe, but in tropical regions. 2 Globulin may more accurately be detected by saturating the urine with sul-. phate of magnesia, which precipitates globulin from its 'solutions. 186 ABNOEMAL SUBSTANCES IN THE URINE. any pathological significance. Hemialbumose seems to be very rarely present in the urine. It was discovered in a case of osteomalacia by Dr. Bence Jones/ and named by him hydrated deutoxide of albumen. It was subsequently found by Kiihue in a similar case, and named hemi- albumose. Its chemical reactions ar,e still imperfectly understood. It is precipitated by nitric acid in the cold, but the precipitate is redis- solved with excess of the acid on heating. It is not precipitated by boiling. Picric acid throws it down. It is considered as identical with the pro-pepton of Schmidt-Miilheim and with the a-pepton of Meissner, and is one of the transitional phases in the peptic and tryptic digestion of albumen.^ Peptone in minute quantities seems to be often present in the urine — and occasionally in large quantities, constituting a con- dition which has been named "peptonuria" — about which, however, very little is known. Peptone is thrown down by picric acid, and by acidulated solution of common salt, but is not precipitated by nitric acid nor by boiling. Mucin. — Traces of mucin in a state of solution seem to be present in all urines, both healthy and morbid ; but not unfrequently mucin is present in considerable quantities in the urine of patients suffering from ail kinds both of grave and trivial disorders. Further researches are required to indicate its real clinical significance. In searching for minute traces of albumen in the urine, the presence of mucin occasions more frequent embarrassment than any other substance. Mucin is pre- cipitated by the organic acids ; and the precipitate is not redissolved by the addition of these acids in excess, nor by boiling. It is not thrown down by the strong mineral acids, but when these are largely diluted, they produce the same effect as the organic acids. The best way of de- tecting mucin is by means of a saturated solution of citric acid. If such a solution be added to urine in a test-tube, in the same way as in the contact method of applying the nitric acid test for albumen — that is to say, if it be allowed to trickle along the sides of the tube until it forms a distinct layer below the column of urine — there will gradually appear, if mucin be present, an opalescent zone immediately above the layer of acid. Acetic and lactic acids are less appropriate for eliciting the mucin reaction than the strong citric acid solution, because, owing to their less specific gravity, they do not so readily sink to the bottom of the tube, and form a distinct layer below the urine. But if acetie acid be mixed with one-third of its bulk of glycerine, it acquires the dure density, and answers perfectly as a mucin test. Sometimes mucin is so abundantly present that the free addition of acetic acid, without any precautions, produces a marked milkiness in the urine. Hcemoglobin and Meihczmoglohin. — These bodies constitute the coloring- matters of the blood, and their presence in urine is recognized by the blood-color which they impart to the secretion. (See Hsemoglobinuria.) Qualitative Testing eor Albumen. — The best tests for albu- men are coagulation by boiling, and nitric acid; in doubtful cases the two tests should be used in succession. 1 Bence Jones, Animal Chemistry, p. 109. 2 See Salkowski, Die Lehre vom Harn., p. 210 ; also Dr. Gowers's case, Lancet, 1878, ii. p. 3. ALBUMEN IN THE U K I N K . 187 Boilwg. — Tl'ii urine possosKinii; itH ukuuI acid roactioti bo boiled in a test-tube, it beconien tui'l)id ifit contain albumen; and thiH turbidity is not removed by the addition of an acid. VVb(;n the urine is turbid from deposition of amorphous urates, ItoiJirif^ alone is a complete — and the best — test for albumen. The deposition of the urates is sufficient evidence that the urine is frankly acid; when such a urine is heated, the urates are speedily dissolved and the urine becomes transparent, but as the tem- perature approaches the boiling point the urine again becomes turbid if it contain albumen. In using the boiling test it is of the first importance to attend to the due acidulation of the urine. For if the urine be alkaline an}^ albumen it may contain is not coagulated on boiling. Again, if the urine be alkaline, or neutral, or oidy slightly acid, it "may become turbid on boiling, from precipitation of the earthy phosphates. Turbidity from this cause is distinguished from that produced by albumen by the addition of a drop or two of acetic or nitric acid. This immediately dissolves a phosphatic precipitate, but has no effect on albumen. To avoid these sources of fallacy, the best way is to acidulate the urine before boiling with acetic acid. Care must, however, be taken not to add too much nor too little acid, otherwise the delicacy of the test is much impaired. The following procedure may be relied on to yield trustworthy results. A test-tube is charged with about three fluid-drachms (10 c.c.) of urine. To this is added a single drop of acetic acid. The upper half of the column is then heated to ebullition. If albumen be present, the upper boiled portion of the column will show opalescence, in contrast with the lower half, Avhich remains unchanged. If the urine be alkaline, it should be carefully neutralized by add- ing successive drops of acetic acid, until the litmus paper shows a distinct, but slight, acidity, and then the iinal single drop of acid is added before boiling. Even if the urine possesses its natural acidity it is better to add a drop of acid if 3"0U want to bring out the maximum sensitiveness of the boiling test. When performed with these precautions the boiling test is the most sensitive and the most reliable of all albumen tests. Nitric Acid. — Nitric acid is an extremely delicate test for albumen ; and it is the first test to use in all cases except when the urine is turbid from urates. The best manner of applying it is to fill a test-tube to the depth of about an inch; then, in- clining the tube, to pour in strong nitric acid in such a manner that it may trickle down along the side of the tube to the bot- tom, and form a stratum some quarter of an inch thick below the urine. Added in this manner there is scarcely an}- mingling of the two fluids, and if albumen be present, three strata or layers will be observed: one, perfectly colorless, of nitric acid' 188 ABNORMAL SUBSTANCES IN THE URINE. at the bottom ; immediately above this an opalescent zone of coagulated albumen; and atop the unaltered urine. If there be only a trace of albumen, twenty or thirty minutes elapse before the opalescent zone becomes visible. This mode of testing for albumen, whereby the reagent is so intro- duced that it forms a distinct and separate layer either above or below the urine, has been conveniently termed by Dr. Oliver the contact method, Mtric acid applied by the contact method is the simplest and least troublesome means of detecting albumen in the urine. The reaction of the urine does not interfere with its operation. Only one caution is necessary. In concentrated urines, and especially febrile urines, the addition of the acid is apt to precipitate the amorphous urates, and thus to occasion a turbidity which might be mistaken for albumen. The two conditions are however easily distinguished by observing the level at which the cloudi- ness begins, and the direction in which it spreads. Albumen begins to coagulate immediately above the stratum of acid, and the turbidity spreads upwards; but the urates first appear at or near the surface of the urine, and the opacity spreads down- wards. Heat also readily resolves the doubt; for the urates speedily disappear when the urine is warmed, but turbidity from albumen is not affected by heat. The urine of patients who are taking cubebs and copaiba is commonly somewhat opalescent, and nitric acid, in the cold, sometimes (not always) increases the opalescence. The sense of smell immediately directs attention to the presence of these drugs, and heat diminishes the opalescence and prevents any turbidity with nitric acid. In urines which are over- rich in urea, nitric acid, in the cold, causes a slow precipitation of a crystalline mass of nitrate of urea, which, however, is so different in appearance from coagulated albumen that it can scarcely be mistaken for it. It is further to be remarked, that if the manner above de- scribed of testing for albumen with nitric acid be not followed, two notable fallacies may be encountered. On the one hand (as was pointed out by Bence Jones), if the. urine be acidified with a small quantity, a drop or so, of nitric acid, the albumen may not be coagulated at all; and on the other hand, if a large quantity of acid (an equal volume) be suddenly added to, and mixed with the urine, the mixture remains perfectly clear, even though it be highly albuminous. Other Tests for Albumen. — Several other substances, besides heat and nitric acid, precipitate albumen ; namely, alcohol, tannin, carbolic acid, ALBUMEN IN THE URINE. 189 chromic acid, acidulated brine/ metaphosphoric acid,'"' ferrocyanide of potassium,' saturated solution of i)icric acid,' tungstate of soda,'' potassio- mercuric iodide," and certain other metallic salts. »Sotne of these have been recently strongly reconiniended as tests foi' albumen in the urine; and it has been claimed on their behalf that they are superior in deli- cacy to heat and nitric acid. Those which have attracted the most attention, and which I have especially subjected to examination, are acidulated brine, tungstate of soda, mercuric iodide, and ferrocyanide of j)otassium. The common defect of these tests is that they not unfrequently give a reaction with normal urines, or with morbid urines, which do not contain serum- albumen. I believe that the most frequent source of fallacy in their use is not peptone nor hemialbumose, but mucin. They all throw down mucin in a manner indistinguishable (without further testing) from albumen. When the contact method is followed, they yield, if the urine contain mucin, an opalescent zone at the junction of the two fluids, and they yield exactly the same reaction if the urine contain albumen. Now the use of nitric acid avoids this fallacy. The opalescent zone produced at the line of contact by nitric acid is albumen (or globulin), and noth- ing else. If mucin be present, there is slowly produced a haze at the middle and upper parts of the column of urine, and not at the line of contact. Sometimes the mucin-haze, with very careful addition of the acid, forms a fairly distinct ring or zone about midway between the con- tact line and the top of the column of urine ; and now and then a urine is encountered in which a double zone is witnessed, one consisting of albumen immediately above the line of junction of the two fluids, and another higher up composed of mucin. This behavior of mucin w-ith 1 Proposed by myself. This test is composed of a saturated solution of common salt acidulated with one per cent, of strong hydrochloric acid. See a paper by the author in The Lancet, 1882, ii. p. 823. 2 Metaphosphoric acid is a veiy sensitive test for albumen — but its solutions change slowly into orthophosphoric acid and then cease to coagulate albumen. This is a fatal objection to its clinical use. ^ Suggested by Dr. Pavy. The objection to this test is that it throws down mucin owing to the strong acidulation with acetic acid which is required to bring out its action. * First proposed by Galippe, and recently strongly advocated by Dr. George Johnson (The Lancet, 1882, li. p. 737, and Albumen and Sugar Testing, Lond. 1884). Applied by the contact method this is a very delicate test for albnmcn^- but inasmuch as it throws down mucin and peptone in a manner quite indistin- guishable from albumen (except by further control testing — by heat or nitric acid), its use involves additional time and trouble. Picric acid also gives a precipitate in the urine of persons taking large duses of quinine. ^ This test was introduced by Dr. Oliver (On Bedside Urine Testing, Lond.. 1883). It is prepared by mixing together equal parts of the saturated solutions of tung- state of soda (one in four), and of citric acid (ten in six), and of water. It is ap- plied by the contact method and is of extreme delicacy — but it is fatally viiiat:d as a clinical test b}^ the fact that it gives a reaction more or less pronounced with most urines both healthy and morbid. ^ Proposed by Ch. Tanret of Paris. It is composed of 2.70 parts of bichloride of mercury and 6.64 parts of iodide of potassium dissolved in lOO pans of water. In applying this test the urine requires to be strongly acidulated with acetic or citric acid. This test is of the most extreme sensitiveness, but it is wholly un- suitable for urine testing for the same reason as the foregoing, namely, that it gives a slight reaction with nearl}' all urines. 190 ABNORMAL SUBSTANCES IN THE URINE, nitric acid is easily understood when it is remembered that while mucin is not thrown down by strong nitric acid, it is thrown down by that acid in a highly diluted state. In regard to highly or even very moderately albuminous urines, all these tests give an unmistakable reaction ; but when we are in search of minute traces of albumen they fail us, simply because their reactions do not distinguish between the presence of albumen and the presence of other proteids which have either no morbid significance or have a significance wholly different from that of albumen. It is for this reason that I have been constrained to abandon the use of acidulated brine. I found it so often necessary, when minute traces of albumen were in question, to control the indications with heat and nitric acid, that it became evident that it cost less time and trouble to resort at once to the more reliable tests. It is, no doubt, desirable that we should possess a test for albumen somewhat more sensitive than nitric acid ; but it is a condition, sine qua non, that such a test shall be equally reliable, and this condition is not fulfilled by any of the tests hitherto introduced. They all, without ex- ception, give a reaction with something that is not serum-albumen, and are, therefore, untrustworthy, and apt to lead to serious misapprehension. The following table brings into strong light the necessity of abiding by the old tests. It gives the results of the examination of the urine of thirty-one perfectly healthy men, most of them students and candidates for insurance. None of these urines gave the slightest reaction by care- ful testing with heat and nitric acid : Reaction. No reaction. Heat 31 Nitric acid . Acidulated brine Picric acid . Tungstate test . Mercuric iodide . 31 11 20 14 17 28 3 26 5 It may be objected that the failure of heat and nitric acid to give a reaction with these urines arose from a want of sufiicient delicacy; but this was not really the cage. I have shown elsewhere ^ that the boiling test, when attention is paid to the due acidulation of the urine, is supe- rior in sensitiveness to any of the new tests. The Quantitative Estimation of albumen in urine is a matter of considerable practical importance, and various plans of attaining this object have been devised. For precise determinations the plan usually followed is to bring a measured quantity of urine to a slightly acid condition ; boil; throw on a weighed filter; wash; dry at 212°; and weigh. This proceeding demands a good deal of time. The filtering is sometimes impossible; and the results obtained are only mod- erately accurate with every care. 1 Glasgow Medical Journal, 1884. ALBUMEN IN THE UJUNE. 191 For a rough-and-ready, but useful, method, there is none superior to boiling the urine in a test-tube with a drop or two of acetic acid. The albumen coagulates in flaices, and presently sinks to the bottom, forming a layer of various thickness. The proportion of albumen is judged of by the depth of this layer as compared to the height of the column of urine in the tube. This proportion may be expressed in numbers, as ^, j-, -^ , and so forth. If the quantity of albumen be too small to form a layer of appreciable depth, the proportion is expressed more loosely, as a "cloudiness" or an "opalescence." The varying density of albuminous urines, and the varying size of the flakes into which albumen coagulates, affect the rapidity and com- pleteness of the subsidence and therefore the depth of the coagu- lated layer, so that only approximate results can be expected from this method. Becquerel ingeniously turned to account the property of albumen to deviate the plane of polarization to the left; and constructed an instrument on a similar plan to the optical sac- charimeter, by which the deviation could be measured, and the percentage of albumen calculated therefrom. It would appear, however, that this instrument, on Becquerel's own showing, is only capable of very limited clinical application. When the quantity of albumen is considerable it gives very exact indica- tions ; but the deviation is too slight for exact estimation in moderately and feebly albuminous urines; it is therefore useless for the bulk of albuminous urines.' Boedecker has proposed a volumetrical method, founded on the property of ferrocyauide of potassium to form an insoluble compound of fixed composition with albumen. Yogel states that he has found this method inaccurate.^ Minimetric Method or Dilution Method. — In 1876 I proposed a mode of estimating albumen in urine, which I think may prove useful in clinical work.^ The principle of the method is easily understood. When an albuminous urine is progressively diluted with water, and tested from time to time with nitric acid, the opacity induced b}' the test becomes gradually fainter and fainter, until at length it ceases to be visible. This point is reached when the urine contains less than about 0.0014 per cent, of albumen. The more albumen the urine contains, the more dilution, of course, it will require to reach the vanishing point of the reac- tion ; and if we could fix this point with accuracy, we should 1 See a clinical lecture by Becquerel, Clinique Europeene, 1859. 2 Boedecker's method is described in Henle and Pfeufer's Zeitsch., 1859, p. 321. ^ For a fuller account of this method the reader is referred to a paper, by the iiuthor, read before the Medico-Chirurgical Society, Feb. 22, 1876. 192 ABNORMAL SUBSTANCES IN THE URINE, have a simple method of estimating albumen in urine. The urine could be diluted until it ceased to react with nitric acid, and the amount of dilution required to reach this point would furnish a measure of the proportion of albumen. But it is not possible to fix this point with accuracy. The opacity produced by the acid fades away so gradually with increasing additions of water, that it is impracticable to decide within many degrees the point at which the reaction ceases to be appreciable. And not only so, but the development of the re- action becomes more and more retarded as the dilution proceeds, until at length it only becomes visible after the lapse of several minutes. To overcome this difficulty, it was found necessary to fix on some arbitrary point or line which would serve as a practicable zero to the scale. After many trials, it was found most con- venient to draw the line at a reaction coming into sight midway between half and three-quarters of a minute after the contact of the acid — that is, to dilute the urine until it gives no reaction for thirty seconds after the addition of the acid, but shows a distinct opalescence at the forty-fifth second. The exact point to be aimed at is a reaction coming doubtfully into view between the thirty-fifth and fortieth second, and appearing still very dim, but unmistakable at the forty-fifth second. It was found pos- sible, after a little practice, to strike this point with sufficient exactness to serve as a practicable zero to the scale. Each dilution with an equal volume is counted as one degree on the scale, and these degrees may be conveniently termed " degrees of albumen." Thus, a urine requiring dilution with forty times its bulk of water to reach the zero reaction, may be described as possessing forty degrees of albumen^a urine requiring three hundred similar dilutions as possessing 300 degrees of albumen, and so forth. The difficulty of the method is to hit correctly the zero re- action. When this point is approached, a little more or a little less dilution makes but a slight difference in the time at which the reaction appears. In order therefore to obtain exact results, it is necessary to conduct the testing with rigid uniformity. The test-tube employed should have an interior diameter of f of an inch (15 millimetres); the acid must be added in the right way, and at the right moment. The operation, too, should be per- formed by daylight, or, if by gaslight, an addition of about five per cent, must be made to the results. The proceeding adopted is as follows : The urine is first tested in the usual way with nitric acid, so as to get a rough idea of the quantity of albumen contained in it, and of the degree of dilution likely to be re- quired to reach the zero. The watch is placed on the table before the operator. A fluid-drachm of the urine is then meas- ALJ5UMEN IN 'JMIE UKINE. 1.93 ured off", and iiiti-oducod into a graduated pint rricaHuro, and water is added up to a few or many ounces, according to tlie degree of dilution likely to be required to approach the zero reaction. The test-tube is then filled to the depth of about an inch with the diluted urine and held widely inclined from the per- pendicular. The eye is now directed to tlie watch, and the acid is added in such a manner that it runs along the lower side of the tube to tlie bottom and forms a distinct layer, about a quarter of an inch deep, below the diluted urine. The acid must be added exactly on one of the quarter-minute strokes. This is the most critical step in the proceeding, and it should be per- formed in the following manner: A pointed glass tube or pipette is dipped to the depth of a couple of inches into the acid and covered with the forefinger. The pipette thus guarded is then passed into the test-tube to within half an inch of the level of the diluted urine, and at the right moment the finger is removed and the charge of acid delivered. As soon as the acid is added, the test-tube is held up to the light against some dark background (such as a black sleeve, a book bound in black cloth, or a dark corner of the room), and as soon as the faintest opalescence is perceived above the level of the acid, the time of its appearing is noted. If this appear at or before thirty sec- onds after the contact of the acid, more water is added, and the testing repeated as before. Thus, by successive additions of water, and repeated testings, a close approximation to the zero reaction is obtained. A fresh dilution is then prepared, and, guided by the previous trials, two or three testings with different dilutions are generally sufficient to indicate with exactness the dilution which produces an opalescence between the thirty-fifth and forty-fifth second after the addition of the acid. If too much water is added in the first instance, the reaction does not appear till after the forty-fifth second. In this case the operation must be recommenced with less water, and proceeded with as in the first case. When the zero reaction is determined, the degree of dilution required to produce it is noted, and expressed in multiples of the unit-volume of urine employed. Thus, if a fluid-drachm was the unit-volume of urine employed, and the zero reaction was obtained when dilution was carried up to fifteen ounces (120 drachms), the urine is recorded as having 120 degrees Of albumen. If the urine is feebly albuminous — indicating less than 20 degrees of albumen — the fluid-ounce should be substituted for the fluid-drachm as the unit-volume. On the other hand, if the urine indicate more than 160 degrees of albumen, the unit- volume should be half a drachm — or, still better, the urine should be previously diluted with water in the proportion of 1 13 194 ABNORMAL SUBSTANCES IN THE URINE. in 2 or 1 in 4, and the result afterwards multiplied by 2 or 4 as the case may be. The actual value in weight of albumen of each degree on the dilution scale was found, by careful comparative experiments with the weighing method, to correspond to 0.0034 per cent., or 0.0148 grain per fluid-ounce of the British Pharmacopoeia. These data supply an easy means of calculating the quantity of albumen per ounce, and also the daily loss of albumen. Suppose that 40 ounces of urine were voided in the twenty- four hours, and that a sample of this urine showed 150 degrees of albumen by the dilution method, then : 0.0148X150=2.22 and 2.22x40=88.8. The urine contained 2 22 grains of albumen per ounce, and the daily loss was 88.8 grains. The time required for the estimation of albumen in urine by this method is from ten to twenty minutes. Clinical Significance of Albumen in the Urine. — In con- sidering this subject all those cases are, of course, excluded in which the occurrence of albumen is only incidental to the pres- ence of some other fluid in the urine, such as blood or pus. The pathological states in which albumen appears constantly or occasionally in the urine may be arranged in the following groups : 1. Acute and chronic Bright's disease of the kidneys. 2. Pregnancy and the puerperal state. 3. Febrile and inflammatory diseases (zymotic diseases, such as scarlet fever, measles, smallpox, typhoid, cholera, yellow fever, ague, diphtheria, etc.; inflammatory diseases, such as pneumonia, peritonitis, traumatic fever, acute articular rheuma- tism, etc.). 4. Impediments to the circulation of the blood (emphysema, heart disease, abdominal tumors, cirrhosis, etc.). 5. A hydrsemic and dissolved state of the blood and atony of the tissues (purpura, scurvy, pj^-semia, hospital gangrene) ; also hfemoglobinnria. 6. Saturnine intoxication. 7. Functional disorders (albuminuria of adolescents, physio- logical albuminuria). 8. Nervous disturbance (neurotic albuminuria). In the first group albuminuria is dependent on structural changes in the kidneys {see Bright's Disease). In the second group albuminuria is sometimes associated with structural changes, and sometimes not {see Connection of Bright's Disease and Pregnancy). In all febrile and inflammatory complaints a trace of albumen is frequently found in the urine ; it usually amounts to no more ALBUMEN IN THE URINE. 195 than a trace, and disappoars on dofervosccnce ; HonietinicH in pneumonia it is not inconsiderable. As intercurrent febrile attacks are common in the course of most chronic complaints, temporary albuminuria has been noted in a great multitude of different diseases. This remark applies especially to chronic tuberculosis, cancer, caries, and necrosis ; and albuminuria under such a condition is to be carefully distinguished from the cases in which genuine Briglit's disease coexists with those complaints. In a zymotic disease there is a double pathological state, namely, pyrexia and the operation of a specific poison; and albumen may appear in the urine either as an incident of the febrile state, when it is comparatively unimportant, or as an indication of serious structural changes in the kidneys, which constitute a grave sequela of the disease. Albuminuria connected with impediments to the circulation of the blood is considered under Congestion of the Kidney. In a dissolved or putrid state of the blood, albumen appears in the urine without being connected with organic changes in the kidney; it is associated with the escape of the coloring matter of the blood {see Hsemoglobinuria). Saturnine Albuminuria. — The occurrence of albumen in the urine of persons poisoned with lead, although repeatedly ob- served, was not regarded as anything more than a coincidence until Ollivier demonstrated, by experiments on animals and clinical observations, the existence of a causal connection between them. Ollivier^ found that dogs, rabbits, and guinea-pigs, when poisoned with repeated doses of carbonate of lead, invariably passed an albuminous urine, and that their kidneys exhibited signs of incipient organic disease. He also collected 15 ex- amples of albuminuria in persons poisoned with lead. Seven of these had temporarj^ albuminuria; in three, the albuminuria persisted during the continuance of the saturnine symptoms ; and in four, genuine Bright's disease had been produced. In addition to these observations, he examined the urine of 37 persons affected with diverse manifestations of lead-poisoning in the Hopital de la Charite : of these, nine had albuminous urine. These observations have been conlirmed by Lancereaux^ and Danjoy.^ Ollivier found that both the urine and the kidneys in those cases contained traces of lead. He inferred that the existence of lead in the kidneys induced an organic lesion of these organs, and that the albuminuria was the consequence of that lesion. This has been proved experimentally b}' Charcot and Grom- 1 Archives Generales, 1863, ii. pp. 530 and 709. 2 Union Medicale, 1863, and Bulletins de la Societe medicale d'Eniulation, nouvelle serie, t. i. p. 182, 1864. 3 Archives Generales, 1864, i. p. 402. 196 ABNORMAL SUBSTANCES IN" THE URINE. bault\ who fed animals on lead salts, and so induced nephritis. Numerous observations on the human subject have clearly estab- lished the, relation between lead poisoning and the granular kidney of Bright's disease {sre Dr. Dickinson on " Albuminuria," p. 882, and Wagner on " Die Bleischrurapfniere," in " Ziemssen's Cyclopged.," '6d edition, vol. ix. p. 291). Functional Albuminuria. — The excessive use of a diet composed exclusively or chiefly of albuminous matters, such as eggs, has been shown by Barreswil, Brown-Sequard and others to cause the urine to become slightly albuminous. Slight and temporary albuminuria appears to occur occa- sionally from very slight disorders. Beneke, when suffering from dj^spepsia, noticed albumen in his own urme four times in as many weeks. Similar observations have been made by others (Parkes). The most important cases, however, which may be classed under this heading, are those of the so-called albuminuria of adolescents, transient, or physiological albuminuria. The urine of young persons, usually at about the time of puberty, not un- frequently contains a small amount of albumen, without any other serious symptom showing itself. In this country special attention has been called to this form of albuminuria by Moxon,^ Rooke,^ Dukes,* and Saundby,^ while on the Continent the most important observations have been those of Leube^, Edlef- sen,'^ Fiirbringer,^ and Runeberg^ In most cases the subjects of the affection show general want of tone, lassitude or anaemia, and often disorders of digestion may be noted. But in many cases the general health is quite perfect. The amount of albumen is usually only slight, but occasionally may be con- siderable. It is a marked feature of nearly all such cases, how- ever, that the appearance of the albumen is intermittent. Thus, the urine passed before breakfast is usually normal, while albumen makes its appearance later on in the day. Occasionally, too, only the urine passed after meals contains albumen. An excess of uric acid or of oxalates, and sometimes a few hyaline casts, may be found. Muscular exertion has a very marked effect in inducing this form of albuminuria. Leube examined the urine of 119 soldiers after a long march, and found albumen in the urine of 19, or 16 per cent. Dr. Dukes has also remarked in schoolboys the effect of muscular exertion in producing albuminuria ; while rest in bed, as shown by Dr. Rooke, fre- quently removes the condition in a short time. 1 Archiv. de Physiol., 1881, p. 126. ^ Guy's Hosp, Eeports, xxiii. p. 233. 3 Brit. Med. Journ., 1878, ii. p. 596. ^ Idem, 1878, ii. p. 794. 5 Idem, 1879, i. p 699. e Vircli. Arch., 72, p. 145. 7 Berlin. Klin. Wochenschr., Sept. 12, 1879. 8 Zeitsch. f. Klin. Medic, 1879, i. p. 340. ^ Virch. Arch., 80, p. 175. ALBUMEN IN THE UKINE. 197 Usually the condition is not of long duration, hut exceptions to tliis rule are sometimes met with. The causes of functional alhuminuria are hy no means under- stood, and prohahly may not he the same in all cases. Some cases may possihly he regarded as food-alhuminuria. Sir Wm, Gull has suggested that the condition is due to atony of the vessels and nerves, and Bamberger also believes it due to vaso- motor change in the kidney, which may cause slowing of the circulation in the glomeruli. This appears to be the most prob- able explanation for most cases. The prognosis in functional albuminuria is favorable — al- though Dr. G. Johnson^ and Dr. Dukes are inclined to think that sometimes the condition may end in Bright's disease. The functional character of the disorder may generally be recognized from the intermittent occurrence of the albumen, from the normal density and coloration of the urine, from the absence of other accompaniments of Bright's disease, such as high arterial tension and hypertrophy of the heart, and from the progress of the case. Neurotic Albuminuria. — Bernard found that irritation of the renal nerves, or of a certain spot in the floor of the fourth ventricle (higher up than the diabetic puncture) caused albumen to appear in the urine of animals. Temporary or intermittent albuminuria is sometimes encountered clinically under circum- stances of disturbed innervation, without structural changes in the kidneys. Dr. G. Johnson^ has pointed out that transient albuminuria occasionall}- follows cold bathing, and Dr. La3'cock^ has seen a similar result in the shivering period of various ague- like attacks. In vascular bronchocele with exophthalmos. Dr. Begbie* has repeatedly observed long-continued intermitting albuminuria. In these last cases the albumen appears during and after digestion (especially after breakfast), and disappears during the periods of fasting. Some cases of this class have an evident affinity with paroxj'smal hsemoglobinuria. Albuminuria is sometimes noticed after epileptic attacks, but the records of the frequency of its occurrence show consider- able difterences. In certain other disturbances of the nervous system albuminuria is noticed, as in cerebral hemorrhage, cere- bral concussion, tetanus, and delirium tremens. [See Wagner in " Ziemssen's Cyclop.," 3d. edit., vol. ix. p. 27.) When albumen is found in urine, the important point to decide is, whether it indicates the existence of organic disease of the kidnej's or not. This question, in any individual case, 1 Brit. Med. Journ., 1879, ii. p. 928. - Ibid., 1873, ii. p. 664. 2 Dublin Journ of Med. Sci., July, 1874. * Edin. Med. Juurn., April, 1874. 198 ABNOKMAL SUBSTANCES IN THE URINE. must be considered chiefly in connection with the three follow- ing points jointly, namely: 1. The temporary or persistent duration of the albuminuria. 2. The quantity of the albumen ; and the occurrence and character of a deposit of renal derivatives. 3. The presence or absence of any disease outside the kidneys which will account for the albuminuria. 1. It has already been mentioned that functional albuminuria is usually only temporary. A persistent duration of albuminu- ria, on the other hand, is very suspicious of organic disease of the kidneys. The importance of distinguishing between tem- porary and permanent albuminuria was insisted upon by Dr. Parkes, and observations relating to this subject will be found in his treatise " On the Composition of the Urine," p. 186. It must be remembered that in the granular kidney of Bright's disease the albuminuria is often intermittent. 2. The greater the quantity of albumen, the more likely is the existence of renal disease; and a "large" quantity of albu- men (|- and upwards) is rarely found, except in undoubted acute or chronic Bright's disease. It is necessary, however, in con- sidering the amount of albumen, not only to have regard to the proportion in a particular specimen examined, but also to the total quantity in the twenty-four hours. This may be surmised by the density of the urine — low density indicating that the quantity of urine passed in twenty-four hours is large, and high density the contrary — but judged more accurately by ascertain- ing what is the actual flow of urine in twenty-four hours. A urine may be only slightly albuminous, but if it be of low den- sity (under 1012) and the daily quantity between three and four pints, the total loss of albumen will be very considerable, and the existence of renal disease strongly indicated. Indeed, of all urines there is none more surel}^ indicative of Bright's disease than a pale, dilute, abundant urine which is, at the same time, more or less albuminous. On the other hand, as a rule, with very few exceptions, when the urine is only slightly albuminous, and at the same time dense and high colored, Bright's disease is not present, and the albuminuria is owing either to pyrexia or to some impediment in the circulation of the blood. The kinds of deposit which indicate most strongly the exist- ence of organic renal disease are, (a) very abundant ones, con- taining casts and much renal epithelium; (6) those containing numerous casts and cells in a state of fatty degeneration. The least indicative of primary renal disease of serious import, are, blood casts, and very transparent casts in scanty numbers. 3. When the urine is found permanently albuminous, and there exists neither pyrexia nor thoracic disease, nor other recognizable condition which can account for the albumen, the ALBUMEN IN THE UKINE. 199 inference is almost irresistible that there exists a primary organic disease of the kidneys. The association of other symptoms will usually confirm tliis diagnosis. {See Bright's Disease.) It has been stated that it is possible to distinguish secondary and functional albuminuria from albuminuria depending on disease of the kidneys, by the fact that certain odorous and pigmentary substances when taken internally make their ap- pearance in the urine in the former case (as in health) but not in the latter. The observations of Dr. Dyce Duckworth do not support this conclusion. He found that iodine, santonine, tur- pentine, and oil of juniper passed through the kidneys, and appeared in the urine, of persons affected with undoubted disease of the kidneys. Some exceptional cases were, however, encountered.^ Pathology op Albuminuria. It would be out of place in a practical treatise to discuss fully the various theories which have been advanced in recent years to explain the presence of albumen in morbid urine. The subject, however, is of so much interest, and has attracted so much attention, that a short review may fitly be here inserted, giving in outline the views of path- ologists on this vexed question. As a preliminary inquiry it must be considered whether albuminuria is an exclusively morbid phenomena, or whether the urine may in the normal condition contain a certain quantity of albumen — a quantity so minute as to escape detection by the ordinary tests. The appearance of albumen in functional albuminuria would by the last view be simply an exaggeration of a physiological condition. We should thus have a sen- sible and insensible albuminuria, analogous to sensible and insensible perspiration. The systematic testing of the urine, especially in candi- dates for life insurance, has brought to light the frequency with which albuminuria occurs when organic disease of the kidneys, or, indeed, of any other organ, cannot be suspected {see above — Functional Albumi-- nuria). It is now certain that a sensible albuminuria is of much com- moner occurrence in healthy persons than has been hitherto supposed. Some of the constituents of the urine which were once considered exclu- sively morbid, have, by the use of finer methods of testing, been found to exist in minute quantities under perfectly normal conditions. For example, it has been shown that minute traces of sugar exist in normal urine — and analogy would suggest that albumen also may in the future be shown to be an ingredient of the normal secretion of the kidney, although, perhaps, present only at certain periods of the day. Such a view is already held by some physicians {see Senator, "Die Albuminurie in gesunden und kranken zustande," Berlin, 1882). The majority of pathologists, however, still hold that every appearance of albumen in the urine is morbid, although it may not necessarily point to a diseased condition of the kidneys. 1 St. Bart. Eeports, vol. iii. p. 215. 200 ABNORMAL SUBSTANCES IN THE URINE. How comes it to pass that while so many other substances are removed from the blood by the kidneys, the albumen is retained? To this ques- tion mainly two answers have been given. The first is that of Von Wittich/ who believed that in the glomeruli albumen really was removed from the blood, but that it was afterwards reabsorbed in the tubules and served to nourish their epithelium. This view has met with many oppo- nents, and direct contradiction has been given to it, by the experiments mentioned below, which showed no coagulated albumen in the glomerular capsule, when the kidney was boiled, or when treated with alcohol or osmic acid immediately after removal from the body. The view to which authorities are now most inclined is that advocated by Heiden- hain.^ He accepts the opinion of Bowman that the urinary salts and water are removed in the glomeruli, and that the specific urinary con- stituents, such as urea, are secreted by the epithelium of the urinary tubules. The separation of the water and salts, however, is not a mere filtration as formerly supposed. The glomerular tuft is covered by a layer of flat epithelium, which, according to Heidenhain, is an active agent in removing the water and salts from the blood, but keeps back the albumen, and prevents it reaching the urine at all. We have, in fact, a true secretion, the glomerular epithelium acting towards the water and salts, as the tubular epithelium towards the urea, uric acid, etc. Moreover, any lesion of this epithelial layer, or a deficiency in its supply of nutrition, would cause it to lose part of its function and per- mit the passage of albumen into the urine. Support is lent to this opinion by a consideration of the part of the kidney into which albumen is exuded when present in the urine. Varied experiments have now placed it beyond doubt that the albumen is, for the greater part at least, poured out in the glomerular capsule. The experiments have been conducted in two ways. The kidneys of amphi- bia have a double blood supply. The glomeruli are supplied from the renal artery, while the tubules are supplied by a sort of portal vein, which springs from the veins of the lower extremity. Nussbaum^ showed that by ligaturing the renal artery in frogs he could shut off the blood supply from the glomeruli, while leaving that of the tubules intact. He then produced an artificial albuminuria in frogs by the injection of egg- albumen into the anterior abdominal vein ; but he found that the excre- tion of albumen immediately stopped when he ligatured the renal artery, although other substances were still secreted by the intact epithelium of the tubules. It could, therefore, be concluded that in this case albumen was only secreted by the glomeruli. Another method employed was that of coagulating the albumen in situ, by treating the kidney with various coagulating agents immediately after removal from the body. For this purpose Cornil* used osmic acid, Ribbert^ strong alcohol, and Posner® boiled the kidney for a short time. When sections of the kidney treated in this way were examined, a mass of coagulated albumen could be seen not only in the tubes, but in the space between the glomerular tuft and its capsule. Hence, it must be inferred that usually the albumen is 1 Virch. Arch., x. p. 325. - Hermann's Handb. der Phvsiologie, Bd. v., part 1. « Pfliiger's Arch., xvii. p. 580. * Journ. de lAnat., 1879. s Clblatt. f. Med. Wissen., 1879. ^ Virch. Arch., 79, p. 311. ALBUMKxV IN THE U K I N K . 201 secreted by the glomeruli. Senator finds an exception to this in the case of venous congestion, where he believes that the albumen is first removed in the tubules, since the increase of pressure in the venous system will be felt here before it reaches the glomeruli. The general conditions which give rise to albuminuria may be classi- fied as follows : I. — Alterations in the Composition of the Blood. Mention has already been made of the classic experiments of Bernard, Lehmann, and Stokvis, by which it was shown that certain foreirjn albu- mens, when present in the blood, passed over into the urine unchanged. Such albumens are egg-albumen and haemoglobin, which are more dif- fusible than serum-albumen ; while others, such as syntonin, myosin, and alkali albuminate, being less diffusible, remain in the bloodvessels (Leh- mann). The presence in the digestive tract of albuminous bodies in excess, may be followed by their absorption and excretion by the kid- neys, in the unchanged state. The late Sir Kobert Christison pointed out, in 1839, that the urine of a person who ate much cheese might con- tain albumen. Bernard, Stokvis, Lehmann, and many others, have also shown that the use of uncooked eggs as an article of diet, or an exces- sive use of them when cooked, may lead to the presence of egg-albumen in the urine. The question of a "food albuminuria" has been investi- gated by Parkes, and more recently by Brunton and Power* and Sparks and Bruce.'' They have proved that albumen may occur in the urine after taking food ; and if present before food, it is increased in amount during digestion. Such observations, however, do not prove that the albumen absorbed is at once excreted by the kidneys, for changes in the blood circulation are coincident, and they also may lead to disturbance of the renal function. It has been surmised that the albumen found in the urine differs slightly from ordinary serum-albumen. Brunton and Power investigated the coagulating-point of the albumen, and found that the albumen after food did in some cases coagulate at a lower tem- perature than ordinary serum-albumen, and that the earlier products of pancreatic digestion showed the same phenomenon. Their experiments, however, did not give constant results. Lupine ^ asserts that the albu- men passed after food is more diffusible, and more easily transformed into peptone by artificial digestion than that passed during fasting. It is not improbable that special forms of albumen, such as hemialbumose, peptones, and possibly transition stages between serum-albumen and these, may be absorbed from the digestive tract and excreted in the urine. Peptones, it is alleged, may be absorbed from pathological exu- dations, as in croupous pneumonia, and during the breaking down of purulent formations in various parts of the body. It is asserted that in fevers and certain other conditions, peptones may be formed in the blood itself by a peculiar fermentative process, and may then appear in the urine. (See Senator, loc. cit. p. 8.) The excretion of other forms of albumen may, however, lead to the exudation of serum-albumen itself. Lehmann and Stokvis showed that 1 St. Bart. Eeports, vol. xiii. 2 Med.-Chir. Trans., vol. Ixii. 3 Kevue Mensuelle, 1880, p. 343. 202 ABNORMAL SUBSTANCES IN THE URINE. albuminuria did not end with the removal of all the foreign albumen injected into the blood, but that a quantity of serum-albumen was passed for sometime. It is, therefore, probable that the passage through the kidney of such foreign albumen may irritate the organ and lead to permanent changes. Seramola^ believes that the lesion of the kidney in Bright's disease is thus produced by the continued excretion of unas- similated albuminoid matters which accumulate in the blood. His opinion, however, seems to rest on insufficient experimental data. The occurrence of functional albuminuria is by some authors attri- buted to derangements of digestion (dyspeptic albuminuria). The late Dr. Murchison^ also advocated the admission of a hepatic albuminuria. The liver, he believed, might be so overworked as to allow a portion of albumen to pass over into the blood in an unassimilated state, to be afterwards removed by the kidneys. With reference to other constituents, the relation of the composition of the blood to albuminuria has, as yet, been insufficiently worked out. Dr. Newman,^ however, has shown experimentally that the amount of albumen secreted is increased by an accumulation of urea in the blood. II. — Alterations in the Circulation of Blood through the Kidneys. These may consist of changes in the quantity of blood supplied to the kidneys, in the blood pressure, or in the rate of blood flow. Our knowl- edge of the action of these changes is derived mainly from experimental pathology ; but it is extremely difficult, and in some cases impossible, to vary one set of relations apart from the others, and, therefore, the re- sults of the experiments and the deductions drawn from them are some- what conflicting. If the renal artery be closed for a few minutes and then reopened, the secretion of urine is stopped for a time, and only gradually re- established. The urine passed after the reopening of the artery con- tains a quantity of albumen, which gradually disappears as the flow of urine becomes normal. (Hermann* and Overbeck.^) A parallel to this experiment is probably seen in the algid stage of cholera. The supply of blood to the kidneys is then interrupted, and the secretion stopped ; but in the stage of reaction, if the patient survive, the urine is found to contain albumen, which gradually disappears as convalescence progresses. Hermann also showed that mere narrowing of the renal artery, without absolute occlusion, would cause a similar result. It cannot, however, be concluded that the results are due to anaemia of the kidney. They have been variously referred to lowering of blood pressure, increase of blood pressure from accumulation of corpuscles in the glomerulus during the stasis, to slowing of the blood stream, and to loss of nutrition of the glomerular epithelium. Similarly, it is a matter of every-day clinical experience that hyper- semia of the kidneys is accompanied by albuminuria. Here, however, we have again the same complication of relations, vascular tension and blood flow being alike altered. 1 Kevue Mensuelle, 1880, p. 239; also Progres Medical, 1883. 2 Diseases of the Liver, 2d edit., p. 573. ^ Journ. of Anatomy and Phvs., vol. xii. p. 608. * Sitzungsb. d. Wien. Acad., "1861. '" Idem, 1863. ALliUMEN IN THE URINE. 203 It has been very generally believed that increase of arterial tension would cause albuminuria. This seemed to be proved clinically by Dr. Mahomed,' who showed that the appearance of albumen in the urine as a sequel of scarlet fever is preceded by a period of high vascular tension. Experimentally, also, the same conclusion is arrived at. Thus, Rob- inson^ and Frerichs'' found that by ligaturing the abdominal aorta below the renal arteries and then removing one kidney, they caused albumen to appear in the urine coming from the remaining kidney. More recently Lepine (loe. cit.) has produced rise of blood pressure and consequent albuminuria by injecting a quantity of salt solution into the crural vein of a dog. An astonishing theory was propounded by Runeberg ("iJeutsch, Arch, f. Klin. Medic," vol. 23), as the result of his experiments on the diffusion of albuminous fluids through animal membranes. He attempted to show that the transudation of albumen was favored by a diminution in the difference of pressure on the two sides of the dialyzing membrane, and hindered by an increase of such difference. Applying his view^ to the kidney, he asserted that the cause of albuminuria was low vascular pressure, which produced increased permeability of the walls of the Malpighian tufts. Runeberg's results were, however, entirely contra- dicted by the careful experiments of Dr. Newman (loc. cit), and also by those of Bamberger^ and Gottwalt.^ Heideuhain, too, has shown that Runeberg's own figures will not bear the interpretation he himself placed upon them, while Bamberger points out that Runeberg has paid no attention to coincident variations of blood flow. It must, therefore, be accepted that low vascular pressure is not a cause of albuminuria. It is not safe, however, to assert that increased pressure in the Mal- pighian capillaries will alone cause albuminuria, for it is impossible entirely to eliminate other influences which may at least assist the high pressure in its work. There is now a fairly general agreement that slowing of the blood stream plays a very active part in producing albuminuria (Bamberger and Heidenhain). Dr. Mahomed*^ groups the two conditions, increased pressure and retardation of blood flow, as the chief factors in the causa- tion of albuminuria. The modes in which these various changes in the blood system of the kidney may be brought about, are of course numerous. Increase of blood pressure in the kidney may be caused by general rise of blood pressure, or locally through the vaso-raotor nerves. The fact that punc- ture of the floor of the fourth ventricle may produce albuminuria is probably to be explained by coincident injury to the vaso-motor centre. Bamberger believes that the vaso-motor system may be efficient in pro- ducing many cases of functional albuminuria. Weakness of the heart's action may cause slowing of the blood stream in the kidney, and venous obstruction may produce not only slowing of the blood stream, but also increase of pressure in the glomeruli. 1 Med. Chir. Trans., vol. 57. -' Med. Chir. Trans., vol. 26. ^ Die Brio;ht'sche Nierenkraiik, Braunscliweio-, 1851. * Wien. Med. Wochensch., 1881. » Zeitsch, f. Physiolog. Cliemie., IV. p. 423. « Glasgow Med. Journ., 1884. 204 ABNORMAL SUBSTANCES IN THE URINE. III. — Alterations in the Structure of the Kidney. These are admitted by all to be efficient causes of albuminuria. The change in structure may affect either the kidney epithelium or the bloodvessels. If it be accepted that the glomerular epithelium in the normal state prevents the albumen exuding from the blood, it is plain that any diseased condition of this epithelium will allow the albu- men to pass through. A similar function has been advocated by Senator for the epithelium of the renal tubes. Not only may gross lesions of these epithelial layers cause albuminuria, but it is also con- sidered that simple lesions of nutrition may lead to loss of function. Thus, Cohnheim^ asserts that every important change of circulation renders the secreting membrane permeable by albumen. The lesions, then, which have been described above, such as narrowing or oblitera- tion of the renal artery, changes in blood pressure, and slowing of the blood stream, would produce their effects by causing disordered nutri- tion of the epithelium covering the glomeruli. The nutritive change may be temporary, or may lead to permanent changes. The proofs of this view, however, are difficult to obtain, and it must at present be considered as sub judice. Increase of interstitial tissue, as is found in granular kidney, may be accompanied not only by changes in the epithelium, but by hindrance to the blood flow, from compression of the capillaries by the new growth. The effect of structural changes in the bloodvessels is manifest in the albuminuria which usually accompanies amyloid degeneration of the kidney. Here we have as the initial lesion a degeneration of the walls of the bloodvessels, which renders them more permeable to albumen. Such are the individual causes of albuminuria, but it will be gathered from what has been said that the causes do not act singly, and however much stress may be laid upon one change in any particular pathological state, that change is almost invariably assisted in its action by others. Thus in the albuminuria of fevers we have structural change, as shown by the cloudy degeneration of the renal epithelium, we have also changes in the blood pressure and in the rate of blood flow, while it is by no means improbable that the albumen of the blood may also undergo modification. XI.— SUGAE IN UKINE. In 1862 Schunck^ announced that, when healthy urine was subjected to boiling with acids, it gradually deposited a resinous substance, and acquired the power of reducing the oxide of copper — in other words, that the presence of a substance having the properties of glucose became apparent in it. This impor- tant observation probably explains the discrepant conclusions of those who have sought for sugar as a normal constituent of 1 Allgemeine Pathologie, vol. ii. p. 815. 2 PMlosophical Msiguzine, March, 1862. SUGAR IN THIS URKVE. 206 healthy urine. Briickc' and licnce JoneH wore alvvays ahle to obtain sugar from healthy urine in not inconsiderable quanti- ties. Bence Jones^ obtained as much as 0.8 to 1.7 grain per pint. If natural urine contain a substance, capable of yielding sugar by a simple decom[)osition, it is quite possible that the sugar found by these observers was, either partly or wholly, an educt of the analysis, and not a preexisting constituent of the urine. This much is certain, that healthy urines and the vast majority of morbid urines, do not contain sugar in quantity capable of being detected by ordinary direct testing. At the same time it is probable that minute traces of sugar, as of nearly every other substance dissolved in the blood, exist in the urine. These traces, however, granting them to exist, have no clinical significance whatsoever. When sugar is present in quantity sufiicient to interest the medical practitioner, it is detectable with certainty by direct testing; and conversely when direct testing reveals the presence of sugar, it is invariably a grave pathological sign, and not a matter of mere physiological curi- osity. In the following observations I have solely in view sugar in these sensible proportions. Tests for Sugar in Urine. (Qualitative Testing.) — Fre- quent mistakes are committed in regard to the presence or absence of sugar in urine, not only by physicians and surgeons, but even by professed chemists. More than once, specimens have been brought to me with the statement that an analytic chemist had found a small quantity of sugar, but in which no sugar really existed — certain fallacious appearances, to which I shall presently refer, having been mistaken for genuine evi- dence. Without proper precautions, sugar testing, like all other testing, is open to fallacies; but with moderate care and observ- ance of a few fixed rules, the detection of sugar is a matter of the most perfect certainty and ,of exquisite delicacy. Before proceeding to describe the best means for this purpose, I will say a word about those tests which are in common use, but which are either unreliable or insufficiently delicate — namely, Moore's test, and the fermentation test. 1. Boiling with Liquor Potassoe^Moore' s Test). — When urine con- taining sugar is boiled with an equal bulk of liquor potasses, the ^ Iwanoff has pointed out some fallacies in Brucke's process. He considers that the greater part of the sugar obtained by Briicke did not preexist in the urine, but was derived from some other constituent (inlican) by the reagents employed. Iwanoff concludes that minute traces of sugar do exist frequently, but hy no means constantly in healthy urine. (Meissner's B^richt in Henle and Pfei.fer's Zeitsch. for 1861, p. 323.) In Bence Jones's proce-s sulphuretted hydn^gen was emploj'ed instead of oxalic acid; but even with tins moditication, the urine would be rendered acid, and tliei'e would be great probability of sugar tieing produced from indican during the long process of evaporation of the large quantities (1000 c.c.) of urine used. 2 Journal of the Chemical Society, 1862, p. 22. 206 ABNORMAL SUBSTANCES IN THE URINE. mixture darkens, and eventually assumes a brandy-brown color. From its easy application, this test, as a preliminary step, and for negative evidence, is of great convenience. It has, however, two faults — (a) it is wanting in delicacy, and (6) it is liable to a notable fallacy. Moore's test does not answer clearly until the proportion of sugar rises to about 0.3 per cent., or one grain and a half to the ounce, By-and-by we shall come to a test twelve times more delicate than this. Again, all high-colored urines of high density become darker when boiled with liquor potassse, although free from sugar; and albuminous urines, even when not high-colored, darken sensibly under the same treatment. This occurs with perfectly fresh liquor potasses ; but if the test have been kept in ordinary white- glass bottles, it very speedily becomes impregnated with lead, which it attracts from the glass, and this offers an additional source of error. The liquor potassse kept in the wards of the Ro^'al Infirmary was found largely impregnated with lead, although it had not been in use more than about six weeks. Liquor potassse thus vitiated, when boiled with certain urines, turns them of a dark porter-brown color. This is something quite different from the slight deepening of the tint which has just been alluded to, and it only occurs in albuminous urines, and not even in all of these. In acute Bright's disease, especially when there was blood in the urine, or when the albumen was abundant and associated with free discharge of renal epithelium, the change of color was most intense; and in one such case the existence of sugar had been inferred therefrom, and announced to the patient and his friends, by the medical attendant, "Where the proportion of albumen was small, and renal desquamation slight, the lead-tainted liquor potassae did not produce so marked an effect. In such urines a slight darkening of color only ensued, much to the same degree as occurred with fresh liquor potassse. It was never found that liquor potassse containing lead produced a dark brown coloration Avith non-albuminous urines, provided, of course, that they were sugar free. The usual slight deepening of the tint took place, but not anything conspicuously greater than with fresh and pure liquor potassse, 2, The Fermentation Test. — When saccharine urine is mixed with yeast and kept in a warm place, it speedily ferments with the production of alcohol and evolution of carbonic acid ; and as no other substance is capable of undergoing this transforma- tion, the occurrence of fermentation with yeast is certain proof of the presence of sugar. Applied to ordinary diabetic urine, fermentation affords very clear indications. The most convenient and elegant way of applying it is the following: A few crumbs of German yeast are put into the bottom of a test-tube ; this is then filled up to SUGAR IN THE URINE. 207 the brim with the suspected urine, covered with an evaporating dish or saucer, and then inverted. The dish and inverted tube are now set aside in a warm place — say on the mantel-piece. The urine soon begins to ferment, gas collects in the top of the inverted tube and expels a })ortion of the urine; and if sugar be abundant, the gas accumulates in such quantities that all the urine is driven out before it. There is a precaution, however, to be observed. Some specimens of yeast spontaneously evolve bubbles of gas : it is therefore desirable, where the indication is doubtful, to perform a parallel experiment with the same yeast mixed with simple water, so that the amount of gas spontaneously yielded b}^ it may be ascertained. German yeast is exceedingly convenient for fermentation experiments, and it has now come into such common use that a pennyworth may be purchased in almost any baker's shop. There are two drawbacks to the clinical application of this test — (a) it takes some hours for its accomplishment, and (6) it does not sufiice for the discovery of minute quantities. Urine is capable of absorbing somewhere about its own bulk of car- bonic acid, so that, unless the amount evolved be greater than this, there will be no accumulation of gas in the top of the tube, and consequently no visible sign of fermentation. According to my experience, urine containing 0.5 per cent., or tw^o grains and a half to the ounce and under, yield no sign to the fermen- tation test. Fermentation is therefore a considerably less sen- sitive method of sugar-testing than Moore's plan of boiling with liquor potassse. There is, however, another manner of applying fermentation to the detection of sugar, which is much simpler and even more delicate than the foregoing — namely, by comparison of the specific gravity of the suspected urine before and after fermenta- tion. This proceeding will be examined more in detail under the head of quantitative testing ; but I may here observe that considerably less sugar than one per cent, may be detected by the lowering of the density after fermentation. 3. Reduction Tests. — The action of grape-sugar on a number of metallic salts in alkaline solution is attended by a reduction of the oxides which they contain to a lower degree of oxidation, or to the metallic state. A similar reducing action has the effect of changing the color of several organic solutions. Accord- ingly some of these substances are resorted to as valuable sugar tests, both qualitative and quantitative. The metallic salts best adapted for this purpose are those of copper, bismuth, silver, chromium, mercury, and tin ; but as the oxide of copper is the most universally known, and with proper precautions the most striking and sensitive, I shall here confine my remarks solely to it. 208 ABNORMAL SUBSTANCES IN THE URINE. The ordinary mode of using the copper, or, as it is called, 'Trommer's test, is to add a drop or two of a solution of sulphate of copper to the suspected urine in a test-tube. Liquor potassae is then added in excess, and the mixture boiled. If the proper proportions have been observed, a red deposit of suboxide of copper falls when sugar is present. Applied in this rough way the operation of the test is very unsatisfactory. If the copper be in excess, a quantity of the protoxide remains undissolved and causes confusion. The liquor potassse likewise obscures the result by producing an intense dark-brown color if sugar be abundant, and the boiling continued beyond a few seconds. In consequence of these and other objections, Trommer's test is regarcled with very little favor by many practitioners, who rely in preference on the easy and ready, though less delicate, method of boiling with liquor potassse. But all the uncertainty attend- ing the employment of the copper test arises from a faulty application, and not from inherent imperfection. When skil- fully used, it possesses a delicacy and certainty that render all other reagents superfluous. The first necessity is to abandon the rough method above sketched, and to prepare beforehand a test solution which shall combine the copper and the alkali in due proportion. This is accomplished by dissolving sulphate of copper in strong liquor sodse with the aid of tartrate of potash. The exact formula for this solution (Fehling's standard copper solution) will be given hereafter. Having prepared the test fluid, it is employed in the follow- ing manner : Fill a test-tube to the depth of three-quarters of an inch or so with the copper solution; heat until it begins to boil, and then add a drop or two of the suspected urine. If it be ordinary diabetic urine, the mixture, after an interval of a few seconds, will turn suddmly of an intense opaque-yellow color, and in a short time an abundant yellow or red sediment falls to the bottom. If, however, the quantity of sugar present be small, the suspected urine is added more freely, but not beyond a volume equal to that of the test employed. In this latter case it is necessary to raise the mixture once more to the boiling-point. It is then allowed to cool slowly. If no suboxide has been thrown down when it has become cold, then the urine may with certainty be pronounced sugar-free. The points of importance in this proceeding are : (a) to boil the test first, and not the urine; and (6) to use an excess of the test. The first point is of importance, because the test-solution is apt to deteriorate by keeping, unless preserved hermetically sealed from the air. When deteriorated by exposure to the atmosphere, a deposit of suboxide takes place from it on simple boiling. Boiling the test, therefore, is a trial of its perfection. SUGAR IN THE URINE. 209 If it remain clear for a minute or two after eVjulliiion, tlic solu- tion is in order, and the testing may be proceeded witli ; but if the solution become somewhat opaque, and a red deposit presently fall from it, this deposit must be first filtered from the clear fluid, which is thereby again rendered fit for use; or — which is, indeed, the better plan — a fresh supply of the test is prepared. The deterioration here spoken of arises from the conversion of a portion of the tartaric acid into racemic acid, which, equally with sugar, has a reducing power on the oxide of copper, and, when present, of course corrupts the analysis. The necessity for using an excess of the test applies equally to an ordinary diabetic urine, as well as to one which contains only a small proportion of sugar, and has a composition ap- proaching the natural standard ; but as the reason for employing an excess is not the same in the two instances, and as there are important diflierences in the operation of the test in the two classes of urine, I shall call attention to them separately. (a) Method of Testing Ordinary Diabetic Urine. — Practically, the urine of a diabetic patient, where the disease is in full career, may be regarded as a solution of grape-sugar in simple water. The natural constituents are in such small proportion, owing to the increased flow, that they do not sensibly interfere with the operation of the test. If, after the test has been heated to ebullition, one drop of diabetic urine be added, the reaction occurs almost instantane- ously, and the suboxide falls of a brick-red color at once; but if several drops of the same urine be added, the precipitate is a rich yellow. This difl:erence in color is merely a question of excess or deficiency of the test. When the copper exceeds the sugar, and the solution still retains its blue color, the suboxide falls red ; but if the sugar exceed the copper, and the blue color have disappeared, the suboxide falls yellow. The common mode of proceeding — that is, boiling the urine first, and then adding the reagent — is very objectionable, inas- much as it may betray the operator into a too sparing use of the test, and thereby entail a failure of the reaction. If the sugar preponderate greatly over the copper, no precipitation whatever ensues, because the excess of sugar dissolves the suboxide, and forms with it a transparent yellow solution. This statement may be readily verified b}^ boiling some diabetic urine in a test- tube, and then dropping in the test-solution. The first few drops occasion a dense, muddy, yellow opacity in the topmost layer; but when the tube is shaken the precipitate is redis- solved. On adding more of the test, however, the opacity becomes permanent, and an abundant deposit presentl}- sub- sides. 14 210 ABNORMAL SUBSTANCES IN THE URINE. (b) Method of Testing where the Quantity of Sugar is Small and the Natural Constituents Approximate their usual Proportions, — The discovery of sugar in such a urine is much more difficult than in the former case. The ordinary ingredients of the urine — urea, uric acid, pigmentary and otlier extractives, the alkaline and earthy salts — seriously affect the delicacy of the test. If grape-sugar be dissolved in simple water, such is the' sensitiveness of the reaction that one grain in ten pints yields a perceptible deposit; but when dissolved in urine, a considerably larger quantity may be present and the test fail to reveal its existence. Nevertheless, enough of delicacy remains to satisfy all the re- quirements of clinical research. A still greater delicacy can be imparted to the test by the method suggested by Seegen (" Brit. Med. Journ.," 1872, i. 469). The urine is filtered repeatedly through animal charcoal until it is completely colorless — a little distilled water is then passed through the filter, and to this water the test is applied in the usual way. An exceedingly minute trace of sugar (0.01 per cent.) can be detected by this procedure. Urine of the kind here considered — with a minute propor- tion of sugar, and the ordinary ingredients almost natural — is met with in the early stage of diabetes, before the disease has acquired its full developm'ent ; also in convalescence from the less severe forms; and not unfrequently towards the fatal close of the complaint. Even in well-marked diabetes there are conditions under which the urine temporarily returns nearly to its natural state. These are : abstinence from saccharine and amylaceous food, and, afo7'tiori^ abstinence from all food; accord- ingly, the morning urine, after the prolonged fast of the night, may, in the less severe cases, be found ahnost sugar-free. A like effect follows the advent of an intercurrent inflammation, as of the lungs or lining membrane of the bowels. In testing for sugar in urines of this description certain pre- cautions are rigidly demanded, otherwise considerable quan- tities of sugar may be wholly overlooked. The most important of these is to use a great excess of the test. When the copper solution is added drop by drop to healthy urine, at a boiling heat, the blue color is immediatel}^ discharged, although not a particle of sugar be present, and the urine assumes a deep amber tint. The degree to which urines exercise this decolor- izing property varies with their strength — that is, with their concentration. A dense urine (sugar-free) will discharge the color from nearly its own bulk of Fehling's standard solution ; but even the most dilute natural urines — those that are almost colorless — have a very considerable power this way. Whatever be the nature of the transformation here involved, it is certain that when the color of the test has been thus discharged, the copper it contains is no longer capable of being precipitated by S U G A R 1 M '1' 1 1 K U R 1 N E . 211 any sugar that may be present in the urhie; and the Hul>oxide is not thrown down until sueh an amount of the sohition lias been added that tlie mixture retains a distinctly green tint after being raised to the boiling-point. To secure an excess of the test, the most certain method is to heat the solution fii-st, as already recommended, and to add the suspected urine after- wards. Another advantage is secured by this proceeding. When the suspected urine contains a considerable quantity of earthy phosphates, the precipitation of these by the alkali of the test is apt to cause embarrassment. The phosphates fall in light, dirty- white tiocculi, which might be mistaken by the unwary for a deposit of suboxide. When the test and urine are mixed together before applying heat, or the test is added to the Ixnling urine, the earthy phosphates fall in such fine fiakes that the transparency of the mixture is impaired; but if the urine be added to the boiling test, the mixture retains its translucency from the phosphates being thrown down in denser masses; and by holding the tube between the eye and the light, the flakes are seen floating in a clear, bluish-green medium. In the class of saccharine urines now under consideration, the suboxide is always precipitated yellow, never red. The operation of the test is exceedingly distinctive, and takes place as follows : The copper solution having been heated to ebul- lition, and something less than an equal bulk of the suspected urine having been added, the mixture is again raised to the boiling-point. It then changes to an intense opaque yellowish- green, and slowly a bright -yellow deposit subsides. If the urine contains less than half a grain per cent, of sugar, the pre- cipitation does not take place immediately, but occurs as the liquid cools — in five, ten, or twenty minutes, and the manner of the change is peculiar. First, the mixture loses its trans- parency, and passes from a clear olive-green to a light greenish opacity, looking just as if some drops of milk had fallen into the tube. This green milky appearance is quite characteristic of sugar. B}^ this proceeding one-tenth of a grain per fluid- ounce, or less than one-fortieth of a grain per cent., can with certainty be detected, and any quantity below this has no pathological signification, and is a matter of only physiological interest. Some of the natural urinary ingredients, and especially urre acid, have been stated to possess the power of reducing the oxide of copper to a state of suboxide, and of becoming thereby the source of a notable fallacy in using this test for the detec- tion of sugar. In practice, however, no fear need be enter- tained on this score ; I have over and over again treated urines containing an excess of uric acid, and even urines thick with the amorphous urate deposit, with the test-solution at a boiling 212 ABNORMAL SUBSTANCES IN THE URINE. heat, but have never obtained the least resenablance to the sugar reaction.^ It is, however, to be borne in mind, that if urine be boiled with the test /or a considerable time, a reddish deposit falls, and the mixture assumes a muddy, dirty fawn appearance, although no sugar be present. This reddish deposit appears to consist of the earthy phosphates tinged red by some of the sub- oxide, reduced, perhaps, through the instrumentality of uric acid. But this reddish deposit is only 'produced after prolonged boiling, and prolonged boiling is of all things the most to be avoided, because the most utterly useless, in performing the test. If simply raising the fluid to the boiling-point, and then allowing it to cool in a warm place, as in a jug of hot water or on the hob, fail to yield an indication of sugar, no amount of boiling will develop a trustworthy reaction. To recapitulate, the best method of detecting sugar in urine is as follows : Pour some of the prepared test-liquid into a nar- row test-tube to the depth of three-quarters of an inch; heat until it begins to boil; then add two or three drops of the sus- pected urine. If the sugar be abundant, a thick yellowish opacity and deposit of yellow suboxide are produced (and this changes to a brick-red at once if the blue color of the test remain dominant). If no such reaction ensue, go on adding the urine until a bulk nearly equal to the test employed has been poured in; heat again to ebullition; and, no change occurring, set aside without further boiling. If no milkiness is produced as the mixture cools, the urine may be confidently pronounced free from sugar, for no quantity above a fortieth of a grain per cent, can escape such a search, and any quantity below that is devoid of clinical significance. Fehling's test may be rendered portable by compressing the solid ingredients into pellets as suggested by Dr. Pavy,^ or by enclosing the fluid in glass capsules (Dr. Ralfe^). In these ways the stability of the test is also permanently insured. The Indigo-carmine Test. — If a solution of indigo-carmine (sulph.-indigotate of soda) be rendered alkaline by carbonate of soda and boiled with a small quantity of grape sugar, the indigo- blue becomes reduced to indigo-white, which causes the blue solution to assume a yellow color. This test, originally intro- duced by Mulder, has been recently recommended by Dr. Oliver,* who makes use of it in the convenient form of test-papers. Two test-papers, one saturated with indigo-carmine, and the other 1 Hagen and Miiller have found that urine free from sugar may show from 0.087 to 0.37 per cent, of reducing agents. See Lancet, 1879, i. p. 606; also Pfluger's Archiv, Bd. xvi. S. 567. 2 Lancet, 1880, i. p. 172. These " pellets " may be obtained from ^Y. T. Cooper, chemist, 26 Oxford Street, London. » Lancet, 1880, ii. p. 192. * Bedside Urii.e Testing, 1883. SUGAR IN TJFE URINE. 213 with carbonate of soda, are diBsolved in a Biiiall quantity of" water, the result being a clear, blue solution. To this, one drop of the suspected urine is added, and the mixture boiled, when, if sugar be present, the blue color will successively give place to reddish-violet, different shades of red, and finally to a pale yellow tint. On standing, the solution reabsorl^s oxygen from the air, and gradually returns to its original hue. In Dr. Oliver's hands, this test has proved not only more convenient, but more delicate than Fehling's. The Picric Acid Test. — When a solution of picric acid is boiled with grape-sugar, in the presence of liquor potassse, the yellow picric acid is reduced to picramic acid, which has a deep red color. Dr. Gr. Johnson^ has introduced this reaction as a test for diabetic sugar in urine; but the method of applying the test will be more fully discussed, when considering its applica- tion to quantitative analysis. Estimation of the Quantity of Sugar in Urine. (Quan- titative Testing.) — In early times medical men judged of the quantity of sugar in diabetic urine by the amount of syrup yielded on evaporation. This was a very rude as well as trouble- some proceeding. A much readier and not less precise method was to calculate the sugar from the specific gravity. Dr. Henry drew up a table, which Prout afterward extended and improved, showing at a glance how much solid matter per pint was con- tained in urines at different densities. When the urine voided amounts to several quarts a day, and the natural urinary ingredi- ents have sunk to a very low proportion, the secretion resembles a solution of grape-sugar in pure water. In this condition the density is a moderately accurate measure of the quantity of sugar; but it is still far from absolute correctness, as may be judged from the following table, drawn up from a number of my analyses : Table showing the uncertain relation of the specific gy^avity to the proportion of sugar tvhere the daily flow of urine rajiged between nine and thirteen pints. Specific gravity. Sujjar per imperial pint. 1045 : 875 grains. 1043 972 " 1042 683 " 1041 920 " 1041 931 " 1040 nil " 1039 683 " 1035 875 " 1034 645 " 1033 635 " But when the flow of urine is no more than two or three pints a day, the natural ingredients come to hold something like their ^ Albumen and Suo'ai" Testino-. London, 18P!4. 214 ABNORMAL SUBSTANCES IN THE UKINE, normal proportions, and contribute very sensibly to raise he density. Accordingly with the diminished flow there is a very greatlj" lessened proportion between the specific gravity and the percentage of sugar. The annexed table shoAvs this relation in the urines of the same patients when the daily excretion had been reduced by dietetic means to between two and three pints. Table showing the lessened and siiU more uncertain relation of the specific gravity to the quajitity of sugar where the daily flow ranged between two and three pints. Specific gravity. 1044 1042 1041 1041 1039 1039 1039 1039 1036 1035 1034 1034 Sugar per imperial pint. 625 grains. 553 " 591 498 " 568 " 608 •' 600 " 446 377 ■' 471 •' 486 ^' 312 On comparing these two tables, it is seen that the density holds a much less constant relation to the proportion of sugar when the daily flow is scanty than when it is abundant. It is also seen that in the former case a given degree of density indicates a much lower proportion of sugar than in the latter. The mean density in the first table is 1039.3, and in the second nearly the same — 1038.6; but the propoi'tion of sugar is much greater in the first, where it averages 813 grains per pint, than in the second, where it is only 511 grains. Of the more accurate processes there are two peculiarly eligible for practical use — the one on account of its speedy per- formance, and the other on account of its easy application. 1. Volumetrical Processes. — These depend in principle on the fact that there is a fixed relation between the amount of sugar present and the amount of metallic salt or picric acid reduced by its action. Thus, Fehling found that one molecule of grape-sugar, or 180 parts, decomposed exactly five molecules, or 1246.8 parts, of sulphate of copper. Accordingly he prepared a solution of copper of standard strength, and applied it to fluids containing grape-sugar; and the quantity of these required to decompose a fixed volume of the standard solution furnished an exact measure of the sugar they contained. The solutions which have been used for the estimation of sugar in the urine are those of sulphate of copper, either in Fehling's SUGAR IN THE URINE. 215 method, or in the modification of it Hiif^f^ested by \)v. Tavy, and of picric acid, as applied by Dr. G. Joiinson,' a. Fehling's Illethod. — Fehling's standard solution is prepared according to the following prescription: Crystals of sulphate of copper . . 84.G4 gnimiues, or 90.', grains. Neutral tartraie of potash . . 173 ' " 304"' " Solution of caustic soda of sp. 2;r. 1.12 ..... 480 c.cm., or 4 fluidounces. , Add water to make up 1000 cuhic centimetres or G fluidounces. Every 10 cb. centira. corresponds to 0,06 gramme of grape- sugar, and 200 grains to 1 grain of sugar. The apparatus re- quired for the performance of the analysis is described and figured at pp. 36 and 37. Mode of Performing the Analysis. — Measure off 200 grains of the standard solution in the 200-grain tube, pour this into the flask, and add about twice its volume of water; then place over a spirit-lamp to boil. While the copper solution is being heated, the urine to be analyzed should be diluted with water to aknown degree. In the ease of ordinary diabetic urines, the best dilu- tion is one in ten. This is obtained by carefully filling the 6 oz, measure with water to the depth of 4J ounces, and then adding urine so as to make up exactly 5 ounces. The mixture will then contain exactly one-tenth of urine, (When the quantity of sugar in the urine is very small, a dilution of one in five, or even the undiluted urine, may be employed,) The next step is to fill the burette (which is graduated to grains) with the diluted urine to 0, Then proceed to add it, in successive small portions, to the boiling copper solution, until the blue color has entirely disappeared. After each fresh addi- tion from the burette the mixture should be raised to the "boil- ing-point, and then allowed to stand a few seconds, so that the precipitated copper may subside, and the observer may see, by holding the flask between the eye and the light, whether the mixture still retains any blue color. As soon as the blue color has disappeared the analysis is complete, and the quantity of diluted urine employed may be read off. The percentage of sugar in the urine can now be readily calculated. Suppose 125 grains had been added from the burette ; this represents one- tenth, or 12.5 grains, of undiluted urine, and contains exactly one grain of sugar; by dividing 12.5 into 100, the percentage of sugar in grains is obtained; or^^.|-=8; the urine contains 8 per cent, of sugar. If the metrical system is preferred, the process would be car- ^ Knapp's method, by which the reduction of cyanide of mercury to the metallic state is applied for the estimation of sugar, is not recommended for urine testing. 216 ABNORMAL SUBSTANCES IN THE URINE. ried out in the following manner : Into a burette graduated in cubic centimetres, 10 cubic centimetres of urine are placed and diluted to 100 cubic centimetres, with water. Place in the flask 10 cubic centimetres of the Fehling's solution (representing 0.05 gramme of sugar), and dilute with about twice its volume of water ; then boil as before. The amount of diluted urine re- quired to reduce the copper in the Fehling's solution is then determined, and the calculation made as follows : Suppose that 12 cubic centimetres of the diluted urine were required; this would represent 1.2 cubic centimetre of urine, which would contain 0.05 gramme of sugar. The number of grammes con- tained in 100 cubic centimetres of urine would be obtained bj the proportion : L2 _ 100 . ^ _ 100 X 0.05 _ 4 26 005 ~ 'x^ ' ' ^ " 1.2 ~ * ■ To determine more exactly the point at which the whole of the copper has been reduced, when the end of the reaction is believed to have been reached, a portion of the fluid in the flask may be filtered. The filtrate should be quite free from blue color, and if acidified with acetic acid and a solution of potassium ferrocyanide added, no brown color should be produced. If, by these means, copper should be found in the filtrate, sufl&cient urine has not been added, and the process must be repeated from the beginning. On the other hand, if a few drops of Fehling's solution added to the filtrate should give a deposit of copper oxide on boiling, too much urine has been added, and the process must again be repeated. For clinical purposes, however, the disappearance of the blue color can be determined by the eye with quite sufficient exactitude. h. Dr. Pavy's Method. — Dr. Pavy has introduced a modifica- tion of Fehling's method, by which the reduced oxide of copper is retained in solution by ammonia. The action of the sugar is then shown, not by precipitation of the copper oxide, but simply by the discharge of the blue color of the solution. The solution recommended by Dr. Pavy is composed as follows : Cupric sulphate ....... 4.158 grammes. Potassic sodic tartrate ...... 20.4 " Potash (caustic) 20.4 " Strong ammonia (sp. gr. 0.880) .... 300 c.cm. Water to 1 litre. Of this solution 10 cubic centimetres are decolorized by 0.005 gramme of sugar. The test may also be kept either in the form of pellets or enclosed in glass tubes each containing 10 cubic centimetres. To make the solution the tartrate of potash and caustic potash are dissolved together in one portion of the water and the sulphate of copper in another portion. Tbe solution of SUGAR IN THE URINE. 217 sulphate of copper is then poured into that of the potash salts, and to this the ammonia is added, the whole bein^ diluted with water to the required amount. The pellets are of two kinds — one containing the tartrate of potash and copper sulphate together with ammonium chloride, the other containing the caustic potash. The two pellets are dissolved separately and the solutions mixed, when the whole will represent 10 cubic centimetres of the original solution. To apply the test a burette is tilled with the urine to be examined, diluted to — preferably — 1 part in 20. There must now be placed in a small flask, 10 cubic centimetres of the copper solution diluted with 20 cubic centimetres of water, and the w^hole raised to the boiling-point. The diluted urine is then run in from the burette drop by drop, until the whole of the blue color has disappeared from the solu- tion. The amount of diluted urine thus required, divided by twenty, will give the number of cubic centimetres of urine con- taining 0.005 gramme of sugar. During the process air must be excluded from the flask, for the colorless solution of cuprous oxide in ammonia soon absorbs oxygen, forming again the blue solution of cupric oxide. For details of the process and for a convenient table, giving the amount of sugar per 1000, cor- responding to the number of cubic centimetres of urine used, the reader is referred to Dr. Pavj^'s paper in the "Lancet," I. p. 376, 1884. The process has the advantage of determining the end-point of the reaction more easil}^ than can be done by Fehling's method, and the ammoniated solution is also more stable than Fehling's solution. c. Johnson's Method. — As previously mentioned, this test de- pends on the power of grape-sugar to reduce a yellow solution of picric acid, in the presence of caustic potash, to a red solu- tion of picramic acid, — the depth of the red color depending on the amount of sugar present. In applying the test a standard solution of picramic acid is required, with the color of which, the result of boiling the urine with picric acid and potash may be compared. A standard solution representing the color pro- duced by the presence of ^ grain of sugar to the ounce of urine, is found convenient; but since the solution of picramic acid is liable to change rapidly on exposure to light, it is better to keep as a standard, a solution of acetate of iron, which, if made according to the following formula, will equal in color the standard picramic acid solution. Liq. ferri perchlor. fort. (sp. gr. 1.338) . . . .1 drachm. Liq. ammon. acetat. (sp. gr. 1.017) . . ' . .4 " Glacial acetic acid (sp. gr. 1.065) . . . . 4 " Liq. ammoniee (sp. gr. 959) . . . . 1 " Distilled water to 4 ounces. 218 ABNOEMAL SUBSTANCES IN THE URINE, 111 tliis method also, it is desirable to dilute the urine, before examining — say to five or ten times its volume. A drachm of the diluted urine is then taken and boiled for sixty seconds with 30 minims of liq. potassae and 40 minims of concentrated solu- tion of picric acid, sufficient water being added to make four drachms of the solution. At the end of the boiling, if the solu- tion is found to be less than four drachms, it must be raised to that amount by the addition of more water. This part of the process is conveniently carried out in a long test-tube marked at the height of four drachms. The deep red solution must now be diluted until its color exactly equals that of the standard solution. This is done in a stoppered tube, twelve inches long and three-quarters of an inch in diameter, graduated into 10 and 100 equal divisions. Attached to this tube is another smaller tube, containing the standard solution. A quantity of the boiled urine and test, is poured in a large tube, until the tenth division is reached and distilled water is added carefully until the colors of the liquid in the graduated tube and that in the smaller tube are exactly alike. The number of degrees of dilu- tion required to produce this is then read off. During the boil- ing the urine was diluted four times, and hence, if it then just equalled in color the test solution it would have contained one grain of sugar to the fluid-ounce. If further dilution were re- quired to bring it to this standard, say from ten to thirty-five divisions, 3.5 grains to the ounce would be indicated. Previous to the admixture with the test, however, the urine was diluted — sa}^ ten times. Hence, the result above obtained must be multiplied by ten, to obtain the number of grains of sugar per ounce of the original urine. A full account of the method will be found in Dr. Johnson's treatise on "Albumen and Sugar Testing," London, 1884. The apparatus required are made by E. Cette, 36 Brooke Street, Holborn, E.G. 2. Differential Density Method. — This method of estimating sugar combines, as I believe, more perfectly than any other, the twin advantages of ease and accuracy. It is founded on the diminution of density suffered by saccharine urine when fermented with yeast. The specific gravity of an ordinary diabetic urine ranges from 1035 to 1050. When it has under- gone fermentation, and all the sugar is converted into alcohol and carbonic acid, the specific gravity is found to have sunk to 1009, to 1002, or even below 1000. This falling off in the density arises from two distinct yet necessarily associated causes — namely, first, the destruction of the sugar, which was the cause of the high density of the original urine ; and, second, the presence of the generated alcohol in the fermented product. Now the loss of density from these causes must evidently stand SUGAR IN THE URINE. 2\U Yjroportionul to the quantity of sugar originally jjiescnt in tlio urine, and must consu(|uently iurnisli a measure of its quantity. The experimental data on vvliich this method is founded are fully detailed in a paper published by the author in the " Memoirs of the Manehester Literary and Philosophical Society" for 1860; also in a paper in the "Edinburgh Monthly Journal" for October, 1861. The mode of experimenting was — first to ascertain by Fehling's method how much sugar was contained in a certain diabetic urine. The urine was then fer- mented by means of German yeast — its specific gravity having been previously ascertained. In twenty-four hours, after the fermentation had ceased, and the scum had subsided, the density was taken again, and by subtracting this from the density l^efore fermentation, the "density lost" was ascertained. And it was found that for every grain of sugar contained in an ounce of urine, one degree of specific gravity had been lost. Experi- ments were multiplied on diabetic urine: corresponding experi- ments made with solutions of sugar of known strength in healthy non-saccharine urine and in pure water, and the issue of all was to establish the conclusion that the number of degrees of " density lost''' indicated as many grains of sitgar per fluid-ounce. In the practical application of the method, the ordinary urin- ometer may be used for taking the densities; but it is well to choose one with a long scale, as some of those in use have very short ones, and it becomes impossible to read the density accu- rately. Still further precision may be attained by dividing the usual scale into two parts on separate instruments. I have had constructed for my own use two perfectly corresponding urin- ometers, on one of which the scale ranges from 995 to 1025, and on the other from 1025 to 1055, each instrument covering 30 degrees of density. The scales are thus rendered so long, and the intervals between the lines so great, that in a clear urine the specific gravity can be easily read to a quarter of a degree ; and even in fermented urine, which does not regain its original transparency, but continues, at least for many days, more or less cloudy, it can be read with certainty to half a degree. Another important point is to obviate errors from variations of temperature. If the density before and after fermentation be taken at widely different temperatures, an error of serious amount may creep into the analysis. The best mode of avoid- ing this is to put up a few ounces of the unfermented urine in a " companion phial," and to place this side by side with that set apart for fermentation, so that, at whatever temperature the fermented product may be when its density is observed, its un- changed alter ego stands near it for comparison at exactly the same temperature. 220 ABNORMAL SUBSTANCES IN THE URINE. The most convenient way of proceeding is the following : About four ounces of the saccharine urine are put into a 12- ounce bottle, and a lump of German yeast about the size of a cobnut or small walnut is added to it. A great excess of yeast is used to hasten fermentation, but a little more or a little less does not sensibly affect the result. The bottle is then covered with a nicked cork (which permits the escape of the carbonic acid), and set aside on the mantel-piece or other warm place to ferment. Beside it is placed a tightly corked 4-ounce phial filled with the same urine without any yeast. In about twenty- four hours the fermentation will have ceased, and the scum cleared off" or subsided. The fermented urine is then decanted into a urine-glass, and its specific gravity taken ; at the same time, the density of the unfermented urine in the companion phial is observed, and the "density lost" ascertained. Fer- mentation is generally complete in about eighteen hours, if the locality be sufficiently warm; and it is desirable to remove the two phials into a cool place two or three hours before the densi- ties are taken, in order that they may attain the temperature of the surrounding atmosphere. The two following examples may serve as illustrations of the method : I. 11. Density before fermentation ..... 1053 1038 Density after fermentation ..... 1004 1013 Degrees of density lost ...... 49 25 Grains of sugar per fluid-ounce .... 49 25 If it be desired to bring out the result as so much per cent., this is accomplished by multiplying the number indicating the " density lost" by the coefficient 0.23. Thus in the first of the above examples 49x0.23=11.27, and in the second 25x0.23= 5.69, which are the amounts of sugar respectively per 100 parts. The time actually consumed in determining the quantity of sugar in urine by this method does not exceed four or five minutes, but the result must be waited for until the succeeding day; this is its chief advantage. Its application is so easy, that a medical friend in attendance on a diabetic patient was able to teach the patient's wife to make the analysis; every morning when he came, she could give exact information as to the quantity of sugar excreted on the previous day. Dr. Hensley^ has investigated the limits of error which the use of this method involves. He finds that the rule arrived at experimentally — namely, that one degree of density lost in fer- mentation corresponds to one grain of sugar per ounce of urine 1 Note on Dr. Eoberts's method of estimating diabetic sugar, by Philip J. Hens- ley, in vol. iii. of the St. Bartholomew's Hospital Eeports. SUGAR IN THE URINE. 221 — agrees very closely with t?)C theoretical result obtained by calculation. Dr. Ilensley concludes that if the above rule be applied to the fluid-ounce measure of the British Pharrnacoprxiia, and sugar be taken as dry crystal lizable glucose (CglT/J/j, the result obtained is slightly too large, but the excess above the true number is less than its sixty-fourth part, that is to say, less than 1.6 per cent. Optical Saccharimetrij . — The property of glucose of rotating the plane of polarization to the right has been taken advantage of to estimate the quantity of sugar in diabetic urine. The best instruments for the purpose are those of Mitscherlich and Soleil. This method is not so universally applicable as the preceding; and the price of the instruments, together with the delicacy required in their manipulation, puts them almost out of reach of ordinary practitioners. Clinical Significance of Sugar in the Urine. — The presence of a large quantity of sugar in the urine is the characteristic feature of diabetes mellitus: but small quantities may be pres- ent in a variety of other circumstances — as after eating exces- sively of amylaceous or saccharine articles of food, from injury or disease of certain parts of the nervous system, from impedi- ments to respiration, etc. This subject, however, can be more conveniently treated in a future page (see Physiological Con- siderations relating to Diabetes). PART II. IRINARY DISEASES-DISEASES OF WHICH THE CHIEF CHAR- ACTERISTIC IS AN ALTERATION OF THE URINE. CHAPTEE I. DIABETES INSIPIDUS. Cases characterized by increased thirst and excessive dis- charge of a watery urine of low specific gravity, free from sugar and albumen, are grouped together under the general designa- tion of diabetes insipidus. The want of uniformity in the course and symptoms of these cases, and in the anatomical changes found after death, indicate that several wholly distinct pathological states are included under this heading. Attempts have been made to classify the cases according to the characters of the urine. Those in which it was supposed that the urine merely contained an excessive amount of water, without any alteration of the total quantity of solids excreted, or of the mutual proportion of the several solid ingredients to each other, have been named Polydipsia (or excessive thirst) : those in which it was supposed that the solid matters, and especially urea, were excreted in excessive quantity, have been named Polyuria; and those in which it was supposed that the urea and other solids were in diminished quantity, have been named Anazoturia (Willis). This classification is, however, valueless in practice : both from the difficulty of assigning a precise standard of composi- tion to the urine under the various conditions of existence, and the tedious and difficult investigations, extending over several days, which are required to ascertain the mean composition of the urine in any particular case. 224 DIABETES INSIPIDUS. The following account of diabetes insipidus has been drawn up from an analysis of one hundred and twenty cases, — either collected from various sources or observed by myself. Etiology. — The liability to diabetes insipidus is very consid- erably greater in males than in females; of one hundred cases, seventy-two were males, and twenty-eight females; the age of the patients at the time of invasion ranged from the extremes of infancy to old age; but the greater number occurred be- tween the ages of five years and thirty years. In the following table an analysis is given of the ages of seventy cases at the time of invasion. Infancy 7 cases. From 20-30 years . . 16 cases From 5-10 years . . 15 " " 30-50 " . . 15 " " 10-20 " . . 13 " " 50-70 " . . 4 " In two, if not three, cas^s the disease appeared to have existed actually from birth. In a very large proportion, no exciting cause whatsoever could be assigned for the disorder. In the remainder, various cir- cumstances were alleged with greater or less probability to have been the exciting causes. These present considerable similarity to the alleged causes of saccharine diabetes, and stand in the following order of frequency : Cerebral disease (tubercle, etc.) Blows on the head, and falls . Intemperance Exposure to cold, and drinking cold fluids while heated 11 Previous febrile or inflammatory) disease ..... j Hereditary influence Muscular effort Exposure to hot sun . Mental emotion In several cases serious organic changes were found in the kidneys. These will be more particularly described in con- nection with the morbid anatomy of the disease. Two cases recorded by Dr. W. Watts (" Lancet," 1848) are referred by him to syphilitic disease and abuse of mercury. Hysteria, grief, neuralgia, or the influence of a nervous con- stitution, are also mentioned as determining causes. In some of the traumatic cases the symptoms set in with maximum intensity on the very day of the accident ; in others there was at first loss of consciousness; and the thirst and. diu- resis came on with the restoration of the faculties, or a few days after. In one case severe nervous symptoms continued for six months after a fall, and the diuresis first broke out at the end of this period. In four of the traumatic cases the symptoms per- sisted for between nine days and a month, and then finally dis- appeared as the cerebral symptoms subsided ; in two others the ETIOLOGY. 225 disorder became permanent, and liad already existed at tlie date of the record, six years in one and seven years in tlie other.' In the cases associated with cerebral disease, tumor of the brain was found in four — and degeneration of the cell-elements in three others. These cases will be noticed more particularly when the morbid anatomy of the disease comes to be treated of. In a case observed by myself (a shopkeeper thirty-five years of age), the disease had come on twenty months previously with sudden, complete, and permanent loss of sight, iirst in the left eye, and six months later in the right. During these twenty months the patient had been in the habit of voiding two or three gallons of urine daily. He was also subject to curious nervous attacks, which recurred at irregular intervals, and lasted from half an hour to periods of several days. They consisted in a perversion of intellect, incoherence, irrepressible impulse to go away from the house, trembling of the limbs and twitch- ing of the muscles. Sometimes the patient w^ould fall into an epileptiform fit, with loss of consciousness, screaming and con- vulsions, but without foaming at the mouth, or biting the tongue. When seen by me he was totally blind, but the intellect was perfect, and the general health — except during the paroxysms — was good. He could walk twelve miles with ease; and in the last eight months he had gained weight to the extent of 40 lbs. The history and general character of the symptoms appeared to point to the existence of vesicular parasites within the cra- nium. The three remaining cases of this group w^ere children supposed to suffer from cerebral tubercle. They all died in convulsions. Of the five cases attributed to intemperance, the symptoms came on in one of them on the day after a severe bout of drink- ing, in which the patient had been insensible for two days. ISTot one of this group is reported as cured ; and one died in two months. Two cases followed exposure to cold; and two followed copious drinking of cold fluids while the skin was hot and per- spiring. One of the latter, related by Vigla, began with un- quenchable thirst and diuresis on the same day, and terminated fatally a few months after. Four cases followed variola, ague, fever, and inflammation of the bowels; all ran a very chronic course, and lasted from four to twenty-four years, with good preservation of health; the symp- 1 Dr. Matthews Duncan has sent me the notes of a case (re«id before the Edin. Obst. Soc, June 10, 1874) of D. Insipidus, in a woman who miscarried at the seventh manth. Fourteen years before she had a blow of great severitj' on the back of the head. Shortly after this she observed that she drank a great deal of water, and had a great flow of urine. This has continued ever since, though she has enjoyed fair health, and is the mother of four healthy children. The qu^ntitv of urine ranged from 20 to 30 pints. 1-5 226 DIABETES INSIPIDUS. toms commenced immediately after recovery from the initial complaint. In two cases, the symptoms commenced immediately after violent muscular effort. One was a boy of twelve, who strained himself in pushing a cart-wheel sunk in the mud. After a few months, the symptoms were subdued by nitrate of potash ; but some months later a relapse occurred, and the patient died sud- denly, from taking, as is alleged, too large a dose of the nitrate (P. Frank — cited by Romberg). The second is a remarkable case, related by Jarrold, in Duncan's "Annals" for 1801. A girl of 19, when going down a flight of steps, slipped ; with very- great exertion she saved herself from falling. Immediately after menorrhagia began, and on the evening of the same day she experienced inordinate thirst and profuse diuresis. She entered the Edinburgh Infirmary, under Professor Gregory, and was speedilj- cured of the hemorrhage by the compound powder of alum. The urine amounted to the enormous quan- tity of 50 lbs. in the twenty-four hours, sometimes even to 60 lbs., and one da,j to 72 lbs. ! Under the influence of lime-water and powdered galls, the urine was gradually reduced to between 5 lbs. and 10 lbs. a day. She left the hospital otherwise in good health. Three cases were attributed to hereditary influence. One of these w-as a man in good health, who had suffered for the long period of fifty-nine years from polyuria. The disorder began in infancy. His father, two brothers, and a sister had suti'ered similarly. Another was a healthy soldier of twenty-four, who had been polyuric for four years. His mother, brothers, and two sisters suffered in the same way. The third was a young lady of nineteen, mentioned by Trousseau (" Clinique Medicale," t. ii. 611), whose grandfather was affected with saccharine dia- betes, and uncle with Bright's disease. She was well-grown and tolerably healthy, and had borne her complaint for six years. All these cases proved incurable.^ Course and SYMPTOMb. — The invasion of the complaint is often quite sudden. Dr. Bennett relates the ease of a woman, thirty-four years of age, who went to her work one morning at six o'clock in her usual health ; at eight o'clock, two hours after, she was suddenly seized wnth intense thirst and diuresis, which became persistent from that time. In several instances it is recorded that an intercurrent febrile or inflammatory disorder temporarily suspended the symptoms. 1 Orsi (Virch. and Hirsch. Jahresb., ii. p. 244, 1881) reports a most remark- able family history. In a family of nine, consisting- of parents, four sons, two daughters, and a maternal uncle, no less than six suffered from Polyuria. Weil (Virch. Archiv, Bd. 9.5) gives a still more remarkable history of a family, in which no less than twenty-two members were the subjects of Diabetes Insipidus. COUKHK AND HYM J"l'OMS 227 III one case, an attack of acute articular rJicuniatisni (treated with nitrate of potash) suspended the disease permanently, after it had existed in intensity for eighteen years. In another in- stance (a girl of nineteen, polyuric from infancy), an attack of pleurisy was treated by a blister, which suppurated for tliirty- five days; at the end of tliis time, both the pleurisy and the polyuria disappeared permanently. In a third case (recorded by Kiilz) an attack of varioloid suspended the symptoms tempo- rarily during the course of the fever. The quantity of urine voided by persons afflicted with insipid diabetes, is usually considerably greater than in saccharine dia- betes; 15, 30, and even 40 pints are frequently mentioned as the daily amount of urine.^ Its specific gravity varies from a little above that of pure water to 1003 and 1007. It is limpid and colorless, and contains but a feeble- proportion of solid matters. The total quantity of urea excreted in twenty-four hours is usually greatly increased. In many cases also the amount of phosphates is much in excess of the normal,^ but the proportion to each other of the remaining normal ingredients of the urine has not been found sensibly altered. The only abnormal sub- stance that has hitherto been detected is inosite. Inosite in small quantities has been found several times ; and it has been suggested that the presence of this substance in the urine was characteristic of the disease. This is, however, not the case. Inosite has been found repeatedly in D. Mellitus and in Albu- minuria. Probably, as Strauss conceives, the appearance of inosite is merely a coincidence of the excessive transudation of watery fluid through the tissues of the body; for he found inosite in the urine of three healthy persons who, for the purpose of experiment, had drunk in the course of a day a large quantity (10 litres) of water.^ The thirst is generall}^ intense; often inextinguishable; in several cases the patients are stated to have drunk their own urine. When the quantity of drink and the quantity of urine were compared, sometimes the one and sometimes the other showed in excess. Careful determinations on this point by Falck, ITeuschler, and others, indicate that if fluids be allowed ad libitum the urine voided is about the same quantity as the drink; but if the imbibition of fluids be compulsorily dimin- ished, the urine is not diminished in the same proportion, and dehydration of the tissues results. 1 A little sjirl of ten, under my care at the Manchester Infirmary, passed rather more than a third of her own weight of urine daily for some weeks — and yet continued in fair health. Her weight was 56 lbs. 2 See Dickinson, loc. cit., and Ralfe, "Lancet, i., 1881. This phenomenon, how- ever, is hardly sufficient to justify the term Phosphatic Diabetes, as introduced bv Teissier. 3 See Gallois's Thesis, De I'Inosurie, Paris, 1864; and Strauss's Thesis, p. 25. 228 DIABETES INSIPIDUS, The skill is generall}^ dry and harsh; sometimes it preserves its natural moisture, and in rare examples sweating has been observed, ^ It is noteworthy that boils and carbuncles are rarely mentioned. Klilz records a case in which spontaneous persistent ptyalism (not caused by mercury) coexisted with D. Insipidus in a girl of eighteen. She was under observation for about four months; and voided daily from 12 to 18 ounces of saliva and 200 to 260 ounces of urine, Kiilz calls attention to the fact that ptyalism is produced in dogs and rabbits (according to the experiments of Eckhard, Nollner, and himself) by puncture of the floor of the fourth ventricle, showing that the controlling nerve-centre of the salivary glands lies closely adjacent to that of the kidneys, and supplying the physiological key to the coexistence of D. Insipidus and ptyalism. Worm Miiller also has reported a case in which the saliva was much increased in quantity,^ The state of the general health varies a good deal. In the greater number of the recorded cases fair health was preserved — in several patients the health was perfect, and some of them became fathers and mothers of families, and went about their usual avocations without other detriment than the inconveni- ence of a constant thirst and incessant calls to void urine. A remarkable example of this kind was communicated by Mr. Maxwell to Dr. Simmons (" Med. Facts and Obs.," vol. ii. ^6). A hale farm laborer, aged fifty-one, who habitually performed the severest tasks, thrashing, mowing, etc., like his fellow-workmen, had been polyuric for twenty-four years. The disorder came on after a fit of ague. The patient drank daily, summer and winter, from 32 to 36 pints of water, and voided urine in pro- portion. Yet he slept well (except that he frequently awoke to drink): he had no pain or ache of any sort; he had an excellent appetite, a moist skin, and perspired freely when he was at work. Dr. Simmons also cites the case of a woman residing in Paris, who had been polyuric from infancy. In due time she married a cobbler, and became the mother of eleven children, of whom, however, only two were living when the case was re- corded. Dr. Willis quotes the history of an artisan, aged fifty- five, who entered the Hotel Dieu, of Paris, for some trifling bruise of the knee, from which he speedily recovered, Fronpi the age of five years he had suffered from a constant thirst, accompanied with a commensurate diuresis. From his sixteenth year he had drunk on an average two bucketsful of water daily. This man continued in good health ; he was the father of several children, and experienced no inconvenience from his infirmity beyond what was inseparable from the frequent calls ' See Yirch. and Hirsch. Jahresber., 1879, ii. p. 246. couk.se and symptoms. 229 to pass water, and the constant necessity for drink. In a boy of ten, under my care, in the Manchester Iniirmary, who had been voidino; about fifteen pints of urine daily for several months, the general health and nutrition were perfect. ]^]xcepting a dry tongue and skin, tliere was no abnormal condition ajiart from the excessive thirst and polyuria. The boy was active and in- telligent, and he ate and slept well, and looked rosy and plump. This high state of health is however exceptional: more com- monly the patients are very decided valetudinarians; and the s_ymptoms from which they suffer bear a resemblance to those of diabetes mellitus, though rarely exhibited in equal severity. These are epigastric and lumbar pains; dry, harsh, hot skin ; painful dryness and heat of the mouth and fauces; emaciation. Sometimes the appetite is voracious, more commonly moderate or indifferent. The temper is querulous; the mental faculties enfeebled; the bodil}^ strength diminished; the sexual functions often abolished. The face is subject to erythematous conges- tion. Enforced abstinence from fluids aggravates most of these symptoms: the body then becomes unbearably hot, the skin suffused, a sense of intolerable sinking, or even of intense pain, is felt in the pit of the stomach, and the intellect becomes con- fused. The loss of rest, the tormenting thirst, the mental worry, at lengtb produce, in most instances, an exhaustion of the bodily vigor; oedema of the feet often appears towards the last. The disease is, however, seldom fatal directly by its own virulence. More frequently the patient succumbs to some concomitant disorder — phthisis, pleuro-pneumonia, or organic disease of the brain. In some cases there was dislike to vegetable aliments, in others to animal food. The cobbler's wife, before alluded to, was very sensitive to alcoholic drinks; a single glass of wine caused uneasy sensations in all her limbs, and a sense of faint- ness. In other instances the patients drank freely of wine or beer, as their condition allowed. In a man observed by Trous- seau, there was a remarkable tolerance of alcoholic stimulants. This man on one occasion drank a litre (a pint and three- quarters) of brandy in two hours; and while in hospital he im- bibed daily a similar quantity without the smallest inconveni- ence. The patient related, that since his illness began he had acquired this singular immunity from the causes of drunkenness. More than once he had laid wagers to drink twenty bottles of wine at a single sitting, and had won his wagers without the least disturbance of the nervous system. Irritability of the bladder, with excessively frequent micturi- tion, was noted in several instances. The duration of the complaint is exceedingly uncertain. 230 DIABETES INSIPIDUS. The traumatic cases generally onlj^ lasted a few weeks or months: on the other hand, one of the congenital cases had endured iifty-nine years, another fifty years, at the date of the record. Out of seventy-seven cases collected, sixteen were reported as complete recoveries; fourteen ended fatally; and the remaining forty-seven were still in progress when reported; though, in some of them, considerable amelioration had taken place. In the sixteen recoveries the duration of the disease was mostly comparatively short, — in nine, it was under a year; in one, four years; in two, eighteen and nineteen years; and the remainder " some " years. In the fourteen fatal cases, the duration was still shorter. In nine of them it was under a year; one died in the short space of seven weeks; two more in two months. The other live survived for periods varying from eighteen months to twenty years. Of forty-seven cases still in progress when reported, the duration of the disease was mentioned in thirty-iive instances : Five had continued for a year or under; five, for between one and two years; twelve, for between two and six years; six, for between six and twelve years; four, for between twelve and twenty-four years; and four, for between twenty-four and fifty- nine years. Morbid Anatomy. — The condition of the organs after death from diabetes insipidus, has only been ascertained in a few cases. I have collected fourteen post-m.ortem examinations; and to these I add one performed by myself In three of these cases the lesions found presented a tolerably close similarity, and con- sisted of an atrophied and degenerated condition of the renal substance; in a fourth, the glandular tissue of the organs was entirely wanting; in a fifth, multiple abscesses were found in the kidneys; in my own case, and in three others, the kidneys were simply hypersemic and somewhat enlarged, and a tumor was found in the brain. ^ In two cases, fatty degeneration of the nervous tissue of the walls of the fourth ventricle was found. As these cases are so few in number, I shall describe them more fully. Case 1. (Dr. Eade — Beale's "Archives," 1861, p. 8.)— A man, aged 65, had suffered from jaundice and neuralgia ; he succumbed in eighteen months to the continual diuresis, and the urgent and incessant calls to void urine. The quantity of urine varied from three to six pints ; spe- cific gravity never exceeded 1008 ; it was free from sugar, albumen, or other morbid ingredient. The autopsy revealed the following : " The 1 In an appendix to the present chapter reference is made to some cases of polyuria (with records of post-mortem examinations), in which a minute quantity of sugar existed temporarily in the urine. ILLUSTRATIVE CASES. 231 infundibula and pelvis of both kidneys were greatly dilated, and the state of sacculated kidney was evidently in process of establishment. Left kidney of natural size. Kight, one-half larger, and of darker color. Both showed depressions along the surface, marking the interlobular portions. Previous to section, the cones could be distinctly felt as much denser than the interpyraraidal portions, giving indeed the sensation of so many little tumors or nodules. On section, both were seen to be pale and flaccid, and evidently undergoing a gradual process of absorption." The bladder was somewhat large and thickened ; the ureters dilated. The thoracic and the other abdominal organs were not diseased. Case 2. (Dr. Eade— Beale's "Archives," 1862, p. 128.)— A man, aged 62, had experienced excessive thirst and diuresis for twenty years. Health fair, until two years before death, when it began to fail, and for the last nine months he was unable to work. The quantity of urine often amounted to between fourteen and sixteen pints, and had never contained sugar or albumen. There was little pain beyond a sense of weariness. The bowels were constipated, and the stomach very irritable with frequent vomiting. At length the bladder became unable to expel its contents, and a typhoid state supervened ; the stomach rejected every- thing, and he died exhausted. Autopsy. — Both kidneys were diminished in size, deeply lobed on the surface, and very dense to the feel in the position of the cones. On section, they were seen to be greatly wasted. The cortical portions very thin, and scarcely to be distinguished from the pyramidal. The cones were nearly absent, or rather were converted into dense fibrous tissue, containing many large cystiform spaces. The mucous membrane of the pelvis was thickened, fibrous-looking, and darkly congested. The pelvic cavities considerably enlarged. Ureters a little dilated. On micro- scopical examination (by Dr. Beale), many of the tubes were found narrow and much wasted, while others were twice their natural diame- ters. The walls of the tubes were firm and thick. The capillary vessels everywhere were surrounded by a considerable quantity of fibrous mate- rial with numerous nuclei. The Malpighian bodies were, for the most part, smaller than in health. The epithelial cells were also smaller, as well as more numerous than in health, and the tubes appeared to be dis- tended in many places by their accumulation. The suprarenal capsules were greatly diseased, and converted into flaccid cysts. The bladder was enlarged, and its walls thin and pale. The other abdominal organs were healthy, except perhaps the liver, which was intensely congested. In neither case does the brain appear to have been examined. Case 3. (NeufFer — cited in Magnant's Thesis.) — A man, aged 28. The disease came on after a drunken bout. There was intense thirst ; the urine amounted to thirteen or fourteen pints a day ; specific gravity 1001 to 1002 ; without trace of albumen or sugar. He emaciated rapidly ; had pain in the epigastrium ; at length frequent vomiting ; itching of the skin, which was dry; enfeebled vision. He died in about two months. Autopsy. — The gastric mucous membrane was pale and swollen; the kidneys Avere notably diminished in size, pale, auremic ; the epithelium 232 DIABETES INSIPIDUS. of the tubes fatty ; bladder contracted ; mucous membrane a little tumefied ; other organs healthy. Case 4. (Dr. Strange— Beale's "Archives," 1862, p. 276.)— The patient was a farm laborer, aged 18, who presented the appearance of a moder- ately stout lad of 15. He was admitted into the Worcester Infirmary on October 19, 1861. The skin and tongue were natural, and the face ruddy; appetite normal; thirst constantly excessive ; bowels generally relaxed. The urine amounted to about twelve pints in the twenty-four hours ; its specific gravity was 1007 ; it contained neither sugar nor albumen. All the history obtainable was, that the patient had been a delicate and backward boy ; that he had had this diuresis for a number of years, and that the medical attendant had always affirmed that the urine did not contain sugar. Dr. Strange, being desirous to ascertain whether the diuresis was kept up by the excessive imbibition of fluids (in accordance with the theory of Prof Bennett and others), restricted the patient to a more moderate allowance of fluids. A warm bath was administered twice a week. Four days after admission (October 23), the urine measured nine pints ; its specific gravity was 1006. On the 26th the bowels were much re- laxed ; urine five pints. On the 28th, a phosphoric acid mixture which he had been previously taking was omitted, and Mist. cret. co. given instead. On this day the patient complained for the first time of head- ache, with weakness and loss of appetite ; there were also some febrile symptoms. On the 29th, the bowels being still relaxed, five minims of tinct. opii, and half a drachm of tinct. catechu were added to the mix- ture. On the 30th he became drowsy, with pain at the back of the head; the diarrhoea continued, with vomiting. Effervescing draughts, with nitric ether, were now administered in lieu of the previous medi- cines ; half an ounce of brandy was given three times a day, and cold applied to the head. On November 2d, the drowsiness and sickness had abated ; the bowels were confined ; the urine three and a half pints, specific gravity 1004. The brandy was omitted, and half an ounce of castor oil administered. As it now appeared that restricting the patient in his drink had resulted in mischief, he Avas allowed to take as much water or barley-water as he pleased. On November 4th, in the morning, he was again drowsy ; in the evening he was seized with convulsions, and shortly afterwards he became comatose and insensible, with dilated pupils and stertorous bi^eathing. He was bled to §x, and much relieved thereby. The coma ceased, and consciousness and speech returned in a quarter of an hour. Mustard was applied to the feet, and a draught containing tinct. canthar. and sp. seth. nit. in camphor water was given every third hour, with a view of restoring the accustomed diuresis. On the morning of the 5th he was conscious, and still had some headache. The diuretic mixture was continued, and a black draught administered immediately. On the 6th he was again found in a semi-comatose state, the pupils were dilated, and there was stertor, with sighing respiration. Six leeches were applied to the temples, mustard to the feet, and cold to the head. Then coma became more profound, and he died at 9 p.m. Autopsy. — The kidneys were found to be reduced to mere sacs, of from twice to thrice the extent of the healthy kidney. There was a complete ILLUSTKATIVB CASKS. 233 absence of all proper parenchymatous 8ul)8ttuic(!, both tuhiihir and cor- tical ; the sacs being divided into a nurrd)er of cells by the intertuhuiar septa which occur in the fo.^tal state. The walls and septa were formed of strong fibrous tissue, lined with what appeared rather serous than mucous membrane, and the cavity and ureters contained a small quan- tity of the same urinous fluid which had been passed during life. The ureters were so much dilated that that on the right side was at first mis- taken for the ascending colon. The circumference of the ureter varied from three to four and a half inches. The kidney and ureter of either side were almost precisely in the same condition. The urine in the ureters and sacs was tested for urea by evaporation and nitric acid, without result. On closer examination no proper kidney substance could be discovered, nor did it appear that there ever had been any tubular or cortical portions; here and there were a few hard cartilagin- ous masses of very small size, closely adherent to the membrane forming the sac. The other abdominal and the thoracic organs were healthy. The brain was not examined. Case 5.— On the 29th of May, 1862, I saw, with Mr. J. Smith, of Stretford Road, a youth of 16 years of age, who was passing a large quantity of a watery urine. He was moderately well-grown, exceedingly emaciated, weighing only 78 pounds. Pulse 127 ; tongue glazed, red in the centre, and covered with a yellowish-brown fur at the sides. The skin was dry and harsh. The patient was troubled with intense and incessant thirst, and voided from nine to twelve pints of urine daily. The appetite was bad. Neither the head nor chest was the seat of any subjective symptom. He gave the following account of himself: Previous to his present illness he was occupied as a clerk in a warehouse, and had enjoyed unin- terrupted health until three months ago. About that time he noticed that he was getting thinner and w^eaker, that he drank a great deal, and never perspired. These symptoms had undergone a gradual and steady increase, and a fortnight ago had sustained an alarming aggravation. The patient could, nevertheless, still go about, and even take the air for short periods. He suffered no pain in any part, but he slept badly, and passed restless nights. The appetite had been indifferent from the very beginning, and it was now altogether lost. The bowels were moved almost daily, but there was a tendency to constipation. Dyspeptic symptoms — heaviness after food, flatulence, and occasional vomiting — bad been noted from the commencement of the illness, but they did not attain a great severity at any time. In searching back among the patient's antecedents for any determin- ing cause, no fact of moment was elicited. The lad had been living in comfort, well-clad, w^ell-fed, and well-housed, with his grown-up sisters. No tuberculous or other family taint could be traced. The case had been treated wdth morphia, bismuth, and permanganate of potash, but with no result beyond a palliation of the dyspeptic symptoms. The urine of the twenty-four hours was carefully collected and measured on six several occasions, and portions sent to me for examina- tion. The characters of it were constant ; it was pale like water, and the specific gravity varied from 1002.7 to 1004. The quantity was' 234 DIABETES INSIPIDUS, between uiiie and ten pints at the time of my visit. It afterwards in- creased to fourteen pints daily. There was neither albumen nor sugar in it, and its reaction was faintly acid. The quantity drank was found, on exact measurement, to be almost precisely equal to the quantity of urine. The amount of urea varied from 0.4 to 0.55 per cent., and from 394 to 505 grains in the twenty-four hours. This was an enormous quan- tity for the weight of the body. According to the mean results tabu- lated by Dr. Parkes, the daily secretion for his weight of 78 pounds should only have been 275 grains. The patient continued without much change beyond a progressive increase of debility and loss of flesh, drinking enormously, and voiding corresponding quantities of urine, until July 5th, when he was suddenly seized with convulsions and insensibility. After the convulsions had ceased, he began to recover some degree of consciousness, and passed into a semi-comatose condition, which persisted for three days, and then passed away. During the period of unconsciousness the diuresis dimin- ished notably; but it returned immediately afterwards, and the patient continued very much as he was before the seizure, for a period of ten days, when he was again taken with convulsions and insensibility, and died on the morning of July 18th. Autopsy. — Thirty hours after death. The body was emaciated to the last degree ; signs of incipient putrefaction appeared on the abdomen, the weather being warm. Chest. — The heart was healthy, but very small ; the lungs were stuffed with crude tubercle throughout their upper lobes, and several small vomicae lay scattered through them. Abdomen. — Five tuberculous ulcers were discovered in the small intes- tines; some of them had penetrated the mucous and muscular coats, and seemed ready to break through the peritoneum. There was no tubercular deposit in the peritoneum generally, nor any in the liver or spleen. The kidneys were voluminous, smooth, flaccid, and the two together weighed eight ounces. On section they showed no disproportion between the pyramidal and cortical portions, nor any other morbid change. Examined microscopically, the tubes and cells appeared normal. Mead. — About two ounces of clear serum escaped from the arachnoid sac. The meninges were free from tubercle, and quite natural. The ventricles were greatly distended, and contained six ounces of clear serum ; their parietes were macerated, and gave way with the slightest traction. A nodule of yellow tubercle, of the size of a hazel-nut, lay embedded in the left hemisphere, in the border of the longitudinal fissure, midway between its extremities, and cropping out on the surface. Another nodule, as large as a garden-bean, was found in the posterior border of the right half of the cerebellum. An undue vascularity prevailed at a few spots of the surface of the encephalon. Apart from what has been related, the brain substance was healthy and of firm consistence. The floor of the fourth ventricle was especially examined ; it was pale and natural, with no tubercular mass in its immediate vicinity. Case 6. (Mascarel— "Gaz. d. Hop.," February 23, 1863.)— The patient was a man, aged 50, pale and thin, without fever, but a devouring thirst. ILLUSTRATIVE CASKS. 235 and a red tongue ; appetite good, hut nc)t voracioiiH. lie drank daily from eight to ten pints of water, and voided urine prfjportionaily. The disease had existed eight months. Seven days after entering the hospital, he became feverish, at first ordy in the night, then continuously, with nausea, and epigastric tenderness. Thirst was intense, l)ut there was no api)etite. Not the least trace of sugar or albumen existed in the urine. The urine showed, after the fever became persistent, on cooling, a slight yellowish-white deposit, not mucous, but as if purulent. This last char- acter was only noticed two days before death. Autopsy. — The left kidney was more voluminous than the right, and eight to ten little abscesses, varying from the size of a pin's head to a small filbert, were found in the cortical part. The smaller abscesses contained almost concrete pus, and the larger ones fluid pus, without any tubercle. The infundibula were filled with a creamy fluid. AIJ the abscesses were near to and reached the surface. The right kidney was of natural size, hypcra^mic and free from dis- seminated abscesses, but a lactescent fluid could be squeezed from the pyramidal portions. The brain was not examined. Case 7. ("Revue d. Hopitaux," 1861.) — A man, set. 35, who had had saccharine urine five years before, was passing daily six to seven litres of urine, sp. gr. 1001-7, not containing either albumen or sugar. The patient was suffering from phthisis. Being seized with acute pulmonary symptoms, the urine fell to a small quantity ; a purpuric eruption came out on the skin, and death took place fourteen days after, without cerebral complications. Autopsy. — The walls of the fourth ventricle were more vascular than usual, and some tawny spots were seen disseminated on the surface. On making transverse sections of the spots, Luys discovered with the micro- scope extensive fatty degeneration of the nerve cells. Cases 8 and 9. (Kien — "Gaz. Hebd.," 1866.) — In one case Kien found great vascularity of the kidneys. In the walls of the fourth ventricle, scattered yellow spots were found, which exhibited under the microscope abundant evidence of fatty degeneration of the nerve elements. In his second case, no changes were found in the kidneys — neither with the naked eye nor with the microscope, beyond congestion of the Malpighian bodies. Nothing was found in the medulla oblongata. Case 10. (Reported by Mosler in Virchow's " Archiv," 43, 225.) — The patient was a girl of 22, who had for many years been suffering from symptoms of tumor of the brain. In the later years of her life_ she was, in addition, suffering from symptoms of diabetes insipidus. After death, a tumor as large as a walnut, of a fibro-plastic nature (Glio- sarcoma of Virchow), was found attached to the floor of the fourth ven- tricle, and filling the entire cavity. Case 11. (Dickinson on " Diab.," p. 184.) — A child of 5 had symptoms of D. insip. for about a year. She died with symptoms of tubercular meningitis. Miliary tubercles and thickening were found at the base of 236 DIABETES INSIPIDUS. the brain near (but not in) the fourth ventricle, and on the upper sur- face of the cerebellum ; no bulky masses of tubercle were found. Case 12. (Dickinson on " Diab.," p. 223.) — A man, set. 60, had suffered from diabetes insipidus for fifteen months, and had been ailing for two months before the polyuria was noticed. Post-mortem there was found malignant disease of the liver and post-peritoneal glands, which had involved and partially destroyed the solar plexus. The kidneys were of normal size, but minutely injected. Microscopically there was found some excessive growth of the tubular epithelium. Case 13. (Ralfe, " Lancet," 1881, I. p. 406.)— A man, set. 24, with a syphilitic history, had suffered from polyuria with increase in the amount of phosphates excreted. Post-mortem there was found a gumma about the size of a small hazel-nut, situated under the floor of the third ven- tricle in the middle line. It was surrounded by some softening of the cerebral substance. Case 14. (Haas, " Prager-Vierteljahresch.," 1875, Bd. 127, p. 12.)— A woman, get. 23, suffered from polyuria, associated with almost complete blindness and tuberculosis. The urine passed varied from five to ten litres a day, and occasionally contained a little albumen. There was found post-mortem tuberculosis of the lungs and intestines. The optic nerves were atrophied, but no change of importance was found in the brain. The kidneys were not enlarged, but were congested. The liver was enlarged and hypersemic. Case 15. (Fazio— see "Lond. Med. Pvecord," 1880, p. 138.)— A woman, aged 21, had suffered for three years from excessive thirst and polyuria, with pains in the head. Dimness of vision was noticed, but no ophthal- moscopic examination was made. At the autopsy a sarcomatous tumor was found in the region of the sella turcica, causing pressure on the brain substance in the neighborhood. I^ature of Diabetes Insipidus. — A review of the post-mortem examinations just recorded, is suflBcient to show that the initial disorder in diabetes insipidus must be looked for elsewhere than in the kidneys. The diverse organic alterations found in the kidneys by Eade, N^eutFer, and Mascarel, were evidently second- ary, and produced by the irritation of the frequent micturition and excessive and long-continued diuresis. Similar alterations are found in the kidneys of persons dying of long-standing sac- charine diabetes. The case of Dr. Strange is certainly very puzzling: one can only conceive a teleological reason for the diuresis, namely, the absolute necessity for an immense transu- dation of watery fluid to make up for tlie imperfection of the glandular apparatus. ^OY can the disease be regarded merely as excessive thirst and a vicious habit of profuse potation. It has been almost invari- ably found that an enforced diminution of liquids fails to arrest NATURE. 2'J7 the diuresis, except purtially. The oh.servutioTis of Kalck, Xeu- scliler, and ISTeuffer, agree perfectly in this: that when the sup- ply of water hy the iriouth is dirniniKluMl, the quantity of urine notable exceeds the ingoing w^ater, and thereby occasions dehy- dration of tlie tissues, with an intolerable aggravation of tlie symptoms. It may be regarded as prol)able tluit the rimnedlate anatomical cause of polyuria is a dilation of the renal capillaries, whereby their walls are thinned and rendered favorable to increased transudation of watery fluid from the blood. But how is this brought about ? It is now generally believed that the minute bloodvessels possess in their circular and longitudinal muscular coats a provision for an active expansion as well as an active constriction of their calibre.^ This provision is under the con- trol of the sympathetic branches of nerves (nervi vasi-motores), and serves to maintain the aqueousness of the blood within certain limits of health. When the tissues and blood are over- charged with w^ater, the renal vessels expand, and permit a copi- ous transudation of an aqueous urine; when, on the other hand, the system is undercharged with water, they contract, and thereby restrict the urinary transudation. In diabetes insipidus this endowment seems greatly impaired; the renal capillaries appear to resemble the iris in glaucoma, which remains in a motionless, semi-dilated state, and neither contracts witli light nor dilates with belladonna. In polyuric subjects the contractile power of the renal vessels is apparently paralyzed; and the power of regu- lating the urinary flow consequently lost. If a healthy person imbibe an excessive amount of w^ater, he rapidly gets rid of the overplus by a sudden and copious diuresis, and then the secre- tion falls quickly to its ordinary rate : but a polyuric subject, under similar conditions, shows very little immediate increase of urine, but a steady, persistent, though less intense, augmenta- tion, lasting many hours, and which is not succeeded by a fall to the ordinary standard. On the other hand, if a healthy person imbibe a lessened quantity of w^ater, the discharge of urine falls in proportion: whereas the polyuric, under the same circum- stances, show^s no such adaptation ; he still continues to discharge an undue amount of urine, which necessitates constant imbibi- tion of new" supplies of water to prevent dehydration of the tissues. On this view, the primary cause of diabetes insipidus must be looked for in some other parts than in the kidneys; namely, in some part of the chain of sympathetic nerves which controls the ^ For a demonstration of the anatomical possibility^ of this endowment I must refer to Schiti''s ingenious researches. See his " Untersuchungen iiber die Zucker- bildung in der Leber," p. 92. Wiirtzburg, 1859. 238 DIABETES INSIPIDUS. action of the contractile tissues of tlie renal vessels. This chain extends from the kidney's to the abdominal ganglia, thence to the spinal cord and the Hoor of the fourth ventricle, where the sympathetic s^^stem seems to have its centre. From above, this centre receives impressions from the encephalon. This theory seems conformable both to experiment and to clini- cal facts. Bernard found that by puncturing a certain spot in the floor of the fourth ventricle, an augmented secretion could be produced of a watery urine, containing neither sugar nor albumen. A large proportion of the cases of diabetes insipidus followed injuries to the nervous centres, or were evidently de- pendent on some derangement of the nervous system. In six cases, palpable disease of the brain was found after death, while the kidneys were healthy. Flatten ("Arch. f. Psychiatrie," XIII. p. 671, 1882} has recorded a case which assists to localize the "poly uric" centre. A patient, after a blow on the head, was attacked by diabetes insipidus. There were also certain permanent symptoms of the cerebral disturbance. Thus, there was paralysis of the left sixth nerve and weakness of the right sixth, with slight deafness on the left side. The probable diagnosis was hemor- rhagic softening near the centres for the sixth nerves. Flatten calls attention to two other cases, one reported by Gayet ( " Gazette Hebdo- mad.," No. 17, 1876), in which paralysis of the right sixth nerve was accompanied by diabetes insipidus; and another, by Kamutz ("Arch, f. Heilkunde," 1873), in which an injury to the head was followed by paralysis of the right sixth nerve and diabetes mellitus. It is, perhaps, worthy of remark in this connection that puncture of the floor of the fourth ventricle, near the nucleus of the trigeminus, has produced increased flow of saliva, while in two cases (Kiilz and Worm Miiller) salivation was observed in diabetes insipidus. In other cases, it is probable that the sympathetic in the ab- domen was the point originally injured.^ Among such may be classed those arising from drinking cold fluids while the body was heated, and perhaps also those following alcoholic excesses. The influence of a lesion of the vagus in producing the disorder is doubtful. Dr. Ralfe (" Lancet," 1876, 1, p. 308 ) has recorded two cases of aortic aneurism accompanied by diabetes insipidus, and he was in- clined to attribute the latter symptom to pressure on the vagus in the ' In reference to this point, see two papers by Eckhardt and Knoll, in Eck- hardt's Beitrage, VI. Heft i. — also Merbach's paper (Kiichenmeister's Zeitsch., 1865, p. 10). Probably the case related by Professor Houghton was of this character. This was a woman who died with symptoms of D. Insipidus, together with dis- tention of the abdomen from fceal accumulation caused by a viterine tumor press- ing on the rectum. The mesenteric glands connected with the colon were enlarged and indurated. The symptoms had lasted nine years. Dublin Quarterly, Nov. 1863. See Dr. Dickinson's case mentioned on p. 235. DIAGNOSIS, rilOGNOSlH, TREATMENT. 239 chest, on the ground that Bernard produced jxjJyuria by irritating the vagus. Further observations, however, are required to support this view. A ibiiture of the disease favorable to the tljcory of its nervous origin, is its occasional sudden onset after events whicli do not directly implicate the urinary organs; and its equally sudden subsidence when a strong impression is made on the system by an intercurrent inflammation. The total and unexpected dis- appearance of the disease, after continuing man}' months or years, is more in accordance with the habit of neuroses or ner- vous diseases than of any other class of maladies. The Diagnosis of diabetes insipidus lies on the surface. A permanent increase of the urine, without sugar or alijumen, sufHces at once to define and to identify it. But it is evident from the facts and considerations before adduced, that to gain a useful clew for treatment, we must attain to more precise notions as to the part originally affected — whether brain, or cord, or abdominal ganglia, and also as to the nature of the lesion in the affected part. The Prognosis is, speaking generally, less serious than in saccharine diabetes; nevertheless, insipid diabetes is a very un- manageable complaint; it generally resists treatment, and not unfrequently runs a fatal course. The gravity of the prognosis in a particular case depends on the severity of the general symp- toms, and on the presence or absence of complications. The cases which affect the general health the least, though mostly proving incurable, appear to be those which arise after inflam- matory complaints, after mental emotion, cerebral injuries, and those which arise early in life without an}' known cause. On the other hand, those which depend on organic disease of the nervous centres are necessarily fatal. Treatment. — Until we obtain a better insight into the path- ology of these cases, our treatment must be necessarily empirical. Hitherto the indications pursued have been mostly contined to efforts to subdue the more palpable symptoms — the thirst and diuresis. The means used for this purpose have been various. J. Frank considered nitrate of potash in large doses as a specific; in some of the recorded cases it proved of decided service ; in others it as completely failed. Camphor and valerian were used in a number of the French cases, and sometimes with sucfcess. Trousseau speaks in high terms of valerian, and cites the authority of Kayer as additional evidence of its eflicacy. Trous- seau gave it in large doses. In one case, which ended in com- plete and permanent recovery in four months, the extract was gradually pushed to the enormous dose of one ounce daily; his ordinary dose would appear to be two and a half drachms a day. Eayer obtained rapid success in a boy who suffered from poly- 240 DIABETES INSIPIDUS. uria, with emaciation and nervous symptoms, by means of the powder of valerian. In the case of the boy alluded to at p. 238, the valerianate of zinc appeared to produce a good effect. It was given in pill, in gradually increasing doses, until 20 grains a day had been reached. The urine fell from 15 to 5 pints a day, and the thirst and dryness of the tongue were greatly diminished. Enforced abstinence from fluids was tried in a number of cases; and, in one recorded by Becquerel, with good effect; but in nearly all the others it was not only unsuccessful, but was followed by decided aggravation of the general suffering, and in some cases by symptoms of threatening or actual ursemic poison- ing. The fate of l)r. Strange's patient is particularly instructive on this point. In one of my own cases opium produced great diminution of the thirst and diuresis, but the patient's distress was so increased that I was compelled to suspend the use of the remedy. Dr. MurrelP obtained good results from the administration of belladonna and ergot, in a case where the disease followed a fall on the head. He believed that here there was a lesion of the sympathetic and consequent relaxation of the renal vessels, which would probably be overcome by the drugs administered. In other hands, also, ergot has met with considerable success. Among other remedies occasionally followed by success were iron, gall-nuts, lime water, cream of tartar, iodide of mercury, iodide of potassium, and pilocarpin. Dr. Kennedy ("Practi- tioner," vol. 20, p. 94) has recorded five cases in which great benefit was obtained from drachm doses of dilute nitro-muriatic acid. One of the most frequent incidents in the history of diabetes insipidus is the temporary suspension of the thirst and diuresis on the occurrence of some intercurrent febrile affection, and in two instances the suspension proved permanent. A hint for treatment may be taken from this. The application of a large blister on the nape of the neck or the epigastrium (according as the associated symptoms and the anamnesis point to the nervous or the digestive system), might in some cases have the same beneficial effect as a spontaneous inflammation. In the case treated with opium, just alluded to, a blister to the pit of the stomach proved of more benefit than any of the numerous means previously employed. The application of the constant galvanic current has been tried, with a promise of success. Dr. M. Seidel tried this treatment in a woman, ?et. 29, suffering from diabetes insipidus. He applied one pole of a strong battery over the loins near the spine, and pressed the other pole as deeply as possible upon the correspond- 1 Brit. Med. Journ., i. 1876. APPENDIX. 241' ing liypocbondrium; each side was daily galvanized for 5 minutes. In 8 days the urine had fallen from 5957 c. c. to 4600 c. c, and after three weeksto 2300 c. c., and next month to 190 i c. c. Simultaneously the weight of the body increased by nine pounds. The amendment was found to be maintained at the end of three months.^ Kiilz obtained very favorable results in two cases treated for some weeks by a constant battery of 80 to 40 elements. He applied one pole as high as possible to the nape of the neck and the other to the loins or epigastrium. The most effective way appeared to be to apply the positive pole to the nape and the negative pole first to the loins for four minutes, and then to the pit of the stomach for four minutes. Dr. Althaus^ has recorded a case in which immediate improve- ment resulted from the application of the constant current. The current was applied to the occiput, its direction being repeatedly reversed. The secondary symptoms — dryness of the skin, epigastric and lumbar pains, etc., must be treated by warm baths, alkaline tonic infusions, sedative and anodyne remedies. APPENDIX. Cases characterized by excessive diuresis and thirst ; urine of very low specific gravity, but containing, or having contained, a trace of sugar. Cases of this type form an intermediate group between in- sipid and saccharine diabetes ; and their existence completes, in an exquisite manner, the ^correspondence between the results obtained by Bernard from artificial injuries to different parts of the floor of the fourth ventricle, and clinical observations. Two cases of this class, following fracture of the skull, are reported by Fischer ("Archives Gen.," Oct. 1852). In one, the sugar amounted to 0.32 per cent. In the other, in which there was a voracious appetite as well as intense thirst, there was 0.5 per cent, on the first day after the accident, and 0.6 per cent, on the third day. The fioor of the fourth ventricle was examiaied in both instances after death, and was alleged to be healthy; in the second case (which terminated in tetanus), the whole brain and cerebellum, so far as could be made out, were uninjured. A third case, arising spontaneously, is related by Trousseau. The disease had already existed four years without serious giving way of the health. The examination of the urine (by 1 Schmidt's Jahrb., Bd. 130, S. 97. '^ Med. Times, 1880, ii. p. 617. 16 242 DIABETES INSIPIDUS. Boucharclat) on two occasions, at considerable intervals of time, showed a trace of sugar. The quantity of urine varied from 12 to 37 litres a day. Among the secondary symptoms were im- potence, lumbar pains, and a remarkable tolerance of alcoholic drinks. This man derived considerable benefit, but was not cured, under the use of valerian. A fourth case is recorded in the " Gaz. des Hopitaux" for 1861. A man, set. 35, was afflicted for many years with poly- uria, passing daily from 10 to 12 pints. of urine, specific gravity 1001-1007. He was the subject of chronic phthisis when in the Hotel Dieu, under Trousseau, in 1861. There was then not a particle of sugar or albumen in the urine; but when he was an inmate of the Hop. St. Antoine, in 1856, a trace of sugar was found. Acute pulmonary symptoms came on at last, with pur- pura. The urine rapidly diminished in quantity, and the patient sank. The autopsy was performed by Luys. The floor of the fourth ventricle was more vascular than natural; large vascular trunks mapped the surface; yellow spots were seen scattered over the upper part, near the crura cerebri. Similar patches were found below the points of origin of the radicles of the portio mollis. On section, the whole gray substance was found unusually vascular, and of a rosy hue. Microscopic examina- tion showed that these alterations in color were due to fatty degeneration of all the nerve cells of the corresponding regions. A fifth case is reported by Dr. lialfe ("Lancet," 1881, i. p. 407). A gentleman, set. 37, had suffered from mild glyco- suria for eighteen months. The glycosuria occasionally disap- peared, but a certain amount of polyuria (2500 c. c. daily) with excessive excretion of phosphates was constant. The patient improved under codeia and opium, with tepid saline douches. A case which may be classed with these occurred to mj'self some years ago. A man of sixty-five was brought into the Manchester Infirmary in an apoplectic fit. He died after lying for six hours in deep coma. During this period he flooded the bed with urine. After death a large quantity of urine was withdrawn from the bladder. It had a specific gravity of 1010, and contained a considerable quantity of sugar. A voluminous clot was found in the brain. CIIAPTEll II. DIABETES MELLITUS. The multiplied researches of recent years on the occurrence of sugar or glucose in the urine, necessitate the adoption of some classification of cases of saccharine urine. Cases of saccharine urine may be primarily divided into two broad classes or divisions. One class consists of instances in which a small quantity of sugar appears in the urine for very short periods, without relevant symptoms — the circumstance being a temporary and incidental consequence of some physiological or pathological antecedent which has little or no affinity to diabetes, as clinic- ally understood. Belonging to this class are examples of sac- charine urine after the administration of chloroform, after eating an excessive quantity of saccharine and amylaceous food, in recovery from cholera, and after a paroxj^sm of whooping- cough, asthma, or epilepsy. These may be designated as cases of incidental glycosuria. In the other class of cases the glycosuria is more intense: it constitutes a permanent symptom, and persists for considerable periods of time, and is associated with a serious departure from health. To this class alone is the term diabetes at all applicable. This second class again is divisible into two groups. In the first, the glycosuria is persistent and intense, and the flow of urine is greatly increased ; this state of urine is associated with thirst, debility, emaciation, and a train of grave, fatally tending symptoms, which constitute a familiar, easily recognized clinical unit3\ This is the classical diabetes of authors, and to this the name diabetes was limited, before our more refined and ready analysis disclosed the presence of sugar in the urine in a number of other and diflferent states. The second group embraces those less serious types in which sugar is present in the urine, sometimes abundantly, some- times scantily, sometimes persistently, sometimes intermittently; always with a weakl}^ condition of health, but without thirst or conspicuous emaciation, often, indeed, with corpulence; without any, or only slight, increase in the quantity of urine, and with- out that fixed tendency to death whicli stamps the first group — occurring also generally in advanced years, or at least beyond the time of early manhood. Some of these milder t^'pes of gly- 244 DIABETES MELLITUS. cosuria will be separately noticed at the end of the present chapter. ETIOLOGY OF DIABETES MELLITUS. In the decade 1851-60, 4546 deaths from diabetes were regis- tered in England and Wales, being an annual average ot 454.^ Of the total number 3032 were males, and 1514 females, show- ing that in this country diabetes is twice more common in men than women. Up to the age of puberty, the two sexes appear to be equally liable to diabetes ; but from that period on to old age the liability of the male sex maintains an increasing ratio, as may be seen from the following table : Table showing the number of deaths from, diabetes, at different periods of life in the two sexes.^ PEEIOB OF LIFE. Under 5 yrs. 5-10 yrs. 10-15 yrs. 15-25 yrs. 25-35 yrs. 35-45 yrs. 45-55 yrs, 55-65 yrs. 65-75 yrs. 75 years and upwards. All ages. Deaths in males. Deaths in females 28 23 40 42 97 78 378 220 468 282 502 261 550 247 500 191 364 144 105 26 3032 1514 Total males and fe-\ males. / 51 82 1 175 598 750 763 797 691 508 131 4546 Dr. Dickinson has shown that diabetes is more common in agricultural than in urban districts, and is also more frequent in the colder parts of the country. Diabetes prevails chiefly among 3^oung and middle-aged adults. It is rare under live years of age. The youngest ex- ample that has come under my notice was a boy of three years; but in the Registrar-General's "Reports" for 1851-60, ten deaths from diabetes under the age of one year are registered, and as many as thirty-two under the age of three years. The mortality from diabetes attains its maximum between the ages of twenty- five and sixty-five years, and maintains itself between these epochs with tolerable uniformity. In extreme old age deaths from diabetes are more rare, not only absolutely, but as com- pared to the mortality from all causes. The development and exercise of the sexual functions appear to have a marked eft'ect in increasing the liability to diabetes in both sexes; and the diminished frequency of the disease in women after the age of lorty-five (as compared with men) cor- responds with the earlier decline of the sexual activity in the 1 In the eight years 1861-8 the annual average of deaths from diabetes was 628. 2 Construc1;ed from the Eegi'-trar-General's Reports, for 1851-60, for England and Wales. Mean population for the decade, 19,000,000. ETIOLOGY. 245 female sex. The maximuni mortality iu males is between forty- live and iifty-five years; in females between twenty-iivo and thirty -five years. Dr. Matliews Duncan has pointed out tliat wliile a sliirht ,ii;]y- cosuria is common in pre7 Bernard's glycogenic theory rests chiefly on the fact that in newly killed animals the blood of the hepatic veins has heen found sensibly richer in sugar than that of the body generally. Pavy attributes this result to rai)id changes which take place during the performance of the experi- ment. He has varied the proceeding in such a mannei- as to avoid these disturbances. lie catheterized the right heart by introducing a tube along the jugular vein. In this way, if the animal remained quiescent, the blood of the hepatic veins was obtained in its normal state. Hepatic blood so obtained, was found to contain only those minute traces of sugar which exist in every part of the circulation. Dr. Robert McDonnell,^ in an admirable series of researches, lias re- peated and varied the experiments of Pavy, and obtained results which do not seem to admit a possibility of doubt that amyloid substance is not converted into sugar in the liver during healthy life. In his memoir on the functions of the liver,'^ McDonnell brings forward some facts and considerations of great weight in support of his view, that the real destiny of the liver-dextrine is to unite with nitrogen (set free by the disassimilation of fibrine and a portion of the albumen of the portal blood) so as to constitute a new protein compound resembling casein, which is being constantly poured into the circulation through the hepatic veins.^ Dr. Pavy appears to insist too absolutely on the absence of any unim- peachable evidence of the disappearance of sugar introduced into the blood, except by its removal through the kidneys. It has been fully made out that sugar and dextrine may be injected continuously into the blood in certain small quantities — that is, so much that the percentage of them in the blood shall never rise beyond 0.2 or 0.3 — without pro- ducing saccharine urine.^ What becomes of sugar so introduced is doubtful. It may not be oxidized, as has usually been believed, into carbonic acid and water; perhaps it is transformed into amyloid sub- stance and lodged in the liver. That it disappears somehow without escaping with the urine cannot admit of doubt. Some experiments of Schiff appear to bear decisively on this point. He induced artificial dia- betes in frogs by puncturing the spinal cord ; he then ligatured portions of the liver, so that the discharge of sugar into the circulation was diminished in proportion to the size of the piece of liver included in the ligature. When a piece equal to about a fifth part of the organ was included in the ligature, sugar was still poured into the circulation, but not in sufficient quantity to produce glycosuria.'' Artificial Glycosuria and Diabetes. — We are led to believe, then, on the evidence above adduced, that although the amyloid matter ^ See Proceedings of the Eoyal Irish Academy, Feb. 13, 1860. 2 Observations on the Functions of the Liver, bj- R. jNIcDonnell, M.D. Dublin and London, 1865. * Pavy's results have been further confirmed by Meissner and Jaeger, and by Schiff and Herzen. The whole of this question is treated at length in the 2d ed. of Dr. Pavy's work on Diabetes. * Schiff, loc. sit. p. 1.S4. ^ That a trace of sugar exists in normal blood (even in flesh-fed animals) seems to be now generally admitted. Bernard, who originally taught this was con- sumed in the lungs, afterwards believed with other physiologists, that it is utilized in the nutrition of the tissues and especially of the muscles. 268 DIABETES MELLITUS. and its ferment must be in close proximity in the hepatic tissue, they do not come into actual contact and react upon each other during healthy life; but they may be brought into conjunction under a variety of unnatural conditions induced by disease or injury; and physiologists are able to bring about these abnormal conditions at will, and to cause sugar to appear in the urine. Artificial glycosuria may be produced in various ways, namely, by cutting or puncturing diverse parts of the nervous centres and certain organic nerves ; by impeding respiration ; putting animals under the influence of anaesthetics and tetanizing substances ; injecting acid sub- stances into the portal veins; and thrusting needles into the liver. Most, if not all, of these injuries, different as they appear, act finally in the same manner, and cause dilatation of the hepatic bloodvessels, and consequent hyperaemia of the organ. This dilatation may (conceiv- ably) be brought about in two ways : either by an increased action of the longitudinal muscular fibres (dilating muscles) of the small vessels^ — this would be an active congestion — or by a paralysis of the circular fibres, whereby the vessels would give way and expand before the pro- pulsive action of the heart. The contractile tissue of the hepatic vessels, like that of the vascular system generally, is under the control of a distinct nerve-arrangement, with a local centre in its neighborhood (probably the cseliac ganglion), and upward pi"olongations by the sympathetic and the spinal cord into the cerebral centres. The separate threads of this communication are, in the lower parts of their course, placed widely apart ; but they approach in the spinal cord ; and in the floor of the fourth ventricle they are collected into a close bundle before their final dispersion into the cerebral hemispheres. An irritation applied to any part of this nervous communication may cause temporary glycosuria ; and in the floor of the fourth ventricle even the puncture of a needle, if it be made exactly at the right spot (midway between the origins of the auditory nerves), is sufiicient. The difficulty of exactly hitting this spot renders the operation somewhat uncertain, except on condition of injuring the surrounding parts exten- sively; and Schiff found it preferalDle to pass in a needle and destroy the whole thickness of the cord at the point of origin of the brachial nerves. This operation never fails to produce temporary glycosuria. In warm-blooded animals, the urine continues saccharine for a few hours ; in frogs, about four days. Schiff gives good reasons to believe that gly- cosuria so produced is caused by an active congestion of the liver. The permanent diabetes, with which practitioners are familiar in the human subject, appears, on the contrary, to be paralytic in its nature, and to be due to a passive congestion of the liver from loss of contrac- tility in the circular fibres of the hepatic vessels. Schiff succeeded in inducing, in rats, a permanent diabetes which may be looked on as the true counterpart of the idiopathic disease in man. This was accom- plished by operating on the spinal cord at a lower point. He passed a ^ See Schiff, loc. cit. p. 92. See also a paper by the same author, Journ. de I'Anat. et de Phys., t. iii. 369. Schiff states that cutting the sciatic nerve, and even the nerves of the anterior extremity, causes a slightly diabetic state in rabbits. PHYSIOLOGICAL CONSIDERATIONS. 269 strong needle into the spinal cord (with the least possible injury to the surrounding parts) and destroyed it, o[)posite the second dorsal vertebra. Rats operated on in this way lived, provided their temperature was arti- ficially sustained, for seventeen and even twenty days, and continued diabetic to the end. Rabbits sometimes out-lived this operation nine days, and continued diabetic to the last day. Animals higher in the scale than rodents do not survive this operation. Temporary glycosuria has also been induced by impeding respiration (Pavy); by poisoning with strychnia and woorali ; by thrusting needles into the liver (Schiff') ; by chloroform and ether inhalations in warm- blooded animals ; in frogs, by tying the afferent veins of the kidneys so as to increase the flow of blood through the liver (SchiflT; ; by injecting stimulants into the hepatic veins (Harley) ; by painfully stimulating a sensory nerve, by stimulating the central end of the divided pneumo- gastric or of the depressor nerve, and by stimulating the first dorsal pair of nerves (Laffbnt). Dr. Pavy has found that strongly pronounced glycosuria is produced in dogs by injecting arterial blood into the portal vein. This, he thinks, " affords an explanation of the glycosuria which follows Bernard's punc- ture of the fourth ventricle and the various lesions of the sympathetic. Without any new agent being called in, sufficient is presented in the state of the blood to account for the production of sugar that occurs. By a vaso-motor paralysis affecting the vessels of the chylo-poietic vis- cera, the blood will reach the portal system without having become dearterialized in its natural way ; and in this state it has been shown to possess the pi'operty of acting within the liver in such a manner as to determine the production of glvcosuria " (" Proc. Roy. Soc. " June 17, 1875). It should also be mentioned that the introduction of large quantities of sugar and starch by the digestive organs occasions glycosuria — show- ing that the assimilating power of the liver over these aliments is not unlimited. Inuline (which replaces starch in the compositae) induces slight glycosuria, even when partaken of in comparatively small quan- tity (Schiff"). Bearing these physiological data in mind, we shall not find any diffi- culty in explaining the circumstances under wdiich temporary glycosuria occurs in the human subject in connection with various injuries and dis- eases; and we obtain some dim insight into the true pathology of clinical diabetes. Dr. Pavy applies his views to the explanation of permanent glyco- suria in the following manner : He urges that in diabetes there is a hyperpemia of the abdominal organs, and esiDecially of the liver, this being probably caused by some affection of the vaso-motor mechanism. Such a hyperemia would cause the blood flowing through the liver to be more highly oxygenated than is normal, and would, therefore, pro- duce glycosuria, as in his experimental results. It must be remembered, in searching for sugar in the urine of persons who present the alleged conditions of glycosuria, that the search will be in vain if there be great disturbance of the general system, and especi- ally if there be fever ; for the amyloid substance speedily disappears from the liver under these circumstances, and consequently no sugar can 270 DIABETES MELLITUS. appear in the urine, however perfectly all the other conditions for its occurrence exist. This is doubtless the reason of the many contradic- tory results of bedside observations on the occurrence of saccharine urine. I have repeatedly examined the urine of patients with obstruc- tion in the chest (emphysema, etc.) in whom there existed great hyper- semia of the liver, without finding sugar ; but it nearly always happens in such cases that the general well-being of the patient is deeply affected, or that there is positive pyrexia. From what has been said above, it is important to remember that in such cases, the hypersemia is of the venous and not of the arterial form. Although we appear to be approaching an exact knowledge of the pathogenetic elements of glycosuria, it is yet manifestly impossible, in the present state of science, to frame a comprehensive and clear theory of diabetes. It would seem highly probable that diabetes consists prox- imately in some disturbance of the destiny and function of the amyloid substance of the liver. But this disturbance may be due originally to disease far away from the liver itself, in some part of the nervous circle which controls this function. Occasionally, as in traumatic cases, it is possible to place the finger on the primary lesion ; but in the immense majority of cases we are left in a sea of conjecture. Further researches conducted in the light of past and future physiological discoveries, can alone reduce these conjectures to order and certainty. DIAGNOSIS AND PROGNOSIS The Diagnosis of diabetes is generally a very simple matter, when attention is once directed to the urine — the existence of sugar in the urine, and diuresis being the only points to be ascertained. The means of detecting sugar and of estimating its quantity have already been fully considered. Care must be taken, however, not to conclude too rashly that this formidable disease exists, from the mere finding of sugar in the urine. It has just been shown that the urine becomes tem- porarily saccharine under certain conditions quite apart from genuine diabetes. Before the existence of diabetes can be de- duced, it must be ascertained that there is a considerable quantity, and not a mere trace, of sugar in urine; secondly, and especially, that its appearance is not temporary, but persistent; and thirdly, that there is a less or greater increase in the volume of the urine. A more recondite diagnosis than this, is at present rarely possible : but it is to be hoped that the time is not very far dis- tant when we shall be able to indicate the seat of the initial lesion in each case, and to refer it to a cephalic, spinal, sym- pathetic, hepatic, or other category, as the symptoms or previous history may point out. Peognosis. — The general prognosis is highly unfavorable: the large majority of the cases terminate fatally. A not incon- PKOGNOSIH. 271 siderable number, however, recover completely; and many more attain to a state of conditional amelioration — tliat is, an ame- lioration which is conditional on the observance of a certain diet and regimen. The special prognosis depends on a variety of circumstances, of which the following are the more important. The younger the patient the less hope of ultimate recovery. All the cases under twenty, which I have seen, have eventually succumbed. In persons advanced in years, the appearance and persistence of saccharine urine is a far less serious aftair: it may continue for many years in oscillating degree with fair preservation of health. It is a curious circumstance that diabetes in corpulent persons is very markedly less formidable than in those of spare habit. Saccharine urine without diuresis is far less serious than when the urine is abundant. Cceteris paribus, the longer the disease has existed, the more unfavorable the prognosis; cceteris paiibus, also, the greater the general severity of the symptoms, the less is the hope of amendment. The ascertained cause of the dis- ease also afiects the prognosis. Cases which can be traced to mental anxiety and traumatic lesions appear to be somewhat more hopeful than those for which no tangible cause can be as- signed. The presence of albumen in the urine, of thoracic or intes- tinal complications, are fatal signs. The existence of permanent amblyopia, or cataract, is a very unfavorable indication. Such cases generally terminate fatally within six or twelve months, and, so far as is now known, alwa^^s eventually; that is, they are essentially incurable cases, though some of them survive many years. The results of treatment furnish important data for esti- mating the gravity of the prognosis. A very favorable circum- stance is the disappearance of sugar from the urine when saccha- rine and starchy matters are withdrawn from the diet. Even great diminution without total disappearance of sugar is a hope- ful sign. On the other hand, the persistence of sugar in quantity on a purely animal diet is a sign that the disease is confirmed and far advanced. A moist perspirable skin, a fair appetite, a stationary condition, are all favorable signs. It must be remembered that when, by treatment, the disease has been brought apparently to a stand-still, a diabetic patient still holds his life by a very frail tenure. To use the expression of Dr. Prout, persons with confirmed diabetes, though apparently in fair health, live as it were on the brink of a precipice. A little undue exposure to wet or cold, an unusual bodily exertion — trifl.es to the healthy — may excite inflammatory complications which prove rapidly fatal. 272 DIABETES MELLITUS. TKEATMENT. The seat^nd nature of the primary lesion are, as we have seen, nearly always concealed ; and we know almost nothing of what may be called a radical treatment of diabetes. But the more prominent symptoms — thirst, inordinate appetite, emaciation, and the copious diuresis, are unquestionably dependent, in great part, on the accumulation of sugar in the blood, and the imperi- ous necessity for its removal. A clear indication for treatment, therefore, is to diminish this accumulation. In our ignorance of any direct means of checking the formation of sugar in the body, we resort to the indirect method of withdrawing sugar and amylaceous substances (which are easily converted into sugar in the primce vice) from the dietary. We endeavor further to combat any existing disorders of the skin, stomach, bowels, and other internal organs, and to allay certain troublesome symp- toms which arise in the course of the disease. By means of a regulated diet, clothing, and habits of life, invaluable help can be rendered to diabetic patients: sometimes so as to open the way to perfect recovery: often, nay generally, so as to relieve suffering and prolong life. Diet. — The plan to be pursued is to withdraw as completely as possible, but not too suddenly, all saccharine and amylaceous articles — the chief of which are bread and potatoes — ^from the diet, and to replace them by appropriate substitutes from the vegetable kingdom, and by animal food. It is well known that human life can be sustained in perfect vigor on a purely animal diet. Ths inhabitants of the arctic regions subsist exclusively on the flesh and blubber of seals, fish, and such produce as the chase of the climate affords. The fur-hunters of British America exist for many successive months, leading a life of great muscular activity, on a flesh diet alone. But in our more settled communities the use of bread and pota- toes is almost a second nature, and deprivation of them is, to the great majority of individuals, an almost unendurable hard- ship. To obviate this difficulty several substitutes for bread have been contrived which are of very great value in the man- agement of diabetes.^ In the choice of substances from the animal kingdom j the 1 Prof. Cantani, of Naples, advocates a more extreme degree of non-saccharine and non-amylaceous diet than any previous writer. He gives his patients abso- lutely, nothing but flesh and fish — forbidding even eggs, green vegetables, and milk. In the way of beverages he forbids all wines, beer, tea, and coffee, and allows only simple water or water with a slight admixture of rectified spirit, or lactic acid. He claims for this rigorous treatment much more complete success than has hitherto been attained by the restricted diet as ordinarily prescribed. His experience, however, is limited to five cases. II Morgagni, 1870. TREATMENT. 273 only doubtful or forbidden articles are milk, honey, and liver. Butclicr'H meat, cheese, butter, fat and oil, ])Oulti'y, <(ame, aggn, iislj, may be used freely in any form. Broths, sou[)S, and jellies, (prepared without meal or sugar) are also permissible ad lihitum. Milk, which contains considerable proportions of a saccharine substance, should, as far as possible, be replaced by cream. Milk, however, is much less deleterious to a diabetic patient than might have been supposed. In a girl with confirmed dia- betes I made the following trial of the effect of milk. For four weeks she was fed on animal flesh and bran cakes; during the succeeding four weeks three pints of milk daily were added to this diet; and for three weeks subsequently, the milk was with- drawn. The annexed table shows the exact results of the treat- ment. Meat diet, and bran 1 cakes ; for four weeks / Meat diet, bran cakes, and three pints of milk ; for four weeks Meat diet, gluten bread, "| and cabbage ; for V three weeks j Average daily quantity of urine. Average quantity of sugar daily excreted. . 55 OZ. 897 grains. . 49 OZ. 1260 grains. . 41 OZ. 1020 grains. Increase of weight. 5 lbs. 5 lbs. 7 lbs. The patient continued to gain weight and to improve in her general condition under the use of milk, although the density of the urine and the excretion of sugar somewhat increased. A limited supply of milk may therefore be allowed. Liver, as found in the butcher's shops, contains a considerable quantity of sugar; it also contains amyloid substance, w^hich is changed into sugar by the saliva and pancreatic juice. Liver is therefore to be avoided by diabetic patients. The edible mol- lusks — oysters, cockles, mussels, etc. — are also imjDroper, on account of the large quantity of amyloid substance contained in their enormous livers. For the same reason, the "pudding"' of crabs and lobsters is objectionable. The prohibited articles among vegetables are much more numerous and important, and the substitutes less perfect and more difficult to find. The oldest substitute for bread is the "bran cake." Thehusk or bran of wheat consists of lignin and an albuminoid substance, and is quite devoid of starch. When this is washed and ground it may be made up into a rude imitation of bread with but and eggs, and constitutes a valuable addition to the diet of a diabetic patient.^ 1 The best formula for bran cakes is the following, supplied by Dr. Camplin : '■'■Formula for Bran Cakes. — Take a sufficiert quantity (say a quart) of wheat bran, boil it in two successive waters for a quarter of an hour, each time straining 18 274 DIABETES MELLITUS. Another important substitute is Bouchardat's "gluten bread." This is prepared by washing out the starch from wheaten flour, and working up the remaining gluten into loaves and cakes. This bread is manufactured on a large scale in France, with the aid of powerful machinery for inflating the dough with com- pressed air, or carbonic acid gas. It forms a light and elegant, and by no means unpalatable bread. Gluten is also ground down into a meal, and may be used for thickening broths and making puddings.^ These preparations are not quite free from starch; all the samples examined by me showed an intense blue colora- tion with iodine. By far the most palatable form of gluten bread is that pre- pared by Mr. Bonthron, of 106 liegent Street, London. He sends it out in the form of small buns, which eat crisp, and keep about a fortnight. Those of them that I have tested were nearly free from starch. Dr. Pavy has introduced rusks and biscuits prepared from the starchless meal of the sweet almond.^ These are more expen- it through a sieve, then wash it well with cold water (on the sieve), until the water runs off perfectly clear ; squeeze the bran in a cloth as dry as you can, then spread it thinly on a dish, and place in a slow oven ; if put in at night let it re- main until morning, when, if perfectly dry and crisp, it will be fit for grinding. The bran thus prepared must be ground in a fine mill and sifted through a wire sieve of such fineness as to require the use of a brush to pass it through ; that which remains in the sieve must be ground again until it becomes qviite soft and fine. Take of this bran powder 3 oz. (some patients use 4 oz.), the other ingredi- ents as follows — three new-laid eggs, 1^ oz. (or 2 oz. if desired) of butter, and about half a pint of milk, mix the eggs with a little of the milk, and warm the butter with the other portion ; then stir the whole well together, adding a little nutmeg and ginger, or any other agreeable spice. Bake in small tins (pattipans), which must be well buttered, in a rather quick oven for about half an hour. The cakes, when baked, should be a little thicker than a captain's biscuit ; they may be eaten with meat or cheese for breakfast, dinner, or supper ; at tea they require rather a free allowance of butter, or may be eaten with cu7^d or any 'of the soft cheeses. " It is important that the above directions as to washing and drying the bran should be exactly followed, in order that it may be freed from starch, and rendered more friable. Mr. White, of Holborn, who made my mill, and was subsequently employed by others, attempted to grind the bran for them, and failed, from not washing and drying the bran, which, in its common state, is soft and not easily reducible to fine powder. In some seasons of the year, or if the cake has not been well prepared, it changes more rapidly than is convenient. This may be pre- vented by placing the cake before the fire for five or ten minutes every day." — (Camplin on Diabetes — Appendix.) These cakes may be had from Blatchley, 362 Oxford Street, London. The mills for grinding the bran are made by Gallop, 119 Cheapside. A diabetic patient of mine says the cakes are much improved by using seven instead of three eggs. The addition of a teaspooniul of bicarbonate of soda is also an improvement. ^ Gluten bread and other gluten preparations made after Bouchardat's formula, are supplied by Van Abbott & Co., Howford Buildings, Fenchurch Street, London. They may also be had of Jewsbury & Brown, Market Street, Man- chester. 2 Almond rusks and biscuits are supplied by Hill, Bishopsgate Street, London. T R K A T M E N T . 275 sive than the fbrogoiug; but i have found that ])atiei)ts relished them as a change. None of these substitutes is as palatable as ordinary bread: but they are of great service; and may l)e used one after the other, as the patient's inclination rrtay direct. When none of these can be had, or when the patient refuses all tliree, as is sometimes the case, resource may be had to "torrefied" bread. Thin slices of ordinary bread are toasted before the fire until they are deeply and thoroughly browned — almost blackened. The starch and gluten are in great part destroyed by the heat, but the hungering diabetic relishes greatly the charred remnants when well buttered and eaten with other articles. Rice, tapioca, sago, semola, macaroni, and vermicelli, all con- tain great abundance of starch, and are therefore inadmissible. Apples, pears, gcwseberries, currants, plums, oranges, and all sweet fruits, are likewise pernicious from the quantity of sugar which they contain. In place of potatoes, turnips, carrots, parsnips, beans, and peas — all of which contain starch or sugar — substitutes may be found in green vegetables — cabbage, endive, spinach, broccoli, Brussels sprouts, lettuce, spring onions, watercress, mustard and garden cress, and celery. There does not seem to be any real advantage in forcibly curtailing beyond a moderate degree, the fluids taken by dia- betic patients. The volume of the urine and the separation of sugar may be temporarily reduced by this means, but the gen- eral distress increases, owing to the more intense impregnation of the blood with sugar. Prout recommends that all fluids be given in a tepid state, as they thus allay the craving for liquids more effectually than when taken cold. In the way of beverages, tea and coifee (without sugar) may be used. Chocolate made with gluten meal, and soda water, may also be used. The free use of wine and spirits, which is especially recommended by liouchardat as a part of the diabetic regimen, is of more than doubtful propriety. Exact observations do not support Bouchardat's views, which are based on theoretical grounds. Griesinger found that the use of red wine, to the extejnt of a bottle and a half or two bottles per day, strengthened with two ounces of rectified spirit, increased considerably both the quantity of urine and the excretion of sugar. In a second observation by the same author, the use of alcoholic drinks caused, in addition to the above effects, a copi- ous diaphoresis of saccharine sweat. The observations of Gar- rod, Camplin, Rosenstein, Siemssen, and Heller, are also un- favorable to the free use of beer, wine, and spirits. They should therefore be used sparingly. The best are those which are most free from sugar, namely, dry sherry, claret, bitter ale, brandy. 276 DIABETES MELLITUS. and whiskey. Those to be avoided are port, sweet and efferves- cent wines, sweet ales, porter, rum, and gin. Tlie use of acid drinks, and especially dilute phosphoric acid, has been highly spoken of in some quarters. Griesinger reports unfavorably of their effects. He pushed dilute phosphoric acid to the extent of an ounce daily. At first, and under the smaller doses, the patient seemed to do very well ; but after ten days, and with the full quantity, the volume of the urine and the pro- portion of sugar slightly increased, and the general state of the patient grew worse. I have frequently employed bitartrate of potash water for the purpose of allaying thirst, with good effect. The patient should be clad from head to foot in flannel, in order to encourage the action of the skin, and defend the patient from the chilly sensations so common in this complaint. A warm bath once or twice a week is also very grateful to the patient, and abates the harsh, arid condition of the skin. The results obtained from the dietetic treatment differ a good deal, according to the intensity of the disease, and the length of time it has existed. The following records illustrate the vary- ing degrees of amendment which may be anticipated in con- firmed cases : In the first two cases the patients were permanently cured. The third and fourth cases were inveterate, and, strictly - speaking, incurable ; in these the quantity of the urine was re- stored (temporarily at least) almost to its natural limits, and the patients gained flesh and strength in a very remarkable degree; sugar, however, still persisted in the urine, and any deviation from the prescribed regimen was sufficient to reawaken the diabetic symptoms in full intensity. In the fifth case, not much more than a temporary arrest of the downward course was attained, and this was speedily followed by a resumption of the untoward march to a fatal termination. Case 1. — C. R., set. 39, of a corpulent habit, came under my care in October, 1861. The urine amounted to eight pints a day; specific gravity 1040 ; it contained a large quantity of sugar. He had lost much weight, but was still in full flesh. The ordinary symptoms of diabetes were present in moderate intensity. C. R. had been dyspeptic for about fourteen years, though his habits had been, in every respect, temperate. He underwent the operation of lithotomy when a child. For the last two years he had perceived that he gradually lost flesh, had an unusual thirst and frequent desire to pass water. During this period, he had to get up three or four times each night to empty the bladder. Latterly the ankles had begun to swell. Most of the teeth were carious, and the gums loose and spongy. For two months the patient was treated as an out-patient of the Royal Infirmary, and enjoined to avoid saccharine and amylaceous articles of food. It was found that the treatment was carried out very inefficiently; he was therefore admitted as an in-patient on December 4, 1861. TREATMENT. 277 For a week, he was abandoned to the ordinary mixed diet of the hospital. During this week lie voided daily on an average 160 ounces of urine; specific gravity, 1085-1040; mean daily excretion of sugar, 5680 grains. He was then put on a diet of animiil suhstances, with cabbage and bran cakes. In the week succeeding the change of diet, the mean daily discharge of urine fell to 60 ounces ; specific gravity, 1022-1026. The sugar fell on the third day to VA grains, on the fourth to 116 grains, and at the end of the week to 48 grains. In the second week the urine fell to its natural volume and density, and the sugar was reduced to a mere trace. This trace persisted for six weeks, when it suddenly disappeared. The patient gained weight at the rate of three pounds a week. He was then made an out-patient, and directed to continue the restricted diet. A trace of sugar reappeared, from time to time, for seveval months, but ceased altogether in about eight months. He gradually resumed the moderate use of ordinary bread, and came to show himself at inter- vals. I saw him last in February, 1865, The urine was found per- fectly free from sugar, and the general health and embonpoint were completely restored. Case 2. — ^T. H., a very stout, florid-complexioned man, 34 years of age, who weighed, when in health, over sixteen stone, came under my care September 19, 1864. He stated that in the previous July, when the weather was very sultry, he perspired very freely, and drank large quantities of cold effervescing beverages. From this period, a violent thirst and frequent desire to void large quantities of urine, tormented him. He lost weight to the extent of about 40 lbs.; he was voraciously hungry, and his strength gradually declined. When first seen by me, the daily discharge of urine amounted to eight pints ; specific gravity, 1048 ; sugar, 7540 grains per day. The general symptoms were mild. The tongue and skin were moist, the teeth sound, the gums only slightly spongy. He complained of incessant thirst, inordinate appetite, pain in the back, and feebleness. He was put on a restricted diet on September 22d, and observed the directions given to him with the most praiseworthy strictness. He was allowed bran cakes, butter, fresh meat, eggs, cabbage, tea and coffee sweetened with glycerine ad libitum. He was cut off from potatoes at once, and, after two days, likewise from ordinary bread, and limited entirely to the articles above enumerated. A warm bath was admin- istered every evening, and a pill containing half a grain of opium and one grain of sulphate of iron was given three times a day. On the third day great improvement had taken place. The' urine was reduced to 50 ounces; specific gravity, 1028 ; sugar, 210 grains. For two days the patient's condition remained in every respect sta- tionary; but on September 28th he did not feel so well. The urine had fallen to 20 ounces, and the sugar to a very small quantity ; the pulse was 98, tongue furred, and a degree of pyrexia prevailed. He sweated profusely after the baths ; and some hemorrhoids, to which he was subject, became very painful, the bowels being confined. 278 DIABETES MELLITUS. This disturbance was attributed partly to the somewhat too sudden revolution in the diet, and partly to the constipating effects of the pills. On September 29th the pills were withdrawn, the baths were admin- istered every other evening, instead of daily, a little ordinary bread was allowed, a dose of castor oil administered, and the patient directed to keep his bed. In a few days this disturbance subsided, and the restricted diet was again rigidly enforced. Rapid amendment set in ; the urine returned to its natural quantity and density; the sugar gradually diminished, and on October 17th it had entirely disappeared from the urine. The restricted diet was adhered to for another fortnight, and then a gradual return to the use of ordinary bread was permitted, the urine being carefully examined for sugar from time to time, but none found. At the beginning of 1865, the bran cakes were discontinued ; ordi- nary bread was allowed freely, and a small portion of potatoes. At the end of January, all restrictions on the diet were withdrawn. The patient had now reached almost his original weight of 16 stone, and felt himself in every respect perfectly well. He was last seen on July 25, 1865. The urine was found ]3erfectly free from sugar. In the first of these instances, a confirmed but mild case of diabetes, of two years' standing, was perfectly and permanently cured by the dietetic treatment in about eight months. In the second instance, diabetes of three months' standing was com- pletely cured in less than a month. Recoveries so complete as these are, unfortunately, rare. The two following are examples of the conditional amelioration, which may be commonly attained, even in severe cases : Case 3. — E. H., a well-grown girl of sixteen, a factory hand, had .been diabetic for three years. She was admitted into the Manchester Infirmary, March 26, 1860. The disease was uncomplicated, and exhibited in great severity the outward signs of diabetes in an advanced stage. There was a harsh dry skin ; a tongue like a piece of broiled ham, and deeply furrowed ; abdominal pains, constant drowsiness, consuming thirst, gross appetite, dry scurfy skin, and great emaciation. For a fortnight after admission, she was put on the common diet of the hospital, which includes a liberal allowance of meat, potatoes, and bread. The state of the urine, during the last six days of this fortnight, was as follows : Mean daily discharge, 210 ounces ; mean daily excretion of sugar, 10,400 grains; average density, 1042. Her weight was 80 lbs. The diet was then changed. Milk and all vegetable compounds were withdrawn ; instead, she was allowed an unlimited supply of eggs, fresh meat, and beef-tea. The patient did not, however, observe my directions strictly, but obtained, and surreptitiously consumed, certain quantities of oranges, sugar, and treacle-toffy. Nevertheless, a remarkable im- provement in her condition took place. At the end of eleven days, the mean results since the change of diet were : Daily discharge of urine, 70 ounces ; sugar, 1860 grains ; average density, 1034. Weight, 81 lbs. Avdl ■iige (liuly i|Uiint.it,v I{;uige of Sugar of iirino. (li'iisity. (^iicli (liiy. Ounces. (■jiraiiiH. First week . 54 1025-1033 11 GO Second week . fi7 1021-1031 970 Third week . 51 1022-1035 870 Fourth week . 49 1019-1035 690 Entire period . 55 1019-1035 897 TKEATMNE'J'. 279 The general health was also much ameliorated ; the skin was softer, the tongue less fiery, the thirst and appetite allayed. On A[)ril 21st, bran cakes were added to the animal diet, and greatly relished by the patient. From this date to May Kith — a |)eriod of 20 days — no further change was made. The results are shown in the fol- lowing table. I have divided the period into weeks, for the purpose of displaying the gradual progress: ' Wfiglit. 11)8. 81 84 85 86 With this increase of weight, her general condition had improved ; the tongue had become pale and moist, but it was still mapped on the surface, and unnaturally smooth. On the I6th of May, milk was added to the previous diet ; the results are given in a preceding page (see p. 273). On June 12th, milk was again withdrawn, and gluten bread substituted for bran cakes. Cab- bage was also allowed with dinner. The flow of urine on this diet averaged 41 ounces, and the sugar 1020 grains per day. The body- weight went on increasing to 98 lbs. Her general condition was now, at the end of eleven weeks of treatment, such, that an unprofessional person would have pronounced her cured. The outward signs of dia- betes had disappeared ; the skin was restored to its natural softness ; the thirst and appetite were no longer inordinate ; the flow of urine was reduced within the normal compass. The patient had gained IS lbs. in weight ; she slept soundly, had neither pain nor ache ; her strength was so far restored, that she was able actively to assist the nurses in the work of the wards. She came from a distant town, and her history after leaving the Infirmary is unknown to me. Case 4. — W. A., a factory hand, ajt. 30, was admitted as an out- patient, October 12, 1859. He presented the usual appearance of diabetes in full career. The disease was uncomplicated, and had ex- isted about a year. The quantity of urine varied from 10 to 15 pints daily, and its density averaged 1044. The patient was directed to observe a restricted diet; and a pill containing a grain of opium, with a quarter of a grain of sulphate of iron, and half a grain of quinine, was ordered three times a day. This treatment was continued — the doses of opium being gradually increased — for seven months. A marked improvement took place ; the diabetic symptoms abated considerably ; the tongue became moist ; the urine fell to five or six pints daily, with a specific gravity of 1040. The sugar averaged 4400 grains. He gained strength and some weight, and was able to resume his occupation for a time. As his condition appeared stationary, he was made an in- patient on May 8, 1860. On his admission, all medicines were discon- tinued, and the patient was allowed the mixed diet of the house. The effect of this change was a sudden reappearance of all the untoward 280 DIABETES MELLITUS. symptoms, with a sense of great debility, and an alarming cough. The condition of the urine was as follows : Daily discharge of urine, 205 ounces ; sugar, 7400 grains ; average density, 1042. Three days of this freedom from treatment had forced him to keep his bed. I now gradually withdrew all amylaceous substances, and substituted meat, fish, eggs, and beef-tea. He was also allowed eight ounces of brandy daily. After the change was completed, the diet was absolutely devoid of starch and sugar. Under this diet, the urine altered greatly for the better. During the first week of the restricted diet, the daily discharge of urine was 61 ounces ; daily excretion of sugar, 928 grains ; average density, 1032. The general symptoms also improved, but not in proportion to the amelioration in the condition of the urine. A second week of the same treatment brought down the urine to : Daily discharge, 56 ounces; daily excretion of sugar, 658 grains; average density, 1028. I was now met with the difficulty which so many have encountered in pursuing this treatment ; namely, a total failure of the appetite, and consequent alarming depression of all the vital powers. To obviate these untoward events, the patient was allowed bran bread and the free use of green vegetables— cabbage, lettuce, and watercresses. A grain of opium was also given three times a day. The diet was therefore still starchless, and almost entirely devoid of sugar. Decided amendment followed this change, and in a few days the returning strength and cheerfulness kept pace with the improved appetite and increasing weight. During the remainder of his stay in the infirmary, a period of two months, no further change of importance was made in the diet or medi- cine. The patient's weight on admission was 97 lbs.; but it rapidly sank in the first few days, and at the end of three weeks it was only 91 lbs. From this time onward, however, the weight began to increase, and it went up gradually to 105 lbs., which point it had reached the week of his discharge. The state of the urine for the last two months was remarkably con- stant. The daily discharge varied from 40 to 60 ounces ; the daily excretion of sugar, from 800 to 1000 grains ; the average density, from 1030 to 1033. The excretion of sugar ruled higher than when the diet was exclu- sively animal. This I attributed to the improved appetite, which enabled the patient to take more nourishment, rather than to any untoward influence exercised by the green vegetables. I might greatly multiply examples of this class ; but it will be more useful to illustrate the less fortunate results for which the practitioner must also be prepared. Case 5. — E. B., a niece of the patient C. R., who made so good a recovery, was admitted into the Royal Infirmary in December, 1862. She had been diabetic for 16 months ; and suffered from excessive thirst, voracious appetite, and great emaciation. The tongue was glazed, skin harsh and dry. There was no complication. The urine amounted to 15 pints a day, and contained over 10,000 grains of sugar, when she lived on a mixed diet. TREATMENT. 281 She remained in hospital two montliH; and was gradually limited to a diet of animal flesh, witli eggs, cabbage, and bran l)read. On this diet she slowly gained three pounds in weight, anrl improved sensibly in her general health. The urine, however, never fell below five pints; usually it oscillated between seven and eight pints, with a specific gravity ranging from lOoO to 1040, and a daily excretion of sugar of 4450 to 7420 grains. After leaving the Infirraary, she speedily relapsed, gradually grew worse, and died in March, 1863, in the Withington Workhouse. Much discredit has been thrown on the dietetic treatment, by a slovenly and incomplete manner of carrying it out. It requires most vigilant watching to keep guard against the ad- mission of forbidden articles. The patient's own craving for them is often too much for his resolution, and most artful de- ceits are practised on the medical attendant. This is especially the case at the beginning of the treatment. After awhile, the patient perceives, from his own experience, the importance of abstaining, and the desire for the forbidden articles diminishes very notably after the lapse of some weeks. Amylaceous com- pounds, too, are often unwittingly administered by the attend- ants. Starchy matter is never absent from the cook's hand ; it enters, in one guise or other, into almost every dish. Then there arises the other difficulty — the rejection by the stomach of the restricted diet. This difficulty is, perhaps, made too much of. A skilful selection and frequent change of articles of diet, usually suffice to reconcile the digestive organs. The field of selection among admissible articles is so wide that, in private practice, the practitioner's resources are almost inex- haustible. Among hospital patients, however, the embarrass- ments on this score are very serious. There are cases of such severity, that not even a temporary amendment can be obtained by the dietetic treatment. I have known more than one such instance in children under ten years of age, in whom the disease ran a rapid course, and proved fatal in a few months. There are also a certain number of chronic cases in which the dietetic treatment proves unsuitable, and hastens rather than retards the final catastrophe. These are, for the most part, long-standing cases — cases, perhaps, which have been beneiited at a previous epoch by that treatment. In two of my Infirmary patients, who were readmitted to the benefits of the charity after an interval of several months, a much more decided amelioration followed the dietetic treatment during the first period of their stay, than during the second. The sugar-forming vice of the diabetic s^'stem appears at first (and throughout in the milder cases) confined to saccharine and amylaceous articles of food; but as the disease becomes in- 282 DIABETES MELLITUS. veterate, the assimilation of the albuminous principles is more and more affected, until, at .length, these yield sugar almost as readily as the former. Griesinger found in a case of this kind, on strict flfesh diet, that three-tifths of the albuminous materials reappeared in the urine as sugar. When matters have come to this pass, it is not to be wondered at, that the patient no longer derives benefit from a restricted diet, which he can only use sparingly, and almost with disgust, and that he should, on the whole,"find himself in a better position when abandoned to ordi- nary mixed fare, which he can consume in abundance, and with relish. Experience is imperative on this point. When a flesh diet, judiciously eked out by appropriate substitutes for bread and potatoes, fails to ameliorate the general condition, it should not be too obstinately persisted in after a fair trial. The practi- tioner should give way first with regard to bread, and hold out longest against potatoes. ITo inflexible and universal rule can be laid down respecting the diet of diabetic individuals, under all circumstances and in all stages of the complaint. Cases will occur, in which the power to take a plentiful supply of a mixed diet, more than compensates for the increasing thirst and freer discharge of urine and sugar. I have also noted that some of the milder types of this disease in which saccharine urine is un- accompanied with diuresis, are made worse by a too restricted diet. (See Appendix to this chapter.) Dr. Donkin^ recommends another mode of carrying out the animal diet treatment — namely, by putting the patient on a diet exclusively composed of skimmed milk, which he administers in quantities of six or eight pints daily — persevering rigidly with the treatment, if necessary, for ten or twelve weeks. I have seen several patients who tried this severe method. Few of them could tolerate it except for a few days — and those who continued longer were rapidly reduced. Three chronic cases I know of, in which the treatment was obstiuately persevered with, ended in fatal exhaustion. One of them had been under my care for a considerable period, and the patient maintained a fair state of health under a moderately restricted diet and the use of opium — three months of the skimmed milk treatment brought the case to a fatal termination. Medicinal Substances in Diabetes ; Supplementary Means. — Some of these are employed under the impression that they possess a really curative power in this disease ; others are re- sorted to simply as adjuvants, to combat some particular symptom. ' The inquiries hitherto made on the supplementary means^ medicinal and other — employed in the treatment of diabetes^ 1 On the Milk Treatment of Diabetes and Bright's Disease. London, 1871. TREATMENT. 283 arc mostly vitiated, by an iii.sufHcieiit separation oftlioir cfibcts, from those of the restricted diet, which is usually conjoined therewith, and a, want of attention to the clinical grouping of the cases. A number of remedies have been extravagantly lauded on diverse hands, and have in this way attained an ephe- meral reputation; but, when tried by accurate observers, they liave proved to be absolutely inert. Unless the points just indi- cated are kept in view, only misleading conclusions can be drawn from any inquiries on this subject. It is quite possible, that remedies which have proved powerless in inveterate cases may be of real service in milder examples of a different type, or in the earlier stages of the disease. A complete revision of the supplementary means of treating diabetes is loudly called for. It may be taken for granted, in the present state of knowledge, that the general basis of all treatment of diabetes must be the dietetic restrictions already described. Other means should be studied with a clear understanding of their supplementar}' and subordinate place. Opium. — This narcotic is unquestionably of great use in the treatment of diabetes — not from its direct influence on the course of the disease, but from its anodyne properties. If no restriction be placed on the diet, opium in doses of from 6 to 20 grains a daj' has always, in my experience, had the power of re- ducing the flow of urine by about one-half; that is to say, of bringing it down to five or eight pints, and this without increas- ing its densit3\ But, notwithstanding this amelioration in the state of the urine, the downward progress of the disease is not arrested; and the effect of the drug seems attributable to its deadening influence on the appetite, rather than to a specific power of checking the formation of sugar. When opium was given to patients under a restricted diet, it did not in my hands exhibit the least power of lessening the flow of urine or the ex- cretion of sugar. Its value depends on its power of inducing sleep, and of allaying the dolorous sensations and irritability which constantly torment diabetic patients.^ There is a great tolerance of opium in confirmed diabetes. Doses of 2, 3, and 5 grains, three times a day, are generally borne without the production of any appreciable narcotism. Dr. Pavy prefers codeia to opium. He finds that this alkaloid yields all the good eflects of the crude drug without some of its disadvantages. He gives it in gradually increasing doses, from a quarter of a grain to two grains three times a day. Other ob- servers have also recommended codeia, but I cannot say that my experience altogether justifies this preference. Alkalies. — Alkaline substances have been specially recom- mended by Miahle, on account of their supposed power of favor- ^ See the author's paper — Brit. Med. Journ., 1860. 284 DIABETES MELLITUS. ing the oxidation and destruction of sugar in the blood. These theoretical views are now overthrown In two of my patients, I made a trial of full doses of the bicarbonate of potash. One of them w'as on a mixed ordinary diet, and the disorder was far advanced. The urine was rendered alkaline for ten days with- out in any way altering the excretion of sugar, or the general condition. In the second case, the patient was on a restricted diet. She took for a fortnight 320 grains of the bicarbonate daily, in divided doses; the urine was thereby rendered freely alkaline. During the week preceding the alkaline treatment, 1160 grains of sugar were excreted daily. In the first week of the alkaline treatment 970 grains a day were separated, and in the second week 870 grains. In the week following the with- drawal of the alkali, the sugar amounted to 690. This observa- tion tends to show that the alkali had no appreciable influence on the excretion of sugar. I have not encountered any difficulty in rendering the urine alkaline in diabetes, as Dr. Pavy seems to have done.^ Rennet and Pepsine have been vaunted in such terms of confi- dence, as to raise hopes which are not destined to be realized. The most remarkable results, obtained from rennet, are those published by Dr. James Gray. He states that of twenty-seven persons treated seven recovered. This is an example of most rare success, and it is to be regretted that the cases are not re- ported with that exactitude and detail which are desirable on such debatable ground. In all of them a rigid adherence to animal diet and bran bread was insisted on; and it seems more than probable that the amendment in each case was due to the restricted diet rather than to the rennet. Dr. Nelson, of Birm- ingham, extols the same remed3^ His cases do not seem to have been severe ones; and the diet was regulated in at least some of them. The reports are much more imperfect than those of Dr. Gray. I gave rennet a resolute trial in one confirmed case. It was prepared in the manner recommended by Dr. Gray, and given in doses of two tablespoonfuls three times a day. The patient took it for more than two months, conjoined with a rigidly re- stricted diet. During this period he improved, and gained 5 lbs. in weight. But he was improving just as rapidly before he began the rennet, and the daily excretion of sugar had not in the least diminished during its use. Griesinger, in two cases 1 The alkaline and ammoniacal phosphates and the carbonate of ammonia have again been tried bv Basham and Pavj% and the citrate of soda by Guyot. See Brit. Med. Journ", 1869, i. 323; and ibid., p. 590; and Syd. Soc. Year Book, 1865-6, 70. Recently the use of ammonia in the form of carbonate and acetate has been strongly recommended in diabetes. (Adamkiewicz, Pfliiger's Archiv., 1879, p. 160.) The evidence in its favor is as yet, however, scanty. TJiKATMENT. 285 accurately observed, found even a sliglit iiicrea.se of sugar during the use of rennet. Other trustworthy reports are equally un- favorable. Parkes' and Leu])uscher^ ibund ])(',|)sine useless. I conceived that it was worth a trial, whether some of the substances which act powerfully on the nervous system, might not exercise a beneficial effect in diabetes. With this view% I exhibited strychnia and belladonna, in gradually increasing doses, until their physiological effects began to be perceived. But not the slightest influence on the excretion of sugar could be discovered during their use. Among the more recent remedies employed in diabetes may be mentioned arsenic,^ iodine, bromide of potassium,* picric acid, and Calabar bean. The last three I have tried and found useless. The evidence in favor of the first two is too slender to excite much hope. I have tried both peroxide of hydrogen and ozonic ether, only to find that the hopes held out with respect to them were altogether delusive.^ Salicylate of soda has been used by several physicians, who have reported very good results from its administration. I have given lactic acid, as recommended by Cantani, repeat- edly and resolutely, without seeing the slightest advantage from its use. Independently of so-called specific remedies, there is a large field for the skilful use of adjuvant means, employed simply for their ordinary therapeutical effects. The obstinate constipation which commonly prevails in diabetes, must be corrected bv a regulated use of castor oil, seidlitz powders, or the ordinary rhubarb and magnesia mixture. Anodynes are called for to subdue pain, nervous exhaustion, restlessness, and insomnia. Dyspeptic symptoms are to be combated by alkahue tonics: and for this purpose I know of no better combination than the bi- carbonate of potash in infusion of calumba, with hydrocyanic acid. The poverty of the blood and the progressive emaciation are best combated by long courses of iron and cod-liver oil. I have already spoken of a solution of bitartrate of potash, as the best means of directly allaying the thirst. When the cravino- for food, and sense of sinking at the epigastrium are trouble- some, a pill containing two or three grains of assafoetida, ad- 1 On the Composition of the Urine, p. 356, note. •' Arch. f. Path. Anat., Bd. xvni. 119. 3 Bulletin de Therap., 1870, xlvi. 519 ; Berlin. Klin. Wochensch., 'So. 12, 1869 ; O. Kees, Lancet, 1864, ii. 436 ; and Leube., Archiv Gen., 1870, p. 602. '1 Austin Flint, Amer. Journ. of Med. Sci., 1870, 282; and Begbie, Edin. Med. Journ., xii. 487. ^ Moleschott has recently recommended iodoform, and has obtained gcod re- sults from its use. (Wiener. Med. Wochensch. No. 17, 1882.) 286 DIABETES MELLITUS. ministered twice or thrice a day, often gives most striking- relief. Diabetic patients often reap considerable benefit from change of air, and a sojourn at watering-places. The Bristol Hotwells, Vichy, and Carlsbad waters have obtained some celebrity for their utility in diabetes. Dr. Murrell has recommended Bethesda water. In milder cases, sea-bathing may be recommended in moderation in the hot season of the year.^ Saccharine Treatment of Diabetes. — Piorry conceived the odd idea that the main evils of diabetes depended on the loss of sugar through the kidnej'S, and that, by compensating this loss by administering sugar internally, these evils could be overcome. Dr. W. Budd, of Bristol, followed up Piorry's lead, and admin- istered 5 to 8 ounces of sugar and 4 ounces of honey to two diabetic patients, with great benefit. Ordinary mixed diet (in- cluding potatoes) was conjoined. These results provoked new trials of this treatment by Dr. Burd, of Shrewsbury, Dr. Sloane, of Leicester, Dr. Bence Jones, and Griesinger, but with results so decidedly unfavorable as to leave no doubt of the inutility of the practice. A full resiime of the results of the saccharine treat- ment of diabetes may be found in a paper by the author in the ''Brit. Med. Journ."'for November, 1860. APPENDIX. Milder Types of Diabetes. The cases brought together under this heading are somewhat miscellaneous; and they do not present those marks of uni- formity, which are required to constitute a homogeneous patho- logical group. Thej' are separated from classical diabetes by certain broad distinctions of clinical importance; but they ex- hibit anions themselves certain disaa^reements which make it evident that they represent more than one type of disease. From ordinary or classical diabetes, these milder types are distinguished by all or some of the following signs: Absence of a fixed tendency to a fatal termination; absence, or only mod- erate degree of thirst, voracity, and emaciation ; slight or tem- porary increase in the quantity of urine; transitory duration; amenability to treatment; slight, moderate, or intermittent glycosuria. ' Bouchardat speaks in high terms of enforced exercise and gymnastics for diabetic patients. See Annuaire de Therap., 1865, p. 291. M1LI>KK TYJ'ES. 287 The greater number of these cases fall within one or other of the three following groups, to each of which illustrative exam- ples are appended : Group I. — Urine persistently saccharine; density 10-30 to 1043; diuresis absent, or very moderate; no excessive thirst or appetite; moderate conservation of strength and flesh; stationary condition. Case 1. — Mr. B., a manufacturer, set. 45, thin but not markedly ema- ciated, able to attend to his business, consulted me May 14, 1861. His health had been feeble for six months. He complained of weakness, loss of appetite, and restlessness. The urine had never exceeded four pints, and usually did not exceed three pints in the twenty-four hours. The specimen sent to me for analysis had a density of 1042, and contained 7.2 per cent, of sugar. There was no inordinate appetite or thirst ; the skin was moist. The patient had tried a diet composed of animal flesh and green vegetables, but had been unable to adhere thereto on account of the total failure of the appetite. During the last four years I have seen this patient several times. His condition continues unchanged, both as to the general health and the state of the urine. He is still a valetudinarian, but goes about his business, and observes a diet, onjy restricted with respect to the use of potatoes. Case 2. — Mr. F., get. 50, formerly engaged in business. He consulted me in November, 1862, and stated that he had been ailing about three years, suffering from indigestion, lowness of spirits, and loss of strength. A twelvemonth before sugar had been detected in the urine. The urine had not at any time exceeded three pints in the twenty-four hours. He has never been troubled with thirst ; the skin is usually moist ; there has been slight emaciation. He has tried a restricted diet without any benefit. Two specimens of urine were handed to me for analysis ; one on November 20, 1862, and the other on April 22, 1863. The former con- tained 7.7 per cent, of sugar, and the latter (which had a specific gravity of 1039) 6.3 per cent. The daily quantity at both dates was three pints. The disorder in this instance appears to have arisen from worry and anxiety connected with business ; but for a period of two years after giving up business he remained in statu quo, no treatment appearing to have any beneficial result. Recently he has been in much better health, has recovered his weight, strength, and cheerfulness, and believes him- self thoroughly rid of his complaint; and yet, the urine has now (February 23, 1865) a specific gravity of 1035, and contains 5.7' per cent, of sugar. In the autumn of 1870 I was called to see this patient again. The sugar had now for a long time disappeared from the urine and was replaced by albumen. He was suffering from general anasarca, and all the other signs of chronic Bright's disease — of which he died in December, 1870. Case 3. — Dr. Latham^ relates a case resembling these in most respects. The patient was a gentleman, set. 40, well known in the profession of the 1 Latham on Diabetes, p. 147. 288 DIABETES MELLITUS. law. The urine at no time exceeded a quart, but it was so sweet " that it might easily have been mistaken for syrup." The dietetic treatment was resolutely tried without any good effect : he died with cough, colli- quative sweats, and other signs of phthisis. Group II. — Glycosuria, temporary or intermittent; thirst and diuresis moderate, or none; little emaciation and loss of strength; the complaint depending on mental anxiety, blows on the head, or concussion of the spine, and terminating in complete re- covery. Case 4. — A gentleman, set. 46, engaged in business, consulted me on March 23, 1862. He had suffered from slight, recurrent, dyspeptic symptoms for more than a year, together with numerous nervous pheno- mena and loss of rest. During this period he had undergone great mental stress in connection with the responsibilities of a large manufac- turing concern. On two occasions he had been seized with some kind of fit, which, from the description given, appeared to be a bastard epilepsy. In one of these he had fallen from his horse ; but there was no direct injury to the head. At my request a specimen of urine was sent for examination. Its specific gravity was 1035, and it contained 5.2 per cent, of sugar ; no albumen or other abnormal ingredient was present. The daily quantity did not exceed three pints. He was put on a moderately restricted diet, and recommended to make arrangements which would relieve him of a large portion of his responsibilities. He continued under my observation for six months. The sugar disappeared in about six weeks, except a trace, which also vanished at the end of four months. His health is now (July, 1865) perfectly restored. One of the most singular instances of glycosuria, persisting for several months, unaccompanied with any of the sj^mptoms of true diabetes, is related by Griesinger (loc. cit. p. 51). Case 5. — A medical student had, during a course of chemical instruc- tion, in the year 18 — , often examined his urine, and found it in every respect normal. He spent the summer of the succeeding year in Switzer- land, and underwent a number of wettings on botanical excursions. Some months later, while in perfect health, the appearance of the urine attracted his attention. On examination it gave an abundant sugar reaction with Trommer's test. He now examined the urine daily, and found the density to vary between 1022 and 1027. The glycosuria per- sisted throughout the following winter, during which he continued to reside in the same moist and foggy locality. In the succeeding spring, Herr returned from Switzerland, and, being much occupied, had no longer any time to bestow on his diabetes ; and when, in the course of the ensuing summer, he examined the urine again, he found it totally free from sugar, nor has a trace been found in it since. During the entire period that the urine contained sugar, he did not experience a single one of the known symptoms of diabetes. MILDEK TYPES. 289 Group III. — Glycosuria in persons advanced in years; of full habit; moderate conservation of flesh and strength; moderate diuresis; moderate amount of sugar; abundance of uric acid deposits; often gout; sugar sometimes present for years, vary- ing greatly in quantity, sometimes intermitting — termination variable. Dr. Bence Jones has published an account of a number of cases of this class.^ Of twenty-nine cases of glycosuria, ob- served by him in the preceding three years, eleven were above sixty years of age, and six of these were above seventy. He supplies the following analysis of these eleven cases: In 2, the disease was intermitting. In 6, the quantity of urine was scarcely, if at all, increased. In 1, the quantity was increased, but the disease had probably existed for sixteen years. In 1, the urine was albuminous, and the diabetic symptoms were very slight. In 1 (about seventy-four years of age), the disease existed in its intensity. In all cases save one, the disease was of exceedingly mild character. Man}^ cases of this kind have come under my notice, of which the two following examples may serve for illustrations : Case 6. — Mr. A,, a surgeon, set. 60, a tall, stout man, of powerful frame, consulted me June 11, 1863. He had noticed for the last four mouths an undue frequency of micturition, with a certain languor un- usual to him, of which, however, he thought little, until the copiousness of the urine excited his suspicions, and induced him to test it for sugar. This led to the detection of his complaint. He had lost some flesh. When I examined him, he had a ruddy complexion and an appearance of health ; the appetite was moderate ; thirst somewhat troublesome ; skin moist ; he went about his usual business — being in extensive practice in a rural district — with scarcely more fatigue than ordinary. The teeth were extensively decayed. The urine amounted to five or six pints daily. A specimen carefully collected for twelve hours was sent to me for examination. It amounted to 68 ounces; specific gravity, 1034; it de- posited uric acid copiously, and contained 6 per cent, of sugar, which indicated a total of 1800 grains in half a day. Mr. A, was gradually put on a restricted diet, with gluten bread. In a week, the urine of twelve hours had come down to 45 ounces ; specific gravity, 1035 ; percentage of sugar, 6.1 ; sugar voided in twelve hours, 1190 grains. Four weeks later, the urine of twelve hours had diminished to 37 ounces ; specific gravity, 1028 ; sugar, 4 per cent. ; quantity voided in twelve hours, 673 grains. The general condition had also greatly im- proved ; he still adhered to the restricted diet. 1 Med.-Chir. Trans., vol. xxxvi. 19 290 DIABETES MELLITUS, I have seen Mr. A. from time to time up to the present date (February, 1865). He is now perfectly restored to his original health and embon- point. The restrictions on his diet have long since been relaxed. He derived considerable advantage from the use of almond rusks and cakes, and from change of air and scene, in the highlands of Scotland. November, 1871. — Mr. A. died suddenly two years ago from a rup- tured aortic aneurism. Case 7. — Mr. M., a retired solicitor, set. 72, consulted me October 17, 1863. He was a florid-complexioned, stout, healthy, and vigorous- looking man for his age. Until sixteen months ago he had always enjoyed excellent health. Sixteen months ago he was seized with a low febrile complaint of un- determined character. He kept his bed for two months, and was greatly reduced by it ; but he gradually recovered, and went to Buxton to com- plete his convalescence. Before going to Buxton he had noticed a sweet taste in his mouth and a certain sweetness of the skin of his hands ; and ■when there he noticed a great thirst and frequent calls to void urine. With the continuance of these symptoms he became rapidly thinner, and sent for his son-in-law, Dr. H., who examined the urine, and dis- covered sugar. Dr. H. found the symptons of diabetes present in moderate intensity; gums spongy; emaciation very considerable; all his embonpoint gone ; he was " reduced to a little old man." The urine amounted to six and ten pints a day ; and his thirst was so tormenting, that he used to prepare for himself a large jugful of oatmeal-water and milk, to drink at night. At this period, he was put on a strict flesh diet, with green vegetables. Great benefit followed this treatment ; and in about two months from the first onset of the diabetic symptoms, he had recovered from the attack, and begun to recover flesh and strength. It was not ascertained whether the sugar disappeared from the urine when the other symptoms subsided. He continued in improved health for five or six months, and regained much of his previous vigor. He then began to suffer from severe lanci- nating pains about the base of the chest. On account of these he sought my aid. He complained of intense pain, of neuralgic character, along the course of the lower intercostal nerves. Up to the day before his visit to me, the pain had been limited to the left side, but it had now invaded the right side ; and a painful circle embraced him, in a line corresponding to the attachments of the diaphragm. The pain was darting, burning, as if a red-hot iron was drawn round him ; it prevailed in paroxysms ; but lately the remissions had never been complete ; and the pain came forward to the mesial line, and descended into the testicles and penis. Nightly opiates were required to induce sleep. He was very nervous and agitated, especially during the paroxysms, but there was no fever. Tongue clean, pulse quiet, ranging from 65 to 80 (he often counted it himself) ; heart's sounds were healthy, and there was no hypertrophy. The pain was much increased by motion of the body, as in walking. There was no thirst ; the quantity of urine was not increased. Micturi- tion frequent at night; appetite pretty fair. MILDER TYPES. 291 At my request he brought me the urine made after dinner on October 18th; its specific gravity was lO-'^O, clear, amber-colored; it contained no trace of albumen, but as much as 5.1 per cent, of sugar. He was ordered 5 grains of quinine, with some carbonate of iron, and a few drop.s of laudanum at night. October 19th. — He brought me the urine made before breakfast; its specific gravity was 1019, and it contained only a trace of sugar. He had passed a much better night than usual. 20th. — Urine before breakfast contained a trace of sugar ; that voided after dinner contained a good deal more. 21st. — Urine before breakfast was quite free from sugar; that after dinner contained 4 per cent. He still complained of the pain round the chest, but in much diminished degree. 25th. — Urine before breakfast free from sugar ; that passed after dinner contained only 0.8 per cent. He was put for a while on a partially restricted diet. The urine con- tinued for some days to show traces of sugar after dinner. After this he left town and went to the country, continuing to improve. This gentleman is now (February, 1865) in'very fair health for his age ; but I cannot state whether or not the urine contains sugar. In patients of this class I have generally found that, although the diahetic symptoms prove mild and amenable to treatment, life is seldom prolonged beyond a few years. The glycosuria may disappear or become insignificant; but the constitution is evidently broken, and they usually die in two, three, or four years, either from cerebral disease or from pulmonary complications. CHAPTER III. aHAVEL AND CALCULUS. Urolithiasis. GENEKAL ETIOLOGY. ' The deaths from stone, in England and Wales, in the five years ending 1866, amounted to an annual average of 168. It is satisfactory to note that the mortality from this cause exhibits a progressive diminution in the last thirty years, as may be seen from the following table constructed from the Registrar-General's Reports : Mortality froTn stone in England and Wales, in five successive quinquennial periods.^ In the 5 years 1838-42 the yearly average of deaths from stone was 297 " 1847-51 " " " 232 " 1852-56 " " " 216 " 1857-61 '' " " 184 " 1862-66 " " " 168 The cause of this diminution is to be chiefly sought for in the earlier detection of the stone, and earlier resort to operation, in recent times ; perhaps also in the improved diet and water sup- ply of the population.^ Calculous disease is much more fatal (as might have been expected) in the male, than in the female, sex. For every female that died, in England and Wales, in the ten years, 1857-66, from the consequences of stone, nearly nine males perished. More deaths from stone occur at an early a^e, and in the waning years of life, than in the intermediate periods, as is shown by the following table : Table showing the number of deaths from stone at different ages in the decade 1857-66 in England and Wales — Males only included. Under 5 years 116 deaths. Between 5 and 15 years 15 " 25 " 25 85 45 55 65 35 45 55 65 75 75 and upwards 114 59 62 73 132 294 517 299 ^ The returns of the years 1843-46 are tabulated differently from the remainder, and cannot, therefore, be included in this table. 2 The suburban district of Hulme supplies considerably fewer"cases of stone to the Manchester Infirmary since the pipe-water has replaced the old pump-water supply. GENERAL ETIOLOGY. 293 The great fatality of stone above tlie age of fifty-live is due, not so much to the greater frequency of stone at that epoch, as to its more severe effects on the constitution, and the less favor- able results of operation in advanced life. The fregumcy of stone is far the greatest under five years of age; and next between ten and fifteen years. It then diminishes rapidly until, the thirty-fifth year. Above this age cases of stone become, again, more and more frequent, until the age of sixty-five. The following table indicates, very exactly, the prevalence of stone at different periods of life. It embraces all the persons who underwent the operation of lithotomy, during given periods of time, at the following hospitals: Guy's, St. Thomas's, Uni- versity College, Norwich, Cambridge, Oxford, Birmingham, Leicester, and Leeds. Table showing the ages of 1827 pe7-sons who under^weni lithotomy at the above hospitals— constructed from statistics collected in Sir H. Thompson's ivork on Practical Lithotomy and Lithotriiy. Under 5 years '*^^ Between 5 and 15 years -^28 " 15 " 25 " '^57 " 25 " 35 " 85 " 35 " 45 " 90 " 45 " 55 " ISS " 55 " 65 " . • ^25 " 65 " 75 " 103 75 " 81 " ' 10 E'o countries or climates are altogether free from calculous disorders; but some localities are considerably more afflicted by them than others. Stone and gravel are common in England, France, Teneriffe, Iceland, and Egypt.^ They are, on the con- trarv, rare in Sweden and Norway, Styria, and some other parts of the Austrian dominions. In Christiania, 3211 patients were treated in the general hospital during a period of four years, and among them there was only one stone case. In the hospital of Gothenburg, in Sweden, which contains sixty beds, not a single case of stone was received in fifteen years. ^ The climatic conditions favorable to the_ prevalence of stone appear to vary within narrow topographical limits. Of the eleven registration districts into which England and Wales are divided, the eastern counties of Norfolk and Suffolk furnVsh the largest proportion of deaths from stone. Next to these come the North Midland counties. The fewest deaths from stone (as 1 The frequency of stone in Egypt is due to the ravages of the Bllharzia htematobia, a minute parasite which infests the urinary organs in hot countries. {See Bllharzia.) 2 Civiale, Traiti^ de I'Affection Calculeuse, p. 580. 294 GRAVEL AND CALCULUS. compared to the total mortality) are furnished b}^ Lancashire and Cheshire, and by the Southwestern counties.^ CLASSIFICATION OF UEINAEY CALCULI, THEIK CHEMICAL CHAEACTBES, OEIGIN", GEOWTH, AND GENEEAL CLINICAL HISTOEY. Urinary calculi may be classified, according to their chemical composition, into eight primary and one secondary species. The primary species are : 1. Uric acid. 2. Urates. 3. Oxalate of lime. 4. Cystine. 5. Xanthine. 6. Urostealith. 7. Bone earth (basic phosphate of lime). 8. Carbonate of lime. The sec- ondary concretion is composed of a mixture of the phosphate of lime and the ammoniaco-magnesian phosphate. In addition to these, which are composed of normal or abnor- mal, but strictly urinary, ingredients, two other species are occasionally found in the urinary passages which have an origin extraneous to the urine. These are Jibrine or blood concretions and prostatic calculi. Urinary concretions always contain, in addition to their proper components, slight admixtures of animal matters, viz., mucus, epithelium, pigment, and, generally also, more or less desiccated blood and pus. The term "gravel" is given to concretions of small dimen- sions, which are not too large to be spontaneously voided by the urethra; the larger masses are called " stones," or " calculi." Calculous formations are said to be primary^ when they are deposited from the unchanged urine, owing to some inherent vice in its composition ; and secondary, when the deposit is due to ammoniacal decomposition of the urine in the lower urinary passages. It is essential to recognize this difference in order to under- stand the mode of growth of urinary calculi, and the principles which should guide their medical treatment. 1 The following table shows the proportion of deaths from stone in each of the eleven registration districts of England and Wales, for every 100,000 deaths from all causes, in the ten years 1857-66. Males only are included. (Constructed from the Eegistrar-General's Eeports.) North- Western South -Western Northern . West- Midland South-Midland Yorkshire . London Monmouthshire South-Eastern North-Midland Eastern and Wales 34 46 54 64 71 75 90 91 93 98 115 CLASSIFICATION OF URINARY CALCULI. 295 It has been already cxi)laincd that vvlieiiovor the urine l)ecorrieH decomposed and anunoniacal, itn earthy constituents are pre- cipitated as a sediment composed of pho8[)liate of hme and the ammoniaco-magnesiau phosphate, often mixed with small quan- tities of urate of ammonia and carbonate of lime. This is identical with the secondary phosphatic deposit on urinary cal- culi/ Its production is due to tlie transformation of urea into carbonate of ammonia. Any obstacle which delays the urine in its channels, and prevents its speedy and complete evacuation, tends to bring about this change. The presence of a calculus in the bladder presents a condition highly favorable to the pro- duction of aramoniacal urine, and to the Y^'ecipitation of the secondary phosphatic deposit. Accordingly, it is found that calculi which have been long detained in the bladder, are fre- quently covered over with a phosphatic incrustation. Indeed, it may be said that this is the proper ultimate stage and last chapter in the history of every urinary concretion, unless its career be cut short by spontaneous expulsion, or removal by surgical operation. The epoch at which the secondary deposit begins to form is quite uncertain, and depends on the concurrence of cystitis. Sometimes small calculi, weighing only a few drachms, are found covered with a thick investment of phosphates ; in other instances large calculi, weighing many ounces, are found with- out any traces of phosphatic incrustation. So long as the urine remains acid the surface of the stone remains free from phos- phates, but as soon as the urine becomes freely ammoniacal, the secondary deposit begins to accumulate. It follows from these facts, that a solvent treatment which may have been applicable in the early existence of a stone, ceases to be so when the urine becomes ammoniacal and a secondary deposit has taken place on its surface. The principal points relating generally to the structure and growth of urinary calculi are embraced, in the following propo- sitions : 1. Calculi may consist entirely of one ingredient, as uric acid, oxalate of lime, cystine, etc. ; or two or more primary deposits may alternate with each other in the form of layers, so as to constitute an alternatinci calculus. 2. The most common alternations are uric acid and oxalate of lime ; but any primary deposit may alternate with any other primary deposit : as cystine with uric acid ; uric acid with bone earth ; or oxalate of lime and bone earth. The last two cases, however, are excessively rare. The number of layers composing 1 The fetid incrustation which covers public urinals is likewise of similar nature. 296 GRAVEL AND CALCULUS. an alternating calculus is quite uncertain ; there ma}^ be only three or four, or twenty or thirty. The thickness of the layers varies conversely with their number, 3. A calculus consisting of only one substance has usually a stratified arrangement, and exhibits an indefinite number of concentric layers. Such is usually the structure of uric acid, oxalate of lime, and phosphatic calculi. But sometimes the cal- culous matter is deposited in vertical lines radiating from the centre. This is the usual structure of cystine calculi. Some- times one portion of a stone has a radiated, and another portion a stratified formation. 4. Most urinary calculi are divisible into a central portion or nucleus, and an outer portion or body. There is also not unfre- quently an outer investment, or crust, of phosphatic deposit. 5. The nucleus may be of the same nature as the body, or dififer from it. The nucleus may consist of uric acid, urates, oxalate of lime, or any other primary formation, or it may be a clot of blood or a mass of mucus ; or, lastly, it may consist of some foreign body introduced from without. 6. The determining causes of the formation of urinary calculi are still but imperfectly known. The more usual are the follow- ing : (a) An excessive proportion of the precipitated ingredient in the urine ; {b) A too acid state of the urine, which diminishes its solvent power over uric acid and the urates ; (c) An alkaline state of the urine. If the alkalescence be due to fixed alkali, the bone-earth phosphate and carbonate of lime are liable to precipitation ; this is, however, a very rare contingency in the human subject, though common in the herbivora. If the alka- lescence be due to carbonate of ammonia, the secondary phos- phates are precipitated; {d) Deficiency of chloride of sodium and the alkaline phosphates in the urine, reduces its solvent power on uric acid (Heller); (e) The presence in the urine of an abnormal constituent of sparing solubility, such as cystine or xanthine; (/) The accidental presence of a body suitable to form a nucleus, such as a small mass of concrete blood, mucus, epi- thelium, or an extraneous body, such as a bit of bougie, a piece of bone, or of a wire or needle, a bit of sealing-wax, and so forth. Considerable light has been thrown on the mode of origin of urinary calculi by an examination of the microscopical structure of their nuclei. Dr. V. Carter found that the actual nucleus consisted nearly always of globular forms of urates and oxalate of lime (dumb-bells and spheroids), and not ordinary crystals of these substances. The researches of liainey and Ord have shown that these globular forms are only produced when pre- cipitation takes place slowly in a colloid medium; and Carter found that a colloid matrix always exists in the nuclear forma- VARIETIES OF URINARY GRAVEL AND (JAI.fJi;iJ 297 tions of urinary calculi. It would therefore appear probable that the initial Btep in the formation of a calculus is the exudation of some colloid — mucus, or some other al})nminoid substance — into the urinary passages. Into this colloid, urates or oxalate of lime, or both, arc precipitated, and combining with it, form molecular aggregations of a globular character, which constitute the foundation of the subsequent growth. Under what con- ditions the colloid is exuded cannot be with certainty explained ; but the probability is that congestive or subinflanmiatory states of the kidneys, such as occur in the febrile state, give occasion to such an exudation and supply a starting-point to a process which does not attract attention until after a long lapse of time.' OF THE PARTICULAK VAKIETIES OF URIJTAEY GEAVEL AND CALCULI. 1. Uric Acid, — This is by far the most frequent species of urinary concretion. It constitutes probably five-sixths of all renal concretions, and of vesical calculi which have only re- cently descended from the kidney. As gravel, uric acid may be passed in the form of small distorted crj^stalline agglomera- FiG. 40. Section of a uric acid calculus. tions, or as little smooth spherical bodies, ranging from the size of a poppy seed to that of a mustard seed, or in flattened warty concretions as large as split peas. All these have a yellowish, brownish, or reddish color. They are derived from the kid- ney, and may be discharged singly or in numbers at irregular intervals. ^ See Carter " On the Microscopic Structure and Formation of Urinary Cal- culi." Lond., 1873. Also Dr. Ord's paper, Med.-Chir. Trans., 1875; and his work "On the Influence of Colloids upon Crystalline Form and Cohesion.'.' Lond., 1879. 298 GRAVEL AND CALCULUS. When retained in the bladder, they grow into flattened oval calculi, sometimes roundish, sometimes elongated like an almond. Theyvary in color from a light fawn to a deep brick-red, accord- ing to the" quantity and nature of the urinary pigment which they contain. Their surface is usually studded with minute tubercles, or mamillations, which are worn into smooth facets if more than one stone coexist in the bladder. Their weight varies from a drachm to an ounce, but sometimes reaches four or five ounces. Uric acid calculi possess considerable hardness; their specific gravity is about 1.5. Uric acid is best recognized by the murexid test, previously described. Its most important properties, from a therapeutical point of view, are its solubility in weak solutions of the carbonates of lithia, potash, and soda, and its insolubility in strong solutions of the bicarbonates of potash and soda, as well as in water and dilute acids. Pathologically, uric acid is closely related to gout. Hence, the frequency of uric acid gravel and stone in the wealthier classes in the middle and later periods of life. The urine, in the subjects of uric acid calculi, is acid, and often high-colored, prone to deposits of uric acid crystals and amorphous urates, The medical treatment of this class of calculi will be described at length in a separate section. [See Solvent Treatment.) 2. Urate Concretions. — The same confusion has existed re- specting the composition of these concretions, as respecting that of the amorphous urate deposit. They are usually designated urate of ammonia, but their chemical nature requires reexami- nation. They constitute small, soft agglomerations in the kidneys — rarely in the bladder; and are almost confined to young chil- dren. Heller^ states that he has found them several times in the kidneys and ureters of sucking infants in the Vienna Found- ling Hospital. They formed small irregular clumps, sometimes heaped together into a mass as large as a kidney bean. Heller encountered similar calculi on two occasions in adults. Calculi wholly composed of urates are very rare, and never reach a large size ; but globular masses of urates nearly always exist in the centre of a urinary calculus, although its bulk may be formed of some other ingredient. The deposition of clumps of urate of soda in the urinary pas- sages is not uncommon in the febrile complaints of infants and young children ; and it seems not unlikely that some of these clumps may be retained in the pelvis of the kidney or in the bladder, and become the nuclei of future calculi ; and that the ■ Harnconcretionen, p. 134. VARIETIES OF UKJNAKY GRAVEL AND CALCULI. 2U\) excessive frequency of calculi in children is due to this cause {see p. 98). The urine from which this variety of concretion is deposited, has an acid reaction, and the medical treatment is identical with that of uric acid calculi. The circumstances under which this concretion is deposited, must be carefully distinguished from those in which urate of ammonia (of undoubted composition) is deposited in an ammoniacal urine mixed with secondary phos- phates. Urate concretions are distinguished chemically by their solu- bility in hot water. 3. Oxalate of Lime or Mulberry Calculus. — Oxalate of lime may be discharged as minute concretions, or gravel, from the kidney, or grow to be a stone in the bladder. In the former case the concretions are usually smooth, rounded, grayish-dark bodies, resembling hemp-seed. Vesical calculi of this class are exceedingly hard, and break into sharp angular fragments when crushed by the lithotrite They are usually of a spherical shape ; their surface is tubercu- lated like a mulberry (Fig. 41), and is usually of a blackish- FiG. 41. Oxalate of lime ur mulberry calcnhis. brown color. Sometimes, however, they are oval and smooth, and of a bluish-gray color. The nucleus of a mulberry calculus is frequentl}^ composed of uric acid; and, conversel}^ (though much more rarely), a uric acid stone may have a nucleus of oxalate of lime. Beale and Carter have further shown, that in the centre of a uric acid nucleus, there is often a microscopic clump of dumb-bells of oxalate of lime. Calculi composed of alternate layers of oxalate of lime and uric acid are more common than those composed of oxalate of lime alone. These laj^ers may form complete concentric cap- sules, or be partial and imperfect. In the latter case the con- cretion is amenable to the solvent and disintegrating action of the alkaline carbonates; in the former it is wholly beyond the. power of such solvents. 300 GRAVEL AND CALCULUS. Oxalate of lime is insoluble in alkaline carbonates and organic acids; but it dissolves in nitric and muriatic acids. When heated before the blowpipe, it first blackens, and finally leaves a bulky white ash of caustic lime, which blues moistened litmus paper. During the formation of oxalate of lime calculi, the urine is always acid. 4. Cystine. — Gravel and calculi of cystine belong to the rarer species, of urinary concretions. They are usually found in the bladder as large calculi, but sometimes they are discharged spontaneously as gravel. I have in my collection two examples of pure cystine calculi passed spontaneously {see Fig. 42). One Cystine calculi spontaneously voided. of them is a small lenticular mass weighing a grain and a half. The other is cylindrical in shape, an inch and a quarter in length, and weighing twenty-seven grains. Both have a crys- talline granular surface and a light yellow color. Sometimes vesical calculi of cystine attain a weight of three or four ounces. They are usually egg-shaped, of a full honey-yellow color, mamil- lated on the surface, and lustrous, as if studded with minute crystals. When cut into, they show a radiated structure, and an obscurely transparent brilliance like yellow beeswax. They are usually composed of pure cystine, unmixed with any other substance. Sometimes the}^ have a nucleus of uric acid. In a specimen in the Museum of Owens College (Fig. 43) the cen- FiG. 43. Section of a cystine calculus, with a nucleus of uric acid, and an external coat of phosjjhate. tral nodule is uric acid ; around this is a body of pure cj^stine ; overlying this a layer of mixed uric acid and cystine ; and enveloping the whole a crust of secondary phosphates, mixed with cystine. Cystine calculi possess the curious property of assuming a pale green color when long exposed to full daylight. The VARIETIES OF URINARY GRAVEL AND CALCULI. 301 specimen just referred to iiftbrded an interesting example of this change. The calculus liad been divided equatorially ; one- half lay in the cabinet with its cut surface downwards, and the other half with the cut surface upwards, exposed to the light. The latter had a delicate emerald-green tint, while the former preserved its original yellow color. Another curious circumstance in the history of cystine, is its tendency to run in families. Dr. Marcet gives an account of two brothers in whose kidneys cystine calculi were found. Both Lenoir and Civiale extracted cystine calculi from the bladders of two brothers. Toel relates the history of two sisters and a mother who voided cystine with the urine. Ebstein^ also has described cystinuria as occurring in two brothers. Cystine calculi are much more friable than uric acid or oxalate of lime. They are easily scraped with the nail, and otfer especially favorable objects for treatment by lithotrity. My late colleague, Mr. Southam, showed me a quantity weigh- ing ninety grains of the fragments of a pure cystine calculus, which had been voided by a little girl four years of age after a single crushing. Cystine is recognized with great facility. If a particle be placed on a watch-glass, or on a slip of glass, and treated with caustic ammonia, it speedily dissolves ; by exposure to the air for a few hours, the volatile alkali exhales, and beautiful six- sided crystals are deposited, which are highly characteristic {see Figs. 14 and 15). Cystine is also soluble in the mineral acids ; and in the tixed alkalies and their carbonates ; but it is precipitated by organic acids and by carbonate of ammonia. 5. Xanthine calculi are excessively rare. [See Xanthine, p. 111.) 6. Fatty or Saponaceous Concretions. Urostealith (of Heller). — In the Museum of the College of Surgeons of Lon- don there are two magnificent specimens of vesical calculi, composed of a central fatty or saponaceous mass surrounded with a thick investment of phosphates (Fig. 44). Both belonged to Hunter's collection, and both are figured and described in the catalogue of calculi published in 1842. They are described as " consisting of the earthy phosphates deposited upon a mass of oleate and margarate of lime,"' This mass is of a light'yel- low color, and its irregularities correspond with those of the cavity in w^iich it loosely lies. At p. 129 of the catalogue, the following ingenious remarks are made respecting the probable origin of these stones : " On account of some real or supposed disease of the bladder, a solution of soap has been injected into 1 Deutsch. Arch., Bd. xxiii. 302 GRAVEL AND CALCULUS. its cavity ; mutual decomposition between the soap and the salts of the urine has been the necessary result; the alkali of the former uniting with, and forming soluble compounds with, the phosphoric and other acids of the urine, while the earthy bases of the urine have precipitated, in combination with the fatty acids of the soap, in the form of a semi-gelatinous sparingly Fig. 44. I- Section of a fatty or saponaceous concretion (firosteiiliik) surrounded with pliospliates. From the Museum of the London College of Surgeons. soluble compound, being in fact an earthy soap; this substance, acting as a foreign body in the bladder, has induced the deposi- tion of the phosphates, and given rise to the formation of a calculus." The fatty or saponaceous masses here described are probably of the same nature as those described by Heller in 1845, and named by him Vrostealith} Only one other case has been pub- lished ; it was observed by Dr. W. Moore in 1853.' Heller's patient was a man, 24 years of age, who passed a number of small concretions about as large as peas. When fresh, they were soft and elastic, like India-rubber, but dried into hard, brittle, wax-like masses. They dissolved readily in caustic potash, forming a soap. They also dissolved readily in ether, but with difficulty in alcohol. In hot water they did not dissolve, but softened. They melted with heat, and eventually burned with a bright yellow flame, exhaling an odor of shellac and benzoin. They contained a large quantity of earthy phos- phates. Dr. Moore's specimens consisted of two very small dark brown 1 Harnconcretionen, p. 146 ; alpo Heller's Archiv, Bd. ii. p. L ^ Dublin Quarterly Journ. of Med. Science, vol. xvii. p. 473. VARIETIES OF URINARY GRAVEL AND CALCULI. 308 calculi, which had a soft wax-like cotisistencc, and a[)pcarod to consist of a lime soap. They partly dissolved in hot alco- hol ; and the solution, when cold, deposited a whitish matter, which exhibited numerous fat globules, but no crystalline plates, Wheu incinerated before the blowpipe they yielded a white, alkaline, calcareous ash. A year later. Dr. Moore received from Dr. R. Adams two calculi taken from the body of this patient. One was a large phosphatic stone, in the centre of which was a cavity containing some of the same dark brown substance. Dr. W. Davy, who examined a portion of this, judged it to be composed of lime "in combination with the fat or waxy substance forming some organic combinations with the fatty acids." 7. Carbonate of Lime. — Concretions of carbonate of lime are very rare in the human subject; Those which have hitherto been encountered were of small dimensions, varying from the size of the smallest visible granules to that of a hazelnut, smooth on the surface, gray, yellowish, or bronze colored — sometimes with a metallic lustre, and generally very hard. The following remarkable case, in which myriads of minute calculi of carbonate of lime were voided with the urine, was described in the first edition of this work as an example of the spontaneous expulsion of prostatic calculi, but a communication I have since received from Dv. Haldane, of Edinburgh, has con- vinced me that they were derived from the kidneys, and not from the prostate. The patient was a gentleman seventy years of age, suffering from enlarged prostate, under the care of Mr. George Hun- stone, of this city. On the 20th of April, 1864, Mr. Hunstone brought me a specimen of the urine for examination. It was ammoniacal, and contained a good deal of pus. At the bottom of the phial were a large number of minute amber-colored cal- culi — the largest of which were about the size of poppy seeds, and the smallest only just visible to the naked eye, as bright specks. On subsequent occasions Mr. Hunstone brought me -additional quantities of urine containing similar bodies. Alto- gether I obtained about eight grains of these calculi ; they were easily separated from the urine by levigation and decantation. Mr. Hunstone stated that the patient had been in the habit of voiding these calculi for some months, at frequent intervals. The patient died some few months afterwards, and, unfortu- nately, no opportunity was afforded of making a post-mortem examination. The largest of the specimens in my possession is about the size of a mustard-seed ; there are a good many as large as poppy seeds ; but several hundreds are less than a quarter of this size, and many thousands are still smaller. They are mostly 304 GRAVEL AND CALCULUS. spherical in shape ; many are rudely cubical or pyramidal. They possess a full amber color, and are linely translucent. Under the microscope they present the appearance represented in Fig. 45, and exhibit an infinite series of concentric lines. The centre or nucleus is variously composed. In some of them it is an object resembling a glandular cell, in others a prismatic crystal, in others amorphous earthy-looking matter. In some, again, the nucleus is double ; in others, treble, or even quadruple (Fig. 45). With polarized light they display a dark cross, as Fig. 45. Carbonate of lime calculi spontaneously voided with the urine — highly magnified. represented in the lower right-hand corner of the figure. When crushed they break into angular fragments. The calculi dissolve rapidly in mineral acids, with abundant disengagement of carbonic acid — leaving ragged, brown, flaky, organic remnants. Acetic acid acts very slowly upon them, without visible disengagement of carbonic acid; but in the course of two or three days all the mineral matter is taken up, and the animal matrix is left, as soft, light balls, preserving the stratified appearance of the original calculi, but with a diminu- tion of their original translucency. They are unaffected by caustic potash. The murexid test yields not the slightest evi- dence of uric acid. When heated to whiteness before the blow- VARIETIES OF URINARY GRA.VKJ. ANJ> CALCULI. 305 pipe, their surfaces fuse into a brilliant iron-gray enamel, which protects the deeper parts. As the incandescent calculi cool, the enamelled surfaces crack into numerous minute polygonal spaces. The solution of the calculi in muriatic acid throws down an abundant, white, flocculent precipitate when saturated with caustic ammonia. These reactions indicate that they are composed of an animal matrix impregnated with carbonate of lime mixed with a little phosphate of lime. Dr. Haldane's communication above referred to contains an account of a case in which calculi, identical in every respect with those just described, were found in the kidney after death. Dr. Haldane's notes are as follows : "W. A., a mason, aged 33, was admitted into the Edinburgh Infirmary under Dr. Gillespie, on the IGth of October, 1856. Fifteen months before admission he strained his hack while engaged in raising a large stone. " Two months afterwards an abscess formed over the upper part of the sacrum, which was poulticed, opened, and matter was discharged. " The abscess healed up, but matter again formed ; the second abscess burst about two months before his admission into hospital. During the greater part of the fifteen months he had been at his work. "When admitted into the hospital he complained of pain in the back and general weakness. There was an opening at the right side of the sacrum, from which pus discharged. A probe could be introduced its whole length, and seemed to pass towards the anterior part of the lumbar vertebrae. He sank gradually, and died on the 21st of April, 1857. "No urinary symptoms were noticed during his residence in the hospital. " I examined the body on the 22d of April. A large accumulation of matter was found in front of the bodies of the lumbar vertebrae ; there was caries of the anterior part of the bodies of the first four. The spinal cord was not affected. " The heart and lungs were natural. "The liver was small, weighing 31 ounces, but was healthy in structure. " The right kidney weighed 5 ounces ; it was anaemic but healthy, except that a few gritty particles were embedded in some of the cones. These were found to consist partly of carbonate of lime. "The left kidney weighed 4 J ounces. In the pelvis was about half a teaspoonful of sandy-looking material, held together by a flocculent substance, which resembled coagulated blood. The sandy matter was in small particles, generally about the size of grains of sand ; some were as large as hemp-seeds. The lining membrane of the pelvis was thick- ened, and at some points appeared slightly abraded. The kidney was a little atrophied, owing to dilatation of the pelvis. The ureters were natural. The bladder was contracted ; it contained about a teaspoonful of urine, which unfortunately was not examined. " I looked upon this case as possibly an example of the calcareous metastasis described by Virchow. When in connection with absorption of bone, carbonate and phosphate of lime are deposited elsewhere." 20 306 GRAVEL AND CALCULUS. Dr. Haldane was good enough to send me a sample of the calculi obtained from the kidney in this case ; and I had no dif- ficulty in deciding on their absolute identity both in naked-eye and microscopic appearance, as well as in chemical composition, with those examined by myself. It seems also highly probable that the history of their occurrence was strictly analogous. In the nineteenth volume of the " Transactions of the Patho- logical Society," Mr. Wagstaffe describes a " large branching calculus," composed of carbonate of lime, removed after death from the right kidney of a man aged forty-two. Several small ones, of similar composition, were also found in the same kid- ney. Dr. Ord also has described calculi composed of carbonate of lime.^ 8. Basic Phosphate of Lime or Bone-earth. — Concretions of this substance alone are very rare. They were formerly confounded with the mixed phosphates which constitute the secondary deposit. They vary in size from a pea to a hen's egg. They are white and chalky in appearance, and of a soft, smoothish exterior, with an earthy fracture. Sometimes their texture is loose, sometimes very compact. Bone-earth rarely alternates with any other deposit; occa- sionally, however, it does so. There is a fine specimen in the museum of the Manchester Infirmary, in which bone-earth alternates with uric acid. When the urine is rendered alkaline by alkalizing salts, or becomes alkaline after a meal, the bone-earth phosphate is sometimes abundantly deposited ; but, from its uncrystalline condition, it has very little te^idency to agglomerate into con- cretions. Patients may pass an alkaline and turbid urine (from this cause) for months, without practically any risk of the formation of a stone. 9. Mixed or Secondary Phosphates (Fusible Calculus). — The composition and production of this deposit from ammo- niacal urine has been already explained. It rarely forms the centre of a urinary calculus ; but more commonly encrusts cal- culi of some other species, or an extraneous body which acts as a nucleus (Fig. 46). Concretions of this substance are fre- quently formed around the inequalities of fungous or other growths of the urinary organs. Calculi of the mixed phos- phates may go on increasing for an indefinite period, and com- pletely fill the bladder, attaining a weight of 10, 20, or even 30 ounces.^ 1 " On the Influence of Colloids," etc., p. 135. ^ Dr. Utterhoeven, of Brussels, withdrew, by the suprapubic operation, from the bladder of a man, aged thirty-nine, an enormous oval concretion weighing 40J ounces, and measuring round its longest diameter 17 inches. I believe this is the largest ever extracted from a living person. It had been growing from the age of twelve. (Leroy d'EtioUes (fils), Traite pratique de la Gravelle. Paris, 1863.) VARIETIES OF URINARY GRAVEL ANJJ CALCULI. 507 In their physical cliaractors, fusible calculi most resemble the bone-earth phosphate. They are usually lax and friable, com- posed of concentric laminfe, or irrei^ular; often studded on the surface with brilliant glistening i^oints of triple phosphate crys- tals. They readily break down under the lithotrite; but the general irritation of the system, and the frequent coexistence Fio. 40. ■^%% Section of a concretion, if a vast mass of tlie mixed pliosphates deposited on a calculus of oxalate of lime.' of grave anatomical lesions in the urinary passages or the kid- neys, render these cases unfavorable subjects for operation. They are especially suited for a solvent treatment by means of acid injections, thrown into the bladder in the manner recom- mended by Sir B. Brodie. Chemically, this concretion is characterized by fusing into^an enamel when strongly urged by the blowpipe. It is very soluble in acids, especially the mineral acids ; but wholly insoluble in water and alkalies. 10. FiBRiNE AND Blood CONCRETIONS. — Marcct givcs an ac- count of a small calculus about the size of a large pea, which was passed, after much suffering, by a gentleman between 50 and 55 years of age. He had been suffering for two or three years from symptoms of urinary calculi, and had previously passed three similar concretions. The specimen examined by Marcet had a yellowish-brown color, somewhat resembling bees- wax. Its hardness was also nearly that of beeswax. Its surface was uneven, but not rough to the touch; it was somewhat elas- 1 From a drawing in tlie possession of Sir. Southam. The history of this stone (which was successfully removed by the recto-vesical operation) is given by 3Ir. Southam in the 42d vokime of the Medico-Chirurgical Transactions. 308 GRAVEL AND CALCULUS. tic. When examined chemically, it answered to the reactions of fibrine. A concretion, about the size of a small pea, was handed to me for examination by my late colleague, Mr. Beever. It had been passed by a man of thirty-five, whose urine was not albu- minous. Its texture was hard and brittle, its external surface rough, its color dark reddish-brown. It swelled into a volumi- nous coal under the blowpipe, and, when fully incinerated, left a very scanty white ash. It was evidently composed of inspis- sated blood. A patient whom I saw with Dr. Holland was in the habit of passing numbers of blood concretions of a softer texture. He had previously suffered from hsematuria. ]SI"umerous similar concretions were found loose in the infun- dibula and pelvis of the kidney, in the case of ruptured kidney already described at p. 153. My collection contains a very fine blood concretion, taken from the bladder of a sheep (Fig. 47). The specimen was pre- FiG. 47. Blood concretion from the bladder of a sheep. sented to me by Mr. Lund. It is as large as a small walnut, very light — weighing only 37 grains. It is nearly spherical, and exceedingly rugged on the surface, which is studded all over with reddish-black warty projections. This dark warty part forms the outer crust of the concretion, is very brittle, and breaks with a lustrous fracture. When sawed through, the rough outside crust is found to be about a line thick : it invests an oval body, which has an even, sharply defined outline. The body has the appearance of baked clay; it is of nut-brown color, and easily scraped with the nail. It breaks with a dull fracture, like a piece of catechu. Examined chemically and microscopic- ally, both body and crust were found to possess the characters of concrete blood. The scanty ash obtained by calcination gave abundant evidence of iron. All these instances appear to have been connected with the occurrence of renal hsematuria. Such concretions sometimes serve as nulclei for uric acid or oxalate of lime calculi.^ 1 Wilson's Lectures on the Urinary Organs, p. 81. DIAGNOSIS OF TJIK HPECIKS. 309 11. Indigo. — Only one example of calculus composed solely of indigo is known. It was described by Dr. Ord in the "Pathological Transactions," vol. xxix., and was found in the pelvis of the riglit kidney of a woman, who had died from a sarcomatous tumor of the left kidney. The calculus was flat and hard, and weighed 40 grains. Its color was dark brown in some parts, in others blue-black, and it left a blue-black mark when drawn across a sheet of white paper. On heating it gave off the odors of burnt indigo, and sublimed in blue prisms of indigo. 12. Prostatic Calculi. — Although these are not, strictly 8pea]'as repeated. The activity of the kidneys oscillates from hour to hour; at one time the urine is secreted abundantly and dilute, and then the degree of alka- lescence necessarily falls ; at another time it is secreted more scantily and more concentrated, and then the degree of alka- lescence rises. W^heu, however, the above dose was exhibited with regularity, every second or third hour, the oscillations rarely passed an alkalescence equivalent to 20 grains to the pint, on the one hand, and 80 grains to the p^iut on the other; and, as a rule, the alkalescence ranged between 35 and 60 grains to the pint — which corresponds, sufficiently exactly, with the maxi- mum solvent power of a solution of carbonate of j)otash in Avater. 320 GRAVEL AND CALCU.LUS. 6. When urine, alkalized by the internal administration of these salts, was passed over the surface of uric acid calculi, at blood" heat, the calculi were found to undergo solution at the mean rate of 12| grains in the twenty-four hours. In performing this experiment it was found that, unless the calculus and the phial were frequently cleansed by immersion in water, the urine became ammoniacal, and the calculus be- came covered over with a crust of the mixed phosphates, which speedily put a stop to the solvent action of the alkalized urine. An important practical deduction flowed from this, viz., that when an ammoniacal state is developed, the solvent ■power of alkalized urine is entirely nullified, by the deposition of the mixed phosphates on the surface of the calculus. The urine of patients taking full doses of the citrate or acetate of potash, is generally clear, and shows no tendency to deposit, even on standing. But this is not invariably the case; it is sometimes turbid from deposition of the amorphous phosphate of lime. Two conditions seemed specially to favor this deposition, namelj^, the febrile state, and the digestion of a heavy meal. The amorphous phosphate is not unfrequently deposited, as we have already seen (p. 78), after a meal, in healthy persons who are not taking any alkalizing medicines; the circumstance is, therefore, not to be regarded as an un- natural or hazardous one. It is, further, to be borne in mind, that the amorphous phosphate differs essentiallj from the mixed phosphates thrown down m an ammoniacal urine. The former is a loose flocculent substance, which shows no tendency to aggregate into concretions; the latter, on the other hand, is partly crystalline, and speedily encrusts any object brought into contact with it. The establishment of this distinction disposes of one objection which has been urged against alkaline solvents. It now remains to bring forward illustrations of the applica- tion of the solvent treatment in practice; to distinguish the cases in which the treatment is applicable ; to lay down direc- tions for carrying it out effectually; and, finally, to examine some of the objections which have been urged against its employment. 7. Illustrations of the practical employment of alkaline sol- vents may be divided into cases of renal calculi, and cases of vesical calculi. One of the first rational attempts to treat renal gravel of uric acid by alkaline solvents, was made by the celebrated Mascagni in his own person. He gives the following account of his case in the " Memoirs of the Italian Society for 1804 :" I had been subject for several years to pains in the lumbar regions, and I voided from time to time gravelly concretions of a yellow-ochre MEDICAL TUEATMENT. 321 and brick-red color. Knowing that gaseous alkaline flmds l.acl been used in such cases, I took some on several occasions with beneht. 1 iinaers of filariee, both in the cortical and pyramidal portions. There were also found '* numerous trans- lucent oil-like tubules of a somewhat varicose appearance run- ning alongside the uriniferous tubes as if tlie lymphatics or minute bloodvessels of the part had been plugged." The organs did not appear otherwise diseased. My former pupil. Dr. Bancroft, now practising in Brisbane, Queensland, Australia, informs me that chyluria is not uncom- mon in that colony. He has detected li]ari?e both in the urine and in the blood of patients so affected, and has also discovered the adult worm which gives rise to them. It may be supposed that aggregations of these little animals in the kidneys, or some other part of the urinary tract, give rise to rupture of the lymphatics and a leakage of their contents into the urinary channels, and in this way produce chyluria. A further account of the life history of the parasite will be found in Chapter XIII., to which the reader is referred. The following abstract of Dr. Mackenzie's case will serve to illustrate the course of chyluria due to filarial embryos, and is specially interesting from the completeness of the observation, and from the light which it throws upon the relations of the filarial embryos to the periods of the disease : F. H. C, aged twenty-six, was born at Madras, and lived in India up to six mouths of coming under the care ot Dr. Mackenzie. About one month after arriving in England he noticed that his urine was increased in quantity, that it contained clots, and appeared slimy. In about a week the urine gradually assumed a milky appearance, and shortly became as " white as milk." On May 6, 1881, whilst lying down in the middle of the day he was seized with a violent pain extending from the left loin to the left testicle. The pain lasted for about twenty-one hours, and during its continuance the urine was of a deep blood color. He gradually lost flesh, the urine became more coi)ious, and formed on standing gelatinous clots. The patient was admitted into the London Hospital, under Dr. Mackenzie, on August 11th. He was then a well-made, healthy-looking man. His appetite was good, but he slept badly, having to rise frequently to pass urine. Xo disease of the chest or abdomen could be detected. His weight was 9 St. 1 lb., Avhile on arriving in England it was 11 st. 8 lbs. The urine resembled rich milk mixed with a little blood. A few minutes after being passed it coagulated to a soft tremulous jelly, the coagulum after- 23 354 CHYLOUS UKINE. wards breaking down. When freshly passed, the urine had a sweet odor, but on standing became fetid. The quantity passed daily was on the average 120 ounces. It had a specific gravity of about 1010, was faintly alkaline or neutral, and contained no sugar. It contained albu- men. When shaken with ether, the urine lost its milky character. The day urine had a brownish tint, almost completely coagulated, and con- tained much blood, while the night urine was more milky, did not form so large a coagulum, and contained less blood. Filarise were found in the urine both dead and alive. The blood contained large numbers of embryo filarise when examined at night time. Between 9 a.m. and 6 p. M. no filarise were found ; at 6 p. m. a few were seen ; these had in- creased in number at 9 p. m., were in the greatest number at midnight, and gradually decreased in number up to 9 A. m., when they had entirely disappeared. At night it was computed that from thirty-six to forty millions of filarial embryos were present in the blood. The hours of meals were altered to four hours later without any effect on the filarise, but the day and night urines were rendered almost alike Complete reversion of the hours of movement and rest, and correspond- ing change in the meal times, caused similar reversion in the filarial periodicity, the maximum number in the blood being then found at noon, and few or none at midnight. Under treatment the patient's health improved and his weight in- creased. On October 21st, after exposure to cold, he had a severe rigor with vomiting, headache, and pain in the epigastrium and right hypo- chondrium. Temperature 104°. The patient coughed without expecto- ration, and had a pain in the right side, increased on coughing. On October 23d the left shoulder was tender and swollen. Later on, a swelling appeared just above the left clavicle, the skin over which was red. This increased in size, gradually assumed the characters of an abscess, and was opened antiseptically on November 4th, pus and blood escaping. Double pleurisy afterwards developed itself, and further col- lections of pus formed in the left arm. The patient gradually lost strength, and died on January 10, 1882. From October 22d no filarise were found in the blood, and while they were seen as usual on October 20th, on the 21st they were very feeble and soon died. At the autopsy there was found empyema of the right side, and on the left side pleurisy. The right lung was collapsed, and the left oedema- tous. The kidneys showed early suppurative nephritis and several wedge- shaped patches were found in the cortex. The thoracic duct commenced in a dense mass of dilated lymph sinuses extending from the bifurcation of the aorta below to the aortic opening of the dia- phragm above. The thoracic duct was pervious for 1* inch above the diaphragm, then filled with loose clot for a similar distance, after which it was lost in a tough, thick mass which was apparently of inflamma- tory origin. The iliac, lumbar, and renal lymphatics were dilated, but especially those in the left renal region. It was supposed that the parent worm had become dislodged in the rigor, and becoming impacted in the thoracic duct, had excited inflam- mation, in the midst of which it perished. TREATMENT. 355 Treatment. — Hitherto the treatment of this disorder has proved very unsatisfactory. It generally persists in spite of every remedy, or disappears without any. The physicians of Rio chiefly recommend salt-water baths, and iron internally. Mineral and vegetable astringents have been tried repeatedly with small evidence of success. The best results have followed large doses of gallic acid. Dr. Waters and J)r. Bence Jones gave from one to two drachms a day. Dr. Bunyan, of George Town, British Guiana ("Lancet," 1846, I. 95), relates a very interesting case, in which the disease had lasted ten months. Various remedies were tried without success. On the advice of an old ncgress, the patient took a decoction of mangrove bark (Rhizophora racemosa), in ounce doses, four times a day. In seven days, he was so greatly im- proved that he discontinued the. medicine for two days, when the symptoms returned. The medicine was resumed in in- creased quantity, and continued for several days, until all the symptoms had entirely disappeared. Afterwards he suffered two returns of his disorder, which were immediately cut short by the use of the mangrove bark. I know not whether the mangrove bark has anti-parasitic properties, but if it has its success in the treatment of chyluria is comprehensible. It would certainly be worth a trial to treat cases of chyluria, in which filarise are found in the blood, by anti-parasitic remedies, and especially by large and sustained doses of the iodide of potassium. The eft'ect of diet was investigated by Dr. Bence Jones. He found that the urine was somewhat less chylous with vegetable than with animal food; he also found that the pressure of a tight belt round the loins relieved the pains in the lumbar regions, and seemed to improve the condition of the urine a little. Dr. Dickinson, in his case, believing that the chyluria was due to regurgitation of chyle from the thoracic duct into the bladder, applied the abdominal tourniquet, with a marked amelioration of the condition of the urine. The effect of indi- vidual applications of the tourniquet diminished after a time, but a slight permanent improvement was observed. The chy- luria finally ceased after the use of injections of perchloride of iron into the bladder. PART III. ORGANIC DISEASES OF THE KIDNEYS, CHAPTER I. CONGESTION OP THE KIDNEYS. Under the title of Congestion of the Kidneys, I propose to consider those less serious, and for the most part secondary, renal derangements which are occasioned either by an undue determination of blood to the organs (active congestion), or some mechanical obstruction to the return of blood from the organs (passive congestion). Renal congestion, both active and passive, if sufficiently intense, is attended by the presence of albumen in the urine (generally in small quantity), sometimes with blood, and casts of the uriniferous tubes. Dropsy is not a symptom proper to renal congestion; when present it depends on other causes, com- monly heart or lung disease. Active congestion is produced by — overdoses of certain irri- tants (cantharides, turpentine, etc.); by exposure to cold; it is a common instance in all febrile and inflammatory complaints; it occurs in saccharine diabetes; probably in some cases of hyper- trophy of the left ventricle; and it is found also in the opposite kidney when one kidney has become disabled. Passive congestion accompanies — regurgitant heart disease; obstructions in the lungs (emphysema, pleuritic effusion); pres- sure on the emulgent veins or inferior cava (pregnancy, abdomi- nal tumors). If the determining cause of the congestion be a persistent one — as in valvular heart disease or diabetes, organic changes are at length produced in the kidneys, which bear a strong resemblance to, if they are not identical with, certain forms of B right's disease. Accordingly, several of the conditions here considered have been arranged by other writers (Johnson, Frerichs, Griesinger, 358 CONGESTION OF THE KIDNEYS. Bamber2:er, Wagner) among the varieties of B right's disease. But although there are unquestionable affinities between the two classes of cases, there are also differences so marked, in their symptoms, progress, and general clinical history, that it only tends to confusion to unite them under one heading. It will greatly facilitate our comprehension of the relations subsisting between certain changes in the composition of the urine, and certain disturbances of the renal circulation, if we take a review of the experimental researches which have been made in this direction. Mr. George Robinson was the first to demonstrate, that a complete or partial impediment to the return of blood by the renal veins caused albumen, blood, and sometimes fibrin to appear in the urine. He operated solely on rabbits. In one set of experiments, he placed a tight ligature round the renal vein : in a second set, the obstruction was made incomplete — a certain amount of blood being still permitted to circulate through the kidneys. In both these sets of experiments the urine invariably became more or less albuminous, and in most cases bloody. The kidney, of which the vein had been thus obstructed, M'as in every instance found heavier than its unin- jured fellow. The proportion between them varied from 1 J : 1 to 3 : ] . Frerichs repeated these experiments on dogs, rabbits, a cat, and a frog, with identical results. In four out of ten experi- ments, he also detected casts of tubes in the urine, and in one, renal epithelium. Weissgerber and Perls, Posner, and Ger- mont^ have repeated these experiments and have obtained similar results. The experiments admit of easy explanation. The blood accumulates behind the impediment, and causes an increased lateral pressure upon the walls of the renal vein and its branches. This tension is transmitted backward to the renal capillaries, which are thereby distended, and their walls attenu- ated, creating a condition highly favorable to the transudation of the serous constituents of the blood through their coats. If the tension be sufficiently great, blood corpuscles escape from the vessels either by diapedesis or actual rupture, and pass with the albumen into the urine. It is probable that these conse- quences take efl"ect earliest in the tubules of the medullary portion of the kidney, for with these the branches of the renal vein come into close relation; thence the pressure is transmitted through the renal capillaries to the Malpighian clusters, where there exist anatomical facilities for ready passage of blood into the urine.^ Cohnheim is of opinion that it is not the mere 1 Theie De Paris, 1882. " See Senator, Die Albuminuric, 1882. EXPERIMENTAL RESEARCHES. 359 increase in blood-pressure which causes alljuriien to transude, but a coincident alteration of the epithelium covering the glo- merulus. Increased pressure in the arterial system does not so easily cause albumen and blood to appear in the urine. Kobinson sought to test the eftect of increased arterial pressure on the composition of the urine, by directing a stronger stream of blood than natural into the kidneys. First he removed one kidney, thinking that the physiological determination to the other might suffice to cause albuminuria. The experiment was repeated five times, and only in one instance did the urine become albumi- nous. He then removed one of the kidneys and tied the abdo- minal aorta below the origin of the renal arteries.^ In this way the utmost impulsion of blood into the remaining kidney was obtained, and both blood and albumen invariably made their appearance in the urine. His seventh experiment is a fair sample of his results. Expt. 7. The left kidney of a middle-sized rabbit was removed, and weighed 54 grains. The aorta was then tied below the origin of the renal arteries. The animal was killed at the end of two hours. The right kidney weighed 85 grains ; it contained six or seven ecchymoses of various extent. The bladder contained about a drachm of urine, which was bloody and albuminous (loc. cit., p. 79). These results have been confirmed by Frerichs and Meyer. In the experiments of Hermann and Overbeck, another method of inducing artificial albuminuria is pointed out. Her- mann's method consisted in tying up the renal arteries for a short time, and then removing the ligature. The urine which was secreted after the reestablishment of the circulation was always found albuminous. Overbeck interrupted the circula- tion in other ways. In one set of experiments, he blew up a bladder previously introduced empty into the heart; in the second set, asphyxia (and consequent arrest of the blood-current) was produced by compressing the trachea. In the former case the obstruction was maintained for about a minute, and in the latter for four minutes. In both classes of experiments, the urine which first flowed after the renewal of the circulation was invariably albuminous, and often bloody. The albuminuria thus provoked, generally lasted a few hours, and then passed away. When desquamation of the renal epithelium occurred, it always /o/foiyecJ the appearance of the albumen. It could not ^ Tying the abdominal aorta without removing one of the kidneys was per- formed twice by Eobinson on weak animals; in one only did albumen appear in the urine. Frerichs states that he could onl3' find traces of albumen in a few cases afier such an operation. Me^^er, on the other hand, saw abundant albumi nuria follow this operation. 3G0 CONGESTION OF THE KIDNEYS. therefore be the cause of it, as Johnson surraised to be the case in the albuminuria of Bright's disease. To explain the results obtained by Hermann and Overbeck, it may be supposed that the temporary stoppage of the blood- current created an obstacle in the renal capillaries — probably an accumulation of blood-corpuscles in the Mai pighian tufts — which, when the circulation was restored, operated to raise the pressure in the minute arteries; in other words, it produced active con- gestion of sufficient intensity to cause albumen and blood to appear in the urine.^ My purpose in calling attention to these researches is to show, that simple hyperaemia or congestion of the kidneys (without inflammation), either from increased impulsion of blood into the kidneys, or from obstruction to the return of blood from the kidneys, is sufficient to determine the appear- ance of albumen and blood and even fibrinous casts in the urine. An impeded circulation through the kidneys cannot, how- ever, long persist, without inducing serious and permanent structural changes in the organs. The presence of blood-cor- puscles, and iibrinous plugs, in the delicate tubular structures, must at length occasion more or less extensive destruction of these structures; and the continued hypersemia must derange the nutrition of the glandular elements. How far these changes are of an inflammatory nature, cannot be precisely indicated. One of the most important results of a long continuance of this state of things appears to be, an excessive production of adven- titious connective tissue, which eventually passes on to contrac- tion and atrophy. To call these changes, " nephritis," is to use a term, which, to say the least, is calculated to mislead. ACTIVE CONGESTIOlSr. {Catarrhal Nephritis of Virchow.) In the course of eruptive and continued fevers, of croup, diphtheria, cholera, erysipelas, pyfemia, acute rheumatism, pneu- monia, and other inflammatory diseases, the kidneys partake in the general hyperaemia of the internal organs. JSTot unfre- quently, however, they are the seat of a disproportionate deter- mination of blood, and albumen appears in the urine. Generally speaking, the amount of albumen, in such cases, is a mere trace, but sometimes it is more abundant, and accompanied with a few blood-corpuscles, transparent casts of tubes, and scattered renal epithelium. There may be, at the same time, some tenderness ' For other possible explanations, see p. 203. ACTIVE CONGESTION. 361 in the loins. As soon as defervescence commences, tiie albumen diminishes, and in a few days vanishes alto^^^ether. The pathological state here described differs from genuine Bright's disease, which may likewise arise in connection with the same febrile maladies, in the absence of anasarca, in the un- diminished excretion of urea, and in the period of its invasion. Albuminuria from congestion coincides with the acme of the pyrexia, and subsides therewith. Genuine Bright's disease, on the contrary, shows itself as a sequela, toward the close of the pyrexial stage or the commencement of convalescence. An examination of the kidneys of persons who have died from the primary fever while laboring under renal congestion, reveals an enlarged and engorged condition of the organs, with minute ecchymoses on the surface, and great engorgement of the stellate veins. A large amount of blood flows from the cut surface of the kidney, and the glomeruli and accompanying vessels stand out as red points and streaks. On microscopic examination, the vessels of the glomeruli and the intertubular capillaries are swollen and gorged with blood-corpuscles, while numerous blood-corpuscles are seen in the lumen of the tubules and between the glomerular tuft and its capsule ; the epithelial cells are swollen, very granular, sometimes show signs of fatty changes, and are frequently detached. The frequency of this complication in zymotic diseases, varies in different epidemics. Rosenstein states that in a severe typhus epidemic, witnessed by him in 1857, the majority of the patients had transient albuminuria, with casts of tubes, and yet no serious consequences followed therefrom. In the sporadic typhoid of this city, albuminuria is decidedly rare. Active renal congestion of a catarrhal nature, maj^ also arise independently of any specific fever, simply from exposure to cold. Such cases are not very common, or perhaps, as Rosenstein sug- gests, they are often overlooked. The symptoms resemble those of a simple febricula, and, unless the urine chance to be ex- amined, the disorder will probably be passed over as such. The following example is from Rosenstein : A. B., oet. 39, previously healthy, experienced on the afternoon of the 7th of October a chill, followed by heat and severe pains in the renal region, which were accompaui<=d with vomiting. When seen she was in a high fever, pulse 120, very thirsty, and without appetite. The urine was scanty, acid, albu'minous ; after standing, it deposited a sediment composed of uric acid, blood-corpuscles, epithelial casts, and free epi- thelium. Pressure on the renal region caused pain. She was cupped on the loins. On the following day the urine measured 27 ounces, specific gravity 1026, otherwise as before reported. On the 16th, the pulse was 92, skin moist and perspiring, general condition good. Urine in twenty-four hours, 28 ounces, specific gravity 1025, acid, free from 362 CONGESTION OF THE KIDNEYS, albumen, containing only a few casts. On the succeeding days increased diuresis in, with diminished specific gravity of the urine. The urine continued free from albumen and formed elements (p. 98). Cases of a similar nature connected with subacute rheumatism are not very uncommon. The following, which I saw with the late Mr. Mellor, may serve as an example : The patient was a young lady of 26, who had been subject, for several years, to frequently recurring attacks of subacute articular rheumatism, which kept her in a continuously weak state of health. On April 14th, she took cold through walking in the wet, and was seized with tonsillitis. As this subsided, the urine was noticed to be bloody and to contain albu- men. On the 15th of May I saw her for the first time, bhe was very pale and thin ; there was considerable fever, pulse 108, the loins were painful and very tender on pressure, skin dry, with a tendency to fre- quent vomiting. Micturition was very frequent (20 times a day) ; the urine amounted to three pints in the twenty-four hours, specific gravity 1010; it contained a good deal of blood and albumen, and deposited uric acid very abundantly. The copious deposit which subsided when the urine was left in repose, contained numerous large transparent casts (some studded with epithelium) and much free renal epithelium. Neither casts nor epithelium showed any signs of fatty degeneration. There was also found a large number of pyelitic cells. Not a particle of dropsy or anasarca existed in any part. The patient was dry-cupped over the loins, after which hot poultices were directed to be kept (frequently renewed) to the same region ; a compound jalap powder was administered, and a citrate of potash mixture. In four days the fever subsided, the pains disappeared, and the skin became moist. At the same time, the urine was far less frequently passed, and it contained much less blood, albumen, and casts. It still continued abundant in quantity, and deposited uric acid very copiously. In the course of four weeks, convalescence was so decidedly estab- lished, that the patient was allowed to sit up. The albumen now scarcely exceeded "a haze" with nitric acid. She was put upon a phosphoric acid mixture, combined with phosphate of iron. On June 24th the patient suffered a relapse. She was again confined to bed, and the previous treatment put in force. In a few days the feverish symptoms passed off; but a good deal of blood, albumen, and renal derivatives continued to be discharged. She was now put upon gradually increasing doses of dilute sulphuric acid, with most excellent effect. The urine steadily resumed its natural characters, and the patient's appetite and strength began to return. . On the 24th of July the urine had become free from albumen and blood, and convalescence was thoroughly established. The case was, from the beginning, regarded as distinct from genuine Bright's disease, and considered as presenting the fea- tures of a catarrhal (rheumatic?) condition of the pyramidal ACTIVE CONGESTION. 363 parts of the kidneys, combined with some dcc^ree of subacute pyelitis. The total absence of anasarca, and the /2;eneral ])or- traiture of the complaint, forbade the idea of acute Bri^^ht's disease; while the state of the urine and tlie progress of the case ajipeared inconsistent with the chronic forms of that formid- able disorder. Certain irritants — cantharides, turpentine, cubel)s, copaiba, nitrate of potash, and carbolic acid' — act as s|)ecial stimuli of the urinary organs; and excite, when administered in excessive doses, liemorrhage from the kidneys and the lower urinary pas- sages. Johnson relates an instance in which half an ounce of turpentine was taken for the expulsion of tape-worm. In a few hours the urine was bloody, and in the deposit "blood-casts" were discovered, together with a few small inflammatory cells, but no epithelium. Six days after, the urine contained less blood and albumen. The casts of tubes were still visible, and contained, besides the blood-corpuscles, a large proportion of inflammatory cells about twice the size of the blood-corpuscles.^ The patient continued to pass more or less blood for some days longer. On the sixteenth day the urine was free from albumen and blood, Bouillaud examined the effects of cantharides acting through the skin. He states that, almost constantly, when large blisters were applied to scarified portions of the skin, albumen appeared in the urine. After death, he found the mucous membrane of the pelvis and ureters, in other cases that of the bladder, in- jected, and covered here and there with false membranes. The kidneys were generally stroHgly congested and studded with minute ecchymoses. Albuminuria after cantharides usually- disappeared in tw^o or three days ; in a few cases it lasted four weeks. Two cases of poisoning by sulphuric acid are related by Leyden and Munk, in which albumen and casts appeared in the urine. ^ Cases have also been described in which the external appli- cation of tincture of iodine, of styrax, and of petroleum, have given rise to albuminuria. Frerichs enumerates irritants of this class among the exciting causes of genuine Bright's disease; and brings forward two cases by Eeinhardt, in which abuse of copaiba and cubebs was 1 Quinine in very rare cases produces congestive liEematuria. This effect ap- pears ti) be due to an idiosyncrasy. I liave known one such person. Two cases are also reported in the Brit. Med Journ. for Januarj', 1870. ^ Were not these renal epithelia? 3 Archiv f. path. Anat , Bd. xxii. S. 237. Hydrochloric acid also caused albu- men, casts, and blood to appear in the urine, in a case reported by Gehle, Berlin, klin. Wochenschr., 1884, No. 22. 3(i4 CONGESTION OF THE KIDNEYS. followed by renal degeneration, which in one of them proved fatal. These cases are, however, as Rosenstein points out, in- conclusive, because it is probable that the kidneys were already diseased before the use of the irritants was commenced. More recent experiments have shown, that genuine organic change in the kidneys may be produced by the internal administration of irritants ; although the exact nature of the change is a matter of dispute amongst the several observers. Cornil,^ by giving cantharides to animals, pro- duced marked alterations in the epithelial cells, such as are found in parenchymatous nephritis. The cells were swollen, completely filled the lumen of the tubules, and contained fat granules and occasionally red blood-corpuscles. In many cells, too, e;lobules of a hyaline material were seen. Similar epithelial changes were found by Browicz.^ Dunin* describes changes in the cells, due to "coagulative necrosis." Aufrecht,^ on the other hand, found interstitial nephritis, and succeeded in pro- ducing even a granular kidney. It is probable that the nature of the change depends on the dose of the poison and the method of its admin- istration, small doses producing mere congestion, larger doses the epithe- lial changes, while small doses given repeatedly cause an overgrowth of interstitial tissue. In a previous section it has been mentioned, that in the later periods of diabetes, albumen not unfrequently appears in the urine. The excessive action of the kidneys in this disease, keeps up a constant congestion of the organs: and, in the course of time, permanent anatomical changes follow — degeneration of the epithelium, increase of interstitial tissue, development of cysts, and other structural alterations, w^hich are sometimes classified with genuine B right's disease. There is yet one other condition which seems capable, in rare instances, of producing an active congestion of the kidneys, sufficiently intense to determine albuminuria. In the compen- satory hypertrophy of the left ventricle, which follows aortic regurgitant disease, the propulsion of blood into the aorta (when the orifice is patulous) takes place with very great force; and the tension of the arterial system at the close of the ventricular sys- tole, rises considerably above the normal maximum, as is indi- cated by the full resistant pulse.^ Practically, however, albu- 1 Journal de I'Anatomie, 1879, p. 402. 2 Centralb. f. Med. Wissensch., 1879, p. 145. » Virch. Archiv, vol. 93, p. 318. * Centralb. f. Med. Wissensch., 1882, p. 849. ^ It is not probable that the mean lateral pressure in the arterial system can ever be raised above the normal degree in compensatory hypertrophy of the left ventricle ; but it is quite conceivable and agreeable to clinical facts, that the maxi- mum tension (attained at the close of the systole) may be excessive, and be counterbalanced, or more than counterbalanced, by undue diminution of tension during the ventricular diastole. PASSIVE CONGESTION. 'J65 minuria traceable to hypertrophy of this kind, is rare. I have repeatedly examined the urine of persons with irnrncnHC enlarge- ment of the left heart, without finding albumen in more than three or four instances. The following is one of these, in which no tenable explanation of the albuminuria could be found except renal congestion from excessive power of the left ventricle. T. H., set. 21, a warehouseman, came under treatment February, 1864, suffering from immense cardiac hypertrophy. The apex beat in the seventh interspace almost in the axillary line, and seven and a half inches from the mid-sternal base. The impulse was strong; the whole body shook at each beat of the heart. The pulses were visible in all the superficial arteries. A loud to-and-fro, roughish murmur was heard over the aortic cartilage, of which the diastolic part was greatly pro- longed. This murmur was heard loudly at the base, but grew weaker toward the apex — beyond which it ceased to be audible. The valvular mischief seemed to be confined to the aortic orifice. There was no sign of serious mitral regurgitation nor any indication of impediment on the right side of the heart. There was total absence of a cyanotic tint; on the contrary, the face was pinkish pale, and the margin of the lips and tongue were of a faint rose; there was no swelling of the veins of the neck nor a trace of anasarca. On the other hand, the pulse was hard, resistant, bisferiens, ranging from 92 to 104. The character of the urine was highly significant. It was not high-colored and scanty, as in venous congestion, but abundant, pale, and of low specific gravity. The daily discharge varied ftom 57 to 65 ounces, the specific gravity from 1010 to 1015. It contained albumen, but only in small quantity ; gen- erally only a haze was produced with nitric acid ; no tube-casts or other renal derivatives could be detected, though often looked for. It was distinctly observed that the proportion of albumen oscillated in accord- ance with the activity of the heart. When the ventricle was in high action the albumen rose ; when it became more quiescent, under the influence of rest and digitalis, the albumen almost vanished for a time. I have recently seen this patient again (March, 1865) and find that his state is still as above described ; there is a trace of albumen in the urine ; but the general condition is wonderfully good. The treatment of active renal congestion will be described with that of passive congestion, at the end of the next section. PASSIVE CONGESTION. The experiments of Eobinson and Frerichs, already cited, show that an impediment or obstruction to the return of blood from the kidneys induces passive congestion of these organs, and, if sufficiently intense, causes albumen and blood to appear in the urine. An impediment of minor degree does not render the urine actually albuminous, but causes it to become scanty, high-colored, dense, and prone to deposit abundance of lithates. 366 CONGESTION OF THE KIDNEYS. Both these degrees of obstruction are frequently witnessed in clinical experience. The obstruction may be seated in the chest, as in cases of valvular heart disease, emphysema, and pleuritic effusion : or in the abdomen, as when a gravid uterus or other tumor presses upon the emulgent veins or the upper course of the inferior cava. Sometimes a cirrhotic liver compresses the latter vein as it lies in the hepatic fossa. The alterations on the side of the urine are not always pro- portional to the degree of obstruction to the circulation. Cases are met with, in which venous stagnation exists in an intense degree, with dropsy, orthopncea, and pulsating jugulars, with- out a trace of albumen in the urine, and others in which the urine changes are strongly marked, while the more general symptoms of venous obstruction are only moderately so. The two examples which follow, afford good illustrations of an unusual degree of renal derangement, secondary to obstruc- tion to the circulation within the chest. In the first case the obstruction was due to old-standing tricuspid regurgitation; in the second to extensive emphysema. Case 1. — A lawjer's clerk, set. 44, came under observation December 6, 1862. He was suffering from oedema of the legs, ascites, and a severe bronchial attack. The features were livid ; but the veins of the neck wer-e not distended. The heart's apex beat in the fifth interspace, a little outside the nipple line. The cardiac dulness extended four inches vertically, and, about the same diagonally from base to apex. The heart's action was very irregular both in force and rhythm ; pulse was 104. A loud blowing murmur was heard at the apex, of mitral regurgitant character, associated with a faint diastolic bruit, which was heard in maximum intensity over the second right costal cartilage. Loud bronchitic rales were heard universally over both lungs. There was copious mucous expectoration, sparsely speckled with blood ; also severe dyspnoea, amounting at times to orthopnoea. The urine was scanty, reddish, specific gravity 1025, with abundant clouds of lithates. It contained a small quantity of albumen (equal to about i). The deposit, examined under the microscope (see Fig. 49), revealed numerous scattered blood-disks ; casts of tubes, mostly per- fectly hyaline, sometimes only visible when tinted with magenta; some casts were dotted with withered renal epithelia or with the nuclei of these; no oily or fatty particles were found. On tracing back the patient's history, it appeared that he had had five attacks of acute articular rheumatism, of which the earliest occurred in his twentieth year. In one of these the heart had become affected. The cyanotic appearance and dropsical symptoms had shown themselves some months previously, but had suddenly assumed a formidable in- tensity a fortnight before, in consequence of a bronchitic attack. With rest and other appropriate means, the bronchial attack subsided in about ten days. The dropsical and dyspnoeal symptoms receded, and a PASSIVE CONGESTION, 367 moderatelj' quiescent state was attained. The urine underwent corre- sponding change ; it became more copious, its density fell, and the albu- men faded to a mere trace ; the casts ren)ained as before. While under observation this man went through three bronchitic attacks. In each, the urine went back to the character given of it in Fig. 49. Casts of tubes and blood-oorpuscles from the urine of a patient witli passive renal congestion. the first report. In the intervals again, the albumen became very- scanty, and on two occasions the urine was found altogether free from albumen. Case 2.-— On October 16, 1862, a strongly built, stout woman, set. 42, was admitted into the Manchester Infirmary, almost in a state of asphyxia. She was intensely blue in the face; could only breathe in the upright posture ; her voice was a faint husky whisper; the tongue was livid; the veins of the neck were enormously dilated ; she looked like a person half choked. There was not a particle of oedema nor any ascites ; the limbs were firm and muscular. There was considerable drowsiness, but no actual coma. The sputum was frothy, not bloody. The examination of the chest revealed extensive capillary bronchitis, in emphysematous lungs ; both bases were somewhat dull. There were no cardiac mur- murs; the superficial cardiac dulness was inappreciable on account of the emphysema. The urine was dusky red, and gave a play of colors with nitric acid (showing bile) ; no sugar in it; it was albuminous to a considerable de- gree (^). In the sediment, which was abundant and composed of lithates, were found numerous tube casts— nearly all hyaline; some of them studded here and there with altered epithelium, or altered blood-disks ; a number of free cells were also found, most of them pus corpuscles, but some with solitary nuclei— evidently renal, and very little altered from their natural appearance. One cast was seen so studded with these as to deserve the name of an epithelial cast. Not a particle of fat was found in the renal derivatives. 368 CONGESTION OF THE KIDNEYS. On the next day but one (October 1 8) the patient seemed to breathe a little easier, but the surface was still intensely cyanotic. Of the urine, the notes state : " somewhat less highly colored ; very much less albu- minous, in fact the urine only becomes hazy with nitric acid ; casts and cells still abundant." Next day the breathing seemed again, if anything, rather easier, but the strength was evidently failing, and the drowsiness was becoming deeper. The urine no longer showed any bile tints, though still of a deep brown color. Albumen could only be discovered in it by very careful testing ; the casts had all but disappeared ; a few short frag- ments (slightly more granular than before) could with difficulty be found and identified. A few blood-corpuscles were seen after diligent searching. October 20th. — There was evident emaciation going on, and steady diminution of strength. Scarcely any nourishment had been taken since admission ; the voice was whispering, and the surface livid. The dyspnoeal symptoms were at a standstill; drowsiness on the increase. 21st. — The urine was now quite free from albumen, and no casts could be found in the deposit. In the course of the succeeding night the patient quietly died, as if in sleep, partly exhausted by want of nourish- ment and the efforts to breathe, partly poisoned by the raephitic condition of the blood. Autopsy, 18 hours after death. The heart weighed eleven ounces ; the valves were healthy ; a few slight atheromatous patches existed in the aorta. The lungs were in a state of excessive and universal emphy- sema ; they bellied out of the cavities, when the chest was opened, like bladders of air. Spots of intense congestion were found here and there on section, and the extreme bases were somewhat oedematous. The liver was enlarged and congested. The kidneys were considerably enlarged, and weighed together tAvelve ounces ; the capsules peeled off readily. On section the pyramidal and cortical substances were distinct from each other, and in due proportion ; both parts were intensely congested, but otherwise natural, both to the naked eye and to microscopical ex- amination. The body was still moderately well nourished ; there was no anasarca in any part, nor any ascites. There is one circumstance in this history v^hich at first sight appears contradictory, namely, the disappearance of the albu- men from the urine, notwithstanding that the obstruction in the chest persisted or even increased, and, indeed, brought the cir- culation ultimately to a standstill. The explanation of this occurrence is, I believe, to be found in the diminishing pressure in the arterial system from the gradual failure of the heart's power. Some of Robinson's experiments bear clearly on this point. He found, on ligaturing the renal veins in rabbits, that vigorous animals exhibited the urine changes (albuminuria, etc.) in far greater intensity than ?(jm^er animals; and he attributed the difference to the fact that in strong animals the powerful contractions of the ventricle served to maintain a greater coun- ter-pressure on the arterial side of the renal circulation, and in TREATMENT. 369 this way intensified the intrarenal pressure or congestion. In the patient before us the pressure on the arterial side was visibly declining from day to day, in conse({uence of tlie inability tfj take food, which diminished tlie mass of the blood, and the progressive poisoning of the blood (from defective respiration) which gradually depressed, and finally annihilated the con- tractility of the ventricle. The state of the kidneys in passive congestion varies with the duration of the obstruction. When the obstruction has been only recently established, as in the woman whose case has just been related, the kidneys are found simply enlarged and en- gorged; they resemble the kidneys of the rabbit, whose renal veins were ligatured by Robinson. They are dark in color, and on section a large quantity of dark blood exudes from the cut surface. Although the whole of the surface is redder than nor- mal, yet the congestion is seen to be most marked in the pyra- midal portion, where dark red, almost black streaks run from the apex to the base of each pyramid. The Malpighian corpus- cles do not present the prominence seen in active congestion. On microscopic examination the veins and capillaries are found to be gorged with blood-corpuscles, while round the vessels red blood-corpuscles may be seen in the neighboring tissue, and even in the tubules themselves. The tubules in many places contain hyaline casts, and the epithelium is usually granular and sometimes fatty. But when the congestion has been in existence for months or years, the kidneys are found to have undergone far more profound alterations. The organs may then be somewhat smaller than normal, but are invariably hard and tough. The external capsule usually peels off easily, and leaves on removal a smooth or slightly granular surface. On section, the same congested state of the pyramidal portion is observed. The proportion of cortical to pyramidal substance is not much altered, but in very chronic cases the cortex may be somewhat atrophied. On microscopic examination, the most characteristic lesion is a great increase on the interstitial tissue between the tubules and round the glomeruli. This tissue is composed of fully formed fibrous tissue, containing but few cells: the basement membrane of the tubules is also thickened and' passes into the thick interstitial tissue. The walls of the arteries are thickened, but there is no endarteritis seen. The convo- luted tubules themselves are some contracted, some dilated, and their cells are usually small and cubical. The exact nature of these latter alterations is a matter of dispute. Frerichs, Bergson, and Bamberger consider them as identical with those in the granular kidney of Bright's disease; but Traube contended that they were essentially different. Cornil is also of opinion that the lesion is not a nephritis. 24 370 CONGESTION OF THE KIDNEYS. Whatever anatomical difficulties there may be in the way of separating these cases from chronic Bright's disease; the clinical distinctions between them are clear and undoubted. Renal dis- order from passive congestion comports itself quite diiierently from Bright's disease of independent origin, and from Bright's disease coming on in the course of chronic disease of bone or phthisis. The contrast between the first and the third is very marked. In the first (passive congestion), the renal affection has no momentum of its own, and makes no independent prog- ress; it oscillates with the rising and falling intensity of the venous obstruction ; it remains throughout a subsidiary com- plication of the primary disease, and assumes none of the special characteristics of Bright's disease (ursemia, etc.). On the other hand, when renal disease declares itself in the course of chronic phthisis, it assumes at once a formidable position. The entire clinical complexion of the case is transformed. Sometimes even the pulmonary disorder is altogether supplanted and thrown into the background by the more rapid progress and fatal course of the renal disease. [See case of M. C. in Chapter IV.) Treatment of Congestion of the Kidneys. — Congestion of the kidneys, whether active or passive, does not often call for separate treatment. Its course and intensity are usually con- tingent on the progress of the primary disorder of which it is a secondary phenomenon. But sometimes active congestion has an independent origin ; in other cases, although secondary, it is sufficiently threatening to demand special attention. Passive congestion from cardiac and pulmonary obstructions can be most efficiently relieved by remedies applied to the primary complaints. But passive congestion from the pressure of a pregnant uterus — cases which will be considered at length in the appendix to this chapter — not unfrequently claims energetic treatment on its own account. The most efficient means of combating active renal conges- tion are complete rest of the body, cupping the loins, brisk purgatives, the warm bath, and other diaphoretics. In the passive cases, cupping can only be of service when the conges- tion is due to a temporary cause, such as pregnancy; in the more common cases, the application of gentle counter-irritants to the loins is more serviceable, namely, tincture of iodine, embrocations, etc. Derivation by the bowels and skin is also an important means of relieving the overloaded organs. APPENDIX. '371 APPENDIX. 071 the connection oj renal congestion, albuminuria, and BrighVs disease, lolth pregnancy and jnierperal eclampsia. The late Sir J. Simpson was, 1 believe, the first to call atten- tion to the occasional presence of albumen in the urine of preg- nant women. The subject has since been studied on many hands with a view to elucidate the connection of the puerperal state, and especially of puerperal convulsions, with Bright's Albuminuria does not usually show itself in pregnancy until the seventh or eighth month, and often not until the approach of labor. Sometimes, however, it appears earlier, even so early as the third month. It is generally attended with oedema of the lower extremities, sometimes also of the face and upper parts of the body. • i r Blot found among the patients of a lying-in hospital, that one pregnant woman in five had albumen in the urine: this estimate'is evidently very much too high for a general average. Abeille found, in private practice, the proportion to be one in ten ; and Vans Arsdale and Elliott, one in fifty-six. (" :N'ew York Journ. of Med.," 1856.) This last estimate is probably the most nearly correct. The albuminuria of pregnancy, and the accompanying ana- sarca, usually go on increasing up to the time of delivery, and then rapidly pass away. As a rule, the albumen is quite gone in forty-eight hours, sometimes even in twenty-four hours ; but it may not wholly disappear for ten or fifteen days. If it con- tinue beyond this last period, the gravest apprehensions of organic renal disease are justified. The urine in the condition in question is usually scanty, of high specific gravity and dark color, contains a large quantity of albumen and a 'little blood, and deposits hyaline tube-casts and urates on standing. Hiller found in one case crystals of haematoidin. If we inquire into the origin of albuminuria m pregnancy, two conditions present themselves, which, altogether or sepa- rately, are capable of explaining its occurrence : these are- (a) alterations in the circulation of blood through the kidneys, and (b) the alterations in the quality of the blood which are proper to the pregnant state. The older observers, and perhaps the majority of tlie modern writers, are of opinion that the principal change in the circula- tion of the kidney is passive congestion due to pressure of the uterus on the renal veins. According to this view, the growing 372 CONGESTION OF THE KIDNEYS. womb mounting into the abdomen necessarily exercises a certain compression on the contents of that cavity, and among other structures, on the inferior cava and renal veins. This mechanicaV pressure occasions a passive congestion of the kid- neys, which, if sufficiently severe, induces albumen to appear in the urine, together with blood and tube-casts. That this is one of the most efficient causes of albuminuria in pregnancy, is indicated by the fact that primiparse, in whom the parts are resistent, and the pressure therefore intense, are disproportion- ately liable to albuminuria; so, too, albuminuria is common where the liquor amnii is in excess ; and in twin pregnancies also albumen does not usually appear in the urine until the later periods of gestation, when the venous stagnation has reached its height. The recent observations of Le3^den have, however, caused doubts as to the correctness of the above view. From the results of several autopsies he showed that the kidney if ex- amined soon after delivery was large, the cortex swollen, pale and ancemic, and that the epithelium had undergone advanced fatty change. When examined at a greater interval from the delivery, the kidney was still pale, but had lost its swollen and fatty condition. The urine, too, differs from that of venous congestion of the kidneys, in containing a large instead of a small quantity of albumen. Leyden's description of the kidneys has since been confirmed by Hiller, but the cause of the anaemia of these organs is not clear. ^ Flaischlen has suggested that the anaemia may be due to irritation from the uterus acting reflexly on the vasomotor system and causing constriction of the renal vessels. Numerous other views have been put forth, but at present a groundwork of facts is wanting. The altered condition of the blood probably contributes more to the establishment of the oedematous swellings, especially in the upper parts of the body, than the mechanical pressure. The blood, in pregnancy, is poor in red corpuscles and more watery than natural — a condition highly favorable to serous transudation, and to the production of anasarca and albuminous urine. The expulsion of the foetus is, as has been stated, commonly the signal for the disappearance of the oedematous swellings, 1 Dr. Dickinson, in his work on Albuminuria, describes cases of the albuminuria of pregnancy in which the kidnej's were found pale and fatty, but he also gives a plate representing the kidney in another case, where venous congestion was well marked. brigiit's disease and pregnancy. 373 and the restoration of the urine to its healthy state; but in a certain number of cases eclamptic convulsions break out about the time of parturition, and of these about 30 per cent, prove fatal; in certain other cases the albuminuria does not disapftear after delivery, but persists, with or without dropsical effusions, until there is no longer any doubt that genuine and confirmed Bright's disease has been established. There has been much dispute as to the exact nature of the connection between the events here enumerated and the puer- peral state. It has been on the one hand alleged, and on the other hand denied, that the pregnant state is an effective ex- citing cause of Bright's disease; it has also been both alleged and denied that puerperal convulsions are of renal (uraemic) origin. There can be no doubt that many of the cases in which Bright's disease coexists with, or follows, the pregnant state, are examples of the coincidence of two mutually independent conditions. Pregnant women are, of course, liable, like other persons, to contract Bright's disease from any of its ordinary causes ; and, again, women who are already the subjects of Bright's disease may become pregnant. But after eliminating the cases belong- ing to these two categories, there are still, as I believe, a con- siderable number in which Bright's disease has been really caused by pregnancy. The Registrar-General's reports furnish some valuable evidence on this point. In the five years 1857-61, there were registered 6220 deaths from Bright's disease. Of these 3699 were males, and 2521 females — being in the propor- tion of 68 females to every 100 males; this was the relative proportion between the two sexes at all ages. But the deaths of women from Bright's disease during the child-bearing years of life (from twenty to forty-five) far exceeded this proportion — being as high as 80 women to every 100 men. After the age of 45, the proportion of deaths from Bright's disease sank again to 59 women for every 100 men. There seems no other con- clusion to be drawn from these numbers, than that the puerperal state is a prolific cause of Bright's disease. A certain number of pregnant women having albuminuria (probably about one in ten) are affected with epileptiform con- vulsions (or eclampsia) before, during, or after labor.^ It is a question of considerable interest whether puerperal eclampsia is due, or not, to uraemic poisoning. The affirmative has been warmly supported by Frerichs, Braun, Litzmann, ^ The liability of albuminuric pregnant women to eclampsia is estimated at a much higher rate than this by Blot, Mej-er, and Devilliers and Eegnauld. The united statistics of these observers give a proportion of about 1 in 4. Taking all pregnancies together — with and without albuminuria — about 1 in 500 are com- plicated with eclampsia. Braun gives the proportion as 1 in 545. 374 CONGESTION OF THE KIDNEYS. Wieger, and others ; and the negative by Scanzoni, Depaul, Rosenstein, and several more. On the affirmative side it has been shov^^n : (1) that eclamptic fits are similar, symptomatically, to ursemic convulsions ; (2) that albumen is almost invariably present in the urine of eclamptic patients; and that in several cases undoubted evidence of or- ganic kidne}^ disease has been found after death ; (3) that, fre- quently, anasarca of the upper parts of the body, and dryness of the skin, coexist with albuminuria, and confirm the diagnosis of Bright's disease. On the opposite side it is alleged : (1) that there are authentic instances (apart from epilepsy, apoplexy, or hysteria) of puer- peral eclampsia without albuminuria;^ (2) that anatomical evi- dence of Bright's disease has only been found in a minority of the cases ; that more frequently the kidneys have only been found congested without any organic alterations which could be identified with any form of Bright's disease ; (3) that other causes (than Bright's disease) have been repeatedly found in the bodies of persons dying of puerperal eclampsia, namely, oedema of the brain, and congestion of the meninges, which probably were not without concern in bringing about the attacks. The want of segregation of irrelevant cases prevents the pos- sibility of a clear analysis of the facts adduced in this dispute. But it is evident that the existence of well-attested cases of eclampsia without a trace of albumen in the urine, is fatal to the universality of the ursemic theory. On the other hand, the not infrequent coexistence of undoubted Bright's disease, leads strongly to the conviction, that, in many cases, the convulsions are truly ursemic. It must not, however, be forgotten, that pregnant women who are the subjects of confirmed Bright's disease frequently pass through labor without the least convul- sive disturbance. As the evidence now stands, puerperal eclampsia cannot always be attributed to one and the same invariable cause. In some instances, the convulsions appear to be essentially of a reflex character, arising from irritation of the generative organs, acting on a nervous system in a state of exalted sensibility. It is at the period when this sensibility attains its maximum, namely, during the act of labor, that convulsions usually break forth. But it is likewise about the same period that the pres- sure within the abdomen becomes most intense, and the stagna- tion in the renal veins and interruption to the secretion of urine most complete. When the act of birth commences there are 1 Among other examples, the followina; may be referred to: Abeille, loc. cit., p. 607; Kiedel, Zeitschr. f. d. Gehurtscheilk., 1858, p. 13; Kossi, ibid., 1863, Bd. ii. S. 72. See, also, Schrdder, Ingerslev, and Lohlein, quoted by Wagner, loc. cit. PUERPERAL ECLAMP.yiA. 375 added to these cauBes of disturbance, violent and general mus- cular contractions causing sutiusion of the features and con- gestion of the cephalic meninges. Several explosive elements are thus brought together at the same period ; and it is scarcely to be wondered at, that the equilibrium of the nervous system should be thereby occasionally overset. The recognition of two or more categories of puerperal eclampsia, is of much importance both for prognosis and treat- ment; and the want of some rational classification of the cases is doubtless one cause of the discrepancies in the experience of different observers as to the beneficial effects of venesection and other plans of treatment. At least three categories seem to deserve to be recognized, viz., 1. Cases depending on confirmed and chronic Brighfs disease. In these the eclampsia must be regarded as mainly or wholly urse- mic; the ultimate prognosis is lethal, and depletive measures are less indicated than chloroform, etc. 2. Cases depe:}iding on 'passive congestion of the kidneys, or on a condition resembling, if not identical loith, acute BrighVs disease. These are usually primi- parse; the phenomena are probably partly ursemic, and partly reflex ; the prognosis is favorable, were the fits once over ; active depletive measures are indicated. 3. Cases depending on reflected uterine irritation and meningeal congestion. In these the urine is not albuminous ; the prognosis is favorable, were the fits over ; they call for active depletory measures. Something remains to be said in the way of diagnostic indica- tion, in cases of pregnancy complicated with albuminuria. The urine of a pregnant woman being found albuminous — how shall it be known, whether there exists confirmed Bright's disease or only a temporary disorder which will harmlessly sub- side after parturition ? The following points tell strongly for confirmed Bright's disease — an abundant flow of pale urine of low density ; presence of granular or fatty casts , a considerable amount of albumen and yet a relaxed state of the abdomen and tissues generally; anaemia; a markedly hypertrophied left ven- tricle ; anasarca equally distributed (or nearly so) over the whole body. The points which, on the other hand, tell in favor of con- gestion, or of acute (and curable) Bright's disease are : evident signs of severe pressure within the abdomen ; the patient being a primipara; the quantity of albumen in the urine appearing to bear a proportion to the existing venous congestion : the urine being high-colored, scanty, and dense ; the anasarca being mostly, or altogether, confined to the lower extremities ; absence of anaemia and cardiac hypertrophy. By attention to these points I have been able, in the cases which have fallen under my observation, to frame a diagnosis which the event has justified. CHAPTER II. BRIGHT' S DISEASE. PEELIMINAEY EEMAKKS. Cases characterized by albuminuria and dropsy, depending on structural changes in the kidneys, are classed together under the general title of Bright's disease. Several different pathological states are doubtless included under this designation ; and the cases present considerable diversity, not only in the acuteness of their course but also in their modes of origin and symptoms. Numerous attempts have been made to divide and classify the various conditions of the kidney found after death from Bright's disease ; and to connect each with its appropriate clinical history. Hitherto none of these attempts has obtained general assent; and a regrettable confusion of nomenclature has been added to the inherent in- tricacies of the subject. Notwithstanding the diversities just referred to, the points of resemblance between the several varieties of Bright's disease are so strong and so numerous, that they form an easily recognized clinical group. This re- semblance arises, in great part, from the circumstance that the structural changes in the kidneys, various as they may be, bring about the same ultimate results, namely, impoverishment of the blood from loss of albumen, with poisoning of it from retention within the body of the excrementitious matters of the urine ; and the more prominent symptoms in Bright's disease arise from this changed condition of the blood, rather than from the direct effects of the structural changes in the kidneys. Opinions are divided, in the first place, as to whether there be a fundamental unity beneath the apparent diversity; in other words, whether the " large, smooth, white kidney," the " small, smooth kidney," the " granular uncontracted kidney," and the "granular contracted kidney," are successive stages of one and the same pathological process, or represent radically distinct diseases. Dr. Bright, whose researches on this subject have made his name so renowned in medical science, expresses himself quite doubtfully on this point. In his introductory remarks to the twenty-three cases tirst published by him, in 1827, he says: PKELIMINARY RKMAKKH. 377 " From the observations which I have mado, I have boon led to believe that there may be several forms of disease to vvhicli the kidney becomes liable in the progress of dropsical affections. I have even thought that the organic derangements which have already presented themselves to my notice, will authorize the establishment of three varieties, if not of three completely sepa- rate forms of diseased structure." But toward the close of the same remarks he observes: "Although I hazard a conjecture as to the existence of these three different forms of disease, I am by no means confident of the correctness of this view. On the contrary, it may be that the first form of degeneracy to which I refer never goes much beyond the first stage; and that all the other cases, together with the second series and the third, are to be considered only as modifications, and more or less ad- vanced states of one and the same disease." (Reports, pp. 67 and 69.) Soon after the period when these sentences were written, a new vantage ground for the study of renal diseases was acquired by the researches of Mr. Bowman, which threw a strong light on the intricate anatomy of the kidney. Histologists of emi- nence both in this country and Germany — Busk, Toynbee, Simon, Henle, Rokitansky, Virchow — and inquirers who have made the subject a special study — Johnson, Frerichs, Bash am, Dickinson, Grainger Stewart, and many more — have worked with unexampled perseverance to ascertain the nature and arrange the varieties of the morbid processes taking place in the kidnej^s in Bright's disease ; and yet the doubt which pos- sessed the mind of Bright has not been wholly cleared away. All this labor has not, of course, been thrown away. On the contrary, much light has been shed on the pathology of the complaint ; and data of importance have been obtained for prognosis and treatment. More especially the examination of the organic admixtures of the urine — renal epithelium and casts of the uriniferous tubes — has yielded to Dr. Geo. Johnson re- sults of the highest clinical value, which claim for him a pre- eminent mention in this field of pathology. Frerichs considers that Bright's disease is essentially one, and that it is of an inflammatory nature. He divides the ana- tomical changes in the kidneys into three forms, which he re- gards as stages of the same fundamental process, namely : • 1. The stage of hypersemia and commencing exudation. 2. The stage of exudation and commencing change of the exudation. 3. The stage of degeneration and atrophy. Dr. Johnson, on the other hand, recognizes several distinct processes under the common heading of Bright's disease — but chiefly two, and both of an inflammatory nature — one charac- 378 bright's disease. terized by a shedding and destruction of the epithelial lining of the uriniferous tubes {desquamative nephritis), and one without such desquamation, and affecting the intertubular structures of the organ (non-desquamative nephritis). He also gives a separate place to " fatty degeneration " and " waxy degeneration " of the kidney. Dr. Dickinson divides Bright's disease into three main varie- ties. 1. Tubal nephritis, in which the uriniferous tubes are the seat of an inflammatory action. This he subdivides into an acute and a chronic form. 2. Granular degeneration, in which there is increase and subsequent contraction of the intertubular matrix of the kidney. 3. Depurative disease, which is the name he gives to amyloid or waxy infiltration of the kidneys. Dr. Grainger Stewart suggests the name " Bright's Diseases " as more truly descriptive than the old designation " Bright's Disease." He classifies the cases as follows : 1. The inflammatory form, of which there are three stages — a. That of inflammation. b. That of fatty transformation. c. That of atrophy. 2. The waxy or amyloid form, of which also there are three stages — a. That of degeneration of the vessels. b. That of secondary changes in the tubes. c. That of atrophy. 3. T'he cirrhotic, contracting, or gouty form. In addition to these he described two mixed types, in which in the one case the waxy form, and in the other the cirrhotic form, is combined with the inflammatory form. It would lead me too far to discuss the merits of these and the many other classifications which have been put forth. I content myself with simply indicating the more important ones. In the following pages the subject wnll be treated from a clinical, rather than an anatomical, point of view, and the cases will be classified under the two main heads of acute and chronic Bright's disease. The former embraces a compact and universally recog- nized group, which formerly w^ent under the designation of "inflammatory dropsy." It corresponds to the acute desquama- tive nephritis of Johnson, to the first stage of Frerichs, and to the acute tubular disease of Dickinson, The latter includes the protracted cases, which either have lapsed into a chronic state from the acute form, or, which is far more frequent, have been chronic from the beginning. Three types of chronic Bright's disease will be recognized. 1. Cases which have lapsed from the acute state (kidney smooth, white, generally large, excep- tionally dwindled). 2. Cases which have been chronic from the beginning (kidney granular, red, contracting). 3. Cases GENERAL ETIOLOGY. 379 associated with waxy or lardaceous (so-called amyloid) degenera- tion of the kidneys. The presence of fat in the renal substance, and in the ci)ithe- lium of the tubes, is not special to any one type of renal degen- eration; but is found associated with anatomical changes of the most varied kinds : it has therefore no claim to a separate con- sideration. GENERAL ETIOLOGY OF BRIGHT'S DISEASE. The special etiology of the several types of Bright's disease will be separately considered in the twe following chapters, but it will be convenient in this place to consider some of the points bearing on the etiology of Bright's disease as a whole. The want of uniformity in our nomenclature of organic dis- eases of the kidneys has considerably lessened the value of the returns of the Begistrar-General in this field of pathology. Cases registered on the certificate of death as " Bright's dis- ease" are entered in these returns as "nephria;" but it is evident that the larger number, even of the cases recognized as Bright's disease during life, are not so registered, but are classified under the heads " nephritis " and " kidney disease." To obtain some idea of the prevalence of Bright's disease, let us take the numbers under these three designations. There were registered in England and Wales, in 1868 : 2076 deaths from " nephria," 495 deaths from " nephritis," 283(3 deaths from " kidney disease," — making a total of 5407. This yields only a proportion of 1.1 •per cent, of the total deaths from all causes — a number which is probably considerably below the true proportionate mortality from Bright's disease. Without admitting, with Mr. Simon, that two-thirds of the cases of Bright's disease run a latent or undiscovered course, it must be allowed that a very large number are overlooked in these returns, and are probably to be found among the 6284 entered as " dropsy," or among those entered under " convulsions," " pneumonia," and other head- ings.^ Bright's disease is about one-third more common among men than women (1215 men to 861 females). The excess of deaths ^ It is evident, however, that Bright's disease is gradually becoming better known in this country, and more frequently identified. In 1852, only 570 deaths were entered under "Nephria." In each successive j^ear the number rose, quite out of all proportion to the increase of the population, until in 1861 it reached 1148, nearly thrice as many as in 1852 ; and in 1868 it reached 2076, nearly four times as many as in 1852. Correspondingly, the entries under " dropsy " dimin^ ished, from 9788 to 7301, and to 6284 for the same three vears. 380 bright's disease. among males, although present at every age, is not equal at the different periods of life : it is most marked between the ages of forty-iive and sixty-five. The mortality from Bright's disease shows a progressive in- crease from childhood up to about the age of 50 ; in the succeed- ing 20 years the mortality continues steady, at a somewhat lower, but still high, rate; the next decade shows a decided diminution as regards Bright's disease, though the general mor- tality at this epoch is at its highest point. These tacts are ex- hibited in the following table: Table showhig the number of deaths registered as " Nephria " {Bright's disease) in England and Wales in 1868, at the different periods of life: Under 5 yrs. 5-15 yrs. 15-25 yrs. 25-35 yrs. 35-45 yrs. 45-55 yrs. 55-65 yrs. 65-75 yrs. 75 years and upwards. Total at all ages. Males . Females 41 34 60 39 87 68 157 133 216 160 247 147 225 148 133 97 49 35 1215 861 Both sexes . 75 99 155 290 376 394 373 230 84 2076 That complex of impressions which is familiarly known as taking cold is the common cause of Bright's disease in its acute form. Cold, operating more slowly and continuously, also con- stitutes a prolific source of chronic Bright's disease. Persons whose occupation exposes them to cold, wet, and the inclemen- cies of the seasons, without adequate protection — those who work in hot workshops, are in the habit of going to cool their reeking bodies in the open air — the indigent classes, who dwell in damp cellars, insufiiciently clad and ill-fed, amid dirt and squalor, furnish a large quota of victims to this disease. Dr. Johnson is at especial pains to explain the modus operandi of this frequent cause of renal disease. He contends that the defective action of the skin causes certain deleterious matters to accumulate in the blood, and that the burden of their elimina- tion is thrown upon the kidneys, which receive injury thereby. It is impossible to accept this view without great limitation, seeing that suppressed cutaneous transpiration ushers in a multi- tude of inflammatory and febrile conditions, without provoking renal disease. When a person " takes cold," it is a fact that the secretion of the skin is very much diminished or altogether sup- pressed: but it is not possible to predicate on what organ the injurious impression will ultimately settle — whether on the bronchial tubes, the pleura, the lung tissue, the kidneys, or some other organ or part of the body; so that it cannot be maintained that there is any special relation between suppressed cutaneous secretion and the genesis of renal disease. GENERAL ETIOLOGY. y81 2^he abuse of spirituous liquors ranks high U8 a doterrnining -cause of Bright's disease. Christisori estimates the proportion due to this cause, in Edinburgh, as three-fourths or four-iifths of all the cases; and he justly remarks that it is not hal>itual drunkards only who show this tendency to renal disease, but dram-drinkers, who are in the constant practice of using ardent spirits several times in the course of the day, without becoming actually intoxicated. "^ Malt liquors — though far less pernicious than spirits — are not without influence to produce Bright's disease when largely in- dulged in. In a journeyman baker, under my care at the Infir- mary, the disease was clearly traced to the habit of fuddling himself with beer from Saturday evening to Monday morning, which the patient had followed for several years. Very frequently, intemperate habits go hand in hand with a grimy skin and exposed occupation ; and the subjects of Bright's disease are found disproportionately numerous among laborers, well-sinkers, cabmen, carters, hawkers, glass-blowers, smelters, and puddlers. A large number of cases arise in connection with some C07i- stitutional vice, more especially tuberculosis or struma, and chronic lead poisoning. Among the easier classes, gout and constitu- tional syphilis are prominent antecedents. It seems now to be fully attested that ague may cause Bright's disease in its various forms.^ Chronic affections of the lower urinary passages (cystitis, stricture, etc.) frequently lay the foundations of renal disease. In a boy of seven, who died in the Royal Infirmary, a small stone no larger than an almond was found lodged near the neck of the bladder. Repeated sounding had failed to detect it during life; operation was consequently not performed. For some weeks before death, general anasarca had shown itself. The kidneys were found wasted to an extreme degree; the cortical substance was reduced to a thin edge no thicker than a shilling; the pel- vis of the kidney and the ureters were dilated, and their lining- membrane thickened and bathed in pus. In cases of this class there is a double influence tending to produce renal degenera- tion, namely, the long-continued exhausting suppuration and direct transmission of the inflammatory process by continuity of tissue. 1 Dr. Dickinson, in his work on Albuminuria, has, in an elaborate chapter, called in question the efficiency of intemperance as a frequent cause of chronic Bright's disease. I have examined his statements at length in a paper in the Brit. Med. Journ. for Nov. 4, 1871, — and have shown, conclusively as I believe, that the arguments he advances are inadequate to shake the old opinion. 2 A full account of the anatomical changes produced in the kidney by ague will be found in a paper by Kiener and Kelsch, Archives des Physiologie,'Feb. 18821 382 BRIGHT'S l^ISEASE. The use of mercurj^, which Wells and Blackall believed capa- ble of producing albuminuria and renal mischief, has not been found by observers of wider experience to have this effect. Raver and Desir, out of forty cases treated with mercury at the Hopital des Yeneriens, only found a slight quantity of albumen in two — in both of which its presence was accounted for by the existence of pus in the urine. Rayer further observes that he had for years used a multitude of mercurial preparations in the treatment of various diseases without ever having observed the production of dropsy. He also states that he had treated a large number of gilders affected with mercurial trembling, and that he had not seen a single case of dropsy with coagulable urine supervene during or after this trembling (see, also, p. 196, note), A certain number of cases of chronic Bright's disease present themselves, in which the most searching analysis fails to indi- cate the exciting cause of the disorder. In some of these the renal affection is only a part manifestation of some widespread cachexy, as an example (M. H.) to be related in Chap. IV., in which fatty degeneration coexisted in the heart, great vessels, brain, and kidneys. CHAPTER III. ACUTE BRIGHT' S DISEASE. Synonyms — Inflammatory Dropsy; Diffuse Nephritis; Acute Desquamative Nephritis (Johnson); Acute Tubal Nephritis (Dickinson). Anatomical Characters. — The kidneys are always more or less enlarged — sometimes to twice their natural size; their sur- face is smooth ; the capsule thin, transparent, and easily stripped off'; their color varies; it is generally a deep dusky red; but sometimes a light fawn, almost white; in other cases it is mottled red and white. The superficial veins are larger and more distinct than natural. When the kidney is cut open the cortical substance is found to be increased very much out of proportion to the pyramidal. The red congested kidney exudes a bloody sanies abundantly from the cut surface; a number of hemorrhagic spots may be generally seen scattered through the cortex or beneath the capsule. The surface of the section is dusky red, and studded with minute darker-red points, which are the engorged Malpighian corpuscles. The 'pale and the mottled kidneys present a contrast of color between the cortex and the pyramids. The latter appear unnaturally red, and from their bases radiating lines of red spread, fan-like, into the cortical substance. The cortical portion is smooth and white, or yellow- ish-white, and spotted like ivory. Under the microscope almost all parts of the kidney may be found affected, but in varying proportions in different cases. Usually the chief alteration is situated in the epithelial contents of the convoluted tubes. The diameters of these are increased, and in extreme examples to twice or even thrice their normal measurement. The epithelial cells are also increased in size, they cannot easily be distinguished one from another, and their free extremities are rounded. The striation of the protopilasm at the base of each cell is no longer seen, but instead an ex- tremely granular condition is observed, which in advanced cases gives place to a collection of fat globules. The nuclei of the cells may be hidden by the swollen protoplasm ; when seen, they are found to be greatly proliferated, and a division of the cell substance taking place round each nucleus, we have a multi- 384 ACUTE bright's disease. plication of the cells.^ Cornil has described in the cell-proto- plasm certain hyaline globules, which apparently proceed from the base to the free margin and discharge themselves into the lumen of the tubule. The epithelial cells may be so hypertro- phied as to fill completely the lumen of the tubule. More commonly the lumen is occupied either by accumulations of cells, consisting of detached epithelium and leucocytes, or by a fibrinous exudation, which in the higher tubules assumes a net or star-like arrangement; but lower down, and especially in the straight tubes, it forms glossy cylinders of various size, accord- ing as the tubes have preserved or have shed their proper lining. In the straight tubes the epithelium gives evidence of similar changes, but to a much less intense degree. Their larger bore and direct course favor the escape of the detached epithe- lium, so that some of them are partially or wholly denuded. In the later stages the cells of the convoluted tubules also break down, and Klein has described, in scarlatinal kidneys, a deposit of lime salts in the cells.^ The interstitial tissue of the kidney may be unaffected, but often shows an infiltration of leucocytes, even at a compara- tively early period. These are situated most commonly round the glomeruli constituting the so-called " pericapsular " neph- ritis; but later on cell-accumulation is found also between the tubules and around the arteries. The arteries and capillaries are distended with blood-cor- puscles, and more or less extensive rupture of the capillaries takes place. The hemorrhages sometimes form a marked fea- ture. Masses of red blood-corpuscles are then found lying in the intertubular tissue, distending the tubules themselves, and occasionally lying between the epithelial cells or embedded in the cell-protoplasm. Klein has described a hyaline thickening of the intima in the arteries, and more especially in the afferent vessel of the glomerulus. The nuclei of the endothelium and of the muscular fibres he also found in a state of proliferation. The morbid process seems to consist essentially in a catarrhal condition of the uriniferous tubes, with a prodigious swelling and proliferation of their epithelial elements. At the first, there is an inflammatory congestion of the organs with rapid swelling 1 A few observers, and most recently Cornil and Brault, have denied that such proliferation of the epithelium takes place, when the inflammation attacks a previously healthy kidney. 2 Litten also has described calcification of the cells. See Yirch. Archiv, Bd. 83, S. 508. 3 Many of the appearances described above have been made use of by some authors as the bases of a classification. Thus, Wagner describes four forms of acute Bright's disease. 1. The hemorrhagic-catarrhal. 2. The hemorrhagic- catarrhal with interstitial change. 3. The acute large pale kidney. 4. The acute lymphomatous kidney. It has not been thought advisable in a work like the present to attempt any classification of the anatomical features. ANATOMICAL ClI A K A CT E US . liH^ and rupture of the capillaries. On that follovvH incroaHed pro- duction of epithelial cells; these rnuhi[)ly, choke up and distend the uriniferous tubes, thereby conn)reHsinf^ the renal ca[)illaries and impeding the circulation through them. When this proliferation has reached a certain degree, the kidneys, which before were of a dusky red, become pale or mot- tled — not so much from an actual deficiency of blood in the organs, but rather, as Dickinson explains, from the white color of the masses of epithelium overpowering the natural red of the parts. The choking-up of the tubes with their own epithelium neces- sarily impedes the depurating functions of the kidneys, and the blood is poisoned with excrementitious matters. The urine becomes scanty in amount, and deiicient in its proper constitu- ents ; it carries with it, as it percolates the diseased ducts, loose epithelium, blood, and fibrinous exudation, or detaches whole tracts of the lining, all of which objects form an abundant grumous sediment in the urine. How soon the change from red to white takes place, depends on the rapidity of the multiplication of the epithelial cells. I have seen the bloodless condition reach an extreme degree in six weeks. Dr. Dickinson states that it may occur within four days. During recent years the attention of pathologists, and also of clinical observers, has been turned to the changes undergone bj- the glomeruli in certain cases of acute and subacute Bright's disease. When the conditions described above are present, the glomeruli are seen on the cut surface of the kidney, as red points; while under the microscope, the capillaries of the Mal- pighian tuft are found injected, and the space between the tuft and the capsule filled with red blood-corpuscles. In the cases of so-called glomerulo-nephritis the glomeruli appear as pale points on tlie section ; and extensive inflammatory changes are found in them, causing almost total abolition of their secreting power, while in the remainder of the kidney little or no change may be seen. The results of different observers show consider- able variance with regard to the exact changes found in the Malpighian corpuscle, but they may briefly be stated as follows : Most frequently an accumulation of cells is seen between the capsule of Bowman and the glomerular tuft. These cells con- sist of a few leucocytes escaped from the vessels, but for the main part, of cells resulting from a proliferation of the epithe- lial lining of Bowman's capsule. Proliferation has also been observed in the thin layer of epithelium covering the tuft and dipping between its divisions, and doubtless this contributes to the cell accumulation in the glomerular cavity. My colleague, 2o 386 ACUTE bright's disease. Dr. Leeeh,^ has described proliferation of both these layers in a case under his observation, and he was able also to trace the development of the cells into a mass of fully formed iibrous tissue tilling up the glomerular space. The glomerular tuft is compressed by the new growth, and the circulation through it is stopped. Hence, its pale appearance when a section of the kid- ney is made. But apart from any exudation between the tuft and the capsule, the circulation through the glomerulus may be interfered with by changes in the tuft itself. These changes are generally evident from the great increase in the number of nuclei in the tuft. The numerous nuclei may in part be due to a proliferation of those portions of the epithelial covering of the tuft which dip down between its several divisions. They may also be the nuclei of leucocytes escaped from the vessels. Ivlebs believed that they were due to inflammatory proliferation of the connec- tive-tissue cells binding together the divisions of the tuft. This view has received but little support, and, indeed, the existence of connective tissue in the normal tuft is denied. Another source of the numerous nuclei has been found in a proliferation of the nuclei of the capillaries themselves. Klein has shown that the capillary walls may be swollen and show the same hyaline change he has described in the afferent artery of the glomerulus. Fried- lander, too, has described changes in the interior of the capillaries of the tuft. In his cases the circulation through the tuft was stopped, not by pressure from without, for the vessels of the tuft were even larger than normal ; but by blocking of the capil- laries with a granular mass containing nuclei, and produced, as he thinks, by a thickening of the capillary wall.^ In the acute nephritis which accompanies or follows the infec- tious diseases, groups of microorganisms have been seen in the kidney. They may be situated in the bloodvessels, causing a thrombosis; or they may be seen in the urinary tubules, and within the epithelial cells. Course and Symptoms. — The invasion of the disease is com- monly abrupt, and traceable to some definite cause. A person takes cold, or falls into a fit of intemperance, and next morn- ing, or in two or three days, the face begins to swell, then the hands and bod}^ generally. In another large class of cases the disease breaks out daring convalescence from scarlet fever 1 On Glomerulo-nephrilis. Brit. Med. Journal, 1881, i. p. 994. 2 The principal works on Glomerulo-nephritis are the following : Klein, Keports to the Privy Council, 1876, p. 39. Greenfield (Atlas of Pa- thology, Syden. Soc). Waller, Journal of Auat. and Phys., vol. xiv. p. 432. Leech, Brit. Med. Journ., 1881, vol. i. p. 994. Klebs, Handb. d. Path. Anat., vol. i. p. 645. Langhans, Virch. Arch., vol. Ixxvi. p. 85. Litten, Charite Annalen, vol. iv. p. 30. Priedlander, Fortschr. d. Medicin, vol. i. No. 3. COURSE AND 8YM]'T0MS. 887 or — much less frequently — some other febrile or zymotic com- plaint. Acute Bright's disease is usually ushered in with chilliness or shivering, headache, nausea, vomiting, pains in the back and limbs, arrest of the cutaneous perspiration and oppression in the chest. Dr. Mahomed has made important observations on a pre-albuminuric stage of Bright's disease following scarlatina. He states that in the desquamative stage of scarlet fever, certain symptoms arise which are premonitory of the appearance of albumen in the urine, namely, high tension of the arterial system as measured by the sphygraograph, and transudation into the urine of the blood-crystalloids as tested by guai- acum and ozonic ether. The almost universal forerunner and probable cause of these symptoms, he says, is constipation. One day passed with- out an action of the bowels is sufficient to give rise to them. If a sharp purgative be administered these symptoms pass away ; if not, they are succeeded by the usual signs of severe renal disturbance. "When fairly established, the symptoms are exceedingly dis- tinctive. The countenance is pale and puffy, with a heavy stupid expression ; the limbs and trunk are anasarcous. The cedematous parts are resistant on pressure, and pit little or none. More or less effusion takes place into the serous cavities, especially the pleura and peritoneum. There is a general febrile movement; the pulse is hard, full, and of high tension, the appetite lost, thirst excessive; the skin is dry, and the whole surface blanched and tumefied. An un- easiness or dull pain is felt in the loins, and the renal regions are tender on pressure. The urine is of a smoky or dusky hue — in some instances dark brown like porter — from the presence of altered blood. On standing, it deposits a copious, flocculent, dirty-brown or chocolate sediment, like the settling from beef-tea. It is very albuminous; it may even become quite solid on boiling. The specific gravity, in the stage of increment, is usually above 1020, often much higher, mounting sometimes to 1030, and in one instance which occurred to me even to 1065. When of high density, the urine is proportionally scanty; it may not exceed 12 or 18 ounces in the twenty-four hours ; in extreme cases it may sink to 4 or 6 ounces, or be, for two or three days, altogether suppressed. The calls to void it are more frequent than in health, especially at night and in the recumbent posture; the patient has to get up three or four times in the course of the night to empty the bladder. The urine is generally acid, and surcharged with pigment; it often deposits the amorphous urates. Very rarely it is alkaline from fixed alkali. The 388 ACUTE BRIGHT'S DISEASE. natural urinous odor is lost; it has a faint unpleasant smell, which has been compared to that of the washings of flesh. The deposit when examined microscopically (see Fig. 50) is found to consist of blood-corpuscles, loose renal epithelium, free nuclei of these, tube-casts, shapeless masses of coagulated fibrine, and the broken debris of all these structures. There are also generally found epithelial cells from the pelvis of the kidney and the bladder. The renal epithelia vary a good deal in their appearance. Sometimes they look almost natural, only somewhat swollen and opaque. More frequently they are much broken down ; their nuclei are set free, or are only invested in part by the granular cell-contents which naturally surround them. The disintegrated epithelium forms an amorphous dark granular Fig. 50. Transparent, granular, blood and epithelial casts from a case of acute Bright's disease ; free renal epithelium ; and blood disks. debris scattered over the field. When very abundant, the epithe- lium communicates a milky appearance to the urine. The free nuclei greatly resemble red blood-disks both in shape and size, but they are devoid of the biconcave figure, and refract light more strongly. A solution of magenta tints them of a deep carbuncle-red. The free blood disks are frequently distorted. When the urine is of high density, they are shrunken, and often puckered at the margins ; on the other hand, when the urine is of a lower density, 1017 and under, they expand, lose their central depressions, and eventually burst, and cease to be recognizable. COURSE AND SYMPTOMS. 389 The tube-casts are al)uiidant, and of varied size and appear- ance. The most common are of " medium " size, transjiarent, beset with epithelial cells or blood disks. Mixed with these may be some " very large " and some " very small " hyaline casts, together with opaque granular casts (Fig. 50), Specks of oil are generally altogether absent ; sometimes, however, a few small ones are seen either on the casts or within the epithelia; but their number is always quite insignificant in the early stages of the disease. The proportion of albumen in the urine during the heiglit of the complaint varies, according to Frerichs, from 8.2 to 12.7, 17.5 and 24.8 per 1000. Christison found 27 and Heller 57 per 1000. The quantity lost in the twenty-four hours varies from 80 to about 400 grains (Frerichs, Gorup v. Besanez). The natural solid constituents of the urine are diminished in propor- tion to the obstruction in the kidneys. The excretion of urea falls to 100 or 200 grains (from 400 to 500 grains in health) and the inorganic salts are considerably lessened. Uric acid main- tains about its usual quantity. The blood becomes speedily deteriorated by the unnatural drain through the kidneys. It becomes more watery and poorer in albumen, while urea, uric acid, and the extractives are unduly accumulated in it. The blood-corpuscles diminish in number as the disease proceeds, and a generally anemic appearance of the body is produced. Fibrine is usually in excess, and the blood displays a buffy coat. The fat and inorganic salts retain their usual proportion. Frerichs supplies the three following analyses of the blood in the early period of acute Bright's disease : I. ir. III. Specific gravity . . . . . 1025 1022 1019 1000 parts of serum contained : Water 908.10 915 88 938.9 Solids . . . . . . 91.90 84.12 61.1 Albumen 81.40 72.00 51.7 Fat . . . . . . 1.42 1.58 \ q. Extractive matters and salts. . 9.09 10.59 j The pulse invariably shows high tension of the arterial system when examined by the finger or by the sphygmograph. In rare cases this may lead to a recognizable hypertrophy of the heart, even before the disease has passed into the subacute stage. Usually, however, cardiac hypertrophy is absent in acute Bright's disease.^ 1 See Wagner, Ziems. Cyclop., 3d ed., p. 131. Also Kiegel, Berl. klin. Wochen.,' 1882, No. 28, and Zietsch*. fiir klin. Med., 1883, p. 260. 390 ACUTE bright's disease. After the disease has persisted for a variable period of a few days. to some weeks, it proceeds to one of three terminations, viz., recovery, death, or lapse into the chronic state. When the case is about to terminate favorably, the urine in- creases in quantity to three or four pints daily ; its density falls below the natural mean (1012-1008); and the blood, renal ele- ments, and albumen gradually diminish and finally disappear from it. At the same time the skin becomes moist, and the serous effusions are reabsorbed. The rate of progress varies extremely. If albumen has totally left the urine in six weeks or two months, the recovery may be considered quick. The shortest period that I have known to elapse, from the first symptoms to complete reestablishment of the normal state, has been ten days. Some cases reach final recovery only after a protracted and interrupted convalescence of many months. The urine during this period continues abundant, of low density, occasionally of pink color from slight admixture of blood. The anasarca is also apt to recur and disappear, and recur again, perhaps several times, accompanied with febrile exacerbations of subacute char- acter. In one such case observed by me the symptoms finally subsided in five months. The patient was seen ten months later, and the urine found perfectly free from albumen. In a second case, a slight admixture of blood continued, in diminish- ing quantity, for more than twelve months. In both these instances, and in a third similar to these, the characters of the urine were uniform; it was copious (three or four pints daily), of low density, slightly mixed with blood, slightly albuminous ; the renal derivatives were devoid of fat, and, throughout the convalescence, comparatively scanty. Not unfrequently, in the ordinary course of recovery from acute Bright's disease, the renal elements — both casts and epi- thelium — show slight signs of fatty changes. This circumstance is apt to embarrass the diagnosis, and lead to the suspicion of the existence of confirmed and chronic Bright's disease, if the case first come under observation in this stage. The doubt can only be solved by watching the progress of the case for a week or two. But matters do not always take this favorable turn ; and two new orders of symptoms arise, and bring life into imminent peril, or involve it in destruction. These are secondai\y inflam- mations of the serous membranes and the lungs, and ursemic intoxication. Of the inflammatory complications, pericarditis is the most surely fatal, but it is rare. Pneumonia is more common; it breaks out without appreciable exciting cause, and usually runs a rapid course to a fatal end. Pleurisy and peritonitis are also DIAGNOSIS. -391 not unfrequeiit, but greatly Ighs to be feared. More or leHH bronchitis exists almost invariably. When the anasarca rises to an extreme degree, the integuments of the legs may inflame, and even mortity. These secondary inflammations are much more common in the later stages of chronic Bright's disease than in the acute disorder. The ursemic phenomena are due to the retention in the blood of the excrementitious matters of the urine. They consist in a train of nervous symptoms — headache, vomiting, diarrhoea, convulsions, and coma — which are frequent incidents, and much to be feared in acute Bright's disease. They usually follow an excessive diminution or suppression of the urine from the in- creasing obstruction in the kidneys. It will be more convenient to postpone their consideration to a future section, when urgemia, in connection with Bright's disease generally, will be discussed. Certain deviations from the usual course and symptoms are not unfrequently encountered. Although serous effusion gener- ally first shows itself in the face, under the eyes, and then invades the trunk and extremities, it may begin elsewhere — in the feet, hands, or scrotum ; or all parts of the body may swell up simultaneously. The effusion, too, may shift its place from time to time, or it may be poured out with disproportionate copiousness in certain localities (lung, pleura, submucous tissue of the glottis), and thereby determine sudden accession of alarming or fatal symptoms. The anasarca commonly disappears some days or weeks, or €ven many months, before the albumen has vanished from the urine; but sometimes the converse is the case, especially in individuals of lax frames and ansemic tendency. When cases of this latter class come under observation for the first time after the urine has become free from albumen, they are very apt to mislead, and their true nature can only be recognized by a careful sifting of the patient's previous history. Diagnosis.— The general symptoms, and the alterations of the urine, are so significant during the height of the attack, that the disorder can scarcely be confounded with an}^ other. But when the pyretic stage is passed, and the case becomes protracted, there is often great difficulty in determiningwhether we have to deal with the declining periods of an acute and curable dis- order, or w^itli a disease which has already lapsed into the chronic and irremediable state, or with a disease which has been chronic from the first. Chronic Bright's disease is subject to occasional febrile recrudescences, which are deceptively like an attack of the acute disorder. The signs that the disease is acute and recent are: free presence of blood and renal epithelium in the urine, absence of fat in the discharged elements, absence of 392 ACUTE beight's disease. long-standing complications, such as hypertrophy of the left ventricle, phthisis, caries, necrosis, and joint disease. A careful consideration of the previous history and of the ostensible cause of the disorder is, also, of diagnostic importance. The less clearly a case can be traced to a definite exposure to cold, a bout of drinking, or to scarlet fever, or some other zymotic disease, the more reason is there, pro tanto, to fear that confirmed Bright's disease is established. Prognosis. — Precise data concerning the fatality of acute Bright's disease are wanting. A large majority of the cases undoubtedly recover. Frerichs reckons the recoveries as two- thirds of the individuals attacked. Probably this proportion is below the truth if the scarlatinal cases be included. The signs of approaching resolution are: increased discharge of urine, diminished impregnation of it with blood and albu- men, subsidence of the febrile phenomena, of the anasarca and serous effusions, and restoration of the cutaneous transpiration. At the same time, the countenance loses its stupid expression and its anaemic hue, and resumes its ordinary healthy aspect. The coexistence of all these signs leaves no doubt of advance toward a favorable issue: but the occurrence of some of them without the others must not lead to too sanguine expectations. The anasarca may disappear totally, and blood cease to tinge the urine ; the quantity of the secretion may increase consider- ably, the pyrexia pass away, and the general well-being of the patient improve greatly; but if the urine continue to contain a considerable amount of albumen, there is strong reason to ap- prehend that the disease is lapsing into a chronic state, or that the amendment is but a temporary lull in the symptoms, to be followed at no distant period by an exacerbation, which shall prove more disastrous than the original attack. Recovery can- not in any case be considered complete, until the urine has be- come perfectly free from every trace of albumen. If the urine become progressively scantier, of higher density, and more abundantly charged with albumen, tube-casts, and renal epithelium, the worst consequences are to be feared. The advent of inflammatory complications, of oedema of the lungs or glottis, and, above all, of decided signs of uremic poisoning, are of equally evil augury, and leave but slender hopes of the final preservation of life. The prognosis is decidedly more favorable in the aged than in the young. I have several times seen the disease in persons over sixty, and once in a man on the verge of eighty ; but in most of them the disease proved mild, and in all of them it issued in recovery. Etiology. — Acute Bright's disease, though not absolutely con- fined to any age, occurs, in the immense majority of cases, in TREATMENT. 3I»3 childhood and youth. The individuals attacked are commonly of good previous health ; in two instances, how^ever, I have seen the disease complicated with acute pulmonary tuberculosis. The exciting cause is usually some delinite exposure to cold (a damp bed, wet clothes, lying or sleeping on the damp ground, sitting in a current of cold air, drinking cold water when in a state of perspiration), or a bout of drinking. A large propor- tion of the cases are sequelae of scarlet fever, or (much more rarely) of some other zymotic disease. Albuminuria, and some- times all the other phenomena of acute Bright's disease, have been described in cases of acute intestinal catarrh. Some cases are due to pregnancy. Treatment. — If the case is seen at the time of invasion, the patient should be at once confined to bed, swathed in flannels, and made to lie between the blankets. The loins should be immediately cupped to eight or twelve ounces (in children to two or three ounces). After the abstraction of blood, a large linseed-meal poultice should be applied, hot, to the loins, and changed every three hours. A hot-water bath or a hot-air bath should be administered every evening, or every second evening. When no conveniences for a hot-water bath exist, an excellent substitute is found in the " blanket-bath." A large thick blanket is wrung as dry as possible out of boiling water, and wrapped round the body of the patient; the bedclothes are then heaped on. In twenty minutes or half an hour, the hot blanket is removed, and the surface quickly dried with a warm soft towel. The bowels should be freely acted on every other morning by an active purge, such as the compound jalap powder. An endeavor should also be made to allay the fever and restore the action of the skin, by citrate of potash draughts, given every two hours, in effervescence, or a mixture of the liq, amnion, acet, in two or three drachm doses, with fifteen drops of tinc- ture of henbane in an ounce of inf lini. Dr. Barlow recom- mends tartar emetic in doses from J to | of a grain. I have myself employed the same remedy with the best effects, every four hours. Dr. Johnson also speaks highly of antimonial wine, sometimes combined with Dover's powder. The diet should be composed of light farinaceous substances, with milk, beef-tea, and broths. Flesh meat in any form is objectionable in the early stage. The abstraction of blood must be cautiously practised, on account of the tendency to aiiEemia in the later periods of the attack; and if the patient's health is broken by previous dis- ease, or is constitutionally weak, even local depletion is better omitted. If severe headache, coma, or convulsions occur, the cupping may be repeated. In very threatening, sthenic cases, where the fever runs high, venesection may be practised. "When the fever has abated, and the anasarca is yielding, the 894 ACUTE bright's disease. more active measures should be discontinued, or pursued in a less active manner; but the eiibrts to restore and maintain the action of the skin should be persevered in. In the later periods, when convalescence has been fairly established, preparations of iron should be substituted for the alkaline and diaphoretic reme- dies. It is always well to begin with small doses, and to feel one's way. A too early resort to ferruginous preparations may be followed by a return of the acute symptoms. When iron is tolerated, it acts with great benefit, and hastens in a marked manner the disappearance of blood and albumen from the urine. My experience agrees with that of Dr. Parkes, that gallic acid exercises no beneficial influence in the acute disorder. The use of mercury is objectionable, on account of the extreme susceptibility of patients suffering from Bright's disease to the physiological effects of the drug. Severe salivation has been known to follow very small doses. In one of my patients two grains of blue pill, administered with extract of colocynth on two alternate mornings, produced profuse ptyalism. The obstinate vomiting which occasionally prevails, may be combated with creasote, or small doses of chloroform, given in iced solutions. A careful revision of the diet should also be made. The gastric symptoms are sometimes due to direct sympathy with the renal irritation, and sometimes to genuine ursemic poisoning. The treatment of uraemia will be considered in a separate section. The secondary thoracic inflammations present great difficulty in their management ; they commonly set in when the patient is no longer in a fit state to bear the ordinary antiphlogistic means; and they run their course with unusual severity and rapidity. Counter-irritants and revulsives may, however, be energetically employed. Cantharides and turpentine should be avoided, from their special irritating effect on the kidneys; but hot-water applications, mustard poultices, and chloroform epi- thems may be applied locally over the chest, and to more distant parts — the calves of the legs, the feet, etc. Dry cupping over the chest is also a safe and sometimes valuable remedy. When a favorable issue has been obtained, unusual care is required to guard against relapses, to which the patients con- tinue liable for a considerable period. The slightest exposure is sometimes sufficient to reawaken the pyrexia, and to cause the reappearance of albumen and blood in the urine. A com- plete suit of flannels is essential ; and, as a rule, the conva- lescent should not be permitted to leave his room until the albumen has disappeared from the urine. When that comes to pass (or before, if the case prove very lingering), change of air to a warm sheltered locality is likely to be highly beneficial, and to hasten the restoration of the impoverished blood. TREATMENT. 395 Objections have been made, on theoretical grounds, to the use of the saline diuretics (acetate and citrate of potash) in acute Bright's disease. Experience has proved, however, that they may be employed with great advantage. They l>ecome changed in the primce vice into alkaline carbonates, and these diminish the acidity of the urine, and render it more bland as it jjerco- lates the renal substance. In a disease which tends to spon- taneous recovery under simple hygienic and prophylactic treat- ment, it is necessarily a matter of extreme difficulty to l;ring home the evidence of the curative power of drugs; but in a considerable number of cases of acute Bright's disease, coming under treatment early, I have obtained almost invariably the best results by the free administration of citrate of potash. And in no instance where the urine has been rendered alkaline in the first week of the complaint, have I observed the more severe ursemic symptoms, or secondary inflammations. In the later periods, when the fever has altogether subdivided, while the urine still continues bloody and albuminous, the same medicament has not proved of any service in my hands. Digitalis and broom-tops may be used freely in any stage to combat the dropsy. Dr. Cbristison recommends a combination of digitalis and bitartrate of potash as superior to either remedy given singly. " The former was usually given in the dose of one or two grains of the powder, in the form of a pill, three times a day, or in the dose of ten, fifteen, or twenty minims of the tincture, three times daily in a little distilled water of cinna- mon or cassia. The cream of tartar was administered thrice a day in the quantity of a drachm and a half, or two drachms, with about five ounces of water. Diuresis may generally be induced by such means in the course of three or four days, sometimes sooner — seldom, however, if delayed beyond the seventh day." Dickinson lays considerable stress on the desirability of encouraging the patient to drink freely of water, with a view of facilitating the elimination of the urinary solids by the kid- neys, and thus diminishing the risk of ursemic intoxication. Hamburger speaks strongly in favor of quinine in scarlatinal dropsy, after the pyrexia has abated. He gives to children li or 2 grains, and to adults 3 to 4 grains, twice a day. Of 47 severe cases thus treated he obtained amendment in 44, either immediately or in a few days. ("Prag. Yierteljahrsch," 1861.) CHAPTER lY. CHRONIC BRIGHT' S DISEASE. ANATOMICAL CHANGES IN THE KIDNEYS. The kidneys of persons dying of chronic Bright's disease present three chief types of alteration, viz. : Type I. — Kidney smooth, tvhite, and enlarged; in extreme cases, rarely met with, kidney atrophic (chronic nephritis). Type II. — Kidney granular, broionish, or red, and contracted (cirrhotic kidney). Type III. — Kidney lardaceous or waxy (so-called amyloid degen- eration). The special clinical history pertaining to each of these ana- tomical types has not been made out with sufficient precision to enable them to be invariably recognized during life; but much light has, in recent years, been thrown on the subject, enough to permit a sjaiopsis of the symptoms, and conditions of origin, of the three types to be presented. These types are not always found simple and unmixed. On the contrary, the main type of alteration present in any case is often complicated by superadded changes belonging to another type. Thus the smooth white kidney becomes not unfrequently affected with waxy degeneration or with interstitial growth ; and the granular and the waxy kidney are each liable to inflam- matory attacks, which bring about changes belonging to the first type. In this way a complex anatomical state is produced which is associated with a complex clinical history. 1. Smooth White Kidney. ( Chronic Nephritis. ) The structural changes in the smooth white kidney are simi- lar in kind to those already described as pertaining to acute Bright's disease, but advanced to a further stage; the surface continues perfectly smooth; the organ is considerably enlarged ; the capsule is thin and easily stripped ofiT. Conspicuous stellate patches of bloodvessels are seen on the white or mottled surface. On section the cortical substance is seen to be greatly increased ; its color is ivory-white, or (in cases of fatty transformation) ANATOMICAL TYPES — SMOOTH KIDNEY. 397 yellowish. The cones retain their usual color, Imt tliey appear conspicuously red from contrast with the abnormal wliiteness of the cortex. The microscopic changes, as (lescri})e(l by Dickinson and Grainger Stewart, are essentially confined to the uriniferous tubes. The epithelial lining of the tube is enormously in- creased in quantity, and the tubes are thereby distended and enlarged. The cells are swollen, generally o[)aque and granular, and often largely charged with oily particles. In the pure form the intertubular tissue is not altered, but commonly it shows a little increase. In the progress of the disease a number of the distended tubes and their contents are broken up into a granu- lar debris, and afterwards absorbed. Transparent fibrinous effusion and blood are sometimes seen within the tubules. The Malpighian corpuscles are either of their natural size or only slightly enlarged, and their capsules are thin, as in the natural kidney. The cones undergo changes of a corresponding char- acter with those of the cortex, but less developed ; and fibrinous casts are found occupying the interior of the straight tubes. The large smooth kidney generally remains large and smooth to the last; but, sometimes, if the patient survive sufficiently long, the enlargement gives place to a progressive dwindling ; and in very extreme cases, the kidney may be reduced to a weight of only an ounce, or even less. This dwindling is, however, not an invariable event, even when the patient sur- vives for some years. Dr. Wilks relates the following case in point : "A young woman, set. 23, had scarlatina three years before death. There was very slight eruption ; dropsy soon followed, which lasted a year. Then the patient was slightly better, but remained an invalid, with oedema of the legs, until the last five months, when very extensive and general dropsy came on and persisted. The urine was then scanty, dark, and contained exudative deposit. She had three epileptiform fits, and death subsequently ensued from pleuritis and pericarditis. Lungs were found very oedematous. The aorta and arteries were covered with an atheromatous deposit; and the kidneys were large and white, with an abundance of deposit, much of which had undergone a fatty change." (" Guy's Hosp. Rep.," 2d series, vol. viii. p. 243.) When the smooth kidney becomes atrophied, the capsule is somewhat thickened, and disposed to adhere to the renal sur- face, and slight superficial depressions make their appearance, giving the organ a slightly granular character. This atrophic condition seems to he brought about by a destruction and gradual absorption of the distended tubules and their epithelial contents. The cortical substance is thus progressively consumed while the pj'-ramidal portions retain 398 CHRONIC bright's disease. their natural dimensions. The bloodvessels are found much thickened, and, according to Grainger Stewart, there is a rela- tive increase of the fibrous stroma, but by no means to so great an extent as in the cirrhotic kidney. The large white kidney is not unfrequently greatly infiltrated with fat. Oily particles are found in great numbers in the sub- stance of the epithelium and lying free in the tubules. It con- stitutes one form of the " fatty kidney." This change some- times begins at an early stage of the disease, but it only reaches an extreme degree in long-standing cases. Fatty transformation is much more frequent when the disease has arisen from cold than when it has followed scarlatina. Synopsis of Symptoms and Conditions of Origin. — The smooth kidne}^ is found in those cases in which chronic Bright's disease has followed on the acute disorder. The invasion of the disease has been sudden, and it can usually be traced to some definite exciting cause, either cold or scarlatina. I have also seen the large white kidney in chronic Bright's disease follow- ing repeated pregnancies, and in a case arising in the course of phthisis. The average age of 106 cases of smooth large kidney, ex- amined by Dickinson, was 28.2 years; in 11 cases of smooth dwindled kidney the average age was 43.6 years; whereas in 250 cases of granular kidney the average age was 50.2 years. Serous efl^usion is an almost invariable coincidence; the body is commonly bloated with dropsy; the face pale and puffy, and the cutaneous surface conspicuously white, smooth and glossy. There is also a markedly greater tendency to secondary inflam- mations, and to ureemic accidents, than in granular kidney, but less to valvular heart disease and hypertrophy of the left ventricle. The urine is generally scanty. Its specific gravity is either normal, or somewhat raised above the usual average. It is pale and cloudy, but sometimes smoky and tinged with blood. On standing, it deposits a quantity of amorphous renal debris and casts of tubes. The casts are of various character, " epithelial," " granular," " fatty," and " hyaline." Cells having the appear- ance of pus-corpuscles are common towards the later periods. The disease is of shorter duration than the granular kidney. In fatal cases the ordinary duration of the disease is under six months. Temporary recoveries and relapses are frequent. Permanent recovery may be hoped for even after the lapse of a year or more. In these protracted cases the albuminuria continues long after the dropsical symptoms have passed away. I have known cases in which abundant albuminuria has per- sisted for more than a year after all other symptoms of disease had ceased. At length the albuminuria has gradually disap- ANATOMICAL TYPES — GRAN ULAK KIDNEY. 399 pearcd, and the reality iXH well an the appearance of health lias been established. Quite exceptionally the disease may be protracted for several years. Dr. Johnson records an instance which endured for ten years, with good preservation of health for a portion of that period. Nine years before death, the urinary deposit clearly indicated fatty degeneration of the kidneys. After death, the kidneys were found dwindled to an ounce and three-quarters for the pair.^ 2. Granular Contracting Kidnky. [Cirrhotic Kidney.) The gland is diminished in size and reduced in weight. In extreme cases the weight of the kidney is reduced to two or three ounces, or less. Its surface is rough, and beset with numerous rounded elevations, varying from the size of a pin's head to a hemp-seed, or even a small pea. The capsule is opaque, thickened, and adherent to the subjacent surface, so that it cannot be peeled ofi' without tearing the glandular structure. In certain spots the capsule sinks into the substance of the cortex, and divides the kidney irregularly — giving it a lobular appearance. On section, the cortex is manifestly atrophied, as compared with the cones, and forms a thin rim of only a line, or less, in thickness around the bases of the pyramids. It has a red, or brownish-red color, and a coarse granular texture. The entire organ is tough and resistant. In the granular kidney produced by gout there may be seen in the pyramidal portion longitudinal white or yellowish streaks, caused by a deposit of urate of soda. When a thin section of a granular kidney is placed under the microscope, the secreting tissue is found to have undergone ex- tensive destruction. The Malpighian bodies are shrunk to half their size, and unnaturally crowded together. Their vascular tufts are embraced in a fibrous and granular investment, and, in extreme instances, compressed into an impermeable knot at the bottom of their capsules. The investment is formed by an increase of the fibrous tissue surrounding the glomerulus, or by a swelling and fibrous thick- ening of Bowman's capsule and its lining epithelium. The vascular tuft itself is not unfrequently transformed into a fibrous mass, and it may also undergo a colloid change. The uriniferous tubes are altered in various ways, and to various degrees. Some are. denuded of epithelium and reduced to mere tubular threads; others, equally denuded, contain glassy 1 Med.-Chir. Trans., vol. xlii p 160 400 CHRONIC bright's disease. fibrinous cylinders; while others are crammed with broken-up epithelium. Many of the convoluted tubes are seen to be much diminished in size and lined by a layer of cubical epithelium instead of the large granular cells commonly found there. Oil is found not unfrequently both in the fibrinous exudation and in the disintegrated epithelium, but not so commonly nor so abundantly as in the smooth kidney. Amid tubes changed to this degree, are found others not much altered, and lined with their proper and healthy epithelial investment. The basement membrane of the tubes is thickened. Between the wasted structures lies a large quantity of adventitious connective tissue, which gives the organ its peculiar toughness. The arteries of the kidney show considerable changes. They may show thickening of all their coats. Dr. George Johnson first pointed out the great increase in the muscular coat, and although his position has been attacked by some, it has been abundantly confirmed by other observers. Dr. Klein has ob- served what is probably the early stage of this change in the scarlatinal kidney, where he found proliferation of the muscle nuclei in the walls of the arterioles. The adventitia frequently shows fibrous thickening, which merges into the general connec- tive tissue of the kidney, while the intima very often is the seat of chronic endarteritis, which may considerably diminish the lumen of the vessel. It is only rarely that the granular kidney is encountered in the early stage of its development. When such is the case, thickening of the capsule and slight granulation of the surface are found to precede contraction, so that the organ at this period preserves its normal volume. The granular kidney, in the con- tracted state, allows injections to penetrate imperfectly. Dick- inson found that when a stream of warm water was propelled through the bloodvessels, a very considerably less quantity passed in a given time than through a healthy kidney — less also than through the large smooth kidney — showing that the permea- bility of the gland to the blood-stream was greatly lessened. In the healthy kidney, the mean discharge through the renal veins in ten minutes was 119 ounces ; in the large smooth kid- ney, 90 ounces; and in the granular contracted kidney, 25 ounces. This diminished permeability is not wholly due to the cirrhotic state of the intertubular matrix, but partly to thicken- ing of the walls of the minute arteries of the kidney, as has been pointed out by Dr. G.Johnson. ("Brit. Med. Journ.," April, 1870.) Thoma has obtained results similar to those of Dr. Dickin- 'son, using as the injecting fluid either defibrinated ox-blood or gelatine solutions. He lays stress on the endarteritis as a cause of obstruction to the blood flow, but also shows that the oblitera- ANATOMICAL 'J'YPES — GKANULAR KIDNEY. 401 tioii of the glomeruli may take part in this, and that the arteries of the kidney allow of more easy transudation through their walls. The influence of the destruction of small vessels is to some extent counteracted by anastomoses wliich are set up. Thus, when the vascular tuft of the gh)meruhis is destroyed, a direct communication is established between the aflerent and efferent vessels; when the glomerulus becomes cystic, a system of capillaries running around the cyst-wall again estab- lishes communication between the afferent and efferent vessels; in addition, the normal anastomoses between the branches of the renal and neighboring arteries become dilated, and carry off a larger amount of blood than usual. Of the intimate nature of the process which finally brings about this state of the kidney, there are conflicting opinions. Dr. Johnson believes that the mischief begins in the epithelial cells, and that the tibrous tissue is the remnant of atrophied tubes. Dickinson and Grainger Stewart describe the process as originating in the intertubular matrix, and as consisting essen- tially in an enormous hypertrophy of the tibrous stroma of the organ. By the pressure and contraction of this tibrous material the uriniferous tubes and Malpighian corpuscles are extensively destroyed, and the size of the kidney is progressively reduced. According to Dickinson, the tibrous growth begins beneath the capsule, and then penetrates into the interior of the cortex. The points where the tibrous processes penetrate are depressed, and when these are numerous and distributed with tolerable regu- larity, the appearance of superticial granulation is produced. The disease thus travels from the surface towards the central parts, and eventually involves the pyramids. It must be admitted, however, that in many specimens the fibrous tissue can be seen grouped round the glomeruli and the arteries, and not proceed- ing from the capsule. Sir William Grull and Dr. Sutton propound a difierent view of the pathology of granular kidney. They assert that the morbid process consists in the deposit of a " hyalin-tibroid " material in the tibrous coats of the small arteries and capillaries. This morbid change is attended with atrophj' of the subjacent tissues : it is not contined to the kidnej's, but may prevail ex- tensively throughout the area vasculosa. Although it gener- ally begins in the kidneys, there is evidence of its beginning primarily in other organs. A brief account of these views is given further on in treating of the connection of Bright's dis- ease with diseases of the heart and vascular system. The development of cysts is very common in the granular kidney. They vary in size from a pin's head to a pea or a hazel-nut ; but many are so minute that they can only be de- tected by the microscope, not being larger than the width of the 26 402 CHRONIC bright's disease. uriniferous tubes. Mr. Simon believes that they are formed by an immense dihitation of epithelial cells — a development that seems incredible, considering the fragility of the outer portions of these cells; and one that would be, so far as I know, without parallel in histogenesis. A better sustained, and more com- monly accepted, view is, that they are produced by obstruction of the uriniferous tubes with exudation, at intervals, or by com- pression of their walls at interrupted spots by the contracting adventitious tissue. The spaces thus enclosed become distended with a serous fluid, and are sometimes found lined with an epithelial layer. Their contents are not urinous, but consist of an albuminous saline solution or of a colloid mass. In the cones they are sometimes elongated and placed end to end like a string of sausages (Dickinson). {See Cysts arid Cystic Degeneration in the Kidneys.) Synopsis of Symptoms and Conditions of Origin. — The granu- lar kidney is found in the vast majority of those cases of Bright's disease which are chronic from the beginning — those which commence insidiously, without definite exciting cause. Dropsy is altogether absent in a considerable proportion (perhaps in a quarter — according to some, in one-half) of the cases, and when present, it is commonly slight and limited to oedema of the ankles and legs, or a puffiness under the eyes. It often dis- appears for a while, and returns again. The disease may run a latent course for months and years. A deep constitutional cachexy is associated with it in a large proportion of cases. The subjects of it are more advanced in years than those of the smooth large kidney (see p. 398).^ The cutaneous surface, though pale and anaemic, has not the con- spicuous whiteness of the preceding type, and the features are often pinched and sallow. With this type of Bright's disease are especially associated hypertrophy of the left ventricle and certain changes in the small arteries and in the retina, which will be more full}^ noticed in a future page. {See Complications.) The urine is copious — three or four pints a day — and of low specific gravity ; the quantity of alibumen is comparatively small; in rare cases it may even be temporarily absent from the urine. Toward the termination of the disease, however, the urine becomes scanty, or even suppressed. The deposit is slight, composed of hyaline and granular casts, with very slight admixture of epithelium, not often fatty: the deposit is often so scanty that it may escape detection, or there may really be none. As a rule, blood is absent. 1 Young persons and e\en children are, however, sometimes the victims of this type of Bright's disease. I saw a remarkable example with Dr. Barlow, in a child of 5 years, of which Dr. Barlow has given an elaborate account in the Lancet for Aug. 1, 1874. ANATOMICAL TYPES. 403 The common predisposing causes are habitual intemperance, gout, lead poisoning, repeated exposure to cold, and extensively distributed fatty degeneration of the tissues. As these two types — the smooth large white kidney, and the granular red contracting kidney — constitute the vast majority of cases -of Bright's disease, the question of the oneness or multiformity of JBright's disease has mostly been limited to the inquiry — whether the latter is the ultimate stage ot the former, or whether the two are distinct from first to last. Reinhardt and Frerichs believe that the large white kidney will, if the patient survive, eventually become granular, red, and contracted. This view has obtained numerous supporters in Germany, and in Rosenstein's work it is adopted without dis- cussion. In this country the opposite view has steadily gained ground; and the evidence brought forward by Johnson, Wilks, and Dickinson appears to place the matter beyond reasonable doubt. In Germany, too, several recent writers, amongst whom are Bartels, Senator, and Ley den, have adopted this view. Johnson found that out of 26 fatal cases of enlarged kidney, observed by himself, there was dropsy in 24, or 92 per cent. ; whereas in 33 fatal cases of contracted kidney, there had been dropsy only in 14, or 42 per cent. He pertinently observes : " If all the contracted Bright's kidneys have passed through a previous stage of enlargement, it is difficult to understand how it can happen that the majority of those patients who have reached the final stage of renal degeneration should escape the dropsy w^hich, in a greater or less degree, troubles nearly all those who die in what is assumed to be an earlier stage of the same disease." ^ Convulsions and secondary inflammations (pneumonia and peritonitis) are more frequent wdth the smooth kidney; whereas hypertrophy of the left ventricle, atheroma, and apoplex}^ are more frequent w^ith the granular kidney. It must, of course, be borne in mind that it is not now dis- puted that the large white kidney does sometimes sufier atro- phic changes, and that in exceptional cases it may at length dwindle to very small dimensions. Johnson and Dickinson and Grainger Stewart adduce several examples of such a change, but the}' insist that even in its further stage of contraction the smooth white kidney is still distinguishable from the granular red kidney. The change of the large white kidney to the atrophic form is oftener accompanied by a similar change in the 1 Med.-Chir. Trans., vol. xlii. p. 156. 404 CHRONIC bright's disease. clinical features; the symptoms then approach in character those of the small red granular kidney. The symptoms of the two varieties of Bright's disease men- tioned above are not yet sufficiently worked out to enable us always to prognosticate from the clinical signs the exact lesion to be found after death. Various " mixed " forms are occa- sionally met with. The small granular kidney is subject to attacks of acute inflammation and congestion, and under the influence of these may show many of the changes of the large white kidney. Leyden has called attention to cases where the symptoms are entirelj^ those of the small red granular kidney, yet after death the kidneys are found large and pale. The microscope in such cases shows excess of interstitial tissue, as in the contracted form, but combined, it may be, with paren- chymatous changes. 3. Lardaceous or Waxy Kidney. [So-called Amyloid Degeneration of Virchow ; Depurative disease of Dickinson.) Most pathologists now distinguish the waxy or lardaceous kidney from the preceding varieties of Bright's kidney. Externally, the waxy kidney is smooth, or sometimes slightly roughened ; the capsule peels off readily. The organ is usually enlarged, sometimes, however, diminished in size. On section the appearance is characteristic. The cortex is bloodless, of a w^hite or yellowish color, with a waxy, smooth, translucent ap- pearance, resembling bacon-rind. The organ is conspicuously tough and hard. On the smooth cut surface, little appearance of the natural secreting structure is seen, but it is dotted over with bright glancing points : these are the changed Malpighian bodies. The cones appear unnaturally red and distinct. This description answers only to extreme degrees ; in slighter cases the change can only be detected by the use of reagents.^ When a thin section thus prepared is examined under the microscope, the w^axy change is seen to affect mainly (sometimes exclusively) the bloodvessels. The Malpighian corpuscles are the parts earliest attacked. Without reagents they appear as shining particles vs^ith thickened capsules; the vascular tufts are greatly swollen and give the characteristic reaction. In advanced cases, the vasa atferentia, with the arteries and capillary network of ^ For naked eye purposes the liquor iodi of the British Pharmacopoeia, diluted with water until it has the color of brown sherry, is recommended as a convenient test for the waxy degeneration (Dickinson). The iodine imparts to the affected portions a mahogany-brown color, whereas the parts not affected take a merely yellowish tinge. For microscopic purposes methyl-violet is the best test. This reagent colors the amyloid pai'ts red, and the healthy parts blue. ANATOMICAL TYPES — WAXY KIDNEY. 405 the cortex, and even the vessels oi' the pyrumids, are similarly chano-ed. The lumen of the hloodvessels is much diminished by the deposit. Dr. Dickinson has described a morbidly rigid character of the renal tubes, when the kidney is examined in the earlier stages. Later on, the epithelial cells of the uriniferous tubes are com- monly withered, often infiltrated with fatty molecules; only rarely are they the seat of the waxy change, but the basement membrane of the tubes is frequently affected.^ Hyaline waxy casts exist in some of the tubules. The stroma of the gland is usually increased in quantity and in some cases to an extreme degree. The kidney, then, may be contracted and may resem- ble in microscopic characters the small red granular kidney. The liver and spleen are usually enlarged, and in a lardace- ous state, when the kidneys are so afiected. Of 77 cases col- lected by Eosenstein, the three organs together were affected in 48; the spleen and kidneys in 20; the liver and kidneys in 4; and the kidneys alone in five cases. The chemical nature of the waxy material has only recently been investigated. Virchow concluded from the violet <^olor produced by iodine and sulphuric acid that it belonged to the same group as starch and cellulose, which likewise yield a violet tint with the same reagents. But the ultimate analyses of C. Schmidt and Kekule show that it contains nitrogen— rand indeed as much as 15 per cent., or almost exactly the same proportion as the protein compounds. ISTeither of the chemists named could produce a particle of sugar from it by boiling with dilute sul- phuric acid. It further resembled albuminous compounds, in yielding a violet color with the cupropotassic solution, in dis- solving completely in dilute caustic potash, and in being precipi- tated from this solution in white flocks by acids. ^ The propor- tion per cent, of carbon, hydrogen, and nitrogen, found by Kekule, in purified waxy matter, from an exquisite specimen of lardaceous spleen, was : C 53.58; H 7.00; N 15.4 — which cor- responds closely with the percentage of the same elements in albumen. Dickinson considers it a variety of fibrin e — but dif- fering from ordinar}^ fibrine in containing about one-fourth less alkali and a somewhat larger proportion of earthy salts. To call it " amyloid " is simply a misnomer, and an unfortunate one, because it leads to confused notions as to the existence of some connection between waxy degeneration and the (genuine) amyloid substance found in the healthy liver. 1 Dr. G. Stewart states that, occasionally, epithelial cells are found on the casts in the urinary deposit, whicli exhibit the peculiar reaction of lardaceous matter. 2 Friedreich says that the "amyloid reaction" (with iodine and sulphuric acid) was obtained by him in perfection, with decolorized fibrine from an old luematocle. 406 CHRONIC BRIGHT S DISEASE, Synopsis of Symptoms and Conditions of Origin. — Waxy de- generation of the kidneys always comes on insidiously and in cachectic persons debilitated by some preexisting wasting dis- ease. In 145 instances collected by Fehr it coexisted with the following disorders ■} Pulmonary tubercle ........ 43 cases. (complicated with caries in 5 cases, with other diseases in 6 cases.) Syphilis 34 " Caries with struma . . . . . . . . 26 " Empyema with fistula . . . . . . . 4 " Dilated bronchi with chronic bronchitis . . . . 3 " Chronic alcoholism . . . . . . . . 5 " Chronic articular rheumatism . . . . . . 2 " Cancer (generally of the uterus) . . . . . 3 " Ague 4 " Chronic nephritis with hydronephrosis . . . . 3 " Chronic peritonitis, scarlatina, variola, cirrhosis of the liver, ovarian tumor, urethral fistula with stricture . . each 1 " Atonic ulcers of the foot . . . . . . . 3 " Without appreciable cause . . . . . ". 9 " It. has also been found in association with gout, rickets, various abdominal tumors, and mercurial intoxication. The aspect of patients with waxy kidneys is pale and cachec- tic, and the course of the disease is essentially chronic. Dropsy is present in the majority of the cases (in 98 out of 152 collected by Fehr); in some it is abundant and general, in others slight and partial. Ursemic symptoms are strikingly infrequent. The urine in the earlier stages of the disease is markedly abundant — 60, 100, or even 200 ounces per day — and Dr. Grainger Stewart has pointed out the important fact that this polyuria is a marked feature even before the urine becomes albuminous, and that this supplies a warning of the approach- ing advent of this form of Bright's disease. The quantity of albumen is at first small, but as the disease advances the urine becomes scantier, the proportion of albumen very great, and the specific gravity high. The color of the urine is commonly pale, and it allows only a very slight deposit to subside. This consists of casts and atrophied renal cells, which are sometimes fatty. Cells resembling those of pus are occasionally found either separate or aggregated round a cast. The tube-casts are usually hyaline, and they do not yield a brown coloration with iodine. Epithelial casts are also sometimes seen. ' A. Fehr. Ueber die Amyloide Degeneration, insbesondere der Nieren. Bern, 1867. - Litten has described cases in which the amyloid change had proceeded to an advanced stasie without albumen appearing in the urine (Berl. klin. Wochensch., 1878, Nos. 22 and 23). Strauss has found that in such cases the arterias rectse are the parts most affected. [See Cornil and Brault, loc. cit.) GENERAL COURSE AND SYMPTOMS. 407 Miinch detected " cor[)ora amyhicea " in the urine of a man with lardaceous kidney; they were constantly present, and were colored violet by iodine and sulphuric acid.' The diagnosis of waxy kidneys rests partly on the coinci- dence of a pale abundant albuminous urine with dropsy, but chiefly on the coexistence or preexistence of one of the wasting diseases of which waxy kidneys are known to be a frequent complication, namely, phthisis, caries, long-continued suppura- tion, and constitutional syphilis. GENERAL COURSE AND SYMPTOMS OF CHRONIC i3RIGHT'S DISEASE. Chronic Bright's disease, in the great majority of instances, begins slowly, imperceptibly. It is rarely detected until it has already existed some months — it may be, years. The attention of the patient is at length awakened by the gradual failure of his strength, the increasing pallor or sallowness of his com- plexion, and his disinclination to exertion; perhaps his sus- picions are aroused by a little puffiness under the eyes, a slight swelling of the ankles at night, unusually frequent calls to void urine, or shortness of breath. In other cases these premonitions are altogether wanting, or perhaps they pass unheeded. The fatal disorganization in the kidneys proceeds silently, amid apparent health, and then suddenly declares itself by a cerebral hemorrhage, a fit of con- vulsions, rapid coma, amaurosis, pulmonary cedema, or a violent inflammation. Or, again, the disease creeps on stealthil}^ in the wake of some preexisting chronic disorder — phthisis, caries, necrosis, joint dis- ease, constitutional syphilis, gout, chronic alcoholism, or ex- hausting suppuration. Or, it may be a continuation or sequela of acute Bright's disease. Lastly, the disease may lie concealed for an undetermined period, and then reveal itself after exposure to cold or a fit of intoxication, in the guise of an acute attack — with rapid general anasarca and scanty sanguineous urine. The principal symptoms of the disease are : albuminous urine with deposits of tube-casts and renal epithelium; dryness of the skin; frequent micturition, especially at night; dropsical effu- sions into the subcutaneous cellular tissue, serous cavities, or pulmonary substance; derangements of digestion: progressive hydrsemia; ursemic phenomena (headache, amblyopia, convul- sions, coma, vomiting, and diarrhoea) ; hypertrophy of the left ' Cited by Parkes. Composition of the Urine, p. 39J:. 408 CHRONIC bright's disease. ventricle ; secondary inflammation of the parenchymatous organs and serous membranes. Few cases present the whole of these symptoms ; and many present only two or three of them. The alterations in the com- position of the urine are the most invariable; they are also the earliest and most distinctive symptoms ; next follow, in the order of constanc}', the deterioration of the blood, the dropsical symptoms, and lastly the ursemic and inflammatory incidents. The disease usually pursues an interrupted course. It is sub- ject to exacerbations from time to time, with intervals of quies- cence. The exacerbations are generally occasioned b}' exposure to cold, or some imprudence in diet or regimen ; sometimes no cause can be assigned for their occurrence. They are marked by pyrexia; and resemble, often closely, an attack of acute Bright's disease. The intervals of quiescence may be longer or shorter, some weeks or months, or a few years; the remission of the symptoms is commonly only partial — the main features of the disease persisting, though in diminished prominence. Some- times, however, the remission is almost complete, and there re- mains little except the albuminous state of the urine to attest the existence of renal mischief. Nay, even this ma}^, in very exceptional cases, be absent, and the nature of the case be flrst revealed at the autopsy. After each exacerbation it is commonly prett}^ evident that the disease has taken a step in advance, and assumed a fuller development; and that, probably, an additional portion of the kidney, hitherto spared or only slightly aflt'ected, has been disabled. But whether it thus proceed per saltayn or more continuously, the kidneys are at length so deeply injured, and their depurative functions so far abrogated, that life falls a forfeit. The immediate cause of dissolution is various. Sometimes the sufferer passes peaceably away exhausted by anaemia, bur- densome anasarca, and defective digestion of food. More fre- quently the final scene is tumultuous. Two of the cases to be hereafter related, terminated amid a pyrexial exacerbation, with formation of clots in the heart. About one-third of the subjects of chronic Bright's disease perish by ursemic poisoning, either in the form of coma and convulsions or irrepressible vomiting and diarrhoea. A considerable number die from the dangerous situation, or intensit}'^, of the dropsical effusion — as when the lungs or glottis are invaded ; or death comes from hydrothorax, or from gangrenous erj^sipelas set up in the tense hydropic integuments of the thighs, legs, or genitals. About one-fifth die by secondary pneumonia, pericarditis, or double pleurisy. The remainder are cut oft' by less closely connected complica- tions — apoplexy, cirrhosis, phthisis, intestinal ulcerations, etc. ILLUSTRATIVE OASES. 40f> From the difficulty of asHigiiiug the exact date of invasi(;ii, the durcUio?) of the disease can only be approximately ascer- tained. Enough is, however, known, to show that it varies within very wide limits. The usual period is from two to three years; but cases may end in six months, or be protracted for four or five years. Exceptional instances have been recorded, in which patients have survived 10 years (Johnson and Kuss- maul), and even 15 (Bright) and 23 years (Oppolzer). The large white kidney is usually fatal much more quickly than the red contracted variety. The following abstracts of cases will serve to exhibit the broad features of the disease, in its more familiar aspects; and prepare the way for a more detailed consideration of the symp- toms and complications : Case 1. Chronic Bright' s disease, latent two years, without dropsy — fatty casts and cells in the urine. Death by urcemic convulsions. — Mr. V., a solicitor, of temperate habits, set. 50. Two and a half years ago, Mr. V. suffered from sciatica, for which he was under medical treatment. At that time a little albumen was discovered in the urine, but slight importance was attached thereto. Mr. V. speedily recovered from his sciatica, and continued in good health, attending to his business, until four months ago, when he became subject to shortness of breath and catarrhal symptoms. These were not severe enough to prevent the patient from pursuing his occupation, until the beginning of April, 1864, when I was requested to see the case with the late Mr. Mellor. The symptoms complained of were, shortness of breath on exertion, and failure of strength ; there was not a particle of oedema (nor had there ever been any) nor ascites. The liver and spleen were not enlarged ; there were no cardiac murmurs ; but there existed slight pra^cordial bulging, and the heart's apex beat in the vertical line of the nipple. The shortness of breath evidently depended on pulmonary oedema. The countenance was pale and sallow, and the body spare, but not con- spicuously emaciated. The urine was copious (three pints), of low density (1012), and highly albuminous (3); it deposited a not incon- siderable flourdike sediment, composed of casts and renal epithelia, many of which showed abundant signs of fatty changes {see Fig. 51). The casts were mostly medium sized ; some were granular and opaque, as at a ; others, in about equal numbers, were nearly hyaline, with only very faint markings, as at h. AVithered epithelia studded some of the casts, or lay scattered free about the field. Botryoidal fat masses lay embedded in some of the casts ; other casts were dotted over irregu-larly with oily particles. Some of the renal cells were similarly dotted in their interiors, while others were entirely changed into round agglomera- tions of fat molecules (granular corpuscles) (c, d'). A few sparse blood- dsks were scattered about. The previous history was singularly barren of etiological indications. The patient's mode of life had been strictly temperate ; and there was no evidence of repeated exposure to cold, nor of gout. Father and mother died at the age of forty-five — the latter of consumption. He 410 CHEONIC BRIGHT'S DISEASE, himself had enjoyed remarkably good health, until the invasion of his present complaint. The treatment adopted was : dry-cupping the chest, warm bath every second day, flannel clothing, cod-liver oil, and iron. The dry-cupping removed the dyspnoea at once, and some general amendment took place in the course of the ensuing month. This gentleman continued under observation until his death, which took place in three months. He improved for a while, and was able to go to Southport for a fortnight, where he derived considerable benefit. He considered himself so well on his return, that he believed a week or Fig. 51. Casts and renal cells from the urine of Mr. v. a a. Gi-anular opaque casts ; 6 6. Hyaline casts ; c, d. Fatty masses. two would complete his recovery. He resumed his usual occupation, and, for a week or two, went daily to his office. But this truce was wholly deceptive ; the condition of the urine never improved. It became progressively scantier in quantity — first it fell to 40 ounces, and then to 30 ounces, while the specific gravity continued to range from 1009 to 1011; and the deposit of casts became more and more opaque- granular, and less and less fatty. Emaciation also progressed, and the shortness of breath returned, and could no longer be kept under by dry-cupping. A persistent feverishness began to prevail; the nights were restless; but during the day the patient was dull, almost drowsy, and indifferent. Not a trace of oedema appeared throughout the com- plaint. The hypertrophy of the heart became progressively more conspicuous. In the last fortnight of life, the urine became very scanty (still of low ILLUSTRATIVE CASES. 411 density), and was totally suppressed for twenty-four hours before death; vomiting recurred frequently, with utter loathing of food, and especially of animal flesh. The sight failed, and two days before death he became completely blind for more than half an hour. The restlessness increased, accompanied with wandering delirium, the tongue became dry, the indifference merged into drowsiness, and, after a fit of convulsions, he died. The general course and symptoms clearly indicated a granular con- tracting kidney; but the friends would not permit a post-mortem examination. Case 2. Chronic Bright' s disease from intemperate habits — sudden anasarca after a wetting. Death from pericarditis. Granular contracted kidneys. — W. M., a carter, at. 40, of intemperate habits, was admitted into the Royal Infirmary, March 1, 1858, with general anasarca and ascites. He had followed his employment, and considered himself in good health, until three months back, when he got a severe wetting, and allowed his clothes to dry on him. Soon after followed lumbar pains and general swelling of the body. On admission there was oedema of the face, trunk, and extremities, and considerable ascites. The skin was dry; the urine, of low specific gravity, contained tube-casts, but no blood. After he had been in the house a fortnight, the urine became scanty, and intense pericarditis set in, which proved fatal on the fifth day. He died comatose with suppression of urine. At the autopsy the kidneys were found granular and greatly atrophied ; scarcely any corti- cal substance remained. Abundance of fibrinous exudation existed in the pericardium; left ventricle immensely hypertrophied — the walls fully one inch thick ; the valves were healthy. The state of the organs after death, indicated that the disease had been really in existence for a hauch longer period than the few months during which symptoms had been noted by the patient. Case 3. Chronic Bright' s disease from repeated pregnancies — recurrent nrcemic convulsions. Granular contracted kidneys. — Mrs. X., ast. 39, became pregnant of her sixth child in the autumn of 1862. About the third month, unusual frequency of micturition at night was observed, and soon after slight osdema of the face and legs. The urine was found to contain albumen. The foetus was expelled without accident at the fifth month, and a few days after all the oedema disappeared ; but the urine still continued albuminous. I first saw her about two months after the miscarriage. There was no oedema of any part. The urine was of low density, and moderately albuminous. The deposit con- tained a few transparent tube-casts, some of which showed slight evi- dences of fatty change ; others were opaque, and studded with withered epithelia (see Fig. 52). The patient continued under observation for above a year, and died, at length, comatose, after repeated attacks of convulsions. Each cata- menial period was marked by great nervous excitement ; and on several occasions convulsions took place at these periods, accompanied with tem- porary amaurosis. Severe headache was a very constant symptom, 412 CHRONIC BRIGHT's DISEASE especially on the days preceding the catamenial periods. After death the kidneys were found granular and atrophied, and the left ventricle much enlarged. Pig. 52. Transparent and opaque casts from the urine of Mrs. X. Case 4. Chronic BrigMs disease from intemperance and exposure to cold — general dropsy, complicated with old chronic peritonitis. Death from syncojje. Smooth white kidney, beginning to contract. Myriads of minute uric acid calculi in the infundibula.- — J. R., set. 48, a French polisher, from Oldham, was admitted into the Royal Infirmary, April 4, 1864. There was great ascites, tense oedema of the lower extremities, with an erysipelatous state of the integuments of the upper and inner parts of the thighs and scrotum ; oedema also of the arms and back of hands. The heart was displaced upwards, and much enlarged ; there were no cardiac murmurs. There was great emaciation, cough, purulent expec- toration, and orthopnoea. The urine was scanty, dark-colored from blood, highly albuminous ; it let fall an abundant chocolate-colored deposit, composed of " blood- casts," " granular casts," and " epithelial casts," with abundance of free renal epithelium and free blood-disks. Mixed with these were a large number of irregularly tailed and spindle-shaped cells, evidently from the pelvis of the kidney {see Fig. 53). The patient stated that he had been ailing twenty weeks ; the symp- toms had come on gradually. The swelling had first appeared in the belly, and the enlargement of the abdomen was still out of proportion to the general dropsy. His habits had been for years intemperate, and he was often exposed to chills, in suddenly passing from his warm work- ILLUSTRATIVE CASES. 413 shop to the cold open air. He had, however, been a healthy man, and had never lost a day's work until his present illness. He went on, with little change in the general symptoms and urine, for twenty-five days, when he became feverish and delirious, apparently from cold, taken by imprudently exposing himself after a warm l^ath. He suddenly fell back dead on April 27th, as the nurse was shifting him for the purpose of making his bed. Fig. 53. Blood-casts, granular casts, blood-disks, tailed and irregular cells from the pelvis of the kidney — from the urine of J. K. Autopsy, 24 hours after death. There was a good deal of anasarca of the lower limbs, forearms, and hands. An enormous quantity of serum escaped from the peritoneal cavity. The peritoneal membrane, in its entire extent, was thickened, or, rather, it was invested with a layer of thin adherent fragile false membrane of a pearly translucency, like the hyaline membrane of a hydatid sac. The intestines were sunk on the spine; there was no recent peritonitis. The liver was covered over with a rough layer of hyaline false membrane, which evidently em- braced it tightly, and had caused it to shrink much below its natural bulk. On section it did not display a cirrhotic structure. The spleen was rather large ; its capsule thick and opaque. The kidneys weighed together eleven ounces. They were firm, and their capsule smooth, but opaque and thickened. The capsule peeled off with only moderate ease, and tore the subjacent tissue a little. The surface of the gland was yel- lowish-white picked with dead white, like ivory. On section, the same appearance was seen to prevail throughout the cortical part. The cortex was, if anything, below its normal proportion. The pyramids were of a faint red color, not unnatural looking. The infundibula were somewhat 414 CHRONIC bright's disease. dilated, and contained (in both kidneys) myriads of very minute yellow, uric acid calculi. These varied in size from a pin's head to an almost microscopic object ; they were lumpy and irregular in shape. The papillge were flattened, some of them almost obliterated. The kidneys were evidently of the " smooth white" species, beginning to pass into a state of contraction. The heart weighed 122 ounces ; the left ventricle was enormously hypertrophied ; its walls seven-eighths of an inch thick. The right ventricle was also hypertrophied, and the tricuspid orifice somewhat patulous. All the valves were perfectly healthy. The lungs were strongly compressed, and partially airless and leathery from pleuritic effusion. PAKTICULAKS OF SYMPTOMS AND COMPLICATIONS. Urine. — The urine is albuminous to most varied degrees. It may become absolutely solid on boiling, or it may contain only the minutest traces of albumen, even in confirmed and fatally tending cases. The red granular kidney is accompanied by but a small amount of albumen in the urine, and even that may in rare cases be present only at certain times of the day.^ The large v^hite kidney, on the other hand, usually causes a large amount of albumen to be passed. Absolute freedom from albumen, even for short intervals, is very rare; I am convinced, that a considerable number of the cases so reported, are examples of imperfect testing. But it must be admitted that chronic degeneration of the kidneys, not distinguishable from some forms of Bright's disease, does exist under certain circumstances, without albumi- nuria. The following example of scarlatinal dropsy, running a chronic course and ending fatally, without albuminuria, occurred in my practice : J. K., set. 8, was admitted into the Royal Infirmary, April, 1864, afilicted with general anasarca. She had had scarlet fever four months before, and during convalescence therefrom (in the third week), was suddenly seized with general swelling of the body, which has continued since. When admitted, she presented a perfect type of scarlatinal dropsy — universal and great anasarca, difficultly pitting on pressure, puffy pasty face, excessive pallor of the surface, shortness of breath. On examining the urine not a particle of albumen could be detected, nor any casts or other renal derivatives ; it was scanty and high-colored. The skin was very dry, and a constant degree of feverishness existed. She remained under observation until her death, four weeks after admission. The oedema remained stationary ; the urine was repeatedly examined, but never found to contain albumen. The feverishness became more intense, the tongue became dry, and the breath very short ; toward the close there was diarrhoea, which helped to carry her off. Autopsy, 24 hours after death. Several deep and old tuberculous ulcers were found in the small intestines. A few nodules of tubercle, 1 Dr. Mahomed maintains that in the pure red conti'acting kidney, no albumen is passed, and that it is only under the influence of an intercurrent affection of the renal epithelium that the albumen makes its appearance. PARTICULARS OB' SYMPTOMS. 415 as big as peas, were grouped under the peritoneum, around the bases of these ulcers. The mesenteric gkmds were enhirged and tubercuhjus. There was no general tuberculosis of the peritoneum. The lunyn con- tained a few old tubercles (of no great size) at the apices. The tuber- culous masses were throughout old and inactive. Both pleurae, contained a large quantity of fluid, and the lungs were much compressed thereby. The liver was excessively bloodless. The hearl was natural. The kidneys were good examples of the "smooth white" Bright's kidney. They were slightly enlarged, and weighed together 7 ounces. The organs were limp, their surface pale and smooth ; the capsule peeled off readily. The most curious thing about them was the existence of certain sharply outlined flat depressions, which differed from the re- mainder of the superficies. The surface generally was of a character- istic fawn-color, picked with dead white ; but at these depressed spots the color was slate-gray, and contrasted markedly, by its blank, gray aspect, with the spotted appearance of the remainder. It was evident that atrophic changes were beginning to take place at these spots. On section, the kidneys presented the usual appearance of the "smooth white" kidney. There was no information as to the state of the urine when the ana- sarca broke out ; but for a month preceding death it was free from albumen, though the general symptoms, and the state of the kidneys after death, bore evidence of the existence of Bright's disease.^ The amount of albumen lost in twenty-four hours varies commonly from 45 to 300 grains. Dr. Parkes observed in one instance as much as 545 grains. The quantity is larger during digestion than during fasting; it may be twice as great. It rises and falls irregularly in the course of the disease — some- times diminishing to a trace, and anon increasing to an intense impregnation. The urine is generally pale, and not quite clear. It deposits, on standing, an amorphous whitish sediment, of renal epithe- lium and tube-casts. It sometimes contains blood — even in quantity — though generally only in microscopic proportion. When there is intercurrent pyrexia, or the case is complicated with phthisis or regurgitant heart disease, the urine may be high-colored, and turbid from lithates. The quantity of urine voided per day varies according to the type of the disease, and the presence or absence of pyrexia, sweating, vomiting, or diarrhoea. The urine is throughout scanty with the large white kidney; I have known it not to exceed 35 ounces on any one day for a period of foar months, and to be under 20 ounces for three successive weeks, and under 12 ounces for several consecutive days. It may even sink to one ' Hamilton, out of sixty cases of scarlatinal dropsy observed by him in Edin- burgh, encountered two, in which there was no albuminuria. 416 CHRONIC bright's disease. •or two ounces. With the granular contracthig kidney, the urine is abundant (three or four pints a day) in the middle periods of the disease ; but it gradually grows scantier towards the termina- tion; in e?:ceptional instances, the diuresis is profuse, and the urine may occasionally amount to five or even nine pints a day.^ These larger quantities have been generally observed .after an attack of ursemic convulsions, or coincidently with sudden subsidence of dropsy. The specific gravity is low when the urine is copious (1006 to 1015) ; but when it is scanty, the sp. gr, may rise to 1030 or even 1040. The reaction of the urine is nearly always acid; and, not unfrequently, it deposits uric acid and oxalate of lime. Occa- sionallj^ I have noted it alkaline from fixed alkali, and twice ammoniacal on emission. The renal derivatives (epithelium and tube-casts) are markedly scantier in the chronic, than in the acute forms of Bright's disease; and it is not uncommon for them to be altogether absent for limited periods. They are, however, sometimes dis- coverable when the urine has ceased (temporarily) to be albu- minous. The appearances of the discharged epithelia and casts present considerable diversities, which supply an important insight into the structural changes going on within the kidney. The epithelial cells may be simply withered ; more rarely they .are totally disintegrated into an amorphous granular debris; in other cases they contain specks of oil, or they may even be wholly converted into an agglomeration of oily particles so as to appear identical with the so-called " granular " or " Grluge's corpuscle." The casts are sometimes similarly speckled with fat, and free oily dots are scattered over the field. Such a con- junction indicates a fatal disorganization of the organs — either large fat kidneys, or contracted granular ones. But the casts most commonly seen in chronic Bright's disease are "small" and " large " hyaline forms, and " granular " opaque ones. Any of these may have a few wasted epithelial cells strewed over them. Perfect " epithelial " casts are rare in chronic cases, and blood ■casts are still more rare, unless there be concomitant tricuspid regurgitation. When intercurrent exacerbations of the renal process, with pyrexia, arise, there will be found (whatever may have been the previous character of the casts) medium-sized and large solid- looking, pale-straw, albuminous casts resembling molten glass [see Fig. 55). Casts of these diverse appearances may be discharged by the ^ Christison, pp. 174 and 186. Pfeufer, in Henle and Pfeufer's Zeitsch., Bd. 1. p. 58. PARTICULARS OF SYMPTOMS. 417 same individual, even during the Barae day. ConclusionH as to the probable state of the kidney can only be drawn from the 'prevailing character of the deposit, and not from one or two individual casts or cells. This diversity in the character of the casts arises from the different condition of the several parts of the gland. In some portions the tubuli may be denuded of their epithelium, and the exudation thrown into them is dis- charged in the form of large hyaline casts ; if the denuded por- tions have undergone subsequent contraction the casts will be small and hyaline. Other tubes, clothed or partly clothed with epithelium, shed some of their cells with the contained exudation, and cause the appearance in the urine of casts more or less studded with epithelial remnants. The longer the exudation is retained within the tubuli, the darker and more granular will it appear, when discharged as casts ; and vice versa, casts speedily discharged are commonly hyaline. Sometimes casts are dark- ened by the coloring matter of the blood; and the opaque gran- ular ones are (sometimes at least) composed of crushed epithelial debris moulded into the form of the tubuli. See Diagnosis. The normal solids of the urine are all diminished in chronic Bright's disease. The urea, is, as a rule, markedly reduced — the daily quantity averaging only about 100 grains ; Frerichs has observed it as low as 15 grains.^ There is no corre- spondence, direct or inverse, between the excretion of urea and the discharge of albumen. "With intercurrent pyrexia the excretion of urea rises. The changes in the blood are the complement of those in the urine. The blood becomes more watery and poorer in albumen and red corpuscles. On the other hand, urea, uric acid, the extractive matters and the pale corpuscles accumulate in it. This alteration in the composition of the blood is deeply con- cerned in the production of the more prominent features of the disease — the aneemia, dropsical effusions, ursemic phenomena, and secondary inflammations. Dropsy is much oftener absent in the chronic than in the acute form. It is much more constant with the smooth large, than with the granular contracted kidney. Of the latter class pro- bably one-third or one-fourth of the cases run their entire course without dropsy. The effusion begins quite as often in the feet and legs as in the face ; it is commonly slight and partial," but sometimes excessive and general. When the heart or liver is diseased, ascites and oedema of the legs become disproportion- 1 Exceptions occur to this rule. Mosler mentions a case of Bright's disease in which 640 grains of urea were voided in one day (Archiv d. Vereins, Bd. xi. S. 513). Schottin found creatine and creatinine increased in the urine in Bright's disease, and the increase was observed to keep pace with the intensity of the uraamic symptoms (Archiv der Heilk., 1860, p. 417). 27 418 CHRONIC bright's disease. ately prominent. The effusion is apt to change its seat capri- ciousl}^; and it comes and goes from time to time. Sometimes it disappears totally for months, and then returns again. More frequently,' after a subsidence of the general dropsy, oedema lingers obstinately in one or two places — over the flat of the tibise, about the ankles, beneath the eyelids, under the conjunc- tival membrane, or about the genitals. The presence or absence of dropsy, generally, but by no means always, corresponds with the abundance or scantiness of the urine; but it has no relation to the amount of albumen. The skin is usually obstinately dry, perspiration is quite exceptional ; and when it occurs, is commonly due to diapho- retic measures of treatment. Profuse sweating does, however, sometimes take place spontaneously, and may even continue for weeks. In one such case under my care an abundant crop of pemphigus vesicles broke out on the surface. The integuments in some cases are excessively pale and glossy, but more com- monly they are sallow and rough. There is little or no tender- ness in the renal region in the chronic cases, and the frequency of micturition is mostly observed at night. Some degree of bronchitis is almost an invariable coincident of Bright's disease both in the acute and chronic form. The pulse in Bright's disease almost invariably reveals high tension of the arterial system, when examined either by the finger or by the sphygmograph. The high tension is shown not by the pulse alone, but also by certain auscultatory signs, amongst which are accentuation of the aortic second sound, and, as was pointed out by the late Dr. Sibson,^ a reduplication of the first sound of the heart, at the cardiac apex. Dr. Broad- bent and Dr. Mahomed have shown that such high tension may precede all other signs of Bright's disease, and appropriate treatment may indeed ward off the more serious manifesta- tions. The retina in Bright's disease, and more frequently in cases of the red granular kidney, shows various changes, some of which are characteristic. Dr. Gowers^ first described a narrow- ing of the retinal arteries, coincident with the high blood pres- sure, the narrowed arteries frequently showing a white border. Inflammation of the optic nerve, and diff"used inflammation of the retina are met with; hemorrhages, too, are frequently seen and are most frequently " flame-shaped," and situated in the nerve fibre layer. The most characteristic lesion, howevei*, is a peculiar appearance of white specks arranged in radiations from the yellow spot. These specks are due to degeneration of the nerve fibres. The renal affection always precedes the retinal 1 Brit. Med. Journ., 1877, I. p. 33. ^ iby,^ igyg^ IJ. p. 743. COMPLICATIONS. 419 changes, although the latter have in many cases first called the attention of the observer to the possibility of Bright's disease being present.' Complications and Connection with Other Diseases. — In long-standing cases hemorrhage from the various mucous sur- faces sometimes occurs. A little haemoptysis is not infrequent, and occasionally severe epistaxis. The digestive organs are nearly always disturbed : at first there is loss of appetite and nausea ; in the later periods frequent or even uncontrollable vomiting is not uncommon. The bowels are alternately bound and loose. Severe fitful diarrhoea, which leaves the dropsy un- diminished, is not uncommon, especially towards the close of the complaint. Not unfrequently, anatomical lesions are found in the intestines which explain these disturbances; in other cases they are manifestly ursemic. Treitz states that urea is discharged into the intestines from the blood, and converted into carbonate of ammonia, which acts as an irritant on the intestinal mucous membrane. The more palpable changes found in the intes- tines are, follicular catarrh, dysenteric ulcers — sometimes with sloughing of the mucous membrane. In 220 cases of Bright's disease collected by Treitz, the following conditions of the in- testines were found after death.^ Hydrorrhoea (intestines filled with yellow-greenish fluid) . 80 times. Blennorrhcea and catarrh . . . . . . . 60 " Croupous and ulceious dysentery . . . . . 19 " Sloughing . . . . . . . . . . 12 " Sanguineous contents without discoverable source of) , ,( hemorrhage ........ / Normal feces . . . . . . . . . 5 " Contents of intestines undetermined. . . . . 11 " Secondary inflammation of the lungs, endocardium, peri- cardium, pleura, peritoneum, or integuments, may break out at any period in the course of chronic Bright's disease. The tendency to these constitutes one of the principal dangers of the complaint. Cardiac hypertrophy, valvular disease, and pulmo- nary tubercle are frequent complications. The following table exhibits the proportionate frequency with which the various organs, other than the kidneys, are found afiected in Bright's disease generally. It contains the result of 406 autopsies, contributed as follows : Bright, 100 ; Christison, 14; Gregory, 37; Martin-Solon, 8 ; Rayer, 48; Becquerel, 45; Bright and Barlow, 10; Malmsteu, 9; Frerichs, 21; Rosen- stein, 114. ' See J. Clifford Allbutt — On the use of the Ophthalmoscope, and Gowers's Medical Ophthalmoscopy. 2 Prag. Vierteljahrschr., 1859. 420 CHRONIC BRIGHT's DISEASE Heart. Lungs. Pleura. Pericar- dium . Perito- neum. Liver. Spleen. Stomach and Intestines. Brain. 125 times liy- 115 times 57 pleu- 30 peri- 4G peri- 41 cir- 58 chro- 36 gastric 14 san- pertrophy. oedema of lungs. risy. carditis. tonitis. rhosis. nic tu- mor. catarrh . guineous apo- 54 times with 38 fatty 85 catarrh and plexy. valvular dis- 52 pneumo- liver. 17 acute follicular ul- ease. ma. splenic tumor. ceration of Intestine. 59 eifu- sion of 65 times with- 8 pulmonary serum out valvular apoplexy. 13 tuberculo- under disease. 4 gangrene . 3Y tubercle. 33 vesicular emphysema. sis of intes- tine. arach- noid- In addition there were : 1 case complicated with cancer of the liver ; 4 cases with cancer of the pylorus ; 2 typhoid ulcers of intestines ; 2 meningitis : 1 meningeal tubercle ; 11 tumor cerebri ; 3 abscess of lung ; 11 nutmeg liver ; 3 lardaceoas liver ; 9 contraction of spleen ; 3 diphtheritis of intestines ; 1 softening of brain ; 6 chronic arachnitis ; 1 suppurative meningitis. Bright' s disease and phthisis. This complication is of frequent occurrence. In the great majority of cases the pulmonary disease is advanced to its later stages before the renal symptoms make their appearance. The long- continued discharge of pus from the lungs gives rise at length to waxy changes in the kidneys, v^^hich are followed by albuminuria and dropsical effusion. This is no doubt the usual history of such cases ; but sometimes the renal disease precedes the pulmonary, and the changes found in the kidneys after death are not invariably of the waxy type. The coexistence of two fatally tending diseases might have been expected to accelerate the inevitable issue ; yet most cases of this class have an exceedingly chronic course, and continue in a stagnant condition for months together. The onset of albuminuria often determines a fall of the temperature.^ In the following remarkable instance, the pulmonary disease (already in its third stage) completely retrograded, and was supplanted by the renal affection. M. C, set. 20, a meclianie, was admitted into the Royal Infirmary, October 27, 1863. He was a well-grown young man, with white pallid features, dry skin, heavy eyes, and moderate oedema of the lower ex- tremities. The abdomen was enlarged from ascites, and the integuments of the flanks and hypogastrium were cedematous ; pulse 112, regular, small ; respirations 21 ; tongue moist, slightly furred. The state of the chest on admission was as follows: Diminished expansion over both apices ; but more on the right side than the left ; conspicuous depression of the right infra-clavicular region. There was almost complete loss of ^See Williams, Brit. Med. Journ., 1883, II. p. 1224. COMPLICATIONS. 421 resonance on the right side as low as the second interspace. The right upper scapular regions were also dull on percussion. Moist crepitation and cavernous rhonchi were heard beneath the clavicle on both sides. Whispering pectoriloquy was very distinct below the right clavicle, and present, though less typically, over the left apex. The heart's sounds were natural ; there was no appreciable hypertrophy. The expectora- tion was copious, airless, purulent. The urine was scanty, araber-colored, specific gravity 1030, intensely albuminous, becoming almost solid on boiling. A slight deposit of withered renal epithelia and transparent tube-casts, without any, or only very faint, signs of fatty changes, lay at the bottom of the glass. The history disclosed perfect health until ten months ago, when the patient began to cough. He attributed these symptoms to cold taken by passing out into the cold air from his hot work-room. His family is tuberculous ; a sister came subsequently under my care with phthisis. He had night perspirations six months ago. Three weeks before admis- sion the ankles began to swell ; but the skin had been dry for three months. Cod-liver oil and iron were prescribed ; a warm bath was adminis- tered every other evening. The patient constantly kept his bed, on account of the swelling in his legs increasing when he sat up. Fig. 54. Transparent hyaline casts, from the urine of M. C , on January 29 (quiescent period). For a period of two months I was unable to attend at the Infirmary on account of illness, but the treatment was carried on during my absence without alteration, and the patient kept continuously in bed. "When I revisited the wards in January, 1865, I found the renal symp- toms somewhat advanced ; but the pulmonary complaint had decidedly 422 CHRONIC BRIGHT'S DISEASE, receded. The urine was very scanty, varying from 12 to 18 and 26 ounces a day, with a specific gravity ranging from 1030 to 1034; it often deposited amorphous urates. On January 29th the urinary de- posit corresponded to the following description : It was scanty, and composed of atrophied renal cells, with a few excessively transparent small hyaline casts, some of which were speckled with albuminous granules and a few doubtful oil particles (see Fig. 54). The patient at this date was in a quiescent state and free from fever. The chest complaint was now altogether in the background ; there was scarcely any expectoration, and the physical signs indicated a marked amelioration. The depression under the right clavicle was less conspicuous, and the movement improved ; the percussion sounds were still unaltered, and the rhonchi still cavernous, but not abundant ; pulse varied from 88 to 100 ; respiration from 20 to 22. During February the urine became still scantier (12 to 20 ounces a day), with a density ranging from 1033 to 1041. It became almost solid on boiling. The anasarca increased, and extended into the face Fig. 55. Massive molten-looking casts, from the urine of M. C, February 28 (pyrexial period). and upper limbs. Occasional vomiting took place, and the appetite failed entirely. In the last week of February the patient insisted on going home. But he had not been out a single day before he took a violent cold, ushered in with repeated shiverings. The anasarca increased rapidly ; respiration became oppressed, and he was readmitted three days later (February 26th) in the following state : Great general dropsy, the urine almost suppressed, distressing oppression of breathing. A compound COMPLICATIONS. 423 jalap powder was administered ; after which he vomited and had three loose motions. On the following day, the patient was very thirsty and feverish ; tongue furred, red at edges; pulse Ti'"^ ; respiration 30; cough very distressing; a scanty expectoration of nummular purulent sputa. He complained loudly of pains in the abdomen, chest, and back, especially when he turned in bed. There was great restlessness. A hot-air bath was administered with the effect of inducing copious sweating, and reducing the oedema somewhat. February 28. — Urine, last 24 hours, only 8 ounces ; it was intensely albuminous and deposited urates. The renal derivatives presented totally new characters ; they are delineated in Fig. 55 ; the new feature was the appearance of massive molten-looking casts of large and medium size. Some of them were slightly granular in spots ; a few were also sparsely studded with epithelium; but there were no proper "epithelial casts ;" there was neither blood nor fat. Some of the large casts lay side by side like thick logs, and appeared as if split in a longitudinal direction at their extremities (Fig. do^. On the 28th the patient grew feebler and more restless ; obstinate vomiting set in, and continued nearly till death, which took place on the morning of the 29th. Only two ounces of urine were passed in the last 24 hours of life. There were neitner convulsions nor coma ; and vision continued good to the last. Autojisy, 30 hours after death. The right lung presented an exquisite example of retrograde phthisis. Half a dozen small cavities were counted in the upper lobe — all of them small, varying from the size of a pea to that of a horse-bean — completely lined with a thick pyogenic membrane. Not a particle of tubercle existed around these cavities nor in any part of this lobe. The pulmonary tissue was dark and. leathery, and very imperfectly aerated. The right apex was condensed, deeply puckered, and traversed in various directions by thick white lines of cicatricial tissue. In the lower lobe of the same lung, a vomica as large as a filbert was found with anfractuous boundaries composed of tuberculous matter. , Small masses of obsolete tubercle — some cretace- ous, others putty-like — were scattered sparsely through the lower lobe. The left lung was crepitant throughout. The upper lobe contained three cavities — one as big as a walnut — lined with pyogenic membrane, and not surrounded by tubercle. Small nodules of tubercle were scat- tered through the upper and middle lobes — some cretaceous, some putty-like, others unsoftened and crude. The inferior lobe of the left lung was highly cedematous. ]S"o fluid existed in either pleura ; but old adhesions pi-evailed sparingly on both sides. The heart was of the usual dimensions ; the walls of the left ventricle were thicker than was to be expected in a case of phthisis. Both sides were filled with firm bulky clots of yellowish fibrine, which closely adhered to the inequalities of the chamber, and sent voluminous pro- longations into the aorta and pulmonary artery. The formation and presence of these clots evidently constituted the immediate cause of dissolution. The liver was large and pale ; the hepatic cells well formed, and not containing more than the usual quantity of fat molecules. 424 CHRONIC bright's disease. The spleen was larger than usual ; its texture soft and natural. The kidneys weighed together 23 ounces, and the two were almost exactly of a size. They furnished a typical example of the large, smooth, mottled kidney. Their surface was perfectly smooth ; the cap- sule, thin and transparent, peeled off readily without tearing the glandular tissue. The prevailing color of the surface was fawn, marbled here and there with red ; the fawn color was picked with dead white, as in ivory. The organs were conspicuously soft and flabby. The red parts of the surface showed minute spotty and sinuous injection of the superficial vessels. On section, the cortex was found greatly hypertrophied ; it stood half or three-quarters of an inch thick on the broad ends of the cones. It had a full fawn color, with broken streaks of red running through it in diverging lines, from the bases of the pyramids. The pyramids were unusually pale, though from the exsanguine state of the cortex, they offered a pretty strong contrast of color with the latter. The epithelial lining of the convoluted tubes was extensively disorganized ; both cell and nucleus were reduced to a granular, fatty debris. Scarcely a single cell approaching perfection could be seen. The Malpighian corpuscles were not altered in size ; but they were penetrated, and rendered opaque, by a granular material. The epithelium of the straight tubes was in much better preservation ; not only the nuclei could be seen, but the out- lines of the cells themselves. A considerable quantity of spindle-shaped fibre-cells were found, also medium-sized, massive-looking casts — resem- bling those found in the urine shortly before death. Two things appeared singular in relation to these kidneys, namely, that the urine should contain so few renal derivatives when the kidney contained such an immense quantity in a disorganized state ; and sec- ondly, that this disorganized material should contain fat in such quantity without there having been any, or scarcely any, in the urinary deposit. Perhaps the degeneration of the epithelium only attained this maximum degree in that last intercurrent febrile attack which immediately pre- ceded death ; if so, the plugging up of the canals of the pyramids with the massive casts, which then appeared for the first time in the urine, and which may have been the determining condition of the suppression of urine, would cause the absence from it of the derivatives of the con- voluted tubes. Bright's Disease and Diseases op the Heart and Vascular System. — The connection of cardiac disease with renal disorder is at least threefold. In the first class of cases, simple hypertrophy of the heart and especially of the left ventricle, is found without valvular incom- petency and without degeneration of the muscular fibres. In this class, which is a numerous one, as the table at p. 420 shows, the cardiac afiection is secondary to the renal. Bright, who was the first to point out this curious coincidence,^ offered two explanations of it — either, that the altered composition of the blood 1 Gny's Hospital Reports, vol. i. p. 390. COMPLICATIONS. 425 exercised an irregular and unwonted stimulation upon the muscular tissue of the heart, or so impeded the circulation in the capillaries, tliat a greater effort of" the ventricle was required to drive the l>lood through the distant minute branches of" the bhmdvesscls. Traube' explains tlie occurrence of simple cardiac hypertrophy in chronic Bright's disease somewhat differently. In his experience the kidneys in these cases are markedly atrophied.^ The contraction of the renal tissue involves de- struction of a certain amount of secreting structure and a diminution of the flow of blood through the organs by reason of the destruction of bloodvessels. Two consequences follow, namely, that a diminished amount of blood passes from the arterial into the venous system, and that a less quantity of fluid is withdrawn from the arterial system for the formation of urine. Both circumstances, but especially the second, operate to increase the tension in the arterial system, and consequently to increase the resistance which the left ventricle has to overcome in dis- charging its contents. The hypertrophy which follows is, therefore, according to Traube, a conservative or compensating change, similar, in the mechanism of its production, to that induced by valvular incom- petency or aortic constriction. If the compensation be complete, the heightened tension in the arterial system occasions a larger transudation of water and even of urea and other urinary solids, through the kidneys, and in that manner materially helps to stave off dropsical effusion and ursemic symptoms. But should some additional obstruction to the cir- culation arise, through intercurrent inflammation of the bronchial tubes, or of the lungs, pleura, or pericardium, the heart — enlarged and strength- ened through it be — no longer suffices to overcome the increased resist- ance, and dropsical effusions or ursemia speedily make their appearance. Traube adduces some apposite examples in which individuals Avith con- tracted kidneys enjoyed fair health, with capability of exertion, and continued free from anasarca and ursemic disturbance, until the advent of some complication disordered the balance of the circulation, and then the urine became scanty, and the familiar symptoms of renal disease, previously latent, broke forth into prominence. The first part of Traube's argument, that the granular kidney offers a resistance to the passage of arterial blood, has been proved by the experi- ments of Dickinson and Thoma mentioned above (see page 400); but whether this obstruction is competent to produce high arterial tension and hypertrophy of the heart is doubtful. Experimental evidence is conflicting. Ludwig ligatured the renal arteries without causing high vascular tension or hypertrophy ; Grawitz and Israel narrowed the renal artery and removed one kidney, but while they did so cause hyper- trophy of the heart, they assert that there was no increased tension. Lewinski,^ on the other hand, by similar experiments obtained both 1 Ueber den Zusammenhang von Herz- und Nieren-Krankheiten, p. 58. ^ In a later communication Traube brings forward evidence to sliow that hyper- tropliy of the left ventricle is an almost constant concomitant of granular and contracted kidney. In 77 cases collected by him from various sources, the left ventricle was found hypertrophied in 93 percent. (Deutsche Klinik, 1859, p. 815). In 187 cases of granular kidneys collected by Dr. Sibson enlargement of the left ventricle (without valvular disease) was found in 128. ^ Zeitschr. f. klin. Medic, vol. i. p. 561. 426 CHRONIC bright's disease. hypertrophy and increased tension. Bamberger objects to the first part of Traube's view, on the grounds that hypertrophy of the heart may be found when there is no destruction of the bloodvessels in the kidney, or where anastomoses have been set up, as was shown by Thnma in the granular kidney; that the ligature of even large vascular trunks does not cause hypertrophy ; and that this view does not apply to the hyper- trophy of the right ventricle, which is also found. Bamberger^ adopts the second part of Traube's view, that the hypertrophy is produced by an increased volume of the blood caused by deficient excretion of fluids. In the granular kidney, where the urine is increased in quantity, he believes that a stage of deficient excretion has preceded, and that the present hyperexcretion is merely due to the balance of the system being set for a higher grade. Dr. George Johnson has discovered that there is a wide-spread hyper- trophy of the muscular walls of the small arteries in chronic Bright's disease. He finds it not only in the arteries of the kidneys, but also in those of the pia mater, the skin, the intestines, and the muscles. He thus explains the production of this hypertrophy and the manner in which it reacts on the left ventricle : " In consequence of the degenera-- tion of the kidneys the blood is morbidly changed. It contains urinary excreta, and it is deficient in some of its own normal constituents. It is therefore more or less unsuited to nourish the tissues — more or less noxious to them. The minute arteries throughout the body resist the passage of this abnormal blood. The result of this antagonism of forces is, that the muscular walls of the arteries and those of the ventricle of the heart become simultaneously and in an equal degree hypertrophied. The persistent overaction of the muscular tissue, both cardiac and arte- rial, is found registered after death in a conspicuous and unmistakable hypertrophy." With this view Dr. Broadbent in the main agrees. He believes, how- ever, that the vitiation of the blood precedes the kidney change. During this prenephritic stage, high tension is produced by the contraction of the muscular walls of the arterioles, but by appropriate treatment the kidney mischief may be avoided. Dr. Broadbent shows that the high tension, even in confirmed Bright's disease, is not permanent, but may temporarily disappear during an attack of pyrexia, or under the in- fluence of nitrite of amyl, which relaxes the arterioles. This tends to show that it is the action of the arterial muscular tissue which produces the high tension, and not a permanent change, such as the capillary fibrosis of Gull and Sutton, mentioned below. Dr. Galabin believes that the impediment to the circulation in chronic Bright's disease lies not as Dr. Johnson supposes in the small arteries, but in the capillaries, and is due to a modification of the capillary attraction between the blood and the walls of the vessels, and that, the arterial pressure being thus increased, the muscular walls of the heart and arteries are both hypertrophied in concert, since both have to act against greater resistance. Sir Wm. Gull and Dr. Sutton have advanced a novel view of the pathology of granular kidney and of the associated changes in the car- ^ Yolkmann's Samml. klin. Vortriige, No. 173. COMPLICATIONS. 427 dio-vascular system. They announce the discovery of a new pathologi- cal change, to which they give the name of " arterio-capillary fibrosis." This consists in the deposit of a " hyalin-fibroid " material in the fibrous coats of the arterioles and capillaries. This change may prevail exten- sively throughout the vascular system — in the kidneys, skin, pia mater, heart, lungs, spleen, stomach, and retina. In its nature it is allied to but not identical with senile changes. It commonly begins in the kid- neys, but it may begin elsewhere ; so that the hyj)ertrophy of the heart with degeneration of the bloodvessels may be found associated with healthy kidneys ; and that when atrophy with granulation of the kid- neys exists it is but part and parcel of a general morbid change. The granular form of Bright's disease is, in their eyes, essentially an example of arterio-capillary fibrosis. This view has been strongly supported by Dr. Mahomed in this country, and by Leyden in Germany. That a wide-spread change in the small arteries of the body exists in Bright's disease seems now well established, but what the nature of that change may be is by no means determined. Thoma showed that there was thickening of the subeudothelial layer of the small arterioles, cor- responding to the similar lesion found in syphilis by Huebner. This condition of the vessels, so far at least as the kidney is concerned, is generally admitted. Thoma was of opinion that the muscular coat instead of being hypertrophied was really atrophied. Ewald, w^ho examined the vessels of the pia mater covering the pons Varolii in sixty- two cases of Bright's disease, could not confirm the discovery of Gull and Sutton. The appearances described by them, he believed, were the results of the reagents employed. On the other hand, he confirmed the opinion of Dr. G. Johnson as to the hypertrophy of the muscular coat, and showed further, that the general vascular change was associated rather with interstitial than with parenchymatous changes in the kidney. Senator described a difference in the character of the hypertrophy according as the kidney change began in the epithelium or in the inter- stitial tissue. In the former case dilatation was combined with hyper- trophy of the heart, while in the latter the hypertrophy was pure. In the first case he believed with Dr. G. Johnson that the retention of excrementitious matters in the blood caused a rise of arterial tension and consequent hypertrophy ; in the second case he believed the hyper- trophy to be due to a general change in the small arteries. His differ- entiation of the two kinds of cai'diac enlargement cannot, however, be sustained, for dilatation of the left ventricle is by no means uncommon in the later stages of granular kidney, and is due to weakening of the heart muscle. BuhP placed the cardiac change in the primary position. He believed that there was initially a myocarditis which caused the hypertrophy. Debove'' and Letulle, in support of this view, have shown that a fibrous growth between the muscular fibres of the left ventricle is common in Bright's disease. The opinion has not met with any considerable sup- port. These views have been sharply criticised, and. are still in dis- pute, but the}^ unquestionably bring into true prominence what 1 Mittlaeiluna;en a., d. path. Institut, Munchen, 1878. 2 Progres Mklical, 1876, No. 52. 428 CHRONIC bright's disease. every observer of extended experience in eases of granular kid- neys must have had strongly impressed on his mind — namely, that the renal disease is not merely a local affair, but that it is, rather, a part of a widespread tissue degeneration involving the entire, or a large, portion of the body. Of the various forms of chronic Bright's disease, the red granular kidney is the most frequently accompanied by hyper- trophy of the heart; less frequently does the association occur with the large white kidney; while with the amyloid kidney the enlarged left ventricle is only rarely found. In the second class of cases, valvular defects and their conse- quences coexist with Bright's disease. Most of these are ex- amples of endocarditis, secondary to the renal disease. But in other cases the cardiac and renal aifections arise independently of each other, and depend on some cause common to both — as in the following example: J. H., set. 48, was admitted into the Manchester Royal Infirmary, November 22, 1862. He had right hemiplegia ; the mental faculties were wholly disordered; there was gay incoherence and insanity; no fever. The heart's apex beat in the fifth interspace, half an inch out- side the nipple line ; a loud systolic bruit was audible at the apex and the mid-sternal base, and extended up the aorta ; a faint diastolic bruit was audible over the second right cartilage. The urine was albuminous to about one-fifth ; there was no dropsy. The patient remained in the Infirmary a month. The mental de- rangement subsided in ten days, and perfect coherence returned. The other symptoms remained unchanged. He returned home; and in a few days was seized with coma, which proved rapidly fatal. The au- topsy revealed : granular red kidneys with abundant presence of fat ; cardiac hypertrophy with fatty degeneration of the muscular fibres ; extensive disease of the mitral and aortic valves with atheromatous patches on the aorta ; two old apoplectic clots were found in the left hemisphere, and wide-spread fatty degeneration of the arteries existed at the base of the brain. In this instance fatty degeneration had simultaneously invaded the heart, the brain, and the kidneys, and produced a triple series of symp- toms — -all essentially independent of each other. The third class of cases are those in which the renal disorder (congestion, etc.) is secondary and subordinate to cardiac disease. These cases have already been fully described in Chap. I. in connection with Congestion of the Kidneys, which see. ITPv^EMIA. Certain phenomena, chiefly affecting the nervo-muscular sys- tem, arising in the course of Bright's disease, have been attri- buted to a poisoned state of the blood, from the retention in it of excrementitious matters which the disabled kidneys are unable UR--EMIA. 429 properly to eliminate. To theise phenomena tlie term urcernic has been applied; they consist of twitchinf(s and convulsions of the voluntary muscles, headache, drowsiness, coma, defects of sight and hearing, vomiting and diarrhfpa. It is a marked feature of urajmic phenomena that those which are of a paralytic nature atfect the sensorium and the special senses, but not the voluntary muscles; while those of an oppo- site kind (exalted irritability) affect the voluntary muscles, but not the sensorium. Delirium is rare, while coma is frequent; paralysis of the limbs is scarcely known (unless there be some anatomical lesion of the brain superadded), while convulsions are frequent. The mode in which ursemic symptoms enter on the scene, and the forms they assume, present great diversity. Generally they begin insidiously with headache or vomiting, followed by heaviness, indifference, and somnolence. These premonitories may either pass away in a few days without further consequence, or they may be succeeded by general con- vulsions and coma. In other instances the patient is at once struck down with convulsions or insensibility without any pre- vious warning, or he becomes suddenly blind, or is seized with uncontrollable vomiting. The most common of these symptoms is headaclie; few indi- viduals with degenerated kidneys altogether escape it. A sense of heavy weight or compression is complained of over the fore- head or vertex. Sometimes the pain is obstinately fixed at the back of the neck, or behind the orbits. The defects of sight consist either in a dimness of vision (am- blyopia), which comes and goes — objects appearing as if veiled in mist — or in rapid and complete, though usually temporary, blindness. The convulsive seizures are often accompanied with temporary loss of sight, which generally persists in greater or less degree for a certain time after the spasms have passed away. The ophthalmoscope reveals no organic change in the eye in genuinely ursemic amblyopia: it is a purely cerebral pheno- menon, and not to be confounded with the hemorrhagic blind- ness (Retinitis apoplectica), which is also not uncommon in Bright's disease, and which is due, as V. Graefe has shown, to rupture of the retinal vessels. In this latter affection (which is in no sense uraBmic) the loss of sight is seldom complete, but is of a more permanent character. The production of it is prob- ably due to hypertrophy of the left ventricle which so commonly accompanies a contracting kidney, and the increased tension in the arterial system consequent thereupon ; it is an occurrence of the same order as the sanguineous apoplexy to which the same individuals are liable. 430 CHRONIC bright's disease. TJrsemic deafness is much less common than amblyopia, and its occurrence is highly exceptional. UrEemic convulsions are of the epileptic type, and, as a rule, they conform strictly to that type — being accompanied with complete insensibility, rolling of the eyes, biting of the tongue, and foaming at the mouth. The paroxysms commonly leave the patient deeply comatose. In exceptional instances consciousness is not wholly lost. In a lady under my care the paroxysms coincided with the cata- menial periods ; during the convulsions the patient knew the persons about her, and called loudly to be held fast. A case is related by Bright in which the spasms at first resembled cramps ; these were followed by twitchings of the hands, arms, shoulders, chest, and legs. The spasms were almost constant, and caused a somewhat hurried mode of expression when the patient spoke, but the intelligence was perfect. As the case proceeded the spasms became more and more severe, with forcible drawing up of the legs, and distortion of the muscles of the face; the faculties were retained to the last.^ An attack of ursemic convulsions may consist of only a single paroxysm : more frequently there occurs a succession of par- oxysms or fits, following each other at uncertain intervals of a few minutes or several hours — the patient lying during the re- missions in a state of profound insensibility, with stertorous breathing, pale face, and dilated pupils ; or in deep drowsiness, but capable of being partially roused, when spoken to or shaken. If a first attack does not prove fatal, it may recur at irregular intervals of weeks or months, or be replaced by ursemic symp- toms of some other order. Instead of the clonic convulsions tonic spasms are occasionally met with, afifecting various muscles. Occasionally, too, the spasms are limited to special groups of muscles and may occasionally cause a condition of opisthotonus.^ Ursemic coma either creeps on very gradually, passing on, in the course of two or three days, into complete stupor; or it culminates quickly — the patient falling down, as if in apoplexy, perhaps while walking in the street, or occupied with his usual avocation. Cases of this class when there is no anasarca, and the previous state of the urine is unknown, are very liable to be confounded with apoplexy or with narcotic poisoning. The following instructive illustrations of such an occurrence are related by Mr. Moore and Dr. Richardson : Case 1, — An old soldier, named Price, was received into Queen's Hospital, Birmingham, with the following symptoms : breathing labori- ous and sometimes stertorous ; when left alone the patient passes into a 1 Guy's Hospital Reports, 1840, p. 139. 2 Jaccoud. Pathol. Interne, 6th edit., vol, ii. p. 439. UBMMIA. 431 state of stupor, answers (juestions seiifiibly when roused; pupils nrioder- ately dilated, indolently sensitive to light. It appeared that I'rice, having suffered some days from diarrhoia, went into a druggist's shop, and asked for a pennyworth of tincture of rhubarb. The shopman added to this dose a few drops from another bottle, and Price swalhjwed the whole before leaving the shop. Immediately after taking the above dose he became drowsy and vomited ; at the suggestion of a neighbor he returned to the shop, and asked the shopman whether he had given him laudanum. The latter told him that he had put in a few drops on account of the severity of his symptoms. Upon again reaching home he fell asleep, and continued sleeping unless temporarily roused. In this state he was taken into hospital, and was treated as a case of opium poisoning. A mustard emetic was ordered immediately; the patient was kept in constant motion, and plied with strong coffee. He improved considerably under the treatment, and talked over his old campaigns with the porter who had charge of him. Next day he relapsed into a lethargic state ; gal- vanism was employed without benefit ; he was now walked round the hospital garden between two men, and strong infusion of green tea was administered, A little improvement followed, but at 2.30 f. m. he re- lapsed once more, and the breathing became more oppressed. As long as he was kept moving he could be made to answer questions ; but in the course of the afternoon the somnolence deepened in spite of the treatment. Ether and ammonia were applied to the nostrils ; cold Avater was dashed over the face and neck ; but at 8 p. m. the drowsiness had become insuperable ; the stertor augmented. Mustard poultices were put to the legs. Venesection was tried, but when four ounces of blood had flowed the pulse became thread-like, and it was thought prudent to desist. The coma increased in intensity; and he died at 2.30 A. M., 44 hours after admission, and 102 hours from the time of taking the dose. A coroner's inquest was held on the case, on account of the suspicion of poisoning ; but the results of the post mortem went to exonerate the druggist, for the kidneys were found granular and greatly atrophied, and the urine left in the bladder was found albuminous. (J. Moore, ''London Med. Gaz.," 1845, p. 821.) Case 2. — A woman, aged 34 years, who was given to drinking, and had recently been treated for primary syphilis, was seized on November 18, 1859, with rigors. She was attended by a neighboring chemist, who, on November 22d, gave her a mixture which, he said, contained dilute nitric acid, nitrate of potassa, syrup of buckthorn, sulphate of mag- nesia, and water. It was afterwards proved by analysis that these were the constituent parts of the remaining portion of the mixture. The medicine was sent in to the woman on the evening of the 22d, and after taking a large quantity of beef-tea, she swallowed one dose of mixture. Five minutes afterwards she became hysterical and convulsed, and the friends believing the woman to have been poisoned, summoned the drug- gist, who in alarm tried to get her to take some ipecacuanha, but without avail. In the course of the night a medical man was called in ; he found the woman in a state of typhoid coma, wdth pupils slightly dilated and immovable, and the body at times convulsed — the convulsions 432 CHRONIC bright's disease. assuming an epileptiform type. Every available means of treatment was carried out, but the coma became more profound, and seventy hours after the administration of the mixture above mentioned, death closed the scene. By the coroner's warrant the body was examined, and a chemical inquiry instituted. The brain was quite healthy; the kidneys were greatly diseased — large, flabby, pale, speckled, soft, and greasy. The analysis disclosed no poison of any sort. (Richardson, " Clinical Essays," p. 135.) Case 3. — A gentleman, set. 63, was driving in an open chaise through the village of Mortlake, in 1853 ; he was observed by his servant, who was by his side, to be constantly drowsy; at last he suddenly seemed to fall into a helpless state and dropped from the chaise. He was con- veyed into a house, and Dr. Richardson was summoned. Dr. R. found hitn suffering from all the signs of narcotic poisoning ; the pupils were fixed and slightly dilated. Some urine was withdrawn from the bladder, and found to be largely charged with albumen. He recovered from the attack ; but three weeks later he suffered again in the same way, and died with typhoid coma — the urine being altogether suppressed for many hours before death, and having been albuminous throughout the illness. (Richardson, "Clinical Essays," p. 141.) The diagnosis of uraemic coma from apoplexy rests on the absence (in the former) of paralysis, and the partial recovery ot consciousness between the convulsive attacks — if there be any. From poisoning by opium, renal coma is distinguished by the dilated or semi-dilated state of the pupils, and by the occurrence of remissions in the insensibility. From ordinarj^ epilepsy the diagnosis — apart from the antecedent history, which, if known, suffices to indicate the nature of the case — is sometimes difficult. The incidents of the seizures are often identical, even to the existence of an aura. In uraemia the respiration frequently assumes the Cheyne-Stokes type. As a rule, ursemic fits want the turgid purplish countenance and asphyxial character of true epilepsy — the face in ursemia being nearly always deadly pale and the breathing easy. Dr. Richardson relates the cases of two children poisoned by belladonna berries, in which the symptoms closely resembled ursemic coma sequential to scarlatina. The insensibility was complete, and the pupils strongly dilated. The examination of the vomited matters and of the urine furnishes, in such cases, the best means of diagnosis. In all cases of convulsions or insensibility^ from doubtful causes, the urine should be forthwith examined, and, if neces- sary, withdrawn by catheter for that purpose. It must not, of course, be forgotten, that sanguineous apoplexy is a not unfre- quent occurrence in chronic Bright's disease, as in the case of J. H, before related (p. 428), Ursemic coma and convulsions may prevail separately; but UR.EMIA. 433 much more commonly the attacks are of a mixed character, and combine several or all the phenomena just enumerated. As a rule, both the quantity of urine and the excretion of urea diminish notably at the period immediately preceding a ursemic attack. Sometimes, however, very great scantiness of urine, or even total suppression (in acute Bright's disease) may exist without evoking any urfemic symptoms. In a case of scarlatinal dropsy related bj'^ Biermer, complete suppression of urine continued for 5 days without uraemia; then followed a further period of 41 days in which urine was secreted, but only in the scantiest proportions (a few teaspoonfuls a dav), and yet no uraemia. At the end of this second period, the urine began to flow abundantly for a short time, and then again became scanty. Three days later urseraic coma set in, followed by convulsions, which proved fatal. If the patient recovers from the coma, various mental symp- toms, such as mania or melancholia, may show themselves.^ Ursemic vomiting and diarrhos.a are common phenomena of Bright's disease. The vomiting which occurs in that disease is not, of course, always ursemic. The digestive functions are notably impaired throughout the complaint, and a heavy or indigestible meal may at any time be rejected, as in dyspeptic states from other causes. When the vomiting is really uremic it takes place without reference to the nature of the contents of the stomach, and is oft-repeated or uncontrollable; the vomited matter is a watery fluid, either distinctly ammoniacal to the smell, or (if acid) evolving ammonia freely when caustic potash is added thereto. The alvine dejections are similarly characterized when due to the same cause. Paroxysms of dyspnoea belong to the least frequent forms of ursemic disturbance — if indeed such attacks have at any time a genuine claim to the designation ursemic. Fournier cites.some cases of this kind. Only the following somewhat doubtful example has fallen under my observation. The case is further remarkable on account of a transitorily ammoniacal state of the urine. W. R. S., a railway porter, set. 58, was admitted into the Manchester Infirmary, December 6, 1860. He was a stoutly made man, who had led an intemperate life. He had been remarkably healthy, and had scarcely ever lost a day's work. Two months before admission, his legs began to swell and then his face. He continued to follow his employ- ment, though with difficulty, until two days before his admission. On admission, there was a general anasarca of moderate degree ; pallid features ; enlarged heart ; copious urine, scantily albuminous, with an abundant deposit of granular and transparent casts, and renal epithe- ' Wagner. Ziemssen's Cvclopwd., Sd edition. 28 " 434 CHRONIC bright's disease. Hum. Neither cast nor epithelium showed any signs of fatty degenera- tion. The urine was sometimes highly acid and deposited urates ; at other times it was highly ammoniacal when voided. On December 27th there occurred a sudden and most intense paroxysm of difficulty of breathing, which threatened suffocation. It resembled in every respect a paroxysm of spasmodic asthma, and lasted five hours. It then passed away, and did not return again with the same intensity ; though slighter attacks of a similar nature occurred on two other occa- sions. On January 11, 1861, repeated vomiting took place ; there was also a severe cough with a watery expectoration and increasing weakness. Somnolence then set in, which gradually passed into coma and proved fatal in three days. The autopsy showed hypertrophied left ventricle; thickened mitral valve ; abundant loose vegetations on the aortic valves. The right auricle and ventricle were filled with a firm voluminous yellow fibrinous clot. With the exception of dense oedema of the inferior lobe of the left lung, the respiratory organs presented nothing abnormal. The kid- neys were found granular with commencing atrophy. The lower urinary passages were quite free from disease. The ammoniacal state of the urine persisted in this patient for several successive days ; and although the secretion was so charged with car- bonate of ammonia that it had a pungent smell, and eflTervesced freely with acids, when quite fresh, the patient experienced no pain or uneasi- ness about the bladder nor during the act of micturition — which was not unduly frequent. The urine contained no pus. The ammonia in this case must have been derived directly from the blood, and not pro- duced, as is usual in ammoniacal urines, by transformation of urea in the lower urinary passages. Such an occurrence betokened a free gen- eration of ammonia in the blood ; there were no ursemic symptoms on the days when the urine was ammoniacal. Did the elimination of ammonia by the kidneys stave off" ursemic accidents? Theories of Uraemia. — The absence of anatomical lesions in the brains of persons who die of ursemic coma and convulsions has constrained pathologists to look elsewhere for the deter- mining cause ; and by general agreement it has been assumed that that cause consists in certain alterations in the composition of the blood, from the accumulation in it of the excrementitious matters (and the products of their decomposition) which, in the healthy state, are removed out of the body by the kidneys. The blood thus poisoned is no longer capable of ministering to the tranquil and healthy operations of the nervo-muscular system, and engenders the various abnormities of motion and sense which have just been described. But pathologists have not. been content with this general appreciation of the matter, and have striven to trace the pheno- mena to the presence of some one, or the derivatives of some one, of these excrementitious substances in the blood. It will THEORIES OF UKiI<:MIA. 435 not be necessary in a, practical work like the present to enter fully into the controversies — still undecided — which have arisen on this subject. It will suffice to indicate the different views which have been enunciated; and to express my own conviction, after a careful review of the observations and experinien adduced on all hands, that none of the exclusive theories of urseinia has made good its claim to acceptance. Hammond and Richardson, following the original notion of Willis, contend that the special poison in these cases is urea.' Frerichs and many more recent observers maintain, on the other hand, that urea is itself innocuous ; that it may be injected into the veins of animals without detriment; that the mischief in uraemia arises from the transformation of the urea accumulated in the blood into car- bonate of ammonia, and that the carbonate of ammonia so generated is the immediate excitant of the nervous symptoms. Frerichs upholds this doctrine by two propositions which he claims to have proved, namely : (1) that carbonate of ammonia invariably exists in the blood of uremic patients, and in that of animals rendered ursemic by removing their kidneys, and can even be discovered in their expired air ; (2) that car- bonate of ammonia injected into the veins of healthy animals produces fits of convulsions with intervening pauses of coma, exactly resembling genuine ursemic attacks. Treitz suggested a modification of this view. According to him, urea is not transformed in the bloodvessels, but is first vicariously excreted into the alimentary canal ; here it is speedily converted by the gastro- intestinal mucus into carbonate of ammonia ; the carbonate of ammonia so formed is then absorbed into the blood, and pi'oduces its poisonous effects. That urea is excreted by the intestines in Bright's disease is undoubted, and its swift conversion into carbonate of ammonia has been proved experimentally by Bernard. This theory of Treitz furnishes at least a rational explanation of ursemic vomiting and diarrhoea, and of the presence of the volatile alkali in the matters so discharged. Since the theory of Frerichs was first promulgated, however, it has been ascertained by Richardson and Hammond that ammonia naturally exists in the blood of healthy animals ; and all subsequent observers (with the sole exception of Petroff) have failed to discover in the blood of animals rendered ursemic by the removal of their kidneys any larger amount of ammonia than exists in the healthy state. It has been like- wise shown that other substances than carbonate of ammonia (chloride of sodium, urine, and urea) are capable, when injected into the blood, of evoking comatose and convulsive phenomena. The subsequent experiments of Oppler, Schottin, Perls, and Zalesky, seem to have given the coup de grace both to the ammonia and to the urea theories of uraemia ; and they indicate, in a very clear manner, that 1 Kichter found that solutions of urea (30 per cent.) applied directly to the sciatic nerves of frogs, produced only slight and uncertain convulsions of the muscles, far inferior to tho^e produced by a solution of common salt. A saturated solution 01 urea produced no convulsions at all. (F. Eitcher, Inaug. Diss-. : Erlangen, 1860.) 436 CHRONIC bright's disease. ursemic manifestations depend mainly and essentially on the accumula- tion in the blood and tissues of those primary products of tissue-meta- morphosis (creatine, creatinine, and other extractives), which, in a later stage of histolysis, are converted into urea and uric acid. Cuffer^ has recently asserted that the ursemic symptoms are due to destruction of the red blood-corpuscles. This may be produced by the various excrementitious matters which accumulate in the blood. He does not, however, reject the idea that the symptoms may, in certain cases, be due to spasm of the cerebral vessels, which view Dr. Hughlings Jackson maintains. Feltz and Ritter^ have asserted, that the poisonous substances accu- mulated in the blood are not the above-mentioned excrementitious matters, but potash salts. Inquirers into the theory of ursemia may be reminded of the remark- able absence of coma and convulsions — the most common features of clinical urtemia — in cases of obstructive suppression of urine. The cases related in Chap. I., Section 5, of the present work show incontest- ably that fatal suppression of urine from blocking up the ureters gen- erally runs its course without the usual symptoms of uraemia as witnessed in Bright's disease. Dr. 0. Rees believes that the tenuity of the blood in Bright's disease is not without influence in the production of the cerebral symptoms. Traube still further developed this idea. He contended that the watery state of the blood predisposes to interstitial transudations ; that the hypertrophy of the left ventricle increases enormously the lateral pres- sure in the arterial system ; that when, from any cause, a still further in- crease in the tenuity of the blood-serum occurs, serous transudation takes place through the cerebral capillaries, and gives rise to oedema of the brain. This oedema causes compression of the minute cerebral vessels, and determines an anaemic state of brain, and thereby ursemic convul- sions and coma. He is further of opinion that the symptoms are of a comatose character when the oedema and anseraia affect the hemispheres, and convulsive when the central ganglia are the parts affected. Jaccoud, in his "Pathologic Interne" (vol. ii. p. 443, 6th edition), asserts that the ursemic symptoms may in various cases be explained by several of the above-mentioned conditions, such as ammonia, creatin- semia, and Traube's oedema and ansemia of the brain. Dr. Mahomed, again, has found small hemoirhages in the cortex of the brain, and these he believes to be the cause of the symptoms. l^one of these theories, considered exclusively, explains satis- factorily the protean phenomena of urgemic intoxication, as v^itnessed at the bedside. The subjects of Bright's disease suffer under a deep abnormality in the composition of the blood and tissues. The blood is unnaturally watery and poor in albu- men ; the blood and tissues are unnaturally charged with the primary histolytic products (creatine, extractives, etc.), and with excrementitious urinary compounds (urea and uric acid,) perhaps 1 These de Paris, 1877. 2 De I'uremie experimentale, 1881. DIAGNOSIS. 437 also with the products of the decomposition of some of tliese. This state appears to induce in the nervous centres a proneness to sudden disorder and loss of equilibrium. A crisis may at any moment be brought about by an exaltation of one or several of the disturbing elements, or by a supervention of some new and different cause of irritation (hysteria, menstruation). A similar hypersensitive state of the nervous system prevails naturally in early life; and an irritation which would be of no moment in an adult (teething, worms, embarrassed digestion, cutanous irritation, etc.), suffices, in an infant, to awaken con- vulsive and comatose phenomena closely resembling those of uraemia. DIAGNOSIS AND PKOGNOSIS. Diagnosis. — Under ordinary circumstances, chronic B right's disease presents symptoms, and a condition of urine, so charac- teristic that it can scarcely be confounded with any other malady. Even when dropsy is absent, a persistently albu- minous state of the urine, apart from heart disease, hardly belongs to any other condition. Temporary albuminuria, as we have seen (see Congestion of the Kidneys), occurs occasionally under a variety of inflamma- tory and febrile conditions, without structural changes of any importance in the kidneys. These cases differ from Bright's disease in the absence of dropsical effusion; the quantity of albumen is also generally very small ; the excretion of urea is natural or even excessive instead of being diminished. When defervescence occurs, it is speedily followed by the total dis- appearance of albumen. The real diagnostic difficulties lie : («) in distinguishing acute and curable cases from chronic confirmed ones; (b) in determining the precise anatomical changes going on in the kidneys ; and (c) in detecting the disease when it is encountered masked by an inflammatory complication or a urjemic paroxysm. (a) The case must be considered as belonging to the chronic and confirmed class, if the disease had crept on insidiousW, or if it be found complicated with chronic phthisis, caries, long- continued suppurations, constitutional syphilis, enlarged liver or spleen, or hypertrophy of the left ventricle. If the invasion have been acute, and the albuminuria still linger after the abatement of the febrile symptoms, time be- comes a necessary element in the diagnosis. With every day that passes by without diminution of albumen in the urine, the fear grows stronger that the disease has become confirmed. In such a conjuncture the character of the urinary deposit supplies important information. If the epithelial elements and blood corpuscles continue to be freely discharged, and no, or only 438 CHRONIC bright's disease. trifling, signs of fatty changes appear in the renal derivatives, there is good reason for confidence that the observer has to do v^ith the declining stages of an acute disorder. If, on the other hand, albumen persist in considerable quantity after the pyrexia has passed away, and after blood has ceased, or almost ceased to appear in the urine, it is probable that the disease has lapsed into a chronic and confirmed state; and if, in addition to these untoward signs, the deposit exhibit marked fatty change, that probability becomes a certainty. It must not be forgotten that patients suffering from chronic Bright's disease are subject to occasional febrile exacerbations, in which the urine becomes scanty, high colored, and perhaps bloody. Such exacerbations are liable to be confounded with the acute disorder ; and when there are no clear indications of chronicity in the previous history, in the character of the renal derivatives, or in the coexistence of complications, the difieren- tial diagnosis of the two conditions may be quite impracticable until the lapse of time shall have cleared up the ambiguity. (b) For the differential diagnosis of the difterent types of degeneration going on in the kidneys, the reader is referred to the synopsis of distinctive symptoms furnished in the first section of the present chapter. (c) When the case comes under notice for the first time, masked by an inflammatory complication (pneumonia, endo- or peri-carditis, etc.), a clew to the primary disorder must be sought in the previous history of the case, and in the associated symptoms. When dropsy (or the history of any) is absent, the primary renal disease is apt to be overlooked, and the case re- garded as one of simple inflammation of the organ affected : the urine (in such cases) assumes a febrile character, urea becomes abundant in it, and its specific gravity rules high. If, under such circumstances, the quantity of albumen in the urine be but small, the absence of Bright's disease may be counted on ; but the converse deduction is not invariably warranted. In pneu- monia I have seen the urine for some days " highly " albuminous without, as the sequel showed, the existence of any renal degen- eration. In pleuris}' and pneumonia (and especially the former) the simultaneous implication of the two sides furnishes a strong presumption (supposing the urine be albuminous) that the inflammation is not simple, but secondary to renal disease. The existence of cardiac hypertrophy without valvular disease, or of notable anaemia, also favors the supposition of Bright's disease. The differential diagnosis of urEemic coma and convulsions has been already pointed out (see p. 432). The absence of casts in an albuminous urine gives no security against the existence of renal degeneration ; indeed, this absence PROGNOSIS. 439 is generally more apparent than real. When the casts are few in number, and small, they subside \'ery ini[)ertectly, and are apt to escape detection, even with the most careful examination.' In other cases the absence of casts is only temporary; and I have known it most absolute in some of those sad hopless cases, where the renal disease is the ultimate upshot of an intractable strumous or syphilitic cachexia. Pkognosis. — The prospects of a patient sufl'ering from con- firmed chronic Bright's disease are exceedingly gloomy. The textural changes in the kidneys are of a kind that do not admit of reparation. The Malpighian bodies become enveloped in an exudation of low plastic material, of which the only tendency is to progressive contraction, and the tubuli are either blocked up with fibrinous plugs or shrivelled into useless fibres. The gland is not, however, equally affected throughout all its parts, and the less injured portions carry on, imperfectly, the depu- rative functions. As the sounder portions become more and more involved — and there is an almost inevitable, though slow, tendency to this — the work done by the kidneys grows less and less, and the blood is more and more contaminated with histolytic and urinous elements, until at length a limit is approached, which is incompatible with life. Long before this extreme limit is reached, however, death is brought about in a large number of cases by one or other of the numerous compli- cations to which the subjects of renal degeneration are obnoxious. In certain more favorable cases the structural changes cease to advance, the dropsical effusions (if any existed) are absorbed, and the condition of the patient remains stationary, perhaps for months, perhaps for years; and he may be able, with proper precautions, to prolong existence in fair comfort, and even to pursue light avocations, for very considerable periods of time. Cases protracted to five or six years are not uncommon, and a few instances are recorded in which the patient has survived for ten, fifteen, or even twenty years. ^ The tenure of life under ^ Some years ago I was consulted by a medical man who was suffering from persistent albuminuria. He himself, and another practitioner, who was well accustomed to such inquiries, had failed, after repeated examinations, to detect a single cast in the urine. The specimen of urine sent to me was set aside for twelve hours in an appropriate urine glass. At the end of that period I could not, after long searching, discover a single cast. Next daj^, however, the urine deposited an abundant sediment of very minute uric acid crj^stals. On again searchiftg for casts I found several without difficulty — the precipitation of the uric acid had carried them down. ^ The protracted survivorship of some cases of chronic Bright's disease is very remarkable — in some rare cases the disease does not prove fatal at all. Possibly in these cashes only one kidney is affected — its fellow remaining sound. That such a possibility exists may be inferred not onW from the great difference in the amount of disease sometimes found in the two kidnej's after death, but more certainly from such a case as that of Dr. Moxon, in which one kidney was in an advanced stage of degeneration, while its fellow was normal. Path. Soc. Trans., V. xix. p. 268. 440 CHRONIC bright's disease. these circumstances is exceedingly precarious, and an imprudent indulgence or exposure may bring life, in a few hours or days, to the verge of destruction; the patient walks, as it were, on a slumbering volcano, which may at any moment awaken its fires with a fatal explosion. But although the final prognosis in chronic and confirmed cases is thus unfavorable, the immediate prospects of the patient may be fair, and there is still hope that by judicious manage- ment amelioration of the more distressing symptoms may be brought about, except in the ultimate stages of the disease, the dyspeptic symptoms, the irregularities of the bowels, the drop- sical accumulations, and the bronchial catarrh, may be combated with good probability of success. The following example is a striking illustration how near an apparent cure the subsidence of the symptoms may proceed, even from an apparently desper- ate extremity. Mr. B., a designer, of sober habits, set. 38, consulted me, May 9, 1862. He was suffering from great and general anasarca with ascites. The urine was scanty and intensely albuminous. There was an abundant deposit of tube-casts and renal epithelium. These structures exhibited the appearances of advanced fatty degeneration. The patient stated that the dropsical symptoms had existed a twelve- month, and had come on gradually — first in the feet, then in the face — without known cause. A fortnight after, I was requested to see Mr. B. at his own house. He was then confined to bed ; the swellings had considerably increased ; the legs were tense, and incapable of being moved from excessive oedema ; the peritoneal effusion was very great. There was severe dyspnoea (orthopnoea) and frequent vomiting. The urine was almost suppressed. Taking into consideration the state of the urine, the character of the deposit, and the time the disease had already existed, together with the threatening gravity of the general symptoms, it seemed hardly possible that the patient could rally to anything like seeming health ; and yet this took place. Compound jalap powders were administered freely, and blanket-baths applied daily. Copious watery motions were pro- duced ; the legs burst, and an immense quantity of fluid drained away. Improvement went on steadily in the course of the ensuing month ; in September the dropsy and ascites had nearly disappeared. A speci- men of urine (of which the flow was copious) was sent to me at this time for examination. It was only slightly albuminous, and after a diligent search I failed to detect any casts. I did not see the patient after this ; but Mr. Briggs, with whom I saw the case, informs me that shortly after, the patient went to Wales, where he continued to improve ; the oedema disappeared almost entirely ; the appetite returned ; and the strength was so far restored that he was able to walk fifteen miles in a day. On his return to town, however, the dropsical symptoms reappeared and increased ; and a cough set in, accompanied with purulent expecto- TREATMENT. 441 ration. The pulmonary symptoms gradually advanced, and he died in September, 1863, about eighteen months after I had first seen him. The favorable and unfavorable signs in Brigbt's disease have relation to the state of the skin, the duration of the disease, the degree of deviation of the urine from its natural quantity and composition, and the existence of complications. The signs which indicate that an unfavorable terminatioji is not far distant are: obstinate dryness of the skin, the urine, which had previously been abundant, becoming steadily scantier without proportionate increase in the specific gravity, evidence that the disease has existed some years, repeated recurrence of urseraic phenomena, excessive serous effusion, excessive cardiac hypertrophy, a persistently feverish state. Speedy death is indicated by the breaking forth of pneumonia or pericarditis, by suppression of urine or uncontrollable vomiting and diarrhcea. The absence of these signs may be construed in a favorable sense, as indicating a stationary state, and the probability that the final issue may be yet far distant. An excessive proportion of albumen in the urine, although a proof of the activity of the morbid process, and therefore a sign of evil augury, is not necessarily prophetic of impending death. In a case which I saw with Mr. Stephens, the urine, which was examined almost daily, became constantly solid on boiling, for a period of more than two months. During this period the patient's condition was stationary ; he was then seized with pneumonia, of which he speedily perished. TEEATMENT. In the management of cases of confirmed Bright's disease, three objects are to be especially aimed at, namely : (a) to hinder the further extension of the structural changes in the kidneys; (6) to prevent the occurrence of ursemic and inflam- matory accidents ; and (c) to palliate or remove certain threat- ening or burdensome symptoms — anaemia, drops}^, dyspeptic and ursemic phenomena, etc. To fulfil the first indication, the conditions under which the complaint originated must be carefully traced out, and the patient removed as completely as possible from their further influence. In some instances this is practicable ; as when the disease follows intemperance or long-continued exposure to wet and cold. In protracted suppurations, necrosis, caries, joint disease stricture of the urethra, and old vesical inflammation, the possibility of the development of renal degeneration should be kept in view by the surgeon, and should have weight in considering the propriety of operation. In all such afi:ections 442 CHRONIC bright's disease. the condition of the urine should be narrowly watched ; and the first appearance of albumen is a warnino^ that the oppor- tunity for operative procedures is slipping away, never to return. There is no evidence that local counter-irritants of the severer class — issues, setons, moxas, etc. — applied over the kidneys, exert any good effect; and the ulcerations they sometimes leave are apt to prove intractable. Mustard poultices, tincture of iodine, or dry cupping may be applied when the loins are the seat of aching pain ; but their influence on the renal lesion is probably nil Blisters are inadmissible on account of their specific irritating effects on the urinary system. The patient should be habitually clothed in flannel, both limbs and trunk ; and the activity of the skin should be further encouraged by moderate walking or carriage exercise, and the occasional use of warm baths and frictions of the surface. The bowels should be opened at least once daily, and the diet should be light and nutritious. Milk agrees well with the majority of this class of patients, and may be freely partaken of ^ Two or three glass of claret or hock daily, or a glass of sound beer, are permissible : but the stronger wines and all spirits agree, as a rule, badly, and should not be allowed unless special circum- stances imperatively call for their administration. Medicinal agents of roborant character should be exhibited from time to time — but especially preparations of iron. I have been in the habit, when the secondary symptoms or complica- tions do not call for special treatment, of contenting myself with giving 15 or 25 drops of the muriated tincture of iron in a wine- glass of water night and morning — combined, in cases of stru- mous affinities, with cod-liver oil. If the tincture produces headache or disturbs digestion, some other chalybeate must be substituted — the citrate of iron, citrate of iron and quinine, the syrups of the phosphate or the iodide of iron, the saccharated carbonate or the ferrum redactum. One or other of these prep- arations can generally be made to agree. It is important to get patients with chronic Bright's disease to take iron, for satu- ration of the system with iron is the best safeguard against the profound ansemia which is a fertile source of danger and distress to the sufferers from chronic renal degeneration. Are there any medicinal substances capable of exercising control over the quantity of the albumen lost by the urine? Exact observations do not give an affirmative answer to this question, though a certain reputation has been gained by the mineral acids (especially nitric acid), iodide of potassium, 1 Drs. Sparks and Bruce have made some very careful observations on the in- fluence of diet in a case of Bright's disease They found that an absolute milk diet, or an absolute non-nitrogenous diet, effected a reduction in the amount of albumen excreted. (Med.-Chir. Trans., 1879, p. 243.) TREATMENT. 448 tannin, and gallic acid. Dr. Parkcs exhibited large doses of tannin and gallic acid without producing any diminution of albumen. Ihavc in a number of cases used gallic acid for a period of many weeks, but could not convince myself in a single instance that it had any favorable influence on the excretion of albumen, and in some instances it occasioned serious gastric disturbance. Oppolzer has recommended alum, and the trials of Heller support this recommendation. Knowing as we do that persons with albuminuria and degen- erated kidneys may preserve passable health for years, so long as digestion is good, the blood not too impoverished, and the complications kept away, the practitioner is not justified in interfering too actively when this stationary condition is main- tained : he should confine himself to the enforcement of sound hj'gienic rules and preventive measures. The patient should be made clearly to understand that he is to treat himself as a valetudinarian; and that in his clothing, his eating, drinking, exercise, and general mode of life, he must go by rule, as the sole condition of not running the most fatal risks. The most effective means of combating the dropsical effusions are hydragogue cathartics and warm baths. For general use there is no hydragogue superior to the compound jalap powder with an additional quantity of the bitartrate. It acts quickly, and procures two or three copious watery stools. The objection to its use is the nausea and sickness which it too often occa- sions. To diminish this inconvenience as much as possible, an active dose (for an adult giij of the bitartrate, and 15 or 20 grains of jalap corrected with a little ginger) should be admin- istered early in the morning twice or thrice a week. The opera- tion of the medicine passes over in a few hours; and the patient has leisure to recruit himself in the intervals between the doses. This proceeding is less harassing than to keep up a continued purgation of less activity. Christison speaks in high terms of gamboge, which he em- ployed in doses of 5 grains, sometimes 7, and very rarely 9 grains, every second day, or in urgent circumstances ever}^ day. To prevent griping he had it finely pulverized with half a drachm of the bitartrate of potash. Colocynth, scammony, and elaterium have also been employed on divers hands. When the serous accumulation is very threatening, and immediate effects are demanded, no remedy is superior to elaterium. It may be given in doses of one-sixth or one-fourth of a grain every three or four hours, until three evacuations have been obtained. In the employment of purgatives, it must not be overlooked that exhausting diarrhoea sometimes occurs spon- taneously in the later periods of the disease, and that the use of. drastics has been known to originate this untoward symptom. 444 chrojStic bright's disease. It is necessary, therefore, to watch the action of these evacuants^ and to desist from their use immediately if the diarrhoea shows signs of proving intractable. Warm baths are unquestionably the most effective of dia- phoretics; they not only promote cutaneous transpiration, but often increase the secretion of urine at the same time. They may be applied in all their varied modifications — warm water^ hot air, steam, or the blanket-bath. When one modification fails another may succeed. Dr. Liebermeister describes as highly efiiective, a method of applying the warm w^ater bath, by which the temperature is gradually raised after the bather is immersed. When the patient first enters the bath the tem- perature is 98° ; it is then gradually raised by the admission of warm water to 108° ; after remaining in the bath about thirty- five minutes, the patient is packed in hot blankets.^ Unpleasant consequences — headache, suffusion of the face, unwonted heat of skin — occasionally follow the use of warm baths, and may even necessitate their abandonment. Generally these inconveniences diminish as the remedy is repeated ; and after a few trials patients with chronic renal disease nearly always take their baths with pleasure as well as with advantage. Of pharmaceutical diaphoretics, Dover's powder, James's powder, and liq. ammon. acetatis have been chiefly used : their effect is very uncertain. Diuretics are of much inferior value to purgatives ; but when there exists a tendency to spontaneous diarrhoea or to severe gastric derangements, we are constrained to abandon the latter for the former. My experience of diuretics has not given me a high opinion of their efficacy. The testimony of authors on their utility is conflicting. In judging of their efifects, some observers have not sufficientlj^ considered that a spontaneous diuresis is the normal outgoing of acute renal dropsy tending to recovery ; and that in patients with contracting kidneys pro- fuse diuresis is an ordinary feature of the quiescent state in the middle periods of the disorder, so that when the urine becomes scanty and the dropsical effusions increase during an intercurrent febrile exacerbation, the reestablishment of the diuresis and the diminution of the anasarca on regaining the quiescent condition,, must not be too hastily attributed to the diuretic which chanced to be employed pending the pyrexial attack. Diuretics of the most opposite classes have been recommended by different writers. Bright, who had but slight confidence in diuretics, was in the habit of prescribing uva ursi and pyrola umbellata. Christison relied on digitalis combined with cream of tartar. Rayer perceived little advantage in digitalis or 1 Prag. Vierteljahrschr. , 1861. TREATMENT. 445 squills, and he found that thcj almost always, at length, de- ranged the stomach. Horseradish tea,' according to his experi- ence, offered of all diuretics the best chance of success. Spruce beer is a much more agreeable beverage, and its diuretic action isprobably not inferior. My late colleague, Dr. Kason VV^ilkinson, has repeatedly obtained good results from its use ; and on his recommendation I have tried it myself in a number oi" cases, with favorable effects; it agrees well with the stomach, and quenches the thirst which not unfrequentl}' torments patients with Bright's disease, more effectually than any beverage I know. Tincture of cantharides was employed by Dr. Wells in seven <;ases, in doses of 30, 50, or even 60 drops per day, with good effect in ffve. Rayer also reports well of it in some cases ; but he adds, not without reason, " it is an uncertain remedy, which might be dangerous in inexperienced hands." I have tried in my own practice dandelion, broom-tops, and belladonna with unsatisfactory results. When other means of evacuating the dropsical effusions fail, and the tension of the integuments threatens erythema and gangrene, there is yet a resource in acupuncture or incision of the legs. This rapid and easy method has the disadvantage that, unless stringent precautions are taken, the punctures are liable to become the focus of erysipelatous inflammation, which may spread and pass into sphacelus, with disastrous consequences. This mishap is quite as likely to follow needle punctures as in- cisions, and after trial of both plans, I prefer the latter. One or two cuts with a lancet should be made lengthwise in the calf of the leg, or one of them may be placed on the dorsum of the foot. The incision should be three-quarters of an inch long, a,nd penetrate fairly into the subcutaneous tissue. To prevent erysipelas the following directions should be carried out ; the incised member should be wrapped in hot, moist flannels ; these should be changed frequently — at first every two or three hours. At every change, the legs, and especially the incised parts, should be thoroughly sponged with warm water, and the flannels which are soaked with the discharge should be completely cleansed before they are reapplied. Traube recommends that the in- cisions be frequently washed with chlorine water. Under such precautions this treatment may be carried out with safety — always with great relief at the time, and sometimes with pro- longed advantage. Dr. Southey^ has introduced, in the form of his capillary 1 Half an ounce of the root infused in two pints of water was the dose with which Kayer Ui-ually began ; this was gradually increased to one or one and a half ounces. The dried root makes a less acrid infusion than the fresh root, of which a smaller quantity must be used (Mad. d. Keins, ii. p. lb'2). 2 Lancet, 1877, I. p. 649. 446 CHRONIC bright's disease. drainage-tubes, a most convenient apparatus for removing the watery accumulations in the limbs. These tubes avoid to a great extent the danger of erysipelas. In those cases which are characterized by a copious flow of urine (contracting kidney), dropsical effusions, if present at all, are usually slight and. partial; and their existence depends chiefly on the watery state of the blood, and the lowered tonicity of the bloodvessels. In these cases, diuretic and cathartic remedies avail little to diminish the oedema ; better results are obtained by ferruginous preparations, tonics, and mineral acids. If the patient's general health can by these means be eifectu- ally improved, the serous effusions will not delay their disappear- ance. It is in cases of this class likewise that change of air, or even a sea-voyage, may be recommended, provided always that the disease be not too far advanced. The treatment of bronchial catarrh and secondary inflammations requires to be undertaken with a remembrance of the primary mischief. Mercury and bloodletting are inadmissible — the former (unless in the most guarded way) on account of the peculiar susceptibility of the system in Bright's disease to mer- curial preparations, the latter on account of the deep undermin- ing of the strength which has already taken place. Internal antiphlogistics — aconite, digitalis, and antimony — may be freely used; also external applications — chloroform epithems, hot poultices, dry cupping, etc. The dyspeptic symptoms are readily controlled in the early periods by a careful revision of the diet, and the use of vege- table bitters, prussic acid, and antacids.^ When obstinate vomiting of ursemic origin sets in, it is very difficult to subdue; creasote, morphia, and ice permitted to melt in the mouth, are the most effective remedies. Diarrhoea of similar origin must be combated by acetate of lead, opium, and sulphuric acid. When urcemic symptoms show themselves, renewed efforts should be made to increase the flow of urine, and to awaken the vicarious activity of the skin and intestines by the measures already described. If coma and convulsions have actually seized the patient, further energetic action is demanded. Frerichs, consistently wnth his view that carbonate of ammonia is the actual poison in these cases, recommends a treatment designed to neutralize the free ammonia, and reduce it to a state of innoc- uous combination. He directs chlorine (which may be inhaled in the gaseous state or taken dissolved in water) and the vege- table acids to be taken internally, the body to be sponged with vinegar, and vinegar to be used in injections. 1 Dr. Lauder Brunton has found arsenic of great service in cases of Bright's dis- ease, where dyspeptic symptoms are prominent. TREATMENT. 447 During the convulsive paroxysm, chloroform inhalation is the most prompt and ready means of controlling^ the spasms. When the uniemic paroxysm hegins with drowsiness and gradually passes on to insensibility, or when convulsions occur only as breaks in a continuously comatose condition, chloroform aftbrds no prospect of relief. Chloral, especially if administered by the rectum, is of great service in controlling the convulsions. At the time when Bright, Christison, and liayer puljlished on this subject, everything in the shape of an apoplectic or con- vulsive seizure was the signal for immediate and copious vene- section; it is not surprising, therefore, to find in the cases they recount that free and repeated bleedings are almost invariably chronicled in the next sentence to that announcing the advent of the uraemic paroxysm. Dr. Richardson has recently advo- cated the same plan. The immediate effect is, unquestionably, in a large number of cases, to relieve the insensibiiit}-; con- sciousness sometimes returns as the blood flows. But the indis- criminate use of this powerful remedy is the surest way to bring it into ultimate disrepute. A distinction should be drawn according as the renal disorder is acute or chronic and according to the strength and general condition of the patient. It must be borne in mind that an impoverished and watery state of the blood is an effective factor in the generation of ursemic pheno- mena, and that a bloodletting, though it may relieve a present attack, increases the predisposition to future attacks. In the ursemic coma of acute Bright's disease, and in certain classes of puerperal eclampsia, the blood is as yet not materially impover- ished, and the type of renal mischief is one that gives full hope of eventual recovery, while the attack itself is of extreme danger. In these, venesection — free, and even repeated — is decidedly and urgently demanded. But the matter stands other- wise when the renal mischief is chronic and incurable. The attacks themselves are not so imminently dangerous as when occurring in the acute form of the disease, patients frequently survive repeated ursemic paroxysms without the aid of venesec- tion ; the blood is commonly thin and poor; and, lastly, there is not any prospect of ultimate recovery. Under these circum- stances loss of blood is more likelj^ to shorten than to lengthen life. Further, as Christison remarks (speaking of advanced renal mischief), when the torpor becomes considerable the .re- moval of blood seems of little or no use. In some of the cases reported by Bright, death occurred from coma on the very da}^ of free and repeated venesection. I can only conceive of two contingencies in which withdrawal of blood, in quantity, is justifiable in chronic renal disease; one is, when coma comes on rapidly in a person whose constitution is not, as yet, seriously deteriorated, and whose prospects of life (abstracting the- 448 CHRONIC bright's disease. uraemia) may extend to many months or some years; the other is, when there is a necessity for temporary restoration of the faculties paramount to the general chance of prolonging life. When the comatose symptoms come on gradually, the meas- ures before enumerated should in every case take precedence of bloodletting. Of late years, a therapeutic agent, most valuable in cases of ursemia, has been introduced, in the form of pilocarpin, the alkaloid of jaborandi. When a dose of the hydrochlorate of pilocarpin (^ to ^ grain) is injected under the skin, profuse sweating follows in a very short time, much to the relief of the urfemic symptoms. The drug is also of use in dropsical states. It is prone, however, to cause symptoms of collapse, which'must he guarded against by the use of stimulants. CHAPTEK Y. SUPPURATION IN THE KIDNEY— RENAL EMBOLISM. Purulent formations in the substance of the kidney arise under three conditions, namely: (1) phlegmonoid inflamma- tions ending in circumscribed abscess; (2) multiple abscesses from purulent infection ; and (3) occasionally from embolism apart from pyremia.^ It is necessary to distinguish between abscess situated in the substance of the kidney, and purulent distention of the pelvis and infundibula, with ultimate sacculation of the organ (pyonephro- sis). These two conditions were confounded under the common name of " abscess of the kidney," until Rayer pointed out the distinction between them. 1. Phlegmonoid Abscess is nearly always confined to one kid- ney. It may be due to external violence (blows or falls on the loins), or to inflammation and suppuration round a calculus or calculi lodged in the substance of the gland, or it may arise as a sequence to suppuration of the lower urinary passages. In the last-mentioned cases the abscess may be due to extension of the inflammation by continuity of tissue along the straight ducts of the pyramids ; sometimes, however, the primary inflamma- tion is confined to the bladder or urethra and no direct con- nection between the two foci of suppuration is evident. Such cases are difficult to explain. Most probably the view pro- 1 Dr. Johnson describes another form of "suppurative nephritis," in which pus is produced in the uriniferous tubes by transformation of the renal epithelium. This condition he found associated with the occurrence of " purulent casts " in the urine. I have frequently noticed casts of this character, but am disposed to explain their appearance diffeientlj^. It is not very rare, in Bright's disease, to find, in the urine, cells attached to fibrinous casts with double or triple nuclei. But this is no more evidence of pus than the occurrence of the pale corpuscles in the blood (which are, anatomically, indistinguishable from pus corpuscles) is evi- dence of pus in the blood. When the renal cells proliferate rapidlj', they assume very much the appearance of pus corpuscles, and display cleft nuclei. The cases adduced by Dr. Johnson are quite inconclusive ; the first (Case -28) was an example of Bright's disease complicated with boils ; pyiemia followed and metastatic abscesses were found in the kidneys and lungs ; the second case (N"o. 29) seems to have been an example of the mottled white kidney acutely developed — complicated with cutaneous erysipelas, but otherwise not unusual in its course. In the third case dropsy and albuminuria of sudden onset had come on in an intem- perate and gouty man. Dr. Johnson found purulent casts in the urine, but after a while they disappeared, and the patient survived nearly a year. To apply the term suppurative nephritis to cases like the last two is likely to mislead, for' they diflfer nowise clinically from typical Bright's disease. 29 450 EENAL EMBOLISM. pounded by Klebs/ that micrococci are the agents of propa- gation, is correct. In not a few cases, the suppuration in the kidney is merely a local manifestation of a general pysemic condition 'starting in the lower urinary passages. An abscess formed in any of these ways may involve the whole kidney in destruction and convert it into a bag of pus. An abscess of the kidney generally opens into the pelvis of the organ, and its contents are discharged by the ureter. This is by far the most favorable issue. Sometimes the pus works its way out in other directions ; it may penetrate the tunica propria posteriorly, and be evacuated in the loins; and recov- eries have taken place even after this event, though generally such cases prove ultimately fatal. A renal abscess, more rarely, bursts into the colon or duodenum, and is discharged by stool; or it penetrates into the peritoneal sac, causing rapid death ; in still rarer cases, it has been known to push into the cavity of the thorax and be evacuated by coughing. The symptoms of circumscribed abscess of the kidney are pain in the afiected organ, fever, hsematuria, successive (often regular) rigors; and, if the collection be sutficiently large, a fulness or fluctuating tumor is perceived in the renal region. When the abscess bursts into the infundibula there is sudden and copious discharge of pus with the urine — or, if it burst into the intestines, with the stools — followed by simultaneous sub- sidence of the tumor. In the absence of fulness in the renal region, or of signs of pointing in the loins, the diagnosis is necessarily uncertain. Perinephritic abscess is sometimes ac- companied with hsematuria, and other signs greatly resembling those of abscess in the renal substance.^ Albuminuria is by no means a necessary symptom of suppuration in the kidney. It may be wholly absent, or the urine may contain a small quantity of albumen. "When abscesses of the kidney form slowly in the course of suppurating disease of the lower urinary passages, they are usually unassociated with any special symptoms, and their existence may not be suspected until the autopsy. Sometimes the contents of a renal abscess, instead of being evacuated, are gradually inspissated; the liquid parts of the pus are absorbed, and the residue is dried up into a puttj^-like mass containing shrunken pus corpuscles mixed with considerable quantities of phosphate and carbonate of lime. When an ^ Handbuch d. path. Anatomie, p. 654. The septic material may reach the kidney through the renal tvibules, or, as pointed out by Mr. Marcus Beck, it may pass into the lymphatics surroundinai; the pelvis and straight tubes of the kidnej^, by means of breaches in the epithelial surface, and so become disseminated through the whole organ. See, also, a paper by Dr. Stevens, Glasg. Med. Journ.,Sept. 1884. ^ See a case by Todd. Clin. Lects. on Ur. Dis., p. 39. RENAL EMBOLISM. 451 abscess dries up in this manner it may lie permanently latent, and £^ive no further trouble. The destruction of one kidney in this way is corn[)en8ated by enlargement of the opposite healthy organ, which is thus enabled alone to carry on the renal function. Treatment. — When external violence has been so inflicted that there is reason to apprehend suppurative inflammation, the loins should be freely cupped or leeched; absolute rest and low diet should be enjoyed for several days, and the bowels kept open by emollient clysters. The same treatment should be followed in principle, but modified to suit the accompanying circum- stances, if abscess is threatened from renal calculi. When signs of pointing in the loins are recognized, they should be encouraged by warm poultices ; and as the pus ap- proaches the surface it should be evacuated, in order to forestal the danger of evacuation by the more dangerous channels of the peritoneum or thorax. Too often the original cause of the suppuration (impacted calculi or disease of the lower urinary passages) is irremovable, and the evacuation of one abscess is liable to be followed by the formation of others, which at length exhaust the patient.' 2. Multiple or Metastatic Abscesses. — Secondary abscesses are sometimes found in the kidneys, as well as other parts of the body, after death from pyaemia. The kidneys are, however, less frequently the seat of such abscesses than the lungs and liver. In 2161 autopsies performed at St. George's Hospital, Dr. Chambers found pysemic abscesses in the kidney 12 times ; in the lungs, 106 times, and 22 times in the liver. The implica- tion of the kidneys has been found in pyaemia from almost every cause — after amputations, lithotomy, lithotrity, and other surgical operations, gangrenous aflJections, carbuncle, glanders, variola, chronic suppurations, especially of the lower urinary passages. In foul" instances Dr. Chambers found the kidneys free from abscesses when the pysemia had arisen from disease of the uri- nary passages themselves. The primar}^ disorder (pyfemia) is of such overwhelming 1 Illustrative cases of abscess of the kidney may be found (in addition to those indicated at the head of tlie chapter) in the following sources: Lancet, 1847, i. p. 335; 1853, i. p. 32; 1863, ii. p. 69; 1873, ii. p. 772. Med. Times and Gaz., 1854, i. p. 23; and ii. pp. 241, 343; 1874, ii. p. 632. Med. Gazette, vol. xis.. p, 888; XXIV. p. 563; xxvii. p. 141; xlv. p. 252. Path. Soc. Trans., 1849-1850, p. 234; vol. V. pp. 178, 179; xiii. p. 131. Gaz. Hebd., 1863, p. 40. Dublin Hosp. Gaz., 1854, p. 147; and vol. i. p. 121. Med.-Chir. Eev. (1824-1834), new series, xii. p. 81 ; xix pp. 159, 234. Med. Commentaries, vii. p. 41. Med. Facts and Obs., vi. No. 3. Encycl. d. Sc. Med., v. 54, p. 19. Wilson, Lects. on Dis. of Ur. Organs, Lond. 1821, pp. 281, 283. Bennet, Clin. Lects., 2d ed., p. 731. Ulrich, cited by Kosenstein, loc. cit., p. 287. Southey, Clin. Soc. Trans., 1869, p. 58. Burritt, Med. and Surg. Eep. of New Orleans, 1868, p. 520. Hough, Amer. Journ., 1870, p. 280, also Arch. Gen., 1869, p. 348. 452 RENAL EMBOLISM. gravity, that the renal lesion becomes by comparison unimpor- tant. 1^0 symptoms are known whereby the existence of multi- ple abscesses in the kidneys can be predicated with certainty during life.' A strong probability that such abscesses exist will arise if, with evident pysemia, the renal regions are painful on pressure and a considerable quantity of albumen be discharged with the urine. Sometimes the secondary abscesses in pyaemia are almost confined to the kidneys, as in the following example : Ou January 9, 1865, I examined the body of a man, aet. about 45, who had died in the Salford Workhouse, a day or two after his admis- sion, of some obscure disease. The bladder was found thickened and contracted ; the mucous membrane softened, red and congested, but not ulcerated. The ureters were dilated to the thickness of a large quill. The kidneys were enlarged to about twice their natural size, and riddled with hundreds of minute abscesses, the largest of which were about the size of a hoarse-bean and the smallest like pins' heads. They were dis- tributed through the substance of the organs and on their surfaces, mostly aggregated into groups varying from the size of a sixpence to that of a florin. Each abscess was surrounded Avith a red inflamed areola. Some of those on the surface appeared thinned away almost to bursting, and in places, resembled a patch of herpetic eruption. Not one of these abscesses had opened into the infundibula ; and if pus had made its way into the ureter from the kidney, it must have drained along the uriniferous ducts. On section it was seen that the little abscesses displayed a general tendency to range themselves end to end, in lines following the direction of the ducts of the pyramids. There were about 8 ounces of urine in the bladder ; it deposited, on standing, an abundant sediment of pus ; it also contained a good deal of albumen — more than the pus accounted for. Careful examination failed to discover casts of tubes of any sort. Both lungs contained a few secondary abscesses ; there was abundant recent pleurisy on both sides. The right heart was somewhat dilated ; otherwise the organ was healthy. The liver was healthy. The pysemia in this case appeared to have arisen from chronic cystitis. The exciting cause of the abscesses is probabl}^ in every instance the presence of micrococci. Often the capillaries in the neighborhood are found crowded with micrococci, and no embolism can be discovered. In some cases, however, a small vessel is blocked by a portion of clot discharged from an in- flamed vein, and, in the manner to be presently described, an infarct is produced which rapidly goes on to suppuration ; the determining cause of pus-formation, even in this case, is most likely the irritation produced by the presence of microorgan- isms. 3. Renal Embolism. — It was well known to Rayer that rheu- matic endocarditis was sometimes attended with the formation RENAL EMBOLISM. 453 of numerous deposits of a yellow color in the kidneys, which he considered to have the nature of plastic lymph. He de- scribed and ligured such cases under the designation of " nephrite rhumatismale.'" But it was not until the doctrine of embolism was worked out by Kirkes, Virchow, and others, that the real nature of these lesions was understood. The loose fibrinous vegetations which beset the aortic and mitral valves in endocarditis are apt to be detached, and swept away with the current of blood into the arterial system, and to be finally impacted in some small artery in the brain, kid- neys, or other part. But it is not solely in endocarditis that such masses are dislodged and carried away. The same may happen in atheromatous erosions of the valves and aorta; or a portion of the fibrinous lining of an aneurism may be detached and whirled away to the kidneys and other places.^ The efifect of the lodgement of plugs or emboli from any of these sources in the arteries of the kidneys varies wnth their magnitude. Small emboli either do not produce any appreciable symptoms, or they merely occasion a dull uneasiness in the renal region; and their existence is only ascertained by in- spection after death. But if one of the larger arteries is plugged up, not only does the occurrence produce symptoms referrible to the kidneys (sudden acute pain in the loin shooting down the ureter), but it may, under favorable circumstances, even be diagnosticated during life.^ In three cases of embolism described by Kirkes (in which death ensued from softening of the brain, consequent on ob- struction of one of the main cerebral arteries, by a fibrinous plug derived from warty vegetations on the valves of the left heart), the kidneys were the seat of numerous masses of yellow deposit surrounded by red areolae. An injection throw'n into the renal artery did not penetrate in the least degree into these yellow patches. The further researches of Yirchow and Beck- mann have added some particulars to the description of Kirkes. The yellow spots are situated almost exclusively in the cortical substance ; they are frequently wedge-shaped, with their bases bulging underneath the tunica propria, and their apices pointing toward the infundibula. They vary in size from a hemp-seed to a hazel-nut. At first they look like red hemorrhagic patches; in the centre of each there soon appears a yellow spot.* 1 Kayer, loc. cit., t. ii. p. 73. Atlas, pi. v. ^ See the history of a case of aortic aneurism, by Murchison and Moore, in vol. xlvii. of the Med.-Chir. Trans., p. 129. ■'' Such a case is related by Traube, loc. cit., p. 77. * From more recent researches, it appears doubtful whether the infarct of the kidney ever assumes the hemorrhagic form, except when occui-ring together with venous stagnation. Certainly, in the post-mortem room, it is nearly always met with in the form of a yellow mass. The reason of this is not clear. 454 RENAL EMBOLISM. This enlarges, and either softens in the centre (breaking down into a fatty debris, more rarely into genuine pus) or finally con- tracts into a cicatricial remnant, with destruction of the adjacent secreting tissue. It is necessarily a matter of extreme difficulty to demonstrate the existence of obstructions or plugs in the minute vessels at or near one of these yellow spots, and some doubt yet hangs over the demonstration. When one of the main branches is obstructed, the embolus is more easily dis- covered, and the appearances are somewhat different. The first efiect of cutting off the arterial supply of a considerable section of the kidney is to produce intense hypersemia of the surround- ing parts, which results in rupture of the capillaries and effusion of blood into the surrounding tissue. In this way a wedge- shaped apoplectic area is formed, embracing the whole thickness of the organ. Cohnheim found that in similarly produced lesions in the frog's tongue, the current in the veins was reversed, and assisted in the congestion of the infarct. As a rule, the effects of embolism in the kidney are of very slight clinical importance; they pass by, in the immense ma- jority of cases, without recognition; their occurrence is always secondary to some much more grave primary disorder, which altogether dominates the prognosis and treatment. Sometimes the larger ones go on to suppuration, and, still more rarely, to gangrene. CHAPTER yi. PYELITIS AND PYONEPHROSIS. Morbid Anatomy. — Inflammation of the pelvis and calices of the kidneys, or pyelitis, may be acute or chronic; it may involve the two sides, or be confined to one. In acute pyelitis the mucous membrane is injected ; some- times minute ecchymoses dot its surface, and blood may be effused on it ; the epithelium is more or less freely shed, and at a later period pus is formed. In rare cases, the surface is lined with false membranes (diphtheritic pyelitis) which are liable to be detached, and to block up the ureter. In chronic pyelitis the mucous membrane has a dead-white color, sometimes gray, or slate ; either it is not at all injected or it is traversed by dilated veins. The membrane is also thickened, and the pelvis and infundibula are dilated. This dilation, as it proceeds, encroaches more and more on the substance of the gland : first the papillae are flattened or obliterated ; next the pyramids, and finally the cortex are gradually annihilated, and the organ is wholly excavated (or sacculated) and transformed into a multilocular pouch filled with pus. Rayer describes and figures examples in which the pelvic membrane was studded with minute vesicles resembling sudamina- When the disease is due to the lodgement of calculi, ulcera- tions may exist on the mucous membrane, and sometimes these have been known to lead to perforation, with effusion of pus and urine into the surrounding cellular tissues, or into the intestines or peritoneum. The accidents usually occur after sacculation and dilatation of the kidney have taken place, but sometimes when the organ does not transcend its ordinary dimensions. When the pus and urine lodged in an excavated kidney fail to find a free exit through the ureter, from blocking up of its channel by a calculus, a clot of blood, thickened pus, tuber- culous or cancerous debris, etc., these fluids accumulate behind the obstacle, and distend the organ into an abscess-like cavity (pyonephrosis), which sometimes forms a palpable tumor in the flank. The matter so incarcerated may open a way for itself in any direction — backward through the loin ; downward along the psoas muscle into the iliac fossa, or under Poupart's liga- ment; upwards into the bronchial tubes, though this is rare; 456 PYELITIS. more frequently it penetrates into the duodenum or colon ; or lastly, into the peritoneum. In the cavity of the inflamed pelvis there are often found, in addition to pus and urine, blood, urinary calculi of various shapes and number, calcareous crusts, hydatids, tubercle, cancer, or whatever other foreign or adventitious matter may have been the cause of the inflammation. If the urine remain acid, uric acid and the urates may be precipitated in the interior of the pelvis ; but if it become ammoniacal, as it commonly does in advanced cases, the mixed phosphates are thrown down. These are sometimes produced in great quantity, and mingling with the purulent contents of the sac, thicken the whole into a semi-fluid mortar-like sub- stance. In other cases, the phosphatic matter forms incrusta- tions, which adhere in places to the walls of the cavity, or lie loose as friable concretions. Sometimes, again, the excavated organ, instead of forming a tumor (or as a subsequent stage to such tumor), slowly contracts, until at length it is reduced to a shrivelled pouch weighing only a few- drachms. In other instances, the pus is gradually inspissated and im- pregnated with mineral matter (carbonates and phosphates of lime and magnesia (until it is converted into a putty or chalk- like material, which fills up the compartments of the sacculated kidney. Sometimes the fibrous septa which separate the com- partments are extensively calcified. In an example of this kind (exhibited by Dr. John Medd to the Manchester Medical Society) which was handed to me for examination, a saw was required to cut the kidney across, and a piece of one of the bony septa which was ground down displayed, under the microscope, the characters of true bone, though in a rudimen- tary state. A fine specimen of similar transformation is pre- served in the museum of the Owens College, of which Fig. 56 is a representation. It rarely happens, in cases of chronic pyelitis, that the other parts of the urinary apparatus are free from disease. The most common combination is chronic cystitis with dilated, thickened, suppurating ureters. The substance of the kidney, or what remains of it, is likewise involved at length in a degeneration of the nature of chronic Bright's disease (pyelo-nephritis) ; and if both kidneys are aftected, the usual symptoms of that dis- order present themselves — general anasarca and characteristic changes in the urine. Etiology. — The symptoms of pyelitis, and the varied acci- dents which it may present during its course, whether acute or chronic, have so direct and intimate a connection with the cause of the inflammation, that practically it is necessary to couple the description of the dififerent species of pyelitis with p:tiology. 457 an etiological condition. This h so far true that the designa- tion pyelitis expresses nothing more than an anatomical fact. As a nosological heading it includes numljers of cases which have little real clinical affinity. In a certain number of cases the inflammation of the pelvis and its appendages is an im- portant, perhaps the most important, feature of the patient's Fig. 5f;. A sacculated kiduey laid open ; the cavities filled with a solid putty -like matter. complaint; but in the majority of cases pyelitis is a subordinate and often insignificant incident in the history of some graver disease. Pyelitis may arise under very varied conditions, viz. : (1) From overdoses of turpentine, cautharides, and other stimulating diuretics. (2) Some degree of pyelitis usually accompanies both acute and chronic Bright's disease and diabetes. (3) Certain general diseases are sometimes complicated with a degree of pyelitis — typhus and other eruptive fevers, pyemia, scurvy, diphtheria, cholera, carbuncle, etc. 468 PYELITIS. (4) From mechanical irritation produced by the presence of a foreign body in the pelvis of the kidney or infundibula — urinary gravel and calculi, hydatids and other parasites, blood- clots, cancerous and tubercular deposits. (5) From stagnation and decomposition of the urine in the pelvis and infundibula. Simple stagnation of the urine (with- out decomposition), from an obstruction in the ureter, usually causes only dilatation (hj^dronephrosis); but if it occur suddenly, the pressure of the dammed-up urine may excite acute pyelitis.^ Severer inflammatory changes occur if the stagnant urine becomes decomposed, and its urea converted into carbonate of ammonia. It is probable that the intractable, generally fatal, pyelitis which sometimes follows pregnancy arises in this way. (6) From extension upwards of inflammation from the bladder. This is a frequent cause of the worst forms of pj-elitis. In whatever manner cystitis may have been engen- dered — whether by a urinary calculus, enlarged prostate, fungous or tubercular disease of the bladder, or stricture of the urethra — it can scarcely persist in intensity for a lengthened period without producing some or all of the following conse- quences : dilatation and suppuration of the ureters, pelvis, and infundibula, suppuration extending into the straight tubes and intertubular spaces with formation of scattered abscesses, and ultimately sacculation of the kidneys and destruction of the renal tissue. The term "surgical kidney" has been infelici- tously applied to this series of changes by some writers. (7) From the extension of neighboring inflammation, such as perinephritic abscess, or inflammation connected with caries of the vertebra, as in a case reported by Dr. Cullingworth.^ (8) From cold and unknown causes. It is very rare that pyelitis is not secondary to some antecedent morbid process or mechanical irritation ; but now and then cases are met with, in which pyelitis exists without any definite antecedent to account for it, as in the following example : In March, 1857, I admitted into the Manchester Infirmary a man greatly emaciated, with hectic symptoms. The urine contained a large quantity of pus ; its reaction was acid ; it contained no casts of tubes, nor more albumen than the pus accounted for. The patient stated that his water had been milky for more than a year, and that his health had been gradually failing for about the same time. He had never passed any gravel, nor had he ever suffered from nephritic colic. As far as he knew, the urine had never been bloody. He attributed his complaint to the nature of his occupation, which was to manufacture bichromate ^ See Si case reported by Brunner in the Verhandl. d. phys.-med. Gesellsch. in "Wurzb., viii. p. 146. 2 Lancet, 1880, i. p. 14. SYMPTOMS. 459 of potash. He died eleven days after admission. At the autopsy the thoracic organs were found perfectly healthy, as were also the liver, spleen, and intestinal tract. When the bladder was opened, some in- jection of the mucous membrane was found, but it was not thickened, and the viscus was not contracted. Both ureters were dilated to about double their usual size, and filled with pus. The two pelves and the infundibula were enlarged, and their lining membrane opaque, and bathed in pus. The kidneys presented very slight signs of disease; the papillae were flattened and yellowish, as if they contained pus within their ducts ; the remainder of the renal tissue appeared healthy. No foreign body was detected in either pelvis, and the path of the urine was free throughout. Death could only be attributed to the long-con- tinued exhausting purulent discharge, which had been allowed to go on without an attempt to check it until within eleven days of his death. Symptoms. — The symptoms of pyelitis are compounded of those directly due to the inflamed state of the pelvis and calices, and of those of the primary lesion which is the exciting cause of the inflammation. Only the former will be dealt with in this connection ; the latter will be described under their appro- priate headings. An aching pain and sense of weakness in the back are rarely altogether absent in pyelitis. This pain may be confined to one loin or afltect both, according as the disease is single or double. Sometimes, however, single pyelitis is accompanied with pain over both kidneys. The pain is increased on pressure. Symptoms of nephritic colic are generally noted at one time or other, or repeatedly, when the disease is due to the lodge- ment of a stone. Similar attacks are also common in pyelitis^ from hydatids ; sometimes also in tuberculous and cancerous pyelitis. The most important direct symptoms of pyelitis are found in the altered characters of the urine. In the early stage the urine contains blood (often only in microscopic quantity), mucus, and epithelial cells from the pelvis and infundibula. The appearance of these last affords the most certain diagnostic indications. The pelvic and infundibular cells are very irregular, spindle-shaped, tailed, three-cornered, elongated, rudely circular, etc. {see Figs. 23 and 53). The urine is usually acid. The quantity of albu- men in it only corresponds to the admixed blood and pus. In the more advanced stages, the characteristic epithelium just referred to is usually replaced by pus, which may be dis- charged in large quantities. The urine is still commonly acid ; but as the sacculation of the kidneys proceeds, the mingled pus and urine are liable to decomposition, and the urine becomes ammoniacal. If the urinarj^ channels remain free, the discharge of pus is constant and regular; but if, as frequently happens, the ureter 460 • PYELITIS. is blocked up by a calculus, a hydatid, a clot of blood, a mass of viscid pus, or other debris, the discharge of pus is for a while arrested ; and if the disease be confined to one side, the urine temporarily recovers its transparency and healthy characters. When the obstacle gives waj^ pus suddenly reappears in great quantity in the urine. If the distention of the pelvis have pro- ceeded to the formation of a tumor in the flank, the intumescence is necessarily greatly influenced by the formation and removal of such an obstacle. When the discharge of pus diminishes, the fulness in the flank increases, and becomes painful; when the course of the pus is reestablished, the tumor suddenly subsides, and the urine becomes again loaded with pus. This train of events throws a strong light on the nature of the case. The stoppage in the ureter may persist for varying periods — a few days or a few months — or it may prove permanent. When both sides are affected the obstruction of one ureter diminishes, but does not entirely dissipate the pus from the urine ; the same is also the case when the impediment is partial. Micturition is always more frequent than natural in pyelitis ; and during the nephritic attacks it is painful and incessant. Rigors are of frequent occurrence, especially when there is tumor; they sometimes assume a quotidian periodicity — recur- ring every evening with tolerable regularity. Well-marked hectic is often present in the later periods. The bowels are frequently disordered. ITnmanageable diarrhoea usually prevails, induced doubtless by the inflam- matory adhesions which take place between the dilated kidney and the colon which passes over it. In other cases (when there is tumor) the bowels are obstinately constipated, and require the frequent use of enemata. This is occasioned by the pressure of the tumor on the colon ; in one case, related by Bright, the descending colon was so contracted from the pressure of a pyone- phrotic tumor, that it was reduced to the condition and appear- ance of a thick cord. The occurrence of tumor in the flank is generally a late event in the course of pyelitis. This tumor is usually the seat of fluctuation, often obscure; and is commonly painful, and tender on pressure. It is dull on percussion, except where it is crossed by the colon. When the tumor is on the right side it is sepa- rated from the liver by the transverse colon ; when, however, adhesions form between the sac and the under surface of the liver, this sign may be wanting. The tumor is subject to im- portant variations of size, as already explained, according to the open or obstructed state of the outflow from it into the bladder. In some cases the tumor is so large that it extends across the middle line ; more commonly it amounts only to a fulness in the loin or in the space between the crest of the ilium and the ILLUSTRATIVE CASES. 461 false ribs. The outline of the abdomen is thus rendered lui- symmetrical. The ultimate issues of pyonephrosis are diverse; scarcely any two cases run a parallel course. The various directions in which the sac may burst have already been noticed (|). 453), and the symptoms vary correspondingly. But the sac may not burst at all, and the patient dies exhausted by the wasting discharge. This is indeed by far the most common termination. Or again, things may take a more favorable turn ; the discharge gradually diminishes, and, tinally, ceases altogether: the sac contracts and dries up, and, if the opposite kidney remain sound, perfect restor- ation to health takes place. Or the restoration may take place differently : the purulent collection, instead of being discharged, dries up into a putty -like mass, and ceases to give further trouble. The following abstract of cases will serve to illustrate the €Ourse and symptoms of some of the chief types of chronic pyelitis. Other illustrations will be found in the chapters treat- ing of parasites, tubercle, and cancer in the kidneys. Case 1. Double calculous pyelitis (Dance, "Archives Gen.," xxix. 149). — A young woman, set. 23, was admitted into the Hotel Dieu, January 12, 1824. She had experienced, two years and a half before, a tedious illness, which commenced with hsematuria, accompanied by fixed and continued pains in the renal region. Subsequently, the urine became turbid and purulent ; it was passed in small quantity and fre- quently. At the end of eighteen months, after the application of a large number of leeches to the loins, the health improved. The renal pains gave place to an habitual sense of weight in the loins ; the urine, however, continued purulent. Three weeks before, the menstrual dis- charge was suddenly suppressed from cold ; and when the patient came under observation the face was drawn, the eyes sunken ; there were severe abdominal pains increased by pressure ; these were especially severe in the lumbar regiou. The urine was turbid, scanty, and voided with pain. Leeches wei^e freely applied. But obstinate vomiting came on, and the patient died in five days. Autopsy. — The kidneys were enlarged to about a third above their ordinary size ; their surfaces were nodulated, and unnaturally hard, but presenting here and there points of fluctuation. On cutting open the organs they were found extensively sacculated and full of pus. The left kidney contained nine calculi, and the right fifteen ; these Avere lodged in the dilated calices. The proper substance of the kidney was expanded and attenuated, but otherwise healthy. The ureters wer.e dark colored, marbled on the surface, and their lining membrane thickened. Case 2. Tumor formed by the left kidney (pyonephrosis), discharging pus copiously both by the urethra and the rectum, depending on a large renal calcidus (Bright, loc. cit., p. 227). — A man, ?et. 40, first seen by Dr. Bright, April 30, 1836, had, for the last twenty years, experienced occasional pain in the left side, Avhich he ascribed to a blow ; he had likewise, at times, felt pain in passing urine, which was then turbid with 462 PYELITIS. deposit ; but about three months only before Dr. B.'s visit, had a tumor been detected or suspected in the left lumbar and iliac regions. He was found considerably emaciated. The urine was neutral, with a very disagreeable smell, and contained a large quantity of pus with a little blood. The whole quantity of pus passed daily was from four to six ounces. A tumor existed on the left side of the abdomen descending far below the umbilicus, hard to the touch, and fixed in the left lumbar and iliac regions. It felt smooth and even, and was rather tender at one point. A month later (June 1st) the tumor appeared to occupy nearly the situation of an enlarged spleen, but Dr. B. thought he felt the colon passing over it. The urine passed in twenty-four hours contained only three ounces of pus. The perspirations were profuse. • June 6. — He had suffered lately a good deal of pain in the left side, and was evidently feverish ; he was accordingly directed to leave off the tonic and nourishing medicines and food he had been taking. 15th. — Two days after the last visit diarrhoea came on, accompanied with tenesmus. The tumor was found now greatly diminished ; and on examining the stools it was evident that a large quantity of pus was passing that way. The discharge of pus with the urine was undimin- ished, but there could be no doubt that the abscess in the kidney had ulcerated into the descending colon. The patient lived for about six weeks after this ; hiccup came on and proved very obstinate ; and pus continued to be discharged both from the urethra and the rectum. Autopsy. — When the abdomen was opened, the left kidney was seen occupying the space from the diaphragm to the brim of the pelvis, and along its whole length passed the descending colon, much contracted. There was a small fistulous opening, not larger than sufficient to admit a goosequill, from the sac into the sigmoid flexure of the colon as it passed over the lower part of the kidney just at the point where peculiar tenderness had been early observed, and here the intestine looked a little di'awn in. The pus was found to have escaped into the psoas and lum- bar muscles very extensively. On removing the left kidney, and examin- ing it more accurately, it was found to contain a large coral-formed, lithic acid calculus, extending its branches into all the cavities of a sac- culated pelvis. The kidney was full of pus, and in several parts cere- briform matter was sprouting into the cavities with most luxuriant growth, into which tufts of vessels were seen entering. Cases of this class being surrounded with more or less obscurity as to the exact state of things v^ithin the abdomen, are more in- structive when the revelations of the autopsy are at hand to illuminate the clinical history; but the nature of some of the cases which end in recovery is so clearly indicated by their symptoms, that they may be- cited with advantage, and without any doubt as to their real nature. The following is from Dr. Todd {loc. cit., Case 48) : Case 3. — A female, set. 25, unmarried. She had been passing pus with the urine at least a twelvemonth before admission into hospital, ILLUSTRATIVE CA8ES. 463 and in considerable and constant quantity. For the last five years she had suffered pain in the loins, referred especially to the region of the right kidney. This pain varied in intensity ; it was generally slight and dull, but now and then severe. There had been no symptoms of an acute attack, nor any rigors or vomiting. She never, to her knowledge, voided blood in the urine, nor ever passed any gravel or calculus ; nor did she ever seem to have suffered from severe pain in the direction of the ureter. Rather more than a twelvemonth before her admission into hospital, she was suddenly attacked with retention of urine, which lasted twenty- four hours ; and immediately after its cessation, she first began to notice in the urine a sediment, which presented a purulent character. This attack of retention of urine was preceded by slight rigors, but the con- stitutional disorder was of so mild a character as not to cause her to lie up at all. When admitted into hospital, pus was passed daily with the urine to the extent of two to four ounces ; yet there was but very slight general ailment. On examination, a very large tumor was found situated in the region of the left kidney, forming a considerable projection beneath the abdo- minal wall. This tumor, which was three times the ordinary bulk of the kidney, was elastic and yielding to the touch, and communicated the sensation of a soft elastic swelling tilled with fluid. There was dulness on percussion all over the surface of the tumor, which was smooth, round, and free from any notches or projections. The tumor was not tender ; the patient could bear it to be handled without pain, unless hard pressure were used, when she complained of a dull pain. Her most urgent symptom was an occasional cutting pain, referred to the neck of the bladder, sometimes accompanied with slight difficulty of micturition. She stated that occasionally she had a sensa- tion of fulness in the left side, which would go off rapidly, as if some- thing had burst, and then there would very soon follow^ an increased flow of pus in the urine. Sometimes as much as eight ounces of pus would be passed in the twenty-four hours. Dr. Todd diagnosticated a stricture of the ureter, probably near the bladder, causing backward pressure on the kidney, with dilatation and sacculation of the organ. Eighteen months afterwards, the patient presented herself again to Dr. Todd. She stated that, on quitting the hospital, she went to Brighton ; there she improved in health very gi-eatly, and the purulent discharge gradually diminished. On a careful examination of the side there was no trace of tumor ; only a few pus globules could be detected in the urine, and it was doubtful whether these were not derived from the vagina the bladder. Case 4. Pyonephrosis from calculus, in the ureter without purulent urine (Howison, " Ed. Med. Jouru.," 1822, p. 557). — A medical prac- titioner, set. 25, had severe and protracted nephritic symptoms on the left side at the age of 15. He recovered from this attack, but during the subsequent years he suffered repeated paroxysms of pain in the left kidney, extending to the umbilicus. The urine was at times scanty, and 464 PYELITIS. once or twice slightly tinged with blood, but it never was observed to be milky, or to contain anything like pus. Between the paroxysms his health was good ; he followed the practice of his profession, and underwent a good deal of fatigue. The most dis- tinguishing symptom in these paroxysms was fixed pain, of a gnawing de- scription, extending from the spine toward the umbilical region, increased by pressure, even the slightest, during the severity of the attack. There was habitual constipation, and a most unusual sensitiveness to cold. His last attack but one occurred in February, 1821 ; he recovered from this in about six weeks, after being bled to 130 ounces. He became lusty and florid after this attack, and was able to take long journeys in his gig ; but riding caused so much pain that he was obliged to give it up. About September he underwent a good deal of fatigue ; and it was supposed that he suffered a good deal of pain, from being observed re- peatedly to bend his body forward for relief, although he would not allow it when questioned. One Thursday evening, towards the end of September, he went to bed earlier than usual, complaining of fatigue. He rose next morning at seven o'clock, and his last fatal attack commenced at eight. The symp- toms resembled those of the former paroxysms ; there was intense pain in the left renal region, and a hardness was perceived when the hand was applied to the seat of pain, with a peculiar sense of crepitation. The symptoms became rapidly aggravated, and, notwithstanding all the means employed, including the abstraction of blood to the extent of 150 ounces (!), he died on the fourth day."^ Autopsy. — The left kidney and pelvis were found converted into a reniform sac, a foot long, and nine inches broad. The surface of this sac was marked out into three lobes. When opened it was found full of a fluid resembling pus, mixed with serum. The renal substance had wholly disappeared, except a few small portions, leaving nothing but a cavernous cyst, consisting of the proper external membrane of the kid- ney and its internal membrane much thickened. It was divided into three large irregular cells, freely communicating with the dilated pelvis, into the apex of which the ureter (of its natural size) opened. The septa between the cells were hard like cartilage with thickened edges. The orifice of the ureter was closely blocked up by a small calculus. Case 5. Stone in the bladder for 16 years — removal by the recto-vesical operation — death Jive years after from pyelitis. — James H., set. 21, was admitted, under my care, into the Royal Infirmary, September, 1858, laboring under symptoms of stone in the bladder. On sounding, a large concretion was forthwith detected. The patient stated that he had been subject to difficulty and pain in making water since he was five years of age. When he came under treatment he was emaciated almost to a skeleton, and unable to leave his bed. Micturition was excessively frequent, the urine ammoniacal, and loaded with viscid pus. By rest in bed and anodyne treatment, the symptoms diminished greatly ^ It seems highly probable from the narrative that death was directly caused by loss of blood ; the patient insisted on venesection ; he tightened the ligature, and bled himself on the night of his death. ILLUSTRATIVE GASES. 465 in severity; and on the 17th of December he was jurlged by my col- league, Mr. Southara, who now took charge of the case, to be fit for operation. The stone was removed by the recto-vesical section. It weighed over 41 ounces, and contained a nucleus of oxalate of lime, overlaid with an immense mass of secondary phosphates. The patient made a slow recovery from the operation. By the end of April, 1859, the fistulous communication between the bladder and rectum appeared closed ; and the patient was discharged in excellent health, rapidly gaining weight. The subsequent history of the case, up to the time of his death, extends over a period of five years. Soon after leaving the Infirmary, the recto- vesical fistula reopened, and it never afterwards could be completely closed. The general health continued good, and no practical inc(m- venience arose from the fistula, lintil about a twelvemonth before his death. The purulent discharge with the urine then began to increase ; he lost flesh, and gradually sank in the early part of 1864. Autopsy. — The bladder, ureters, and kidneys were removed entire. The bladder was contracted and thickened ; the ureters were dilated to the size of a little finger, and were long and tortuous ; both kidneys were extensively sacculated, but not enlarged, and filled with pus ; and the secreting tissue w^as reduced to a thin layer of cortical substance scarcely half an inch thick. Case 6. Pyelitis, with tumor — coming 07ifive months after jjccriurition — improvement. — B. F., set. 33, a married woman, who had had nine chil- dren, was admitted under my care into the Royal Infirmary, on Novem- ber 30, 1866. She was suffering from a tumor in the right flank and purulent urine. Her last child was born 14 months ago, and five months afterwards she was suddenly seized, while scouring the floor, with stabbing pain in the right side, just under the costal cartilages. This continued off and on for some time, and kept her to bed for days together at times. Some- where about the same time, she also perceived a small lump in the right flank, which was painful on pressure. About three months later she noticed a white discharge in the urine, and this has continued ever since. She has never had rigors nor pain in micturition. The bowels have been irregular, diarrhoea alternating with constipation. State on Admission. — The patient was considerably emaciated, with a dirty sallow skin and complexion. The lungs, heart, and liver pre- sented no signs of disease. The abdomen was flaccid and somewhat promi- nent. In the right loin a smooth, elastic, globular tumor was felt which was not distinctly fluctuating. The tumor was about as large as a child's head ; it occupied the entire right flank, and extended inwards almost to the umbilicus and downwards into the right hypochondrium. It was perfectly immovable, and very tender on manipulation. The flank was dull on percussion, but the front of the tumor was traversed by the ascending colon, which could sometimes be distinctly traced over its sur- face either by palpation or percussion. Between the tumor and the hepatic limits a line of clear percussion could be traced (see Fig. 57). The urine was acid, specific gravity 1020, turbid, with a thick deposit of pus at the bottom of the glass. It only contained albumen to a degree corresponding with the quantity of pus. 30 466 PYELITIS. The patient remained in the Infirmary for three weeks. About three ounces of pus were discharged daily with the urine. In the second week of her stay, a febrile exacerbation took place, the tumor became more painful, and the temperature rose to 101° in the morning — its usual average being about 99°. The pyrexia subsided in three days, and this was coincident with the discharge of a large quantity of pus. One day she voided as much as eight ounces of pus with the urine. The tumor was considerably reduced in size, and became more flaccid after Fig. 57. Case of B. F. Diagram showing the position of the tumor. this, and the appetite and strength improved. The reaction of the urine was throughout acid, though often only faintly so. She was dis- charged, at her own request, on December 23d. Though the correctness of the diagnosis was not, in this case, verified by a post-mortem examination, it scarcely admitted of any doubt. The acid reaction of the urine, and the corre- spondence in the size and tension of the tumor with the removal of pus discharged in the urine, together with the physical signs, clearly indicated the existence of a pyelitic tumor ; and it is probable that the origin of it was connected with old pyelitis coming on during the patient's last pregnancy. Case 7. Pyelitis with tumor, after parturition (Bright's " Memoirs on Abdominal Tumors, New Syd. Soc." p. 212). — A woman, set. 30, was admitted into Guy's Hospital, June 18, 1832. She had a large abdomi- DIAGNOSIS. 467 nal tumor. It occui)ied a situation which extended over nearly half the abdomen, not very different from that of a greatly enlarged spleen, but running back more completely into the lumbar region, and there affording a tense, somewhat elastic feel. It appeared to be perfectly fixed ; even when the patient was turned completely on the right side, it did not shift its place. It felt as if fixed to the ribs themselves, under their margins, which were obviously protruded a little by its bulk. To- wards the lower parts, and particularly below the crest of the ilium, and descending towards the pelvis, the enlargement felt much softer and less tense. Dr. B. was at once convinced that the tumor depended on a diseased kidney, and it seemed likely that the softness of the lower part might arise from a portion of the intestine, which probably was the colon passing over the kidney. Three years before, the patient had suffered for many months from frequent micturition, with pain and forcing — the urine being occasionally tinged with blood. Eighteen months after, she was put to bed with a living child, and about six weeks subsequently, she first discovered the tumor. Since that, however (nine months before her admission;, she had borne another living child, and about Christmas she began to pass considerable quantities of what she considered " matter" with the urine. On admission she was feeble, and looking hectic, with frequent calls to pass urine, and pain in doing so. The urine, which was acid, con- tained pus. Some days the quantity of pus was very small ; but on other days as much as six or eight ounces of pure pus were collected ; and after a large discharge, the tumor was often decidedly reduced for a day or two. The bowels were costive. About the 13th of July, chest symptoms set in, with diarrhoea, under which she sank. Autopsy.- — The tumor proved to be the distended left kidney reaching from the diaphragm to the brim of the pelvis. The descending colon, contracted like a thick cord, ran longitudinally on the surface of the tumor. The tumor was adherent to the colon and the lumbar parietes. The flattened pancreas lay across its surface, on its anterior and inner aspect. The ureter was thickened, and resembled an artery, but its canal was by no means proportionably large. It was traced to the bladder, where its orifice formed a permanent opening, into which a goosequill could easily have been inserted, and the membrane was tuber- culated. The bladder was exceedingly small ; the uterus natural. The tumor contained about a pint and a half of healthy, well-formed pus, lodged in cells communicating with the pelvis of the kidney, and apparently formed by the distended infundibula. The right kidney was healthy, as were also the other abdominal organs. Diagnosis. — (a) Pyelitis loithout Tumor. — In the iirst stage of the complaint, the presence of the characteristic epithelium of the pelvis and calices in the urinary deposit, generally suffices to indicate the nature of the disease. When the urine has become purulent, these may still be found mixed with the pus corpuscles ; but in more advanced cases this valuable sign is no longer available, and the source of the discharged pus must be 468 PYELITIS. traced by other indications. These indications are often more of a negative than positive character. "When pus is discharged with an acid urine, and signs of disease of the iDladder, prostate, and urethra are absent, the prima facie inference is, that it comes from the pelvis of the kidney : ^ this interference is strengthened almost to a certainty, if tenderness exist in either loin, or if there be any history of antecedent nephritic colic. It is much easier to recognize the existence of pyelitis when it stands alone than when it coexists with, and perhaps is the consequence of, chronic disease of the lower urinary passages. Pyelitis is a common complication of old-standing cases of cystitis, enlarged prostate, and urethral stricture. In the absence of tumor in the flank it may be impossible, in such cases, to arrive at a positive certainty as to the coexistence of pyelitis. Little help can be obtained from the character of the urine, because it bears the stronger impress of the vesical, prostatic, or urethral disorder : but a careful weighing of the following points will generally lead to a correct conclusion. The upper urinary passages are likely to be involved when the quantity of pus is very great — two or three ounces or more per day ; when, with a large discharge of pus, the urine is only feebly ammoniacal ; when the loins are painful on pressure ; and the febrile movement and the decay of strength seem out of proportion to the vesical or urethral mischief; lastly, when the latter has been in existence for several years. (h) Pyelitis with Tumor— Pyonephrosis. — Cases of this class do not usually present much diagnostic difficulty. There is an elastic fluctuating enlargement on one side of the abdomen, occupying the situation of a renal tumor, and a great discharge of pus with the urine. This discharge is apt to vary from time to time; and the dimensions of the tumor are observed to in- crease and decrease in inverse correspondence. When the outlet from the sac is permanently sealed the nature of the lumbar tumor is much more obscure. It is liable to be mistaken for hydronephrosis, a hydatid cyst, a perinephritic abscess, or an abscess or cyst of the spleen,^ or liver. The diag- nosis, in such a case, turns first on the existence of a tumor pre- senting the physical signs of a renal tumor {see Diagnosis of Cancer of the Kidney); secondly, on the evidence of fluidity of its contents ; and thirdly, on the signs that that fluid is purulent (recurrent rigors and hectic). ^ For the diagnostic signs of the sources of pus discharged with the urine, see p. 147. 2 Gaffe records a case of pyonephrosis in a Portuguese physician, residing in Paris, which was mistaken for a cyst of the spleen. No pus had ever appeared in the urine ; indeed, there were no urinary symptoms at any time. Nelaton punc- tured the supposed cyst and withdrew 4| litres of pus. The patient survived 55 days. (Gaz. des Hop., 1855.) PROGNOSIS. 469 Procjnosis. — The prospects of a patient suffering from pyelitis differ greatly according as one or both sides are affected, arjd according to the nature of the exciting cause. Double pyelitis arrived at the purulent stage is a disoi'der of very grave consequence, whatever may have been its mode of origin, and usually ]>roves fatal in the end. When the disease is confined to one side, the issue may be favorable, either with or without destruction of the kidney. Cases of this last class are not infrequent : numerous examples have been recorded in which one kidney has been found, after death from some other cause, bearing the marks of previous sacculation and suppura- tion. Sometimes nothing is found in the situation of the kidney beyond the capsule of the gland tightly embracing a urinary calculus; in others, an empty cellular sac; in others, a saccu- lated pouch completely filled with, concrete pus. An example is reported by KussmauP in which pyonephrosis was encountered (post-mortem) apparently in an earl}' stage of obsolescence. The patient died of constitutional syphilis, with lardaceous liver and spleen, and Bright's degeneration of the left kidney. The right kidney was converted into a soft, thick-walled tumor, as large as a child's head, situated in the right hypochondrium. It was filled with thick, inodorous pus; the renal tissue had totally dis- appeared. The sac had contracted adhesions to all the surround- ing parts. The ureter was adherent to the wall of the sac, so that the escape of the pus was prevented. A probe, however, could be passed along it into the dilated pelvis. The disease was evidently of old date ; no symptoms (beyond the physical signs of tumor) referable to it were observed during life ; and the cause of its production could not be clearly made out after death. The gravity of pyelitis has a close connection with the nature of its original cause. Cancerous and tuberculous pyelitis in- variably prove fatal : the prognosis is almost equally hopeless when the disease is secondary to enlarged prostate, intractable disease of the bladder, or urethra. The prospect is more favor- able, though still exceedingly grave, in cases which follow preg- nancy, or depend upon renal gravel, calculus, or hydatids. "When pyelitis is secondary to some acute disease (zymotic fevers, etc.) it is of very slight consequence, and speedily passes away with the subsidence of the primary disorder. Rupture of the sac into the thoracic or peritoneal cavities is speedily fatal. Rupture into the intestine generally, if not always, proves ultimately fatal ; but the sac may open through the loin with a favorable issue ; though this is exceptional. 1 Wiirzb. Med. Zeitsclir., 1863, p. 43. 470 PYELITIS. Treatment. — The chief general indications in the manage- ment of cases of pyelitis are : to remove the exciting cause, and to arrest or control the purulent discharge. When pyelitis is secondary to Bright's disease, diabetes, scurvy, purpura, diphtheria, typhus or other zymotic fever, the gravity of the primary disease so overshadows the secondary affection that the latter rarely demands separate attention. It is only in the rare hemorrhagic examples when the loss of blood by the urine becomes threatening, that the internal administra- tion of astringents and styptics becomes necessary. The particular treatment applicable to the different species of pyelitis will be found described under the several headings of Concretions in the Kidney, Parasites, Tubercle, Cancer, etc. The following observations will find their application in those cases, both acute and chronic, in which the inflammation of the pelvis and infundibula is a leading feature of complaint, and the source of the more important symptoms. If the attack be acute, and accompanied with pain in the renal region, frequent and painful micturition, bloody urine, and fever, the loins should be cupped to eight or twelve ounces ; the cupping should be followed up with warm baths and hot poultices to the loins. Warm diluents should be freely admin- istered. Opium and other anodynes are sometimes demanded on account of the intensity of the suffering and evidence of spasm of the ureter. In chronic cases, when the secretion of pus is profuse, the eflfbrts of the practitioner must be directed to lessen the dis- charge, and to bring the renal tumor, if there be any, to a state of contraction or of obsolescence, and throughout to keep up the general health to the highest possible standard. Among the remedies which are available to check the dis- charge of pus are, the mineral acids, alum, vegetable astringents, tincture of cantharides, balsamic and terebinthine substances. These last are only applicable when the disease is thoroughly chronic, and a stimulant to the mucous membrane is required. The metallic astringents have also been occasionally employed with success, when other m.eans have failed. Mosler relates the following instance of the good efifects of acetate of lead, in a case of uncomplicated pyelitis arising (presumably) from cold : David G., set. 19, cutler, came under treatment in August, 1861. In the spring of the year he had been working in a very cold place, and his illness commenced with a smarting pain in passing water. This was followed by the appearance of pus in the urine. When the case came under observation, it was quite uncomplicated ; the only complaint was smarting in making water, and a desire to void it about every hour. Compression of the urethra caused no pus to appear at the orifice ; the pus was thoroughly mixed with the urine, giving the latter a turbid TREATMENT. 471 appearance. After standing, a layer of pus subsided to the bottom of the vessel, about half an inch thick. The microscope brought to view pus corpuscles and various forms of epithelial cells, some of which were fatty. The albumen was no more than corresj)onded to the amount of pus. The reaction was acid, and continued so throughout. At first vegetable astringents in large doses (10 grains of tannic acid thrice daily) were employed ; then balsamic remedies in the form of Griffith's mix- ture, etc. ; then alkalies f sod. bicarb, .^^iij daily ). The quantity of pus remained stationary, in spite of all these remedies ; but the smarting in passing water had mostly ceased. In the beginning of October, the patient complained for the first time of pain in the right lumbar region. At that time there were blood-cor- puscles in the urine, as well as pus and epithelium. The pus had in- creased. The alkalies were now combined with the use of warm baths ; the blood soon disappeared, and the pains ceased, but the pus continued undiminished. On the 1st of January, 1862, the use of acetate of lead was com- menced in doses of three grains three times a day. At the end of eight days the dose was increased to four grains three times a day. The effect of the treatment on the amount of pus was marked ; on the tenth day the quantity was visibly diminished, and shortly afterwards it disappeared altogether. Some months later the patient presented himself again ; the urine was found quite free from pus, and the general health blooming. These large doses produced colicky symptoms toward the end of the second week ; and there was at the same time a decided, though not great, diminution in the daily quantity of urine. The tincture of the sesquichloride of iron has sometimes proved of signal service, as in the following example : B. H., a woman, set. 51, was admitted under my care into the Royal Infirmary, in December, 1862, in a state of extreme weakness and ema- ciation. On examining the urine it was found acid, loaded with pus mixed with some blood. Micturition was frequent with smarting pain. Careful and repeated exploration of the bladder failed to detect a stone. The right kidney was painful on pressure, and the anamnesis disclosed obscure history of renal calculus. There was no fulness in the loin. The daily quantity of pus was estimated at three ounces. The deposit in the urine contained no cellular elements except pus and blood. She was first put on a mild alkaline treatment, with generous diet, and six ounces of wine. No improvement followed ; she continued to lose ground, and was unable to leave her bed ; the tongue became dry at times, and symptoms of severe hectic showed themselves. The alka- lies were then discontinued ; and 30 drops of tincture of steel in h wine- glass of water, administered three times a day ; the wine was increased to 10 ounces. This treatment was continued for many weeks, and gradual amendment set in. Blood disappeared wholly from the urine, and the discharge of pus was reduced to less than half an ounce. The general health improved proportionally; and in March, 1863, the patient was able to leave the hospital in a fair w^ay of recovery. She afterwards presented herself among my out-patients from time to time for some 472 PYELITIS. months, and steadily gained strength. At length she went to her work (weaving), and I heard nothing more of her until April, 1864. All her symptoms had returned in great severity some weeks before. She de- clined to comply with my recommendation to enter the Infirmary, and, four weeks after, I heard of her death. Among the general means designed to keep up the vigor of the system, the most important are cod-liver oil, quinine, nour- ishing diet, and, above all, change of air. Sea-side localities are preferable, and even sea-bathing may be recommended, if the patient's strength permit. When renal tumor exists, it may be treated like abscesses in other situations, by incision and free drainage, with antiseptic precautions, and in this way a complete cure may be eiFected. As a rule, however, it is not advisable to take any steps with a view to procure evacuation of the sac through the integuments, unless there be decided indications of pointing. It must be remembered that there is always a chance (supposing the dis- ease to be confined to one side) that, with rest and patience, the pus may become inspissated, and the abscess pass into a perma- nently obsolescent state ; or that gradual emptying of the sac may take place with final atrophy of the renal tissue. The advantages of an expectant treatment are strikingly illustrated in the following case, recorded by Henninger : The patient received a blow on the left lumbo-renal region in 1848. Obscure, persistent renal pains followed the accident. Three years after, the patient had nephritic colic on the left side, which recurred in periodi- cal paroxysms, resembling ague. In 1852, the attacks recurred about every three days ; they were followed by the discharge of a highly purulent urine. Mixed with the pus were found epithelial cells and crystalline deposits. A tense elastic tumor was discovered in the left hypochondrium, extending as far as the vertebral column. After a paroxysm, and discharge of pus with the urine, this tumor was only doubtfully perceptible, but in exploring along the course of the ureter, a body as large as a nutmeg was discovered in the iliac fossa, in the track of the ureter. The nature of the case was now clearly made out to be calculous pyelitis with tumor. The advice of M. Schutzenberger was to establish a fistulous opening in the renal region with a view to provide a safe outlet for the pus, and thus relieve the neuralgic parox- ysms. On consulting with Prof. Sedillot, it was agreed to wait the progress of events, in the hope that the renal tissue would be gradually absorbed, and the kidney reduced to a membranous pouch, which, on the cessation of the secretion of urine, might eventually contract. These hopes were realized. A merely palliative treatment was adopted ; and six months afterwards the patient saw an end to his sufferings ; he has continued since in uninterrupted health.^ 1 Henninger, These do Strasbourg, 1862. TREATMENT. 473 There are cases, indeed, in which the distention of the sac becomes so great, that the peril of rupture into the peritoneum exceeds the risk of making an opening through the integu- ments. The radical treatment of unilateral pyonephrosis by removal of the kidney, although several successful cases are reported, must yet be considered as subjudice.^ '^ See the discussion in the Clinical Society of London. Lancet, 1882, i. p. •'>27. CHAPTER YII. CONCRETIONS IN THE KIDNEYS. Close examination of sections of the kidney sometimes reveals the existence of numerous yellowish or brownish strise, running from the papillte toward the base of the pyramids. These are due to the precipitation of amorphous urates within the straight canals. This is generally only a post-mortem phenomenon : the cooling of the body after death diminishes the solubility of the urates, and causes them to be precipitated in the uriniferous tubes. In newly born infants who have breathed, such strise are very frequently found, especially when death occurs between the second and fourteenth days after birth. Virchow is of opinion that such a deposit is due to the excessive excretion of urates due to the increased metabolism of tissue consequent upon the establishment of respiration. In a few cases, however, the deposit has been found in children who have never respired (Hoogeweg and Martin, Ebstein). A similar precipitation may, however, occur during life, and constitute the first link in a chain of consequences which leads, eventually, to the production of urinary gravel and stone. Uric acid and oxalate of lime may also be deposited in the same manner, and furnish the nuclei of future calculi. * Such concre- tions may be permanently impacted in the uriniferous ducts, and render these impervious, and themselves cease to grow ; or they lodge in diverticula or pouches connected with the ducts, and increase in size amid the renal tissue ; or, lastly, and most frequently, they are rolled down along the ducts by the stream of urine, and deposited in the infundibula and pelvis of the kidney ; and even many thousands of minute calculi, formed in this manner, may be encountered after death, in these situations (see case of J. R., p. 412). Agglomerations of larger size may begin in the same way, or the precipitation may first occur in the infundibula and pelvis. In number, size, and shape, renal concretions present the greatest diversities. A kidney may contain only one concretion, three or four, or several hundreds. In size they vary from a pin's head, or a hemp-seed, to a horse-bean; and if a concre- tion become permanently lodged in the pelvis or its appendages, it may go on increasing to a weight of several drachms or SYMrTOMS. 475 ounces. Such a calculus ih UHually moulded to the divisions of the pelvis, and assunies various i^rotesque, branched, or arbo- raceous, forms. The cwniomical changes produced by renal concretions are, congestion of the kidneys, abscesses, pyelitis, pyonephrosis, and hydronephrosis. These are considered under their respective headings. Symptoms. — The existence of concretions in the kidney is usually indicated by an aching pain in the loins, occasionally rising into violent paroxysms (nephritic colic). This pain is characterized by its tendency to shoot along the course of the ureters down to the testicles and the inside of the thighs; it is also commonly attended with a sense of faintness, nausea, or even vomiting. The urine, in these cases, is voided with undue frequency, often with pain at the end of the penis, and it is apt to contain blood, pus, and epithelium from the pelvis of the kidney. The colicky paroxysms are determined by dislodgement of the concretions from one of the infundibula into the cavity of the pelvis, or from one part of the pelvis to another; but the most severe attacks are caused by the passage of it into the ureter. The descent of a calculus along the ureter into the bladder is productive of very distinctive symptoms. The patient is sud- denly seized with intense pain in the region of the affected kid- ney, accompanied with a deadly faintness, sometimes with cramp and sickness. The pain radiates in various directions, but chiefly along the ureter to the bladder, scrotum, end of the penis, and the inside of the thigh. The testicle is retracted ; there is in- cessant desire to make water, but the flow of urine is either partially or wholly suppressed. In the former case, the urine is high-colored, often mixed with blood, and voided in drops with burning pain. Violent and frequent vomiting follows ; the skin is covered with a cold sweat; there is constant restlessness; the patient tosses from side to side, and assumes in succession a score of different positions in the hope of relief. If the symp- toms are not speedily relieved, a febrile movement is produced, which, sometimes, attains a high degree, with hot skin, quick pulse, and incessant thirst. After these symptoms have continued a certain time — it may be hours, it may be days — relief comes, often quite suddenly. The patient feels something drop into the bladder, and, all at once, his agony is past. Sometimes, how^ever, the concretion fails to clear the ureter, and becomes impacted in some part of its course. In this case, the subsidence of the symptoms is more gradual, and less complete. In other, fortunately still rarer, instances the opposite ureter has already been rendered 476 CONCRETIONS IN THE KIDNEYS. impervious by the impaction of a calculus on some previous occasion, and the blocking up of the hitherto open channel is followed by total anuria, which leads to a rapidly fatal issue. {8ee Suppression of Urine.) Renal calculi are sometimes wholly latent. They may even attain a large size, and destroy extensive portions of the gland, without betraying their presence by a single symptom. Or, again, renal symptoms may exist for a longer or shorter period, and then wholly and finally cease. This latter event may occur under two circumstances; either the concretion completely occludes the ureter, and determines gradual atrophy of the kidney, or it becomes encysted in a lateral pouch or diverticu- lum, and ceases to impede the flow of urine and to irritate the mucous membrane.^ The Diagnosis of a calculus, or calculi, in the kidney or pelvis (except in latent cases) is not generally attended with much dif- ficulty. The locality, distribution, and paroxysmal recurrence of the pains, with the pyelitic characters of the urine, are usually sufficient to indicate the cause of suffering. Neuralgia of the lower intercostal and abdominal nerves sometimes presents great severity, and a paroxysmal character. It is distinguished from renal colic by the absence of blood, pus, and transitional epithelium in the urine. More difficult to distinguish are those cases in which nephritic colic is produced by the impaction of blood-clots or hydatids in the ureter ; indeed, absolute certainty cannot often be obtained in these cases until the appearance of gravel, hydatids, or clots in the urine sets the question at rest. The antecedents of the patient sometimes throw an important light on the diagnosis, and a knowledge of the nature of a fore- going attack will furnish a key to an existing one. In the absence of colicky paroxysms — where the symptoms consist only of obscure lumbar pains and slight disturbances of micturition, careful and repeated examination of the urinary deposit becomes the principal means of arriving at a precise diagnosis. If the symptoms be due to calculus, the deposit will, in all probability, contain scattered blood-disks and spindle- shaped, tailed, and irregular epithelial cells from the upper urinary passages. These may be accompanied with pus corpus- cles, and minute agglomerations of uric acid, dumb-bells of oxalate of lime, or some other form of calculous deposit {see Fig. 58). These unnatural conditions of the urine are intensified by violent exercise, and diminished or altogether suppressed when the patient maintains a state of rest. 1 In one ca=e the calculus was discharged externally through a fistulous opening in the loin. (Path Trans., vol. xxvi. p 128.) In another case, the stone worked its way into the muscles and remained there for seven years, when it was removed by operation. (Amer. Journ. Med. Sciences, April, 1881.) TREATMENT. 477 The Treatment of renal concretions must be modified accord- ing to the existing symptoms and the anatomical changes wliich may be inferred to have taken place in the kidneys. During the paroxysms of renal colic, the remedies indicated are warm baths, emollient enemata, cupping the loins, and, in highly sthenic cases, venesection. The dolorous spasm of the ureter must be combated by free administration of opium. This drug is freely tolerated in cases of this class, and full doses should be repeated until the system is plainly brought under its Fig. 58. Octahedra and dumb-bells of oxalate of lime embedded in a mucoid flake — in the freshly voided urine from a case of renal gravel. influence. When the irritability of the stomach is such as to prevent the absorption of the drug, it should be introduced per rectum or by subcutaneous injection. Belladonna may be sub- stituted where opium disagrees. The secretion of the urine should be encouraged by warm demulcent drinks; hot poultices should be applied to the loins or abdomen, as the local symptoms indicate. Change in the position of the patient sometimes sufiices to dislodge a calculus which lies upon, but has not become fully engaged in, the orifice of the ureter. Manipulation of the abdo- men in the course of the ureters may also facilitate the descent of the concretion. Sir James Simpson witnessed relief follow complete inversion of the hody.^ In the intervals of the nephritic attacks, or when none exist, the treatment must be conducted either with a view to dissolve the concretion [see Solvent Treatment of Urinary Calculi) or 1 Edin. Med. Journ., 1858-9, p. 76. 478 coNCEETiojsrs in the kidneys, according to the rules laid down for the management of chronic pyelitis. When abscesses form, or pyo- or hydronephrosis is established, the modes of treatment de'scribed under these head- ings must "be followed out. Incising the kidney through the loins, and extracting the offending calculi through the wound (nephrotomy), is a method of treatment as old as the time of Hippocrates. It is, however, not recommended by modern surgeons, except when suppura- tion has taken place, and the abscess is manifestly pointing in the loins. When such an abscess is opened, exploration should be made with a probe, and if concretions are detected thereby, cautious endeavors may be made to remove them by suitable instruments. (Hevin and Yelpeau — Oldheld, " These de Paris," 1863; see, also, " Gaz. Hebd.." 1867, p. 767; " Lancet," 1882, i. p. 184; 1883, i. p. 278.) Extirpation of the kidney, or nephrectomy, is an operation which has been performed several times in recent years. Eight cases are collected in the "American Journal of Medical Sciences" for January, 1873, p. 277. Six died and two recovered. An- other case of recovery after excision of an injured kidney is recorded by Brandt. (" Wien. Med. Woch.," 1873, and " Ed. Med. Journ.," May, 1884.) Dr. Campbell records a case of cystic tumor of the left kidney which was mistaken for an ovarian cyst, and removed, together with the kidney, by operation. The patient slowly recovered. (" Ed. Med. Journ.," July, 1874.) Still more recent successful cases of nephrectomy will be found mentioned in the "Lancet, 1882. i. p. 1070; 1882, ii. p. 568, p. 892; 1883, i. p. 423, p. 424, p. 548, p. 963; while the present position of renal surgery may be gathered from the discussions in the Clinical Society of London reported in the " Lancet," 1882, i. p. 527, and ii. p. 942, and in the Medico-Chirurg. Society ; see " Med. Times and Gaz.," 1883, i. p. 624. CHAPTER YJII. HYDRONEPHROSIS. When any impediment exists to the flow of urine from the kidneys the secretion accumulates behind the obstruction and distends the parts above. The tirst effects of the pressure of the accumulated urine are felt in the higher portions of the ureter and the pelvis of the kidney : these parts become dilated. Then the renal substance is compressed, and becomes partially or wholly atrophied and absorbed ; so that the organ is at length hollowed out into a pouch or bag, consisting of the fibrous cap- sule of the kidney. When these changes are associated with suppuration of the lining membrane the condition termed pyo- nephrosis (already described) is produced. But in a consider- able number of instances the obstruction is unaccompanied with purulent formation ; the distention proceeds painlessly and gradually. This is the case when the impediment arises from some congenital malformation ; also when it is incomplete, or is established by degrees. To this condition the terms " dropsy of the kidney" and " hydrorenal distention" have been applied; but both designations have given place to the term hydrone- phrosis, introduced by Rayer, and now generally adopted. Morbid Anatomy. — Some years ago I exhibited to the Man- chester Medical Society a typical example of what may be called a fully developed hydronephrosis. It consisted of a large mem- branous bag, 13 inches long by 8 inches broad. It represented the right kidney of a woman, who, during life, was supposed to be the subject of ovarian dropsy. She had been twice tapped under that impression, and died of peritonitis after the second operation. It proved, after death, to be the right kidney and pelvis monstrously dilated. When filled with fluid the cyst had a lobed or sacculated exterior, like an enormous colon. The ureter was incorporated with the posterior wall of the cyst, and opened obliquely into the dilated pelvis, with a valvular ari'ange- ment resembling that at the entrance of the ureter into the bladder. The channel was pervious to a probe ; but the valve- like deformity of its orifice (evidently congenital) prevented the free escape of urine. On cutting open the cavity a complete fibrous skeleton of the kidney was disclosed {see diagram. Fig. 59). The pelvis was dilated to the size of a large cocoanut, and formed a sort of 480 HYDRONEPHROSIS. antrum^ in tlie interior of which seven smooth rounded openings were situated, large enough to admit the Uttle finger. Each of these openings led into a rudely pyramidal chamber, the bulging base of which corresponded to one of the external lobulations. These chambers were separated from each other by strong membranous septa ; but they communicated indirectly with each Fig. 59. Diagram of a fully developed hydronephrosis. other through the openings into the enlarged pelvis. Not a particle of kidney substance existed in any part; but three flat- tened fibro-cartilaginous nodules were found embedded in the outer wall of the sac. The fibrous membrane which composed the pouch and septa was exceedingly tough and strong, much resembling the dura mater. The outer membrane evidently consisted of the thickened and hypertrophied tunica propria, and was continuous with the fibrous structure of the dilated pelvis. The septa corresponded to some of the embryonal divi- sions of the kidney ; and the circular openings represented the chief divisions of the pelvis. From this type there are many variations. The sac may not be nearly so large : it may not exceed the dimensions of the healthy organ : it may be even smaller. The chambers vary much in depth, and in number; there may be only two or three ; or the whole sac may consist of only a single cavity. The cyst may be composed in varying proportions of expanded pelvis and dilated kidney : sometimes the expansion is almost confined to the former, which is transformed into a globular swelling occu- pying the hilus of the kidney. The absorption of the secreting tissue is not usually complete. The stagnating urine exerts its MOBBID ANATOMY. 481 pressure in the first instance upon the i)api]]8e wljich boconio flattened, and, as it were, eit'aced ; then the bodies of tlie i)yra- mids are compressed and gradually atrophied; lastly the cortex is encroached on, more and more, until it is reduced to mere islets of reddish tissue on the membranous parietes; and, at lengtli, if life be sufKciently prolonged, these disappear, and not a vestige of tlie glandular tissue remains. When only one kidney is involved, a compensating hyper- trophy of the opposite organ takes place, and the urinary func- tion goes forward unhindered so long as the latter continues sound, and its channels of excretion free. There is nothing astonishing in this ; but it is very unexpected to find that de- struction of tlie secreting tissue may proceed to an extreme degree in both kidnej-s without evoking marked symptoms of deranged urine secretion. A person may apparently exist for a time with the two kidneys wholly reduced to membranous sacs devoid of any tubular structure. In Dr. Strange's case, already cited (p. 232), in which profuse diuresis had existed from infancy, not a particle of renal substance could be detected in the renal sacs after death, though life had been protracted to the age of eighteen years. Another equally remarkable case is related by Faber,' The subject of it was a little boy, who had been ventri- cose from birth, and in weak health. The urine generally pre- sented nothing abnormal ; but on two or three occasions the boy suffered from severe paroxysms of strangury, with symptoms resembling those of stone in the bladder. JSTotwithstanding these drawbacks, the boy was in better health the last year of his life than he had been for the previous four years, and was able to go about. When he had reached the age of 5i^ years he fell from a chair and died suddenly in consequence. The autopsy revealed the following state of the urinary organs. Both kid- neys were converted into large pouches or sacs, containing no trace of kidney substance. The renal pelves were likewise greatly distended, and the ureters so completely resembled the small intestine that the dissector held them several times in his hand in the belief that they were a coil of intestine. The bladder contained a little turbid urine ;* its walls were greatly thickened. There was no disease of the prostate, neck of bladder, nor urethra. The entrances from the bladder into the dilated ureters were sufficiently open. In these and similar cases the atrophy of the secreting tissue had doubtless been going on slowly and progressively, from the time of birth. It cannot be assumed that complete sacculation of the kidneys and total absence of renal tissue existed from birth ; for, as was pointed out by Eayer, infants with congenital 1 Wiirtz. Correspondenz-Blatt, Bd. xii. 266. 31 482 HYDRONEPHROSIS. double hydronephrosis are not viable. Life is probably eked out in such cases by the vicarious activity of the skin and bowels, which undertake some portion of the depurative functions prop- erly belonging to the kidneys. Death commonly takes place, in cases of this class, quite suddenly — sometimes with violent ursemic phenomena. Of 52 cases collected by me, the hydronephrosis was confined to one kidney in 32 instances, and affected both (double hydro- nephrosis) in 20 cases. When the hydronephrosis was single, the right side was more frequently affected than the left (^19 right, and 13 left). Hydronephrosis sometimes attains enormous dimensions; and fills the abdomen w^ith a soft fluctuating intumescence, reaching from the borders of the ribs to the pubes. Eayer cites an in- stance in .which sixty pounds of fluid were withdrawn from the sac. But the most extraordinary example which I have dis- covered is the following, related by Mr. Samuel Glass in the Philosophical Transactions for 1747 : Mary Nix had been remarkable all her life for the preternatural size of her belly. Her mother stated that her daughter was born dropsical ; t)ut otherwise she proved healthy; and, notwithstanding the steady increase in the size of the abdomen, she lived to be near 23 years of age. She is described as a tall and well-proportioned woman, except for the enormous size of her belly; and, for one of so unwieldy a bulk, to have been brisk and active. The menses, which appeared at the usual time of life, continued regular until within eight months of her death. The only complaint was of a pain occasionally felt in making water. On the suppression of the catamenia, there succeeded a certain amount of dyspnoea, loss of appetite, and emaciation, with swelling of one of the legs, and ulcerations. These symptoms gradually increased until her death. On taking the dimensions of her body before dissection, the circum- ference of the abdomen was found to be just six feet four inches, and from the xiphoid cartilage to the os pubis she measured four feet and half an inch ! The cutaneous vessels distributed on the abdomen were remarkably large. The thorax being laid open, the diaphragm was observed to be forcibly protruded into that cavity. The base of the heart lay under the right clavicle, and its apex on the most convex part of the diaphragm ; which convexity advanced as high as the third rib. The lungs were surpris- ingly small, scarcely exceeding in magnitude those of a new-born child. When the abdomen was opened a vast cyst was displayed, from which 30 gallons of a light, coffee-colored, limpid fluid were withdrawn. The fluid was not in the least fetid. In figure, color, thickness, and magni- tude, this enormous bag very much resembled the uterus of a cow at the end of gestation. The whole inside was scabrous, and looked as if par- boiled, and here and there was observed a small quantity of a cofiee- colored sediment. On the left interior part was discovered the orifice MORBID ANATOMY. 483 of a duct (ureter) which opened obli()uely into the cavity oi" the sac, and would easily admit a large goosequill. From this opening the tube advanced about twelve inches between the membranes of the bag obliquely upwards, and towards the right, from whence it was deflected downwards and passed between the fold of the broad ligament into the bladder. .The abdominal viscera were thrust aside in various directions. The left kidney and ureter were healthy. The fluid contents of hydronephrotic cysts are generally altered urine. Urea, uric acid, as well as the alkaline and earthy urinary salts, have been found therein. Prout detected urea and uric acid in the contents of a double hydronephrosis from a stillborn infant. Generally speaking, the fluid is much more watery than ordinary urine ; and sometimes the organic urinous matters only exist in traces. The fluid may be variously colored ; it may contain a little blood, pus, and epithelium, and it is nearly always more or less albuminous. In the following two cases the contents of the cyst consisted of a substance resembling colloid material. The flrst is de- scribed by Dickinson : The patient was an old woman of seventy. For twelve years she had perceived a tumor in the left hypochondrium, which at length filled the belly. Constipation alternated with diarrhoea. The patient stated that she occasionally passed " nasty stuff" by the urethra, and that the tumor diminished in size for a time after that occurrence. She at length died of pneumonia. The left kidney was found converted into a large sac about a foot long, divided by septa into compartments. These com- partments were filled with a gelatinous substance, which, under the microscope, presented the usual appearances of colloid matter. It lay, however, quite loose in the cyst, altogether unattached to the parietes. There was no obstruction whatever found in the ureter, nor in any part of the urinary channels. Dickinson supposed that an obstruction — probably from a calculus — existed at some previous period, which led to sacculation of the kidney ; and that the colloid matter was deposited subsequently. ( " Path Soc. Trans.," vol. xiii. p. 137.) The second case is reported by Prof. Dumreicher, of Vienna, and is remarkable in many ways : A girl of 13 had observed a swelling in the abdomen from her tenth year. This grew to an enormous size ; the circumference of the aTado- men, which was uniformly distended, measured 44 inches. The percus- sion sound was dull, except over a space of four square inches on the left side below the navel. Fluctuation was perceived over the swelling. Prof. Skoda, under whose care the girl first came, diagnosticated an ovarian cyst ; but he pointed out the possibility of hydronephrosis. The case then passed to the care of Prof. Dumreicher, who, on account of the dyspnoeal distress, punctured through the abdominal wall, and with- 484 HYDRONEPHEOSIS. drew 18 quarts of a colloidal brown-colored fluid. The circumference of the belly now fell to 30 inches, and the relief to the patient was great. Six weeks later, 16 quarts more were withdrawn ; and an injection com- posed of one ounce of tincture of iodine, in 4 ounces of water, with a drachm of iodide of potassium, was introduced into the cyst. This pro- •oeeding proved of no effect. In about a month 14 quarts more were •evacuated, and the injection repeated. Severe iodism followed, and continued for a couple of days. The patient then rapidly improved, and left the hospital. In about three months she returned, larger than ■ever. The belly now measured 462" inches, and the breathing was much embarrassed ; the heart's apex beat in the third interspace. In the course of the succeeding five months the patient was tapped four times, and an, aggregate quantity of 37 quarts of fluid was withdrawn — making a total, from the beginning, of 85 quarts ! The fluid changed character as the tappings were repeated ; it became more and more mixed with blood, and at length with pus. On one occasion a drachm of the crystallized sesquichloride of iron, dissolved in six ounces of water, was injected. This was followed by severe symptoms. At the last, a fistulous passage into the cyst was kept open by an elastic catheter, through which the cyst was evacuated twice daily, and washed out with warm water. Notwithstanding these precautions, the contents of the cyst grew daily more foul, and the patient's strength steadily diminished. She died after having been under observation about a year. On open- ing the belly the cyst was found to be the right kidney enormously dilated. The sac was intimately adherent to the liver ; and the right lobe of the latter was so compressed that it was reduced to half the size of the left lobe. The csecum and the end of the ileum were fixed by adhesions to the front of the cyst ; the rest of the bowels were thrust into the left hypochondrium. When opened, the sac was found in some places thin, in others several lines thick ; it was divided into compart- ments, of which the parietes were traversed by broad membranous bands in various directions, which divided the cavities into a number of small loculi. In these latter a number of cysts with yellowish contents were situated. The anatomical cause of the distention was not very clearly made out ; but it appeared to consist in a congenital obliquity of the origin of the ureter, whereby a valvular condition was induced, which impeded the flow of urine. The ureter, after its origin in the cyst, ran in a half circle, downwards and backwards, intimately adherent to the cyst walls and compressed by them. A small supernumerary renal artery arose from the aorta a few lines below the principal branch. The left kidney was enlarged, but healthy. ("Wiener Med. Halle," 1864, p. 189.) Etiology. — The anatomical conditions which lay the founda- tions of hydronephrotic distention of the kidney are exceed- ingly varied. Out of 52 cases which were collated for the pur- pose of the present article, there existed congenital malforma- tion in 20 cases — affecting the kidney, the ureter, or the renal artery. In two of these, a supernumerary renal artery crossed and compressed the ureter near its origin ; in four, the ureter ETIOLOGY. 485 was congeiiitally imperforate ; in three, the ureter entered obli- quely into the pelvis of the kidney, creating a valve-like impedi- ment, which necessarily increased as the pelvis expanded. In a case of double hydronephrosis, observed by myself, the details of which follow, the left ureter was greatly narrowed at its origin, and passed obliquely into the dilated pelvis; while the right ureter, which was perfectly normal in calibre, was com- pressed at its point of exit from the pelvis by an irregular branch of the renal artery. In a case recorded by Dr. Simpson, the ureters were dilated to the thickness of the small intestine in their entire course, except at intervals where they were folded on themselves, wdiile their vesical orilices were so contracted from thickening of the vesical walls, that they barely admitted the stilette of a blowpipe. In a case recorded by I)r. Hare a very curious deformity was found in both ureters, which he thus describes : " On taking the mass (the dilated kidney) in the hands, and pressing very tirmly, no liuid escaped by the ureter ; examining into the cause of this, it was found that the ureter, at a little distance from its origin, was coiled on itself — like a turn and a half of a cork-screw brought closely together, and that this coil was adherent to the lower part of the dilated pelvis ; above this part, the ureter was slightly dilated ; below it, not at all. The coils just mentioned acted as a valve-like obstruction to the course of the urine, for on gently dissecting aw^ay, with the point of a scalpel, the tissue which held the coils together and united them to the tumor, the retained fluid rushed readily out by the end of the ureter in a full stream.^ In 13 out of the 20 congenital cases, the hydronephrosis was double — that is, it affected both kidneys. Two of these perished stillborn, one lived six hours, one thirty, and one thirty-six hours, while one died twenty days, and another between three and four months after birth : but Dr. Hare's patient (just men- tioned) survived to the age of thirty-eight years ; and the re- maining four lived for periods varying from five and a half to twenty years. We must assume, in these latter cases, that the impediment to the urinary flow was at first incomplete (though the malformation was congenital), and that its eflfects were not fully developed until a subsequent period, and then probably with extreme slowness. In an instance cited by Eayer, the obstruction (congenital) was constituted by an imperforate urethra;^ the bladder ureters, 1 Med. Times and Gaz., 1858, i. 234. "^ In a case which occurred in the practice of the late Dr. Kitchie, that of a male child, who died thirty-six hours after birth, an imperforate urethra was the obstructing cause ; the pelvis of each kidney was dilated so as to admit the tips of two fingers. The kidneys themselves retained the lobulated character of the foetal organs. 486 HYDRONEPHROSIS. and kidneys were distended into capacious sacs (loc. cit., iii. 504). Phimosis also is given as a cause of hydronephrosis.^ Congenital hydronephrosis is often associated with mal- formations of other organs — imperforate anus, harelip, club- foot, etc. Of the 32 cases in which the obstruction arose later in life, it was due, in eleven instances, to the impaction of a calculus in the ureter ; and a similar impediment, although not actually found, was inferred to have existed at some previous period in three others. In five cases, a narrowing or obliteration of the ureter existed near its origin or its termination, produced pre- sumably by some past inflammatory or ulcerative process, fol- lowed by subsequent constriction. In three cases reported by Dr. Simpson, the ureter, which was of normal, or greater than normal calibre, was compressed immediately above the pelvic brim by a thickened tendinous band of the peritoneum, appar- ently the result of old inflammatory action. In six instances, the ureters were compressed near their entrance into the bladder by a pelvic tumor — gravid uterus, ovarian cyst, or a cancerous growth : cases of this class are no doubt much more frequent than these numbers indicate; but they are generally slight in degree, and seldom go on to the production of a palpable tumor in the flank.^ In a number of the cases collated, a mechanical cause for the distention could not be assigned, or such a cause was only obscurely indicated. In some of these, no doubt, a more care- ful inquiry would have solved the difiiculty ; but still there are cases which must at present be regarded as mechanically inex- plicable. In a few cases hydronephrosis has followed upon an injury to the region of the kidney.^ It is probable that in such cases the injury has been followed by inflammation and consequent formation of cicatricial tissue which has compressed the ureter. The two following cases illustrate in a striking manner how a congenital malformation, which, at first, only offered a slight obstruction to the course of the urine, comes, step by step, to 1 See a case reported by Dr. James in the Edinburgh Medical Journal, 1877, p. 135. He believes that the frequent micturition was the proximate cause, the contractions of the bladder preventing the iiow of urine through the ureters. 2 Stadfeldt found dilatation of the ureter common in women dying in childbirth, even when there was no lateral displacement of the womb. In sixteen post- mortem examinations he found such a dilatation nine times ; it almost always begins where the ureter crosses the common iliac. Hydronephrosis from this cause (^puerperal) is much more frequent on the right than the left side. Out of twelve cases, Stadfeldt found it only once on the left. (Monatsschr. f. Geburtsk, 1862, p. 71.) 3 See Croft, Brit. Med. Journ., 1881, i. p. 123 ; Hicks, New York Med. Eecord, April 17, 1880, and Solier, Lyon Med., No. 45, 1880. ILLUSTRATIVE CASES. 487 coiiBtitute a greater obstruction, and at length produces fatal results : T. S., 'Jit. 20, came under my care February 28, 1807. He had been subject, from the age of two years, to attacks of obstruction of the bowels, continuing for four or five flays, and recurring at uncertain in- tervals of a few weeks or months. During these attacks — which of late had been more frequent and more severe — the abdomen became swollen and tender, and there were sickness and vomiting. The condition of the urine had never attracted any attention. When I was called to see him, he was suffering from one of these attacks. The bowels had not been moved for five days; the abdomen was distended and painful, and there was frequent vomiting, which was not stercoraceous. The urine was reported to be exceedingly scanty. On the next day (March 1) he passed only four ounces of urine. The characters of this specimen were peculiar. It was mixed with blood, and its specific gravity was only 1008; no renal casts were found, but a large number of transitional epithelial scales, such as line the pelvis of the kidney. The sickness had ceased, but the condition of the abdomen and the constipation remained the same. On examining the loins, it was found that there was distinct bulging in both lumbar regions ; the bulged portions had an elastic feel and com- municated to the fingers an obscure sense of fluctuation. Both loins were dull on percussion, and the dulness reached forward to a line extending from the costal margins to the anterior spines of the crista ilii. On the next day — seventh day of intestinal obstruction — he passed three ounces of urine, similar in character to that before described. On the eighth day, there was total suppression of urine. On the ninth day, copious discharges of urine took place, amounting in the course of the day and night to more than a gallon. The appearance of the secretion was almost normal. It was straw-colored and clear; it contained no albumen, and only microscopical evidence of blood. It was only un- natural in its specific gravity, which ranged in the different specimens from 1005 to 1007. The bowels still continued without a passage ; but a sensible softening of the abdomen had taken place, and the elastic swelling on the left side was very decidedly diminished in size. On the tenth day the urine flowed freely, and fully a gallon was voided before night. It had the same characters as the urine passed the previous day. About midnight, on the tenth day, the intestinal obstruction likewise gave way, and an immense quantity of semi-liquid feces was evacuated. It was now hoped that speedy recovery would — at least for a time — take place ; but on the eleventh day the general symptoms were alarming ; no urine was secreted, the tongue and teeth became coated with sordes, and the prostration was extreme. On the twelfth day, death took "place, preceded by a fit of convulsions, no urine having been discharged for sixty hours. Autopsy. — On opening the abdomen, two soft, lobulated tumors were found, one in each lumbar region; these were the enlarged and saccu- lated kidneys. The left kidney was ten inches long by about seven broad — the right about a quarter less. To the bulging inner sides of the left kidney, the descending colon was firmly adherent by a broad 488 HYDRONEPHROSIS. attachment for the space of about three inches. It was here that the intestinal obstruction lay; the bowel was contracted at this spot, and tightly stretched over the distended kidney in such a manner as to pre- vent the free passage of feces. The kidneys, ureters, and renal arteries were carefully dissected out with a view of ascertaining the mechanical cause of the impediment to the flow of the urine, which produced the mischief. On the left side (Fig. 60), the renal artery was normal in its distribu- tion ; but the ureter presented an anomaly. At its origin from the dilated pelvis, the ureter was exceedingly narrowed; its bore was so Fig 60. Left kidney, s)iowing the narrowing at the commencement of the ureter and the obliquity of its entrance into the dilated pelvis (about one-fourth the aotvial size). contracted that only a fine probe could be passed along it. The entrance of the ureter into the pelvis was also oblique, so that a valve-like obstruc- tion was thereby constituted. The action of this latter impediment was clearly shown when the sacculated mass, after being separated from its connection, was held in the hand, and subjected to various degrees of pressure. With moderate pressure no urine escaped from the cut end of the ureter ; but when the mass was strongly compressed, the obliquity of the origin of the ureter was for the time effaced, and urine escaped freely. The same thing doubtless happened during life. When the distention of the kidney was moderate, the course of the urine was obstructed ; but when the urine accumulated and the distention became great, the obstruction was at length overcome, and the contents of the sac escaped. The lower portion of the left ureter was free from obstruc- tion, and of the usual dimensions. When this kidney was laid open, it ILLUSTRATIVE CASES. 489 (with the pelvis) was seen to be converted into one large lobulated sac, filled with urine (,?ee Fig. 61). The renal substance was reducer! to a thin layer, varying from a line to two lines in thickness, which formed the outer boundary of the sac. There were no traces of the pyramids. The infundibula and calices were enormously dilated, and constituted the sacculations which gave the mass its lobular character. The series of changes which brought the left kichiey to the state in which it was found, were probably something as follows : The narrow- ing at the commencement of the ureter was doubtless congenital, and Pig. 61. Tlie left kidney cut open (about one-fourth the actual size). constituted, from birth, a slight impediment to the free escape of urine, and occasioned gradually, in the course of years, by the distending force of the accumulating urine, a dilatation of the pelvis and infundibula, and a progressive excavation of the kidney. As the pelvis became enlarged and distended with urine, it acquired a more globular form, and the orifice of the ureter was, in consequence, carried upwards and assumed an oblique direction, so that an additional obstacle to the escape of urine was thereby created, and one which could only be overcome at intervals, when the pressure from behind became extreme. The ad- hesion of the colon was doubtless an event of later occurrence, and was the consequence of irritation and inflammation produced by the intermittent pressure against it of the distended kidney and pelvis. It is quite clear that, when this adhesion had once taken place, temporary obstruction of the bowel would arise whenever the kidney became dis- tended with urine beyond a certain point; and that when the increasing 490 HYDRONEPHROSIS. accumulation of urine at length overcame — in the manner already explained— the obstacle to its escape, the renal sac emptied itself, and the intestinal obstruction was also, for the time, removed. In this way may be explained the recurring attacks of constipation and the manner in which relief was accomplished. The right kidney was in the same sacculated condition as the left, but the destruction had not been carried to so extreme a degree. The mechanical cause of the sacculation on this side was- essentially different from that on the left side. There was no narrowing of any part of the right ureter ; but at its point of exit from the pelvis it was crossed by an irregular branch of the renal artery (see Fig. 62). On this (the Kight kiduey (about one-fonrth the actual size), showing the abnormal distribution of the renal artery. right) side, two renal arteries arose from the aorta. The upper artery, after giving off the suprarenal branch, passed into the upper part of the hilus of the kidney. The lower artery divided soon after its origin into two branches, of which one passed into the hilus in the usual way ; but the other branch passed downwards to the lower part of the kidney, and, in its course, crossed in front of the ureter just as the latter emerged from the pelvis of the kidney. It is evident that the slight constant pressure of this branch produced a certain degree of impediment to the flow of urine, which in process of time brought about hollowing and sacculation of the kidney. The diagnosis w^as made out in this case with accuracy ; and the proposal to puncture the renal sacs was only prevented from being carried out by the large discharges of urine on the ninth and tenth day of the obstruction. Had such punctures been made, however, the relief obtained could only have been tempo- ILLUSTRATIVE CASES. 491 rary : the destruction of renal tissue liud gone too far to leave any hope of permanent cure. A young man of twenty, otherwise in good health, had suffered, from time to time, from paroxysms of pain, f )llowed by nausea and vomiting. On the -'kl of February, 1857, he was seized with one of these })aroxysms, accompanied with obstinate constipation. The vomiting became intrac- table ; the vomited matters contained blood and sarcime ; and no passage could be obtained by the bowels. On examining the abdomen, a doubt- fully fluctuating swelling was detected in the right flank. The symp- toms were attributed to an organic affection of the liver. Under a continuance of these symptoms death took place in Ave days. At the autopsy, a bladder-like tumor as large as the fist was found in the right hypochondrium, situated between the liver, the colon, and the duodenum ; it was united by adhesions to the two latter. The colon was not constricted at the adherent spot ; but the duodenum was so tightly stretched over the tumor that its calibre was almost effaced. The stomach was greatly distended, and filled with a dark-colored fluid. A closer examination of the tumor revealed the following: It con- sisted of the pelvis of the right kidney, greatly distended. The right renal artery was abnormally distributed ; it divided close to its origin into two branches, one of which ran to the upper, and the other to the lower part of the hilus. The lower branch crossed the ureter near its origin, and exercised a certain compression upon it. The enlarged pelvis pressed forward between the two branches of the renal artery, in such a manner that the origin of the ureter was drawn beyond the level of the lower renal artery, compelling the ureter to loop itself round this branch in order to reach the bladder. Thereto was added a third mechanical obstacle, namely, the adhesion of the ureter in the first part of its course to the outer surface of the distended pelvis, for the space of three-quarters of an inch. The enlarged pelvis contained amraoniacal urine, mixed with blood and mucus. The corresponding kidney was long and narrow, but other- wise healthy, and scarcely atrophic. The left kidney was natural. (Boogard, "Arch. f. d. Hollandische Beitr. z. Natur und Heilk.," Bd. i. p. 196.) The explanation of these appearances seemed to be this : First, the lower renal artery compressed the ureter, and pre- vented the pelvis of the kidney from properly emptying itself until a certain pressure was exerted on its walls by the accumu- lated urine. This impediment was intensified by the curving of the ureter round the lower renal artery. The pressure so exercised probably excited inflammation and adhesion of the ureter to the outside of the expanded pelvis, and again of the latter to the colon and duodenum. The symptoms during life were thus explained. The periodical attacks of nausea and vomiting depended on the periodical dilatation of the sac and the pressure of it on the duodenum. Evacuation of the sac, when the pressure of the accumulated urine reached a sufficient 492 HYDRONEPHROSIS. height to overcome the obstructions, caused the paroxysms to subside. In the last paroxysm the resistance proved more obstinate; the duodenum became altogether occluded — hence the constipation ; and the portal vessels became probably im- plicated — determining effusion of blood into the stomach, and hfematemesis. Hydronephrosis arises under such a variety of anatomical conditions, that its general etiological relations oifer, as might have been expected, little that is characteristic. No age is exempt — not even foetal life; nor is any especially liable : the two sexes, in the cases collated by me, were found nearly equally represented — 25 were males and 23 females ; in 4 infants the sex is not mentioned. The Symptoms of hydronephrosis depend mainly on the nature of its anatomical cause and on the size of the sac. If the sac be small and the opposite kidney sound, symptoms may be altogether wanting; old age may be reached without suspicion that one of the kidneys has been changed into a membranous sac, and the anomaly may be first discovered at the autopsy. Generally, however, the distention goes on to the formation of a palpable tumor in the abdomen ; and sometimes, as we have seen, this tumor attains an enormous size. Setting aside the cases which perished stillborn, or within a few weeks of birth, there existed among the 42 remaining instances 25 in which abdominal intumescence was detected during life ; in 19 of these the tumor was confined to one side, in 6 a double tumor existed. In its topographical character a hydronephrotic tumor pre- sents the general physical signs of renal tumor. The swelling is situated in the flank; it reaches backwards in the lumbar region to the spine, upwards into the hypochondrium, down- wards into the iliac region, and forwards to the umbilicus — en- croaching on these regions variously according to its magnitude. The colon is usually in front of it ; and the small intestines are thrust into the opposite side of the abdomen. Of the several displacements of the organs on either side I need not add any- thing to what is detailed in the chapter on cancer of the kidney, where the general characters of renal tumor are fully described. The special characteristics of hydronephrosis are its soft undu- lating feel ; an outline, which is sometimes distinctly lobulated; and the evidence of fluctuation. There is one peculiarity which is pathognomonic when present, namely, the sudden diminution or disappearance of the swelling coincidently with the sudden discharge of a large quantity of urine. This sign is not always available; but it is sufficiently frequently met with to give it an SYMP'J'OMS. 493 important diagnostic value. It occurred in 9 out olthe 25 cases in which the existence of a tumor was clinically ascertained. In Dr. Hare's case of double hydronephrosis, already alluded to, subsidence of the tumor on the right side took place, from this cause, on several occasions the tumor each time reappear- ing : that on the left side also disappeared but did not return. Such cases of " intermittent hydronephrosis " are very rare. Another case of the kind reported by Mr. Thompson will be found below (see page 497). Mr. Henry Morris has collected six cases in which the affection was intermittent. To these he has added one case observed by himself, where the intermittent hydronephrosis of the right side was due to a villous growth of the bladder, obstructing the orifice of the ureter, but where the disappearances of the tumor were not associated with any ab- normal excretion of fluid. The tumor is usually quite painless, and unaccompanied by any inconvenience except from its bulk. Occasionally, how- ever, tenderness exists over it ; and the action of the bowels is irregular. When the dilatation arises from the impaction of a €alculus, symptoms of nephritic colic occur at the time when the impaction takes place ; or from time to time thereafter, if, as is most usual, some quantity of urine still continues to trickle past the calculus. Similar paroxysms are recorded in two instances where no calculus existed. The state of the urine usually furnishes no information : in the great majority of cases it is natural; sometimes, however, it contains a little pus ; but never in quantity. During the attacks of nephritic colic it may contain blood; and be discharged with great pain, retraction of the testicle, vomiting, etc. The history of these attacks sometimes yields an important clew to the nature of the case. When both kidneys are aifected, symp- toms indicating defective elimination of urine (ursemia) neces- sarily show themselves at length. A hydronephrosis implicating one kidney only may, as we have seen, cause little or no incon- venience for many years, even though its bulk be considerable. The opposite kidney performs a double duty and becomes corre- spondingly enlarged. An individual in this condition, however, leads an existence of considerable peril : for if anything happen to impede the function of the single kidney on which life de- pends, dangerous symptoms necessarily arise. Rayer supplies the following instructive example : M. v., set. 64, had experienced, at the age of 22, pain in the right renal region, shooting obliquely towards the bladder in the direction of the ureter. This pain proved obstinate, and increased more and more ; the urine was occasionally bloody, and sometimes of a dark color ; the patient became pale and thin. Little by little the urine ceased to con- 494 HYDEONEPHROSIS. tain blood, and reassumed its normal characters ; the general condition was perfectly restored ; and for a long series of years M. V. enjoyed blooming health. About the year 1820, M. V. began to grow stout ; the belly became remarkably large ; and latterly his great size considerably impeded pro- gression. On the 18th of September, 1834, M. V. experienced an uneasiness in the abdomen which constrained him to keep his bed ; pains were felt all over the abdomen, but especially towards the region of the left kidney. This region was tender on pressure ; the patient passed no urine ; and the bladder was not distended. During ten days M. V. had no desire to void urine, and at the end of this period he only passed two glasses of a citrine color. On examining the abdomen a voluminous tumor was detected, extending obliquely from the right hypochondrium to the left iliac fossa. Obscure fluctuation was felt in the tumor, which was considered to be formed by the distended right kidney (this was con- firmed at the autopsy). The condition grew more and more serious as the suppression of urine continued — the tongue became covered with a slimy coating ; the features altered ; the nights were sleepless ; the pulse failed ; hiccough supervened ; and the patient expired on the loth of October, 1834. On opening the body the right kidney was found prodigiously dis- tended, and converted into a pouch filled with 7 lbs. 11 ozs. of a viscid fluid ; the tumor was 16 inches long from above downwards, and 7J inches broad. The ureter was dilated at its origin, but soon underwent a sudden constriction ; in this strangulated part a little calculus could be felt which had completely obstructed the duct. Below this obstacle, the ureter resumed its ordinary dimensions. The left kidney was con- siderably tumefied and reddened. The pelvis was notably dilated and covered with vascular ramifications ; the left ureter, like the right, con- tained a small calculus lodged five inches below the pelvis. The bladder and other abdominal organs were healthy. The state of the right kid- ney explained perfectly the former ailments of M. V., and death was the consequence of the disabling of the solitary kidney on which his life had so long depended. (" Mai. des Reins," t. iii. p. 490.) Terminations. — Hydronephrosis may terminate in various ways. The obstacle may be dislodged, and the contents of the sac discharged, without subsequent reaccumulation. If, in such a case, a portion of the renal tissue be preserved, the organ will be enabled, in part, to resume its function. If the distention has been long established, and the secreting tissue extensively or totally absorbed, the organ after evacuation of the fluid shrivels up into an empty sac. These may be regarded as the most favorable modes of termination. I find that out of 40 fatal cases, which supply intbrmation as to the cause of death, 16 perished from some other disease. jSTearly all of these were slight, unilateral cases, which were latent during life. Five cases of double hydronephrosis per- ished stillborn or soon after birth from abeyance of the urinary DIAGNOSIS. 495 function. In 19 cuscs death took place at a later age us a direct or indirect consequence of the renal distention. Of these 19, one died wearied out with the bulk of the tumor and dysenteric diarrhcjoa caused thereby. Mr. Glass's patient died from jjressure of the vast sac on the respiratory organs. Five cases, in which double hydronephrosis was established gradually, died from pro- gressive abolition of the renal function — four of them with dis- tinct ursemic symptoms, one of whom (see -p. 487) had also intes- tinal obstruction due to constriction of the descending colon, which had become lirmly adherent to the ?iydronephrotic kid- ney. Two more, with single hydronephrosis, died from suj)- pression of urine through impaction of a calculus in the opposite ureter. In four cases, repeated tapping was followed by suppu- ration of the sac and exhausting hectic : in one, Dr. Hiller's case, the patient succumbed to acute tuberculosis. In another case, the second tapping was succeeded by fatal peritonitis. Pressure of the tumor on the adherent duodenum, and conse- quent intestinal obstruction, caused death in one instance (p. 491). It is remarkable that only in one solitary instance (to be presently cited) was death caused by spontaneous rupture of the sac. Diagnosis. — -The diagnosis of hydronephrosis is certain and easy only when subsidence of the tumor occurs simultaneously with a sudden excessive discharge of urine, or when trustworthy history of such an occurrence can be obtained. When this symptom is absent, the recognition of the disease depends on the ascertainment of the existence of a fluctuating renal tumor, and the absence of the signs of suppuration. Tlydronephrotic tumors have most frequently been confounded with ovarian cysts,^ ascites, and hydatid cysts. From an ovarian cyst, hydronephrosis is distinguished by the presence of the colon in front of the swelling, and by the absence of a boAvel sound on percussion in the corresponding lumbar region. Ascites is distinguished, when the hydronephrosis is single, by the existence of dulness in both flanks : but when the renal tumor is double, and both flanks are consequently dull as in ascites, the latter condition is recognized by the change of level assumed by the fluid when the posture of the patient is altered — dulness from dilated kidneys being flxed in its limits however the position of the patient may be changed. A hydatid cyst is generally identified by the escape of hydatid vesicles with the ^ An interesting case of an attempted removal of an immense liydronephrotic kidney, mistaken for an ovarian cyst, — followed by the death of the patient, is reported in the Archiv. f. klin. Chir., 1865. The cause of the hydronephrosis was a valvular flap of membrane at the origin of the ureter, which prevented the free escape of urine. Another case, in which the patient died on the twentj^- second day after the operation, is reported in the Berl. klin. Wochenschr. , vi. 23, 1869. 496 HYDRONEPHROSIS. urine, and sometimes by the presence of a hydatid fremitus. In the absence of these symptoms it may be quite impossible to establish the differential diagnosis of these two conditions by physical signs, and inferences must be drawn from the history. It may be of use to remember, that while hydronephrosis is not unfrequently double, a hydatid cyst is scarcely ever so. Pyonephrosis is distinguished by the purulent character of the urine — actual or historical — also by the existence of more severe constitutional symptoms, and especially of hectic and recurrent rigors. Circumscribed abscess of the kidney, and perinephritic abscess, are distinguished by their more acute course, the pres- ence of pain and the signs of suppuration. The Prognosis, although necessarily grave, is less serious than in other kinds of renal tumor. When the affection is unilateral, not onl}^ may life be indeffnitely prolonged, but there is always a chance that spontaneous evacuation of the sac may take place, or that the cyst ma}^ be punctured with success. If the opposite (hitherto sound) kidney show symptoms of deranged function, the gravity of the prognosis is immensely increased. When both kidneys are affected the issue is unavoidably fatal at length ; but many years may elapse before the atrophy of the secreting tissue, or the completeness of the obstruction, reaches a degree incompatible with life. Treatment. — If the disease be unilateral, and inferred to depend on the impaction of a calculus in the ureter, precautions should betaken against a similar occurrence taking place on the opposite side. The patient should be directed to keep the urine adequately diluted by systematic potation, especially on going to bed, and to avoid a too highly animalized diet. In the absence of this indication an attempt may be made to overcome the obstacle, or, if that be impossible, to facilitate the passage of the urine past it. To this end, the tumor should be carefully manipulated or shampooed, from time to time. As the swelling is usually painless, this can be accomplished without difficulty. In a little girl of eight, who came under my care in the Manchester Infirmary, this treatment seemed to be followed by success. She had a soft, obscurely fluctuating tumor on the left side of tVie abdomen, about the size of a child's head, which was considered to be hydronephrosis. This was diligently manipulated in every direction, with the aid of a lubricating ointment, on alternate mornings. After the third manipulation, she suddenly passed a large quantity of urine, and the tumor forthwith subsided, and did not again return so long as the patient continued under observation. If evacuation cannot be obtained in this manner, further interference is in my opinion not justified unless the expansion of the sac be such that its pressure threatens serious mischief. TREATMENT. 497 Under these circumstances tappint^ may l^e rcBortod to. TJjc following case, related by Mr. Thompson, of iS^ottingliam, furnishes an example of the successful adoption of this plan ; and the reasons set forth by the writer for the selection of the spot chosen for puncture seem to deserve attention. This case is likewise the solitary instance I have discovered, in which death was caused by bursting of the sac into the peritoneum. The patient came under Mr. Thompson's observation in May, 1851. He was at that time suffering from great pain in the region of the left kidney. There were considerable enlargement and tenderness on pres- sure extending over the left hypochondriac, lumbar, and iliac regions. Dulness on percussion also existed in these regions. Symptoms of nephritic colic had existed for a considerable period. Similar symp- toms had been observed on a previous occasion, which were suddenly relieved after passing, all at one time, more than a chamber-pot full of water, of the color of port wine. On the present occasion, a similar event took place ; in about a week the sac had entirely emptied itself through the ureter and bladder. The symptoms disappeared, and the patient apparently soon recovered. In November he began again to suffer from the same symptoms, which increased up to January 27, 1852. At this time the side was greatly enlarged and tender. There was an obscure sense of fluctuation, and the dulness extended to the right as far as the linea alba; backwards to the spine; downwards to the lowest part of the iliac fossa. The organs in the chest were dis- placed upwards. The patient's sufferings were now so great that it was determined to draw off the fluid with the trocar. There was no doubt that the sac containing the fluid was a dilated kidney, or a cyst con- nected with the pelvis of that organ ; and in either case Mr. Thompson was disposed to select the interval between the last two (floating) ribs near their anterior extremities at which to introduce the trocar. Mr. T. fixed on this spot for the following reasons : 1. Supposing the fluid to be contained in a sac having communica- tion with- the pelvis of the kidney, the kidney would lie behind the sac, partly upon the last two ribs, and partly upon the quadratus lumborum muscle, its normal situation upon this side ; and if the instrument were introduced at the place indicated, and its point directed a little forward, it would penetrate the sac without any risk of wounding the kidney. 2. If the sac consisted of a dilated kidney, the point selected would still be the best, as it would be near the part at which the organ began to dilate. 3. It would be behind the peritoneum, and therefore there would be less risk of wounding that membrane. 4. If the patient had been tapped in front, the trocar must have passed through the peritoneum twice : first, that portion lining the abdominal muscles, and, second, that in front of the sac; and, sup- posing no adhesion to have taken place between these two parts, when the instrument was withdrawn, some of the contents of the sac might have escaped into the cavity of the peritoneum and given rise to inflam- mation. Besides, there would have been more danger of wounding some 32 498 HYDRONEPHROSIS. of the bowels, should any portion have become adherent by inflanamation between the walls of the abdomen and the sac. The operation was therefore performed between the last two ribs near their extrefaities. An incision was made through the integuments and muscles; a small exploring trocar was then introduced; and as there was evidence of the existence of fluid, a larger instrument was inserted, with its point directed slightly forward, and eight quarts of dark-colored fluid were drawn off". It was a singular fact (which was explained on examination of the specimen after death), that soon after this fluid was removed, the further contents of the sac flowed in the natural direction along the ureter. The patient soon recovered ; but it was necessary to repeat the opera- tion in December, 1852, when 3^ quarts of fluid were extracted ; soon after which, as before, the sac emptied itself through the natural pas- sages. The patient soon got well, and did not require the operation again until near eight years afterwards (March, 1860). At this time seven quarts were taken away; not long after which the fluid again found its way along the natural passages, and the patient again made a quick recovery, and remained well until September, 1861. When then seen by Mr. T., he was suffering from his old symptoms. On the 5th ot October he was suddenly seized with pain in the abdomen, with difficulty of micturition, cold sweats, rapid pulse, and an anxious countenance. He went on pretty well until the 10th of October, when he suddenly became worse and died. The post-mortem examination revealed intense peritonitis. Three pints of dark-colored fluid (resembling that found in the sac) were removed from the right hypochondriac and epigastric regions. The sac proved to be the distended left kidney — it contained four pints of fluid ; a hole was discovered toward the left side anteriorly, where the rupture had taken place. The descending colon lay before and toward the left side of the sac; the ureter entered the cavity of the sac obliquely through the wall of the cyst. This obliquity of the entrance of the ureter offered a probable explanation of the closure of that tube when the sac was full, and the open state of it when the sac was empty. The rupture doubt- less took place on the 5th of October, when the peritonitis began; and in all probability there was some escape of fluid, but not much at that time; a further and larger escape took place on the 10th, after which the patient rapidly sank. There was no stone found in the bladder, nor any obstruction in the lower course of the ureter. (J. Thompson, " Path. Trans.," vol. xiii.) The early history of the case caused Mr. Thompson to sur- mise that the patient had formerly voided urinary calculi; but none were ever found. It is quite as possible that the obliquity of the entrance of the ureter into the pelvis of the kidney v^as a congenital malformation, and that this constituted the real cause of the hydronephrosis. Dr. Hiller relates another case of congenital hydronephrosis repeatedly tapped, in front, w^ith temporary success : ILLUSTKATI Vi<: CASKH. 499 The patient was born with great enlargement of the abdomen, simu- lating ascites, for which it was mistaken till he was nearly four years old. It was then ascertained to be an enormous cyst springing from the right lumbar region. From its great size it caused dilficulty of breath- ing and prevented his walking. The cyst was tapped in front, and 102 fluid-ounces of clear non-albuminous fluid were drawn off, iiaving all the characters of dilute urine. The fluid rapidly re-collected, and on a second tapping was found to be albuminous and purulent, but still to contain a considerable quantity of urea. Attempts were made to estab- lish a permanent fistula anteriorly, and then posteriorly; but on each occasion the fluid after a time ceased to flow. Much irritation and depression followed the several tappings, so that the patient's life seemed to be endangered. After one of the operations a quantity of fluid was passed from the bladder exactly similar to that from the cyst, and quite unlike what was usually passed from the urethra; a temporary com- munication thus obviously being established between the cyst and the bladder. When the case was reported, the patient had been left without operation for some months, and had regained his strength ; but the cyst remained, varying from time to time in size, and the urine was often purulent and fetid. It was presumed that there was some congenital malformation of the right ureter which rendered it liable to occlusion, but admitted, under some circumstances, of the passage of fluid. (" Brit, Med. Journ.," April 8, 1865.) The follow^ing is an abstract of the completion of this case : The patient remained under occasional observation between the above date and July 16, 1868, when he was admitted into hospital under Dr. Hillier, suffering from headache and feverishness. During this interval he had been once tapped, and a quantity of urine-like fluid was drawn off. Acute tuberculosis manifested itself, the patient gradually sank, and died on the 5th of August. On post-mortem examination, the great distention of the abdomen was found to be due to the presence of a large cyst, which filled the greater part of the cavity. The cyst, which meas- ured twenty-seven inches in circumference over the long diameter, and twenty-four over the short one, appeared to take the place of the right kidney — the suprarenal capsule, apparently normal, being attached to it. The ureter proceeded from the lower part of the cyst, to which it was attached for about an inch ; the orifice of the ureter at its vesical extremity was found smaller than usual. When a small dressing-probe, which was with difficulty passed up the ureter, reached within two inches of the cyst, and was then withdrawn, fluid could be squeezed out of the cyst through the ureter into the bladder guUatim. This could not be done previous to the passage of the probe. The cyst contained 83 ounces of clear fluid of a pale lemon color and urinous smell, specific gravity 1002, very slightly acid, with the faintest trace of albumen, and presenting under the microscope a few broken-down cells of large size. The left ureter was about an inch in diameter at its upper two-thirds, natural in size below, but contained calculous matter, forming an obstruc- tion to the flow of fluid, which could, however, be easily overcome. The pelvis of the left kidney was dilated sufficiently to contain a small 500 HYDRONEPHROSIS. pigeon's egg, and contained a little calculous matter, found on examina- tion to consist of uric acid. Tubercles were found in the brain, lungs, liver, and spleen. (" Med.-Chir. Trans.," lii., 1869.) When the tumor is on the left side, as in Mr. Thompson's case, mentioned above, the best point for tapping, is just ante- rior to the last intercostal space. Mr. Morris has tested this in the post-mortem room and has found that in no instance was the spleen injured. On the right side, however, such a puncture would pierce the liver, and Mr. Morris here recommends a spot " half way between the last rib and the crest of the ilium, be- tween two inches and two inches and a half behind the anterior superior spine of the ilium." In recent years the whole mass has been successfully removed by abdominal incision {see cases by Dr. Savage and Mr. Know- seley Thornton in the " Lancet," 1880, vol. I.). CHAPTER IX. CYSTS AND CYSTIC DEGENERATION OF THE KIDNEYS. Cysts are found in the kidneys under four practically different circumstances, namely : 1. Scattered cysts in kidneys otherwise healthy. 2. Disseminated cysts in the atrophic form of Bright's disease. 3. Congenital cystic degeneration. 4. General cystic degeneration in adults. 1. Scattered Cysts in Kidneys Otherwise Healthy. — It is not uncommon to find on the surface of healthy kidneys one or more cysts, with delicate walls, varying in size from a pea to a marble or walnut. One or more of similar appearances may also be found in the interior of the gland, chiefly in the cortical substance. Such cysts are filled with a yellowish albuminous fluid — usually difliuent, sometimes gelatinous, — containing phos- phates and carbonates, sometimes a large quantity of choles- terine, and very rarely urea and uric acid. Cysts of these dimensions do not produce any symptoms during life ; and their efiects on the functions of the gland are insignificant. Sometimes, however, cysts of this class attain a monstrous size, and form a tumor recognizable during life. Mr. Csesar Hawkins gives an account of a remarkable case in which the right kidney of a boy, six years of age, had an enor- mous cyst attached to it. The cyst filled the entire right side of the abdomen from the false ribs to Poupart's ligament. The at- tached kidney was healthy in its structure, and the ureter free. In the wall of the cyst, separated by a distance of five inches from the kidney, there was inserted a small mass about the size of a walnut, which projected into the cavity of the cyst. This body proved to be a third kidney, consisting of a single lobule, with the cortical and tubular part perfect; and having a single mammillary process and calyx; but no excretory duct could be traced. The urine had been natural. The cyst was punctured during life ; and about five pints of fluid were found in it 'after death. The fluid contained neither albumen nor any of the special urinary ingredients. Dr. Hare ("Path. Soc. Trans.," vol. iv. p. 199) describes a very similar cyst taken from a man aged sixty-two. A "tumor was detected during life on the right side, stretching from the ribs to the pubes. After death, a large cj^st was found connected with the right kidney. The lower half of the gland was partly 502 CYSTIC DEGENEKATION OF THE KIDNEYS. spread out over a portion of the tumor, and partly absorbed. The upper half was healthy; nor did it (nor the opposite kid- ney) contain any other cyst, with the exception of one, about as large as a hempseed. The large cyst contained an almost trans- parent, pale, yellowish-green fluid, quite limpid and diffluent when the cyst was first opened : but after the fluid had been ex- posed a few minutes to the air it set into a tremulous jelly. In neither of these two cases was the pelvis of the kidney nor ureter dilated. In both cases the disease was doubtfully traced to external violence. 2. Disseminated Cysts in the Atkophic Form of Bright's Kidney. — These have already been noticed in connection with Bright's disease (see p. 401.) 3. Congenital Cystic Degeneration of the Kidneys. — A considerable number of these curious cases have been published, and most of them have been collated by Yirchow in two elabor- ate papers (Gesammelte Abhandlungen, pp. 837 and 864). Kidneys in this condition present an enormous proportionate bulk, being as large as, or larger than, the kidneys of adults. In all but two cases both kidneys were affected. In several instances embryotomy was required to effect delivery, on account of the immense size of the abdomen. The foetus (generally expelled prematurely) is necessarily stillborn if both sides are afiected, on account of the pushing up of the dia- phragm, and the mechanical obstacle thus created to the expan- sion of the lungs. Dr. Lever (" Path. Soc. Trans.," 1848-9, p. 74) has recorded the following typical example. The foetus was one of eight months. It was clubfooted and clubhanded ; it had six fingers on the left hand and as many toes on each foot. There was a hernia cerebri (encephalocele ?) at the posterior part of the head. The thoracic and abdominal viscera were natural, except the kid- neys. The right kidney weighed 4 oz. 6 drs.; the left, 4 oz. 1 dr.: they were irregular on the surface from numerous project- ing cysts. On a section being made through the centre of each, it was found that all traces of kidney structure had disappeared, and that its place was occupied by an infinite quantity of cysts of diflterent sizes, forming the whole mass of the organ ; the calices were in part normal, but large, and the pelvis of each kidney was perfect, with the exception that it formed a blind sac, with no opening; that is to say, there were no ureters. The bladder was small and empty; there was no trace of ureters on its external surface ; but internally, at the spots where the ureters should have entered, there were small imperforate papillae. The structure of these kidneys was examined by Dr. Gull under the microscope. He could not detect any secreting CONGENITAL CYSTIC ]) EG E N K II A 'I' J O N . 503 tissue, and considered the cysts to be obstructed and dilated Malpighian capsules.' The degeneration has not always been found in so extreme a degree as in this case of Dr. Lever. Generally, some remnants of secreting texture (uriniferous tubes and Malpighian tufts) have been detected in the interstices between the cysts. In some cases the external surface is smooth, while the interior presents a spongy or cavernous structure, which, under the microscope, resolves itself into myriads of minute cysts. The researches of Virchow and Foster have fully demonstrated, that the cysts in these cases are originally produced by dilatation of short sections of the uriniferous tubes into pouc?ies ; these pouches afterwards become enlarged and separated from each other, and at length form distinct cysts. They are lined with a tessellated epithelium, and contain, at iirst, a urinous fluid, which at a later period, when the cyst attains a larger size, becomes albuminous. It is curious that malformations of the pelvis of the kidney, of the ureter, bladder, or urethra, or of some other part of the body, nearly always coexist with congenital cystic degeneration of the kidneys. Sometimes, however, the lower urinary pass- ages are perfectly open. Virchow flrst pointed out the mechanical cause of this dis- ease. In all the cases examined by him, there was found an im- perforate state (atresia) of the straight ducts which terminate on the papillae; and he conjectures that this had arisen from intra- uterine inflammation of the ducts of the papillae, which ended in adhesion of their parietes and closure of their calibre. He further believes that the usual cause of this inflammation is the impaction of uric acid or the urates (Harnsaure-infarct), in the straight canals {see p. 474). The closure of the excretory ducts necessarily causes stagnation and accumulation of the urine throughout the entire organ, and leads to dilatation of the ^ Dr. Duffey ("Dub. Quart. Journ.,"xli. p. 438) has described the following case in an anencephalous foetus at the full time. The fourth and fifth fingers of both hands and the corresponding toes on the right foot were united by a web up to the second phalanges, and there was a sixth digit similarly united to the entire length of the fifth. The left foot was normal. The abdomen was 18 inches in circum- ference. There were two tumors found in the abdomen, which proved to be the kidneys, lying on and adherent to which were the ovaries and Fallopian tubes leading to a bifid uterus. The kidneys presented the usual lobulated appearance of the foetal organs, but on section numerous small transparent cysts were found of the size of peas, in a matrix of a light grayish color, from which they could not be detached, and which contained a clear serous fluid. The distinction between the cortical and medullary portions was totally obliterated, but the outline of the calices could be distinctly traced. The ureters were pervious; bladder empty. The right kidney, even after exposure to the air for some days, weighed 6 oz. ; the left was apparently of equal size. 504 CYSTIC DEGENERATION OF THE KIDNEYS. uriniferous tubes and Malpighian capsules, and the ultimate for- mation of cysts, ^ 4. General Cystic Degeneration of the Kidneys, in Adults. — This is a somewhat rare condition, though most museums contain specimens. There are two very fine examples in the collection of the Owen's College. In this form of disease the organs are more or less enlarged, so as sometimes to weigh several pounds, and to constitute tumors in the abdomen recog- nizable during life. Both kidneys are always aft'ected ; but not, generally, in an equal degree. The substance of the gland is converted into a mass of closely aggregated cysts, lodged in an abundant matrix of connective tissue {see Figs. 63 and 64). The cvsts do not communicate with each other, nor with the calices —except in rare cases, when some of them suppurate and open into the pelvis. They range in size from a pin's head to an orange, and have walls of varying thickness. Their contents also vary: some contain a limpid yellowish or reddish serum; others a gelatinous substance. The fluid within the cysts always contains albumen, but not urinary ingredients. The interior of the cysts is lined with epithelium usually of the tes- sellated variety ; and sometimes blood-disks, pus-corpuscles, and cholesterine crystals are found within them. In far advanced cases the secreting tissue of the kidney is almost entirely de- stroyed; more frequently remnants of renal tissue are found in the fibrous matrix between the cysts and in the pyramidal portions. The pelvis, ureter, and bladder are open, and usually healthy. Two or more cysts may become confluent by absorp- tion of some parts of their walls, and then an irregular cavity is produced, with fibrous bands or freena passing from side to side. Quekett attributed the formation of these cysts to dilatations of the Malpighian capsules; but the observations of Dr. Conway Evans,^ and Dr. Bristowe,^ on what appear to have been incipi- ent cases, lead to the conclusion that they are formed, as in the congenital cases, by expansion of sections of the uriniferous tubes, and occlusion and atrophy of the intermediate portions. Independent sacs are thus constituted, which at first are so ' Koster argues that this view is incorrect. He attributes the origin of the cystic kidney to an abnormal development analogous to atresia ani, non-development of the urethra, and similar conditions ; and urges in support of this view the total absence of the renal calices and pelvis, and also the ureters in many cases of this disease. Kupfer's investigations into the development of the kidney, showing that the blastema for the tubuli uriniferi is developed by itself, independently of the evolution of the WolflBan duct (which becomes ureter and renal pelvis), will if con- firmed lend greatly to strengthen the theory advocated by Koster. Origin of the Congenital Kenal Cystoid. " Nederlandsch. Arch. v. G-en. in Naturkunde, 1867, translated by W. D. Moore, Dub. Quart. Journ., xlvi. 256. 2 Path. Trans., vol. v. p.' 183. -^ Ibid., vol. ix. p. 309. IN ADULTS. 505 niiiiute that they can only be seen with the niicroBCOpe, but at a liater period they enhirge into visible cystH.' The clinical history of these cases has been but imperiectly studied. Of fifteen cases which I have been able to collect — including one contributed by myself — ten were men and live women; most of them were about the middle age; ten were Fig. 63. General cystic degeneration of the kidney in an adult — i'lom a preparation in the Museum of the Manchester Infirmaiy — one-fourth the actual size. between forty and fifty years of age; one was " old," one was thirty-nine, and the youngest thirty. The S3miptoms during life are not very distinctive. The course of the disease is essentially chronic; the secretion of urine goes on to an advanced period, without marked diminution — it may even be greatly increased. An unnaturally low density of the urine would appear to be a tolerably constant feature, at least in advanced cases. The end (if the patient die of the renal affection and not of some compli- cation) is usually sudden, with manifestations of uraemic coma and convulsions. In a case cited by Eayer, there were recurrent 1 A form of cystic kidney somewhat different from that described in the text is found associated with a similar degeneration of the liver. It must not be con- founded with putrefactive changes in these organs. (See Brit. Med. Jouru.. 1884, i. p.61.) 606 CYSTIC DEGENERATION OF THE KIDNEYS. attacks of excessively violent lumbar pains, severe gastric symp- toms, abundant discharge of a watery urine, and lastly, convul- sions, delirium, and coma. In another case recorded by the same author, the patient — whose only previous suiFering con- sisted in old-standing dyspeptic symptoms — was suddenly seized with coma, resolution of the members, and convulsive upturning of the eyes, which proved fatal in twelve hours. In two cases reported by Dr. Whipham,* the closing symptoms were bronchitis with urgent dyspepsia, without coma or convulsions. Albumin- uria and recurrent hpematuria are among the most constant symp- toms. In Dr. Conway Evans's case, the urine was, however, not albuminous on the day of death, nor two months previously. Death was caused in this case by cardiac disease, and the renal degeneration was not, comparatively speaking, very far ad- vanced.^ The latent and insidious course of the disease, with sudden stormy termination, is well illustrated in the following example, which occurred in my practice : On Saturday evening, October 28, 1871, I was requested by Mr. R. Heathcote to see Mrs. S., a married lady of forty-eight. He informed me that the patient was the mother of several children, of whom the youngest was four years old. The menses still continued, but irregu- larly. Some three months previously she had been under his care for neuralgia and anssmia, which yielded readily to quinine and iron. Since then she had been in her usual fair health up to the previous Monday, when she was suddenly attacked with vomiting. The vomiting con- tinued, almost incessantly, during the current week, and no urine had been voided since Tuesday. Early on Saturday morning, she was seized with an epileptic fit ; this was succeeded by two more in the course of the day. At noon, about six ounces of urine were withdrawn by catheter. This was of normal appearance, but it contained a moderate amount of albumen. When I saw her in the evening, the vomiting still persisted, accom- panied with devouring thirst. The patient was nearly fully conscious. There was great restlessness, with tossing of the limbs and moaning. ^ Path. Soc Trans., vol. xxi. p. 244. ^ [Three cases of cystic kidney have died in the Manchester Eoyal Infirmary during the last three years. The first case had shown mental depression and stupor for a fortnight before admission, and died a weelt afterwards with ursemic symptoms. The second case died from ursemic coma two days after admission, and no reliable history could be obtained. Before death the urine was scanty and contained a large quantity of blood. Both kidneys were cystic, and the left had two ureters, proceeding from entirely separate pelves of the kidney ; the two divisions of the kidney were equally affected by the cystic transformation. In the third case, the kidney change was found only in the regular course of a post- mortem examination. The patient had died from chronic cerebral meningitis, and during life there was neither albuminuria nor any other symptom of kidney mischief. Microscopic examination showed a certain amount of true kidney struc- ture, but the glomeruli, renal tubes, and arteries were surrounded by a great quantity of fibrous tissue. — R. M.] ILLUSTRATIVE CASES. 507 The bowels had been opened by injection. The pupils were strongly contracted, and the tongue was dry. On examining the loins, I detected two soft elongated swellings or tumors, one on each side, in the renal regions. The tumors appeared about the same size, and might be about as large as a cocoanut, but of greater length. They did not fluctuate. Both flanks were dull on per- cussion. ^ I ventured to express the opinion that we had to do with cystic Fig. 64. */"* ---/. ' %K Left kidney of Mrs S. — showing complete cystic transformation of the organ — about onf-half the actual size. degeneration of the kidneys, basing the diagnosis on the urtemic com- plexion of the symptoms, the existence of two soft renal tumors with albuminuria. If this diagnosis were correct, there could be no question of curative treatment. It w^as suggested, however, that the lumbar swellings might possibly consist of fecal accumulation. The treatment was accordingly directed to remove these. Sulphate of magnesia ene- 508 CYSTIC DEGENERATIOiSr OF THE KIDNEYS. mata were ordered to be repeatedly administered, and belladonna in pill was given by the mouth. Nothing availed. In the course of the night the patient had six epileptic fits, and when we saw her on Sunday morn- ing she was barely conscious. The stomach was, however, much quieter, and she had been able to retain a considerable amount of liquid nourish- ment. No urine had been voided, but 16 ounces were withdrawn by catheter. This was pale amber, clear, faintly alkaline ; it was slightly albuminous (abt. -^■^), specific gravity 1013. After it had been kept for twelve hours, it deposited a copious sediment of triple and amorphous phosphates, and spheres and dumb-bells of urate of ammonia, but no casts of tubes could be detected. During the course of Sunday and Sunday night, the epileptic seizures recurred again and again, and death took place on Monday morning, after an illness of almost exactly a week. Autopsy. — The body was tolerably well nourished. Only the abdo- men was examined. All the organs in it were healthy except the kidneys. The kidneys presented typical examples of cystic degenera- tion (see Fig. 64). They were considerably enlarged, and appeared to consist entirely of a congeries of large and small cysts. The right weighed 28 ounces, and the left 26 ounces ; they were of an elongated, oval form, between eight and nine inches in length, and four inches in thickness. On section of the right kidney, not a particle of normal renal tissue could be seen ; the entire organ was converted into cysts and intervening fibrous tissue. The left kidney was not so completely degenerated. The cortical substance was all transformed into cysts and fibrous matrix ; but the pyramids were not wholly destroyed. The papillse could still be distinguished, together with a short length of the annexed portions of the pyramids. These presented a pale-red striated appearance. Judging roughly, about a twentieth part of the renal tis- sue might be said still to exist, and on the services of this remnant the patient's life must have latterly depended. It is most strange that life could have been protracted until this extreme degree of destruction had been reached The cysts varied in size from a pea to a walnut ; most of them were as large as marbles. Their contents were (generally) a clear yellow, highly albuminous serum. Some were opaque and semi-solid, either yel- lowish or dark red. These diflferences depended on two circumstances, namely, the degree of inspissation and degeneration of the contents, and on eflTusion of blood into the cysts. Under the microscope, the yellow semi- solid contents were found to be composed of free fatty and albuminous granules and large numbers of so-called "granular corpuscles.'" A few plates of cholesterine and crystals of triple phosphate were also found. No traces of urea or uric acid could be detected. The following example from Bright's memoir on abdominal tumors (" ISTew Syd. Soc.'s Publications," vol, vi. p. 208) show^s the successive appearance of a renal tumor first on the left, then on the right side of the abdomen, and gives an excellent picture of the disease. Mr. , about thirty, seen by Dr. Bright, November, 1835. His aspect bespoke a man laboring under some formidable chronic disease. ILLUSTRATIVE CASES. 509 He was evidently much emaciated and greatly enfeebled. He passed a moderate quantity of urine, which was acid, light-colored, and albu- minous. His present illness dated about two years back, at which period he had decided htcmaturia, which continued at intervals for some time. Since that, he had never considered himself in health ; he had, however, pursued his usual occupation till lately, but for the last four months he had been more decidedly an invalid. A tumor was to be distinctly ascertained in the left lumbar space, where it appeared pretty firmly fixed (see Fig. 65). It might be fairly grasped by the hand so placed Fro. 65 Diagram showing tlie situation of the tumors in the case of a patient with general cystic degeneration of both kidneys (after Bright). that the thumb was near the spine, and the finger advanced into the hypochondriac region. The history of the case, the state of the urine, and the situation of the tumor, all led to the easy decision that the tumor depended on enlarged kidney. When felt in front, the spleen, or the descending colon loaded with feces, suggested themselves ; but the fact that it seemed to belong rather to the posterior than the anterior "part of the abdomen, and its fixed feel would have removed these doubts had not the history of the case pointed so distinctly to the kidney. The exact nature of the renal disease was less obvious. The very consider- able enlargement of the organ did not belong to the usual history of albuminous urine, and the general loss of power bespoke some formid- able organic disease. He was ordered a well-regulated nourishing diet. The emplast. ammoniaci c. hydrarg. was applied to the seat of the 510 CYSTIC DEGENERATION" OF THE KIDNEYS. tumor; and the uva ursi in infusion, and slight alkaline preparations, were directed to be taken. Under this treatment flattering reports were at first received, but the disease advanced, all the symptoms became worse, enlargement of the right kidney also became pex'ceptible, the urine remained moderately coagulable (about a pint and a half in twenty- four hours), and he suffered a great deal of pain at the neck of the bladder, from the frequent passing of fibrinous coagula of a slight pinkish- yellow color, about an inch long, and apparently moulded by the urethra. His emaciation became extreme, and he had frequent returns of hsema- turia. From the middle of February he was completely confined to his bed, expecting death daily. In the first week of April he experienced some slight convulsive seizures, and fell into a state of coma for a few hours before his death, which occurred about the 10th of April. Both kidneys presented most extreme specimens of vesiculated dis- ease ; the left was the largest, and was probably eight or ten times the natural size, while the right was at least six times the size of the healthy kidney. The whole appeared made up of a congeries of vesicles, from the size of a pigeon's egg to a pea ; and the substance of the kidney was almost obliterated ; nothing but a thin layer of secreting structure re- maining, and that greatly altered from the natural texture. The pelvis of the kidney and the mamillary processes alone retained a tolerably healthy appearance; the lining membrane of the pelvis had no undue vascularity, and was perfectly smooth ; the mammillary processes, though somewhat flattened, showed, when divided, the healthy organization; the ureters were healthy, but the renal vessels, particularly the veins, were large. The other viscera were healthy, and the bladder contained half a pint of urine. The enormous size which the kidneys sometimes attain in this disease, and the abrupt termination of life, are illustrated by the following remarkable case recorded by Dr. Hare (" Path. Soc. Trans.," 1850-1, p. 131) : A man, set. 46, was seen in January, 1850, for an attack of pleurisy. Under treatment, he recovered and returned to his business, until the 5th of March, when Dr. Hare was again called in. The night pre- viously he had passed a considerable quantity of very bloody urine, which had, apparently, given him great relief from a constant pain he had in the left loin. On examination of the abdomen, which had lately become larger than usual, a tumor was found, extending from the car- tilages of the false ribs of the left side to about an inch below the level of the umbilicus, and forwards to within about an inch of the median line. On percussion it was dull, and there was no interval of resonance between the tumor and the cartilages of the ribs; and the dulness on percussion extended upwards beyond the lower margin of the latter; the anterior border was rounded, but presented no signs of fluctuation. In April, a considerable alteration was observed to have taken place in the turaiOr ; it still felt solid and without fluctuation ; the lower border extended an inch and half below the level of the anterior superior spine of the ilium. Its anterior border was deeply notched on a level with the umbilicus, and percussion was resonant at this notch, as also for ILLUSTRATIVE CASES. 511 some distance obliquely across the tumor. It presented very much the physical signs of a double tumor, or of two tumors; on placing (jne hand over the lower part of the abdomen, and pressing with the other against the left loin, although the tumor could i)e very slightly moved, it appeared to move as one mass. iJr. Bright, who also saw the case, spoke confidently as to its being "all kidney with intestine passing C)ver it, and thus giving the appearance of two tumors ;" there was also now a slight interval of resonance between the cartilages of the false ribs and the tumor. The urine, which had contained blood two or three times, was now clear. On the 9th of December, he fell suddenly from his chair, convulsed and insensible ; this was followed by sleepiness, numbness in both hands, and frequent twitchings. On the 12th, when seen by Dr. Hare, he had a vacant expression, wandered a little, but answered sharply when spoken to; there were slight twitchings of the upper extremities. Pulse 72; feet and legs rather edematous. The tumor appeared much the same as in April, except that it extended rather beyond the median line, and that the notch, at its anterior border, was less marked. Urine pale, without sediment, specific gravity 1008, containing one-tenth albumen. On the 13th, he had two fits, somewhat similar to those on the 9lh, and he died on the 16th, probably from the presence of urea in the blood. Autopsy. — The left side of the abdomen was occupied by an enormous tumor which proved to be the left kidney, the intestines being pushed over to the right side. The tumor also extended under the intestines half-way across the right half of the abdomen ; its upper surface was adherent to the diaphragm, and it had so compressed the spleen, that the latter formed, as it were, a cap to the kidney ; the pancreas was carried forwards, and was adherent transversely to the anterior surface of the tumor, near its upper part ; the descending colon, somewhat con- tracted, was likewise adherent to its anterior surface, but perpendicularly, so as to divide it into nearly equal portions. The kidney measured 151 inches in length, 9J in breadth, and about 23 in circumference, and weighed exactly 16 lbs.; it still retained some- what the kidney shape, but its surface was uneven from the projection of diflTerent cysts. It consisted of one enormous congeries of cysts, vary- ing in size from a small pea, to a cavity holding more than a pint of fluid ; the larger cysts were at the surface, the smaller ones being about the centre; many of the smaller cysts projected more or less into the cavity of the larger ones : they presented different tints, from a dark purple, to a light straw-color (the latter much more rare than the for- mer), according to the color of the contained fluids ; the darker fluid was generally the thickest, and at the bottom of those cysts the're was more or less of a dirty-red grumous-looking matter, which was wanting in those containing the lighter- colored fluid. The thickness of their walls varied generally in proportion to their size, the larger having the thickest parietes. No trace of the proper structure of the kidney was discoverable. The fluid, under the microscope, showed an immense number of blood-disks (more abundant in the darker fluids^, some oil 512 CYSTIC DEGENERATION OF THE KIDNEYS. globules, exudative corpuscles, portions of the tubules of the kidney, and a considerable number of plates of cholesterine. The right kidney presented incipient disease of the same kind, and was enlarged to double its natural size. There was a slight hypertrophy of the heart, and a hernia above the umbilicus ; the remaining viscera were natural. In the following case described by Dr. Gray ("Path. See. Trans.," vol. vi. p. 267), the disease appeared to be occasioned by external violence : death was not preceded by cerebral sj-mptoms, but by vomiting and hiccough, possibly of ursemic origin. A man, set. 40, much emaciated and ansemic, who had been very in- temperate when young, was admitted into St. George's Hospital, March 7, 1855. He dated the commencement of his present illness seven years ago, when he received a severe injury of the back ; for some time after this accident he passed blood in his urine. He then partially recovered, but during the three following winters he often passed a small quantity of blood, and suffered much from pain in his loins. Five weeks before his admission into the hospital, he fell on his right hip, and then the hsema- turia and pains in the loins returned in an aggravated form. When first admitted, he was in a very weak and exhausted condition ; the pulse was exceedingly feeble, and the urine was loaded with blood ; vomiting and hiccough supervened, and he died exhausted on the 10th of March. Autopsy. — There was extensive cystic transformation of both kidneys ; and to such an extent had the disease proceeded that the natural struc- ture of the glands could in no part be detected. The right kidney weighed 3 lbs. 10 ozs. ; the left, 3 lbs. They were each about ten inches in length, lobulated on their surfaces, and composed of numerous sepa- rate cysts, varying in size from a pea to a small apple. The contents of some of the cysts were transparent and colorless, of others faint yellow, of others chocolate. The color in these last appeared to depend on blood-disks and their debris. The pelvis of the kidney and the ureter were not dilated. All the other organs were natural, with the exception of the lungs, which were oedematous. The primary lesion in this class of cases is possibly the same as in the congenital cases, and consists in a progressive occlusion of the ducts of the pyramids, leading at a later period to sac- cular dilatations of the tubes of the cortex, and finally to the formation of myriads of separate cysts. The cause of the oc- clusion, in most cases, is probably an interstitial inflammation, leading to the formation of contractile fibrous tissue. Thorn (Inaug. Diss. Bonn., 1882) found in one case that the inflamma- tion had begun in the ureter and pelvis of the kidney, and had NATURE AND TREATMENT. 513 thence proceeded to the pyramidal portion. It in [)robab]o that the epithelium of the tubes also undergoes Honio active change, but of what nature is uncertain.' Conceivaljly the calibre of the ducts may be obstructed by plugs of coagulated blood. In Dr. Gray's case, just related, the latter explanation would appear to be a not improbable one. General cystic degeneration has evident affinities with the granular atrophic forms of Bright's disease, and probably requires a similar treatment. ^ See Cornil and Brault, Siir la Pathologic du Kein, Paris, 1884, p. 203. Chot- insky (Inaug. Diss. Bonn., 1882) asserts that, in the fcetal form, proliferation of the epithelium plays a part in blocking the tubes. 33 CHAPTER X. CANCER OF THE KIDNEY. Cancerous growths of the kidney may be primary or secondary. Primary cancer is attended by its proper symptoms and physical signs : it runs a distinctive course, and constitutes the cause of death. Secondary cancer, on the other hand, occasions neither symptoms nor physical signs : it is either a part-manifestation of a general cancerous cachexia, or an incident in the progress of primary cancer of some other organ ; and its existence is usually unsuspected until the autopsy. It is therefore necessary to con- sider the two conditions apart, the latter indeed very briefly, as it has little, if any, clinical interest. A.— PEIMAKY CANCEK OF THE KIDNEY. The following description is based on an analysis of 68 cases, of which 64 were collected from various sources, and 4 con- tributed by myself. In all of them the disease was followed to its fatal termination, and the diagnosis verified by dissection after death. The cases naturally fall into two groups — children and adults; and it will be desirable occasionally to distinguish the one class from the other. The first group embraces 25 cases under the age of ten years — indeed all, except 3, under five years. The second group includes 43 adults between the ages of nineteen and seventy. Morbid Anatomy. — The species of cancer found in the kidney is almost invariably the encephaloid (fungus hsematodes).^ It varies greatly in consistence and vascularity. In one instance it is described as being as soft as the milt of a fish ; more com- monly it is about as hard as human brain. The mass is seldom of uniform consistence throughout, and it is frequently the site of extensive hemorrhages. Cavities containing as much as a pint or more of clotted or fluid blood, or of blood mixed with 1 Two cases are reported in the Path. Soc. Trans., xxi. pp. 239, 241, in one of which Mr. De Morgan found the cancerous matter arranged in a villous manner ; and in the other, recorded by Dr. Murchison (a case of villous disease of the bladder), the mucous membrane lining the pelvis and calices of both kidneys was studded with long villous processes. MORBID ANATOMY. 515 cancerous detritus, have sometimes been found within the tumor.^ Scirrhus is very rare in the kidney. Wilson mentions such a condition, but his description is vague. Rayer in one instance found a mass resembling mammary scirrhus in the midst of an encephaloid kidney ■? and Dr. Walshe, among the unpublished drawings of Carswell, discovered one of scirrhus of the kidney: "the entire organ was converted into a gray-colored substance, somewhat transparent, and of the hardness of fibrous tissue. It was intersected in various directions by pale-colored bands which were opaque and lirmer than the intermediate gray substance. It yielded only a small quantity of serosity on pressure, and pre- sented few or no bloodvessels." (Walshe, loc. cit., 380.) Colloid cancer has been occasionally found forming a part of an encephaloid kidney. Epithelioma has not, so far as I know, been found in the kid- ney in the primary form in more than two cases. In one case published by Robin the right kidney of a man aged fifty-one was replaced by a large mass of adventitious tissue, of which part was soft and part hard. Both portions were composed of cells of epithelial character, most of them closely approaching the appearance of pavement epithelium, and attaining in the softer portions enormous dimensions. Some of the largest measured -^ of a millimetre in length. ISTone were found dis- posed in nests as in an ordinary cutaneous epithelioma.^ The second case was observed by Waldeyer, and quoted by Birch- Hirschfeld in his " Lehrbuch der Pathologic," p. 1041. Encephaloid invades the kidney sometimes in the nodular, sometimes in the infiltrated, form. It always begins in the cortical substance, and afterwards involves the pyramids. Th epithelium of the renal tubules is first afi'ected, and then the connective tissue.* The tunica propria is commoul}^ thickened into a strong fibrous membrane. When the whole organ is uniforml}^ infiltrated, its natural shape and position may be tolerably preserved, even when it is 1 The late Dr. Hilton Fagge described a peculiar variety of cancer of the kid- ney, in which fatty degeneration had occurred, and which he stj-led, after Cornil and Kanvier, Carcinoma lipomatosum. (See Path. Trans., vol. xxvii. p. 204.) 2 A similar case is reported by Dr. E. E. Townsend, Jr., of Cork. (Dub. Quart. Journ., xlv. 219.) ^ Ch. Robin. Memoire sur I'Epithelioma du Rein. Paris, 1855. See also Lebert, Anat. Pathol., ii. 351. Mr. Hoyle, in a patient w^io died in the Man- chester Royal Intirmary, found epitheliomatous nodules in the kidney secondaiy to similar growths in the lungs, and in each organ describes cell-nests. (Joui'n. of Anat and Phys., vol. xvii. p. 509.) * Cattani w^as able in one case to trace the development of the cancer cells from the renal epithelium. Dr. Norman Moore observed a similar appearance, and Dr. Sharkey traced the cancer cells to proliferation of the cell-lining of Bowman's capsule. (Path. Trans., vol. xxxiii.) 516 CANCER OF THE KIDNEY. enlarged to many times its original volume. But when a nodule grows from one end of the gland, leaving the remainder exempt, an irregular tumor is formed, which may assume shapes, and grow into- situations very embarrassing for the diagnosis. The exempted portions rarely preserve their healthy state; the secreting structure wastes and degenerates ; or it suppurates — though this is rare. It is a marked characteristic of primary renal cancer, that it forms a tumor generally of large, often of gigantic proportions, which may stretch from the loin to the umbilicus, and from beneath the ribs to the pubes, and weigh many pounds. In 31 out of our 68 cases, exact information is given as to the weight of the tumor. In 16 children its average weight was 8J lbs.; the smallest was 1 lb. 9 oz. and the largest 31 lbs.! In 15 adults the average weight of the tumor was 9J lbs.; in one case the growth was about the size and weight of the natural kidney ; in another it weighed 15 oz.; in two others it weighed IJ lb.; in several it varied from 3 to 11 lbs., and in two attained a weight of 27 lbs. The enormous masses found in young children are really remarkable. In one example, recorded by Mr. Spencer Wells, a growth weighing between 16 and 17 lbs. was taken from the body of a child only four years of age (" Path. Soc. Trans.," xiv. 179). The surface of an encephaloid kidney is usually soft, irregu- larly lobulated, and of unequal consistence. I^Tot unfrequently it yields a deceptive sense of fluctuation, especially in certain spots. Renal encephaloid is liable to the same accidents (degenera- tion, softening, suppuration, hemorrhage) as soft cancer else- where. In an instance mentioned b}^ Bright, the softened mass burst into the peritoneum ; in another, by Rayer, a cancer of the right kidney ulcerated into the duodenum ; in a third, by Abele,^ the disease broke through the abdominal parietes a fort- night before death, and formed a fungous ulcer through which a portion of the colon protruded and ultimately mortified. The tumor generally contracts extensive adhesions to the sur- rounding parts. The colon is invariably found in front of the growth — though sometimes flattened and empty. The other abdominal viscera are thrust aside as the tumor enlarges : the small intestines are pushed over into the opposite flank. When the growth afiects the right kidney, the liver is displaced to the left, often twisted on its transverse axis so that its upper surface takes a vertical direction and applies itself to the costo-abdomi- nal wall. This distortion has been especially observed where, as in Doderlein's case, the growth protrudes from the upper end 1 Schmidt's Jahrb., Bd. v. S. 379 MORBID ANATOMY. 517 of the kidney, and makes its way into the ri^ht Ijypochondriun). When the tumor is constituted by the left kidney tlie stomacli is pushed to right, and the s[)leen carried Ijigh up into the vault o*f the diaphragm.' The thoracic viscera are displaced upwards more or less accordir)g to the bulk of the tumor, and in various directions according to the side affected. Among other effects on the adjacent parts, caries of the vertebra? was twice found : more or less compression of the inferior cava generally exists towards the later periods, occasioning codema of the legs and sometimes (though rarely) ascites. The pelvis of the kidney was found generally more or less involved, and, in the majority of cases, the ureter was perma- nently occluded by extension of the cancerous growth into it, or by blood-clots, or by the pressure of the main tumor. The renal veins in several instances contained encephaloid matter ; and in some of the cases it could be traced as far as the vena cava. In the overwhelming majority of cases only one kidney was affected. Out of 67 instances which supply information on this point, the disease was confined to one kidney 60 times. In seven cases both kidneys were involved ; but in three only of these did the disease appear to be primary on both sides; in the other four one kidney was the seat of primary cancer, which formed a tumor, while its fellow only contained small secondary nodules. In the 60 unilateral cases, each kidney was affected an equal number of times. The primary disease in the kidney was associated with secon- dary deposits elsewhere in 31 out of 51 cases which give details on this point : in the remaining 20 cases all other parts were exempt. The most frequent seats of secondary deposits w^ere the lymphatic glands in the hilus of the kidney, and the verte- bral and mesenteric glands. These glands formed in some of the cases a large tumor, which — as in a case to be presently re- lated — transcended the dimensions of the renal tumor, and greatly embarrassed the diagnosis. The lungs and liver were also often affected; the other organs more rarely; but instances are on record in which almost every conceivable combination existed. The following table exhibits the distribution of the secondary deposits in the 31 cases already alluded to: 1 In Case 2, reported a few pages further on, the position of the spleen was exceptional ; it was carried downwards toward the iliac fossa in front of the tumor. 518 CANCEK OF THE KIDNEY, Kidneys alune affected ....... 20 oases. Secondary deposits found elsewhere . . . . . 31 " Seat of secondary deposits : Lumbar, mesenteric and vertebral glands . . . 15 " Lungs . . . . . . . . . . 14 " Liver . . 14 " Suprarenal capsules . , . . ... . . 4 " Omentum .......... 3 " Heart 3 " Vertebrae and rib ........ 3 " Costal surface of pleura . . . . . . . 1 " Bladder, uterus, penis, and testicle — each . . . 1 " The infrequent association of primary renal cancer with can- cerous deposits in the lower urinary passages, which this table shows, is somewhat remarkable, and is scarcely what one would expect, considering the close anatomical and functional relations of these parts.^ Etiology. — Renal cancer prevails at two distinct epochs of life — in early childhood, and in adult age. During adolescence the liability to it sinks to a minimum. Children under five years of age appear especially liable to renal cancer : 22 out of 67 cases occurred at this early period ; 3 others between seven and ten years : the remainder were distributed pretty equally between the ages of nineteen and seventy. The annexed table shows more exactly the relation of age to the frequency of renal cancer : 25 children 0-1 1-2 2-3 3-5 7-8 10 yr. yrs. yrs. yrs. yrs. yrs. 2 6 6 8 2 1 19 yrs. 20-30 yrs. 30-40 yrs. 40-50 yrs. 50-60 yrs. 60-70 yrs. Above 70 yrs. 36 adults^ .... 1 7 5 4 9 9 1 1 I had an opportunity of examining a man (set. 40) who died at the Royal Infirmary with extensive cancer of the stomach, combined with primary cancer of the right kidney. The latter organ was wholly converted into an encephaloid mass. I could not detect any traces of secreting structure in it : the mass was somewhat smaller than the natural kidney, and about the same shape. The left kidney was quite healthy, and greatly hyperlrophied. The right ureter was per- vious, but shrunk to about half its usual size. The left ureter was somewhat more capacious than natural. The right suprarenal capsule was wholly converted into a cancerous mass. There was very extensive cancerous disease (in nodules) of the liver, and of the vertebral glands. " In seven adults the exact age is not ffiven. SYMPTOMS. 519 The male sex is considerably more liable to renal cancer than the female. Sixty-six cases, in which the sex was distinguished, supplied 47 males, and 19 females. The jireponderance of the male sex is not so great in childhood as in adult age. Of 24 children, 15 were boys and 9 girls; of 42 adults, 32 were men and only 10 women. The great disproportion between the frequency of renal cancer in men and in women may possibly be explained by the marked preference shown by cancer for the generative organs in the female. The exciting cause of renal, as of other cancers, is wrapped in obscurity. In a few instances, a blow or fall on the loins was the immediate precursor and supposed cause of the first symp- tom ; but the disease had doubtless already been in existence before the accident, though concealed. In a case mentioned by Manzolini (" Schmidt's Jahrb.," B. 94, S. 74), a boy was kicked in the left side ; this was followed by hsematuria for fourteen days. Shortly after, a swelling appeared in the left loin, which event- ually proved to be an encephaloid growth of the left kidney. Symptoms and Physical Signs. — The distinctive symptoms of primary cancer of the kidney are : tumor in the abdomen and hcematuria. In every case in which the disease was the deter- mining cause of death, one or both of these symptoms were present.^ Abdominal tumor is by far the most constant sign of renal cancer, and usually the earliest one noticed. Out of 64 cases there were only 3 in which a distinct intumescence could not be felt in the site of the kidney or thereabouts ; and in these three there was hsematuria. In the remaining 61 cases a tumor was easily ascertained to exist in the abdomen ; and in all but three it was of such size and prominence that it could not escape the most cursory examination. It is noteworthy that in all the children a large — nearly always an enormous — tumor existed. The tumor presents itself iirst in the anterior lumbar region, between the margins of the ribs and the crista ilii ; it then grows forward to the umbilicus, upwards into the hypochou- drium, and downwards into the iliac and inguinal regions: in extreme cases it fills the entire belly. The tumor may, or may not, be covered with a ramification of enlarged superficial veins. The colon, and sometimes a portion of the small intes- tines, lies in front of it. This position of the colon furnishes 1 Lebert states that he has known an instance in which the disease ran a hitent course throughout : but he does not say whether in that instance the renal disease was really the cause of death. In a case of primary cancer of both kidneys re- ported by Dr. Fleming to the Dublin Pathological Society (Dub. Quart. .Journ., xliv. 235), the patient stated that he never had had hajmaturia, and there was no tumor traceable in the abdomen. 520 CANCER OF THE KIDNEY. an important diagnostic mark of all renal tumors. Percussion over the tumor is dull, except where the colon intervenes.' To. the hand the tumor feels smooth or irregularly lobulated, with rounded obtuse margins. The lobulations are often of unequal hardness, and a deceptive sense of fluctuation may be felt in places, or in the tumor generally. In Langstaff's case, a distinct and persistent pulsation was perceptible in the tumor ; and a similar phenomenon was noted in Bristowe's case (" Med. Times and Gaz.," 1854, ii. 395). The fixity of the growth is usually a marked characteristic.^ The second symptom in importance is hsematuria. Details on this point are supplied in 59 cases. Of these, 28 exhibited no trace of hsematuria throughout their entire course. In 31 cases there was hsematuria; but in 5 of these, there existed other possible causes for it than renal cancer (calculi, Bright's disease, external violence). These figures, even with this abatement, do not sufficiently express the danger of relying too strongly on hsematuria as a sign of renal cancer. In 6 instances hsematuria occurred only for a few weeks at the beginning of the complaint, and then altogether ceased — the urine thereafter continuing normal. In one case there was hsematuria for a short period at first, and none during the remainingfour years of life. In another case (Case 1, shortly to be detailed) hsematuria was present for some months, and at once disappeared on the voiding of a small calculus — it did not recur during the subsequent five years of life. In other cases hsematuria did not appear until toward the last few moments of life — perhaps years after the detection of a tumor in the loin. The absence of hsematuria seems to depend generally on the occlusion of the ureter, either by the pressure of the tumor or the extension of the disease into it. ^ This position of the colon was however not discovered in all the cases — gener- ally, no doubt, from defective examination ; but in some cases the detection of the gut may prove impossible, from its being compressed between the tumor and abdominal wall, and emptied of flatus. In doubtful cafes, it might be of service to inject air per rectum, in order to inflate the collapsed gut. The following remarks, by Bright, deserve to be borne in mind in searching for tumors of the kidney : " In those diseases," he says, " in which it (the kidney) most rapidly increases, the enlargement shows itself much more towards the anterior part of the abdomen than towards the loins, not only because the firm structure of this part is more calculated to conceal a tumor, but also because, in the other direction, it meets with less immediate resistance ; so that it often hap- pens, while we are examining the lumbar region with the greatest care, and ob- taining but a doubtful evidence of fulness and hardness by the eye and by the touch, and by a careful comparison of the two sides, we can scarcely place the hand upon the anterior or even the lateral part without becoming at once sensible of the existence of a distinct tumor ; and then, probably, by pressing that tumor backward, the other hand clearly informs us of its connection with the loins." (Loc. cit., 199.) ^ In the Lancet for March 18, 1865, is an account of a case of movable kidney affected with malignant disease. The tumor was mistaken for an ovarian growth, and operation for its removal commenced. The intestines were all behind the tumor. SYMPTOMS. 521 When hEeraaturia is present, it is a sign of very great value, ' and its character and features deserve attentive study. As a rule, it is irregularly intermittent and profuse. It recurs at intervals of a few days or weeks, usually without any ai»[)recia- ble cause. The tumor is not, of course, insensible to external violence : and in more than one instance a blow or fall on the loin has been the immediate precursor of the appearance of blood in the urine. In some cases the hemorrhage is excessive, and followed by rapid ansemia and exhaustion, though this is rare. Generally the loss of blood is moderate, sometimes insignificar)t, and requiring the microscope for its detection. The tormation of clots in the bladder, and their impaction in the urethra, is sometimes a source of severe suffering, and occasions excessive irritability of the bladder. Other changes in the composition of the urine are sometimes found, but they are not distinctive. Of course, albumen always exists in the urine when it contains blood ; more rarely albu- minuria occurs independently of h?ematuria, from genuine Bright's disease affecting either the exempted portions of the cancerous kidney, or the opposite organ. Not unfrequently, epithelial cells from the pelvis of the kidney and ureter are found in the urine, mixed with the blood. The presence of cancer cells in the urine is a sign which usuall}^ figures prominently in the catalogue of symptoms of renal cancer, but its value is very doubtful. In all the later cases, especially where there was hsematuria, the urine was carefully examined for cancer cells, but without success. Rosenstein mentions a case in which a cancerous villus was actually found projecting into the ureter, yet no cancer cells could be detected in the urine during life. It is by no means an easy matter to identify cancer cells in the urine, in consequence of their similarity to the tran- sitional epithelium of the pelvis and ureter. It must be further remembered, that any cancer cells which could find their way into the urine, must have escaped from parts of the growth which were broken dow^n and degenerated; and to identify character- istic forms, in the ichorous detritus even of an external cancer, is more than I have ever succeeded in accomplishing : how much greater the difficulty, when that detritus has been further disin- tegrated by the action of the urine ! In two examples of renal cancer, with hsematuria, wdiich I have had an opportunity of observing, repeated and careful examination of the urine failed to discover the presence of cancer cells or of cells which might be mistaken for them.^ ' Mr. Moore believes that lie succeeded in identifving cancer cells in the urine drawn after death from the bladder of a man in whose kidneys cancerous nodules were found ; but his description rather accords with the appearances of the epithe- lial cells which are alwaj^s freely detached from the vesical mucous membrane after death. (Med.-Chir. Trans., xxxv. 4G6.) 522 ' CANCER OF THE KIDNEY. The other symptoms which have been noted in cases of renal cancer are less distinctive and constant than tumor in the abdo- men and hsematuria. The most important is pain in the hypo- chondriumand loin. This is sometimes an early symptom, and may show considerable severity. The pain is commonl}^ inter- mittent; it shoots down in the course of the ureter to the inside of the thighs. It does not appear to be ever associated with re- traction of the testicle. Pain is, however, wholly absent for long periods in a large number of eases : the tumor itself may be perfectly painless on handling, and give no inconvenience except from its weight and size. Gastric symptoms — nausea, vomiting, anorexia, — are com- mon, and in several cases they were noted among the earliest symptoms. In other cases, again, none of these existed : the appetite was excellent; in five cases (all children) it was even voracious. The general health varied exceedingly. In the majority of cases, rapid emaciation took place, going on at length to an extreme degree, with failing strength, and yellowish discolora- tion of the skin. In other cases, many months, or even years (in adults), passed over after the detection of the tumor, before the health seriously gave way. The cancerous tint is not often mentioned in the list of S3'mptoms, but this may have been from the brevity of many of the reports. The bowels are generally disordered when the tumor attains a large size ; diarrhoea, or obstinate constipation prevails ; or the two conditions alternate. Towards the later periods, anasarca of the legs often sets in, and it may even extend over the whole body. Signs of consti- tutional irritation also present themselves, and become per- sistent. Life is at length worn out by gradual exhaustion of the vital powers : sometimes death is more suddenl}^ induced by rupture of the tumor. When there is no hsematuria the urine is commonly normal ; the healthy kidney becomes hypertrophied, and performs double duties. In no instance did ursemic symptoms arise. The duration of the disease from the first appearance of symp- toms to the fatal termination varied exceedingly. The duration was much shorter, as might have been anticipated, in children than in adults. Among the former, 19 cases are available for comparison : the mean duration was nearly seven months; the minimum was ten weeks, and the maximum " over a year." In adults (21 cases available) the disease continued on an average two and a half years ; the extremes ranged from five months to seven years; 8 died under the twelvemonth, 7 under three years, 2 survived four years, 3 six years, and 1 seven years. ILLUSTRATIVE GASES. 52;} These numbers, as well as those having reference to the age of the patients, disagree with the statements currer)t in hooks; and some of the numerous errors in the diagnosis of renal cancer may be traced to mistaken impressions as to the prevail- ing age and survivorship of patients so aliected. The supposi- tion of Walshe, endorsed by Lebert, that cancer of the kidney runs a more rapid course than other internal cancers, is not only unsupported by these large numbers, but the contrary is clearly established, namely, that, as a rule, death is longer delayed in renal cancer than in primary cancer of any other internal organ.' The reason of this tolerance must be looked for in the duplica- tion of the organ, the facility with which one kidney undergoes a compensating hypertrophy when its fellow is disabled, and takes upon it the work of the pair ; also the free room for enlargement which is atforded in the lumbar region, and the comparatively innocuous effects of displacement on the abdomi- nal organs.^ The following examples will serve to illustrate the chief features of the disease. Case 1. Encephaloid cancer of the left kidney; secondary cancer of left pleura. — Mr. E., set. 70, was visited by me with Mr. Jonathan Wilson, in March, 1868. He was suffering from an enormous tumor in the left flank. It appears that five years ago he suffered from profuse and re- peated hsematuria. After some months he voided a small calculus, and then the symptoms disappeared. He continued in good health for five years, and then came under treatment again for shortness of breath and general debility. Being somewhat fat and ventricose, he had not become aware himself of any tumor in the side; but when the abdomen was examined, a very large solid growth was discovered, filling the entire of the left half of the belly. How long this had been growing there was no evidence to show. The tumor occupied the left hypochondriac and lumbar regions, reaching forwards to the umbilicus and downwards almost to the crest of the ilium. Its front boundary had a rounded out- line ; its surface was wholly dull on percussion, even as far back as the spine; no bowel could be perceived in front of it. It felt hard, rigid, and perfectly fixed in its position. There was a moderate amount of ascites, with pleuritic eflTusion on the left side as high as the third rib; the other organs were healthy. ' The mean duration of cancer of the pylorus, according to the combined statis- tics of Lebert, Herrich and Popp, and Valleix, is under a year : out of 71 cases, 48 died within the year, and ahiiost all the remainder (23 cases) within Uv6 years. The majority of hepatic cancers terminate probably under eight months — certainly under a year (see Kohler, pp 308, 37(J). Walshe estimates the mean duration of cancer of the lungs at 13.2 months (loc. cit., p 348) ; and he thinks cancer of the brain rarely lasts over a year. (Ibid., p. 496.) 2 Three exceptional cases of cancer of the kidney, which apparently lasted respectively 12, 14, and 16 years, will be found in the Lancet, 1877, i. p. 194, and p. 567. It must be remembered in connection with such cases that a benign tumor may exist for some time and then undergo transformation into a malignant growth. 524 CANCER OF THE KIDNEY. The general condition was greatly depressed, the countenance sallow, the appetite almost lost. He lay continuously on his left side, and com- plained of great and constant pain in the left loin. There was no oedema of the feet or hands. The urine was scanty, high-colored, and charged with lithates ; but there was no albumen or blood, nor had there been any for the last five years. The patient was heavy and unwieldy, and unable to turn himself in bed ; bed-sores formed, and he gradually sank from exhaustion, after having been under observation for a month. Autopsy. — When the abdomen was opened, the tumor was found to be the left kidney, wholly changed into an enormous encephaloid mass. It was twelve inches long, eight broad, and five thick ; it had an ovoid shape, and weighed eleven pounds. Its surface was smooth, and covered with a tough investment of fibrous tissue. In front of the tumor ran the descending colon, which was not adherent, but perfectly empty, and contracted to the size of the finger. On cutting open the tumor, it was found to consist of firm, yellowish-white, encephaloid matter, scattered through which were several masses of soft, clotted blood. There was no vestige of renal tissue. The ureter was healthy, but occluded by the pressure of the growth. The renal vessels were also healthy. The spleen was pushed up into the vault of the diaphragm, and lay above the tumor. The left pleura contained a large amount of sanguinolent fluid ; on its costal surface were several cancerous nodules, as large as filberts. The other organs were healthy. The right kidney weighed seven and a half ounces, and was quite free from cancer. No calculous concretion was found in either kidney. Case 2. Encephaloid cancer of the left kidney ; unusual position • of spleen and pancreas; calculi in the right kidney. — F. M., a toy-dealer, aged 44, residing at Northwich, was admitted into the Manchester In- firmary in March, 1868. His illness began two years and a half ago with slight and temporary hsematuria. Fourteen months ago more violent ha3maturia took place, which has continued more or less ever since. His medical attendant discovered a lump in the left side a twelvemonth ago, and since then he has gradually become weaker and thinner, and the lump, has steadily increased in size. On admission he was extremely emaciated, countenance of a greenish sallow appearance, drawn and suggestive of suflfering ; tongue red and dryish ; p. 94, r. 24. No oedema of any part. The abdomen was much enlarged, especially on the left side, and on palpation a large solid tumor, as large as a man's head, was felt on the left side of the abdomen, occupying the epigastric, hypochondriac, and lumbar regions. The limits of the tumor, as ascertained by palpation and percussion, were as fol- lows (see Fig. QQ). The anterior margin could be traced from a little to the right of the ensiform cartilage, running downwards an inch and a half to the right of the middle line. About an inch above the um- bilicus, the outline twined abruptly to the left, crossed the middle line, and then descended obliquely into the iliac fossa, as low as the crest of the ilium. Upwards, the growth extended beneath the ribs, bulging these out, almost as high as the nipple. Posteriorly, the growth occu- pied the whole lumbar region, and caused a marked fulness in the site ILLUSTRATIVE CASES, 525 of the kidney. The area of the tumor was dull on percussion, except in the epigastrium, and along the left costal margin, where a tympanitic note indicated that the stomach lay in front of it. The descending colon could easily be traced in front of the tumor — it was often loaded with masses of scybala. Over the lower part of the tumor, in the iliac fossa, there lay a detached portion, resembling, both in shape and in Fig. m. Diasram showing the position and relation of tlie tumor in the ease of F. 31 : g, stomacli ; c, colon ; s, spleen. feeling, a somewhat enlarged spleen ; this portion was freely movable upon the main tumor, and had no intestine in front of it. The upper part of the tumor in the epigastrium had a nodular tuberous feel, and was covered by bowel. Along the costal margin a large artery could be felt pulsating on the surface of the tumor ; this artery communicated a distinct thrill to the finger, and was the seat of a loudish systolic mur- mur. The general surface of the tumor was smooth and tensely elastic — not fluctuating, but different parts varied sensibly in their degree of softness and hardness. The growth was immovably fixed in its position, and meandering veins coursed over the skin, covering its outer and more prominent portions. There was also an abundant varicocele on the left ■ side, and the veins of the penis were very large and tortuous. The urine contained blood, partly in small, round, or filamentous clots, and partly mingled with the urine. There were no casts, and the quantity of albumen was not greater than the blood accounted for. The organs ijj the chest were healthy, but they were considerably dis- 526 CANCER OF THE KIDNEY. placed upwards by the pressure of the abdominal tumor. The heart's apex beat in the fourth interspace, and the cardiac dulness mounted as high as the second rib. The liver was also pushed upwards; its upper margin corresponding with the fifth rib in the vertical line of the nip- ple. The patient complained of a good deal of pain of a gnawing char- acter in the left loin and in the groin. The patient remained in the Infirmary for six weeks. During this period the physical signs underwent no marked change ; the tumor slowly enlarged, and the strength and flesh continued to decline. The urine always contained more or less blood, but the quantity was never really large, and very often it required the microscope to detect it. It was noticed that there was generally more blood in the urine after pro- longed manipulation of the tumor. The bowels were exceedingly torpid, and required the frequent use of enemata for their relief. Beyond the use of these and of anodynes to procure sleep and allay the pain, no remedial means were attempted. After leaving the Infirmary, he returned to Northwich, and placed himself under the care of Mr. Williams, of that town. He continued to sink very gradually as the tumor enlarged, and died on October 8th — five months after his discharge from the hospital, eighteen months after the first discovery of the tumor, and three years after the first appearance of hi«maturia. Careful inquiries respecting the hsematuria elicited the following par- ticulars : Blood first appeared in the urine three years before death. For three weeks at that time pure blood was repeatedly voided ; then for a period of twelve months no more blood was seen. Again about a pint of blood was voided, and after this it continued in greater or less quantity until his death. The blood was nearly always more or less clotted. I went over to Northwich to make the autopsy with Mr. Williams. The emaciation had reached the most extreme degree compatible with life ; the muscular tissue had almost vanished. Our astonishment was great to find the abdomen sunk so as scarcely to constitute a notable tumor. This had arisen apparently from the oozing out of the tumor of a considerable quantity of a bloody fluid, which we found in the peri- toneal cavity. When the belly was opened, we found a large subglobular mass, occupying the whole of the left side. This proved to be the left -kidney, converted into a mass of soft cancer. Overlapping its upper end was the empty stomach, and along the great curvature of this viscus coursed, with very tortuous windings, an artery as large as the radial (right gastro-epiploic). This was evidently the source of the pulsation felt during life at the costal margin. Riding freely on the lower and inner (or right) border of the tumor and the adjacent portions, lay the spleen, forming a flattened oval cake, 7 inches long by 4 inches wide. This was the movable spleen-like body felt during life near the iliac fossa. Between it and the stomach stretched the transparent layers of the gas- tro-splenic omentum. The colon, contracted and empty, passed in front of the inner portion of the tumor, under the spleen, and again in front of the lower part of the tumor, crossing it obliquely near its right mar- gin. The body and tail of the pancreas ran horizontally right across the ILLUSTRATIVE CASES. 527 tumor, midway between the border of the stomach and the sjjieen, behind the folds of the gastro-splenic omentum. The tumor constituted u somewhat flattened and elongated sphere, in parts with a lobular or tuberculated surface, and in part smooth. It occupied the entire vault of the diaphragm (jn the left side, the epigas- trium, and the left lumbar region as low as the crest of the ilium. It was immovably fixed here, and adherent to the diaphragm and to the soft parts of the loin. The spleen and stomach were not adherent; the pancreas and omentum were loosely adherent. The tumor, in the epi- gastrium, extended two inches beyond the middle line, pushing aside the liver and pressing on the vena cava and its branches. Some of the mesenteric veins were also compressed and enormously distended ; the varicocele was quite effaced after death. The tumor weighed six pounds. At its lower part the vestiges of the kidney could be recognized — still preserving the outline of the gland. The ureter, somewhat smaller and more transparent than natural, but still pervious, could be traced into the remains of the pelvis. On dividing the tumor, the mass was found to consist of a soft cellular encephaloid matter, deeply infiltrated in parts with blood. The scanty remnants of the kidney, in the form of a thin layer of indurated cortical substance, was stretched over the lower part of the tumor. The pelvis consisted of three or four communicating loculi, filled with a yellowish, gelatinous material. The right kidney was of its usual dimensions, and its substance healthy ; but the infundibula were dilated, and contained eight phosphatic calculi, varying from the size of a horse-bean to that of a hempseed, together with a multitude of smaller granules of the same nature. All the other organs of the body were healthy, and there were no secondary can- cerous deposits anywhere. The positions of the spleen and pancreas were quite excep- tional in this case. The spleen is usually carried up above the tumor into the vault of the diaphragm: here it la}' in front, and was pushed downwards into the iliac fossa. The pancreas is generally left undisturbed in its normal situation ; but in this case it was stretched in front of the tumor. Both these condi- tions were probably due to the morbid growth having com- menced at the upper end of the kidney. It is almost certain that the hsematuria in this case was not altogether derived from the left (or cancerous) kidney. The earlier and more profuse bleedings were in all probability so derived ; but the scantier hemorrhage of the later periods could not have had this source, because the pelvis of the left ki.dney when examined after death only contained a clear yellow fluid, and the secreting substance of the organ was completely de- stroyed. The scantier but more constant haematuria, from which the patient suffered while in the Infirmary, was, doubtless, de- rived from the right kidney, in the infundibula of which a number of calculous concretions were found after death. In further evidence of this it should be mentioned, that the urine-, 528 CANCER OF THE KIDNEY. while the man was under observation, always contained small calcareous particles composed of phosphate of lime — exactly similar in composition to those found in the kidneys at the autopsy. • A typical example of infantile renal cancer was shown to me by Dr. Lloyd Roberts. The following are his notes of the case : Case 3. — W. A. McE., aged six months, was sent to me by Dr. Cran, of Salford, on May 1, 1871, suffering from abdominal tumor. The mother stated that at the child's birth the nurse thought he had a "full stomach." When a fortnight old he suffered from a severe attack of abdominal pain and flatulency, requiring the attendance of Dr. Cran. After this he remained pretty well until the age of three months, when it was observed that his abdomen ^yas larger than it ought to be ; and it continued from this time to enlarge. The child was subject to frequent attacks of diarrhoea during the earlier months of his life, the stools appearing like " boiled moist cabbage ;" but latterly four or five days would elapse without any evacuation, the motions being dry, hard, and yellow. Up till the time of death he passed water freely ; it was always clear and free from blood. The appetite was voracious, but he never seemed to rest until he had vomited his food. He suffered much from thirst. On the first of May the following was his condition : He was much emaciated. The veins of the abdominal wall were much distended. The abdomen measured 21 inches over the umbilicus, and was almost entirely filled by an immovable tumor of somewhat irregular shape. There was universal dulness over the abdomen, with the exception of the left hypo- chondriac and hypogastric regions, where a clear bowel-sound was elicited on percussion. On the 7th of July, the abdomen measured 24 inches, having increased three inches in a little over two months. The child died on 14th July. At the autopsy, the liver was found thin and stretched over the surface of a large tumor, which was found occupying the entire abdomen, except the left inguinal region, into which the intestines had been pushed. There was no fluid in the peritoneal cavity. The liver, which was pale, but seemed otherwise healthy, was connected with the tumor by loose cellular adhesions, which were easily separable by the fingers, so that the entire tumor was removed without the aid of a knife. It was found to be a tumor of the right kidney, and weighed 5? lbs. The growth was irregularly kidney-shaped, and traces of renal structure were detected at its posterior part. On section, it was found chiefly composed of soft, brain-like structure, with several large cysts containing fluid, which on microscopic examination was seen to be crowded with caudate and poly- gonal cells. The same bodies, in a fibrousdooking stroma, were detected in the solid portions of the tumor. The left kidney was rather larger than usual, but was healthy in structure. No cancerous deposit was found in any of the other viscera. Case 4. Primary cancer of the right kidney, and of the lymphatic glands in the hilus. Secondary cancer of the liver, left lung, and supra- renal capstde (from the notes of Dr. Renaud). — Hannah Hilton, set. 59, ILLUSTRATIVE CASKS. 529 a married woman, who had borne children, the last from eight to nine years ago, ceased to menstruate six years ago. She first noticed a small and hard tumor in the right iliac space two years since, which made very little progress, and gave no pain or incon- venience for many mouths. She came under treatment in the early part of December, 1845, for a chronic diarrh(x;a, which had for some time past baffled all remedies. The evacuations were most copious, of a dirty olive color, passed without pain or accompanied with tormina. This ultimately yielded to the sulphate of copper. I first examined the tumor about twelve months ago. It was painless, hard, and not bigger than a footal head, rising a little out of the right pelvic region. About a month from this, the tumor began to be painful and to increase. A feeling of crumpling parchment was noticed at its inner and lower portion. Shortly afterwards it began to extend upwards and backwards, in the direction of the loin ; there were flying pains also. The uterus, examined manually, was found free from the tumor, and apparently healthy. The color of the skin was somewhat dirty, and this, together with the crumpling, were thought sufficiently suspicious to warrant a belief that the real nature of the disease was malignant degeneration of the right ovary. I now lost sight of the case until three weeks prior to death, when I discovered that the tumor had gradually extended itself backwards, and that four weeks ago it began rapidly to grow, and spread in all direc- tions, causing great pain and watchfulness. The woman emaciated very fast, was of a deep and dirty-brown color, had sunken eyes, and a look of suffering. The nature of the disease remained no longer doubtful, for the nodular portions of the fungus hsematodes could be most dis- tinctly felt beneath the abdominal walls. The feeling of crumpling was also more general, as also an occasional gurgling as of air, in the intes- tines. There had been no uterine hemorrhage, no difficulty or pain in passing urine, and nothing unusual in the character of the secretion. Opiates relieved the pain greatly. She died on February 17, 1847, Autopsy. — Body greatly emaciated. In the abdomen there was a large fungoid tumor, extending quite across and to the right side and loins ; passing obliquely over it was the colon, which was partially adherent, as were also some of the small intestinal folds. The tumor was not at all adherent to the interior of the abdominal walls. The uterus and ovaries were quite free from any disease, and were merely bound together with false membranous bands. The tumor had no pedicle, and though most carefully removed there were no connections found other than such as had been set up through peritoneal irritation. The abdominal cavity did not contain any dropsical effusion. The entire mass being removed, together with the liver, to which it was adherent, the right kidney was found so entirely degenerated into encephaloid matter, and so closely incorporated with the tumor, that nothing but a most careful dissection could have detected its true nature. It was enlarged to double its usual size, and no vestige of its proper structure remained ; the vessels were, however, found entering the hilus ; and the suprarenal capsule, also affected with encephaloid cancer, was in its usual position, and, in size and shape, bore a resemblance to a very large chestnut. In the large tumor, which appeared to have its origin in the lymphatic 34 630 CANCER OF THE KIDNEY. glands of the hilus, were some cysts, filled with a grumous matter or with a semi-transparent jelly-like substance. The great mass was a homogeneous and soft cancer, breaking down in most parts, but in some places as hard as cheese. The tumor was rounded, and about four inches thick, where it lay in the loin on the right side, and gradually became more thin toward the left margin, where it dipped beneath the stomach, surrounding the aorta and vena cava, in one portion of which cancerous matter was found. The extreme breadth of the tumor was nine inches. The lower margin of the liver was cancerous where the tumor came in contact with it, and some other small cancerous tubera were found on its surface. The gall-bladder contained many calculi. On the surface of the lower lobe of the left lung were several tubera, and one as large as a small apple. The heart, left kidney, spleen, right lung, and other parts were healthy, and free from all traces of disease. Dr. Hounsell has kindly furnished me w^ith the notes of the following hitherto unpublished case. It illustrates the usual features of the disease as it appears in children. Case 5. Encephaloid disease of the right kidney in a child (from the notes of Dr. Hounsell, of Torquay). — Richard Bradford, four years of age, was admitted as out-patient of the Torbay Infirmary about ten days before his death. He was suffering from a large tumor occupying the umbilical, right hypochondriac, and lumbar regions. Its surface was dull on percussion, and the dulness was continuous with that of the liver. The child was of a sallow appearance, and much emaciated. The tumor had been detected three months previously, and had grown rapidly. Haematuria had been noticed shortly before the discovery of the tumor. Autopsy. — The tumor was found to involve the right kidney; it weighed 10 lbs. 142- ozs. ; it was smooth on the surface, and to the touch felt firm in some places, and soft, almost fluctuating, in others. Near it lay a supplementary tumor about the size of an orange. On cutting open the tumor it was found to consist of soft brain-like substance, con- taining two or three large cysts filled with about half a pint of dark fluid. The tumor sprang from the upper portions of the kidney, and had absorbed all the organ except two of the pyramids, which remained intact. The ureter, the left kidney, and all the other organs were healthy. The liver was adherent to the tumor, and the ascending colon ran along its lower border, and could not be detected in front of the growth during life. Case 6. Enormous malignant disease of the left kidney ("Lancet," 1856, i. 626). — J. B., aged six years, was admitted into the Middlesex Hospital, under Dr. Hawkins, May 29, 1855. J. B., born of healthy parents, was one of a family of ten children, of which five were still living, the others having died of acute infantile diseases. When the child was six weeks old his mother noticed that both left extremities were larger than the right; the skin was looser, and the muscles she describes as being less firm than those of the opposite side. She was so struck with the difference that she consulted a medical man about it. ILLUSTRATIVE GASES. 531 At three years of age the chihl had whooping-cough, and shortly after measles, but he never had scarhit fever. The abdonion, the niotlier believes, was always rather larger than could be considered natural, but this had not been to a marked extent. With these exceptions, the child had fair health until the middle of April, 1855 (six weeks before admis- sion), when he was suddenly seized with sickness; and from his appear- ance the mother believed him to be very ill, and though far better on the following day, so much as to be able to walk out of the house, he did not regain his appetite for about a week. During this illness the mother accidentally discovered a tumor in the upper part of the left side of the abdomen. It then appeared to be almost circular, and about two inches in diameter. It was not perceptible to the eye, but its lower margin could be distinctly felt; it was very hard, but not painful, nor did moderate pressure cause any inconvenience. She believes that it gradually increased in size after she first discovered it, till she brought the child to the hospital, and during this time she noticed that he had quite regained his appetite, which had, in fact, become voracious, and though he appeared fatigued after moderate exercise, he was able to walk without effort. State on Admission. — Rather emaciated ; abdomen very much swollen, especially on the left side, where the veins were enlarged and tortuous ; the left extremities were considerably larger than the right, owing to the soft parts being much firmer and the muscles apparently better devel- oped ; there was, however, no difference in length. Upon manipulation, a tumor could be felt, of somewhat globular form, about three inches in diameter, occupying part of the left hypochondriac, left lumbar, and umbilical regions; its lower margin was well defined, but its upper boundary could not be ascertained — the dulness on percussion, Avhich was complete over all parts of the tumor, being there continuous with that of the spleen. The patient ate, drank, and slept well, was able to sit up the greater part of the day, walked frequently up and down stairs, and did not complain of pain. From this time the patient continued under observation until his death, a period of nearly twelve months. The tumor continued rapidly to grow, until it attained enormous proportions. On the 1st of August, the fol- lowing note was taken : " The tumor extends half an inch below the umbilicus, and about the same distance to the right of the mesian line ; the abdomen generall}' is much more swollen, and the veins are much larger. The patient walks about the garden for an hour or two every day, and though taking a large quantity of food, and eating very fre- quently, is daily becoming more emaciated. He appears to suffer no inconvenience, except that caused by the bulk of the tumor, the large size of the abdomen being such as to impede progression. He. com- plains of thirst, and evinces a desire to drink frequently of cold water. The bowels act with regularity; and the urine, which is frequently voided, and in quantity rather above the natural standard, presents no abnormal appearances." The patient continued to go about till September, and to walk up and down one flight of stairs to and from the ward without assistance. About the middle of the month, after having spent some time in the garden of the hospital, he fancied himself unable to get back, and was 632 CANCER OF THE KIDNEY. then for the first time carried upstairs. After this, he was almost con- stantly confined to his bed. The tumor gradually increased in size unt^^il his death ; for some time previous to which, indistinct fluctuation could be felt in some parts of it. The abdomen, about the middle of Decem- ber, measured in circumference 36 inches, and at the end of March upwards of 42 inches. For the last two months he suffered much from dyspnoea ; and for the last three weeks, had constant orthopnoea, and daily increasing oedema of the left leg. The appetite, however, re- mained inordinate till the last; and the bowels, which had continued to act regularly till within a short time of his death, had recently become somewhat constipated. He sank gradually, and died April 7, 1856. The annexed drawing of the patient was taken shortly before death, by Mr. J. Z. Laurence, and kindly placed by him at my disposal. Fig. 67. Enormous cancer of the left kidn. From a drawing by J. Z. Laurence. Autopsy (fifty-four hours after death). — The whole of the abdomen, except the right inguinal region, was occupied by a large globular tumor, anteriorly firmly adherent to the parietes, and covered by peritoneum ; posteriorly, lying in contact with the psoas muscle ; the small intestines were thrust down to the right inguinal region ; the spleen and liver were DIAGNOSIS. 533 driven upwardd into tlic thorax ; the wliolc of tlie transverso colon was firmly adherent to the tumor; and a ])ortion of the descending colon, which ran along the front, was for a short distance embedded in it. The tumor, when removed from the body, weighed thirty-one ])ounds. Traces of kidney structure could be recognized, as if spread out over the entire substance; large masses of medullary cancer were visible on its surface. Upon section, the centre was f.uind to be occupied by several pints of dark, thick fluid, floating in which were several fragments of the broken- down cancerous mass ; the more solid portions varied in consistence from that of firm medullary cancer to gelatinous matter in a semi-fluid state, large masses of it being found in every stage of degeneration ; the kidney on the opposite side was much enlarged. No cancerous deposit was found in any of the other viscera.^ Diagnosis. — We have seen that in nearly all cases of primary cancer of the kidney, a palpable tumor exists in the flank. If profuse hfematuria coexist with such a tumor, scarcely a doubt can remain as to the seat and nature of the disease.^ But when there is no hsematuria, the diagnosis becomes more diificult ; hideed, there is scarcely any morbid condition which has been so frequently misapprehended. Renal cancer has been generally mistaken for enlargements of the surrounding organs — of the liver, spleen, ovary, or uterus; but sometimes for ascites, aneu- rism of the aorta, or perinephritic abscess. It has ako been mistaken for tumors of the kidney of a different character — for pyonephrosis, hydatid, cystic degeneration, and hydronephrosis. Some of these errors were doubtless unavoidable; but most of them arose from an imperfect knowledge of the diagnostic marks of renal tumors, and from the undue weight attached to the absence of heematuria. As a positive sign, associated with abdominal tumor, hsematuria — profuse, spontaneous, and recur- rent — is of the highest significance ; but its absence signifies comparatively little. In nearly half the cases collected by me, haematuria was wholly absent from the first to last ; and in those cases in which hematuria was noted, intervals of many weeks or months elapsed in several of them, during which the urine was perfectl}^ normal. In those numerous cases, therefore, in which the observer derives no help from the examination of the urine, he must rely on his skill to ascertain the anatomical relations and nature of the abdominal tumor. In prosecuting this inquiry, he will. espe- cially endeavor to eliminate tumors of the liver, spleen, and 1 Some further particulars of the post-mortem appearances in this case are sup- plied b_y Dr. Van der Byl (Path. Soc. Trans., vol. viii.). 2 The coexistence of these two symptoms is not, however, absolutely diagnostic of renal cancer. In a case of enormous enlargement of the spleen (leucocythsmic) in the Manchester Infirmary, there was profuse ha?maturia for several days. After death, some months subsequently, the kidneys and bladder were found perfectly healthy. 534 CANCER OF THE KIDNEY. ovaries — these being, from their comparative frequency, the most likely to lead astray. If the intumescence occupy the right side, it may be distin- guished fr5m hepatic tumor, especially when not very large, by the possibility of tracing its upper limits below the margins of the ribs; the side of the hand can generally be so inserted at the edge of the ribs, that the tumor can be clearly felt to lie below it, and the liver above it. Along this line a coil of intes- tine usually lies, and yields a tympanitic sound on percussion. This sign is lost, however, when the renal growth contracts ad- hesions to the under surface of the liver; also when it projects disproportionately into the right hypochondrium, and displaces the right lobe of the liver. When this is the case, assistance may be obtained by feeling for the thin margin of the liver as it lies applied to the abdominal wall. Another important sign in such a case is the position of the colon. Hepatic tumors have no intestine in front of them (unless there be malposition of the viscera), and yield a dull note over their entire surface. Renal tumors, on the other hand, have the ascending colon in front, passing obliquely from below upwards and to the left; and the passage of flatus along the gut, or the clear percussion note over it, will rarely fail to indicate its position. A splenic enlargement is distinguished by the following signs : absence of the descending colon in front; its rigid, somewliat thin borders (not rounded); its extension upwards under the ribs ; its mobility ; generally, a tympanitic note is obtained in the extreme left lumbar region; often, on deep percussion, a bowel sound is perceived through its substance, which is not thick (a renal tumor is absolutely dull on the deepest percussion); antecedent history of ague or remittent fever, or evidence of leucocythsemia on examination of the blood ; the direction of the enlargement is downwards and inwards to the epigastrium and umbilicus, and not toward the iliac fossa. It also rises higher toward the axilla than a renal growth. When the latter rises from the upper and forepart of the kidney, and pushes forwards and upwards rather than downwards, the diagnosis becomes very difficult, and depends mainly on the absence or presence of the colon in front of the enlargement, and hints derived from the previous history or the state of blood on microscopic examina- tion. When the tumor presses forwards and downwards toward the umbilicus and the pubic and iliac regions, it is apt to be mis- taken for ovarian tumor. The commemorative symptoms may here yield valuable information, though the statements of patients on such points are ' alwaj^s to be accepted with reserve. An ovarian growth begins in the iliac fossa, and ascends ; a renal growth begins in the flank between the ribs and the crest of the PROGNOSIS. 535 ilium, and descends. An ovarian tumor has no bowel in front of it, and the bowels are pushed into the ]um])ar ret^ion, where a clear sound can be elicited — exactly in the spot where the dulness is most complete when the tumor arises from the kid- ney.^ This last sign also serves to distinguish uterine from renal enlargements. An encephaloid kidney can only be confounded with ascites when it is extremely soft, and tills the entire abdomen. The two conditions may be distinguished by the circumstance, that in ascites both flanks are dull, whereas in renal tumor one is dull and the other resonant. When the tumor has been satisfactorily made out to be con- nected with the kidney, there still remain difficulties in deciding its nature. Malignant growths generally give a distinct impres- sion of their solid structure. This distinguishes them from hydatid, purulent, and hydronephrotic cysts; but the consistence of the tumor is often very difficult to appreciate : if it be small and deep-seated, and the abdominal walls thick, the sense of fluctuation in a fluid cyst may be exceedingly obscure; on the other hand, encephaloid tumors sometimes yield a quasi-fluctua- tion which is very deceptive. In these doubtful cases, the pres- ence of pus, or blood, or hydatids in the urine, of rigors, of nephritic colic, or of cancerous cachexia, supplies hints which incline the judgment in this or in that direction. Prognosis. — The ultimate termination is, of course, always fatal. In judging of the probable survivorship of the subjects of renal cancer, the age of the patient is of great importance : the mean duration of the disease is at least three times as great in adults as in children. There is, however, nothing like exact proportion observed in this respect. In a girl of twenty-one, whose case is described by Langstaff, the disease lasted (with hsematuria) for six years. Contrary to what might have been expected, the occurrence of htematuria does not appear to hasten the final catastrophe: the mean duration is almost exactly the same in the hemorrhagic cases, as in those in which the urine was throughout normal. The disease appears in some cases to become dormant for a while, making no appreciable progress for many mouths. In an instance of this kind recorded by Dr. Brinton, the stationary condition (which Dr. B. had flattered himself might pass into permanent obsolescence) came suddenly to an end, with death 1 A case is reported by Dr. Greenhalgh (" Tumors Complicating Pregnancy," St. Earth. Hosp. Eeps., vol. i. 85), in which a tumor supposed to be ovarian acted as a complication in two pregnancies ; and the propriety of removal was about to be entertained when the patient again became pregnant She died without obvious cause three weeks after delivery at the full term, and the autopsy showed that the supposed ovarian tumor was really the left kidney in a very advanced stage of cerebriform disease. It weighed 27 lb. 3 oz. 636 CANCER OF THE KIDNEY. of the patient, through copious hemorrhage into the tumor. (" Brit. Med. Journ.," June 13, 1857.) Treatment. — The management of a disease so hopeless is a melancholy dntj. When the tumor is painless, and the urine natural, there is little for the practitioner to do beyond placing the patient in favorable hygienic circumstances. When the tumor is tender, or there are signs of local inflammation in its vicinity, warm baths or emoUent applications may be used from time to time. It may be doubted whether it is prudent to inter- fere with a moderate hsematuria. The losses of blood do not on the whole act disadvantageously. When, however, the hemor- rhage becomes excessive, means must be used to control it. Ice may be applied to the tumor, and acetate of lead or gallic acid administered internall3^ The clots which form in the ureter and bladder sometimes occasion the most poignant suffering by blocking up the urethra, and causing retention of urine. The impacted masses should be pushed back into the bladder by means of the catheter, and the coagula broken up by washing out the organ with warm water. As the disease advances, severe constitutional irritation sets in, which requires to be palliated by opiate and other anodyne medicines.^ B.— SECONDAEY CANCER OF THE KIDNEY. Secondary cancerous deposits occur in the kidneys, in the form of nodules varying from the size of a pea to that of a marble or walnut. Ten to twenty such nodules are not unfre- quently found scattered through the cortical substance: the intervening renal tissue shows no sign of disease; the urine is normal, and no pain or other symptom betrays their presence during life, The following case oflers an example, marked by some very unusual incidents, of extensive cancerous disease of the urinary organs, involving primarily the bladder and its vicinity, extending thence to both kidneys, of which the right was undergoing sacculation from compression of the corre- sponding ureter by the cancerous mass at the base of the bladder. In January, 1862, I was requested by Dr. Crompton to see with him a shopkeeper, aged 38, who was then suffering from hsematuria and paralysis of the bladder. The patient gave the following account of 1 A curious case is reported in the Philadelphia Medical and Surgical Reporter for 1861, p. 126. A man of 57 had had a tumor in the right hypochondrium for six years. It was supposed to be " cystic disease " of the liver ; and his surgeons deliberately proceeded to remove it by operation. The tumor (which weighed 2J lbs.) v/as accordingly removed, but on examination it proved to be the right kid- ney, wholly converted into an encephaloid mass. The patient survived fifteen days. SECONDARY CANCER OF THE KIDNEY. 587 himself: Three years previously, without known cause, "he had an attack of hieraaturia, accompanied with excessively frequent micturi- tion, pains in the back and bottom of the belly, but without vomiting or retraction of the testicle. These symptoms passed off, under medical treatment, in two months, and (apparently) comi)lete recovery soon ensued. After an interval of three years, during which the patient's health continued in every respect undisturbed, the present attack abruptly commenced. The patient was seized, six weeks before my visit, with violent pains in the loins and hypogastrium, accompanied by painful and excessively frequent micturition and bloody urine. All these symp- toms came on simultaneously. There was neither sickness nor vomiting. The attempts to void urine were incessant — every ten or fifteen minutes during the day, and so constant at night that the patient scarcely obtained any sleep. Matters continued thus for three weeks ; the patient, meanwhile, did not keep his bed, and he attended, as well as he was able, to his duties in the shop. But a new train of symptoms now showed themselves. The incessant micturition was succeeded by a total inability to empty the bladder, and the legs and belly began to swell rapidly. At this conjecture Dr. Crompton's aid was obtained. On examining the patient he found con- siderable ascites, anasarca of the lower extremities, and retention of urine. Three pints of a sanguinolent urine were immediately with- drawn by catheter from the distended bladder ; the patient was directed to keep his bed, and treated with alkaline diluents and nightly seda- tives. Great relief followed this treatment, but the patient still con- tinued unable to void a drop of urine spontaneously, and catheterism had to be practised twice a day. His condition at the date of my visit was as follows : There was extreme pallor of the surface ; considerable emaciation ; no pyrexia ; the tongue was moist, slightly furred. The legs were no longer oede- matous, but considerable ascites still remained. The bladder was dis- tended almost to the umbilicus ; there was no pain, and the loins were not sensitive to pressure; nor was there any tumor to be felt in the renal region ; the movements of the patient were active, and he was cheerful and lively. About a quart of bloody urine was removed by catheter, A little pure blood came through the instrument first, then almost clear urine, and as the bladder became empty, the urine again became ruddy, the last few drops being almost pure blood. Dr. Crompton stated that a little bleeding always followed the morning and evening catheterism, A careful examination of the urine yielded the following: It was feebly alkaline from fixed alkali (derived from medicine") ; specific gravity 1007 ; on standing, the blood-corpuscles subsided, and formed a very red, slightly clotted layer, at the bottom of the urine-glass. Under the microscope there were found, in addition to the blood-disks, a few corpuscles with cleft nuclei — probably pale blood-corpuscles — but no renal elements — neither epithelium, nor casts, nor any suspicious (quasi- cancerous) cells of any sort, though diligently looked for. The propor- tion of albumen was no more than corresponded to the blood present. The patient from this time gradually but steadily improved. The 538 CANCER OP THE KIDNEY. bladder slowly recovered the power to expel its contents ; the urine became less and less bloody, and finally clear, and free from albumen. Eight months afterwards (August 26, 1862) the patient waited on me. He was still- pale and thin, but reported himself well, and had for the last six months been able to pursue his avocation. I heard nothing more of the case until June 22, 1863, when I was summoned to visit the same man with Dr. Nesfield, under whose care the patient came after Dr. Crompton's departure from town. I found him in a desperate condition — emaciated to a skeleton ; so weak that he could not turn in bed, nor raise his head from the pillow. There was no anasarca nor ascites. Great pain was complained of in the right renal region, but no tumor or fulness existed there. The urine was loaded with pus, and highly ammoniacal. Six days after, the patient died. Autopsy. — On opening the abdomen and pushing aside the small intes- tines, a cancerous mass, half as large as the fist, was found implicating the base of the bladder, especially about the entrance of the right ureter. Within the viscus, a soft sprouting fungus of the size of a hen's egg, was seen springing from the trigone ; it was rounded in shape, elevated about an inch above the level of the mucous membrane, and very red. On and about it, occupying the inequalities of its surface, lay a quantity of calcareous or phosphatic matter, deposited in irregular masses. Small masses of a similar nature had been observed to come away with the urine for some weeks before death. The right kidney was a little larger than natural ; it felt flaccid and hollowed. On section, six cancerous nodules as large as marbles, and several smaller ones, were counted in the cortical substance. None of these were softened, nor communicated in any way with the pelvis of the kidney. The organ was sacculated to a considerable extent. The pyramids were in great part absorbed, and the remainder of the renal structure was converted into a reddish, leathery substance. The pelvis and infundibula were much dilated. The ureter was enlarged to the size of the index finger, and near its entrance into the bladder, its calibre was almost effaced by the cancerous mass at the base of the bladder, through which it passed. Broken fragments of calcareous matter lay scattered in the dilated pelvis, which, together with the ureter, contained a quantity of urinous ammoniacal pus. The left kidney contained eight or ten nodules similar to those in the right. The intervening renal tissue was perfectly healthy; the ureter was free, and the pelvis undilated. This case presented several points of difficulty. At the time of my first visit the symptoms indicated pretty clearly an affection of the bladder: and as no stone could be detected on sounding, and no pus passed with the urine, the probability of the existence of a bleeding fungus seemed strong. The other possibility was renal calculus. The previous history favored the latter view ; the patient had recovered perfectly from his first attack of hsematuria three years before — a result quite conformable with the idea of renal calculus, but much less so with that of fungus of the bladder. Then again, how explain APPENDIX. 5^9 the ascites and anasarca? Thoy could not be attributed to the losses of blood and hydricniia conserjuent thereu[)on, for they passed away before the htematuria ceased. It a[)peared more likely, that the dropsical symptoms and the paresis of the bladder were companion phenomena, of a paralytic nature, pro- duced by the reilex results of the antecedent intense irritability of the bladder, acting upon the nerves of the bladder and of the bloodvessels of the lower half of the body. APPENDIX. Sakcoma of the Kidney. — [See Robson, "Brit. Med. Journ.," 1876, I. p. 232; Baginski, "Deutsch. Med. Wochenschr.," 1876, ]^o. 10; Geddings, "Trans. Americ. G-ynfec. Society," 1877, p. 479; Whitehead and Dreschfeld, "Brit. Med. Journ.," 1881, II. p. 741; Fotherby, "Brit. Med. Journ.," 1882, I. p. 157; Heath, "Brit. Med. Journ.," 1882, II. p. 100; Abercrombie, "Pcith. Trans.," xxxi. p. 168; Bay and Thornton, "Path. Trans.," xxxii. p. 142; also see Yirch. and Hirsch., " Jahresber,," 1880, vol. ii. p. 212; and Cornil and Ranvier, "Histologic Pathologique," 2d edition, 1884, vol. ii. p. 638.) Many of the cases mentioned above under the head of Cancer of the Kidney were observed before the differentiation between carcinoma and sarcoma had been generally demonstrated. It is probable that a considerable number of the older cases would now be classed with the latter variety of tumor. In those cases in which the sarcomatous nature of the growth has been recog- nized, the tumor has usually been found to be composed of small round cells, or of these mixed with spindle cells. Lympho- sarcoma of the kidney is by no means rare, especially in young subjects. Clinically no sign has yet been observed, which will serve to distinguish sarcoma from carcinoma of the kidney. The clinical features of such growths may be illustrated by the fol- lowing account of a case under the care of my colleagues, Dr. Dreschfeld and Mr. Walter Whitehead. A. L., aged 46, came to the out-patients' department of the Man- chester Royal Infirmary for the first time on April 4, 1882, complaining of the occasional passage of blood in his urine. He stated that he had always enjoyed good health; he had suffered from gonorrhoea, but not from syphilis. He was a well-built but spare man of very dark com- plexion ; he had a slightly atheromatous pulse and beginning arcus senilis. On the right side of the abdomen a small firm, freely movable globular tumor could be felt ; its upper border was about one inch below and separate from the liver; its lower border was in a line with and about two inches to the right of the umbilicus. Percussion gave a dull 540. CANCER OF THE KIDNEY. sound, and no bowel could be detected over the tumor. It was perfectly painless. The patient had been aware of its presence for some time, but felt no. inconvenience from it. Percussion of the lumbar regions behind gave a duller sound on the right than on the left side, but no fulness could be detected on that side. The urine was uniformly dark red, containing a considerable amount of blood intimately mixed with it. Microscopically examined, it showed, besides blood-corpuscles, some large round cells with large nuclei, which filled up nearly the whole of the cell. There were no renal casts. The remaining organs were nor- mal. A diagnosis was made of tumor of the right kidney, probably of sarcomatous nature. In the further progress of the case the tumor increased in size. It still remained painless, and extended downwards and to the side, so that it could be easily grasped by one hand being applied to the right lumbar region behind and the other over the tumor in front ; it could thus be moved both laterally and vertically; the surface of the tumor felt smooth and inelastic. At the beginning of August the patient complained of feeling weaker, and of suffering from flatulence and occasional vomiting. The case being one where an operation was indicated, Mr. Whitehead removed the growth on September 5th, but the patient died on September 9th. The growth proved to be a large round-celled sarcoma of the kidney, and at the autopsy no secondary growths were found. A sarcoma in which striated muscular fibres are found, occurs very rarely and always in young children. Specimens of such a tumor were exhibited at a meeting of the Pathological Society on 'Nov. 1, 1881, by Mr. Eve and Dr. Dawson Williams. The explanation offered by Cohnheim of the presence of muscular fibres in these tumors, is that, owing to a faulty segmentation of the protovertebrse, some of the germinal muscle-cells are mixed from the first with the rudiments of the uro-genital organs and these germinal cells afterv^ards develop into a pathological new growth. The Committee of the Pathological Society considered that the tumors mentioned above were developed from the remains of the Wolffian body. Only twelve such cases have been as yet described, and of these the following is a list : Eberth— Virch. Arch., vol. 55, p. 518. Cohnheim — Ibid., vol, 65, p. 64. Brodowski— Ibid., vol. 67, p. 205. Marchand— Ibid., vol. 73, p. 289. Brosin— Ibid., vol. 96, p. 453. Kocher and Langhans — Deutsche. Zeitsch. f. Chirurg., Bd. ix. Huber — Deutsches Arch. f. klin. Medicin., vol. xxiii. p. 312. Landsberger — Berl. klin. Wochensch., 1877, p. 497. Osier (2 cases) — Journal of Anat. and Physiol., vol. 14, p. 229. Eve — Path Trans., vol. xxxi. p. 164. Williams — Ibid. CHAPTEK XJ. BENIGN GROWTHS IN THE KIDNEY. In the records of medicine a number of cases n)ay be foiuic], in which the kidneys were the seat of adventitious growths of osseous, fibrous, fibro-fatty, cartilaginous, or glanduhir tissue. Generally speaking, such growths do not, unless they are large enough to constitute a palpable tumor in the abdomen, produce any appreciable symptoms during life; and they offer more of a pathological than clinical interest. They are all extremely rare. 1. Osseous Growths, — Mention has already been made of the ossification which sometimes takes place in the fibrous septa which separate the compartments of a sacculated kidney (see p. 456). Sometimes a fibrous or cartilaginous tumor growls in the sub- stance of the kidney, and subsequently ossifies, transforming a large part of the organ into a bony mass. The tunica propria has also been known to undergo ossification. Rayer states that Dr. EUiotson sent to him two bony shells formed by the ossified tunica propria and pelvis of the kidney, taken from a man who died with symptoms of apoplexy. 2. Fibrous and Fibro-fatty Growths. — Dickinson and Bris- towe have each recorded a case, in which the major part of the kidney was replaced by a morbid growth, composed of a matrix of fibrous tissue, in the interstices of which were soft masses of free fatty matter unenclosed in cells. In Dickinson's case the tumor weighed 6 lb. 7J oz., and formed a perceptible tumor in the right hypochondrium. After death, a coil of intestine was found in front of the tumor, but so compressed and empty that its nature was not likely to be recognized during life. Wilks records a case in which a tumor was found on the right side of the abdomen six years before death ; it was partly solid and partly fluid, and was by some diagnosed as cancerous. On post- mortem examination, the right kidney was found converted into a tumor the size of a young child's head. This was found to consist of a solid growth on one side bearing a striking resem- blance to the fibro-cartilaginous tumors sometimes met with in the neck, but which was found, on microscopic examination, to consist exclusively of fibrous tissue; and on the other side a cyst was found, which on section was seen to be due to the enor- mously distended pelvis. The new growth had slowly invaded and 542 BEISIGN GROWTHS IN THE KIDNEY. destroyed the renal tissue, while it gradually distended the cap- sule, and thus preserved the general form ojp the kidney. In the case described by Godard, the lower half of the kidney was converted into a large mass of ordinary adipose tissue. A calculus of considerable size was lodged in the dilated pelvis. A somewhat similar transformation is described by Dr. Hullett Browne, complicated with calculous pyelitis, and renal fistula opening in the left loin (" Path. Soc. Trans.," xiii. 132). Adipose tissue is, in other cases, deposited in great quantity, not in, but around the kidneys, so as evidently to interfere with their functions. In the museum of the Manchester School of Medicine there is a preparation in which a pale and atrophied kidney is enveloped in a firm investment of dense, granular, fibro-fatty tissue, fully an inch thick. The same tissue pene- trates deeply into the hilus, so as to compress the bloodvessels and excretory channels. 3. Lymphatic Growths. — Yirchow, Friedreich, and Bottcher have described growths or deposits in the kidneys of leucocy- thsemic individuals, similar to those found under the same cir- cumstances in the spleen and lymphatic glands. 4. Syphilitic Deposits in the Kidneys. — It seems well ascer- tained that the waxy or lardaceous type of chronic Bright's dis- ease is frequently due to constitutional syphilis. Out of 145 cases, collected by Fehr, 34 were attributed to this cause [see p. 406); and in 27 cases of constitutional syphilis examined by Dr. Moxon,^ the kidneys were found lardaceous in no less than 12 instances. The occurrence of gummy tumors and cicatrices (such as occur in the liver) is rare, though not unknown, in the kidneys of syphilitic persons. Both Cornil and Lancereaux give ex- amples. In Lancereaux's case there were found on the surface and in the thickness itself of the cortical substance of the kidneys small tumors of the size of a pea, of a yellowish-white color, and presenting, on examination by the microscope, the cellular and nucleated elements found in gummy syphilitic tumors elsewhere.^ Dr Moxon gives a remarkable case, in which a gummy tumor, as large as a small potato, existed in the left kidney of a syphi- litic woman. It had a regular nodose outline, and was composed of a yellowish substance, quite uniform in appearance, and 1 A Contribution to the History of Visceral Syphilis, by Dr. Moxon. Guy's Hosp. Eep., 1868. 2 Lancereaux. Treatise on Syphilis — Syd. Soc. Trans., vol. i. p. 298. A case of syphilitic gummy tumors of the kidney is recorded at great length (with a drawing) by Paolucci from the Clinique of Prof. Cantani, of Naples, in II Morgagni for June, 1874, p. 413. )S'ee also Professor Greenfield, Kesume of Eenal Pathology in the Syden. Society's Atlas. BENIGN GROWTHS IN THK KIDNEY. 543 which was firm, hurd, and toui^li. It yielded no juice on Hcrap- ing. Under the microscope, the mass was found to consist of small corpuscles crowded together, first obscuring, and then de- stroying and replacing the proper tissue, and then themselves perisliing into a heap of fat grains and globules — all wljich exactly corresponds to the usual character of syphilitic gummata. The general character of tlie kidney was that of the large [)ale lardaceous kidney/ 5. Wagner has published two cases in which one kidney was converted into a large tumor, composed apparently of a con- bination of epithelial structure, fibrous tissue, and glandular (pancreatic) sarcoma. Both were female children — one nine months and the other eight years old. 1 The power of the syphilitic poison to produce acute Bright's disease appears doubtful. Lancereaux cites two cases of albuminuria reported by Perroud, which accompanied the secondary period of syphilis — some four or six months after the indurated chancre — and which appear to have issued favorabl3\ The late Mr. Bradley, of this town (Brit. Med. Journ., 1871, i. p. 116), has al.so recorded a case of acute Bright's disease, with general anasarca in an infant sufi'ering from con- genital syphilis. The renal affection subsided pari pasHU with the disappearance of the cutaneous syphilis. Until further proof, it may be doubted whether these were not examples of a fortuitous coincidence of two independent morbid condi- tions. CHAPTER XII. TUBERCLE OF THE KIDNEY. Deposits of tubercle in the kidney may be frimary or secon- dary. In the former case the kidney and its appendages are the seat of extensive disease, which runs on, attended with severe urinary symptoms, generally, if not always, to a fatal conclu- sion. In the latter, the deposits form as a part-manifestation of general tuberculosis, or constitute incidents in the course of primary tubercle of the lungs, intestines, or some other organ ; secondary deposits rarely give rise to symptoms, and are mostly unsuspected until the autopsy. The comparative frequency of tubercle in the kidney may be judged of by the following numbers, which must be understood to embrace both primary and secondary deposits — the latter being, especially in children, by far the most frequent. Out of 1317 tuberculous subjects, examined in the Pathological Institu- tion of Prague (out of a total of 6000 bodies), tubercle in the kidneys was found 74 times, or in the proportion of 5.6 per cent, of all tuberculous subjects.^ Among 315 tuberculous children, Rilliet and Barthez found tubercle in the kidneys 49 times, or in the proportion of 15.7 per cent. Prom these statis- tics we may gather that the kidney is nearl}^ three times more liable to deposits in tuberculous children than in tuberculous adults.^ A— PKIMAKY TUBERCLE OF THE KIDNEYS. ( Tuberculous Pyeiitis. ) The statements made in the following pages are mainlj^ based on an analysis of 35 cases, derived from various sources. Morbid Anatomy. — The disease (which always implicates more or less extensively the excretory apparatus as well as the gland itself) begins in the kidney, and extends downwards into the pelvis, ureter, and bladder; or it begins in the pelvis, and spreads upwards into the kidney, and downwards towards the bladder; or all these parts may be invaded simultaneously or 1 Prager Vierteljarsch , Bd. 1. S. 1 (1856). 2 I omit the statistics of Dr. Chambers, because there are some discrepancies in. his tables which 1 have been unable to reconcile. MORBID A N A 'I' O M Y 546 in quick succession. In the kidney, the deposit begins in tiie form of gray or yellow nodules in the cortical part: these after- wards coalesce into larger masses of crude tubercle, and extend into the pyramids. These masses at length soften in the centre, and eventually open into the infundibula. In this way abscess- like cavities arise, with anfractuous boundaries of tuberculous matter, which communicate with the pelvis, and discharge pus and broken masses of tubercle into the stream of urine. In the pelvis and ureter, the deposit first begins in the sub- mucous cellular tissue,^ where it forms a rough, granular, semi- transparent or opaque layer. It consequently softens and disintegrates, causing extensive destruction of the superjacent mucous membrane, which is discharged in shreds with "the urine, mixed with pus and blood. The deposit is sometimes so abundant and uniform in the ureter, that that tube is converted into a thick rigid cylinder, of which the available bore is greatly narrowed, or even altogether obliterated. In a specimen sub- mitted to me by Dr. Leech (case to be presently related), the interior of the pelvis was thickly encrusted with calcareous matter, and one of the ureters was completely occluded near its centre by an oval mass of tubercle about the size of a horse-bean. Extensive destruction of the renal tissue eventually takes place, both from the encroachment of the tubercle masses, and from sacculation and dilation of the organ by the blocking up of the ureter (pyonephrosis). Sometimes no vestige of the secreting tissue remains ; but more commonly certain portions are pre- served, and these may present a moderately healthy appearance, or be far advanced in degeneration. In other cases the ureters are open and dilated, and admit free passage to the urine, pus, and tubercular debris ; the kidney then maintains its normal dimensions, or it may even be contracted. Actual tumor (pyonephrosis), detectable during life, is men- tioned in 7 out of our 35 cases. It seldom reached great dimen- sions, but in one instance related by Ammon, it filled the entire side of the abdomen, from the false ribs to the crest of the ilium. The disease is sometimes limited to one side, but much more frequently it invades both. Out of 32 cases which supply in- formation on this point, the two sides were afiected in 19, and one side alone in 13 cases. Of the latter, the right kidney was aiFected 7 times and the left 6 times. In addition to the kidney itself, and its immediate appen- dages (pelvis and infundibula), the disease almost invariably involved the ureter (in 30 out of 32 cases), and very frequently the bladder (in 21 cases). The urethra was involved in 7 cases. 1 See an observation by Dr. Handfield Jones, in the^^first vol. of the Path. Soc. Trans., p. 283. 35 546 TUBERCLE OF THE KIDNEY. In the male sex, the disease not unfrequently implicates the generative organs (prostate nine times, vesiculpe seminales six times, testicles four times) ; but it is otherwise in the female sex. Out of nine females, in only one instance (to be presently related) were any of the generative organs involved/ The disease very rarely runs its entire course without the occurrence of tuberculous deposits in other and unconnected parts of the body. Thirty cases were examined with sufficient minuteness to supply information on this point. The lungs were affected 28 times; the abdominal glands, 14 times; the intestines, 19 times; the osseous system, 5 times; the perito- neum, 5 times; the spleen, 3 times; and the liver, once. In one case the ulceration (tuberculous) in the bladder opened a communication with the rectum (Basham) ; in another a vesico-vaginal fistula resulted from a similar cause (Mosler) ; in a third, the suppurated kidney burst into the peritoneal sac (Lundberg, Schmidt's " Jahrb.," Bd. xci. S. 74). Etiology. — The direct exciting cause of renal tubercle is generally inscrutable. Cold is the cause most frequently men- tioned ; the patients came, in several instances, from conspicu- ously tuberculous families. Men are more liable to this com- plaint than women — in the proportion of 21 of the former to 12 of the latter. JSTo age is altogether exempt. The youngest case noted was a child of three years and a half, and the oldest (mentioned by Dittrich, and not included in the table) was a man of seventj'-one; but the greater number occurred in the middle periods of life. The following table gives the precise ages in 31 cases : From to 10 years 4 cases. " 10 to 20 " 5 " " 20 to 30 " 6 " " 30 to 40 " 9 " " 40 to 50 " 6 " " 50 to 60 " 2 " Symptoms. — The symptoms are mainly those of chronic pyelitis, conjoined, in a considerable majority of the cases, with those of chronic cystitis. The complaint begins with a dull pain in one or both lumbar regions, accompanied with frequent micturition. At the same time the urine becomes turbid, and sometimes mixed with blood. When the disease 1 The mutual independence of tuberculosis of the urinary and generative systems in the female, is further shown in a converse manner by Dittrich. Out of 45 cases of tuberculosis of the female genital organs, he only found one in which the disease also implicated the urinary organs (Arcbiv der Heilkunde, 1868, p. 804). Virchow describes an additional example of this rare conjunction, in which urinary tuberculosis was associated with secondary deposits in the vagina (Archiv fiir Path. Anat., Bd. v. S. 405). S Y M J' T O M S . 547 is fully established, the urine is charged with a large quantity of pus, which forms a thick, yellowish layer at the bottom of the vessel.^ Blood is also usually present, either in microscopic quantity, or sufliciently to tinge the urine. The lucniaturia is, however, never profuse ; in several instances it was noted that small, thready clots of blood were passed. Under the micro- scope, there are found, in addition to the pus and blood-corpus- cles, a number of oval and irregularly tailed cells from the bladder and upper urinary passages, together with granular detritus, broken masses of softened tubercle, shreds of connec- tive tissue and elastic fibres. The reaction of the urine is feebly acid. Very few exceptions to this rule exist, and those are due to ammoniacal decomposi- tion of the urine from detention in some part of its course, as in Hosier's case, from the tumid state of the external genitals. The urine is necessarily albuminous from the presence of pus, but usually only in a slight degree. Casts of tubes are only mentioned once. Micturition is always excessively frequent; often dolorous. In two cases, temporary alleviation of the pains followed each micturition : this was not observed in other cases. As the disease advances, great emaciation takes place, accom- pianied with hectic fever, sometimes marked by chills and rigors of tolerably regular recurrence. Persistent pains are felt in the back, in the lower part of the abdomen, and often along the urethra. When the kidney is sacculated and enlarged, so as to form a tumor in the flank, the swelling is usually painful ; it may, or may not, yield distinct fluctuation. Sometimes the tumor dis- plays variations in its size: it enlarges when the ureter is dammed-up by the discharged debris, and becomes more painful, at the same time the quantity of pus in the urine diminishes — or, if the stoppage be complete, temporarily disappears. Anon the course of the pus and urine is reestablished, and the tumor subsides and becomes less painful. In the progress of the case, or towards its termination, the lungs and intestines generally betray the advance of tuberculous disease. Cough and oppression of the chest, or uncontrollable diarrhoea, make their appearance. Gastric symptoms (nausea, vomiting, hiccough) are unusual ; but in some cases, as in the two about to be related, they are a marked feature of the com- plaint. The absence of intestinal tuberculosis, accompanied with obstinate constipation, appears to favor their occurrence. If both kidneys are affected, the extensive destruction of 1 At intervals the urine may be copious and limpid, containing no albumen, and giving no deposit. (Tapret.) 548 TUBEKCLE OF THE KIDNEY. secreting tissue is liable to give rise to ursemic phenomena. The quantity of the urine is usually below the average ; but excep- tionally, as in a case recorded by Sir Risdon Bennett (" Path. Soc, Trans.," viii. p. 284), the urine is abundant and of low specific gravity. Usually death occurs from the exhaustive effects of the protracted and profuse suppuration, or from the severity of the pulmonary or intestinal complications. The following cases will serve as illustrations of the course of the disorder and of the appearances generally found after death. Case 1. Tuberculous disease of the right kidney and ureter, and of the bladder, urethra, and prostate; absentee of left kidney and ureter. — J. P., a packing-case maker, set. 23, was admitted into the Manchester Royal Infirmary, under my care, March 27, 1871. He was suffering from old- standing discharge of large quantities of pus with the urine, mixed with a little blood. The disease had existed nine months ; the emaciation Fig. 68. Tlie right kiduej' of J. P. laid open — about one-half of the actual size. was extreme. There were distinct signs of consolidation in the apices of both lungs, but no cough or expectoration. Profuse night-sweats and an elevated temperature in the evenings bore evidence of hectic fever. The tongue was dry and red; the lower part of the belly was the seat ILLUSTRATIVE CASES. 540 of a dull aching, and micturition was both frequent and painful. He sank from exhaustion a few days after his admission into hospital. Autopsy (30 hours after death). — Pleura universally adherent on right side ; no adhesions on left side. There was a large amount of gray tubercle iii the upper lobes of both luv.rjs, the lower lobes being free; the tubercle was associated with a quantity of pigmentary deposit. No cavities or purulent exudation observed. Heart and pericardium healthy. Liver enlarged, soft, and friable, preseuting a pale surface on section ; spleen healthy. The left kidney, suprarenal capsule, and ureter were absent. The right kidney was considerably enlarged, and weighed 14i ounces. On section, there was a large cavity at the upper part, occupying one- fifth of the entire kidney, filled with pus, and two other very much smaller purulent cavities in the central part of the organ (see Fig. 08). The cortical portion was seen to be much hypertrophied, but pale, except the parts situated between the pyramids, which were dotted over with red points ; the pyramidal portion was atrophied and almost entirely absent. The pelvis was dilated and divided into pouch-like enlarge- ments, the lining membrane being studded over with small whitish deposits of tubercular matter, which could be traced along the ureter to the bladder, and thence along the urethra. About half an ounce of pus escaped from the ureter on section. The ureter was dilated at its com- mencement and near its termination, where it easily admitted the fore- finger ; but the opening into the bladder was so small that it could not be detected until a probe had been passed from without. A slight depression marked the position for the entrance of the left ureter, of which, however, no trace could be found. The fundus of the bladder was covered with tubercular deposit, which was limited to this part, the body and summit being entirely free. The mucous membrane of the affected part was much broken down in structure, and in parts almost ulcerated through ; the walls of the bladder and ureter were consider- ably thickened. The spermatic cords and vesiculce seminales were normal, being perfectly free from tubercle. The prostate was involved in the disease, and partially disintegrated. Case 2. Pericarditis, tvlth subsequent adhesion; cirrhosis of liver, and enlarged spleen, follotved eight years after by tube^^cular pyelitis and gen- eral tuberculosis. — I first saw G. P., a grocer, set. 27, in 1860. He was then suffering from plastic pericarditis, with immense enlargement of the spleen and considerable enlargement of the liver. His illness had been brought about by intemperance. He was in the habit of taking great quantities — as much as a quart a day — of gin. From this illness he slowly recovered, at least so far as to be able to go about and look after his business; but the enlargement of the spleen remained. I'saw this man occasionally until 1867. He persisted, with some intermis- sions, in his intemperate habits, and failed in his business. In August, 1867, he appeared among my out-patients at the Infirmary. The spleen was now decidedly smaller, and the heart appeared quite healthy ; but he was complaining of frequent micturition and of passing blood with the urine. The blood first appeared in the previous June, and had con- tinued ever since. In jSTovember, 1867, 1 admitted him as an in-patient into the Infirmary. His condition was then as follows : he was some- 560 TUBERCLE OF THE KIDNEY. what emaciated, skin moist, finger-ends slightly clubbed, no oedema anywhere, pulse 96, respiration 20, tongue dry and fiery-red. The abdo- men was rather tumid ; the liver extended from the nipple to two inches below the costal margin ; the spleen measured nine inches vertically. The urine was loaded with pus, and with enough blood to give it a full red tinge. The proportion of blood to pus in this case was much greater than is usually the case in tubercular pyelitis. There were no casts in the urine, and the albumen did not exceed the proportion due to the admixture of pus and blood. The patient remained in the Infirmary fourteen days, and underwent little or no change. He did not keep his bed. Pulse varied from 70 to 80, respiration 20. He continued to pass rather more pus and rather less blood ; but there was always enough of the latter to color the urine, and often small clots. The tongue re- tained the same " broiled ham " appearance. It is to be remarked that the spleen was now much smaller and the liver larger than when I first saw him seven years before. He was again made an out-patient, and I saw him from time to time. He continued without much change, passing purulent and bloody urine at very frequent intervals, until the end of January, 1868, when he was seized with uncontrollable vomiting, under which he sank on Feb- ruary 2d. Autopsy. — Emaciation only moderate ; no oedema. The liver was cirrhotic in an advanced degree, the spleen enlarged ; but both organs (especially the spleen) were much smaller than they had been eight years ago. The lungs were thickly studded with gray granulations from base to apex. The pericardium was adherent throughout, but it was not thickened, and the heart itself was healthy. Both kidneys were deeply aflfected with tuberculous pyelitis. The pelves were much enlarged, and studded with broken-down, ulcerated tubercle. A few ■ masses of yellow, unsoftened tubercle were found in the right kidney, about the bases of the pyramids. The pyramidal portions were in great part destroyed by the encroachment of the distended pelves. The ureters were lined throughout with ulcerated tubercle ; the bladder and urethra also were partially affected in a similar manner. The peritoneum was adherent almost throughout, and contained here and there tuberculous granulations. The next case occurred in the practice of my colleague, Dr. Leech, who kindly furnished me wnth the notes of the case, and with the anatomical preparations. Case 3. Tubercle in both kidneys, ureters, bladder, and urethra; in the prostate gland and vesiculce seminales ; also in the lungs and mei^enterio glands. — W. P., set. 53, a brewer, had been ailing three years. His dis- ease began with pain and difficulty in micturition. The urine was thick, and sometimes mixed with blood ; though he made water very fre- quently, he did not think that he passed an excessive quantity. Except for short intervals, he had suffered from the same symptoms for the last three years. His urine had been occasionally quite clear, but generally thick, and often dark. He had never complained of much pain in the lumbar region. ILLUSTRATIVE CASES. 551 About nine months before liis deutli, the i)aticnt begun to vomit fre- quently, especially after taking food ; for the last five months vomiting after meals had been constant, frequently accompanied with pain in the epigastrium. The general health had gradually failed during the last three years; but he lost flesh and strength more rapidly during the last twelve months. lie worked occasionally, however, up to six months before his death. For many months he had felt a gnawing pain just over the pubes, increased by pressure; this was less severe during the last six months of life. Five months before his death the edges of the meatus urinarius began to ulcerate, and the ulceration gradually widened the orifice to d(juble its natural size. In the course of the last six months two small abscesses formed in the scrotum, both of which were opened, and subsequently healed. He had been in the habit of taking large quantities of beer, but not much spirits ; he contracted gonorrhoea many years ago, but he never had any venereal sores. About a week before his death, he was in the following condition : Emaciation very great ; countenance sallow ; meatus urinarius much enlarged and ulcerated ; severe'pain is felt along the urethra and in the glans penis, especially after voiding urine. The ulceration can be seen to extend for a depth of nearly half an inch into the urethra. The urine contains abundance of pus and a small quantity of albumen ; no casts Avere found. The urine is passed very frequently, and in small quantities. He vomits after everything he takes, even after simple water, or a little brandy and water. What he brings up is a brownish liquid; it contains no sarcinae ; sometimes a little blood comes up; but he thinks it is derived from the back part of the nose, where he feels pain and rawness. The abdomen is flat, or rather depressed ; the epi- gastrium is very painful on pressure. In the right hypochondrium a little hard mass can be felt on deep palpation, and there is dulness at this spot on deep percussion. There is also considerable pain on pres- sure in the hypogastric region. He complains of aching pain over the lower ribs on both sides. The bowels are very constipated, and have been so for some time. The day before his death he vomited a considerable quantity of blood. The sickness and vomiting were somewhat relieved for a short time by effervescing draughts, with morphia, but only for a day or two. After- wards the vomiting became continuous ; he vomited, or attempted to vomit, every half hour or so. There was no delirium till the day before his death, which took place on the 27th of December, 1864. Autopsy. — Stomach of normal size ; mucous membrane congested in parts ; no thickening of, or deposit in, the walls ; pyloric valve thickened and somewhat contracted. Liver healthy. Mesenteric glands much enlarged ; some of them contained small cretaceous masses. Lungs : left contracted and full of miliary tubercles ; right contained hard masses of tubercle at apex. Kidneys: left of natural size; on the outside, Avhite, slightly raised spots are seen through the fibrous covering. On removing the latter_, the surface of the cortex is seen marked wdth small white nodules, 552 TUBERCLE OF THE KIDNEY. some of which are collected into patches; to these patches the tunica propria is tightly adherent. On section, several large cavities are opened into, containing pus. The largest of these is situate in the upper part of the kidney, and is lined by a smooth membrane, except at its opening into the pelvis, where some calcareous matter is deposited. All the other cavities open into the pelvis ; some of them have irregular anfractuous boundaries of softening tubercle ; these likewise are more or less completely lined with calcareous matter, composed of carbonate and phosphate of lime. The whole of the pelvis is encrusted with the same earthy material, which can also be followed for some distance down the ureter. In the cortical and pyramidal parts of the kidney intervening between the cavities, the renal tissue is studded with soft nodules of disintegrating tubercle, varying in size from a pin's head to a pea. The submucous tissue of the pelvis and ureter is the seat of a thick granular layer of gray tuberculous matter, softened in parts ; the ureter is thereby converted into a thick, rigid, uneven tube, with a narrowed calibre. The right kidney is much smaller than the left. The pyramids are occupied by abscess-like cavities full of pus. The septa between the pyramids are in some places preserved, in others partially broken down. The pelvis is greatly contracted, almost obliterated ; in one or two places there are narrow communications between the sacs of pus in the pyra- mids and the unobliterated parts of the pelvis. The ureter is completely occluded, midway between the kidney and the bladder, by an oval nodule of yellow crude tubercle about the size of a horse-bean. The whole of the mucous membrane of the bladder is strewed with deposits of tubercle. These are sparsely scattered and scanty, except over the trigone ; here the deposit is very abundant, in the form of small granulations rather larger than a pin's head. A few similar granulations are seen in the prostatic part of the urethra. The prostate gland is somewhat enlarged on the under surface, and contains two small tuberculous nodules. One of the vesiculce semihales also contained soft tuberculous matter. Case 4. Tubercle of the left kidney, pelvis, and ureter ; of the bladder and urethra ; also of the pericardium, lungs, peritoneum, and mesenteric glands. — A needlewoman, 33 years of age, strongly built, whose father seems to have died of phthisis, took cold in consequence of a severe wetting in the autumn of 1859, about a year before her death. Her first symptoms were those of cystitis, with moderate fever. The fever soon disappeared ; but the pain in the bladder, which radiated upward into the left loin, and the urgency and burning pain of micturition, together with a turbid condition of the urine, remained, and persisted through the winter. Impairment of digestion and emaciation were also observed. About half a year from the commencement of her complaint, fever- ishness returned ; pain and urgency of micturition increased, and blood appeared in the urine. From this time (February, 1860) the patient became the object of exact observation. She was already markedly emaciated, pale with a hectic flush on each cheek ; she suffered from headache, often from palpitation ; the appetite was bad, the bowels con- 1 L hUti T K A T 1 V E CASES. 558 fined, and there was moderate fever ; the desire to pass water was con- stant, and the pain in the hhidder, shooting into the left loin, great. The urine was scanty, tinged with blood, with a thick deposit of pus and blood-clots. The urethra was somewhat swollen and tender; and after micturition the bladder still contained several ounces of unevacuated urine. These symptoms maintained themselves without essential cliange for six months, until she died on the 4th of September. The loss of flesh continued without interruption, and reached an extreme degree. Hectic fever prevailed, with evening exacerbations — the temperature rising to 38.5°-39.5° C, and sometimes to 40'' C. From the end of March, severe paroxysms of chills and rigors, followed by heat and sweating, occurred at irregular intervals. At the end of July, night sweats and bed-sores were noted. Gastric symptoms were throughout prominent. They increased and diminished. For days together the patient would suffer from severe epigastric pains, nausea, vomiting, and disgust of food. From the end of May, she occasionally suffered from paroxysms of hiccough, lasting several hours. In the last moments of life she was troubled with bilious vomiting, and towards the end she had diarrhoea. The quantity of urine was invariably scanty, though the patient some- times drank a good deal. The proportion of blood in the urine gradually diminished from the beginning of March, and the blood-clots sometimes were absent for several days, yet the blood never disappeared altogether. The quantity of pus increased. From May onward there appeared occasionally in the urine sloughy shreds of cellular tissue, elastic fibres, swollen bladder-epithelium, and little yellow broken masses of detritus. On the 8th of July, some epithelial renal casts were for the first time discovered in the urine. At the end of April a vaginal examination revealed the existence of a small hard swelling at the base of the bladder (this was proved at the autopsy to be due to a tuberculous thickening at the point of entrance of the left ureter). The patient began to complain of pains in the chest soon after her admission into hospital ; then a dry cough came on, and later on, a slight dulness on percussion was perceived in the left infra-clavicular region. In the later periods she also complained of oppression in the chest; but she never expectorated, and there never existed any of the more open symptoms of pulmonary tuberculosis. It was a singular and inexplicable circumstance, that a short time before death an improvement took place, which lasted several days; all the pains and the fever disappeared, the appetite returned, and the strength was so far restored that she was able, unassisted, to sit up, although before she was scarcely able to turn in bed. Autopsy. — Emaciation had reached the most extreme degree. The brcdn and its membranes were healthy. Some tuberculous granulations were found in the otherwise healthy pericardium at the base of the right auricle. Heart healthy. The lungs and pleurce were studded with gray and yellow granulations. The left apex contained several gray nodules as large as w'alniits. The liver contained no tubercle, but its peritoneal investment was thickly covered with gray granulations; the organ was adherent, by its convex surface, to the abdominal wall. A mass of 55i TUBERCLE OF THE KIDNEY, tuberculous glands, as large as a pigeon's egg, occupied the portal fissure. The' perito7ieum covering the spleen, intestines, and mesentery was thickly covdred with tuberculous granulations. The mucous membrane of the intestinal canal was throughout free from tubercle. The right kidney was itself healthy, together with its pelvis and ureter; but its capsule was studded with miliary tubercles. The left kidney presented its usual form and size, but its capsule was converted into a thick membranous covering which enclosed the degen- erated gland. In the upper half of the organ were found one large and two smaller cavities, separated incompletely from each other by undestroyed renal tissue. These cavities were tilled with a greenish- yellow mucopurulent fluid, and their anfractuous walls were composed of reddish and yellow cheesy deposit. The reddish and yellow mate- rials, in the form of smaller and larger nodules, were deposited in close contact with each other. These cavities stood in direct continuation with the raucous membrane of the pelvis, which was similarly degen- erated and thickened. In the lower half of the organ was another and a larger cavity, similarly constituted with the others, and, like them, communicating with the pelvis. The undestroyed portions of the kidney had a pale red color, and con- tained in the lower parts of the gland several small, roundish, grayish, and yellowish cheesy nodules. The coats of the left ureter were several lines thick, firm, and rigid ; the mucous membrane tumid, friable, yel- lowish, and the seat of numberless miliary tubercles ; in many places the ureter was superficially eroded into roundish ulcers, with firm raised edges. The walls of the bladder were three lines thick ; its cavity was con- tracted ; its inner surface reddened, and riddled with ulcers having tuberculous margins. The peritoneal surface of the viscus was studded with tubercles. The serous coverings of the generative organs were in the same condition, but the organs themselves, with the exception of the ovaries, were healthy. The ovaries contained several gray tuberculous nodules. The lumbar glands contained cheesy matter. (Kussmaul, " Wiirzb. Med. Zeitsch.," Bd. iv. S. 24.) The Duration of the disease varies from a few months to two or even three years. Only 14 out of our 35 cases supply moderately exact information on this point. Five died under six months; live in six to twelve months; three in one to two years ; and one survived three years. The Diagnosis of tubercle in the kidney and its appendages turns mainl}' on the existence of signs of chronic pyelitis, joined with collateral evidence of tuberculosis, and the absence of any other assignable cause of pyelitis (calculi, hydatids, etc.). Ex- amination of the urine furnishes important information; not only is the urine abundantly purulent, but it also contains a quantity of granular debris, sometimes mixed with broken masses of tuberculous matter (insoluble in acetic acid), shreds of connective tissue, and beautiful meshes of elastic fibres from TREATMENT. 555 the cast-otf patches of disintegrated mucous mcTiibrane. JJuring recent years the tubercle-bacillus has been discovered in such urine by Rosenstein/ and also by Babes.^ Its detection adds great support to the diagnosis.^ The severity of the general symptoms — the progressive and great emaciation and failure of strength — must also be taken into account. When evidence of pulmonary phthisis, or ulceration of the bowels exist, they supply a valuable indication; but it should not be forgotten that, although tubercles almost invariably exist in these cases in tlie lungs or intestines, they often run a latent course, or are not in a sufficiently advanced stage to be clinically detected. From cancerous pyelitis (without tumor) the diagnosis is generally established without difficulty by the characters of the urine. In cancer, the urine (if not normal) is bloody rather than purulent; in tubercle, it is- always immensely purulent, and only slightly, or not at all, bloody. It need scarcely be stated that primary tubercle of the kidney is not capable of diagnosis until it has softened and commenced to be discharged. The Prognosis is excessively grave, if not absolutely fatal. A hope of recovery can only be conceived to exist in those cases (if there be, indeed, any such) in which the deposits are confined to one kidney, without implicating the excretory appendages. One does not see, a priori, why tuberculous masses in the kidney should not be evacuated by the urinary channels, in the same way that similar masses in the lungs are sometimes evacuated by the bronchial tubes, provided the tendency to the deposition of tubercle be arrested. Kidneys apparently undergoing a pro- cess of this sort have, in ver}^ rare instances, been found in the inspection of the bodies of persons who bear the marks of past tuberculosis. Dr. Bennett describes a case in which it appeared probable that such a train of events had taken place.* If the disease involve both sides, or implicate the bladder and urethra, or be complicated with pulmonary or intestinal tuber- culosis, no hope of a favorable issue can be entertained. The Treatment should be conducted on the principles which guide the management of tuberculous diseases generally. The strength should be supported by cod-liver oil, mineral acids, and other tonics, combined with a nutritious diet and a moderate allowance of stimulants. Opiates are generally requi*red to 1 Ceiitralbl. f Med. Wissench., 1883, p. 65. ^ i})i(j.^ p. 145. ^ To detect tubercle-bacilli, allow the urine to stand for a short time, and jjlace a little of the pus between two cover glasses. Dry each glass carefully ; stain like phthisical sputum, with aniline-water-magneta, decolorize with 2o per cent, solution of nitric acid, and s'tain the ground substance with methyl-blue. The tubercle-bacilli then appear red, while the other matters in the field of the micro- scope are blue. * Clin. Lects., 2d ed., p. 734. 556 TUBERCLE OF THE KIDNEY. insure rest and some alleviation of pain. These means may be supplemented b}^ the occasional use of the warm bath. To check excessive secretion of pus, the muriated tincture of iron may be given in doses of 15 to 20 drops thrice a day (see Treat- ment of Chronic Pyelitis, p. 470). B.— SECONDAEY TUBERCLE OF THE KIDNEY. Secondary tubercle is deposited in the kidneys in the form of minute yellowish nodules and granulations, varying in size from a pin's head to a pea. The little masses are scattered over the surface and through the interior of the gland, chiefly in the cortical part. In places they run together into groups or patches as large as a sixpence or a shilling. The intermediate parts of the kidney are either altogether healthy, or only show signs of congestion immediately around the deposits. When the pyramids are affected, the little granulations sometimes evince a disposition to assume a linear arrangement parallel with the straight ducts. Such deposits are not uncommon in acute general tuberculosis ; much less frequent in persons who have died from pulmonary or intestinal tubercle. The deposits are generally confined to the substance of the kidney, without participation of the pelvis and ureter. Secondary tubercle is greatly more common in the kidneys than primary. Out of 91 cases of renal tubercle tabulated by Dr. Chambers, 76 were secondary, and 15 primary. Both kid- neys are nearly always implicated in the former. As a rule, no symptoms referrible to the kidneys are observed during life. The urine presents merely febrile characters, and contains neither pus nor blood. If, however, the deposit take place with excessive rapidity, pains in the back and other indi- cations of renal disturbance may occur. In the following case, by Colin, deposition of tubercle in the kidneys, occurring in the course of chronic phthisis, was thus diagnosticated during life. A soldier, aged twenty, suffering under chronic phthisis, was suddenly seized with violent lumbar pains accompanied with an intense rigor. Next day, these pains were so violent as to cause the patient to cry out; the lumbar muscles were in a state of strong contraction, and exquisitely tender. There was high fever, with a corresponding state of the urine. Three days later, acute meningitis set in, which destroyed the patient in four days. The autopsy revealed exudation of lymph (but no tubercle) on the meninges ; old pulmonary mischief, with recent deposit of miliary granulations in the lungs; tbe spleen was studded with similar granulations. The kidneys were markedly enlarged, the capsule easily detached ; about thirty yellow nodules, as SECONDARY TUBERCLE OP^ THE KIDNEY. .557 large as pins' heads, were scattered on their surface. On the convex border of each kidney there existed, in perfect sym- metry, two whitish patches al)out the size of a two-franc piece, composed of an aggregation of a large number of granulations identical with the preceding. Sections of the organs revealed an immense number of similar granulations scattered in the cortical substance, and to a less degree in the pyramidal portion. It was calculated that each kidney contained from 300 to 400 of these granulations. ("Gaz. Ilebd.," x. p. 39.) CHAPTER XIII. ENTOZOA IN THE KIDNEYS. The parasitic worms which infest the kidneys are: Echinococ- cus hominis or hydatid, Bilharzia hcematobia, Filaria sanguinis hominis, Fentastoma denticulatum, and Strongylus gigas. The first named is by far the most common in these latitudes ; the second is the most common in Egypt, Cape of Good Hope, and certain other hot countries; the last two are of extreme rarity. Some- times intestinal worms wander into the kidneys and urinary passages [erratic worms) ; and in some notable instances, objects which were not parasites at all, or which were parasites wholly foreign to the human body, have been described and figured as genuine parasites of the urinary organs [spurious worms). Fig. 69. I.— HYDATIDS IN THE KIDNEY. [Echinococcus Hominis.) Hydatids in the kidneys are comparatively rare; they are much less common than hydatids in the liver and even in the lungs ; they are more frequent than hydatids in the other organs and tissues of the body.^ JSTatural History. — A hydatid tumor consists of an adventitious outer capsule, composed of fibrous tissue, which is organically connected with the texture of the organ in which it is situ- ated. Within this, and unconnected with it ex- cept by contact, lies the hydatid cyst itself. This latter varies in size from a walnut to an adult's head. The cyst-wall varies in thickness accord- ing to the size of the cyst, from about a line to a tenth of a line or less, and is composed of an opalescent tremulous substance resembling boiled white of egg. When examined more closely it is found to have a laminated structure (Fig. 69), and to be composed of an immense number of thin lamellae or layers, which, under the microscope, exhibit a perfectly homogeneous ^ Davaine gives the following rough approximations of the relative frequency of h3-datids in the different organs and tissues : Liver 166 Wall of a hydatid cyst, showing the la- minated structure — not magnified. [After Davaine.] Lungs . Kidneys Pelvis . Brain . Osseous system Parietes of the body Heart Orbit . NATURAL III STORY, 559 structure. Within the cavity of the cynt a uuriiljor of fiecondary or daughter cysts float freely in a watery saline fluid, which is devoid of albumen.' The daughter cysts vary in size from an orange to a pea or pin's head : they may be even much smaller than this, and require a microscope for their detection. A mother cyst may, however, be barren : that is, contain only fluid contents; but this is rare. More commonly twenty, thirty, a hundred, or even many thousand secondary cysts float within it. The structure and attributes of the secondary cysts are identical, in every respect, with those of the parent; and their walls display the same characteristic lamination. Sometimes this constitutes the entire anatomy of a hydatid cyst; but as a general rule additional structures are found, which indicate a more advanced phase of development : these are : a germinal membrane lining the interior of the cyst, and certain minute animalcules growing therefrom which are termed echinococci [scolices or tcenia- heads). Human echinococci. A A group of ecljjnococci, still adhering to the germinal membrane by their pedicles, magnified -lO times B. An echinococcus magnified 107 times ; the head is invaginated in the caudal vesicle ; a pedicle is attached to it. 0. The same compressed ; the head retracted, the suckers and the hooks are seen in the interior. D. Echinococcus magnified 107 times ; the head is protruded from the caudal vesicle. B. Crown of hooks magnified 350 times [After Davaine ] The germinal membrane is a thin, transparent, homogeneous, (unlaminated) tough membrane, which forms an interior sac closely applied to the inside of the hj^datid vesicle. "When detached and emptied it shows a tendency to contract and curl on itself in a peculiar manner. The echinococci (Fig. 70) are minute ovoid animated beings, just visible to the naked eye. When magnified they are found ^ This is not strictly correct. I have twice detected a not inconsiderable trace of albumen in the fluid of hydatid cysts of the liver. 560 HYDATIDS IN THE KIDNEY, Fig. 71. to consist of a head resembling that of a tapeworm, provided with four suckers and a double crown of hooks (E). When the head, is stretched out (D) it is seen to be connected by a short thick neck to a " caudal vesicle," which is somewhat larger than the head. The head is generally retracted within this caudal vesicle ; and then the little body assumes a spheroidal iigure with the crown of hooks in its interior (B C), The echinococci are developed on, or rather in, the germinal membrane. They grow in groups of six to ten individuals, and are at first encapsuled in the substance of the germinal membrane. As they increase in size they burst through their capsule, and are then found attached, each by a short stalk or pedicle, to the germinal membrane (A). By-and-by they break loose from this attachment and float at large in the hydatid vesicle, sometimes with a portion of their stalks still adherent. Both the echinococci and the germinal mem- brane are liable to perish (from inflammation or some other cause), and then only scattered hooks or shreds of membrane are found floating in the turbid contents of the hydatid vesicle. A marvellous light has been thrown in recent years on the zoological position of these w^orms, chiefly by the researches of Siebold and Van Beneden. It has been ascertained that the hydatid worm found in man^ constitutes the encysted phase in the development of a very minute tapeworm which infests the dog. The tapeworm in question (Fig. 71) is the Tcenia echinococcus of Siebold [Tcenia nana of Van Beneden). Th^ entire adult animal is so small that it scarcely exceeds the size of a millet-seed. It consists of but three segments, of which only the last is fruitful. When this segment arrives at maturity it is cast oflT and a new one developed in its place. Myriads of these worms are sometimes found in the intes- tines of the dog, and their eggs are discharged in countless numbers with the excrements. The eggs so discharged are scattered far and wide ; and some of them find their way with the food into the stomachs of men and other creatures suitable for their further development. Arrived there, the embryo is liberated; and, after penetrating the mucous membrane, it '/(ii. ei r / Tasnia echinococcus, magnified 22 times — [After Van Beneden.] The same species infests the pig, monkey, sheep, and ox. MORBID ANATOMY. 561 burrows its way, or is carried by the blood current, to some distant organ, where it is arrested. Having thus lodged itself, it presently reappears as a hydatid vesicle, in which, finally, are developed the echinococci as before explained. Dogs in their turn become infested with the corresponding tfenia by feeding on the oftal of slaughtered sheej), pigs, etc., which had been infested with hydatids. The ecliinococci therein contained develop in their intestines into the taenia echinococcus : and so the circle of transformation and development recommences.^ In the records of medicine may be found some seventy or eighty instances in which hydatids existed in the kidney or were passed by the urethra. In a number of these, the fact is simply mentioned ; but in sixty-three cases some fuller details are communicated, and from an analysis of these the following account is drawn up. It is necessary to remark that when hydatids are discharged by the urethra, it may be assumed as almost certain that they are derived from a cyst situated in the kidney. In the great majority of the cases, proof of this was obtained either from the examination of the body after death, or from the plain indica- tion of the symptoms during life. In some cases, however, this w^as not so; and it remained opened to conjecture whether the parent cyst was not situated in the vicinit}^ of the ureter or bladder, and opened directly into those channels. Such an occurrence seems, however, extremely rare, and I have only been able to find one instance in which actual proof of this was obtained.^ Morbid Anatomy. — The left kidney is more frequently the seat of hydatids than the right : out of 42 cases, the left kidney was affected 22 times and. the right 18 times, and both organs ' For further information and details of experiments see — Gervais and Van Beneden, t. ii. p. 270 et seq. ; Davaine, loc. cit., Synopsis, 7 and 24; and Siebold's memoir on tape and cystic worms, bound with the second vol. of Kiichenmeister's Manual of Parasites. Syd. Soc.'s Translation. ^ In the Med. Times and Gaz. for 1855, i. p. 161, a case is referred to, on the authority of Mr. Birkett, in which hydatids were withdrawn by catheter from the bladder. After death a large hydatid tumor was found between the bladder and rectum, pressing upon the neck of the former. Rayer (loc cit., iii. 354, foot-note) relates an instance in which a hydatid tumor in the left iliac fossa opened into the rectum, with expulsion of hydatid vesicles with the stools and discharge of pus and gas by the urethra. He cites another (p. 554, note), in which hydatid^ were passed by stool, and afterwards a large hydatid escaped by the urethra ; but there is no information as to the seat of the c^'st, the patients having recovered. There is another case, recorded by Mr. Fynney in an appendix to the second vol. of the Memoirs of the Medical Societj'' of London, in which hydatids were passed with the urine from a ejst which in all probability existed between the bladder and rectum. Immediately before the discharge of the vesicles the patient felt some- thing give way in the neighborhood of the bladder. The patient died in a few weeks ; but the exact seat of the cyst was not verified by post-mortem inspection. Cases of this class can be distinguished from renal hydatids by manual examina-- tion through the rectum or vagina. 36 562 HYDATIDS IN THE KIDNEY. together only twice. The less liability of the right kidney depends probablj^, as Beraud suggests, on the larger bulk of the liver intercepting a greater proportion of the embryos which travel from the intestine rightwards, than the smaller bulk of the spleen does of those which travel leftwards. In rare instances, hydatids have been found in the liver and other organs as well as in the kidney. As a rule, the cyst is lodged in the substance of the kidney; sometimes, however, between the capsule and the gland. As the cyst grows it encroaches more and more on the renal tissue, and eventually may entail total destruction of the organ. It forms a roundish, elastic, fluctuating tumor, projecting from the surface of the kidney, and varying in size from an egg to an adult's head. The cyst has a natural tendency to make its way toward the pelvis of the kidney, and discharge its contents by the ureter. When it is situated in the pyramidal portion, this event takes place early, before the cyst has attained any great dimensions : but, when situated in the cortical part, or beneath the capsule, the cyst may exist for years, and grow to a large size, before it bursts into the infundibula. It may even not burst at all ; and, still more rarely, it may penetrate upward into the chest and be evacuated through the bronchi, or open into the intes- tines and be discharged by stool. Sometimes, after opening in one direction, it eft'ects a second opening in another direction. In no instance on record has the cyst burst into the peritoneum. The following table exhibits the relative frequency of these various modes of opening in our 63 cases : The cyst opened into the :^ Pelvis of kidney . . . . in 47 cases "] Pelvis of kidney and lungs . . 1 " | Hydatids discharged by Pelvis of kidney and intestines . 3 " f the urethra. Pelvis of kidney and stomach . 1 " J Lungs alone . . . in 1 case | ^^ hydatids discharged Did not open at all .... I [\ \ by the urethra. Opened artmcially .... J " J '' Hydatid cysts of the kidney, like hydatid cysts elsewhere, are liable to certain accidents. They may contract adhesions to surrounding parts; occasion inflammation and abscess in their vicinity, and the cyst may burst into such an abscess. The cyst 1 No authenticated cases exist of a hydatid cyst of the kidney opening in the loins. Payer (iii. 578) mentions two examples of hydatid cysts in the loins, which suppurated and burst externally in the lumbar region. He seems to infer that the cysts in these cases were connected with the kidney : both ended in recovery. It is more probable, however, that the cysts were lodged superficially in the muscular tissue of the lumbar region. In a later case of this kind which ended fatally, it was ascertained post-mortem that the cyst lay surperficial to the kidney and un- connected with it. ILLUSTRATIVE CASES. 563 itself may suppurate; or it may perish, and its gerrrihial raeru- brane and echinococci be destroyed; the fluid it contains may then be absorbed, and the whole crumple up into a hard de- pressed nodule, whicPi henceforth lies dormant and obsolete. This obsolescence may ensue without bursting of the sac, or it may follow complete evacuation of its contents. The contrac- tion and obsolescence of a hydatid cyst are accompanied by deposition of a whitish cretaceous and sebaceous material be- tween it and the adventitious capsule, and within its own cavity. This deposit was formerly erroneously supposed to be of a tuberculous nature. Under the microscope it is found to consist of amorphous phosphate of lime, crystals of triple phos- phate, cholesterine plates, and fattj^ granules. Amid this debris, echinococci hooks and shreds of laminated membrane may be found. Hydatid cysts are also liable to external violence, especially when they form a palpable tumor in the flank. A blow or fall has in more than one instance been the apparent cause of the bursting of the sac into the pelvis of the kidney ; and the patient has dated his symptoms from the occurrence of some such accident. The opening of the cyst into the pelvis of the kidney is soon followed by the passage of secondary or daughter vesicles along the ureter into the bladder, from which they are expelled sooner or later with the urine. The first of the two following cases illustrates the ordinary mode of evacuation by the ureter; the second by the ureter and lungs : Case 1. Hydatid vesicles voided by the urethra, at intervals, for twenty years, with symptoms resembling nephritic colic. Hydatid cyst found in the left kidney (Chopart, loo. cit., p. 78). — A young lady of 25 was seized with a violent pain in the left lumbar region, with all the symptoms of nephritic colic. There was difficulty of micturition, tension, and ten- derness of the abdomen. The bladder was full of urine, but some obstruction prevented its flow, though there was constant desire to pass it. In the course of the night the emptying of the bladder was efiected, with discharge of a large number of hydatids. Wlien the discharged vesicles were examined on the following morning, the majority were found ruptured, and consisted of loose membranes only; some were entire, and contained a turbid fluid. The patient was relieved b.y the evacuation ; but the pain returned again in less severity two days after. This pain commenced in the kidney, and when it diminished in that organ it increased at different points in the course of the ureter, and became more acute at the entrance of this canal into the bladder. When the hydatids had reached the bladder the pain in all these parts was replaced by a sort of lassitude. The patient stated that she had been subject to similar attacks for twenty years ; and that they always terminated in a discharge of little 564 HYDATIDS IN THE KIDNEY. bladders full of water. Some of these were as big as a pigeon's egg ; others were much smaller; the latter always came away first. The attacks recurred at irregular intervals ; she was sometimes six months, a year, two; or even three years without an attack. In some of the attacks the efforts at micturition would be long unavailing, until at length, by increased effort and pressure on the belly, the hydatids would shoot out with a sort of noise, and then the urine followed in full stream. Four years later, the patient died ; it is not stated from what cause. The left kidney was found converted into a thick and firm hydatid sac, filled with vesicles. The pelvis and ureter were greatly dilated. The right kidney was healthy. Case 2. Hydatid cyst of the right kidney, which opened first into the ureter and subsequently into the right lung. Hydatid vesicles discharged with the urine and by coughing (Beraud, loc. cit., p. 63). — Madame B., set. 54, had experienced, for several months, pains in the right lumbar region and occasional difficulty of micturition ; otherwise the health was good. On August 30, 1851, she was suddenly seized with such violent pain in the right kidney that she was obliged to be carried home. M. Fiaux, who was called to the case, found extreme distention of the bladder ; a catheter was introduced, and the urine withdrawn presented nothing unusual. The patient passed a good night, and was quite restored in a couple of days. On September 15th, she went to St. Denis, where she was seized with the same symptoms as before. She succeeded, after great efforts, in expelling by the urethra a little membranous vesicle as big as a pigeon's egg, and immediately afterwards she passed abundance of water, and was relieved. On the 26th, the pains returned ; they commenced in the right lumbar region, and radiated towards the pelvis and the right thigh. She tried to pass water several times during the night, without success. The bladder reached almost to the umbilicus. A large quantity of clear urine was withdrawn by catheter with immediate relief. From the 8th to the 23d of October, retention of urine recurred on three occasions, and the urine withdrawn did not present any pecu- liarities. On November 2d, the pain in the kidney returned with great severity ; it mounted to the liver and descended along the ureter to the thigh ; there was thirst, hot skin, with tenderness and meteorism of the abdo- men. The patient had passed water several times during the night, but in very small quantities. The urine was turbid, with a glairy deposit at the bottom of the vessel. From this date to the 22d, the pain dimin- ished ; the urine continued turbid, and contained pus. On the 24th, the patient had a violent rigor, and the renal pain became more severe than ever. Vomiting occurred several times during the night, and three or four liquid stools were passed. She also voided urine several times. M. Fiaux now observed, for the first time, in the urine, shreds of membrane having the characters of hydatids. On examining the right flank, an oblong tumor was found below the liver, apparently united to it, extending to the iliac fossa and having a breadth of about MORBID ANATOMY. 565 4] inches. The tumor was hard, and tender on pressure ; no loop of intestine passed in front of" it ; the lumbar region behind jjresented a tol- erably prominent bulging. It was no longer doubtful that this was a hydatid tumor of the right kidney in a state of inflammation. From this time hydatid fragments continued to be discharged with the urine from time to time, and the lumbar fulness became more pro- nounced. On the 22d of December, under the advice of Gendrin, steps were taken to open the tumor, and several caustic issues were established on the front of it. But on the 2d of January violent pain set in at the base of the right lung, with cough, mucous expectoration, and fever. Frequent shivering occurred the next day, and the pain and fever continued. January 7. — The oppression was increased. Violent fits of coughing occurred, with abundant purulent expectoration, of a fetid urinous odor ; and this was mingled with membranes similar to those discharged with the ui'ine. She continued to cough up hydatid shreds and urinous pus and to become gradually weaker until January 22d, when she died in a fit of suffocation, after having discharged seven or eight hydatids. Autopsy. — The small intestine was thrust to the left ; the ascending colon bordered the tumor, and was intimately connected therewith in its lower two-thirds. The right lung was indurated at its base, and united to the diaphragm. Behind the cyst was a purulent collection, as large as an orange, which communicated with the cavity of the cyst. The liver, left lung, and stomach were healthy. The tumor was found adherent to the lower surface of the liver. It was constituted by the right kidney, Avhich was converted into a sac as large as a child's head. Few remains of the renal tissue were found. On cutting open the sac, it was found to communicate by two distinct openings with the dilated pelvis of the kidney and the abscess. The latter again, which occupied the vault of the diaphragm behind the liver, communicated by a perforation through the diaphragm with a ragged cavity in the base of the right lung. All these cavities, with the pelvis of the kidney, the bladder, and the bronchi, contained a purulent fluid and numerous hydatid vesicles. Ill rare cases, the secondary cysts contain a tertiary series (granddaughter cysts). Baillie mentions such an instance in the body of a soldier, whose kidney was found to contain a large hydatid cyst. Some of the secondary cysts in this instance merely contained fluid ; others contained small vesicles floating in their interior.^ Occasionally, crystals of uric acid have been found adhering to the expelled hydatids ; and in Mr. Barker's case, to be pres- ently related, Mr. Queckett found in the interior of some of the cysts crystals of triple phosphate, uric acid, and oxalate of lime. In four cases calculi were found with the hydatids in the kidney or bladder; or were passed by the urethra. 1 Baillie, Morbid Anat., 5th eel., p. 294. 566 HYDATIDS IN THE KIDNEY. The Symptoms differ essentially according as the cyst has forced a passage for its contents into the pelvis of the kidney, or elsewhere, or still maintains its integrity. In the latter case the cyst remains wholly latent until it attains sufficient bulk to form a palpable tumor in the flank. As" the tumor grows, it displaces the viscera in its neighborhood, generally without further mischief; but sometimes inflammatory adhesions or suppuration take place in its vicinity and occasion intercurrent attacks of pain and feverishness. In eighteen out of our sixty- three cases, tumor in the side was discernible during life. It varied in size from an orange to an adult's head, and presented a rounded form and an elastic feel. In some instances fluctua- tion was distinctly perceived in it; in others obscurely; in others not at all. The peculiar thrill characteristic of hydatid tumors (hydatid fremitus) was observed only in a few instances. In order to evoke this sign, the fingers of the left hand should be laid upon the tumor, and tapped sharply with the fingers of the right, A thrill is then communicated to the overlaid fingers, which has been compared to the vibrations of a repeater watch held in the hand. A similar sensation is communicated to the ear when the stethoscope is applied and the tumor tapped with the fingers.^ Sometimes the fremitus is absent under conditions which appear favorable to its production. In a case reported by Livois (cited by Beraud) even Rayer was unable to detect anything beyond ordinary fluctuation, and diagnosed a hydro- nephrosis. After death the kidney was found converted into an enormous hydatid sac containing multitudes of secondary vesicles, varying from the size of a grain of millet to a hen's egg. The topographical characters of the tumor agree with those of renal tumors in general. The colon is usually found in front of the intumescence : but it is important to know that this is not invariable. Beraud communicates a case from Nelaton's clinique, in which the descending colon ran along the outside of a hydatid tumor of the left kidney : in Fiaux's case, already related (p. 564), the ascending colon coursed along the inner border of the tumor, and no intestine separated it from the abdominal parietes. When the cyst bursts into the pelvis of the kidney, the escape of its contents by the urethra constitutes a capital symptom. This may occur with or without symptoms referrible to the renal region (tumor, nephritic colic, etc.). Entire vesicles mixed with broken ones are usually voided; in other cases only fragments are passed, or a milky detritus in which echinococci 1 The history and theory of the hydatid fremitus may be found discussed at length (with an account of Davaine's experiments) in Meissner's Beitrasje zur Lehre von dem Vorkommen des Echinococcus, etc. Schmidt's Jahrb., Bd. 116, S. 183. SYMPTOMS. 567 hooks, laminated shreds, and oil particles rna^' be detected by the microscope. The discharge of vesicles takes place in paroxysmal attacks at wholly irregular intervals. In exceptional cases, only one paroxj'sm is experienced, during which the cyst is seemingly entirely evacuated, and then finally contracts. In the great majority of cases, however, the first attack is succeeded by many others. The interval between them may be a few weeks, or a few months, or many years. In a case reported by Tomo- witz, the second attack occurred three years after the first. In Quinquerez's case, seven years elapsed between the first and second discharge of hydatids ; then the attacks followed each other more frequently, at intervals of one or more years, for ten years; in the last year they recurred every four or six weeks. An attack is usually ushered in by sharp pain in the loin, sometimes with a sensation as of something giving way inter- nally. The pain shoots down along the ureter to the inside of the thigh. It may be attended with rigors, sickness, and hic- cough — though this is rare ; then follow colicky spasm in the course of the ureter, indicating the descent of vesicles along that canal — sometimes aggravated by suppression of urine and retraction of the testicle. These symptoms continue a few hours or several days, and they commonly cease suddenly, often with a feeling as if something had dropped into the bladder. The urethra is next forced, and new symptoms arise — retention of urine, excessively frequent desire to pass water, with severe pain extending to the end of the penis. When the vesicles are expelled, relief follows. The number of vesicles discharged during an attack varies from one or two to several dozens. The urine is often tinged with blood or mixed with pus. The force required to effect the final expulsion is sometimes sufficient to propel the vesicle a considerable distance with an audible thud. The paroxj^sms are sometimes determined by some evident exciting cause, such as a blow or fall, or by horse or carriage exercise. In Zinkeisen's case the attacks usually followed the use of spirits and strong cofiee.^ After each discharge of hydatid vesicles the tumor (if any exist) may subside sensibly. On the other hand, rapid enltirge- ment of the tumor, from distention of the pelvis with accumu- lated urine, may follow the impaction of a vesicle in the n refer. Repeated discharges occasion dilatation of the passages, and enable the patient to void larger vesicles with less pain. 1 Schmidt's Jahrb., Bd. 116, S. 290. 568 HYDATIDS IN THE KIDNEY. The following examples illustrate the eccentric course and usual symptoms of renal hydatids : Case 3. . Repeated discharge of hydatid vesicles with the urine; tumor in the left lumbar region — final recovery (Lettsom, " Memoirs of the Medi- cal Societies of London," vol. ii. p. 32). — A gentleman, aged 32, was thrown off his horse in February, 1780, and received an injury in the lumbar region. This was followed by considerable hsematuria. In a fortnight all the consequences of his fall had disappeared; but in the following June he spat blood ; this also passed rapidly away. Three years later, he was seized with shivering and a violent pain in the left lumbar region. A few days after, he perceived an enlargement in the hypochondrium. This increased gradually until February, 1784. After the first month the tumor was so little painful that he was enabled to take a journey of 130 miles to London to consult Dr. Lettsom. A fluctuating tumor as large as an infant's head was detected in the left hypochondrium, extending from the spine to the umbilicus and from the ribs to the os innominatum. As the swelling augmented the pain increased, and the patient suf- fered considerably from the action of walking and from motion in general. At length (February 20th) some difficulty in making water was experienced, and for many hours there was a total obstruction of urine. The same night there was great pain with violent rigors ; but early in the morning the patient experienced the most happy relief by the discharge of a large quantity of thick pus with the urine, which was followed the next day by the escape of numerous hydatids. In a few days the tumor subsided, and the purulent discharge ceased ; after this, he continued recruiting his health for nearly a fortnight, when his side enlarged again, after exercise in a coach, probably by a large hydatid stopping up the ureter ; rigors and strangury succeeded as before, and the tumor became as large as in the first instance, until the latter end of March, when he experienced a second discharge in every respect like the former, excepting that the hydatids were larger. His health and strength again returned, until his side filled a third time, after exercise on horseback, and continued swelling until the 25th of April, when he was again relieved by a third discharge ; the hydatids now passed were considerably larger than those of the preceding attacks. The passages now became so open, that he frequently discharged hydatids after walking or riding, without enlargement or pain of the side ; or if he felt uneasy or perceived a tendency to tumescence, by pressing his hand upon his side he could squeeze the vesicles into the bladder, where they would remain some time before they were dis- charged ; but the hydatids became at length so considerable in size that it was with great difficulty they passed the urethra. The last vesicle which he voided (on the 12th of July) was so very large that it stopped up the urethra, and remained in it for a considerable time, until the weight of the accumulated urine forced it away. The earliest hydatids voided burst in their exit ; and they gradually increased in magnitude in every successive discharge ; the first which he passed were not bigger than the skin of a green pea, and the last about the size of a pullet's egg. ILI.USTKATI VE CASES. 569 Since this last discbarge his health was gradually rtestabiished ; he was able to enjoy, without the least inconvenience, thereafter, the chase and every other species of exercise as well as ever he did. Case 4. Discharge of JiydatMs by the urethra hi, periodical paroxymiH occurring yearly for a period of tldrty-aeven yearn (Vigla, '' Bulletin de la Soci6te Anatoniique," 1838. Cited by Beraud, loc. cit., p. 57 j. — A healthy woman, tet. 37, had suffered from her infancy with her present symptoms, which occur in annual paroxysms. Every winter, and gen- erally in the month of January, she experiences in the left renal region a pain, which speedily becomes severe and forces her to relinquish her occupation. There is no fever ; nor vomiting ; but the appetite is lost ; the urine remains natural. At the end of two or three days of this con- dition, she voids a very large number of hydatids, mingled with a turbid urine. This emission takes place two or three times a day, for three or four days, and then she returns to her ordinary health. Sometimes, but very rarely, similar attacks occur in the course of the year, but slighter ; these latter consist of a violent pain in the same place, not last- ing more than two or three hours, at the end of which an emission of urine with discharge of hydatids ensues, and the pains disappear. These slighter attacks have never recurred more than once or twice in the same year. In the year 1828 one of the annual January attacks was observed by M. Vigla. The prodromata — that is to say, the pain and uneasiness — were accompanied with feverishness ; but this was attributed to a coexisting acute pulmonary catarrh. At the end of four days, as usual, the emission of urine charged with hydatids commenced, and continued for four days. The quantity of vesicles which she rendered was enormous; for she passed urine twice or thrice on each of these three days, and every time from 40 to 50 large hydatids were found in the urine, without counting the little ones. The larger ones passed the first, but ruptured and empty; the largest of all surpassed the size of a pigeon's egg. The smaller ones were voided entire, and full of a semi- transparent fluid ; some were smaller than a pea. There were no symptoms referrible to the bladder. Case 5. Hydatid cyst of the right kidney ; suspicion of pregnancy ; dis- charge of hydatid vesicles by the urethra (Babington, "Med. Times and Gaz.," 1855, i. p. 160). — A healthy single woman, set. 27, was admitted into Guy's Hospital on February 8, 1854. About the age of 23 she was one day kicked in the abdomen by a child which she was carrying upstairs. The kick gave her much pain, and on the night following she discovered for the first time a tumor about the size of an egg in her right side. The tumor gradually increased, and in the course of a year became so large as visibly to distend the abdf)raen. About this time the. men- strual function was suspended, and the increasing size of the abdomen caused her great trouble, by exciting suspicions in the minds of her rela- tives that she was pregnant. The enlargement, however, continued beyond the usual period of utero-gestation, and anxieties as to the nature of the disease took the place of the suspicious alluded to. She was now sent up to London from her home in Oxfordshire, and was admitted into St. Bartholomew's Hospital under Dr. Hue. The tumor was at this time stationary, and her general health good. After a few weeks' stay in the hospital she was discharged, and returned to service, where she 570 HYDATIDS IN THE KIDNEY. continued without material change ia her condition until about a year prior to her admission into Guy's Hospital, under Dr. Babington, when she began to pass "skins and little bladders," Avith the urine. These bodies continued to be voided afterwards in large numbers. Often a vesicle would get impacted in the urethra, and require to be pulled out with the fingers. At first neither blood nor matter was ever present in the urine. About two weeks before admission, however, after having been confined to bed for several days with intense pain in the side, she suddenly felt a sensation as if something burst within her, and shortly afterwards matter and blood began to escape by the urethra. The tumor had meanwhile much diminished in size, and at the time of her admission there was no visible enlargement of the abdomen. During her illness she had lost some flesh, but still retained a fairly robust appearance. On examination of the abdomen, a large mass apparently about the size of a foetal head, but flattened, was easily felt in the right hypochon- driac or lumbar region. It was not tender, and felt firm. The patient remained under Dr. Babington's care for several moaiths, during which vast numbers of hydatid vesicles were passed. The vesicles varied much in size, some were broken and others whole. The urine contained also much pus. The girl somewhat improved in health, and the tumor became decidedly smaller before she left the liospital ; at the time of her discharge, she still continued to void occasionally pus and hydatid vesicles. Case 6. Frequent discharge of hydatid vesicles by the urethra — ne- phritic colic and suppression of urine. No tumor in the flanh (Dr. Barker, loc. cit., p. 5). — A young man, set. 28, came under the notice of Dr. Barker, of Bedford, on December 17, 1853. He was suffering from a dull aching pain in the loins, particularly on the left side, with frequent desire to pass urine, and slight difficulty in voiding it. The urine was healthy. On the 22d of December he experienced greater difficulty than ever in passing urine in the early part of the night, and for some hours he was unable to pass a single drop. Early in the morning he passed four little hydatid cysts with immediate relief. Subsequently he recovered sufficiently to follow his occupation during the summer of 1854, suffering nothing more than an occasional frequent desire to void urine. On September 10, 1854, he passed six cysts ; but with less pain than on the previous occasion — a result which the patient attributed to taking 10 drops of oil of turpentine, which had been recommended to him, and which greatly increased the diuresis. The urine after the passage of the cysts was tinged with blood. On November 16th he passed four cysts. The passage of these was preceded by severe pain in the left kidney, by the passage of several pieces of clotted blood, and by considerable difficulty in voiding urine. Indeed, for two entire days he passed no urine. On this occasion he took 19 drops of turpentine, within two hours, in divided doses. Shortly after taking the turpentine, the pain in the left kidney suddenly ceased, with a sensation which, to use the patient's own words, seemed to indi- cate that " something had suddenly broken in the kidney." He then TERMINATION. 571 complained of pain along the left iliac region, which continued fur- several hours, and ceased as suddenly as the previous })ain had fhnie. Alter this, all attempts to void urine were accompanied with pain along the urethra, premonitory to the expulsion of the cysts from that [)assage. He continued in good health, with the exception of occasional dull aching pain in the lumbar region, especially the left side, until Decem- ber 9th. He then i)assed five cysts, but all smaller than the previous ones; and no more were passed until December 81st, when he awoke in the morning with acute pain in the loins, and all the symptoms pre- viously described as occurring on November 16th. During the day he passed twenty cysts — one at 8 A. M. ; eleven at 1 p. m. ; five at 7 v. M. : and three at 11 p. M. The cysts passed in rapid succession, and some were of a size as large as a small walnut. On January 1,1855, a single cyst was passed in the morning; on the 2d two others ; on the 3d cme; and on the 10th two. From this last date up to December 8th (beyond which the history is not carried), he continued to suffer frequently from attacks of pain and diflSculty in passing urine, followed (»ften by the expulsion of cysts, between seventy and eighty of which he brought to Dr. Barker. Careful examination failed to detect any abdominal enlargement. The urine often contained a small quantity of blood during and after the expulsion of the cysts; it was often loaded with lithates and phos- phates; occasionally, crystals of uric acid were found attached to the outer surface of the cysts. The general health suffered little. Alto- gether upwards of 150 cysts were passed; they varied in size from a pin's head to a walnut. The larger vesicles contained echinococci ; but many of the smaller ones did not contain any. The duration of the symptoms is altogether uncertain. In some of the cases permanent recovery followed one or a few discharges of vesicles. Other patients went on passing hyda- tids for three, ten, twenty, and even thirty years. A discharge of vesicles having once taken place, there are no means of ascer- taining whether any more will follow. Neither the number of vesicles voided, nor the frequency of the discharges, supplies any reliable indication. The only sign of value is the lapse of time since the preceding attack : the longer the interval the less probability of recurrence. The usual termination is recovery. Out of sixt^'-three cases, recovery was assumed to have taken place in twent}^; in most of these the attacks had ceased for some years. In sixteen cases, vesicles continued to be discharged at the date of the record; in nineteen cases the termination, was fatal: and in eight we are left without information. Of the nineteen fatal cases, death took place in nine from causes other than the hyda- tid disease (phthisis, cancer, gangraena senilis, etc.) : so that only in ten (sixteen per cent.) was the fatal issue attributable to the parasite. Death was brought about in these ten cases in diverse ways — by bursting of the cyst into the bronchi, by pleurisy 572 HYDATIDS IN THE KIDNEY. from pressure of the tumor on the thoracic cavity, suppuration of the sac, etc. In a case reported by Dr. Blackburn, the left kidney was the seat of a hydatid cyst which had burst into the pelvis of the organ, where a large calculus was also found; the right kidney was congenitally absent : so that the abrogation of the function of the left (and unique) kidne}^ proved necessarily fatal.i Etiology. — Hydatids are not uncommon in England, Erance, and Germany : more rare in America and India. There is, however, no country so fearfully infested therewith as Iceland. According to Eschricht (speaking of hydatids in any part of the body), a sixth part of the population are afflicted with this parasite. The frequency of the disease is due to the vast number of dogs in that country, which live in intimate contact with the inhabitants, and are greatly infested with the taenia echinococcus. The ova of the parasite, discharged with the excrements of the dogs, foul the dried fish which forms a large part of the food of the population. The embryo of the parasite thus finds its way into the stomach, and thence travels into different parts of the body, giving rise to hydatid cysts. The use of uncooked meat and salad is evidently an easy source of infection, in places where dogs are numerous and live in close intercourse with their masters. Dr. Barker's patient had been for a year a vegetarian. Men appear more subject to renal hydatids than women — the proportion, in our sixty-three cases, was forty-one men to twenty-two women. In only one instance was more than one member of a family affected : in that case, a husband and wife passed hydatids by the urethra.^ The mean age, in forty-seven cases, was thirty-four years : the youngest was only four years, and the oldest seventy-five. The Diagnosis presents no difficulty when a tumor exists in the side and hydatid vesicles are voided with the urine. When the vesicles are broken in the passage, the laminated structure of the pieces, or the finding of echinococci-hooks, decides the nature of the discharge. So long as the parent cyst remains intact, the urine preserves its normal characters, and the diagnosis turns on the characters of the tumor in the flank. Hydatid fremitus, when present (which is rare), is a valuable sign ; but its absence, as we have seen, has little significance. Hydatid tumor of the kidney is most liable to be confounded with hydronephrosis; and in the absence of discharge of vesi- cles, or their debris, with the urine, and of hydatid fremitus, the 1 Lond. Med. Journ., 1781, p. 126. 2 Gay, Med. Times and Gaz., 1855, T. 160. PROGNOSIS. 573 diagnosis is extremely difficult or impossible : it rests chiefly on the indications of the previous histoiy. When vesicles are voided with the urine, and no tumor cun be detected in the flank, the seat of the parent cyst is sometimes indicated quite clearly, to be the kidney, by signs of nephritic colic — in other cases, more obscurely, by pains in the back and loins or about the crest of the ilium. When these indications fail, a careful examination of the pelvis should be made through the rectum or vagina: if no evidence be found of a tumor between these parts and the bladder, it may be inferred, almost with certainty, that the parent cyst is situated in the kidney.' The Prognosis is generally favorable — much more so than in hydatid cysts of other internal organs (the uterus excepted), on account of the facility and safety of evacuation b}' the urinary passages. It is most favorable of all when the discharge of hydatids by the urethra is unassociated with tumor in the abdomen. In no such case has a fatal result been recorded : the cyst in such cases may be inferred to be small, and to be situated in the pyramidal structure of the kidney, w^hence its contents find easy exit through the infundibula. When a renal tumor exists, the issue is still likely to prove favorable if the cyst has opened into the urinary passages. There is, however, some risk that a second opening ma}- be formed in a less safe direction (into the lungs), or that the cyst, or the parts around, ma}^ suppurate. This latter contingenc}' is by no means rare, nor is it necessarily fatal. In several instances large quantities of pus were discharged with the vesicles, and yet the issue was favorable. In three cases, in which vesicles were discharged both by stool and with the urine, the termina- tion was favorable. In an instance recorded by Fleckles, a woman who had had a tumor in the side for many years voided frequently hydatids by the urethra, and subsequently a large quantity by vomiting. At the date of the report the case was going on favorably.^ In the two cases in which the cj'st burst into the cavity of the thorax, the termination was fatal. When the cyst fails to open a passage for its contents into the pelvis of the kidney, the prospects of the patient are much more serious. The tumor is liable to attain very great dimensions, 1 Prof. Otto Spiegel berg (Arch, fiir Gyniikol., i. 1, p. 146, quoted in Schmidt's Jahrb., Bd. 146, 1870) records the case of a woman, fet. 42, who for lifteen months had had a tumor in the right hypogastrium. It was movable, distinctly fluctuat- ing, and about the size of a man's head ; and extended downwards towards the brim of the pelvis. It could be felt and moved from the vagina, and was fallen for an ovarian cyst. On proceeding to perform ovariotomy, when the cyst was opened, two echinococcus membranes escaped, which cleared up the diagnosis. A portion of the kidney was left behind. The patient died 26 hours after the opera- tion. 2 Schmidt's Jahrb., Bd. 87, S. 205. 57-1 HYDATIDS IN THE KIDNEY. and, by its pressure, to excite inflammation in the surrounding parts, or within the chest; or the cyst itself may suppurate and be transformed into a vast abscess. The operation of puncturing such a cyst is one of considerable danger. Treatment. — The indications to be held in view are, to destroy the life of the parasite, to facilitate the evacuation of the cyst, and to combat the accessory symptoms and complications. Whether medicines administered internally have any real power to destroy the life of a hydatid parasite, or to facilitate the evacMation of a hydatid cyst, may be greatly doubted. jSTevertheless, oil of turpentine has obtained a certain reputation on the strength of its tseniafuge properties. The echinococcus of the hydatid vesicle is undoubtedly identical with the head of a certain species of tapeworm; but the condition of a parasite free in the intestinal canal, is widely difi'erent from the encysted state of the same parasite in the substance of the kidney, where remedies can only reach it indirectly, by the circuitous route of the circulation. Turpentine was given in a large proportion of the recorded cases; but there is little evidence that it had any beneficial influence beyond its diuretic effects. The escape of the vesicles in Dr. Babington's case, was thought to be favored by a course of iodide of potassium.^ A variety of other vermifuge and diuretic medicines have been used, with more or less show of success — calomel, nitrate of potash, the caustic alkalies, hemlock, taraxacum, etc. Beraud states of his patient, that whenever he took white wine, and beverages containing nitre, he voided a much larger number of vesicles than at any other times. On two different occasions he was made to take 20 grains of nitre in dandeloin tea, and each time the desired effect was speedily produced.^ Electro-puncture has also been practised with a view to kill the worm ; but without evidence of success. When the cyst has opened into the pelvis of the kidney, the practitioner is able, in diverse way, to facilitate the expulsion of the vesicles, and to moderate the severity of the accompanying symptoms. Anodynes, especially opium, the warm bath, free use of diluents, are indicated during the passage of the vesicles; if the nephritic paroxysm be intense, blood may be abstracted from the loins by cupping. Sometimes mechanical aid is required to assist the liberation of the vesicles. Dr. Lettsom's patient helped their transit along the ureter by pressing them forward with his fingers; and in several cases it is noted, that patients (mostly women) have used the fingers to dislodge vesi- 1 In two cases of hydatids of the liver, I have seen the cyst gradually and com- pletely contract a^'ter a course of very large doses (30 grains t. d.) of iodide of potassium. 2 Gaz. d. Hop., Aug. 11, 1832. Beraud, loc. cit., p. 93. BILHAKZIA H^MATOIilA 575 cles impacted in the orifice of the urethra. The use of tlie catheter is sometimes required to relieve the retention of urine caused by vesicles engaged in tlie urethra or pressing against the neck of the bladder. When the cyst remains closed, measures should be taken to evacuate its contents. In similar cysts of the liver I have, in four cases, adopted the following plan with uniform success, I employ a tubular gold needle — like tlie needle employed in sub- cutaneous injections, except that it is about twice as long. The base of the needle is mounted on apiece of India-rubber tubing three feet in length, and furnished with a small stopcock at its lower end. The tube is first filled with water by suction, and the stopcock closed. The needle is then thrust into the most prominent part of the cyst, and the lower end of the tube is placed in a vessel on the floor. When the stopcock is opened, the fluid begins to run — the column of liquid in the tube acting after the manner of a siphon, and exercising a soliciting force on the contents of the sac.^ The wound made by these fine needles is so minute that there is no risk of extravasation into the peritoneum- — and certainly no risk of peritonitis, as I have tested in a large number of instances. In two of my cases simple puncture by the needle has been suflScient, with only a withdrawal of a drachm or two of the contents, to destroy the life of a hydatid parasite, and to cause it to pass very gradually into obsolescence and absorption.^ It must, however, be remembered that evacuation of a renal hydatid is not so urgently called for as the evacuation of a hydatid of the liver; because in the former there is a natural tendency to spontaneous evacuation by the urinary channels, with very little risk to life, whereas, a hydatid of the liver has no such read}^ means of escape. II.— BILHAKZIA H^MATOBIA.— Co6&o;(^. [Distoma Hcematobiuni — Bilharz.) This parasite was discovered by Bilharz, while conducting, with Griesinger, an investigation into the diseases of the Egyptians. Bilharz named it Distoma Haematobium; but later writers have erected it into a separate genus, which CobboLd has named Bilharzia in honor of the discoverer. It is an elongated, ^ This plan is substantially like an operation with the more recently introduced aspirator, but the force used is of more gentle and safer character, — see a paper by the author "On Exploration and Tapping" in the Liverpool and Manchester Medical and Surgical Keports for 1873. ^ For a case of hydatids of the kidney successfully treated by aspiration, see Brit. Med. Journ., 1877, ii. p. 471. " ~ ' - 576 BILHARZIA H^MATOBIA, Fig. 72. Bilharz , aighly magnified, h i g, the male ; ab c, the female. [After Bilharz.] soft-skinned, bisexual entozoon, three or four lines in length, of the trematode or fluke kind (Fig. 72). It inhabits the branches of the portal system, and the minute veins of the pelvis of the kidney, ureter, and bladder. So common is it among the Egyptians, that Griesinger found it 117 times in 363 autopsies. The male (A ig) is comparatively thick and short, and provided with a gynse- cophoric canal, in which the longer, filiform female [a b c) is lodged during the copulatory act. The Qgg (Figs. 73 and 74) are oval bodies, ^tq of ^^ inch long, with a spiny projection from the anterior end. The embryo, when newly escaped, is flask- shaped, and provided with cilia (Fig. 74). This creature does not produce much mischief in the larger veins ; but when lodged in the smaller vessels of the mucous and submucous tissue of the urinary and intestinal tracts, it engen- ders severe and often fatal disorganiza- tion. Griesinger found that, in the large intestines, it gave rise to a disease resembling dysentery, and that it was a frequent complication of that disease, but not the essential cause of it. The ravages of the Bilharzia produce much more serious results in the urinary channels than in the intestines. It chiefly aflects the bladder, but frequently also the ureter and pelvis of the kidney. In the bladder, it gives rise to injected and ecchymotic raised patches, varying from the size of a lentil to that of a shilling, covered with a tough mucus, or with grayish-yellow, bloody exudation, which contains masses of ova. In more advanced stages the patches are more elevated, discolored, mixed with pigment specks, smooth and leathery, or soft, friable, and encrusted with gravelly matter, composed of uric acid and other urinary deposits, mixed with ova and blood. In other cases, the patches resemble nodules or condylomata, over which the mucous membrane is sometimes preserved uninjured, some- times thickened, injected, adherent, or detached. When the parasite invades the ureter and pelvis of the kidney, its effects are still more destructive. The calibre of the ureter is narrowed at the affected spot. Above the constriction, the ureter is dilated from accumulation of urine; the pelvis is also distended, and a hydronephrotic condition is produced. Or, MORBID ANATOMY AN1> SYMP'J'OMS. 577 inflaramation and suppuration are Hot up, and Hovere pyelitis ensues. In one instance, Griesini^er found the kidney distended into an enormous sac filled with })us — the renal tissue being wholly destroyed. In addition to these direct results, urinary concretions are often foi-nicd on masses of ova, and grow into large calculi. This accounts for the frequency and endemic prevalence of calculous disorders in Egypt. Griesinger remarks: "These various changes in the mechani- cal state and nutrition of the uro-poietic apparatus fail not to react most deleteriously on the entire organism. A series of cases have fallen under our notice, in which they produced general ill-health, and, at length, death. Most of these indi- viduals werefinall}' cut off, v^ith shattered constitutions, by pneu- monia, dysentery, and the like. . . . The direct signs of the disease are to be sought in the uro-poietic system, but especially in the urine. Repeated hsematuria in sickly individuals, from unknown causes, often came before us in Egypt. We no longer doubt that the symptoms were produced by distoma-processes. The eggs of the distoma were found by Bilharz in the urine of a boy who, during convalescence from typhus, suffered from hsematuria.' Symptoms of pyelitis, or slight aflection of the bladder, must be present in many cases." . . . "Cases also came before us which awoke a strong suspicion that the Distoma dis- ease sometimes runs its course as an acute, severe, and painful disorder. We found on two occasions, in the bodies of persons who had rapidly died from an unknown acute disease, abundant recent distoma-changes in the bladder, recent pyelitis, and a uniform dark-red hypersemia of the kidneys. In other cases of supposed rapid typhus, the same changes were found in the bladder and ureter." These researches open a wide held for conjecture. Not only may urinary derangements and uraemia be occasioned by the ravages of the parasite, but septic infection may arise from the accumulation of heaps of dead and dying animals in the portal vessels; or the animals may creep into the general circulation, and iind their way into organs of vital im- portance; in one instance distoma eggshells w^ere found in the blood of the left ventricle. In a note to his remarkable paper, Griesinger throws out the conjecture that the endemic hsematuria of hot countries may be due to the presence of this worm in the urinary passages. A most interesting confirmation of this conjecture has been sup- plied by the researches of Dr. John Harley. Dr. Harley had an opportunity of examining the urine of three gentlemen who 1 Griesinger states that the clinical aspect of the subject onl}- began to engage their attention when he and Bilharz were about lo quit Egypt. 37 678 BILHARZIA H^MATOBIA. had resided at the Cape of Good Hope, and who had been sub- ject to the endemic hsematuria of that country. One of them still continued to be affected with slight hsematuria; the other two considered themselves cured of the hsematuria, but were subject to gravel. In the deposit from the u.rine of all three, Dr. Harley detected numerous ova of the Bilharzia. The con- dition of the urine in the first case is thus described by Dr. Harley: "Pale-amber colored, sp. gr. 1017.6, acid, deposits a deep layer of dirtyish-white flocculent matter, amongst which were two short opaque. filaments about the -^j of an inch in diameter, of a brownish color and soft consistence, two shorter and wider fragments of the same substance, a little reddish mass of the size of a hemp-seed, like a little clot of blood, and nu- merous white specks. The clear limpid urine, when acidulated with nitric acid and heated, deposited a trace of albumen." Uric acid, oxalate of lime, and urates were also sometimes found. The deposit, examined microscopically, was found to contain pus corpuscles ; and the filamentous bodies and coagula contained embedded in them great numbers — sometimes thirty or forty, or more — of bright, highly refractive, oval bodies, which were iden- tified as the ova of Bilharzia (Fig. 73). These observations Fm. 73. Ova of Bilharzia hjematobia, found in the urine of a patient suffering from the endemic hreniaturia of the Cape of Good Hope, a, filament of mucus containing ova embedded, X 50; b, ova as they appeared in the fresh urine, X 100- [After Harley.] seem to establish the parasitic origin of the endemic hsematuria of Cape Colony, and render it extremely probable that the endemic hsematuria of Mauritius and other hot climates has a similar origin. An example of this curious disease came under my notice in the person of a groom, w^ho had been in the employ of the Viceroy of Egypt. I am indebted to m}^ friend Dr. Simpson for an opportunity of examining the case. MORBID ANATOMY AND SYMl'TOMS. )79 William Ray, set. 19, was admitted into the Manchester Infirmary under Dr. Simpson, in February, 1871. He stated that rather more than two years ago he went to Cairo, as groom in the service of the Viceroy of Egypt. After a stay of some months, he went to Alexan- dria for the summer, returning to Cairo in the winter. He returned to this country about four months ago. While in Egypt he had been in the habit of drinking the water of the Nile unfiltered, and of eating water-cresses freely; with one or two exceptions, he invariably rode his horse bare-backed. About four months after his arrival in Cairo, he observed that he passed bloody-looking urine, and shortly afterwards he Bilharzia in urine. I. Free embryos, showing the different shapes they assume as they swim about in the urine. 2. Ova containing unhatched embryos. 3. Emptj' shells from -which the embryos have escaped. suffered pain in the back and perineum when riding. Since then he has persistently passed turbid urine containing blood. He is now very ansemic and thin, but in fair health apart from the urinary affection. On the 10th of March I examined the patient's urine. The specimen was a fair sample of what is generally passed. It was smoky and turbid, with an abundant reddish-white deposit in which might be seen Jittle flakes of blood-clots; it was neutral to test-paper, specific gravity 1010, and contained a little albumen — rather more than the blood and pus would account for. Under the microscope, the deposit was seen to con- sist mainly of pus, mixed, however, with blood, both in the form of shreddy clots and as free corpuscles. Both ova and free embryos of the Bilharzia heematobia were present in considerable numbers (see Fig. 74). The embryos, in the mature ova (2), exhibited slow expand- ing and contracting as well as oscillating movements; these expansile movements were especially seen in the cervical narrowing, which at one time became very marked, and anon was almost effaced. The free embryos (1) moved actively in the urine for some hours after its emis- sion. They were covered all over, with the exception of the head, with 580 BILHARZIA HJEMATOBIA. long vibrating cilia, by means of which they moved in various directions, with intervals of quiescence. At times an embryo could be seen racing across the field of the microscope with such speed that the eye could scarcely follow it — at other times, the movement consisted in stretching out the body to its full length, and then retracting it to an oval or ball- shape. When moving across the field, the body turned over and over on its longitudinal axis. Sometimes the head was retracted into the interior of the body. A number of empty eggshells, with irregular openings in them, or in fragments, were also seen scattered over the field. This patient continued under observation for two or three weeks, and then left the hospital without leave. In this case all the ova had terminal spines — not lateral ones — so that they reserabled exactly the ova found by Harley in the cases from South Africa. Dr. Harley states that in his cases he never " met with a free living embryo in the urine. Eggs, which split open and liberate active embryos immediately after they are placed in water, remain quiescent for an indefinite time when left in the urine, and all attempts to hatch them in this fluid kept fresh and warm had invariably failed" (" Med.-Chir. Trans.," vol. 54). In the case just recorded this was certainly not the case — the embryos moved actively in the urine for several hours after its emission. It does not appear that a man aft'ected with this disease is capable of transmitting it to his wife. The wife of one of Dr. Harley's patients had three or four healthy children, and the husband had been passing numbers of the eggs of the parasite every day of their married life — yet the lady had never had the slightest symptoms of the parasitic disease, and the urine was free from all traces of the parasite. It seems probable that the parasite usually gains entrance into the body through the stomach by means of drinking infected water or eating salad, to which the minute animal or its embryos or ova adhere. Dr. Harley suggests that it sometimes obtains admission through the skin, that the minute leech-like animal Axes itself to the skin of a person in bathing or wading, and implants the ova in some superficial vein. If such be the case, it is easy to understand that the hatching process and irritation attending the movements of free embryos would result in an indolent form of ulceration, and that the little animals might be carried by the circulation from the legs to the urinary organs. It is certain that new colonists in the Cape are very apt to be attacked by indolent sores on the legs, and it seems not unlikely that their origin may thus be accounted for. Of the treatment of this parasite, Dr. Harley observes : " I have found that a draught composed of ti\^xv each of oil of turpen- tine and male fern, and in^v of chloroform, in §ij of tragacanth FILARIA SANaUINIS HOMINIS. 581 mixture, given every morning, brought away great iiumherH of tlie ova. The sahne condition of the urine in much diminished, and the renal irritation and pain due to the presence of crystal- line concretions are much relieved by the administration of bi- carbonate of potash in copious draughts of water. The alkali dissolves the uric acid, which I believe to be the cementing medium of the oxalic deposits, and thus the disintegration of the calculi is facilitated, and their formation prevented." From the researches of Siebold on the trematode worms, it may be assumed, that between the ciliated embryo above men- tioned and the adult sexual worm, there are two other distinct forms, which serve to complete the chain of metamor[)hoses connecting these two extremes of development. Fresh water mollusca and fish are probably the victims selected by the para- site during its development through these intermediate stages. Harley on these grounds suggests the following prophylactic measures in districts affected with endemic hsematuria: 1. The water should be conve^^ed from its source to its destination in covered channels, so that the ova contained in the urinary and fecal products of those infested with the parasite may be pre- vented mixing with it. 2. Drinking water should be filtered. 3. Salads which may entangle small mollusca containing para- sites, and uncooked mollusks and fish (as smoked fish), should be carefully avoided. When the ravages of the parasite are confined to the bladder and prostate local means may be employed. Dr. Harley tried the effects of injections of wormwood, quassia, and iodide of potassium. He obtained good results only with the last. He recommends a solution of 20 or 30 grains of the iodide in 5 ounces of tepid water to be injected every second or third day. III.— FILAEIA SANGUINIS HOMINIS.— iyew;is In 1872 Dr. T. R. Lewis made the interesting observation that, in India, chylous urine always contained large numbers of a minute nematoid worm, to which he gave the name of Filaria Sanguinis Hominis. Further observation led him to the discovery that the same worm was present in the blood of chj^uric patients, and in such numbers that a single drop of blood extracted from the finger almost invariably showed the presence of one or several filarise. The symptoms found coincident with this worm by Dr. Lewis were past or present chyluria, and, less frequently, persist- ent diarrhoea, conjunctivitis, deafness, elephantiasis of the scrotum or legs. In one case filariiTe were found abundant!}' in the blood of a man three years after the chyluria had ceased. The Filaria Sanguinis Hominis is a long narrow worm about the breadth of a red blood-disk and -i^-^ of an inch in length {see 582 FILARIA SANGUINIS HOMINIS. Fig. 75). When examined in fresh drawn blood it exhibits very active, wriggling, snake-like movements. It consists of a deli- cate hyaline tubular envelope closed at both ends. "Within this the worm "elongates and contracts. Under a magnifying power of 600 diameters transverse strise can be detected and granular aggregations, but no distinct evidence of oral and anal orilices, nor of any other structure. Its habitat is the blood, and, owing to its minute size, it is capable of circulating through the capilla- ries. Whether it is capable, like the trichina, of inducing gen- eral febrile disease is uncertain — though one of Dr. Lewis's cases Fig. 75. Filaria Sanguinis Hominis — from a drop of blood obtained by pricking the finger of a European woman suffering from chyluria. A few blood-dislss are introduced to show the relative size of the rilarise. X 300. [After Lewis.] indicates this pretty strongly. It local effects are supposed to depend on the formation of aggregations of filarise which block up the capillaries, and cause by their active movements irrita- tion and rupture of the blood channels and lymphatics, and thus ' lead to the appearance of chyle and blood in the urine, to discharges from the cutaneous surfaces, with thickenings and inflammation of the skin and intestinal mucous membrane — giving rise to hy- pertrophv (elephantiasis) of the integument, diarrhoea, and so forth. Dr. Bancroft, of Brisbane, discovered iilariae in the blood of persons suffering from chylous urine in Queensland, Australia. He kindly sent me some specimens preserved in glycerine and water enclosed in hermetically sealed capillary tubes. I had no FILARIA SANGHJINIS IIOMINIS. 588 difficnlty in identifying these with the filarise described by Lewis. Dr. Biiiicroft infers from his experience that the disease is not coninuinicated frona person to person in tlie same family, but thinks that it may be communicated by drinking contaminated water. Dr. Bancroft found it much easier to detect the filarise in the blood than in the urine. The iilaripe found by Dr. Bancroft were also submitted for examination to Dr. Cobbold, who identified them with Lewis's filari.Te, and showed that they were only the embryo form of a worm of which the adult was as yet wanting. Dr. Bancroft, in 1877, after renewed searchings, was able to announce the discovery of the adult worm, which was styled by Dr. Cobbold Filaria Bancrofti. The specimens first examined were obtained from a lymphatic abscess of the arm and from a hydrocele of the spermatic cord, and were discovered to be examples of the female worm. It is about three inches in length, and at the thickest part about -Jq- of an inch in diameter. A complete uterine system terminates in a vaginal pouch, opening near the head, and from the genital opening large numbers of the embryo filariee are discharged. The discovery of the adult worm has since been confirmed by Lewis and Manson, the latter of whom saw the parasite in situ in a dilated lymphatic. The male worm has not yet been discovered. The blood of a patient who is the host of the parasite, does not contain the embryo filarise at all times of the day, but a most remarkable periodicity has been observed in their appear- ance. In ordinary circumstances, the filarite make their appear- ance in the blood at sunset, increase in numbers up to midnight, and then gradually diminish, to disappear entirely at about nine or ten o'clock in the forenoon. Manson showed that this perio- dicity was interfered with by a febrile attack, but Mackenzie {see page 353) made the remarkable observation that the perio- dicity could be completely reversed by causing the patient to rest in the daytime and to be active and take his meals during the night. Under such conditions the rise and fall in the num- bers of the filarise were again observed, but at similar hours of the day and not of the night. The fate of the filari^e in the body is as yet doubtful. In Dr. Mackenzie's case the number of filari?e in the blood was estimated at from thirtj^-six to forty millions, at the period of the greatest number. It is now apparent that a piatient may for a long period be the host of this parasite without showing any morbid symptoms. It is evident then that some additional circumstances must occur to cause the severe symptoms mentioned above, which are probably due to obstruction of the lymphatic channels. Manson is of opinion that this event is nothing else than an abortion of the parent worm. In the early stages of its development the 584 STRONGYLUS GIGAS. tilar'uil embryo ]ies curled up in its capsule, but as it nears matu- rity, gradually elongates and stretches its capsule until it as- sumes the thread-like form in which it is usually observed. In this shape it is able to pass freely through the various lymphatic and hfemic capillaries. If, however, the embryo be discharged into the blood stream before the process of elongation is com- pleted, according to Manson its more rounded shape renders its passage along the smaller lymph capillaries impossible, and the lymph stream is hence obstructed. The researches of Manson have also revealed the interesting fact that the female of a certain species of mosquito acts as the intermediary host to the parasite. The embryo iilarise shows a tendency to curl round any fine object with which they are brought into contact. In this way, it is believed, they curl round the proboscis of the mosquito, and are so transferred to the stomach of the insect. This is rendered probable by the fact that the blood found in the stomach of the mosquito con- tains more filarise than the blood of the host. Most of the filarise embryos are either digested or passed out with the feces of the mosquito. Some, however, develop and are finally liberated by the death of the mosquito and disintegration of its body. Their future transference to man is probably by means of drinking water. IV.— STRONGYLUS GIGAS,.— Rudolphi. [Eustrongylus Gigas — Diesing.) This is the largest of the nematoid worms, and in its general conformation resembles a gigantic lumbricus. The male meas- ures from ten inches to a foot in length, and a quarter of an inch in breadth, while the female has sometimes a length of more than a j^ard. It is distinguished from the common round worm by its reddish color (which is, however, apparently due to the sanguineous fluid in which it is usually bathed), its greater size, and the existence of six nodules or papillae round the mouth. The Ascaris lumbricoides has only three oral papillse. The worm is almost peculiar to the kidney and urinary pas- sages, and is very rarely found elsewhere. It inhabits weasels, the North American mink, and has been found in the dog, wolf, horse, ox, and some other animals; according to Schneider certain kinds of fish are the intermediate bearers. It is of ex- treme rarity in the human subject. Of the seventeen alleged cases collected by Davaine, he only classes seven as even prob- able instances. There are none of recent occurrence ; and it is evident that most of the alleged cases were really examples of lumbrici, which had penetrated into the urinary passages from the intestines. ERRATIC WORMS. ;j85 A very fine apecinioti in prcsei'ved in tlio niuHcuni of the London College of Surgeons, wliich I have had an oj»[)ortiniity of examining. It is an undoubted strongyluH, more than a foot long. It originally belonged to Brookes's museum, and is entered in Brookes's catalogue as " an uncommonly fine speci- men of an enormous worm (strongylus gigas) found in the kidney of a patient of the late Thomas Sheldon, I^^sq." Fio. 76. V— PENTASTOMA BENTlCU'LATUM.—RHdo/j./u,. This is a very minute encysted parasite, about a line and a half long, club-shaped, with a double pair of hooks, and devoid of sexual organs {see Fig. 76). It is conjectured by Davaine to be the larva of pentastoma tsenioides, which infests the frontal sinuses of dogs and horses. ISTo symptoms are known to be produced by it. The only known instance in which the parasite was found in the urinary organs is the following : In making the autopsy of a painter, sixty-two years of age, who died of Bright's disease, Wagner found on the convex border of the right kidney a small, whitish, slightly raised oval patch of fibrous appear- ance, about one-seventh of an inch long. It was situated under the capsule of the kidney. This little body was hollow in the interior : it contained a yellowish mass, which on exami- nation disclosed the presence of a worm, which was recognized as the pentastoma denticulatum of Rudolphi. This worm is common on the surface of the liver in goats, oxen, rabbits, cats, and some other animals. It has also recently been found on the surface of the liver in man, by Zenker in Dresden, ITeschl in Vienna, and by Virchow, Wagner, and Frerichs in other parts of Germany. Cobbold states that Dr. Murchison, during the time he held the office of Pathologist at the Middlesex Hospital, diligently searched for it without success. Pentastoma tlenticulatum, greatly magnifled. [After Zenker.] VI.— ERRATIC "WORMS. Intestinal worms sometimes penetrate into the urinary pas- sages, and are voided with the urine. In women thread worms occasionally creep into the bladder through the urethra; and in both sexes lumbrici, and joints of tapeworm, have been 586 SPURIOUS WORMS. known to creep into the bladder through fistulous communica- tions caused by abscesses, passage of pins, lithotomy, etc. VII.— SPURIOUS WOEMS. The spiroptera hominis of Rudolphi, the diplosoma crenata of Farre, and the dactylius aculeatus of Curling, have been clearly proved by Schneider and Cobbold to be examples of imposition — witting or unwitting on the part of patients. The history of the so-called diplosoma crenata of Farre furnishes one of the most remarkable examples ever put on record of long-continued and successful deception practised on scientific inquirers. The following references may be consulted on the subject : W. Law- rence, " Med.-Chir. Trans.," vol. ii. 385; A. Farre, " Beale's Archives of Medicine," vol. i. p. 290 ; A. Schneider, " Reichert and Dubois's Archiv," 1862, p. 275 ; Cobbold, " Entozoa," pp. 403, 409; CurHng, "Med.-Chir. Trans.," vol. xxii. p. 274. CHAPTEE XIY. ANOMALIES OF POSITION, FORM, AND NUMBER OF THE KIDNEYS. The kidnejs are subject, like other organs, to certain devia- tions from their natural situation, form, and number. Most of these deviations are cono;enital ; others are acquired later in life throus^h accident or disease. Some of them are appreciable during life, and are liable to be confounded with wholly dif- ferent pathological states; others are entirely latent, and are, so long as the healthy state is maintained, nowise detrimental to the subject of them, but bring greatly increased risks, under certain contingencies of obstruction to the course of the urine. I.— ANOMALIES OF POSITION. The kidneys may occupy an unnatural situation, and remain permanently y?2:?; — St. Bartholomew's Hosp. Rep., vol. x. Druitt— Med. Times and Gaz., 1873, vol. i. p. 408. Begbie— Edin. Med. Journ., May, 1875. Forest and Finlayson — Glasgow Med. Journ., 1879. Saundby — Birmingham Med. Journ., vol. xi. Mackenzie — Lancet, 1884. Lichtheini — Volkmann's Samml. klin. Vortrage, 134. Ehrlich— Zeitsch. f. klin. Medicin., iii. p. 383. Boas— Deutsch. Arehiv. f. klin. Medicin., 1883. 608 BIBLIOGRAPHY. PART II. CHAPTER I. Diabetes Insipidus. Willis — Urinary Diseases, p. 1. Lond., 1838. jTalck — Beitr. z. Lehre von d. Einfache Polyurie. Deutsche klin., 1853. ISTeufter — ^Ueber D. Insip. Tubingen Thesis, 1856. Canstatt's Jaliresb., 1857, iv. 234. Trousseau — Cliniqiie Medicale, 1. ii. p. 611. Magnani — Du Diabete Insipide. Strasburg Thesis, 1862. P. Eade — On Diabetes Insipidus. Beale's Archives, vols. ii. and iii. W. Strange — Case of Diab. Insip. Beale's Archives, vol. iii. Andersohn — Nichtzuckerfuhrender Harnruhr. Dorpat Thesis, 1862. Merbach — Ein Fall von Poljuirie. Kiichenmeister's Zeitsch., 1865, p. 10. Lancereaux — De la Polyurie. Paris Thesis, 1869. Strauss — Einfache Zuckcrlose Harnruhr. Tubingen Thesis, 1870. Dickinson — On Diabetes. Lond., 1875. Kiilz— Diab. Mell. u. Insip. Marburg, 1875. Senator — Ziemssen's Cyclopaedia, vol. xvi., 1877. Lecorche — Traite du Diabete. Paris, 1877. CHAPTER II. DiABKTES MeLLITUS. Prout — Stomach and Renal Diseases, chap. ii. Bouchardat—AnnuairedeTherap., 1841, 159; 1846, Suppl. 162 ; 1848,227; 1849, 136; 1855, 147; 1865, 291; and Clinique Europ., 1859, 217. Garrod — Gulstonian Lects. on Diabetes. Brit. Med. Journ., 1857. Griesinger — Studien liber Diabetes. Arch. d. Phys. Heilk., 1859. Ptivy — Diabetes: its Nature and Treatment. Lond., 2d edit., 1869; Croonian Lectures. London, 1878. p,-itz — Du Diabete dans ses rapports avec les maladies cerebales. Gaz. Hebd., 1859, 264. Eischer — Diabete consecutif aux trauraatismes. Arch. Gen., 1862. Bernard — Legons de physiologic. Paris, 1858 ; Clinique Europ., 1859, 81 ; Lon- don Medical Record for 1874. Erance — (Diabetic cataract). Guy's Hosp. Rep., 3d series, vol. vi. 226. V. Graefe — (Diabetic cataract). Archiv. f. Ophthalm., 1858. Lecorche — (Amblyopic diabetique). Gaz. Hebd., Nov. 1861; Traite du Diabete. Paris, 1877. Marchal jde Oalvi — Recherches sur les Accidents Diabetiques. Paris, 1864. Roberts, W.— On the Treatment of Diabetes. Brit. Med. Journ., 1860. Gray — (Treatment). Glasgow Med. Journ., vol. iv. SchifF (J. M.) — Untersuchungen liber die Zuckerbildung in der Leber. Wiirz- burg, 1859. BIBLIOGRAPHY. 609 Harley — On Diabetes. Lond., 1800. Donkin — Skim-milk Troutmcnt of Diabetes and Bright's Disease. Lond., 1871. Kill/.— Beitrjlge z. Path. u. Therap. d. Diab. Mell. Marburg, 1874. Dickinson — On Diabetes. Lcmdon, 1875. Seegen— Diab. Mcll., 2d ed., Berlin, 1875. Senator — Zierns. Cyclop., vol. xvi., Eng. Trans,, 1877. Lauder Brunton — Keynolds's System of Med., vol. v. London, 187'J. Frerichs — Ueber den Diabetes. Berlin, 1884. CHAPTER III. Gravel and Calculus. Marcet — On Calculous Disorders. Lond., 1819. Prout — Nature and Treatment of Gravel and Calculus. Lond., 1821. Magendie — De la Gravelle. Paris. Civiale — Traite de I'Atfection Calculeuse. Paris, 1838. Crosse — A Treatise on Urinary Calculus. Lond., 1841. Catalogue of Calculi in the Museum of the College of Surgeons. Lond., 1842. Kees — On Calculous Disease. Lond., 1850. Heller — Die Harnconcretionen. Vienna, 1860. Leroy d'Etiolles (Eils)— Traite pratique de la Gravelle. Paris, 1863-4. Beale — Urine, Urinary Deposits, and Calculi. 3d ed. Lond., 1809. Carter — Microscopic Structure and Formation of Urinary Calculi. Lond., 1873. Medical Treatment of Oravel and Calculi. Chevallier — On the Dissolution of Gravel and Stone in the Bladder. (Trans- lated by Edwin Lee.) Med. Gaz., 1837, p. 430. Ch. Petit — Du Traitement Medical des Calciils Urinaires par les Eaux de Vichy. Paris, 1834. Ch. Petit — Nouvelles Observations de Guerisons, etc. Paris, 1837. Ch. Petit — Du Mode d'Action des Eaux Minerales de Vichy. Paris, 1850. Civiale — Du Traitement Medical de la Pierre. Paris, 1840. Thompson (Sir H.) — Preventive Treatment of Calculous Disease, and the Use of (Solvent Remedies. Lond., 1873. CHAPTER IV. Chylous Urine. Prout — Stomach and Renal Diseases, 5th ed., p. 112. Rayer — Maladies des Reins, torn. iii. p. 387. Bird — Urinary Deposits, 5th ed., p. 416. Bence-Jones — Phil. Trans. 1850; and Med.-Chir. Trans., vols, xxxiii. and x'xxvi. Beale — Urine and Urinary Deposits, 3d ed., p. 299. Waters — Med.-Chir. Trans., vol. xlv. p. 209. Carter— Ibid., vol. xlv. p. 189. Priestley— Edin. Med. Journ., 1850, p. 945. Bouchardat — Annuaire de Therapeutique, 1802, p. 200. Pearse — Med.-Chir. Trans., vol. xxxiv. p. 127. Ackermann — Deutsche Klinik, 1808, ISTos. 23 and 54. 39 610 BIBLIOGEAPHY. Isaacs — American Journ. of Med. Sci., April, 1860. Elliotson — Med. Times and Gaz., Sept. 19, 1857. Dutt— Lancet, 1862, vol. ii. p. 87. Begbie— Ed,. Med. Journ., Aug. 1862. Eggel — Inaug. Diss. Tubingen, 1869. Lewis — On a Hismatozoon in Human Blood: its Relation to Chylaria and other Diseases — and the Pathological Significance of ISTematode Hsematozoa. Calcutta, 1874. Dickinson — Path. Trans., vol. xxix. p. 891. Mackenzie — Path. Trans., vol. xxxiii. p. 394. Sonsino — Med. Times and Gaz., I. 1882. Manson — On Filaria Sanguinis Hominis. London, 1883. PART III. CHAPTER L Congestion of the Kidneys. Robinson— Med.-Chir. Trans., 1843, p. 51. Ererichs — Die Bright'sche Nierenkrankheit, 1851. Hermann — Sitzungsberichteder mathem-naturw. Classeder Kais. Akad. Vienna, 1861, p. 26. Overbeck — Ueber den Eiweissharn, Ibid., Eeb. 1868. Bouillaud — Archives Generales. 4me Serie, torn. xvii. p. 99. Johnson — Diseases of the Kidney. Lond., 1852. Virchow — Archiv f. path. Anat., Band iv. Traube — Ueber den Zusammenhang von Herz- und Nieren-Krankheiten. Berlin, 1856. Bamberger — Archiv f. path, Anat., Bd. xi. S. 16. Rosenstein — Path. u. Therap. d. Nieren-Krankheiten. 2d ed. Berlin, 1870. J. Vogel — Krankh. d. Harnbereit. Org., Erlangen, 1865. Weissgerber and Perls — Arch. f. exper. Pathologie, 1876, vi. p. 118. Posner — Virch. Archiv, vol. 79, p. 311. Cornil and Brault — Pathologie du Rein. Paris, 1884. Appendix. Lever — Guy's Hospital Reports, 1848, p. 495. Devilliers and Regnauld — Archives Generales, 1848. Frerichs, 1. c, p. 211. Wieger — Schmidt's Jahrbiicher, Band 87, S. 57. Braun — On Ursemic Convulsions in Pregnancy and Parturition. Translated by Dr. Matthews Duncan. Edin., 1857. Rosenstein, 1. c, p. 62. Abeille — Traite des Maladies a urines albumineuses et sucres. Paris, 1863. Braxton Hicks — Trans, of Obst. Soc, viii. 823. BIBLIOGRAPHY. 611 Barnes — Ibid. Schroder — Lehrbuch d. Gebtirtsch., 5lh ed., 1877. Leyden — Zeitsch. f. klin. Mcdicin., Bd. II. S. 171. Hiiler— Ibid., Bd. II. S. 085. Bartels — Ziemssen's Cyclofjsod., Eng. Trans., vol. xv. p. 304. Wagner — Ibid., Morbus Brightii, 3d ed., p. 193. Flaischlen — Zeitsch. f. Geburtsch., vol. vii. CHAPTER II. Briqht's Disease. Bright — Eeports of Medical Cases, vol. i. Lond., 1827. Also papers in Guy's Hospital Reports for 1836 and 1840. Christison — On Granular Degeneration of the Kidneys. Edin., 1839. Osborne — On Dropsies Connected with Suppressed Perspiration and Coagulable Urine. Lond., 1835. Rayer — Traite des Maladies des Reins. Paris, 1839, 1840. Johnson (Geo.) — On Diseases of the Kidneys. Lond., 1852; also Med.-Chir. Trans., vol. xlii., and Ibid. vol. Ivi. ; and Lectures on Bright's Disease. Lond., 1873. Simon — Med.-Chir. Trans., vol. xxx. p. 153. Rees (G. 0.) — On the Nature and Treatment of Diseases of the Kidney. Lond., 1850. Prerichs — Die Bright'sche Nierenkrankheit. Braunschweig, 1851. Todd — Clin. Lects. on Certain Dis. of Urin. Organs. Lond , 1857. Wilks — Guy's Hosp. Reports, 2d series, vol. viii. Dickinson — Med.-Chir. Trans., vols, xliii. and xliv., and on the Pathology and Treatment of Albuminuria. Lond., 1868. Friedreich and Kekule — Arch. f. Path.'Anat., Bd. xvi. S. 50. Beckmann — Ibid., Band xiii. S. 94. Wagner — Archiv der Heilkunde, 1861, p. 481. Rosenstein — Path. u. Therap. d. Nierenkrankheiten. 2d ed. Berlin, 1870. Grainger Stewart — Bright's Diseases of the Kidneys. 2d ed. Edin., 1871. Traube — Ueber den Zusammenhang von Herz- und Nierenkrankheiten. Berlin, 1856; also Deutsche Klinik, 1859, p. 6; und Schmidt's Jahrbucher, 1862, No. 3. C. Schmidt — Ann. de Chem. u. Pharm., Band Ix. S. 250. Richardson (B. W.) — On Ursemic Coma. Clinical Essays. Lond., 1862. Petroff — Zur Lehre von der Uramie. Archiv f. Path. An., Bd. xxiv. S. 91. Treitz — Ueber Urjim. Darmaftectionen. Prag. Vierteljahrschrift, 1859. Hammond (W. A.) — On Un'emic Intoxication. Amer. Journ. of Med. Sc, 1861, Goodfellow — Diseases of the Kidney and Dropsy. Lond., 1861. Schottin—Arch. d. Heilk., 1860, p. 417. Bernard and Barreswil — Archives Gener., 1847, p. 449. Virchow — Archiv f. path. Anat., Bd. vi. and viii. Oppler — Beitr. z. Lehre v. d. Arch. f. path. Anat., Bd. xxi. S. 260. Zalesky — Untersuch. u. d. Uramischen Process. Tub., 1865. Harley — On Albuminuria. Lond., 1866. 612 BIBLIOGRAPHY. Basham — On Dropsy. 3d ed. Lond., 1866. Gull and Sutton— Med.-Chir. Trans., vol. Iv. 273. Galabin— On the Connection of Bright's Disease with Changes in the Vascular System. Lond., 1874. Mahomed — Etiology and Pre-albuminuric Stage of Bright's Disease. Med.-Chir. Trans., vol. Ivii. 197. Lancet, i., 1879. Broadbent — Lancet, 1875, ii. p. 902. Klein — Keports to the Privy Council, 1876, p. 39. Greenfield— Atlas of Pathology, Syden. Soc. Southey— Brit. Med. Joarn., I, 1881. Bartels — Ziemssen's Cyclop., Eng. Trans., vol. xv. •Wagner — Ibid., Morbus Brightii, 3d edition. Thoma — Virch. Archiv., vol. Ixxi. pp. 42 and 227. Ewald — Ibid., vol. Ixxi. p. 453. Senator — Virch. Archiv, vol. Ixxiii. pp. 1 and 313. Leyden — Zeitsch. f. klin. Medicin, vol. ii. p. 133. CHAPTER V. Suppuration in the Kidney ; Eenal Embolism. Howship — A Practical Treatise on the Complaints Affecting the Secretion and Excretion of the Urine. Lond., 1833, p. 21. Kayer — Malad. des Eeins, tom. ii. and iii. Johnson — Diseases of the Kidneys. Lond., 1852. Todd— Clin. Lect. on Urin. Dis. Lond., 1852. Kirkes — Med.-Chir. Trans., vol. xxv. Virchow — Gesammelte Abhandlungen, p. 602. Traube— Ueber den Zusammenhang von Herz- und Nierankrankheiten, p. 77. Beckmann — Archiv f. path. Anat. Bd. xli. S. 59. Chambers — Decennium Pathologicum— Kidneys. Brit, and For. Med.-Chir. Kev, , vol. xxxvi. p. 489. Moxon— Thrombosis of Pvenal Veins. Path. Soc. Trans., 1869, p. 227, and 1870, p. 248. F. J. Eoberts — Eenal Abscess, Eeynolds's System of Medicine, vol. v. p. 595. M. Beck — Consecutive Nephritis, Ibid., p. 529. Ebstein — Ziemssen's Cyclop., Eng. Trans., vol. xv. p. 543. CHAPTER VI. Pyelitis and Pyonephrosis. Eayer — Loc. cit., t. iii. Bright — Memoirs on Abdominal Tumors (New Syd. Soc), p. 224. Howison — Case of Sero-purulent Distention of Kidney. Edin. Med. Journ., 1822, p. 557. Basham— On Dropsy. 3d ed. Lend., 1866, p. 348. Oppolzer — "Wiener Med. Wochenschr., 1860. Todd — Clin. Lects. on Dis. of Urin. Organs. Lond., 1852. Chuckerbutty — Lancet, 1860, ii. Mosler— Archiv der Heilkunde, 1863, p. 420. Kussmaul — Wiirzb. Med. Zeitsch., 1863, p. 56. BIBLIOGRAPHY. 613 Mackey— Brit. Med. Juurii , J8G'J, vol. i. p. 087. Stevens— Glasgow Med. Journ., 1869, p. 257. Michaelis— Zur Lehre, v. d. Pyol. Wien. Mod. Presse, vol. xi. 33, 84. Wells, S. — Dublin Quart. Journ., vol. xliii. p. 131. Pathological Soc. Trans., vol. i. j). 117; x. p. 209; xix. p. 278; xxi. p. 278; xxi. p. 25. Charles— Brit. Med. Journ., March 20, 1875. Bbstein — Ziemssen's Cyclop., Eng. Trans., vol. xv. p. 562. CHAPTER VII. Concretions in the Kidneys. Eayer — Loc. cit. t. iii. p. 10. Virchow — Gesammelte Abhandl., p. 833. Rosenstein — Loc. cit., p. 425. Vogel — Krankh. d. Ilarnbereitend. Organe, p.' 684. Leroy d'Etiolles (flls) — Traite prat, de la Gravelle, p. 235. Oppolzer— Wien Med. Presse, vii. 27, 35, 36, 37. Eustace Smith — Calculus of the Kidney in Children, Lancet, 1882, i. p. 266. Cases of— See Path. Soc. Trans , xviii. p. 181; xix. pp. 270, 281; xxi. p. 253; xxiv. p. 148; xxvi. pp. 128 and 132; xxix. pp. 155 and 160; Schmidt's Jahrb., Bd. 138, S. 87 ; Bd. 140, S. 44 ; Bd. 145, S. 30. Dub. Quart. Journ., vol. 1. p. 481; Lancet, 1873, ii. 810; 1874, ii. 695; Ibid., 1874, ii. 1; Med. Times and Gaz,, 1882, p. 165. CHAPTEPv VIII. Hydronephrosis. Glass^Phil. Trans., 1747. Johnson — Monthly Med.-Chir. Journ., 1816 (July). Konig — Krankheiten der ISTieren. Leipzig, 1826, p. 152. Eayer — Maladies des Reins, torn. iii. p. 476. Lee— Med.-Chir. Trans., xix. 238. Hare— Med. Times and Gaz., 1857, i. 29. Kussmaul— Wurzb. Med. Zeit., Bd. iv. Heft I. Stadfeldt— (Etiology of) Monatsschr. f. Geburtsk., 1862, p. 69, Parre— Lancet, 1861, ii. 472. Rosenstein — Nieren Krankheiten, 2d ed., 352. Dumreicher — Wiener Med. Halle, March 27, 1864. Strange — Beale's Archives, vol. iii. Simpson, A. R. — Glasgow Med. Journ., New Ser. ii. 332. Friedreich— Virch. Arch., vol. 69, p. 308. Schottelius — Ibid., vol. 71, p. 268. Morris — Med.-Chir. Trans., vol. lix. p. 227. English— Zeitsch. f. Chirurg., Bd. xi. S. 11 and 252. See, also— Path. Soc. Trans., vii. 262, 263, 265; ix. 318; xiii. 128, 137, 147, 151 ; xiv. 195; xvi. 164 ; xviii. 167, 171. Brit. Med. Journ., 1874, ii. 401; 1878, ii. p. 457. Lancet, 1880, i. pp. 610 and 870. Med. Times and Gaz., 1876, i. p. 546; 1882, i. p. 661. Wien. Med. Wochenschr., April, 1876.. Virchow and Hirsch. Jahresber., 1880, 1881, and 1882. Gazette des Hopi- taux, No. 30, 1882. 614 BIBLIOGRAPHY. CHAPTEfl IX. > Cysts and Cystic Degeneration of the Kidneys. Eayer — Mai. des Keins, t. iii. p. 507. Bright — Memoirs on Abdominal Tumors (New Syd. Soc), p. 208. Hawkins — Med.-Chir. Trans., xvii. p. 175. Coote— Med. Times, 1851, ii. p. 197. Virchow — Gesammelte Abhandlungen, pp. 837, 864. Siebold — Monatssch. f. Gerburtskunde, 1854. Beckmann — Archiv f. Path. Anat. , ix. p. 221. Forster — Pathol. Anat., p. 357. Striibing— Deutsches Arch. f. klin. Medic, Bd. 29, S. 579. Path. Soc. Trans.— 1848-9, p. 74; 1850-1, p. 131 ; 1851-2, pp. 377, 379, 384; iv. pp. 193, 199; V. p. 183; vi. p. 267; ix. pp. 309, 334; xix. p. 274; xxi. p. 244; xxxi. pp. 164 and 167. See, also, Brit. Med. Journ., 1883, i. p. 1177; and Progres Med., No. 20, 1883. CHAPTEE X. Cancer op the Kidney. Wilson— Dis. of Urin. Organs. Lond., 1821, p. 284. Otto — Neue Beobachtungen zur Anat. u. Path. Berlin, 1824. Konig — Krankh. der Nieren. Leipz., 1826, p. 242. Langstaif — Med.-Chir. Trans., vol. vii. p. 294. Bright — Memoirs on Abdominal Tumors. New Syd. Soc, vol. vi. Bayer — Mai. des Eeins, t. iii. p. 675. Walshe — Nature and Treatment of Cancer. Lond., 1846. Lebert— Traite d'Anat. Path. Paris, 1857, vol. ii. Kohler — Krebs- und Scheinkrebs-krankheiten. Stuttgart, 1853, p. 414. Basham — On Dropsy, 3d ed., p. 417. Doderlein — Inaug. Diss. Erlangen, 1860. Eosenstein — Nierenkrankheiten, 2d ed., p. 403. Kussmaul— W-iirzb. Med. Zeitschr., 1863, p. 24. West — Diseases of Infancy and Childhood. Lond., 1852, p. 490. Braidwood — Liverp. Med. Surg. Eep., vol. iv. Path. Soc Trans., i. pp. 120, 281 ; vii. p. 268 ; viii. p. 286 ; x. p. 188 ; xiv. p. 179 ; xxi. pp. 249, 252; xxii. p. 171 ; Ibid., p. 173; xxiv. p. 149; xxv. p. 172; xxvi. p. 132; xxvii. p. 204; xxxiii. pp. 195, 199, 219. Edin. Med. Journ., xvi. p. 381 ; xix. p. 160; New Ser. i. p. 149. Journ. f. Kinderkrankh., xxix. p. 396; xxxv. p. 426; xxxvii. p. 292. Perewerseff — Virchow's Archiv., lix. p. 227. Neumann — Essai sur le Cancer du Eein. Paris, 1873. Lancet, 1873, i. p. 131 ; and Ibid., 1874, ii. p. 49 ; 1877, i. pp. 194 and 567 ; Brit. Med. Journ., 1881, i. p. 806. Kiihn — Deutsches Arch. f. Klin. Medic, xvi. p. 806. Weigert — Virch. Archiv, vol. Ixvii. p. 423. Eohrer— Ibid., p. 492. Cattani — See Yirch. and Hirsch. Jahresber., 1882, ii. p. 194; also see Ibid., 1883, ii. p. 221 ; and Progres Med., 1883, No. 20. BlBLlOGKArHY. 616 CHAPTEK XI. Bknion Gkowth« in tub KrnNEY. Rayer — Mai. des Eeins, iii. 605. Godard— Substitution graisseuse du Kein. Paris, 1859. Virchow — Gesammelte Abhandlung«n, p. 208. Heath— Adipose Transformation of the Kidney. Path. Soc. Trans., x. 199. Dickinson— Fibro-fatty Tumor of the Kidney. Path. Soc. Trans., xiv. 187. Bristowe — A Tumor of the Kidney. Ibid., p. 189. Wilks— Fibrous Tumor of the Kidney. Path. Soc. Trans., xx. 224. Wagner— Archiv der Heilkunde, 1860, Heft iv. Friedreich— Archiv f. Path. Anat., Bd. xii. Bottcher — Ibid., Bd. xiv. CHAPTER XII. Tubercle of the KiDNisY. Rayer — Mai. d. Reins, t. iii. p. 618. Carswell— Pathological Anatomy, pi. ii. tig. 5. Basham— On Dropsy, 3d ed., 384. Rosenstein — Nierankrankheiten, 2d ed., p. 387. Rilliet and Barthez— Malad. des Enfans, t. iii. p. 852. Chambers— Decennium Pathologicum. Med. Times and Gaz., 1852, ii. 403. Schmidtlein— Ueber die Diagnose d. Phthisis Tuberculosa der Harnwege. Deutsche Klinik, 1863. Kussmaul— Beitrage zur Anat. u. Path. d. Harnapparats. Wiirzb. Med. Zeitsch., Bd. iv. S. 24. ' Mosler— Beitrage zur Path. u. Therap. d. Krankh. d. Harnwege. Archiv d. Heilkunde, 1863, p. 299. Colin— Nephrite Tuberculeuse aigue. Gaz. Hebd., t. x. p. 39. Southey— Brit. Med. Journ , 1867, i. p. 444. Ellis— Ibid., 1869, ii. p. 324. McDowell— Ed. Med. Journ., xv. p. 1093. Klob— Oester. Zeitsch. f. pract. Heilk., xiv. 9, 10. Cases-Schmidt's Jahrb., Bd. 140, S. 44; and Ibid., Bd. 144, S. 219. Virchow and Hirsch's Jahresbericht, 1876, ii. p. 232; 1877, ii. p. 228; 1880, ii. p. 212; 1881, ii. p. 205. Tapret— Archiv Gen. de Med., May and July, 1878. Bierry — These de Paris, 1878. Jean — France M6dicale, 1878. Picard— Gaz. Hebdom., 1879, No. 27. Gaultier— These de Paris, 1882. CHAPTER XIII. I. — Hydatids in the Kidneys. Chopart— Traite des Malad. des Yoies Urinaires. Ed. by Segalas. Paris, 1855. Rayer — Malad. des Reins, t. iii. p. 545. Barker— On Cystic Entozoa in the Human Kidney. Lend., 1856. 616 BIBLIOGRAPHY. Davaine — Traite des Entozuaires. Paris, 1860, p. 524. Gervais and Van Beneden — Zoologie Medicale. Tom. ii. 274. Beraud — Hydatides des Keins. Paris Thesis, 1861. Curling— Med. Times and Gaz., 1863, ii. 164. Collection of cases in Med. Times and Gaz., Peb. 17, 1855. Sieveking — Lancet, Sept. 10, 1853. Simon— Ibid., Sept. 24, 1853. Durand — Assoc. Medical Journal, March, 1851. Tomowitz— Schmidt's Jahrb., Bd. 116, S. 200. Quinquerez — Ibid. Meissner — Beitrage zur Lehre von dem Yorkommen des Echinococcus beim Menschen. Schmidt's Jahrb., Bd. 116, S. 188. Adams (Dr. Leith)— Lancet, Oct. 1, 1864. Cobbold — Parasites. London, 1879, p. 112. Simon — Die Echinococcus-Cysten der Nieren. Stuttgart, 1877. Eomestan — These de Paris, 1881. Cases— Gaz. Hebd., 1868, p. 702; Schmidt's Jahrb., Bd. 146, S. 292. Mouvement Medical, Nov. 9, 1872. Path. Soc. Trans., xxv. p. 173; xxix. p. 155; Vir- chow and Hirch. Jahresber., 1878, ii. ; St. Bart.'s Eeports, vol. xii. p. 255. II. — BiLHARZIA HiEMATOBIA. Bilharz — Zeitsch. fiir Wissenschaftliche Zoologie. Bd. iv. Griesinger — Beobachtungen liber die Krankheiten von Egypten. Archiv d. Physiolog. Heilk. 1854, p. 561. Davaine — Entozoaires. Synopsis, No. 38. Cobbold — Parasites, p. 38. Harley (Dr. John) — Endemic Hematuria of the Cape of Good Hope. Med.-Chir. Trans., vol. 47, p. 55; Ibid., vol. 52; and Ibid., vol. 54. III. — FiLARiA Sanguinis Hominis. Lewis — On a Hajmatozoon in Human Blood. Calcutta, 1874. Also Lancet, 1877, ii. p. 453. Bancroft— Path. Trans., vol. xxix. p. 407; Lancet, 1877, ii. p. 70. Cobbold — On Parasites. London, 1879, p. 180. Manson — Filaria Sanguinis Hominis. London, 1883. Wykeham Myers — Med. Eeport of Inspector-General of Customs. China, 1881. Sonsino —Med. Times and Gazette, i. 1882. Mackenzie — Path. Trans., vol. xxxiii. p. 394. IV. — Strongtltts Gigas. Davaine — Entozoaires. Synopsis 99, and p. 267. Cobbold — Parasites, p. 208. V. — Pentastoma Denticulatum. Davaine — Entozoaires, pp. Ixxxviii. and 293. Wagner — Archiv der Physiologische Heilkunde. 1862, p. 681. Cobbold — Parasites, p. 259. BIBLIOGRAPHY. G17 CHAPTER XIV. Anomaliks op Position, Form, anjj Numbicr of the Kidnkys. Chopart — Malad. d. Voies XJrinaires Edit, by S('ga]as. Paris, 18')"), p. -vS. Rayer — Malad. d. Reins, t. iii. 769. Durham — Guy's IIosp. Reports, 1860, p. 404. Rosenstein — Nierenkrankheiten. 2d ed., 474. Vogel — Krankh. d. Ilarnbcreitonden Organe. Erl., IHG^j, p. 706. Klebs— Handb. d. Path. Anat., p. 604. Ebsteiri — Ziomssen's Cyclop., Eng. Trans., vol. xv. p. 761. Ziegler— Lehrbuch d. Path. Anat., 1883, 2d vol., p. 391. Beamer — See Lancet, 1878, i. p. 581. ' Movable Kidneys. Hare— Med. Times and Gaz., 1858, i. p. 7 ; and 1860,1. p. 30 Oppolzer — Ibid., 1857, i. 575; and Clin. Europ., 1859, No. 2. Fritz — Archives Generales, Aug. and Sept. 1859. Henoch— Klinik. d. Unterleibs-Krankh. Berlin, 1858. Bd. iii. S. 367. Becquet — Archives Generales, Jan. 1865. Dietl— Wiener Med. Woch., 1864, p. 563. Rollet— Path. u. Therap. d. Beweg. Niere. Erlane-., 1866. Sawyer — Floating Kidney. Bi'i-mingham Med. Rev. Landau — Die Wanderniere der Frauen. Berlin, 1881. See, also, Med. Times and Gaz., 1882, i. p. 202. Report of Committee of Pathological Society. Path. Trans., xxvii. p. 467. Newman — On Malpositions of the Kidney. Glasgow Medical Journal, August, 1883 ; where, also, a complete account of the literature will be found. Cases— See Lancet, 1862, ii. p. 139 ;- 1863, i. p. 521; ii. p. 363; 1872, ii. p. 713; Med. Times and Gaz., 1857, p. 651 ; 1858, i. p. 331 ; ii. p. 36 ; 1859, ii. p. 426; 1860, i. p. 9; 1864, July 9; 1872, ii. p. 328; Midland Joiirn., Jan. 1858; Prag. Vierteljahrschr., Bd. 51; Yirchow's Archiv, Bd. Iii. S. 95; Berl. Klin. Wochenschr., 1866, iii. p. 41 ; Brit. Med. Journ., 1869, i. 541 ; ii. p. 211 ; 1870, i. p. 35; 1874, i. p. 453; Path. Soc. Trans., xvii. p. 165; Glasg. Med. Journ., 1870 (New Series), ii. 553. INDEX OF SUBJECTS. ABSCESS of the kidney, 449 Abscesses, multiple, in the kidney, 451 Acid of the urine, 77 Albumen in the urine, 185 forms of, 185 tests for, 186 quantitative estimation of, 190 clinical significance of, 194 causes of, 194 Albuminuria, functional, 196 permanent, 198 experiments on the production of, 199, 358 in diabetes, 250 in connection with pregnancy, 371 saturnine, 195 neurotic, 197 pathology of, 199 Alkaline urine, from ammonia, 82 from food, 77 from medicines, 80 from the cold bath, 81 from disease, 81 Amblyopia in Bright's disease, 418, 429 in diabetes, 255 Ammoniacal urine, 82 Amyjoid degeneration of the kidneys, 404 Amyloid substance in the liver, 265 Anazoturia, 223 Anomalies of position of the kidneys, 587 form of, 604 number of, 605 Apparatus for urine testing, 36 Azoturia, 131 BACILLUS of tubercle in urine, 555 Bacteruria, 177 Baruria, note, 131 Bile in urine, tests for, 47 Bilharzia ha^matobia, 575 Blood in urine. See Hematuria. tests for, 150 Bran cakes, 273 Bright's disease — general, 376 classification of, 377 general etiology of, 379 oneness or multiformity of, 403 secondary affections in, 419 Bright's disea.se — acute, 383 anatomical characters of, 383 course and symptoms of, 386 diagnosis of, 391 prognosis of, 392 etiology of, 392 treatment of, 393 Bright's disease — chronic, 396 anatomical changes in the kid- neys in, 396 granular kidney in, 399 smooth white kidney in, 396 lardaceous kidney in, 404 course and symptoms of, 407 duration of, 409 urine in, 414 dropsy in, 417 pulse in, 418 retina in, 418 complications of, 419 and phthisis, 420 and cardio-vascular changes, 424 diagnosis of, 437 prognosis of, 439 treatment of, 441 riALCULUS, indigo, 309 \J urinary, 292 general etiology of, 292 Calculi, urinary, 294 classification of, 294 origin and growth of, 296 varieties of, 297 diagnosis of species of, 309 medical treatment of, 311 preventive treatment of, 811 solvent treatment of, 315 renal. .SeeConcretionsintheKidneys blood and fibrinous, 307 prostatic, 309 Cancer of the kidney, 514 primary, 514 morbid anatomy of, 514 etiology of, 518 symptoms and signs of, 519 hjematuria in, 521 diagnosis of, 538 duration of, 522 treatment of, 536 secondary, 586 620 INDEX OF SUBJECTS. Cancerous matter in urine, 170 Carboluria, 48 Carbonate ., W. D. A Dictionary of the Terms Used in Medicine and the Collateral Sciences. Eevised, with numerous additions, by Isaac Hays, M. D., late editor of The American Journal of the Medical Sciences. In one large royal 12mo. volume of 520 double-columned images. Cloth, $1.50; leather, $2.00. It is the best book of definitions we have, and ought always to be upon the student's table. — Southern Medical and Surgical Journal. MOJDWELL, G. F., F. B. A. S., F. C, S., Lecturer on Natural Science at Clifton College, England. A Dictionary of Science : Comprising Astronomy, Chemistry, Dynamics, Elec- tricity, Heat, Hydrodynamics, Hydrostatics, Light, JSIagnetism, Mechanics, Meteorology, Pneumatics, Sound and Statics. Contributed by J. T. Bottomley, M. A., F. C. S., William Crookes, F.R.S., F.C.S., Frederick Guthrie, B.A., Ph. D., R. A. Proctor, B.A., F.E.A.S., «a. F. 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In one handsome 12mo. volume of 293 pages. Cloth, $2. Just ready. In the progress of physiological study no fact I of three or four which have been written within a was of greater moment, none more completely few years by American physicians. It is in several revolutionized the theories of teachers, than the respects the most complete. The volume, though discovery of the circulation of the blood. This small in size, is one of the most croditable con- explains the extraordinary interest it has to all tributionsfroman American pen to medical history medical historians. The volume before us is one | that has appeared. — Med. d- Surg. Rep., Dec. 6, 1884. ELLIS, GBOBGE VINEU, Emeritus Professor of Anatomy in TJniversity College, London. Demonstrations of Anatomy. Being a Guide to the Knowledge of the Human Body by Dissection. From the eiglith and revised London edition. In one very handsome octavo volume of 716 pages, witli 249 illustrations. Cloth, $4.25 • leather, $5.2o. JEtOBBBTS, JOHN B., A. M., 31. J>., P)-of. of Applied Anat. and Oper. Surg, in Phila. Polyclinic and Coll. for Graduates in Medicine. The Compend. of Anatomy. For use in the dissecting-room and in preparing for examinations. In one 16mo. volume of 196 pages. Lim^D cloth, 75 cents. DBAJPEM, JOMN C, 31. D,, LL. D., Professor of Chemistry in the University of the City of New York. Medical Physics. A Text-book for Students and Practitioners of Medicine. In one octavo volume of 725 pages, with 376 woodcuts, mostly original. Cloth, §4. In a few days: From the Preface. The fact that a knowledge of Physics is indispensable to a thorough understanding of Medicine has not been as fully realized in this country as in Europe, where the admirable works of Desplats and Gariel, of Robertson and of numerous German writers constitute a branch of educational literature to which we can show no parallel. A full appreciation of this the author trusts will be sufficient justification for i:)lacing in book form the sub- stance of his lectures on this department of science, delivered during manv rears at the University of the City of Kew York. Broadly speaking, this work aims to impart a knowledge of the relations existing between Physics and Medicine in their latest state of development, and to embody in the pursuit of this object whatever experience the author has gained during a long period of teaching this special branch of applied science. BOBBBTSON, J. 3IcGMBGOB, 3L A., IT. B., Muirhead Demonstrator of Physiology, University of Glasgoic. Physiological Physics. In one 12mo. volume of 537 pages, with 219 illustra- tions. Limp cloth, $2.00. Just ready. See Students' Series of Jfanuals, page 3. The title of this work sufficiently explains the ' ments. It will be found of great value to the nature of its contents. It is designed as a man- ; practitioner. It is a carefulh^ prepared book of ual for the student of medicine, an auxiliary to ; reference, concise and accurate, and as such we histext-bookinphysiology,anditwouldbepartieu- ' lieartily recommend it.— Journal of the American larly useful as a guide to his laboratory experi- , Medical Association, Dec. 6, 1884. BBLL, F. JBFFMBT, 31. A., Pi-ofessor of Comparative Anatomy at King's College, London. Comparative Physiology and Anatomy. Shortly. See Students' Series of 3Tanuals, page 3. 8 Lea Brothers & Co.'s Publications — Physiolog-y, Chemistry. DALTOJSr, JOSW C, M. D., Professor of Physiology in the College of Physicians and Surgeons, New York, etc. A Treatise on Human Physiology. Designed for the use of Students and Practitioners of Medicine. Seventh edition, thoroughly revised and rewritten. In one very handsome octavo volume of 722 pages, with 252 beautiful engravings on wood. Cloth, 15.00 ; leather, $6.00 ; very handsome half Eussia, raised bands, |6.50. The merits of Professor Dalton's text-book, his smooth' and pleasing style, the remarkable clear- ness of his descriptions, which leave not a cliapter obscure, his cautious judgment and the general correctness of his facts, are perfectly known. They have made his text-book the one most familiar to American students. — Med. Record, March 4, 1882. Certainly no physiological work has ever issued from the press that presented its subject-matter in a clearer and more attractive light. Almost every page bears evidence of the exhaustive revision that has taken place. The material is placed in a more compact form, yet its delightful charm is re- tained, and no subject is thrown into obscurity. Altogether this edition is far in advance of any previous one, and will tend to keep the profession posted as to the most recent additions to our physiological knowledge. — Miehiqan Medical News, April, 1882. One can scarcely open a college catalogue that does not have mention of Dalton's Physiology as the recommended text or consultation-book. For American students we would unreservedly recom- mend Dr. Dalton's work.- Fa. ilfed. if oni/ii^,July,'82. FOSTEB, MICHAEL, M. D., F. M, S., Professor of Physiology in Cambridge University, England. Test-Book of Physiology. Third American from the fourth English edition, with notes and additions by E. T. Eeiohert, M. D. In one handsome royal 12mo. volume of over 1000 pages, with about 300 illustrations. Cloth, $3.25 ; leather, $3.75. In a few days. A notice of the previous edition is appended. A more compact and scientific work on physiol- ogy has never Deen published, and we believe our- selves not to be mistaken in asserting that it has now ueen introduced into every medical college in which the English language is spoken. This work conforms to the latest researches into zoology and comparative anatomy, and takes into consid- eration the late discoveries in physiological chem- istry and the experiments in localization of Ferrier and others. The arrangement followed is such as to render the whole subject lucid and well con- nected in its various parts. — Chicago Medical Jowc nal and Examiner, August, 1882. FOWEM, HENMY, M, B., F, M. C, S., Examiner in Physiology, Royal College of Surgeons of Ejigland. Human Physiology. In one handsome pocket-size 12mo. volume of 396 pages, with 47 illustrations. Cloth, $1.50. See Students' Series of Manuals, page 3. The prominent character of this work is that of judicious condensation, in which an able and suc- cessful effort appears to have been made by its accomplished author to teach the greatest number of facts in the lewest possible words. The result is a specimen of concentrated intellectual pabu- lum seldom surpassed, which ought to be care- fully ingested and digested by every practitioner who desires to keep himself well informed upon this most progressive of the medical sciences. The volume is one which we cordially recommend to every one of our readers. — The American Jour- nal of the Medical Sciences, October, 1884. This little work is deserving of the nighest praise, and we can hardly conceive how the main facts of this science could have been more clearly or concisely stated. The price of the work is such as to place it within the reach of all, while the ex- cellence of its text will certainly secure for it most favorable commendation — Cincinnati Lancet and Clinic, Feb. 16, 1884. CABJPFJSTTFB, WM. B., 31. D., F. M. S., F. G. S., F. B. S.^ Registrar to the University of London, etc. Principles of Human Physiology. Edited by Henry Power, M. B., Lond., F. R. C. S., Examiner in Natural Sciences, University of Oxford. A new American from the eighth revised and enlarged edition, with notes and additions by Francis G. Smith, M. D., late Professor of the Institutes of Medicine in the University of Pennsylvania. In one very large and liandsome octavo volume of 1083 pages, with two plates and 373 illus- trations. Cloth, $5.50 ; leather, $6.50 ; half Eussia, $7. FOWNES, GEOMGE, Fh. J>. A Manual of Elementary Chemistry; Theoretical and Practical. Re- vised by Henry Watts, B. A., F. E. S. New American edition. In one large royal 12mo. volume of over 1000 pages, with 200 illustrations on wood and a colored plate. Cloth,. 12.75 ; leather, $3.25. In press. A notice of the previous edition is appended. The book opens with a treatise on Chemical of late years, the chapter on the General Principles Physics, including Heat, Light, Magnetism and of Chemical Philosophy has been entirely rewrit- Electricity. These subjects are treated clearly ten. The latest views on Equivalents, Quantiva- and briefly, but enough is given to enable the stu- lence, etc., are clearly and fully set forth. This dent to comprehend the facts and laws of Chemis- last edition is a great improvement upon its prede- try proper. It is the fashion of late years to omit cessors, which is saying not a little of a book that these topics from works on chemistry, but their has reached its twelfth edition.— OAio Medical Re- omission is not to be commended. As was required corder, Oct., 1878. by the great advance in the science of Chemistry Wohler's Outlines of Organic Chemistry. Edited by Fittig. Translated by Ira Remsen, M. D., Ph. D. In one 12mo. volume of 550 pages. Cloth, $3. GALLOWAY'S QUALITATIVE ANALYSIS. New I CARPENTER'SPRIZE ESSAY ONTHEUSEAND edition. Abuse of Alcoholic Liquors in Health and Dis- LEHMANN'S MANUAL OP CHEMICAL PHYS- ease. With explanations of scientific words. Small lOLOGY. In one octavo volume of 327 pages, 12mo, 178 pages. Cloth, 60 cents. with 41 illustrations. Cloth, S2.25. | 9 Lea Brothers & Co.'s Publications — CheraiHtry. FBANKLAND, B., I), 6.X., Jb\ U.S., &JAPP, Ph. J>., F, I. C\, Assist. I'm/, iif (;hi;rninlT School of Hciance, -y in the Normal London. Profesnor of Chr.mistri/ in the. Normal School of Science, Jjondon. Inorganic Chemistry. In one luindaome octavo volnme of 000 pagoH, with 51 woodcuts and 2 litliogriiphic pltitoH. Cloth, $1175; leather, |4. 75. TnprenH. This work on ch^iientary cherniKtry is hased upon princifjles of chxssification, nomen- clatui'o and notation which IiavcJheon proved by nearly twenty years experience in teaching to impart most readily a sound and accurate knowledge of the science. ATTFIELJy, jrOJIN,lPli' D., Profensor of Praciicnl Chemistry to the Pharmaceutical Society of Orcnt Britain, etc. Chemistry, General, Medical and Pharmaceutical ; Including the Chem- istry of the U. B. Pharraacopojia. A Manual of the General Principles of the Science, and their Application to Medicine and Pharmacy. A new American, from the tenth English edition, specially revised by the Author. In one handsome royal 12mo. volume of 728 pages, with 87 illustrations. Cloth, $2.50 ; leather, $3.00. to put himself in the stufle-nt's piano and to appre- ciate his stato of mind. — American Chcfnical Jour- nal, April, 1884. A text-book which passes through ten editions in sixteen years must have good qualities. This remark is certainly applicable to Attfield's Chem- istry, a booli which is so well Icnown that it is iiardly necessary to do more than note the appear- ance of this new and improved edition. It seems, however, desirable to point out that feature of the book which, in all probability, has made it so popular. There can be little doubt that it is its thoroughly practical character, tlie expression being used in its best sense. The author under- stands what the student ought to learn, and is able It is a book on which too much praise cannot be bestowed. As a text-book for medical sofiools it is unsurpassable in the present state of chemical science, and having been prepared with a special view towards medicine and pharmacy, it is alike indispensable to all persons eng.aged in those de- partments of science. It includes the whole chemistry of the lastl'harmacopoeia. — Pacific Medi- cal anil Siigrical Jnurnal, Jan. 1884. BLOXAM, CHABLFS X., Professor of Cliemistry in King's College, London, Chemistry, Inorganic and Organic. New American from the fifth Lon- don edition, thoroughly revised and much improved. In one very handsome octavo volume of 727 pages, with 292 illustrations. Cloth, $3.75; leather, $4.75. Comment from us on this standard work is al- most superfluous. It differs widely in scope and aim from that of Attfield, and in its way is equally beyond criticism. It adopts the most direct meth- ods in stating the principles, hypotlieses and facts of the science. Its language is so terse and lucid, and its arrangement of matter so logical in se- quence that the student never has occasion to complain that chemistry is a hard study. Much attention is paid to experimental illustrations of chemical principles and phenomena, and the mode of conducting these experiments. The book maintains the position it has always held as one of the best manuals of general chemistry in the Eng- lish language. — Detroit Lancet, Feb. 1S84. The general plan of this work remains the same as in previous editions, the evident oVjject being to give clear and concise descriptions of all known elements and of their most important compounds, with explanations of the chemical laws and principles involved. We gladly repeat now the opinion we expressed about a former edition, that we regard Bloxam's Chemistry as one ot the best treatises on general and applied chemistry. — American Jour, of Pharmacy, Dec. 1883. SIMON, W,, Ph, J}., M. n., Professor of Chemistry and Toxicology m the College of Physicians and Surgeons, Baltimore, and Professor of Chemistry in the Maryland College of Pharmacy. Manual of Chemistry. A Guide to Lectures and Laboratory work for Beginners in Chemistry. A Text-book, specially adapted for Students of Pharmacy and Medicine. In one 8vo. vol. of 410 pp., with 16 woodcuts and 7 plates, mostly of actual deposits, with colors illustrating 56 of the most important chemical reactions. Cloth, $3.00 ; also without plates, cloth, $2.50. Just ready. This book supplies a want long felt by students of medicine and pharmacy, and is a concise but thorough treatise on the subject. The long expe- rience of the author as a teacher in schools of medicine and pharmacy is conspicuous in the perfect adaptation of the work to Ine special needs of the student of these branches. The colored plates, beautifully executed, illustrating precipi- tates of various reactions, form a novel and valu- able feature of the book, and cannot fail to be ap- preciated by both student and teacher as a help over the hard places of the science.— 3/ari/^ana Medical Journal, Nov. 22, 1884. MFMSFW, IMA, M, D., Ph, !>., Professor of Chemistry in the Johj^ Hopkins University, Baltimore. Principles of Theoretical Chemistry, with special reference to the Constitu- tion of Chemical Compounds. Second and revised edition. In one handsome royal 12mo. volume of 240 pages. Cloth, $1.75. Just ready. The book is a valuable contribution to the chemi- cal literature of instruction. That in so few years a second edition has been called for indicates that many chemical teachers have been found ready to endorse its plan and to adopt its methods. lin this edition a considerable proportion of the book has been rewritten, much new matter lias been added and the whole has been brought up to date. We earnestly commend this book to every student of chemistry. The high reputation of the author assures its accuracy in all matters of fact, and its judicious conservatism in matters of theory, com- bined with the fulness with which, in a small compass, the present attitude of chemical science towards the constitution of compounds is con- sidered, gives ita value much beyond that accorded to the average text-books of the day. — American Journal of Science, March, 1884. 10 Lea Brothers & Co.'s Publications — Chemistry. CSABLES, T, CUANSTOVJSr, M. D., F, C, S., M. S., Formerly Asst. Prof, and Demonst. of Chemistry and Chemical Physics, Queen's College, Belfast. The Elements of Physiological and Pathological Chemistry. A Handbook for Medical Students and Practitioners. Containing a general account of Nutrition, Foods and Digestion, and the Chemistry of the Tissues, Organs, Secretions and Excretions of the Body in Health and in Disease. Together with the methods for pre- paring or separating their chief constituents, as also for their examination in detail, and an outline syllabus of a practical course of instruction for students. In one handsome octavo volume of 463 pages, witli 38 woodcuts and 1 colored plate. Cloth, |3.50. The work is thoroughly trustworthy, and in- formed throughout by a genuine scientific spirit. The author deals with the chemistry of the diges- tive secretions in a systematic manner, which leaves nothing to be desired, and in reality sup- plies a want in English literature. The book ap- pears to us to be at once full and systematic, and to show a just appreciation of the relative import- ance of the various subjects dealt with. — British Medical Journal, November 29, 18S4. Dr. Charles' manual admirably fulfils its inten- tion of giving his readers on the one hand a sum- mary, comprehensive but remarkably compact, of the mass of facts in the sciences which have be- come indispensable to the physician ; and, on the other hand, of a system of practical directions so minute that analj'ses often considered formidable may be pursued by any intelligent person. — Archives of Medicine, Dec. 1884. B.OFFMAWW, F., A.M., JPh.JD., & FOWFM F.B., Fh.D., Public Analyst to the State of Neio York. Prof, of Anal. Cheni. in the Phil. Coll. of Pharmacy. A Manual of Chemical Analysis, as applied to the Examination of Medicinal Chemicals and their Preparations. Being a Guide for the Determination of their Identity and Quality, and for the Detection of Impurities and Adulterations. For the use of Pharmacists, Physicians, Druggists and Manufacturing Chemists, and Pharmaceutical and Medical Students. Third edition, entirely rewritten and much enlarged. In one very handsome octavo volume of 621 pages, with 179 illustrations. Cloth, $4.25. We congratulate the author on the appearance of the third edition of this work, jiublished for the ■first time in this country also. It is admirable and the information it undertaljes to supi)ly is both extensive and trustworthy. The selection of pro- cesses for determining the purity of the substan- ces of which it treats is excellent and the descrip- tion of them singularly explicit. Moreover, it is exceptionally free from typographical^rrors. We have no hesitation in recommending it to those who are engaged either in the manufacture or the testing of medicinal chemicals. — London Pharma- ceutical Journal and Transactions, 1883. CLOWES, FMANK, D. Sc, London, Senior Science- Master at the High School, Newcastle-under-Lyme, etc. An Elementary Treatise on Practical Chemistry and Qualitative Inorganic Analysis. Specially adapted for use in the Laboratories of Schools and Colleges and by Beginners. Third American from the fourth and revised English edition. In one very handsome royal 12mo. volume of about 400 pages, with about 50 illustrations. Cloth, 12.50. In a few days. The d emand for four editions of this work proves the success of Professor Clowes' effort to provide a simple, concise and trustworthy guide to qualitative analysis. The use and preparation of apparatus, and the directions for working have been so fully and clearly detailed that the book is admirably adapted not onl}^ to relieve the teacher of unnecessary labor, but also to answer all the requirements of self-instruction. BALFF, CMAMLFS M., M. D., F. M. C. F., Assistaiit Physician at the London Hospital. Clinical Chemistry. In one pocket-size 12mo. volume of 314 pages, with 16 illustrations. Limp cloth, red edges, $1.50. See Students' Series of Manuals, page 3. This is one of the most instructive little works that we have met with in a long time. The author is a physician and physiologist, as well as a chem- ist, consequently the book is unqualifiedly prac- tical, telling the physician just what he ouglit to know, of the applications of chemistry in medi- cine. Dr. Ralfe is thoroughly acquainted with the latest contributions to his science, and it is quite refreshing to find the subject dealt with so clearly and simply, yet in such evident harmony with the modern scientific methods and spirit. — Medical Record, February 2, 1884. CLASSFJS-, ALFXANDFB, Professor in the Royal Polytechnic School, Aix-la-Chapelle. Elementary Quantitative Analysis. Translated, with notes and additions, by Edgar F. Smith, Ph. D., Assistant Professor of Chemistry in the Towne Scientific School, University of Penna. In one 12mo. volume of 324 ptges, with 36 illust. Cloth, |2.00. It is probably the best manual of an elementary nature extant insomuch as its methods are the best. It teaches by examples, commencing with single determinations, followed by separations, and then advancing to the analysis of minerals and such products as are met with in applied chemis- try. It is an indispensable book for students in chemistry. — Boston Journal of Chemistry, Oct. 1878. GBFFWF, WILLIAM M., M. D., Demonstrator of Chemistry in the Medical Department of the University of Pennsylvania. A Manual of Medical Chemistry. For the use of Students. Based upon Bow- man's Medical Chemistry. In one 12mo. volume of 310 pages, with 74 illus. Cloth, $1.75. It is a concise manual of three hundred pages, I the recognition of compounds due to pathological giving an. excellent summary of the best methods conditions. The detection of poisons is treated of analyzing the liquids and solids of the body, both with sufficient fulness for the purpose of thestu- forthe estimation of their normal constituents and | dentor practitioner. — Boston Jl. of C%e»i., June, '80. Lea Brothers & Co.'s Publications— Pharni., Mat. Med.,Therap. 11 PABJRISM, MDWAHn, Late Professor of the Theory and Practice of Pha/rmacy in the Philwlelphia Colleye of Pharmacy. A Treatise on Pharmacy : designed as a Text-book for the Student, and 'dn a Guide for the Physician and Pharmaceutist. Witli many Formulae and Prescriptions. Fifth edition, thoroughly revised, by Thomas S. Wikoani), Ph.G. In one liandsome octavo volume of 1093 i)ages, with 2-")6 illustrations. Cloth, $5 ; Icatlier, $6. No tlioronghgoing phannacistwill fail to posse.ss himself of so useful a guide to practice, and no physician who properly estimates Iho value of an accurate knowledge of the remedial agents em- ployed by him in daily practice, so far as their miscibility, compatibility and most effective meth- ods of combination are concerned, can afford to leave this work out of the list of their works of reference. The country practitioner, who must always bo in a measure his own pliarmacist, will find it indispensable. — Louisville Medical News, Each page bears evidence of tlie oaro bestowed upon it, and conveys vaUiablo information from the rich store of the editor's experience. In fact, all that relates to practical pharmacy— apparatus. processes and dispensing — has been arranged ana described with clearness in its various aspects, so as to afford aid and advice alike to the studentand to the practical pharmacist. The work is judi- ciously illustratea with good woodcuts — American Journal of Pharmacy, .Taniiai-y, IHSi. There is nothing to equal Parrish's PAar-wacj/ March 29, 1S84. I in this or any other language. — London Pharma- This well-known work presents itself now based ccutical Journal. upon the recently revised new Pharmacopceia. | BMUWTOJV, T, LAJUJEM, M, I),, Lecturer on Materia Medica and Therapeutics at St. Bartholomew's Hospital, London, etc. A Text-book of Pharmacology, Materia Medica and Therapeutics. In one handsome octavo volume of about 1000 pages, with over 200 illustrations. Cloth, $5.50 ; leather, $6.50. In press. It is with peculiar pleasure that the early appearance of this long expected work is announced by the publishers. Written hy the foremost authority on its subject in Eng- land, it forms a compendious treatise on materia medica, pharmacology, pharmacy, and the practical use of medicines in the treatment of disease. Space has been devoted to the fundamental sciences of chemistry, physiology and pathology, wherever it seemed necessary to elucidate the proper subject-matter of the book. A general index, an index of diseases and remedies, and an index of bibliography close a volume which will undoubtedly be of the highest value to the student, practitioner and pharmacist. HEMMAmS-, D}\ l7, Professor of Physiology in the University of Zurich. Experimental Pharm.aeology. A Handbook of Methods for Determining the Physiological Actions of Drugs. Translated, with the Author's permission, and with extensive additions, by Hobert Meade Smith, M. D., Demonstrator of Physiology in the Universitv of Pennsylvania. In one handsome 12mo. volume of 199 pages, with 32 illustrations. Cloth, $1.50. Prof Hermann's handbook, which Dr. Smith has translated and enriched with many valuable addi- tions, will be gladly welcomed by those engaged in this department of physiology. It is an excellent little book, full of concise information, and it should find a place in every laboratory. It ex- plains the various methods and instruments used, and points out what lines of investigation are to be pursued for studying different phenomena, and also how and what particularly to observe. — A/nerican Journal of the Medical Sciences, Jan. 18S1. MAISCH, JOJBTJSTM., JPhar, !>., Professor of Materia Medica and Botany in the Philadelphia College of Pharmacy. A Mianual of Organic Materia Medica; Being a Guide to Materia Medica of the Vegetable and Animal Kingdoms. For the use of Students, Druggists, Pharmacists and Physicians. New (second) edition. In one handsome royal 12mo. volume of 550 pages, with 242 illustrations. Cloth, $3.00. Just ready. This work contains the substance, — the practical "kernel of the nut" picked out, so that the stu- dent has no superfluous labor. He can confidently accept what this work places before him, without any fear that the gist of the matter is not in it. Another merit is that the drugs are placed before him in such a manner as to simplifj' very much the study of them, enabling the mind to grasp them more readily. The illustrations are most excellent, being very true to nature, and are alone worth the price of the book to the student. To the practical pnysician and pharmacist it is a valuable work for handy reference and for keeping fresh in the memory the knowledge of materia medica and botany already acquired. We can and do heartily recommend it. — Medical and Surgical Re- porter, Feb. 14, 1SS5. BRUCE, J, MITCSELL, M. J>., F, B. C. P., Physician and Lecturer oyi Materia Medica and Therapeutics at Charing Cross Hospital, London. Materia Medica and Therapeutics. An Introduction to Eational Treat- ment. In one pocket-size 12mo. volume of 555 pages. Limp cloth, $1.50, Just ready. See Students' Series of Manuals, page 3. One of the very latest works upon Materia j recommend it as one of the very best for either Medica and Therapeutics, replete with informa- medical student or practitioner of medicine. — tiou abreast -of the times, we unhesitatingly | Cincinnati Medical Keus, August, ISSi. GBIFFITS, MOBEBT EGLESFIELD, M. D, A Universal Formulary, containing the Methods of Preparing and Adminis- tering Officinal and other Medicines. The whole adapted to Physicians and Pharmaceut- ists. Third edition, thoroughly revised, with numerous additions, by Johjc M. IVIaisch, Phar. D., Professor of Materia Medica and Botany in the Philadelphia College of Pharmacy. In one octavo volume of 775 pages, with 3S illustrations. Cloth, $4.50 ; leather §5.50. 12 Lea Brothers & Co.'s Publications — Mat. Med., Therap. STILLB, A., M.I),,LL.J>., & MAISCM, J. M., JPJiar. D,, Professor Emeritus of the Theory and Prac- Prof, of Mat. Med. and Botany in Phila. tice of Medicine and of Clinical Medicine College of Pharmacy, Sec'y to the Ameri- in the University of Pennsylvania. can Pharmaceutical Association. The !N"ational Dispensatory : Containing the Natural History, Chemistry, Phar- macy, Actions and Uses of Medicines, including those recognized in the Pharmacopoeias of the United States, Great Britain and Germany, with numerous references to the French Codex. Third edition, thoroughly revised and greatly enlarged. In one magniiicent imperial octavo volume of 1767 pages, with 311 hne engravings. Cloth, $7.25; leather, $8.00 ; half Russia, open back, $9.00. With Denison's " Ready Keference Index " $1.00 in addition to price in any of above styles of binding. Just ready. In the j^resent revision the authors have labored incessantly with the view of making the third edition of The National Dispensatoby an even more complete represen- tative of the pharmaceutical and therapeutic science of 1884 than its first edition was of that of 1879. For this, ample material has been afforded not only by the new United States Pharmaco2)ceia, but by those of Germany and France, which have recently appeared and have been incorporated in the Dispensatory, together with a large number of new non- ofiicinal rem.edies. It is thus rendered the representative of the most advanced state of American, English, French and German pharmacology and therapeutics. The vast amount of new and important material thus introduced may be gathered from the fact that the additions to this edition amount in themselves to the matter of an ordinary full-sized octavo volume, rendering the work larger by twenty-five per cent, than the last edition. The Therapeutic Index (a feature peculiar to this work), so suggestive and convenient to the practitioner, contains 1600 more references than the last edition — the General Index 3700 more, making the total number of references 22,390, while the list of illustrations has been increased by 80. Every effort has been made to prevent undue enlargement of the volume by having in it nothing that could be regarded as superfluous, yet care has been taken that nothing should be omitted Avliich a pharmacist or physician could expect to find in it. The appearance of the work has been delayed by nearly a year in consequence of the determination of the authors that it should attain as near an approach to absolute ac- curacy as is humanly possible. With this view an elaborate and laborious series of examinations and tests have been made to verify or correct the statements of the Pharma- copceia, and very numerous corrections have been found necessary. It has thus been ren- dered indispensable to all who consult the Pharmacopoeia. The work is therefore presented in the full expectation that it will maintain the position universally accorded to it as the standard authority in all matters pertaining to its subject, as registering the furthest advance of the science of the day, and as embody- ing in a shape for convenient reference the recorded results of human experience in the laboratory, in the dispensing room, and at the bed-side. Comprehensive in scope, vast in design and splendid in execution, The JSTational Dispensatory may be justly regarded as the most important work of its kind extant. — Louisville Medical News, Dec. 6, 1884. We have much pleasure in recording the appear- ance of a third edition of this excellent work of reference. It is an admirable abstract of all that relates to chemistry, pharmacy, materia medica, pharmacology and therapeutics. It may be re- garded as embodying the Pharmaeopceias of the civilized nations of the world, all being brought up to date. The work has been very well done, a large number of extra-pharmacopoeial remedies having been added to those mentioned in previous editions. — London Lancet, Nov. 22, 1884. Its completeness as to subjects, the comprehen- siveness of its descriptive language, the thorough- ness of the treatment of the topics, its brevity not sacrificing the desirable features of information for which such a work is needed, make this vol- ume a marvel of excellence. — Pharmaceutical Re- cord, Aug. 15, 1884. FAMQVMAMSOW, BOBEMT, M. D., Lecturer on Materia Medica at St. Mary's Hospital Medical School. A Guide to Therapeutics and Materia Medica. Third American edition, specially revised by the Author. Enlarged and adapted to the U. S. Pharmacopoeia by Feank Woodbxjby, M. D. In one handsome 12mo. volume of 524 pages. Cloth, $2.25. Dr. Farquharson's Therapeutics is constructed upon a plan which brings before the reader all the essential points with reference to the properties of drugs. It impresses these upon him in such away as to enable him to take a clear view of the actions of medicines and the disordered conditions in which they must prove useful. The double-col- umned pages — one side containing the recognized physiological action of the medicine, and the other the disease in which observers (who are nearly al- ways mentioned) have obtained from it good re- sults — make a very good arrangement. The early chapter containing rules for prescribing is excel- lent. — Canada Med. and Surg. Journal, Dec. 1882. STILLJE, ALFMEJD, M, D., LL, !>,, Professor of Theory and Practice of Med. and of Clinical Med. in the Univ. ofPenna. Therapeutics and Materia Medica. A Systematic Treatise on the Action and Uses of Medicinal Agents, including their Description and History. Fourth edition, revised and enlarged. In two large and handsome octavo volumes, containing 1936 pages. Cloth, $10.00 ; leather, $12.00 ; very handsome half Russia, raised bands, $13.00. We can hardly admit that it has a rival in the in pharmacodynamics, but as by far the most eom- multitude of its citations and the fulness of its plete treatise upon the clinical and practical side research into clinical histories, and we mustassign of the question. — Boston Medical and Surgical Jour- it a place in the physician's library; not, indeed, nai, Nov. 5j 1874. as fully representin g the present state of knowledge Lea Brothers & Co.'s Publications — Pathol., HiHtol. 13 COATS, JOSBPJI, M. J>., I\ F. JP. S., Pathologist to the QlnHijow Wc.nlarn Injlrmnry. A Treatise on Pathology. In one very liandsome octavo volume of 829 pages, with 339 beautiful illustrations. Cloth, 15.50; leather, 10.50. The work before ns treats the snbjont of PaHi- ology more exteriHivcIy than it in usually treated in similar works. Medical students as well as physicians, wlio desire a worlc for study or refer- ence, tliat treats the sulijects in the various de- partments in a very thoro'ugli manner, biitwithout prolixity, will certainly give this one the prefer- ence to any with which wo are ac its dc- partmentof medicine, that is notas fully elucidated asourpre^ent knowli'dge will admit.— Cincinnati Medical Newn, Oct. laaa. GBBEIf, T. MBNIIY, M. J)., Lecturer on Patliologi/ mid Morbid AnaUnny at Charing-Cross Jlospilal Medical School, London. Pathology and Morbid Anatomy. Fifth American from the sixth revised and enlarged English edition. In one very liandsome octavo volume of 482 pages, with 150 fine engravings. Cloth, |2.50. Just ready. The fact that this woll-linown treatise lias so rapidly reached its sixth edition is a strong evi- dence of its popularity. The author is to be con- gratulated upon the thoroughness with which lie has prepared this work. It is thoroughly abreast with all the most recent advances in pathology. No work in the English language is so admirabljr adapted to the wants of the student and practi- tioner as this, and we would recommend it most earnestly to every one. — Nashville Journal of Medi- cine and Surijery, Nov. 1884. WOODHEAIf, G. SIMS, M, D., F. JR. C. J?. B., Demonstrator of Pathology in the University of Edinburgh. Practical Pathology. A Manual for Students and Practitioners. tiftil octavo volume of 497 pages, with 136 exquisitely colored illustrations. In one beau- Cloth, $6.00. It forms a real guide for the student and practi- tioner M'ho is thoroughly in earnest in his en- deavor to see for himself and do for himself. To the laboratoiy student it will be a helpful com- panion, and all those who may wish to familiarize themselves with modern methods of examining morbid tissues are strongly urged to provide themselves with this manual. The numerous drawings are not fancied pictures, or merely schematic diagrams, but they represent faithfully the actual images seen under the microscope. The author merits all praise for having produced a valuable work. — Medical Record, May 31, 1884. It is manifestly the product of one who ha> him- self travelled over the whole field and who is .'^killed not merely in the art of histology, but in tlie oV^ser- vation and interpretation of morbid changes. The work is sure to command a wide circulation. It should do much to encourage the pursuit of path- ology, since such advantages in histological study have never before been otfered. — The Lancet, Jan. 5, 1884. SCHAFBB, BJyWAMD A., F. B. S., Assistant Professor of Physiology in University College, London. The Essentials of Histology. In one octavo volume of about 300 pages, with about 325 illustrations. In press. COBWIL, v., and BAJSmBB, L., Prof, in the Faculty of Med. of Paris. Prof, in the College of France, A Manual of Pathological Histology. Translated, with notes and additions, by E. O. Shakespeare, M. D., Pathologist and Ophthalmic Surgeon to Philadelphia Hospital, and by J. Henry C. Simes, M. D., Demonstrator of Pathological Histology in the University of Pennsylvania. In one very handsome octavo volume of 800 pages, with 360 illustrations. Cloth, |5.50 ; leather, |6.50 ; half Kussia, raised bands, $7. KLBIJSr, B., M, D., F, B. S., Joint Lecturer on General Anat. and Phys. in the Med, School of St. Bartholomew's Hosp., London. Elements of Histology. Inonepocket-sizel2mo. volume of 360 pages, with 181 illus. Limp cloth, red edges, $1.50. See Students^ Series of Manuals, page 3. Although an elementary work, it is by no means superficial or incomplete, for the author presents in concise language nearly all the fundamental facts regarding tlie microscopic structure of tissues. The illustrations are numerous and excellent. We commend Dr. Klein's Elements most' heartily to the student. — Medical Becord, Dec. 1, 1883. FBFFBB, A. J., M. B., M. S., F. B, C, S., Surgeon and Lecturer at St. Mary''s Hospital, London, Surgical Pathology. In one pocket-size 12mo. volume of 511 pages, with 81 illustrations. Limp cloth, red edges, $2.00. See Students' Series ofllanuais, page 3. It is not pretentious, but it will serve exceed- ingly well as a book of reference. It embodies a great deal of matter, extending over the whole field of surgical pathology. Its form is practical, its language is clear, and the information set forth is well-arranged, well-indexed and well- illustrated. The student will find in it nothing that is unnecessary. The list of subiects covers the whole range of surgery. The book supplies a very manifest want and should meet with suc- cess. — New York Medical Journal, May 31, 1SS4. SCHAFER'S PRACTICAL HISTOLOGY. In one I OGT. Translated by Joseph Leidt, M. D. In one handsome royal 12mo. volume of 308 pages, with I volume, very large imperial quarto, with 32© 40 illustrations. 1 copper-plate figures, plain and colored and des- GLUGE'S atlas of pathological HISTOL- I cnptive lett€r-prese. Cloth, $4.00. 14 Lea Brothers & Co.'s Publications — Practice of Med. FLINT, AUSTIN, M. !>., Prof, of the Principles a?id Practice of Med. and of Clin. Med, in Bellevue Hospital Medical College, N. F. A Treatise on the Principles and Practice of Medicine. Designed for the use of Students and Practitioners of Medicine. With an Appendix on the Eesearches of Koch, and their bearing on the Etiology, Pathology, Diagnosis and Treatment of Phthisis. Fifth edition, revised and largely rewritten In one large and closely-printed octavo volume of 1160 pages. Cloth, $5.50 ; leather, $6.50 ; half Eussia, $7. Koch's discovery of the bacillus of tubercle gives promise of being ^ the greatest boon ever conferred by science on humanity, surpassing even vaccination in its benefits to mankind. In the appendix to his work, Professor Flint deals with the subject from a practical standpoint, discussing its bearings on the etiology, pathology, diagnosis, prog- nosis and treatment of pulmonary phthisis. Thus enlarged and completed, this standard work will be more than ever a necessity to the physician who duly appreciates the re- sponsibility of his calling. A well-known writer and lecturer on medicine recently expressed an opinion, in the highest de- gree complimentary of the admirable treatise of Dr. Flint, and in eulogizing it, he described it ac- curately as "readable and reliable." No text-book is more calculated to enchain the interest of the student, and none better classifies the multitudi- nous subjects included in it. It has already so far won it3 way in England, that no inconsiderable number of men use it alone in the studyof pure medicine; and we can say of it that it is in every way adapted to serve, not only as a complete guide, but also as an ample instructor in the science and practice of medicine. The style of Dr. Flint is always polished and engaging. The work abounds in perspicuous explanation, and is a most valuable text-book of medicine. — London Medical Neics. This work is so widely known and accepted as the best American text-book of the practice of medicine that it would seem hardly worth while to give this, the fifth edition, anything more than a passing notice. But even the most cursory exami- nation shows that it is, practically, much more than a revised edition ; it is, in fact, rather a new work throughout. This treatise will undoubtedly continue to hold the first place in the estimation of American physicians and students. No one of our medical writers approaches Professor Flint in clearness of diction, breadth of view, and, what we regard of transcendent importance, rational esti- mate of the value of remedial agents. It is thor- oughly practical, therefore pre-eminently the book for American readers. — St. Louis Clin, Bee, Mar. '81. MAMTSMORNE, MBNRT, M. J>., LL. !>., Lately Professor of Hygiene in the University of Pennsylvania. Essentials of the Principles and Practice of Medicine. A Handbook for Students and Practitioners. Fifth edition, thoroughly revised and rewritten. In one royal 12mo. volume of 669 pages, with 144 illustrations. Cloth, $2.75 ; half bound, $3.00. Within the compass of 600 pages it treats of the history of medicine, general pathology, general symptomatology, and physical diagnosis (including laryngoscope, ophthalmoscope, etc.), general ther- apeutics, nosology, and special pathology and prac- tice. There is a wonderful amount of information contained in this work, and it is one of the best of its kind that we have seen. — Glasgow Medical Journal, Nov. 1882. An indispensable book. No work ever exhibited a better average of actual practical treatment than this one ; and probably not one writer in our day had a better opportunity than Dr. Hartshorne for condensing all the views of eminent practitioners into a 12mo. The numerous illustrations will be very useful to students especially. These essen- tials, as the name suggests, are not intended to supersede the text-books of Flint and Bartholow, but they are the most valuable in aflfbrding the means to see at a glance the whole literature of any disease, and the most valuable treatment. — Chicago Medical Journal and Examiner, April, 1SS2. BMISTOWE, JOHN STEM, 31, 2>., F. jK. C. F,, Physician and Joint Lecturer on Medicine at St. Thomas' Hospital. A Treatise on the Practice of Medicine. Second American edition, revised by the Author. Edited, with additions, by James H. Hutchinson, M.D., physician to the Pennsylvania Hospital. In one handsome octavo volume of 1085 pages, with illustrations. Cloth, $5.00 ; leather, $6.00 ; very handsome half Eussia, raised bands, $6.50. The reader will find every conceivable subject I are appropriate and practical, and greatly add to connected with the practice of medicine ably pre- its usefulness to American Tea,deTS.— Buffalo Med- sented, in a style at once clear, interesting and ical and Surgical Journal, March, 1880. concise. The additions made by Dr. Hutchinson | WATSON, SIM TM03IAS, M. !>., Late Physician in Ordinary to the Queen. Lectures on the Principles and Practice of Physic. A new American from the fifth English edition. Edited, with additions, and 190 illustrations, by Henry Habtshoene, a. M., M. D., late Professor of Hygiene in the University of Pennsylvania. In two large octavo volumes of 1840 pages. Cloth, $9.00 ; leather, $11.00. LECTURES ON THE STUDY OF FEVER. By A. HiTDSON, M. D., M. R. I. A. In one octavo volume of 308 pages. Cloth, $2.50. STOKES' LECTURES ON FEVER. Edited by John William Moore, M. D., F. K. Q. C. P. In one octavo volume of 280 pages. Cloth, $2.00. A TREATISE ON FEVER. By Robert D. Lyons, K. C. C. In one 8vo. vol. of 354 pp. Cloth, $2.25. LA ROCHE ON YELLOW FEVER, considered in its Historical, Pathological, Etiological and Therapeutical Relations. In two large and hand- some octavo volumes of 1468 pp. Cloth, $7.00. A CENTURY OF AMERICAN MEDICINE, 1776—1876. By Drs. E. H. Clarke, H. J. BiGELOw, S. D. Gross, T. G. Thomas, and J. S. Billings. In one 12mo. volume of 370 pages. Cloth, $2.25. Lea Brotheus & Co.'s Publications — Systems of Med. 1 5 For Hale hy Suhscriptiovi Oiiily. A System of Practical Medicine. BY AMERICAN AUTHORS. Edited by WILLIAM PEPPER, M. D., LL. D., • PROVOST AND PKOFESSOR OF THE THEORY AND PRACTICE OP MEDICINE AND OF CLINICAL MEDICINE IN THE XJNIVEliSITY OF PENNSYLVANIA, Assisted by Louis Starr, M. D., Clinical Professor of the Diseases of Children in the Hospital of the University of Pennsylvania. In five imperial octavo volumes, conhdninc/ about 1100 pages each, with illustrations. Price per volume, cloth, $5 ; leather, $6 ; half Russia, raised hands and open buck, $7. Volume I. (General Pathology, Sanitary Science and General Diseases) contains 1094 pages, with 24 illustrations and is ju'st ready. Volume II. (General Diseases [con- tinued] and Diseases of the Digestive System) will be ready June 1st, and the subsequent volumes at intervals of four months thereafter. The publishers feel pardonable pride in announcing this magnificent work. For three years it has been in active preparation, and it is now in a sufficient state of forward- ness to .justify them in calling the attention of the profession to it as the work in which for the first time American medicine is thoroughly represented by its worthiest teachers, and presented in the full development of the practical utility which is its preeminent characteristic. The most able men — from the East and the AVest, from the North and the South, from all the prominent centres of education, and from all the hospitals which afford special opportunities of study and practice — have united in generous rivalry to bring together this vast aggregate of specialized experience. The distinguished editor has so apportioned the work that each author has had assigned to him the subject which he is peculiarly fitted to discuss, and in which his views will be accepted as the latest expression of scientific and practical knowledge. The practitioner will therefore find these volumes a complete, authoritative and unfailing work of reference, to which he may at all times turn with full certainty of finding what he needs in its most recent aspect, whether he seeks information on the general principles of medi- cine, or minute guidance in the treatment of special disease. So wide is the scope of the work that, with the exception of midwifery and matters strictly surgical, it embraces the whole domain of medicine, including the departments for which the physician is accustomed to rely on special treatises, such as diseases of women and children, of the genito-urinary organs, of the skin, of the nerves, hygiene arid sanitary science, and medical ophthalmology and otology. Moreover, authors have inserted the formulas which they have found most efficient in the treatment of the various affections. It may thus be truly regarded as a Complete Library of Practical Medicine, and the general practitioner possessing it may feel secure that he will require little else in the daily round of professional duties. In spite of every effort to condense the vast amount of practical information fur- nished, it has been impossible to present it in less than 5 large octavo volumes, containing about 5500 beautifully printed pages, and embodying the matter of about 15 ordinary octavos. Illustrations are introduced wherever they serve to elucidate the text. As material for the work is substantially complete in the hands of the editor, the pro- fession may confidently await the appearance of the remaining volumes upon the dates above specified. A detailed pi'ospectus of the work will be sent to any addi-ess on appli- cation to the publishers. It is a large undertaking, but quite justifiable in this country as authorities on the particular topics the case of a progressive nation like the United on which they deal, whilst the others show by the ■States. At any rate, if we may judge of future way they have handled their subjects that they Tolumes from the first, it will be justified by the are fully equal to the task they had undertaken, result. We have nothing but praise to bestow * * * ' A work which we cannot doutet will make upon the work. The articles are the work of a lasting reputation for itself. — London Medical writers, many of whom are already recognized in \ Times and Gazette, May 9, 18S5. BJEYWOZDS, J. MUSS JELL, M, J>., Professor of the Principles and Practice of Medicine in University College, London. A System of Medicine. With notes and additions by Henry Hartshorne, A. M., M. D., late Professor cf Hygiene in the University of Pennsylvania. In three large and handsome octavo volumes, containing 3056 double-columned pages, with 317 illustra- tions. Price per volume, cloth, $5.00 ; sheep, |6.00 ; very handsome half Eussia, raised bands, $6.50. Per set, cloth, $15 ; leather, $1S ; half Kussia, $19.50. Sold only by subscription. There is no medical work which we have in 1 himself in need of. In order that any deficiencies times past more frequently and fully consulted i mav be supplied, the publishers have committed when perplexed by doubtsf as to treatment, or bv ; the preparation of the book for the press to Dr. having unusual or apparently inexplicable svmp- Henrv Hartshorne. whose judicious notes distrib- toms presented to us, than "Reynolds' System of uted 'throughout the volume afford abundant evi- Medicine." It contains just that kind of informa- denee of the thoroughness of the revision.— .i*H«r- tion which the busy practitioner frequently finds icnn Journcl of the Medical Sciences, Jan. 1880. 16 Lea Brothers & Co.'s Publications — Clinical Med., etc. STILLB, ALFUBJy, M. D., XX. D., Professor Emeritus of the Theory and Practice of Med. and of Clinical Med. in the Univ. of Penna. Cholera: Its Origin, History, Causation, Symptoms, Prevention and Treatment. In one handsome 12mo. volume of about 175 pages, with a chart. Cloth, $1.25. Shortly. The threatened importation of cholera into the country renders peculiarly timely this work of an authority so eminent as Professor Stills. The history of previous epi- demics, their modes of propagation, the vast recent additions to our knowledge of the causation, prevention and treatment of the disease, all have been handled so skilfully as to present witji brevity the information which every practitioner should possess in ad- vance of a visitation. FLINT, AUSTIN, M, X>. Clinical Medicine. A Systematic Treatise on the Diagnosis and Treatment of I>iseases. Designed for Students and Practitioners of Medicine. In one large and hand- some octavo volume of 799 pages. Cloth, $4.50 ; leather, $5.50 ; half Eussia, $6.00. It is here that the skill and learning of the great •clinician are displayed. He has given us a store- feiouse of medical knowledge, excellent for the stu- dent, convenient for the practitioner, the result of sl long life of the most faithful clinical work, col- Bected by an energy as vigilant and systematic as ffiintiring, and weighed by a judgment no less clear &han his observation is close. — Archives of Medicine, Dec. 1879. To give an adequate and useful conspectus of the •extensive field of modern clinical medicine is a task •of no ordinary difficulty; but to accomplish this con- sistently with brevity and clearness, the different subjects and their several parts receiving the attention which, relatively to their importance, medical opinion claims for them, is still more diffi- cult. This task, we feel bound' to say, has been executed with more than partial success by Dr. Flint, whose name is already familiar to students of advanced medicine in this country as that of the author of two works of great merit on special subjects, and of numerous papers exhibiting much originality and extensive research. — 2 he Dublin Journal, Dec. 1S79. By the Same Author. Essays on Conservative Medicine and Kindred Topics. In one very hand- some royal 12mo. volume of 210 pages. Cloth, $1.38. JBMOADBBJSTT, W. S., M. X>., M M. C. I*., Physician to and Lecturer on Medicine at St. Mary^s Hospital. The Pulse. In one 12mo. volume. See Series of Clinical Manuals, page 3. ^CSMEIBBM, DM, JOSMBH, A Manual of Treatment by Massage and Methodical Muscle Ex- ercise. Translated by Waltek Mendelson, M. D., of New York. In one handsome octavo volume of about 300 pages, with about 125 fine engravings. Preparing. FINLAYSON, JAMBS, 31. D., Editor, Physician and Lecturer on Clinical Medicine in the Glasgow Western Infirmary, etc. Clinical Diagnosis. A Handbook for Students and Practitioners of Medicine. With Chapters by Prof. Gairdner on the Physiognomy of Disease ; Prof. Stephens on Diseases of the Female Organs; Dr. Robertson on Insanity; Dr. Gemmell on Physical Diagnosis ; Dr. Coats on Laryngoscopy and Post-Mortem Examinations, and by the Editor on Case-taking, Family History and Symptoms of Disorder in the Various Systems. In one handsome 12mo. volume of 546 pages, with 85 illustrations. Cloth, $2.63. This is one of the really useful books. It is at- tractive from preface to the final page, and ought to be given a place on every office table, because it contains in a condensed form all that is valuable in semeiology and diagnostics to be found in | Jan. 1879. bulkier volumes; and because of its arrangement and complete index it is unusually convenient for quick reference in any emergency that may come upon the busy practitioner. — N. C, Med. Journ., FBNWICK, SAMUBL, 31. D., Assistant Physician to the London Hospital. The Student's Guide to Medical Diagnosis. From the third revised a,nd enlarged English edition. In one very handsome royal 12mo. volume of 328 pages, with 87 illustrations on wood. Cloth, $2.25. TANNBM, TM03IAS MAWKBS, M. D. A Manual of Clinical Medicine and Physical Diagnosis. Third American from the second London edition. Eevised and enlarged by TiiiBUKY Fox, M. D., Phy- sician to the Skin Department in University College Hospital, London, etc. In one small 12mo. volume of 362 pages, wjth illustrations. Cloth, $1.50. FOTMBMGILZ, J. 31., 31. D., Bdin., 31. JR. C. P., Lond., Physician to the City of London Hospital for Diseases of the Chest. The Practitioner's Handbook of Treatment ; Or, The Principles of Thera- peutics. New edition. In one octavo volume. Preparing. STURGES' INTRODUCTION TO THE STUDY OF CLINICAL MEDICINE. Being a Guide to the Investigation of Disease. In one handsome ,12mo. volume of 127 pages. Cloth, $1.25. DAVIS' CLINICAL LECTURES ON VARIOUS IMPORTANT DISEASES. By N. S. Davis, M. D. Edited by Frank H. Davis, M. D. Second edition. 12mo. 287 pages. Cloth, $1.75. Lea Brothers & Co.'b Publications — Hygiene, Eleetr., I*ract. 17 BICHAJinSON, J?. TF., 31. A., M.D,, LL, J>., F.ll.S., F,S,A, Fellow of the Royal CoUcr/e of Physicians, London. Preventive Modicine. In one octavo volume of 729 pages. Cloth, $4; leather, $5; very handsome lialfKiiKHia, raised bands, I^.^O. Dr. Richardson has Hiicceedcd in producing a j the quoslion of dlflcaselflcomprehenBlve, masterly worlc wliich isi elovaU^din conf.f.ption, cnmproyif'n- find fully ahroftst with tho latest and best knowl- sive in sn,opo,s('i(uitifi() in character, syst(irnatio in '•' — '" " " •■"'■ ' — ' " ""'■ —"-"■•-'■'• arrangement, and which is written in a clear, eon- ., Prof, of Blatcria Medic.a and General T lierapeulics in the Jefferson Med. Coll. of Phil a., etc. Medical Electricity. A Practical Treatise on the Applications of Electricity to Medicine and Surgery. Second edition. In one very handsome octavo volume of 292 pages, with 109 illustrations. Cloth, $2.50. The second edition of this woi-k following so soon upon the first would in itself appear to be a sufficient announcement; nevertheless, tlie text has been so considerably revised and condensed, and so much enlarged by the addition of new mat- ter, that we cannot fail to recognize a vast improve- ment upon the former work. The author has pre- pared his work for students and practitioners — for those who have never acquainted themselves with the subject, or, having done so, find that after a time their knowledge needs refreshing. We think he has accomplished this object. The book is not too voluminous, but is thoroughly practical, sim- ple, complete and comprehensible. It is, more- over, replete with numerous illustrations of instru- ments, appliances, etc. — Medical Record, November 15, 1882. A most excellent work, addressed by a practi- tioner to his fellow-practitioners, and therefore thoroughly practical. The work now before us has the exceptional merit of clearly pointing out where the benefits to be derived from electricity must come. It contains all and everything that the practitioner needs ill order to understand in- telligently the nature and laws of the agent he is makmg use of, and for its proper application in practice. In a condensed, practical form, it pre- sents to the physician all that he would wish to remember after perusing a whole library on medical electricity, including the results of the latest in- vestigations. It is the book for the practitioner, and tlie necessity for a second edition proves that it has been appreciated by the profession. — Physi- cian and Surgeon, Dec. 1882. TMB YEAB'BOOK OF TBEAT3IENT. A Comprehensive and Critical Review for Practitioners of Medi- cine. In one 12mo. volume of 320 pages, bound in limp cloth, with red edges, $1.25. This work presents to the practitioner not only a complete classified account of all the more important advances made in the treatment of Disease during the year ending Sept. 30, 1884, but also a critical estimate of the same by a competent authority. Each department of practice has been fully and concisely treated, and into the consideration of each subject enter such allusions to recent pathological and clinical work as bear directly upon treatment. As the medical literature of all countries has been placed under contri- bution, the references given throughout the work, together with the separate indexes of subjects and authors, will serve as a guide for those who desire to investigate any thera- peutical topic at greater length. The contributions are from the pens of the following well-known gentlemen: — J. Mitchell Bruce, M.D. ; T. Lauder Brunton, M.D., F.R.S. ; Thomas Bryant, F.R. C.S.; F. H. Champneys, M.B. ; Alfred Cooper, F.R.C.S. ; Sidney Coupland, M.D. ; Dyce Duckworth, M.D. ; George P. Field, M.R.C.S. ; Reginald Harrison, F.R. C.S. ; J. Warrington Haward, F.R.C.S. ; F. A. Mahomed, M.B. ; Malcolm Morris, F.R.C.S., Ed. ; Edmund Owen, F.R.C.S. ; R. Douglas Powell, M.D. ; Henry Power, M.B., F.R.C.S.; C. H. Ralfe, M.D. ; A. E. Sansom, M.D.; Felix Semon, M.D.; Walter G. Smith, M.D. ; J. Knowsley Thornton, M.B. ; Frederick Treves, F.R.C.S. ; A. DE Watteville, M.D. ; John Williams, M.D. MABBBSBCOJSr, S. O., 31. B., Senior Physician to and late Led. on Principles and Pi-actice of Med. at O-uy's Hospital, London. On the Diseases of the Abdomen ; Comprising those of the Stomach, and other parts of the Alimentary Canal, CEsophagus, Caecum, Intestines and Peritoneum. Second American from third enlarged and revised English edition. In one handsome octavo volume of 554 pages, with illustrations. Cloth, $3.50. PAVY'S treatise ON THE FUNCTION OF DI- GESTION; its Disorders and their Treatment. From the second London edition. In one octavo volume of 238 pages. Cloth, $2.00. CHAMBERS' MANUAL OF DIET AND REGIMEN IN HEALTH AND SICKNESS. In one hand- some octavo volume of 302 pp. Cloth, 82.75. BARLOW'S MANUAL OF THE PRACTICE OF MEDICINE. With additions by D. F. Cokdie, M. D. 1 vol. 8vo., pp. 603. Cloth, S2.50. TODD'S CLINICAL LECTURES ON CERTAIN ACUTE DISEASES. In one octavo volume of 320 pages. Cloth, $2.50. HOLLAND'S MEDICAL NOTES AND REFLEC- TIONS. 1 vol. 8vo., pp. 493. Cloth, $3.50. 18 Lea Brothers & Co.'s Publications — Throat, liiings, Heart. COHEN, J. SOLIS, M. J>., Lecturer on Laryngoscopy and Diseases of the Throat and Chest in the Jefferson Medical College. Diseases of the Throat and Nasal Passages. A Guide to the Diagnosis and Treatment of Affections of the Pharynx, CEsophagus, Trachea, Larynx and Nares. Third edition, thoroughly revised and rewritten, with a large number of new illustrations. In one very handsome octavo volume. Preparing. SBILBJR, CARL, M. D., Lecturer on Laryngoscopy in the University of Pennsylvania. A Handbook of Diagnosis and Treatment of Diseases of the Throat, Nose and Naso-Pharynx. Second edition. In one handsome royal 12mo. volume of 294 pages, with 77 illustrations. Cloth, ipl.75. It is one of the best of the practical test-books I the essentials of diagnosis and treatment in dis- on this subject -with which we are acquainted. The eases of the throat and nose. The art of laryngos- present edition has been increased in size, but its copy, the anatomy of the throat and nose and the eminently practical character has been main- j pathology of the mucous membrane are discussed tained. Many new illustrations have also been with conciseness and ability. The work is pro- introduced, a ease-record sheet has been added, ] fusely illustrated, excels in many essential feat- and there are a valuable bibliography and a good j ures, and deserves a place in the office of the index of the whole. For any one who wishes to i practitioner who would inform liimself as to the make himself familiar with the practical manage- I nature, diagnosis and treatment of a class of dis- ment of cases of throat and nose disease, the book eases almost inseparable from general medical will be found of great value.— iVei« York Medical practice. With advanced students the book must Journal, June 9, 1883. he very popular on account of its condensed style. The work beforp .^^ i.? a concise handbook upon 1 — Louisville Medical News, June 26, 1883. BMOWJVB, LMNNOX, F. B, C. S., Bdin., Senior Surgeon to the Central London Tliroat and Ear Hospital, etc. The Throat and its Diseases, Second American from the second English edi- tion, thoroughly revised. With 100 typical illustrations in colors and 50 wood engravings, designed and executed by the Author. In one' very handsome imperial octavo volume of about 350 pages. Preparing. FLINT, AUSTIN, M. D., Professor of the Principles and Practice of Medicine in Bellevue Hospital Medical College, N. T. A Manual of Auscultation and Percussion ; Of the Physical Diagnosis of Diseases of the Lungs and Heart, and of Thoracic Aneurism. Third edition. In one hand- some royal 12mo. volume of 240 pages. Cloth, $1.63. It is safe to say that there is 'not in the English language, or any other, the equal amount of clear, exact and comprehensible information touching the physical exploration of the chest, in an equal number of words. Professor Flint's language is precise and simple, conveying without dubiety the results of his careful study and ample ex- perience in such wise that the young will find it the best source of instruction, and the old the most pleasant means of reviving and complementing their knowledge. — American Practitioner, June, 1883. BY THE SAME A UTHOR. Physical Exploration of the Lungs by Means of Auscultation and Percussion. Three lectures delivered before the Philadelphia County Medical Society, 1882-83. In one handsome small 12mo. volume of 83 pages. Cloth, |1.00. A Practical Treatise on the Physical Exploration of the Chest and the Diagnosis of Diseases Affecting the Respiratory Organs. Second and revised edition. In one handsome octavo volume of 591 pages. Cloth, $4.50. Phthisis: Its Morbid Anatomy, Etiology, Symptomatic Events and Complications, Fatality and Prognosis, Treatment and Physical Diag- nosis ; In a series of Clinical Studies. In one liandsome octavo volume of 442 pages. Cloth, $3.50. A Practical Treatise on the Diagnosis, Pathology and Treatment of Diseases of the Heart. Second revised and enlarged edition. In one octavo volume of 550 pages, with a ]3late. Cloth, $4. QMOSS, S. B., M.B., LL.B,, B.C.L. Oocon., LL.B, Cantab. A Practical Treatise on Foreign Bodies in the Air-passages. Intone octavo volume of 452 pages, Avith 59 illustrations. Cloth, $2.75. FULLER ON DISEASES OP THE LUNGS AND AIR-PASSAGES. Their Pathology, Physical Di- agnosis, Symptoms and Treatm^ent. From the second and revised English edition. In one octavo volume of 475 pages. Cloth, $3.50. SLADE ON DIPHTHERIA; its Nature and Treat- ment, with an account of the History of its Pre- valence in various Countries. Second and revised edition. In one 12mo. vol., pp. 1.5S. Cloth, $1.25. WALSHB ON THE DISEASES OF THE HEART AND GREAT VESSELS. Third American edi- tion. In 1 vol. 8vo., 416 pp. Cloth, $3.00. SMITH ON CONSUBIPTION; its Early and Reme- diable Stages. 1 vol. 8vo., pp. 253. Cloth, $2.25. LA ROCHE ON PNEUMONIA. 1 vol. Svo. of 490 pages. Cloth, $3.00. WILLIAMS ON PULMONARY CONSUMPTION; its Nature, Varieties and Treatment. With an analysis of one thousand cases to exemplify its duration. In one Svo. vol. of 303 pp. Cloth, $2.50. JONES' CLINICAL OBSERVATIONS ON FUNC- TIONAL NERVOUS DISORDERS. Second Am- erican edition. In one handsome octavo volume of 340 pages. Cloth, $3.25. Lea Brothers & Co.'s Publications — Nerv. and Ment. Dis.,;etc. 19 MITCHELL, S. WBIB, M. J>., Physician to Orthopaadic Hospital and the Infirmary for Diseases of the Nervous System, PhiUi., etc. Lectures on Diseases of the Nervous System; EHpecially in Women. Second edition. In one 12mo. volume of 288 pages. Cloth, §1.7.0. JvM rejuly. So great have been the achievements of the system perfected by the author for the treat- ment of hysterical and nervoii.s di.seaHOH that the profcKHJon will welcome the second and enlarged edition of a work which gives in detail the methods of enforced rest, massas^c and systematic feeding on wliich thia mode of treatment is based. Many of these lectures are original studies of well-known diseases, and others deal with suljijects which have been hitherto slighted in medical literature or which are almost unknown to it. The interest lies in the keen insight into the nature of the subject and in the suggeHtions which the author manages to throw into his accounts. The lectures must command the thoughtful attention and careful study of all who desire to rciid what is best in medical science.— JT/ie Loiulon Lancet, JMay Ki, 1S80. HAMILTOlSr, ALLAJ^ lIcLAWJE, M. D., Attending Physician at the Hospital for Epileptics and Paralytics, BlackweWs Island, N. Y. Nervous Diseases ; Tlieir Description and Treatment. Second edition, thoroughly revised and rewritten. In one octavo volume of 598 pages, with 72 illustrations. Cloth, $4. When the first edition of this good book appeared we gave it our emphatic endorsement, and the E resent edition enhances our appreciation of tlie ook and its author as a safe guide to students of clinical neurology. One of the best .and most critical of English neurological 'ournals, Brain, has characterized this book as the best of its kind In any language, which is a handsome endorsement from an' exalted source. The improvements in the new edition, and the additions to it, will justify its purchase even by those who po.ssess the old. — Alienist and Neurologist, April, 1882. TTIKE, DANIEL MACK, 31. I)., Joint Author of The Manual of Psychological Medicine, etc. Illustrations of the Influence of the Mind upon the Body in Health and Disease. Designed to elucidate the Action of the Imagination. New edition. Thoroughly revised and rewritten. In one handsome octavo volume of 467 pages, with two colored plates. Cloth, $3.00. It is impossible to peruse these interesting chap- ters without being convinced of the author's per- fect sincerity, impartiality, and thorough mental grasp. Dr. Tuke has exhibited the requisite amount of scientific address on all occasions, and the more intricate the phenomenathe more firmly has he adhered to a physiological and rational method of interpretation. Guided by an enlight- ened deduction, the author has reclaimed for science a most interesting domain in psychology, previously abandoned to charlatans and empirics. This book, well conceived and well written, must commend itself to every thoughtful understand- ing. — Neiv York Medical Journal, September 6, 1884. CLOUSTON, THOMAS S,, 31. D., F. M. C. JP., L. M. C. S., Lecturer on Mental Diseases in the University of Edinburgh. Clinical Lectures on Mental Diseases. With an Appendix, containing an Abstract of the Statutes of the United States and of the Several States and Territories re- lating to the Custody of the Insane. By Chables F. Folsom, M. D., Assistant Professor of Mental Diseases, Medical Department of Harvard University. In one handsome octavo volume of 541 pages, illustrated with eight lithographic plates, four of which, are beautifully colored. Cloth, §4. The practitioner as well as the student will ac- cept the plain, practical teaching of the author as a forward step in the literature of insanity. It is refreshing to find a physician of Dr. Clouston's experience and high reputation giving the bed- side notes upon which his experience has been founded .ind his mature judgment established. Such clinical observations cannot but be useful to the general practitioner in guiding him to a diag- nosis and indicating the treatment, especially in many obscure and doubtful cases of mental dis- ease. To the American reader Dr. Folsom's Ap- pendix adds greatly to the value of the work, and will make it a desirable addition to every library. — American Psychological Journal, July, 1884. J|@^Dr. Folsom's Abstract may also be obtained separatelv in one octavo volume of IDS pages. Cloth, $1.50. SAVAGE, GEOMGE H., 31. D., Lecturer on Mental Diseases at Guy's Hospital, London. Insanity and Allied Neuroses, Practical and Clinical. In one 12mo. vol- ume of 551 pages, with 18 typical illustrations. Cloth, $2.00. Just ready. See Series oj Clinical Manuals, page 3. As a handbook, a guide to practitioners and stu- dents, the book fulfils an admirable purpose. The many forms of insanity are described with char- acteristic clearness, the illustrative eases are care- fully selected, and as regards treatment, sound common sense is everywhere apparent. We re- peat that Dr. Savage "has written an excellent manual for the practitioner and student. — Am- erican Journal of Insanity, April, 1SS5. PLATEAIB, W. S., 31. D., E. M. C. E., The Systematic Treatment of Nerve Prostration and Hysteria. one handsome small 12mo. volume of 97 phages. Cloth, $1.00. In Blandford on Insanity and its Treatment : Lectures on the Treatment, Medical and Legal, of Insane Patients. In one very handsome octavo volume. 20 Lea Brothers & Co.'s Publications — Surgery. GBOSS, S, n., 31. D,, LL, D., D. C. L. Oxon., ii. D. Cantab, f Emeritus Professor of Surgery in the Jefferson Medical College of Philadelphia. A System of Surgery : Pathological, Diagnostic, Therapeutic tfind Operative. Sixth edition, thoroughly revised and greatly improved. In two large and beautifully- printed imperial octavo volumes containing 2382 pages, illustrated by 1623 engravings. Strongly, bound in leather, raised bands, $15; half Eussia, raised bands, $16. Dr. Gross' St/sfeni of Surqery has long been the standard work oh tliat subject for students and practitioners. — London Lancet, May 10, 1884. The work as a whole needs no commendation. Many years ago it earned for itself the enviable rep- utation of the leading American work on surgery, and it is still capable of maintaining that standard. The reason for this need only be mentioned to be appreciated. The author has always been calm and judicious in his statements, has based his con- clusions on much study and personal experience, has been able to grasp his subject in its entirety, and, above all, has conscientiously adhered to truth and fact, weighing the evidence, pro and con, accordingly. A considerable amount of new material has been introduced, and altogether the distinguished author has reason to be satisfied that he has placed the work fully abreast of the state of our knowledge.— i¥ed. Record, Nov. 18, 1882. His System of Surgery, which, since its first edi- tion in 1859, has been a standard work in this country as well as in America, in "the whole domain of surgery," tells how earnest and lakiori- 0U3 and wise a surgeon he was, how thoroughly he appreciated the work done by men in other countries, and how much he contributed to pro- mote the science and practice of surgery in his own. There has been no man to whom America is so much indebted in this respect as the Nestor of surgery. — British Medical Journal, Blay 10, 1884. ASSMUMST, JOMW, Jr., 3£. D., Professor of Clinical Surgery, Univ. of Penna., Surgeon to the Episcopal Hospital, Philadelphia. The Principles and Practice of Surgery. Fourth edition, enlarged and revised. In one large and handsome octavo volume of about 1100 pages, with about 575 illustrations. In press. GOULD, A. JPEAMCB, 31. S., 31. B., F. M. C. S,, Assistant Surgeon to Middlesex Hospital. Elements of Surgical Diagnosis. In one pocket-size 12mo. volume of 589 pages. Cloth, $2.00. Just ready. See Students' Series of Manuals, page 3. and if practitioners would devote a portion of their leisure to the study of it, they would receive immense benefit in the way of refreshing their knowledge and bringing it up to the present state of progress. — Cincinnati Medical News, Jan., 1885. The student and practitioner will find the principles of surgical diagnosis very satisfactorily set forth with all unnecessary verbiage elimi- nated. Every medical student attending lectures should have a copy to study during the intervals. GIBWBY, F. !>., 31, J)., Surgeon to the Orthopoeaic Hospital, New York, etc. Orthopaedic Surgery. For the use of Practitioners and Students. In one hand- some octavo volume, profusely illustrated. Preparing. MOBJEMTS, JOH]^ B., A. 31., 31. D., Lecturer on Anatomy and on Operative Surgery at the Philadelphia School of Anatomy. The Principles and Practice of Surgery. For the use of Students and Practitioners of Medicine and Surgery. In one very handsome octavo volume of about 500 pages, with many illustrations. Preparing. BBLLA31Y, BiyWABD, F. M. C. S., Surgeon and Lecturer on Surgery at Charing Cross Hospital, Examiner in Anatomy Royal College of Surgeons, London. Operative Surgery. Shortly. See Students' Series of Manuals, page 3. STI3ISON, BBWIS A., B. A Prof, of Pathol. Anat. at the Univ. of the City A Manual of Operative Surgery, of 477 pages, with 332 illustrations. Cloth, |: This volume is devoted entirely to operative sur- gery, and is intended to familiarize the student with the details of operations and the different modes of performing them. The work is hand- somely illustrated, and the descriptions are clear and well-drawn. It is a clever and useful volume ; ., 31. n., of New York, Surgeon and Curator to Bellevue Hasp. . In one very handsome royal 12mo. volume 2.50. every student should possess one. This work does away with the necessity of pondering over larger works on surgery for descriptions of opera- tions, as it presents in a nutshell what is wanted by the surgeon without an elaborate search to find it. — Maryland Medical Journal, August, 1878. SARGENT ON BANDAGING and OTHER OPERA- TIONS OF MINOR SURGERY. New edition, with a Chapter on military surgery. One 12mo. volume of 383 pages, with 187 cuts. Cloth, $1.75. MILLER'S PRINCIPLES OF SURGERY. Fourth American from the third Edinburgh edition. In one 8vo. vol. of 638 pages, with 340 illustrations. Cloth, 13.75. MILLER'S PRACTICE OF SURGERY. Fourth and revised American from the last Edinburgh edition. In one large 8vo. vol. of 682 pages, with 364 illustrations. Cloth, $3.75. PIRRIE'S PRINCIPLES AND PRACTICE OF SURGERY. Edited by John Neill, M. D. In one 8vo. vol. of 784 pp. with 316 illus. Cloth, $3.75. COOPER'S LECTURES ON THE PRINCIPLES AND PRACTICE OF SURGERY. In one 8vo.to1. of 767 pages. Cloth, $2.00. SKEY'S OPERATIVE SURGERY. In one vol. 8vo- of 661 pages, with 81 woodcuts. Cloth, $3.25. GIBSON'S INSTITUTES AND PRACTICE OF SURGERY. Eighth edition. In two octavo vols, of 965 pages, with 34 plates. Leather $6.50. Lea Brothers & Co.'s Publications — Surg-ei-y. 21 ericitbbn; joitw b,, Bz n. s., f, it. c. >s'.. Professor of Suryery in University Collcjc, London, etc. The Science and Art of Surgery; licin^ a Treatise on Surgical Injuries, Dis- eases and Oi)erations. 1^'rom the ciglith and enlarged Englifih edition. In two large and beautiful oetavo volumes of 231G pages, illustrated with 984 engravings on wood. Cloth, |9; leather, raised bands, $11 ; half Ilussia, raised bands, $12. Jmt ready. After the profession has placed its approval upon a work totho exteiitof piir(!lianing seven editioriw, it does not iieec^/•oiest work on surgery for medical -students we think there can be no doubt. The author seems to have understood just what a student needs, and has prepared the work accordingly. — Cincinnati Medical IVews, January, 1885. By the same Author. Diseases of the Breast. In one 12mo. volume. Preparing. See Series of Clinical Manuals, page 3. ESMABCJa, Dr, FBIEimiCM, Professor of Surgery at the University of Kiel, etc. Early Aid in Injuries and Accidents. Five Ambulance Lectures. Trans- lated by H. E. H. Princess Christian. In one handsome small 12mo. volume of 109 pages, with 24 illustrations. Cloth, 75 cents. The course of instruction is divided into five sections or lectures. The first, or introductory lecture, gives a brief account of the structure and organization of the human body, illustrated by clear, suitable diagrams. The second teaches how to give judicious help in ordinary injuries — contu- sions, wounds, haemorrhage and poisoned wounds. The third treats of first aid in cases of fracture and of dislocations, in sprains and in burns. Next, the metliods of affording first treatment in cases of frost-bite, of drowning, of suffocaiion, of loss of consciousness and of poisoning are described ; and the fifth lecture teaches how injured persons may be most safely and easily transported to their homes, to a medical man, or to a hospital. The illustrations in the book are clear and good. — Medi- cal Times and Gazette, Nov. 4, 1882. TRBVES, FRFDERICK, F. B. C. S., Assistant Surgeon to and Lecturer on Surgery at the London Hospital. Intestinal Obstruction. In one pocket-size 12mo. volume of 522 pages, with 60 illustrations. Limp cloth, blue edges, $2.00. Just ready. See Series of Clinical Manuals, page 3. A standard worlc on a subject that has not been I justice to the author in a few paragraphs. Intes- so compretiensively treated by any contemporary (inai Obstruction is a work tliat will prove of English writer. Its completeness renders a full equal value to the practitioner, the student, the review difficult, since every chapter deserves mi- pathologist, the physician and the operating sur- nute attention, and it is impossible to do thorougli | geon. — British Medical Journal, Jan." 31, 18S5. BALL, CM Alt LBS B., 31. Ch., Dili}., F. It. C. S. B., Surgeon and Teacher at Sir P. T)un''s Hospital, Dublin. Diseases of the Rectum a.nd Anus. In one 12mo. volume of 550 pages. Preparing. See Series of Clinical Manuals, page 3. BUTLIN, MBNMT T., F. B. C. S., Assistant Surgeon to St. Bartholomew's Hospital, London. Diseases of the Tongue. In one 12mo. Manuals, page 3. Shorlly. volume. See Series of Clinical DMUITT, ItOBBBT, 31. B. C. S., etc. The Principles and Practice of Modern Surgery. From the eighth London edition. In one 8vo. volume of 687 pages, with 432 illus. Cloth, $4 ; leather, $5. 22 Lea Brothers & Co.'s Publications — Surg-ery. MOL3IES, TIMOTMT, M. A.r Surgeon and Lecturer on Surgery at St. George's Rospital, London. A System of Surgery ; Theoretical and Practical. IN TREATISES BY VAEIOUS AUTHOES. American edition, ti-iokoughly revised and re-edited by John H. Packard, M. D., Surgeon to the Episcopal and St. Joseph's Hospitals, Philadelphia, assisted by a corps of thirty-three of the most eminent American surgeons. In three large and very handsome imperial octavo volumes containing 3137 double- columned pages, -with 979 illustrations on wood and 13 lithographic plates, beautifully colored. Price per volume, cloth, $6.00 ; leather, $7.00 ; half Eussia, |7.50. Per set, cloth, $18.00 ; leather, $21.00 ; half Eussia, $22.50. Sold only by subscription. Volume I. contains General Pathology, Morbid Processes, Injuries in Gen- eral, Complications of Injuries and Injuries of Eegions. Volume II. contains Diseases op Organs of Special Sense, Circulatory Sys- tem, Digestive Tract and Genito-Urinary Organs. Volume III. contains Diseases of the Eespiratory Organs, Bones, Joints and Muscles, Diseases of the Nervous System, Gunshot Wounds, Operative and Minor Surgery, and Miscellaneous Subjects (including an essay on Hospitals). This great work, issued some years since in England, has won such universal confi- dence wherever the language is spoken that its republication here, in a form more thoroughly adapted to the wants of the American practitioner, has seemed to be a duty owing to the profession. To accomplish this, each article has been placed in the hands of a gentleman specially competent to treat its subject, and no labor has been spared to bring each one up to the foremost level of the times, and to adapt it thoroughly to the practice of the country. In certain cases this has rendered necessary the substitution of an entirely new essay for the original, as in the case of the articles on Skin Diseases, on Diseases of the Absorbent System, and on Anaesthetics, in the use of which American practice differs from that of England. The same careful and conscientious revision has been pursued throughout, leading to an increase of nearly one-fourth in matter, while the series of illustrations has been nearly trebled, and the whole is presented as a complete exponent of British and American Surgery, adapted to the daily needs of the working practitioner. In order to bring it within the reach of every member of the profession, the five vol- umes of the original have been compressed into three by employing a double-columned royal octavo page, and in this improved form it is offered at less than one-half the price of the original. It is printed and bound to match in every detail with Eeynolds' System of Medi- cine. The work will be sold by subscription only, and in due time every member of the profession will be called upon and offered an opportunity to subscribe. The authors of the original English edition are men of the front rank in England, and Dr. Packard has been fortunate in securing as his American coadjutors such men as Bartholow, Hyde, Hunt, Conner, Stimson, Morton, Hodgen, Jewell and their colleagues. As a whole, the work will be iBolid and substantial, and a valuable addition to the library of any medical man. It is more wieldly and more' useful than the English edition, and with its companion work—" Reynolds' System of Medi- cine" — will well represent the present state of our science. One who is familiar with those two works will be fairlv well furnished head-wise and hand- wise.— T/is Medical Keics, Jan. 7, 1882. STIM80JV, LEWIS A,, B, A., M, J>., Professor of Pathological Anatomy at the University of the City of New York, Surgeon and Curator to Mellevue Hospital, Surgeon to the Presbyterian LTospital, N'eiv York, etc. A Practical Treatise on Fractures. In one very handsome octavo volume of 598 pages, with 360 beautiful illustrations. Cloth, $4.75 ; leather, $5.75. the surgeon in full practice. — iV". O. Medical and Surgical Journal, March, 18S3. The author gives in clear language all that the practical surgeon need know of the science of fractures, their etiologj"-, symptoms, processes of union, and treatment, according to the latest de- velopments. On the basis of mechanical analysis the author accurately and clearly explains the clinical features of fractures, and by the same method arrives at the proper diagnosis snd rational treatment. A thorough explanation of the patho- logical anatomy and a careful description of the various methods of procedure make the book full of value for every pra,etitioner. — Centralhlatt fur Chirurgie, May 19, 18S3. The author has given to the medical profession in this treatise on fractures what is likely to be- come a standard work on the subject. It is certainly not surpassed by any work written in the English, or, for that matter, any other language. The au- thor tells us in a short, concise and comprehensive manner, all that is known about his subject. There is nothing scanty or superficial about it, as in most other treatises ; on the contrary, everything is thor- ough. The chapters on repair of fractures and their treatment show him not only to be a profound stu- dent, but likewise a practical surgeon and patholo- gist. His mode of treatment of the different fract- ures is eminently sound and practical. We consider this work one of the best on fractures ; and it will be welcomed not cnly as a text-book, but also by MAMSS, SOWABD, F. M. C. S., Senior Assistant Surgeon to and Lecturer on Anatomy at St. Bartholomew's Hospital, London. Diseases of the Joints. In one 12mo. volume. Preparing. See Series of Clinical Manuals, page 3. PICK, X. PICKBRING, F. It. C. 8., Surgeon to and Lecturer on Surgery at St. George's Hospital, London. Fractures and Dislocations. In one 12mo. volume. Preparing. See Series of Clinical Manuals, page 3. Lea Brothers & Co.'s Publications — Frac, DiHloc, Ophthal. 23 HAMILTON, FBANKH., M, JD., ZL, D., Surgeon to Bellevue UoHpital, New York. A Practical Treatise on Fractures and Dislocations. Sevcntd edition, thoroughly revised and much improved. In one very handsome octavo volume of 998 pages, with 379 illustrations. Cloth, $5.50 ; leather, $6,50 ; very handsome half liuesia, open back, $7.00. Just ready. Hamilton'a i^reat experience and wide acquaint- ance with ttie ntorature of the subject have enabled him to complete the labors of Malgaigno and to place the reader in possession of tho (idvanees made duriug thirty years. The editions have fol- lowed each other rapidly, and they introduce us to the methods of practice, often so wise, of his American colleagues. More practical than Blal- gaigne's worlv, it will serve as a valuable guide to the practitioner in tho numerous and embarrass- ing cases which come under his observation. — Archives Ginh'ales do Medecine, Paris, Nov. 1884. This work, which, since its first appearance twenty-five years ago, has gone through many editions, and been Vnucli enlarged, may now be fairly regarded as the authoritative hook' of refer- ence on the subjects of fractures and dislocations. Eacli successive edition has been rendered of greater value through the addition of more re- cent work, and especially of the recorded re- scarciies and improvements made by the author himself and his countrymen. — British Medical Journal,, May 0, 1885. With its first appearance in IS.TO, this work took rank among tho classics in medical literature, and lias ever since boon quoted by surgeons the world over as an authority upon the topics of which it treats. Tiie surg(!')n, if one can be found who does not already know the work, will find it scientific, forcible and si;holarIy in text, exhaustive in detail, and ever marked by a spirit of wise con- servatism. — Louisville Medical News, .Jan. 10, 188.5. For a quarter of a century the author has been elaborating and perfecting his work, so that it now stands as the best oi its kind in any lan- guage. As a text-book and as a book of reference and guidance for practitioners it is simply invalu- able. — Neiv Orleans Med. andSarg. Journ'l, Nov. 1884. JTILBM, MJEJSTMY E,, F. M, C. S., Senior Ass^t Surgeon, Royal Westini aster Ophthalmic Hasp. ; lat6 Clinical AssH, Moorfields, London. A Handbook of Ophthalmic Science and Practice. In one handsome octavo volume of 460 pages, with 125 woodcuts, 27 colored plates, and selections from the Test-types of Jaeger and Snellen. Cloth, $4.50 ; leather, $5.50. Just ready. This work is distinguished by tlie great num- ber of colored plates which appear in it for illus- trating various patliological conditions. They are very oeautiful in appearance, and .have been executed witli great care as to accuracy. An ex- amination of the work shows it to be one of high standing, one that will be regarded as an authority among ophthalmologists. The treatment recom- mended is such as the author lias learned from actual experience to be the best. — Cincinnati Medi- cal News, Dec. lSS-4. It presents to the student concise descriptions and typical illustrations of all important eye affections, placed in juxtaposition, so as to be grasped at a glance. Beyond a doubt it is tlie best illustrated handbook of ophthalmic science which has ever appeared. Then, what is still better, these illustrations are uearl.v all original. AVe have examined this entire work with great care, and it represents the commonly accepted views of advanced ophthalmologists. We can most heartily commend this book to all medical stu- dents, practitioners and specialists. — Detroit Lancet, Jan. 1SS5. WELLS, J. SOELBEMG, F. B. C, S,, Professor of Ophthalmology in King's College Hospital, London, etc. A Treatise on Diseases of the Eye. Fourth American from the third London edition. Thoroughly revised, with copious additions, by Charles S. Bull, M. D., Surgeon and Pathologist to the New York Eye and Ear Infirmary. In one large octavo volume of 822 pages, with 257 illustrations on wood, sis colored plates, and selections fi-om the Test- types of Jaeger and Snellen. Cloth, $5.00 ; leather, $6.00 ; half Russia, $6.50. The present edition appears in less than three j shows the fidelity and thoroughness with which years since the publication of the last American edition, and yet, from the numerous recent inves- tigations that have been made in this branch of medicine, many changes and additions have been required to meet the present scope of knowledge upon this subject. A critical examination at once the editor has accomplished his part of the work. The illustrations throughout are good. This edi- tion can be recommended to all as a complete treatise on diseases of the eye, than which proba- bly none better exists. — Medical Record, A\ig. IS, '83. JSTETTLESMIP, EDWAHn, F. M, C. S,, Ophthalmic Surg, and Lect. on Ophth. Surg, at St. Thoinas'' Hospital, London. The Student's Guide to Diseases of the Eye. Second edition. With a chap- ter on the Detection of Color-Blindness, by William Thomson, M. D., Ophthalmologist to the Jefferson Medical College. In one royal 12mo. volume of 416 pages, with 138 illustrations. Cloth, $2.00. This admirable guide bids fair to become the favorite text-book on ophthalmic surgery with stu- dents and general practitioners. It bears tkrough- out tlie imprint of sound judgment combined with vast experience. Tlie ilfustratious are numerous and well chosen. This book, within the short com- pass of about 400 pages, contains a lucid exposition of the modern aspect of ophthalmic science. — Medical Record, June 23, 1883. BMOWNE, EUGAM A., Surgeon to the Liverpool Eye and Ear Infirmary a)id to the Dispensary for Skin Diseases. How to Use the Ophthalmoscope. Being Elementary Instructions in Oph- thalmoscopy, arranged for the use of Students. In one small royal 12mo. volume of 116 pages, with 35 illustrations. Cloth, $1.00. LAWSON ON INJURIES TO THE EYE. ORBIT AND EYELIDS: Their Immediate and Remote Effects. 8 vo., 404 pp., 02 illus. Cloth, §3.50. LAITRENCE AND MOON^S HANDY BOOK OF OPHTHALMIC SURGERY, for the use of Prac- titioners. Second edition. In one octavo vol- ume of 227 pages, with 65 illust. Cloth, S2.75. CARTICR'S PRACTICAL TREATISE ON DISEAS- ES OF THE EYE. Edited by John Gbeex, M. D. In one handsome octavo voliime. :24 Lea Brothers & Co.'s Publications — Otol., XJrin. I>is.,Deiit. BVBNBTT, CHARLBS M., A, M., M. D., Professor of Otology in the Philadelphia Polyclinic ; President of the American Otological Society. The Ear, Its Anatomy, Physiology and Diseases. A Practical Treatise ■for the use of Medical Students and Practitioners. New (second) edition. In one handsome ■octavo volume of 580 pages, with 107 illustrations. Cloth, $4.00; leather, |5.00. Just ready. carried out, and much new matter added. Dr. We note with pleasure the appearance of a second ■edition of this valuable work. When it first came out it was accepted by the profession as one of the standard works on modern aural surgery in the English language; and in his second edition Dr. Burnett has fully maintained his reputation, for the book is replete with valuable information and suggestions. Tlie revision has been carefully Burnett's work must be regarded as a very valua- ble contribution to aural surgery, not only on account of its comprehensiveness, but because it contains the results of the careful personal observa- tion and experience of this eminent aural surgeon. — London Lancet, Feb. 21, 1885. POLITZEU, ADAM, Imperial- Royal Prof, of Aural Therap. in the Univ. of Vienna. A Text-Book of the Ear and its Diseases. Translated, at the Author's re- quest, by James Patterson Cassells, M. D., M. K. C. S. In one handsome octavo vol- ume of 800 pages, with 257 original illustrations. Cloth, $5.50. The work itself we do not hesitate to pronounce the best upon the subject of aural diseases which has ever appeared, systematic without being too diffuse on obsolete subjects, and eminently prac- 'tical in every sense. Tlie anatomical descriptions of each separate division of the ear are admirable, and profusely illustrated by woodcuts. They are followed immediately by the physiology of the section, and this again by the pathological physi- ology, an arrangement which serves to keep up the interest of the student by showing the direct ap- plication of what has preceded to the study of dis- ease. The whole work can be recommended as a reliable guide to the student, and an efficient aid to the practitioner in his treatment. — Boston Medr ical and Surgical Journal, June 7, 1883. MOBBMTS, WILLIAM, M. D., Lecturer on Medicine in the Manchester School of Medicine, etc. A Practical Treatise on Urinary and Renal Diseases, including Uri- nary Deposits. Fourth American from the foui'th London edition. In one liand- some octavo volume of about 650 pages, with 81 illustrations. Cloth, |3.50. Just ready. This excellent book has now reached its fourth edition, and not too soon, for the third has been exhausted for some years, and it is one of those works which no good physician's or surgeon's library should be without. The profession is sin- cerely to be congratulated that he has been able amidst his many public and private duties to pre- sent a new edition of this standard work, thoroughly brought up to the present date. — Lon- don Medical Record, May 15, 1885. GMOSS, S. D., M. !>., LL. J>., J>. C. X., etc. A Practical Treatise on the Diseases, Injuries and Malformations of the Urinary Bladder, the Prostate Gland and the Urethra, Third • edition, thoroughly revised by Samuel W. Gross, M. D., Professor of the Principles of Surgery and of Clinical Surgery in the Jefferson Medical College, Philadelphia. In one octavo volume of 574 pages, with 170 illustrations. Cloth, |4.50. MORRIS, SB WRY, M. B., F. R. C, S., Surgeon to and Lecturer on Surgery at Middlesex Hospital, London. Surgical Diseases of the Kidney. In one 12mo. volume. Preparing. See ■Series of Clinical Manuals, page 3. LUCAS, CLBMBJSTT^M. B., B. S., F. R. C. S., Senior Assistant Surgeon to Guy's Hospital, London. Diseases of the Urethra. In one 12mo. volume. Preparing. See Series ■ of Clinical Manuals, page 3. TSOMFSON, SIR SBJS^RT, Surgeon and Professor of Clinical Surgery to University College Hospital, London. Lectures on Diseases of the Urinary Organs. Second American from the third English edition. In one 8vo. volume of 203 pp., with 25 illustrations. Cloth, $2.25. By the Same Author. On the Pathology and Treatment of Stricture of the Urethra and Urinary Fistulse. From the third English edition. In one octavo volume of 359 pages, with 47 cuts and 3 plates. Cloth, $3.50. COLBMAW, A,, L. R. C. F., F. R, C, S., Bxam. L, D. S,, Senior Dent. Surg, and Lect. on Dent. Surg, at St. Bartholomew's Hosp. and the Dent. Hosp., London. A Manual of Dental Surgery and Pathology. Thoroughly revised and ■adapted to the use of American Students, by Thomas C. Stellvs^agen, M. A., M, D., D. D. S., Prof, of Physiology at the Philadelphia Dental College. In one handsome octavo volume of 412 pages, with 331 illustrations. Cloth, $3.25. iBASHAM on renal diseases : A Clinical I ome 12mo. vol. of 304 pages, with 21 illustrations. Guide to their Diagnosis and Treatment. In | Cloth, 82.00. Lea Brothers & Co.'s ]*ublications — Venereal, Impotence. 25- BJJMSTEAJy, F. J., M. JJ., LL. />., Late Professor of Vcneredl Diseases at the Col/nf/e of Pkysicmns and Surgeons, New York, etc. and TAYLOR, M. TT., A. M., M. n,, Surgeon to Chari/i/ H'osjiil/U, Ken; York, Prof, of Venereal and Skin J>ijieaHeH in the Univergily of Vermont, Pres. of the Am. iJermalological Ass'n, The Pathology and Treatment of Venereal Diseases. Indufling the results of recent investigations upon tiie Huhject. Fil'tli edition, reviseil ., PYofessor of the Principles of Surgery and of Clinical Surgery in the Jefferson Medical College. A Practical Treatise on Impotence, Sterility, and Allied Disorders of the Male Sexual Organs. Second edition, thoroughly revised. In one very hand- some octavo volume of 168 pages, with 16 illustrations. Cloth, $1.50. The author of this monograph is a man of posi- tive convictions and vigorous style. This is iusti- fied by his experience and by his study, which has gone liand in hand with his experience. In regard to the various organic and functional disorders of the male generative apparatus, he has had ex- ceptional opportunities for observation, and l:is book shows that lie has not neglected to compare his own views with tliose of other authors. The result is a work which can be safely recommended This work will derive value from the high stand- ing of its author, aside from the fact of its passing so rapidly into its second edition. This is, indeed, a book that every physician will be glad to place in his library, to be read with profit to himself, and with incalculable benefit to his patient. Be- sides the subjects embraced in the title, which are treated of in their various forms and degrees, spermatorrhoea and prostatorrhcea are also^" fully considered. The work is thoroughly practical in to both physicians and surgeons as a guide in the character, and will be especially useful to treatment of the disturbances it refers to. It i: the best treatise on the subject with which we are acquainted. — 7Vie Medical Kcws, Sept. 1, 1883. general practitioner. — Medical liecord, Aus 1883. the IS, CULLEMIEB., A., & BUMSTEAD, F. J., 3I.I>., EE.J)., Surgeon to the Ildpital da Midi. Late Professor of Venereal Diseases in the College of Physieian» and Surgeons, New York. An Atlas of Venereal Diseases. Translated and edited by Free>[an J. Bum- stead, M. D. Iu one imperial 4to. vohmie of 328 pages, double-cohimns, with 26 plates, containing about 150 figures, beautifully colored, many of them the size of life. Strongly bound in cloth, $17.00. A specimen of the plates and text sent by mail, on receipt of 25 cts. HILL ON SYPHILIS AND LOCAL COIvTAGIOUS ; FORjrS OP LOCAL DISEASE AFFECTING DISORDERS. In one 8vo vol. of 479 p. Cloth, S5.-25. : PRINCIPALLY THE ORGANS OF GENERA- LEE'S LECTURES ON SYPHILIS AND SOME ; TION. In one Svo. vol. of i;4t3 pages. Cloth, §2.25. 26 Lea Brothers & Co.'s Publications — Diseases of Skin. SYDB, J. NEVINS, A. M., M, D., Professor of Dermatology and Venereal Diseases in Mush Medical College, Chicago. A Practical Treatise on Diseases of the Skin. For the use of Students and Practitioners. In one handsome octavo volume of 570 pages, with 66 beautiful and elab- orate illustrations. Cloth, $4.25 ; leather, §5.25. The author has given the student and practi- tioner a work admirably adapted to the wants of each. We can heartily commend the book as a valuable addition to our literature and a reliable guide to students and practitioners in their studies and practice. — Ant Journ. of Med. Sci., July, 1883. Especially to be praised are the practical sug- gestions as to what may be called the common- sense treatment of eczema. It is quite impossible to esasgerate the judiciousness with which the formuiie for the external treatment of eczema are selected, and what is of equal importance, the full and clear instructions for their use. — London Medi- cal Times and Gazette, July 28, 1883. The work of Dr. Hyde will be awarded a high position. The student of medicine will find it peculiarly adapted to his wants. Notwithstanding the extent of the subject to which it is devoted, yet it is limited to a single and not very large vol- ume, without omitting a proper discussion of the topics. The conciseness of the volume, and the setting forth of only what can be held as facts will also make it acceptable to general practitioners. — Cincinnati Medical News, Feb. 1883. The aim of the author has been to present to his readers a work not only expounding the most modern conceptions of his subject, but presenting what is of standard value. He has more especially devoted its pages to the treatment of disease, and by his detailed descriptions of therapeutic meas- ures has adapted them to the needs of the physi- cian in active practice. In dealing with these questions the author leaves nothing to the pre- sumed knowledge of the reader, but enters thor- oughly into the most minute description, so that one is not only told what should be done under given conditions but how to do it as well. It is therefore in the best sense " a practical treatise." That it ia comprehensive, a glance at the index will show. — Maryland Medical Journal, July 7, 1883, Professor Hyde has long been known as one of the most intelligent and enthusiastic representa- tives of dermatology in the west. His numerous contributions to tiie literature of this specialty have gained for him a favorable recognition as a careful, conscientious and original observer. The remarkable advances made in our knowledge of diseases of the skin, especially from the stand- point of pathological histology and improved methods of treatment, necessitate a revision of the older text-books at short intervals in order to bring them up to the standard demanded by the march of science. This last contribution of Dr. Hyde is an effort in this direction. He has at- tempted, as he informs us, the task of presenting in a condensed form the results of the latest ob- servation and experience. A careful examination of the work convinces us that he has accomplished his task with painstaking fidelity and with a cred- itable result. — Journal of Cutaneous and Venereal Diseases, June, 1883. FOX, T,, M.D,, F.M. C. JP., and FOX, T, C, B.A., M,JR, aS., Physician to the Department for Skm Diseases, University College Hospital, London. Physician for Diseases of the Skin to the Westminster Hospital, London. An Epitome of Skin Diseases. With Pormul83. For Students and Prac- titioners. Third edition, revised and enlarged. In one very handsome 12mo. volume of 238 pages. Cloth, $1 .25. The third edition of this convenient handbook calls for notice owing to the revision and expansion which it has undergone. The arrangement of skin diseases in alphabetical order, which is the method of classification adopted in this work, becomes a positive advantage to the student. The book is one which we can strongly recommend, not only to students but also to practitioners who require a compendious summary of the present state of dermatology. — British Medical Journal, July 2, 1883. We cordially recommend Fox's Epitome to those whose time is limited and who wish a handy manual to lie upon the table for instant reference. Its alphabetical arrangement is suited to this use, for all one has to know is the name of the disease, and here are its description and the appropriate treatment at hand and ready for instant applica- tion. The present edition has been very carefully revised and a number of new diseases are de- scribed, while most of the recent additions to dermal therapeutics find mention, and the formu- lary at the end of the book has been considerably augmented.— T%(3 Medical News, December, 1883. MOJEtMIS, MALCOL3I, M, D., Joint Lecturer on Dermatology at St. Mary^s Hospital Medical School, London. Skin Diseases ; Including their Definitions, Symptoms, Diagnosis, Prognosis, Mor- bid Anatomy and Treatment. A Manual for Students and Practitioners. In one 12mo. volume of 316 pages, with illustrations. Cloth, $1.75. for clearness of expression and methodical ar- rangement is better adapted'to promote a rational conception of dermatology — a branch confessedly difficult and perplexing to the beginner.— 5't Louis Courier of Medicine, April, 1880. The writer has certainly given in a small compass a large amount of well-compiled information, and his little book compares favorably with any other which has emanated from England, while in many points he has emancipated himself from the stuD- bornly adhered to errors of others of his country- men. There is certainly excellent material in the book which will well repay perusal. — Boston Med. and Surg. Journ., Blarch, 1880. To physicians who would like to know something about skin diseases, so that when a patient pre- sents himself for relief they can make a correct diagnosis and prescribe a rational treatment, we unhesitatingly recommend this little book of Dr. Morris. The affections of the skin are described in a terse, lucid manner, and their several charac- teristics so plainly set forth that diagnosis will be easy. The treatment in each case i's such as the experience of the mosteminent dermatologists ad- vises. — Cincinnati Medical News, April, 1880. This is emphatically a learner's book; for we can safely say, that in the whole range of medical literature there is no book of a like scope which WILSON, FBASMUS, F, M. S. The Student's Book of Cutaneous Medicine and Diseases of the Skin. In one handsome small octavo volume of 535 pages. Cloth, $3.50. MILLIBR, THOMAS, M. D., Physician to the Skin Department of University College, London. Handbook of Skin Diseases ; for Students and Practitioners. Second Ameri- can edition. In one 12mo. volume of 353 pages, with plates. Cloth, $2.25. Lea Brothers & Co.'s Publications — Din. of Women. 27 AJSr AMERICAJSr SYSTEM OF GYNMCOLOGY. A System of Gynaecology, in TreatisofS by Various Authors. Editefl by Matthew D. Manj^, M. ]>., I'roiessor of Obstetrics an., MATTHEW T). MANN, M. D., HENRY F. CAMPBELL, M. D., ROBERT B. MAURY, M. D., BEN.JAMIN F. DAWSON, M. D., C. K. PALMER, M. D., WILLIAM GOODELL, M. D., WILLIAM M. POLK, M. L., HENRY P. GARRIGUES, M. D., THADDEUS A. REAMV, M. D., SAMUEL W. GROSS, M. D., A. D. ROCKWELL, M. £>., JAMES B. HUNTER, M. D., ALBERT H. SMITH, M. D., WILLIAM T. HOWARD, M. D., B. STANSBURY SUTTON, A. M,, M. D., A. REEVES JACKSON, BI. D., T. GAILLARD THOMAS, M. D., EDWARD W. JENKS, M. D., CHARLES S. WARD, M. D., WILLIAM H. WELCH, M. D, THOMAS, T. GAILLAJRD, M. J>., Professor of Diseases of Wo^nen in the College of Physicians and Surgeons, JV. Y. A Practical Treatise on the Diseases of Women. Fifth edition, thoroughly revised and rewritten. In one large and handsome octavo volume of 810 pages, with 266 illustrations. Cloth, §;5.00; leather, |6.00; very hxindsome half Eussia, raised bands, $6.50. The words which follow "fifth edition" are in i vious one. As a boolc of reference for the busy this case no mere formal announcement. The I practitioner it is unequalled. — Boston Medical any alterations and additions which have been made are j Surgical Journal, Apri I 7, 1880. both numerous and important. The attraction j It has been enlarged and carefully revised. It is and the permanent character of this book lie in ' a condensed encyclopajdia of gynsecological rnedi- tha clearness and truth of the clinical descriptions cine. The style of arrangement, the masterly of diseases; the fertility of the author in thera- ! manner in which eaeli subject is treated, and the peutic resources and the fulness with which the j honest convictions derived from probably the details of treatment are described; the definite j largest clinical experience in that specialty of any character of the teaching; and last, but not least, j in this country, all serve to commend it in the the evident candor which pervades it. We would | highest terms to the practitioner. — Nashville Jour. also particularize the fulness with which the his- of Med. and Surg., Jan. 1881. tory of the subject is gone into, which makes the i " That the previous editions of the treatise of Dr. book additionally interesting and gives it value as | Thomas were thought worthy of translation into a work of reference.— iondon Medical Tiihes and • German, French, Italian and Spanish, is enough Gazette, July 30, 1881. to give it the stamp of genuine merit. At home it The determination of the author to keep his [ has made its way into the library of every obstet- book foremost in the rank of works on gynsecology i rician and gynascologist as a safe guide to practice. is most gratifying. Recognizing the fact that tliis ' No small number of additions have been made to can only be accomplished by frequent and thor- the present edition to make it correspond to re- ough revision, he has spared no pains to make the j cent improvements in treatment. — Pacific Medical present edition more desirable even than the pre- | and Surgical Journal, Jan. 1S81. EJyiS, AMTHUM W., M. D., Zond., F,M, C. P., M, M, C. S,, Assist. Obstetric Physician to Middlesex Hospital, late Physician to British Lying-in Hospital. The Diseases of Women. Including their Pathology, Causation, Symptoms, Diagnosis and Treatment. A Manual for Students and Practitioners. In one handsome octavo volume of 576 pages, with 148 illustrations. Cloth, |3.00 ; leather, |4.00. It is a pleasure to read a book so thoroughly [ The greatest pains have been taken with the good as this one. The special qualities which are i sections relating to treatment. A liberal selection conspicuous are thoroughness in covering the j of remedies is given for each morbid condition, vrhole ground, clearness of description and con- the strength, mode of application and other details ciseness of statement. Another marked feature of 1 being fully explained. The descriptions of gjTiBe- the book is the attention paid to the details of ' cologieal "manipulations and operations are full, many minor surgical operations and procedures, j clear and practical. Much care has also been be- as, for instance, the use of tents, application of ■ stowed on the parts of the book which deal with leeches, and use of hot water injections. These j diagnosis — we note especially the pages dealing are among the more common methods of treat- I with the differentiation, one from another, of the ment, and yet very little is said about them in '■ different kinds of abdominal tumors. The prac- many of the text-books. The book is one to be \ titioner will therefore find in this book the kind warmly recommended especially to students and I of knowledge he most needs in his daily work, and general practitioners, who need a concise but com- j he will be pleased with the clearness and fulness plete resume of the whole subject. Specialists, too, ' of the information there given. — The Practitioner, will find many useful hints in its pages. — Boston ' Feb. 1882. Med. and Surg. Journ., March 2, 1882. ■ BAMWES, MOBEMT, JSf. D., F. JR. C, JP., Obstetric Physician to St. Thomas' Hospital, London, etc. A Clinical Exposition of the Medical and Surgical Diseases of Women. In one handsome octavo volume, with m;merous illustrations. Xew edition. Preparing. WEST, CJETAMEES, M. D. Lectures on the Diseases of Women. Third American from the third Lon- don edition. In one octavo volume of 543 pages. Cloth, §3.75 ; leather, $4.75. CHURCHILL ON THE PUERPERAL FEVER \ MEIGS ON THE NATURE, SIGNS AND TREAT- AND OTHER DISEASES PECULIAR TO WO- i 3IENT OF CHILDBED FEVER. In one 8vo. MEN. InoneSvo. vol. of 464 pages. Cloth, $2.50. | volume of 346 pages. Cloth, 82.00. 28 Lea Brothers & Co.'s Publications — Dis. of Women, Midwfy. EMMET, THOMAS ADniS, M. !>,, LL, D,, Surgeon to the WomarCs Hospital, New York, etc. The Principles and Practice of Gynseeology ; For the use of Students and Practitioners of Medicine. New (third) edition, thoroughly revised. In one large and very handsome octavo volume of 880 pages, with 150 illustrations. Cloth, ?5 ; leather, $6. {Just ready.) Excerpt from the Author's Preface to the Second Edition. So great have been the advance and change of views during the past four years in Gynseeology, that the preparation of this edition has necessitated almost as much labor as to have rewritten the volume. Every portion has been thoroughly revised, a great deal has been left out, and much new matter added. The chapters on the relation of education and social condition to development, those on pelvic cellulitis, the diseases of the ovary and on ovariotomy, together with that on stone in the bladder, have been nearly rewritten. The chapters on prolapse of the vaginal walls and lacerations of the vaginal outlet, the methods of partial and complete removal of the uterus for malignant disease, the surgical treatment of fibrous tumors, diseases of the Fallopian tubes, and the diseases of the urethra, are essentially new, with the views and experience of the author in a form which has not been presented to the profession before. To these chapters not less than one hundred and seventy-five pages of new material have been added. endeavors to represent the actual state of gynse- cologieal science and art. — British Medical Jour- nal, May IC, 1885. Any work on gynseeology by Emmet must always have especial interest and value. He has for ni any years been an exceedinglj^ busy prac- titioner in this department. Few men have had his experience and opportunities. As a guide either for the general practitioner or specialist, it is second to none other. No one can read Emmet without pleasure, instruction and profit. — Cincinnati Lancet and Clinic, Jan 31, 1885. We are in doubt vchether to congratulate the author more than the profession upon the appear- ance of the third edition of this well-known work. Embodying, as it does, the life-long experience of one who has conspicuously distinguished himself as a bold and successful operator, and who has devoted so much attention to the specialty, we feel sure the profession will not fail to appreciate the privilege thus offered them of perusing the views and practice of the author. His earnestness of purpose and conscientiousness are manifest. He gives not only his individual experience but DVWCAW, J. MATTHEWS, M.I^,, LL, D,, F, M. S. E., etc. Clinical Lectures on the Diseases of "Women ; Delivered in Saint Bar- tholomew's Hospital. In one handsome octavo volume of 175 pages. Cloth, $1.50. They are in every way worthy of their author ; indeed, we look upon them as among the most valuable of his contributions. They are all upon matters of great interest to the general practitioner. Some of them deal with subjects that are not, as a rule, adequately handled in the text-books; others of them, while bearing upon topics that are usually treated of at leugtli in such works, yet bear such a stamp of individuality that, if widely read, as they certainly deserve to be, they cannot fail to exert a wholesome restraint upon the undue eagerness with which many young physicians seem bent upon following the wild teachings which so infest the gynfeeology of the present day.— iV. Y. Medical Journal, March, 1880. HOLfGE, HVGHL., M. D., Emeritus Professor of Obstetrics, etc., in the University of Pennsylvania. On Diseases Peculiar to Women; Including Displacements of the Uterus. Second edition, revised and enlarged. In one beautifully printed octavo volume of 519 pages, with original illustrations. Cloth, |4.50. By the Same Author. The Principles and Practice of Obstetrics. Illustrated with large litho- graphic plates containing 159 figures from original photographs, and with numerous wood- cuts. In one large quarto volume of 542 double-columned pages. Strongly bound in cloth, $14.00. * ^ * Specimens of the plates and letter-press will be forwarded to any address, free by mail, on receipt of six cents in postage stamps. TARWLEM, S., and CHAWTMEJJIL, G. A Treatise on the Art of Obstetrics. Translated from the French. In two large octavo volumes, richly illustrated. MAMSBOTHAM,. EMAWCIS H., 3L D. The Principles and Practice of Obstetric Medicine and^ Surgery: In reference to the Process of Parturition. A new and enlarged edition, thoroughly revised by the Author. With additions by W. V. Keating, M. D., Professor of Obstetrics, etc., in the Jefferson Medical College of Philadeli^hia. In one large and handsome imperial octavo volume of 640 pages, with 64 full-page plates and 43 woodcuts in the text, contain- ing in all nearly 200 beautiful figures. Strongly bound in leather, with raised bands, $7. ASHWELL'S PRACTICAL TREATISE ON THE | American from the third and revised London DISEASES PECULIAR TU WOMEN. Third edition. In one 8vo. vol., pp. 520. Cloth, $3.50. Lea BiurniKKS & ('(j.'k Puijlicationk — Midwifery. 29 PLAYFAIM, W. S., M. T>., F, It. C. P., Professor of ObnUdric Medicine in Kiivfs ColU. Fdin., C/ivlrnl ]''rofr!Iidwfy., Dis. CMlcln. LEISSMAN, WILLIAM^M. D., Regius Professor of Midwifery in the University of Glasgow, etc. A System of Midwifery, Including the Diseases of Pregnancy and the Puerperal State. Third American edition, revised by the Author, with additions by John S. Pakby, M. D., Obstetrician to the Philadelphia Hospital, etc. In one large and very handsome octavo volume of 740 pages, with 205 illustrations. Cloth, |4.50 ; leather, $5.50; very handsome half Russia, raised bands, $6.00. preparation of the present edition the author has The author is broad in his teachings, and dis- cusses briefly the comparative anatomy of the pel- vis and the mobility of tlie pelvic articulations. The second chapter is devoted especially to the Soudy of the pelvis, while in the third the female organs of generation are introduced. The structure and development of the ovum are admirably described. Then follow chapters upon the various subjects embraced in the study of mid- wifery. The descriptions throughout the work are plain and pleasing. Ifc is sufficient to state that in this, the last edition of this well-known work, every recent advancement in this field has been brought forward. — Physician and Surgeon, Jan. 1S80. We gladly welcome the new edition of this ex- cellent text-book of midwifery. The former edi- tions have been most favorably received by the profession on both sides of the Atlantic. In the made such alterations as the progress of obstetri- cal science seems to require, and we cannot but admire the ability with which the task has been performed. AVe consider it an admirable text- book for students during their attendance upon lectures, and have great pleasure in recommend- ing it. As an exponent of the midwifery of the present day it has no superior in the English lan- guage. — Canada Lancet, Jan. 1880. To the American student the work before us must prove admirably adapted. Complete in all its parts, essentially modern in its teachings, and with derruDustrations noted fo^r clearness and precision, it will gain in favor and be recognized as a work of standard merit. The work cannot fail to be popular and is cordially recommended. — N. O. Med. and Surg. Journ., March, 18S0. SMITH, J. LBWIS, M. D,, Clinical Professor of Diseases of CJiildren in the Bellevue Hospital Medical College, N. Y. A Complete Practical Treatise on the Diseases of Children. Fifth edition, thoroughly revised and rewritten. In one handsome octavo volume of 836 pages, with illustrations. Cloth, $4.50 ; leather, |5.50 ; very handsome half Eussia, raised bands, $6. " ' which we venture to say will be a favorable one. — Dublin Journal of Medical Science, March, 1883. There is no book published on the subjects of which this one treats that is its equal in value to the physician. While he has said just enough to impart the information desired by general practi- tioners on such questions as etiology, pathology, prognosis, etc., he has devoted more attention to the diagnosis and treatment of the ailments which he so accurately describes ; and such information is exactly what is wanted by the vast majority of " family physicians." — Va. Med. Monthly, Feb. 1882. This is one of the best books on the subject with which we have met and one that has given us satisfaction on every occasion on which we have consulted it, either as to diagnosis or treatment. It is now in its fifth edition and in its present form ia a very adequate representation of the subject it treats of as at present understood. The important subject of infant hygiene is fully dealt with in the early portion of the book. The great bulk of the work is appropriately devoted to the diseases of infancy and childhood. We would recommend any one in need of information on the subject to procure the work and form his own opinion on it, KBATING, JOMWM,, M. D., Lecturer on the Diseases vf Children at the University of Pennsylvania, etc. The Mother's Guide in the Management and Feeding of Infants. one handsome 12mo. volume.of 118 pages. Cloth, $1.00. In Works like this one will aid the physician im- mensely, for it saves the time he is constantly giv- ing his patients in instructing them on the sub- jects here dwelt upon so thoroughly and prac- tically. Dr. Keating has written a practical bookj has carefully avoided unnecessary repetition, -ana successfully instructed the mother in such details of the treatment of her child as devolve upon her. He has studiously omitted giving prescriptions, and instructs the mother when to call upon the doctor, as his duties are totally distinct from hers. — American .Journal of Obstetrics, October, 1881. Dr. Keating lias kept clear of the common fault of works of this sort, viz., mixing the duties of the mother with those proper to the doctor. There is the ring of common sense in the remarks about the employment of a wet-nurse, about the proper food for a nursing mother, about the tonic effects of a bath, about the perambulator versus the nurses, arms, and on many other subjects concerning which the critic might say, "surely this is obvi- ous," but which experience teaches us are exactly the things needed to be insisted upon, with theVich as well as the poor. — London Lancet, January, 28 1882 A book small in size, written in pleasant style, in language whi ch can be readily understood by any mother, and eminently practical and safe; in fact a book for which we have been waiting a long time, and which we can most heartily recommend to mothers as the book on this subject. — New York Medical Journal and Obstetrical Review, Feb. 1882. OWBW, EDMJJWU, 31, B., F, M. C. S., Surgeon to the Children's Hospital, Cheat Orniond St., London. Surgical Diseases of Children. In one 12mo. volume. Preparing. See Series of Clinical Manuals, page 3. WEST, CMAMLES, M, D., Physician to the Hospital for Sick Cliildren, London, etc. Lectures on the Diseases of Infancy and Childhood. Fifth American from 6tli English edition. In one octavo volume of 686 pages. Cloth, $4.50 ; leather, $5.50. By the Same Author. On Some Disorders of the Nervous System in Childhood. In one small 12mo. volume of 127 pages. Cloth, $1.00. CONDIE'S PRACTICAL TREATISE ON THE DISEASES OF CHILDREN. Sixth edition, re- vised and augmented. In one octavo volume of 779 pages. Cloth, $5.25; leather, $6.25. Lea Brothers & Co.'s Publications — Med. Juris., Miscel. 31 TIBY, CHARLBS MEYMOTT, M. B,, F, C, S,, Professor of Chemistry and of Forensic Medicine and Public Health at ike London. Hospital, etc. Iiegal Medicine. Volume II. Legitimacy and Paternity, Pregnancy, Abor- tion, Bape, Indecent Exposure, Sodomy, Bestiality, Live Birtli, Infanticifie, Asphyxia, Drowning, Hanging, Strangulation, Suffocation. Making a very handsome imperial oc- tavo volume of 529 pago«. Cloth, $G.OO; leather, $7.00. Volume I. Containing 664 imperial octavo pages, -with two beautiful colored plates. Cloth, |6.00 ; leather, $7.00. The satisfaction expressed with the first portion of tills work is in no wise lessened by a perusal of the second volume. We find it characterized by the same fulness of detail and clearness of ex- pression whicli wo had occasion so liighly to corn- mend in our former notice, and which render it so valuable to the medical jurist. The copious tables of cases appended to each division of the subject, must have cost the author a proditjious amount 'if labor and research, but they constitute one of the most valuable features of the book, especially for reference In medico-legal trials. — American Journal of the Medical Science)), April, 1884. TAYLOR, ALFRED S., M. D., Lecturer on Medicai Jurisprudence and Chenmtry in Ouy^s Hospital, London. A Manual of Medical J^urisprudence. Eighth American from the tenth Lon- don edition, thoroughly revised and rewritten. Edited by John J. Keese, M. D., Professor of Medical Jurisprudence and Toxicology in the University of Pennsylvania. In one large octavo volume of 937 pages, with 70 illustrations. Cloth, $5.00 ; leather, $6.00 ; half Russia, raised bands, $6.50. The American editions of this standard manual j have for a long time laid claim to the attention of | the profession in this country; and the eighth comes before us as embodying the latest thoughts and emendations of Dr. Taylor upon the subject i to which he devoted his life with an assiduity and j success which made him facile princeps among 1 English writers on medical jurisprudence. Both I the author and the book have made a mark too deep to be affected by criticism, whether it be j censure or praise. In this case, however, we should | only have to seek for laudatory terms. — American Journal of the Medical Sciences, Jan. 1881. This celebrated work has been the standard au- thority in its department for thirty-seven years, both in England and America, in both the profes- sions which it concerns, and it is improbable that it will be superseded in many years. The work i.3 simply indispensable to every physician, andnearly so to every liberally-educated lawyer, and we heartily commend the present edition to both pro- fessions. — Albany Law Journal, March 26, 1881. By the Same Author. The Principles and Practice of Medical Jurisprudence. Third edition. In two handsome octavo volumes, containing 1416 pages, with 188 illustrations. Cloth, $10 ; leather, $12. Just ready. For years Dr. Taylor was the highest authority in England upon the subject to which he gave especial attention. His experience was vast, his judgment excellent, and his skill beyond cavil. It is therefore well that the work of one who, as Dr. Stevenson says, had an "enormous grasp of all matters connected with the subject," should be brought up to the present day and continued In its authoritative position. To accomplish this re- sult Dr. Stevenson has subjected it to most careful editing, bringing it well up to the times. — Amerv- can Journal of the Medical Sciences, Jan. 1884. By the Same Author. Poisons in Kelation to Medical Jurisprudence and Medicine. Third American, from the 6hird and revised English edition. In one large octavo volume of 788 pages. Cloth, $5.50 ; leather, $6.50. FEFFER, AUGUSTUS J., M. S,, 31. B., F. R. C. S., Examiner in Forensic Medicine at the University of London. Forensic Medicine. In one pocket-size 12mo. volume. Preparing. See Siudentf^ Series of Manuals, page 3. LEA, MENRY C. Superstition and Force : Essays on The Wager of Law, The "Wager of Battle, The Ordeal and Torture. Third revised and enlarged edition. In one handsome royal 12mo. volume of 552 pages. Cloth, $2.50. This valuable work is in reality a history of civ- ilization as interpreted by the progress of jurispru- dence. . . In " Superstition and Force " we h.ave a philosophic survey of the long period intervening between primitive barbarity and civilized enlight^ enment. There is not a chapter in the work that should not be most carefully studied ; and however well versed the reader may be in the science of jurisprudence, he will find much in Mr. Lea's vol- ume of which he was previously ignorant. The book is a valuable addition to the literature of so- cial science. — Westminster Review, Jan. 1880. By the Same Author. Studies in Church History. The Rise of the Temporal Power— Ben- efit of Clergy — Excommunication, octavo volume of 605 pages. Cloth, $2.50. The author is pre-eminently a scholar. He takes up every topic allied with the leading theme, and traces it out to the minutest detail with a wealth of knowledge and impartiality of treatment that compel admiration. The amount of information compressed into the book is extraordinary. In no other single volume is the development of the New edition. In one very handsome royal Just ready. primitive church traced with so much clearness, and with so definite a perception of complex or conflicting sources. The fifty pages on the growth of the papacy, for instance, are admirable for con- ciseness and freedom from prejudice. — Boston T)-aveUer, May 3, 1SS3. Allen's Anatomy .... American Journal of the Medical Sciences American System of Gynajcology . American System of Practical jiledicine *Ashhurst's Surgery .... Ash well on Diseases of Women Attfield's Chemistry .... Ball on the Bectum and Anus Barker's Obstetrical and Clinical .Essaj's, Barlow's Practice of Medicine Barnes' Midwifery *Barnes on Dise'ases of Women Barnes' System of Obstetric Medicine Bartholow on Electricity Basham on Renal Diseases . Bell's Comparative Pliysiology and Anatomy Bellamy's Operative Surgery Bellamy's Sui'gical Anatomy Blandford on Insanity , Bloxam's Cliemistry . , . Bowman's Practical Chemistry *Bristowe's Practice of Medicine , Broadbent on the Pulse Browne on tlie Ophthalmoscope Browne on the Throat . . . • Bruce's Materia Medica and Tlierapeutics Brunton's Materia Medica and Therapeutics Bryant on the Breast .... *Bryanl's Practice of Surgery *Bumstead on Venereal I)iseases , *Burnett on the Ear , . . . Butlin on the Tongue .... Carpenter on the Use and Abu.se of Alcoliol *Carpeuter's Human Physiology . Carter on the Eye .... Centurj^ of American Medicine Chambers on Diet and Regimen Charles' Physiological and Pathological Chem, Churchill on Puerperal Fever Clarlieand Lockwood's Dissectors' Manual Classen's Quantitative Analysis Cleland's Dissector Clouston on Insanity Clowes' Practical Chemistry Coats' Pathology .... Cohen on the Throat .... Coleman's Dental Surgery Condie on Diseases of Children Cooper's Lectures on Surgery Cornil on Syphilis .... *Cornil and Ranvier's Pathological Histology Cullerier's Atlas oi Venereal Diseases Curnow's Medical Anatomy Dalton on the Circulation *Dalton's HumanPhysiology Dalton's Topographical Anatomy of the Brain Davis' Clinical Lectures Draper's Medical Physics Druitt's Modern Surgery Duncan on Diseases of Women *Dunglison's Medical Dictionary . Edis on Diseases of Women . Ellis' Demonstrations of Anatomy Emmet's Gynsecology *Erichsen's System of Surgery Esmarch's Early Aid in Injuries and Accid'ts Farquharson's Therapeutics and Mat. Med. Fenwick's Medical Diagnosis Finlayson's Clinical Diagnosis Flint on Auscultation and Percussion Flint on Phthisis .... Elint on Physical Exploration of the Lungs Flint on Respiratory Organs Flint on the Heart *Flint's Clinical Medicine Flint's Essays . . . • ♦Flint's Practice of Medicine Folsom's Laws of V. S. on Custody of Insane Foster's Physiology .... ♦Fothergill's Handbook of Treatment . Fownes' Elemeniary Chemistry Fox on Diseases of the Skin . Frankland and Japp's Inorganic Chemistry Fuller on the Lungs and Air Passages Galloway's Analysis .... Gibney's Orthopaedic Surgery Gibson's Sui-gery .... Gluge's Pathological Histology, by Leidy Gould's Surgical Diagnosis *Gray's Anatomy ... Greene's Medical Chemistry . Green's Patliologj' and Moi'bid Anatomy Grithlh's Universal Formulary Gross on Foreign Bodies in Air-Passages Gross on Impotence and Sterility . Gross on Urinary Organs *Gross' System of Surgery Habershonon the Abdomen ♦Hamilton on Fractures and Dislocations Hamilton on Nervous Diseases Hartshorne's Anatomy and Ph.vsiology . Hartshorne's Conspectus of thelNIed. Sciences Hartshorne's Essentials of Medicine Hermann's Experimental Pharmacology Hill on Syphilis ..... Hillier's Handbook of Skin Diseases Hoblyn's Medical Dictionary Hodge on Women .... Books marked * 6 3 27 15 20 28 9 21 29 17 29 27 29 17 24 3,7 3,20 6 19 14 3,16 23 ■18 11 11 3,21 21 25 24 3,21 23 14 17 10 27 6 10 5 19 10 13 18 24 30 20 25 13 25 3,6 7 8 7 16 7 21 28 4 27 7 28 21 21 12 16 16 18 18 18 18 18 16 16 14 19 8 16 8 26 9 18 3 20 20 13 3,20 5 10 Hodge's Obstetrics .... Hotlmann and Power's Chemical Analysis Holden's Landmarks .... Holland's Medical Notes and Reflections *Holmes' System of Surgery - Horner's Anatomy and Histology Hudson on Fever Hutchinson on Syphilis Hj'de on the Diseases of the Skin . Jones (C. Handfield) on Nervous Disorders Juler's Ophthalmic Science and Practice Keating on Infants King's Manual of Obstetrics . Klein's Histology La Roche on Pneumonia, Malaria, etc. La Roche on Yellow Fever . Laurence and Moon's Ophthalmic Surgery Lawson on the Eye, Orbit and Eyelid Lea's Studies in Church History Lea's Superstition and Force Lee on Syphilis Lehmanli's Chemical Physiology *Leishman's Midwifery . . Lucas on Diseases of the Urethra Ludlow's Manual of Examinations Ijyons on Fever . Maisch's Organic Materia Medica Marsh on the Joints Medical News Meigs on Childbed Fever Miller's Practice of Surgery . Miller's Principles of Surgery Mitcliell's Nervous Diseases of Women Morris on Diseases of the Kidneys Morris on Skin Diseases Neill and .Smith's Compendium of Med. Sci. Nettieship on Diseases of the Eye . Owen on Diseases of Children *Parrish's Practical Pharmacy Parry on Extra-Uterine Pregnancy Parvin's Midwifery Pavy on Digestion and its Disorders Pepper's Forensic Medicine . Pepper's Surgical Pathology Pick on Fractures and Dislocations Pirrie's System of Surgery Playfair on Nerve Prostration and Hysteria *Playfair's Midwifery . Politzer on the Ear and its Diseases Power's Human Physiology . Ralfe's Clinical Chemistry Ramsbotham on Parturition Remsen's Theoretical Chemistry . *Reynolds' System of Medicine Richardson's Preventive Medicine Roberts on Urinary Diseases Roberts' Principles and Practice of Surgery Robertson's Physiological Physics Rodwell's Dictionary of Science Sargent's Minor and Militarj' Surgery Savage on Insanity, including Hysteria Schafer's Essentials of Histology, Schafer's Histology Schreiber on Massage . Seller on tlie Throat, Nose and Naso-Pharynx Series of Clinical Manuals Simon's Manual of Chemistry Skev's Operative Surgery Slade on Diphtheria Smith (Edward) on Consumption Smith (H. H.) and Horner's Anatomical Atlas *Smith (J. Lewis) on Children StlUe on Cholera ... *Stillfi & Maisch's National Dispensatory *Still6's Therapeutics and Materia Medica Stimson on Fractures .... Stimson's Operative Surgery Stokes on Fever ..... Students' Series of Manuals . Sturges' Clinical Medicine Tanner on Signs and Diseases of Pregnancy Tanner's Manual of Clinical Medicine . Tarnier and Chantreuil's Obstetrics Taylor on Poisons .... *Taylor's Medical Jurisprudence . Taylor's Prin. and Prac. of Med. Jurisprudence *Thomas on Diseases of Women Thompson on Stricture Thompson on Urinary Organs Tidy's Legal Medicine .... Todd on Acute Diseases 13 I Treves' Applied Anatomy n Treves on Intestinal Obstruction . Take on the Influence of Mind on the Body Walshe on the Heart .... Watson's Practice of Physic . *Wells on the Eve .... West on Diseases of Childhood Weston Diseases of Women West on Nervous Disorders in Childhood V/illiarns on Consumption . Wilsons Handbook of Cutaneous Medicine AVilson's Human Anatomy . Wiiickel on Pathol, and Treatment of Childbed Wiihler's Organic Chemistry Wood head's Practical Pathology Year-Book of Treatment 28 are also botmd in lialf Kussia. LEA BROTHERS & CO., Philadelpliia. COLUMBIA UNIVERSITY LIBRARIES |l!!|| >» ' 0052051390 188 H ^ Copy 1 ^