Plate i. 
 
 
 
 
 
 
 I. 
 
 PALE YELLOW. 
 
 
 
 
 
 
 11. 
 LIGHT YELLOW, 
 
 
 
 
 
 
 HI. 
 
 YELLOW. 
 
 
 
 
 
 
 IV. 
 
 REDDISH YELLOW. 
 
 
 
 
 
 :-^'mm^ 
 
 V. 
 
 YELLOWISH RED. 
 
 
 
 
 
 ^^^^^^^^^^^^^^^^^^^^^^^^^^^^ 
 
 VI. 
 
 RED. 
 
 
 
 
 
 ^^^^^1 
 
 VII. 
 
 BROWNISH RED. 
 
 
 
 
 
 I^HI^I 
 
 VIII. 
 
 REDDISH BROWN. 
 
 
 
 
 
 
 IX. 
 
 BROWNISH BLACK. 
 
 
 
 Scale of Urinary Colors, according to Vogel.
 
 Clinical 
 Examination of the Urine 
 
 AND 
 
 Urinary Diagnosis 
 
 A Clinical Guide for the Use of Practitioners and 
 Students of Medicine and Surgery 
 
 J. BERGEN OGDEN, M.D. 
 
 INSTRUCTOR IN CHEMISTRY, HARVARD UNIVERSITY MEDICAL SCHOOL ; ASSISTANT IN CLINICAL 
 
 PATHOLOGY, BOSTON CITY HOSPITAL ; MEDICAL CHEMIST TO THE CARNEY HOSPITAL; 
 
 VISITING CHEMIST TO THE LONG ISLAND HOSPITAL, BOSTON. 
 
 ILLUSTRATED 
 
 PHILADELPHIA AND LONDON 
 
 Vv^. B. SAUNDERS & COMPANY 
 1 90 1
 
 Copyright, 1900, 
 By W. B. SAUNDERS & COMPANY. 
 
 PRESS OF 
 W. B. SAUNDERS & COMPANY.
 
 I ; - - 
 
 TO 
 
 3£Dwar2) Sticftncg XUHooJ), a./IR., /1B.2).» 
 
 PROFESSOR OF CHEMISTRY, HARVARD UNIVERSITY MEDICAL SCHOOL, 
 
 AS A SLIGHT TOKEN OF HIGHEST ESTEEM AS 
 
 A TEACHER AND FRIEND, 
 
 THIS VOLUME 
 
 IS RESPECTFULLY DEDICATED BY 
 
 THE AUTHOR.
 
 PREFACE. 
 
 The design of this work is to present in as concise a 
 manner as possible the chemistry of the urine and its rela- 
 tion to physiologic processes ; the most approved working 
 methods, both qualitative and quantitative ; the diagnosis 
 of diseases and disturbances of the kidneys and urinary 
 passages. 
 
 Since most of the books on the urine at the present time 
 are devoted almost exclusively to urinary chemistry, and 
 since a knowledge of urinary diagnosis is obtainable only 
 by an extended search through various works on medicine, 
 surgery, pathology, and chemistry, I have long felt the need 
 of a treatise which takes up in detail the subject of urinary 
 diagnosis and the application of information furnished by 
 careful chemic and microscopic examination of the urine. 
 
 The work naturally falls into two parts. 
 
 In Part I chemic and microscopic methods are described 
 in detail, and numerous illustrations, many of which are 
 original, have been introduced, thus enabling the student 
 and practitioner who has not had special training in urinary 
 analysis to obtain accurate results. 
 
 In Part II special attention has been paid to diagnosis, 
 which includes our present knowledge of the character of 
 the urine, the diagnosis and differential diagnosis of dis- 
 turbances and diseases of the kidneys and urinary passages, 
 whether they be local or general, medical or surgical ; a 
 brief enumeration of the prominent clinical symptoms of 
 each disease ; and, finally, the peculiarities of the urine in 
 certain general diseases of the body. 
 
 My chief object, therefore, in presenting this w'ork is to 
 furnish the student and practitioner with a more complete 
 clinical guide to urinary diagnosis than I have heretofore 
 met with in a single volume. 
 
 No attempt has been made to incorporate in this volume 
 more than a limited number of references to the literature 
 
 9
 
 10 PREFACE. 
 
 on the various urinary subjects that have been considered. 
 Those references given are, for the most part, to subjects 
 that are still under discussion, or to those that are com- 
 paratively new to medical literature. 
 
 Numerous books and original monographs have been 
 consulted, and the views of standard authorities have been 
 freely quoted in this work. I have endeavored in all cases 
 to give full credit to the various writers throughout the text. 
 If in any instances I have been remiss, I take this oppor- 
 tunity of thanking those who have unwittingly aided me by 
 their researches and writings. 
 
 In conclusion, I wish to express my sincerest thanks to 
 Dr. Edward S. Wood for the many valuable suggestions 
 he has given me in the production of this volume. 
 
 J. Bergen Ogden. 
 
 July, igoo.
 
 CONTENTS 
 
 PAGE 
 
 Introduction 17 
 
 CHAPTER I. 
 
 Constituents of Normal Urine 21 
 
 Physical Properties of Urine . 24 
 
 CHAPTER. II. ,,-— "^v 
 
 Organic Constituents of Normal Urine (_At-^ 
 
 Urea 41 
 
 Table of Approximate Proportions of Urea in Urine, for Clinical 
 
 Use ,^55"-: 
 
 Uric Acid 59- 
 
 Xanthin Bases yi 
 
 Nucleic Acid 75 
 
 AUantoin 76 
 
 Kreatin and Kreatinin 78 
 
 The Aromatic Substances in Urine 80 
 
 Urinary Coloring-matters 90 
 
 Other Organic Constituents of the Urine 96 
 
 CHAPTER III. 
 
 Inorganic Constituents of Normal Urine 99 
 
 Chlorides 9^ 
 
 ■ Phosphates 'v|o^^- 
 
 Sulphates in 
 
 Carbonates 115 
 
 Iron . . 116 
 
 Hydrogen Peroxide 1 16 
 
 CHAPTER IV. 
 
 Abnormal Constituents of Urine 117 
 
 Proteids 117 
 
 Albumin 118 
 
 Globulin 122 
 
 Albumoses 134 
 
 Peptone 136 
 
 Method of Separation and Identification of Proteids 139 
 
 Nucleo-albumin 140 
 
 Hemoglobin 142 
 
 Fibrin 143 
 
 CHAPTER V. 
 
 Carbohydrates . 145 
 
 Glucose 145 
 
 Lactose 164 
 
 11
 
 12 CONTENTS. 
 
 PAGE 
 
 Levulose 165 
 
 Laiose 166 
 
 Substances Allied to Sugar 167 
 
 Inosite . 167 
 
 Glycuronic Acid 169 
 
 Cane Sugar 170 
 
 Acetone 171 
 
 Diacetic Acid 174 
 
 Bile 175 
 
 Biliary Acids 178 
 
 Ehrlich's Diazo Reaction 182 
 
 Various Metallic Substances 184 
 
 Hematoporphyrin 187 
 
 Melanin 190 
 
 Ptomaines and Leucomaines. — Toxicity of Urine 191 
 
 CHAPTER VI. 
 
 Urinary Sediments 199 
 
 Methods of Obtaining Urinary Sediments 200 
 
 The Preparation of Sediments for Microscopic Examination . . . 206 
 
 Urinary Sediments 207 
 
 Nonorganized Sediments 208 
 
 Organized Sediments 230 
 
 Extraneous Substances Found in Urine 261 
 
 Preservation of Urinary Sediments 261 
 
 Micro-organisms 263 
 
 Parasites 267 
 
 CHAPTER Vn. 
 
 Urinary Concretions 270 
 
 PART 11. 
 
 Diagnosis 282 
 
 CHAPTER Vni. 
 
 Disturbances and Diseases of the Kidneys 282 
 
 Active Hyperemia 282 
 
 Passive Hyperemia 289 
 
 Acute Diffuse Nephritis 292 
 
 Subacute Glomerular Nephritis 300 
 
 Chronic Interstitial Nephritis 305 
 
 Senile Interstitial Nephritis 313 
 
 Chronic Diffuse Nephritis 314 
 
 Amyloid Infiltration 317 
 
 CHAPTER IX. 
 
 Diseases of the Kidneys (Continued) 321 
 
 Tuberculosis of the Kidneys 321 
 
 Renal Calculus 324 
 
 Abscess of the Kidney 326 
 
 Renal Embolism 327 
 
 Tumors of the Kidney 328 
 
 Cystic Disease of the Kidneys 329
 
 CONTENTS. 13 
 
 CHAPTER X. 
 
 PAGE 
 DlSE.\SES OF THE URINARY TRACT BELOW THE KiDNEY PROPER . 33 1 
 
 Pyelitis 33^ 
 
 Acute Pyelitis 33^ 
 
 Chronic Pyelitis 333 
 
 Calculous Pyelitis 335 
 
 Hydronephrosis 337 
 
 Pyonephrosis 339 
 
 Ureteritis 34^ 
 
 Cystitis 342 
 
 Acute Cystitis 342 
 
 Chronic Cystitis 344 
 
 Tuberculosis of the Bladder 34^ 
 
 Tumors of the Bladder 34^ 
 
 Prostatitis 35' 
 
 Acute Prostatitis 35' 
 
 Prostatic Abscess ... 353 
 
 Chronic Prostatitis 353 
 
 Tubercular Prostatitis 35^ 
 
 Cancer of the Prostate ■- 357 
 
 Urethritis 357 
 
 Chyluria " 3^0 
 
 Hemoglobinuria 3"2 
 
 Pneumaturia , 3"4 
 
 Uremia 3"5 
 
 Diabetes Mellitus 3^8 
 
 Diabetic Coma 373 
 
 Diabetes Insipidus 375 
 
 CHAPTER XI. 
 
 The Urine in Diseases outside of the Urinary Tract .... 378 
 
 Fever Urine 37^ 
 
 Urine of Chronic Disease (not Renal) 379 
 
 Typhoid Fever 380 
 
 Yellow Fever 381 
 
 Typhus Fever 382 
 
 Relapsing Fever 382 
 
 Pneumonia 383 
 
 Pulmonary Tuberculo.sis 384 
 
 • Malarial Fever . . 385 
 
 Erysipelas 3°^ 
 
 Cholera 387 
 
 Scarlet Fever 388 
 
 Diphtheria 39° 
 
 Smallpox • 390 
 
 Acute General Peritonitis 39 ^ 
 
 Intestinal Obstruction 39' 
 
 Acute Yellow Atrophy of the Liver 392 
 
 Hysteria . . 393 
 
 Cerebrospinal Meningitis 393 
 
 Melancholia 394 
 
 Acute Myelitis 394 
 
 Epilepsy 395 
 
 Acute Articular Rheumatism 395 
 
 Gout 396 
 
 Anemia 397 
 
 Scurvv 397
 
 14 CONTENTS. 
 
 PAGE 
 
 Carbolic Acid Poisoning 398 
 
 Poisoning by Phospliorus and Arseniureted Hydrogen 398 
 
 APPENDIX A. 
 
 Method of Recording Urinary Examinations 400 
 
 Order of Applying Tests 403 
 
 Method of Making Diagnoses of Diseases of the Kidneys from the 
 
 Urine 403 
 
 APPENDIX B. 
 
 Reagents and Apparatus for Qualitative and Quantitative 
 
 Analysis of Urine 406 
 
 Liquid Reagents 406 
 
 Solid Reagents 4°? 
 
 Apparatus 407 
 
 INDEX 409
 
 CLINICAL 
 
 EXAMINATION OF THE URINE 
 
 AND 
 
 URINARY DIAGNOSIS.
 
 URINARY ANALYSIS. 
 
 INTRODUCTION. 
 
 The urine is an aqueous solution of organic and inor- 
 ganic substances excreted and secreted by glands called 
 the kidneys. Assuming that the reader is acquainted with 
 the gross and minute structure of the kidneys, it remains 
 for us to consider some of the physiologic processes which 
 are concerned in the production of the urine. The very 
 close relation which exists between the blood-vessels and 
 the uriniferous tubules suggests at once the fact that the 
 fluid called urine is the product of nature's effort to re- 
 move from the body, by way of the blood, those substances 
 which are no longer useful to the tissues of the body ; in 
 other words, the urine is essentially a solution of waste- 
 products of the body. 
 
 Having carefully studied the minute structure of the 
 kidneys, we find that, unlike other secreting organs, they 
 consist of two parts, so distinct in structure that it seems 
 almost impossible to resist the conclusion that their func- 
 tions are different, and that the mechanism by which the 
 urine is secreted is of a double kind. The uriniferous 
 tubules, on the one hand, with their characteristic epithe- 
 lium, appear to be merely secreting structures ; while, on 
 the other hand, the Malpighian capsules with their glom- 
 eruli are structures wdth insignificant epithelium, strongly 
 suggesting that their function is rather one of the nature of 
 a filter than of a secreting structure. Such is the theory 
 of Bowman, since he first pointed out that certain constit- 
 uents of the urine only are put forth by the uriniferous 
 tubules, which act in a manner similar to other secreting 
 glands, and that the other constituents, including water 
 and various soluble and diffusible salts from the blood, are 
 apparently filtered out by the glomeruli. It is very evident 
 from the vascular arrangement in the kidney that the 
 
 2 17
 
 18 INTRODUCTION. 
 
 capacity of the kidney for work is closely dependent on the 
 flow of blood through it, and this appears to be controlled 
 largely by the vasomotor and vasodilator nerves, which are 
 supplied by the anterior roots of the eleventh, twelfth, and 
 thirteenth dorsal nerves. 
 
 The theory of Ludwig, based on the varying degrees of 
 blood pressure in the glomeruli, and the elimination of cer- 
 tain constituents of the blood by diffusion or osmosis, can 
 hardly be considered tenable in the light of recent physi- 
 ologic research. In this theory Ludwig did not consider 
 the importance of the renal epithelium in the secretion of 
 urine, as has been well demonstrated by the experiments 
 of Heidenhain, who found that by injecting a solution of 
 sodium indigo-sulphate into the blood of an animal not 
 only the urine became blue, but the epithelial cells lining 
 the convoluted tubules and the looped tubes of Henle 
 were also colored blue, while there was not the slightest 
 trace of blue in the Malpighian bodies. By first dividing 
 the spinal cord of an animal and J:hen injecting the indigo 
 solution, he also demonstrated the fact that the renal 
 epithelium has distinct eliminativ^e power. He found the 
 following : That no urine reached the bladder, and the epi- 
 thelium lining the convoluted tubules as well as those of 
 Henle was stained blue the same as before ; that when the 
 animal was killed, a sufficient period after the injection, the 
 epithelium was found to be free from coloring-matter, and 
 the indigo compound had passed into the lumen of the 
 tubules, where, in the absence of water from the glomeruli, 
 it had crystallized. It often happens in some diseases of 
 the kidneys in which the renal tubules become stripped of 
 their epithelium that the urea and other products of the 
 metabolism are no longer so thoroughly removed from the 
 body, but remain in the blood, and frequently cause the 
 symptom known as uremia, often when the watery constit- 
 uent is eliminated in abundance. 
 
 It is, therefore, fair to conclude that the renal epithelial 
 cells are normally actively engaged in the process of secre- 
 tion, and that the water and some of the soluble salts of 
 the urine are secreted largely by the glomeruli, the func- 
 tion of which is regulated chiefly by the varying degrees 
 of blood pressure. 
 
 Too much can not be said regarding the importance of 
 an accurate examination of the urine, — both chemic and
 
 INTRODUCTION. 19 
 
 microscopic, — for it is by this means only that the condi- 
 tion of the kidneys — whether healthy or diseased — and 
 their capability for work can be definitely determined. 
 Furthermore, by the correct interpretation of the results of 
 modern methods of urinary analysis, the variations in the 
 body metabolism — nutrition and waste — can also be deter- 
 mined, and such information is often of the greatest impor- 
 tance to the physician in judging of the diagnosis and 
 prognosis of disease. While it is impossible to diagnosti- 
 cate all diseases from an examination of the urine, it is, 
 nevertheless, a fact that an extensive disease, whether in 
 the kidneys or not, can not exist in the human organism 
 without showing its effect in the urine. This is more espe- 
 cially true in connection with diseases and disturbances of 
 the kidneys, when any deviation in the urine from the nor- 
 mal furnishes us with the only reliable data concerning the 
 nature of the diseased process. 
 
 It is, therefore, essential that the practitioner and student 
 of medicine should become perfectly familiar with those 
 features of the urine that are characteristic of certain dis- 
 eased conditions ; and also to become acquainted with 
 those alterations of the urine found in various functional 
 disturbances of the body, such as derangements of gastric 
 and intestinal digestion, etc. 
 
 Nomenclature. — The student of medicine is frequently 
 confused b)- the complicated nomenclature of the diseases 
 of the kidneys. He finds that the various diseased condi- 
 tions of these organs have received a variety of names, and 
 that the terms employed indicate a number of pathologic 
 conditions. This is partly due to the fact that a given 
 cause does not always produce the same anatomic lesions 
 in the kidneys, and partly to the fact that a marked lack of 
 uniformity exists between the terms used by the pathologist 
 and those used by the clinician in the description of any 
 given kidney disease. What is certainly needed are more 
 numerous and more thorough clinical observations, and, 
 in every instance possible, a careful study of these observa- 
 tions in connection with the pathologic findings. 
 
 As Councilman ^ has said : " For the present, the classi- 
 fication of the diffuse lesions of the kidney must be founded 
 on the character of the anatomical lesions. A classification 
 
 ' " American Journal of the Medical Sciences," July, 1897.
 
 20 INTRODUCTION. 
 
 on an etiological basis is the most scientific and the simplest, 
 but we know little or nothing of the etiology of these dis- 
 eases. Various forms of disease in other organs, partic- 
 ularly of the heart, are often found associated with them. 
 Bacteriological investigation has shown in many cases the 
 presence of certain organisms in the kidney. In most 
 cases the bacteria are found in some other lesions and in 
 the blood, and their presence in the kidney is but a part of 
 a general septicemia. Moreover, the same condition in 
 the kidney may be associated with a variety of organisms, 
 and the same organism may be associated with widely dif- 
 ferent anatomical lesions." 
 
 The nomenclature which the author has adopted in this 
 work is calculated to be abreast with recent pathologic 
 investigation. The term cJironic parciicJiyniatous nephritis, 
 which was introduced by Virchow (1852), has been re- 
 placed by the term subacute glomerular nephritis. This 
 change is based upon the fact that the lesion which was 
 formerly thought to be confined to the epithelial constit- 
 uents of the kidney has recently been found to involve 
 chiefly the glomeruli ; also because the disease is sub- 
 acute rather than chronic in duration. 
 
 In the use of the word nephritis it must be understood 
 that the lesions referred to are not necessarily inflamma- 
 tory ; while inflammatory exudation in some form is fre- 
 quently present, it is safe to say that the majority of lesions 
 of the kidneys are not inflammatory. 
 
 We shall frequently refer to diffuse lesions of the kidney, 
 such as acute diffuse nephritis and chronic diffuse nephri- 
 tis. By the term diffuse we do not mean that all parts of 
 the kidney are equally affected. It has been demonstrated, 
 by the study of degenerations and the effect of poisons, 
 that in some instances the most marked changes are in the 
 convoluted tubules, while in others they are in the loops 
 of Henle or in the collecting tubules. All parts of the 
 kidney are equally exposed to the action of chemic irri- 
 tants, but all may not be equally susceptible. Likewise, in 
 glomerular lesions of the kidney the accompanying degen- 
 erative lesions in the renal epithelium may be in part or 
 wholly secondary to the lesions of the glomeruli. In other 
 words, in diffuse lesions of the kidney various parts of the 
 organ may be primarily or secondarily affected, but usually 
 not all parts are affected to the same extent.
 
 CHAPTER I. 
 
 CONSTITUENTS OF NORMAL URINE» 
 
 The complexity of the urine eHminated under normal 
 conditions is well shown by the following classification of 
 Hoppe-Seyler : 
 
 1. Urea and allied substances : Uric acid, allantoin, 
 oxalic acid, xanthin, guanin, kreatinin, and thio- (sulpho-) 
 cyanic acid, 
 
 2. Fatty and other nonnitrogenous substances : Fatty 
 acids of the series C.iHj^Oj ; oxalic, lactic, glycerophos- 
 phoric acids ; minute quantities of certain carbohydrates (?). 
 
 3. Aromatic substances: The ethereal sulphates of phe- 
 nol, kresol, pyrocatechin, indoxyl, and skatoxyl ; hippuric 
 acid ; aromatic oxyacids. 
 
 4. Other organic substances : Pigments ; ferments, espe- 
 cially pepsin ; mucous and humous substances ; kynurenic 
 acid. 
 
 5.. Inorganic salts : Chlorides of sodium and potassium ; 
 potassium sulphate ; sodium, calcium, and magnesium 
 phosphates ; silicic acid ; ammonia compounds, and cal- 
 cium carbonate. 
 
 6. Gases : Nitrogen and carbonic acid. 
 
 Quantitative Composition of Normal Urine. — A num- 
 ber of estimations of the constituents of normal urine have 
 been made, but the following table by Parkes gives the 
 most accurate determination thus far known : 
 
 AMOUNTS OF URINARY CONSTITUENTS ELIMINATED IN 
 TWENTY-FOUR HOURS (PARKES). 
 
 By an Average Man Weigh- Per Kilogram of 
 Constituents. ing Sixty-six Kilograms. Body-weight. 
 
 Water 1500.00 grams. 23.000 grams. 
 
 Total solids 72.00 " 1. 100 " 
 
 Urea 33- 18 " 0.500 " 
 
 Uric acid 0.55 " 0.008 " 
 
 Hippuric acid 0.40 " 0.006 " 
 
 21
 
 22 CONSTITUENTS OF NORMAL URINE. 
 
 AMOUNTS OF URINARY CONSTITUENTS ELIMINATED IN 
 TWENTY-FOUR HOURS (PKKK.Y.?,). — {Continued.) 
 
 By an Average Man Weigh- Per Kilogram of 
 Constituents. ing Sixty-six Kilograms. Body-weight. 
 
 Creatinin 0.91 grams. 0.014 grains. 
 
 Pigment and other organic sub- 
 stances 10.00 " o. 151 " 
 
 Sulphuric acid 2.01 " 0.030 " 
 
 Phosphoric acid 3.16 " 0.048 " 
 
 Chlorine 7-8.00 " 0.126 " 
 
 Ammonia 0.77 " 
 
 Potassium 2.50 " 
 
 Sodium 11.09 " • • 
 
 Calcium 0.26 " 
 
 Magnesium 0.21 " . . 
 
 Yvon and Berlioz ^ have carefully studied the urines of 
 both male and female, and have constructed the following 
 comparative table, which includes the amounts of some of 
 the more important urinary solids, excepting chlorides : 
 
 Male. Female. 
 
 Quantity (per diem) 1360 c.c. iioo c.c. 
 
 Specific gravity 1022 " 1021 " 
 
 Urea (per liter) 21.5 grams 19. grams 
 
 " (per diem) 25.6 " 20.5 '< 
 
 Uric acid (per liter) 0.5 " 0.55 " 
 
 •' " (per diem) 0.6 " 0.57 " 
 
 Phosphoric acid (per liter) 2.5 " 2.4 " 
 
 " " (per diem) 3.2 " 2.6 " 
 
 Collection of Urine for Analysis. — The whole quantity 
 of urine for twenty-four hours should, in all cases, be col- 
 lected, thoroughly mixed, and carefully measured. If the 
 entire secretion for twenty-four hours can not be conven- 
 iently submitted for analysis, a sample (from four to eight 
 ounces) of the mixed urine, together with a statement of the 
 quantity eliminated in twenty-four hours, will suffice. 
 
 A four or five pint bottle, perfectly clean, is perhaps the 
 most convenient receptacle for the urine during its collec- 
 tion. The botde should be well corked after each addition 
 of the urine, and should stand in a cool place. The urine 
 should never be collected or allowed to stand in an open 
 or, above all, in an unclean vessel. Every effort should be 
 made to avoid the introduction of particles of dust, fecal 
 matter, expectorated matter, and the like, all of which seri- 
 ously interfere with the subsequent analysis of the urine, 
 
 1 "Lancet," vol. 11, 1888, p. 629.
 
 COLLECTION OF URLXE. 23 
 
 It should be borne in mind that the urine begins to un- 
 dergo the process of decomposition within a few hours after 
 it has been v^oided, although the changes are usually very 
 slight and unimportant, providing the urine is kept cool. 
 In order, however, to guard against decomposition of the 
 urine during its collection, it is advisable to put into the 
 bottle one ounce of a cold saturated aqueous sohition of boric 
 acid (about four per cent.), or tivo or three drops of formalin 
 (not more) ; stopper tightly, and then add the urine imme- 
 diately after each micturition. The ounce of boric acid 
 solution is to be deducted from the total quantity of urine 
 when it is measured. 
 
 A convenient time to begin to save the urine is at 7 a. m. 
 At that hour, or such other time as may be decided upon, 
 the bladder should be emptied, and the urine thrown away ; 
 then all the urine voided in the subsequent twenty-four 
 hours, including the amount of urine in the bladder at 7 
 A. M. the next day, will represent the total quantity for 
 twenty-four hours. It is often important to collect the day 
 and )iight urine separately ; in such cases the urine voided 
 between 7 a. m. and 7 p. m. is to be placed in one bottle, 
 and that voided between 7 p. m. and 7 a. :ni. in another 
 bottle, carefully labeling each. 
 
 For the qualitative exannnation a single specimen of 
 urine, the product of one micturition, may be collected. 
 Since there is a marked variation in the urine at different 
 times of day, a specimen should be taken at a time when 
 the urine is most likely to contain the largest proportion 
 of morbid elements — /. c., about midday or between three 
 and four hours after a meal. For the purpose of compari- 
 son such a sample should, however, always be accom- 
 panied by another specimen collected in the morning on 
 rising — /. e., at a time when the urine contains the smallest 
 proportion of abnormal elements. As previously indicated, 
 the urine should always be poured into a perfectly clean 
 bottle, and should be submitted for examination in a per- 
 fectly fresh condition, — that is, before decomposition has 
 begun, — since the morphologic elements, such as casts, 
 epithelium, etc., in a urine that has decomposed may dissolve 
 or become so altered that they are beyond recognition.
 
 24 CONSTITUENTS OF NORMAL URINE. 
 
 PHYSICAL PROPERTIES OF THE URINE. 
 
 Quantity. — For a healthy adult the average quantity of 
 urine in twenty -four hours is 1500 c.c, or about 50 fluid- 
 ounces. The normal variation is between 1200 and 1600 
 c.c, according to the size, habits, and sex of the individ- 
 ual — for example, a female of average size usually passes 
 less urine in twenty-hours than an averaged-size male. 
 Furthermore, a small adult, male or female, may not elimi- 
 nate more than 1200 c.c, and yet be in a state of perfect 
 health. The habits of the person have, perhaps, the 
 greatest influence on the twenty-four-hour quantity in 
 health ; the habitual ingestion of considerable quantities of 
 liquids, liberal eating, and the like, may cause the quantity 
 to reach 1600 c.c, or even more. On the other hand, 
 exercise, free perspiration, the ingestion of very little liquid, 
 may result in the elimination of a small quantity of urine, 
 even below 1200 c.c. 
 
 The quantity of urine in health varies considerably with 
 the time of day, the largest amount being passed in the 
 afternoon, the least at night, and the mean quantity in the 
 forenoon. 
 
 The total quantity of urine for twenty-four hours should 
 be accurately measured in every case in which the urine is 
 to be examined, and it is frequently necessary, particularly 
 in disease of the kidneys, to measure the urine every day 
 for a period of one, two, or three weeks, in order to ascer- 
 tain the average daily quantity. Upon the total quantity 
 depend all quantitative determinations, and, therefore, intelli- 
 gent inferences as to the capability of the kidneys for work. 
 
 Diminished Quantity. — A diminished quantity of urine 
 in twenty -four hours — that is, less than i 500 c.c. — has the 
 following causes : (i) Small quantity of liquid taken ; (2) 
 free perspiration ; (3) fever ; (4) diarrhea ; (5) vomiting, and 
 the following renal disturbances and diseases : (6) most 
 cases of active hyperemia ; (7) passive hyperemia ; (8) first 
 and second stages of acute diffuse nephritis ; (9) subacute 
 glomerular nephritis ; (10) toward death in all diseases. 
 
 Increased Quantity. — The causes of an increased quan- 
 tity of urine in twenty-four hours are as follows: (i) 
 Large quantity of liquid taken ; (2) diuretic treatment ; 
 (3) nervous excitement and some diseases of the nervous 
 system (frequently in hysteria, and temporarily in cerebral
 
 COLOR OF URINE. 25 
 
 hemorrhage) ; (4) diabetes melHtus ; (5) diabetes insipidus ; 
 (6) convalescence from acute diseases in general, and the 
 following disturbances and diseases of the kidneys : (7) 
 convalescence from a severe active hyperemia ; (8) con- 
 valescence from an acute diffuse nephritis ; (9) chronic inter- 
 stitial nephritis ; (10) chronic diffuse nephritis ; (i i) amyloid 
 infiltration. 
 
 Oliguria is the term applied to those cases in which the 
 quantity of urine is very small, typically seen during the 
 acute stage of an acute disease, also in those chronic dis- 
 eases that are attended with extensive dropsy. 
 
 Anuria is applied to cases in which there is no urine, or 
 when only an exceedingly small quantity is passed — in 
 other words, complete, or almost complete, supprcssio)i of 
 uri)ic. This condition is. most commonly seen shortly be- 
 fore death, particularly in extensive disease of the kidneys. 
 Total, or nearly total, suppression may last several days — 
 from five to ten. 
 
 Polyuria is a term signifying the excretion of a large 
 quantity of urine without any reference to the quantity of 
 total solids in twenty-four hours. Hydruria is a term 
 signifying the excretion of a large amount of urine — in other 
 words, a polyuria — with either a normal quantity or a 
 diminution in the total solids for twenty -four hours : for 
 example, in marked cases of chronic interstitial nephritis, 
 the solids are notably diminished. 
 
 Obstructive suppression occurs when there is a partial 
 or complete obstruction to the outflow of urine through 
 the ureters, and is sometimes found to be due to the pres- 
 ence of impacted calculi in both ureters ; also to the pres- 
 sure of a new growth, and occasionally by valves or twists 
 of the ureters. In a case reported by Farlow^ obstruction 
 was caused by a new growth of the uterine appendages, 
 and almost complete obstruction lasted for twelve days. 
 
 Retention of urine is the result of an obstruction to the 
 outflow of urine through the urethra, as by a tight urethral 
 stricture, the presence of a calculus in the urethra, or by 
 some mechanical obstruction in the region of the neck of 
 the bladder. 
 
 Color. — I. The color of the urine under normal 
 conditions is straw or amber yellow. This, however, 
 
 ^ J. W. Farlow, "Boston Medical and Surgical Journal," cxx, p. 333.
 
 26 CONSTITUENTS OF NORMAL URINE. 
 
 varies considerably even within the range of perfect health. 
 The color may be said to vary with the dilution or concen- 
 tration of the urine. Thus, a very dilute urine has a pale 
 color and may be almost colorless, containing a relatively 
 small amount of coloring-matter, and in health is usually 
 the result of copious drinking. On the other hand, a con- 
 centrated urine usually has a Jiigli color, contains a relative 
 excess of the normal coloring-matter, and is seen when too 
 little water is taken, also after free perspiration and vigor- 
 ous exercise. It is evident, therefore, that in health the 
 color may range from a very pale or watery color through 
 the yellows to a high or deep red. For practical purposes 
 the color may be termed pale, normal, and high, according 
 to circumstances. 
 
 Vogel has constructed a scale of colors of the urine from 
 nature. (See Frontispiece.) These colors are expressed 
 as (i) pale yellow; (2) light yellow; (3) yellow; (4) 
 reddish-yellow ; (5) yellowish-red ; (6) red ; (7) brownish- 
 red ; (8) reddish-brown ; (9) brownish-black. Vogel classi- 
 fies these colors into groups of three ; the first three being 
 yellow, the second three being red, and the last three 
 brown or black. In applying the chart the urine should 
 first be filtered if not already perfectly transparent. It 
 should then be poured into a glass vessel at least three or 
 four inches in diameter, and examined by transmitted light. 
 This color chart is of considerable value as a means for 
 comparison. 
 
 2. {(.i) Under pathologic conditions there is a greater 
 variation than in health, the color being due either to an 
 increase or diminution of the normal pigments, or to the 
 addition of one or more pathologic coloring-matters. Very 
 pale urines are usually attended with a large quantity 
 of urine, as in chronic interstitial nephritis, chronic dif- 
 fuse nephritis, amyloid infiltration, well-advanced convales- 
 cence from acute nephritis, diabetes mellitus, and diabetes 
 insipidus. On the contrary, the urine may have a pale 
 color with a diiniuished quantity of urine, as in the inactive 
 stage of subacute glomerular nephritis, and in certain 
 chronic affections elsewhere in the body, particularly those 
 accompanied by marked diminution in the normal solids in 
 the urine. 
 
 The urine may have a normal color in certain pathologic 
 conditions, particularly in active hyperemia of the kidneys,
 
 COLOR OF URlxN'E. 27 
 
 frequentl)- in the early stage of chronic interstitial nephritis, 
 and rarely in subacute glomerular nephritis. Occasion- 
 ally, in diabetes mellitus when the quantity of urine is in- 
 creased to three or four liters, the color is normal, the 
 result of an absolute increase of the coloring-matters. 
 
 Urines having a Jugh color are almost invariably seen in 
 the early stage of acute disease, also usually in active and 
 passive hyperemia of the kidneys, active stage of subacute 
 glomerular nephritis, and in certain diseases elsewhere in 
 the bod}', notably liver diseases, acute articular rheumatism, 
 and frequently in cases of chronic rheumatism and chronic 
 gout. 
 
 From the foregoing it is seen that, either in health or 
 disease, the urine may be pale, iioruial, or highly colored ; 
 consequently, as far as the color alone is concerned, only 
 negative inferences can be deduced concerning the existing 
 pathologic condition. 
 
 [b) A dark or smoky urine should always be recog- 
 nized, for it invariably indicates the presence of an ab- 
 normal pigment. Great care should be taken not to 
 confound a dark color with a high color. This abnormal 
 pigment is most commonly found to be decomposed blood 
 pigment (methemoglobin or hematin), although it is fre- 
 quently seen after carbolic acid has been taken, and occa- 
 sionally after its use as an external application. It is also 
 occasionally seen after the use of pJienol compounds, 
 especially certain drugs, such as salol (when taken in large 
 doses), guaiacol, etc. A urine after the ingestion of phenol 
 is usually normal in color when passed, but on standing 
 exposed to the air soon becomes dark, and may, if allowed 
 to stand a still longer time, become almost black — the 
 result of the decomposition product of the phenol (hydro- 
 chinone). A urine containing bile pigment in the form of 
 bilirubin often has a dark color ; when such a urine is 
 shaken, the foam will be found to have a decided yellow or 
 greenish-yellow color, and as the urine stands exposed to 
 the air, it soon takes on a greenish, and if much bile is 
 present a marked green, color. The presence in the urine 
 of an abnormal pigment called melanin may cause a dark 
 urine ; the freshly passed urine usually has a normal color, 
 but on standing exposed to the air it gradually grows 
 darker from above downward, due to the slow oxidation of 
 the chromogen, — melanogen, — which results in the pigment
 
 28 CONSTITUENTS OF NORMAL URINE. 
 
 melanin. Alcaptoii, which has a strong affinity for oxygen, 
 produces a dark-colored urine. The urine is usually normal, 
 or high in color, when passed, but on standing exposed to 
 the air rapidly absorbs oxygen, and a dark color results. 
 
 (c) A black urine is generally produced by unusually 
 large amounts of those substances which cause a dark or 
 smoky urine, particularly methemoglobin, melanin, and 
 alcapton. 
 
 {li^ A bloody urine indicates the presence of normal 
 blood and its pigment, oxyhemoglobin. A urine which has 
 a slightly bloody tint should always be distinguished from 
 one having a high color. 
 
 {e) A blue urine is of very rare occurrence. It is due to 
 the presence of free indigo, a result of the decomposition 
 of the indoxyl, which, in all such instances, is present in 
 enormous quantity. Blue urine has been seen in cholera 
 and rarely in typhus fever. When methylene-blue is taken 
 into the stomach, it is absorbed and eliminated in the urine, 
 to which it gives a marked blue or green color. 
 
 (/) Urines having a greenish tint are occasionally seen, 
 particularly after the use of an abundant quantity of milk, 
 also in the inactive stage of a subacute glomerular ne- 
 phritis, chronic diffuse nephritis, amyloid infiltration, and 
 in some diabetic urines with a high percentage of sugar. As 
 previously mentioned, a urine containing bile may, after the 
 bilirubin has become oxidized, have a marked green color. 
 
 iyg) The urine frequently has an abnormal color after 
 the ingestion of certain vegetable substances, such as santonin, 
 which imparts a yellow color, and rhubarb and senna, which 
 cause a brown or reddish color. 
 
 The following table of Halliburton ^ shows the nature 
 and origin of the chief variations in tint : 
 
 Color. Cause of Color. Pathologic Condition. 
 
 Nearly colorless. Dilution or diminution of Various nervous condi- 
 
 normal pigments. tions, hydruria, dia- 
 
 betes insipidus, granu- 
 lar kidney. 
 Dark yellow tobrown- Increase of normal or oc- Acute febrile diseases, 
 red. currence of pathologic 
 
 pigments. 
 Milky. Fat globules. Chyluria. 
 
 Pus corpuscles. Purulent disease in urin- 
 
 ary tract. 
 
 ^ "Chemical Physiology," 1841, p. 712.
 
 TRANSPARENCY. 
 
 29 
 
 Color. 
 
 Orange. 
 
 Red or reddish. 
 
 Brown to brown- 
 black. 
 
 Greenish-yellow, 
 greenish-brown, 
 approaching black. 
 
 Dirty green or blue. 
 
 Brown-yellow to red- 
 brown, becomes 
 blood-red on addi- 
 tion of alkalies. 
 
 Cause of Color. 
 Excreted drugs, e. g. , 
 
 Unchanged hemoglobin. 
 
 Pigments in food (log- 
 wood, madder, bilber- 
 ries, fuchsin). 
 
 Hematin. 
 
 Methemoglobin. 
 
 Melanin. 
 
 Hydrochinone and cate- 
 chol. 
 
 Bile pigments. 
 
 A dark blue scum on sur- 
 face with a blue de- 
 posit, due to excess of 
 indigo - forming sub- 
 stances. 
 
 Substances introduced 
 into the organism with 
 senna, rhubarb, and 
 chelidonium. 
 
 Pathologic Condition. 
 
 Santonin, chrysophanic 
 acid. 
 
 Hemorrhage or hemo- 
 globinuria. 
 
 Small hemorrhages. 
 Methemoglobinuria. 
 Melanotic sarcoma. 
 Carbolic acid poisoning. 
 
 Jaundice. 
 
 Cholera, typhus ; seen 
 especially when the 
 urine is putrefying. 
 
 Transparency.— Freshly passed normal urine is gener- 
 ally a perfectly transparent fluid ; as far as can be deter- 
 mined by inspection, it is free from solid suspended mat- 
 ter After such a urine has stood a short time (one-half 
 to four hours), however, a light flocculent cloud, consisting 
 of mucus, cells, etc., will be found to occupy the_ center of 
 the column of urine, and if the urine be not highly con- 
 centrated, it usually settles to the bottom of the urine glass. 
 This flocculent cloud is generally not sufficient to render 
 the urine turbid. A perfectly normal, freshly passed urme, 
 may however, be turbid and have a milky appearance, due 
 to a precipitation of earthy phosphates. Such a urine is 
 frequently seen after a hearty meal, especially following the 
 ingestion of vegetable food, and is the result of the elimina- 
 tion of the alkaline salts of the food.-alkaline carbonates, 
 —which render the urine neutral or alkaline, and precipitate 
 the earthy phosphates ; it is perfectly physiologic and 
 usually of short duration, lasting only two to three hours 
 when the urine again becomes clear and transparent. A 
 urine turbid from phosphates may be temporarily seen alter 
 every meal ; but, on the other hand, in some individuals 
 the after-meal urine is rarely, if ever, turbid from this cause. 
 Any urine which is permanently turbid at the time it is 
 voided may safely be considered pathologic.
 
 30 CONSTITUENTS OF NORMAL URINE. 
 
 The total twenty-four-hour urine should in all cases be 
 perfectly clear and transparent. A clear, freshly pas.sed 
 normal urine may, after it becomes cool, and especially if 
 allowed to stand in a cool or cold place, become turbid by 
 the separation of amorphous urates, which soon settle to the 
 bottom of the glass and form an abundant, usually pink, 
 sediment. This deposit of urates is most often seen in 
 highly concentrated, although perfectly normal, urines. It 
 may, however, be seen in the urines of disease, as in respi- 
 ratory and circulatory diseases, and also in the active stage 
 of subacute glomerular nephritis. A deposit of amorphous 
 urates is readily dissolved upon the application of heat. 
 
 Bacteria frequently cause a marked turbidity in urines, 
 and especially albuminous urines which have stood some 
 time exposed to the air. The urine furnishes a favorable 
 medium for the growth of bacteria, and often within twelve 
 hours from the time the urine was passed it will be rendered 
 very turbid. Such urines do not settle well, if at all, prob- 
 ably owing to the constant motion of the bacteria. Fur- 
 thermore, bacteria can not be removed by filtration through 
 ordinary filter-paper, the filtrate being usually as turbid as 
 the unfiltered urine. 
 
 A urine which has undergone alkali)ic dccompositio)i is 
 generally rendered turbid by both bacteria and earthy 
 phosphates ; such permanently alkaline urines should be 
 distinguished from tho.se temporarily alkaline (after-meal 
 urines) ; the former being ammoniacal, while the latter are 
 alkaline from fixed alkalies (absence of ammonia). 
 
 A urine containing a large amount of pus is invariably 
 turbid from the pus in suspension. Purulent urines also 
 usually contain bacteria, which are either present when the 
 urine is passed or grow very rapidly when the urine is 
 allowed to stand exposed to the air. 
 
 Chyle in the urine causes a milky turbidity, due to the 
 presence of very finely divided fat. Such a urine is of rare 
 occurrence. (See Chyluria.) 
 
 Odor. — Normal urine usually has a pleasant, aromatic 
 odor, due, it is believed, to the presence of extremely small 
 quantities of volatile acids — phenylic, taurylic, damaluric, 
 and damolic acids. This aromatic odor is most marked in 
 urines which are concentrated. The so-called " urinous 
 odor" is due to the products of decomposition, and is a 
 putrescent, repulsive odor, in which ammonia is plainly dis-
 
 REACTION. 31 
 
 tinguishable ; all urines, if allowed to decompose, have a 
 urinous odor. An ammoniacal or urinous odor is only im- 
 portant when it is present at the time the urine is passed, 
 thus showing that the urine has decomposed inside the 
 body. When a urine containing a large amount of albumin 
 or a large quantity of pus decomposes, it may evolve the 
 odor of sulphuretted hydrogen, which is formed from the 
 sulphur in the albuminous matter. The H2S in ammoni- 
 acal urine combines with the ammonium to form ammo- 
 nium sulphide, hence the combined odor of sulphuretted 
 hydrogen and ammonium. 
 
 A strong odor of sulphuretted hydrogen to the urine 
 may accompany the evacuation of an abscess, located in the 
 region of the intestine, into the urinary tract ; a purulent 
 urine from this cause usually has also a distinct fecal odor. 
 When urines containing cystin decompose, HgS is evoked, 
 formed from the sulphur in the cystin. 
 
 The urine frequently has a peculiar odor after the inges- 
 tion of certain vegetable substances and certain drugs ; 
 thus, it has a characteristic odor after eating asparagus, 
 and an odor of violets following the inhalation of the 
 vapor of oil of turpentine, or following its absorption from 
 the skin or digestive tract. The absorption of terebene 
 gives to the urine the same odor of violets. The urine has 
 a peculiar odor after the use of copaiba, sandalwood oil, 
 cubebs, tolu, etc. 
 
 The odor of the freshly passed urine is of very little clin- 
 ical importance, excepting in those instances in which it is 
 ammoniacal or evolves the odor of sulphuretted hydrogen. 
 
 Reaction. — The reaction of the normal, twenty-four- 
 hour, mixed urine is ahva\-s acid. This acidity is due 
 to acid sodium phosphate (monosodic acid phosphate, 
 NaH2P04). It is believed that the monosodic acid phos- 
 phate of the urine is partly derived from a chemic combi- 
 nation taking place between the disodic acid phosphate 
 (Na2HP04, neutral or alkaline in reaction) in the blood, 
 and uric acid, also in the blood, according to the following 
 equation : 
 
 Na^HPO, ~ H.CjH.X.O, = NaH^PO, -f NaHC-H^NPj. 
 
 It was formerly supposed that traces of uric and hippuric 
 acids contributed to the acidity of the urine, but such is 
 probably not the case, as has been shown by the experi-
 
 32 CONSTITUENTS OF NORMAL URINE. 
 
 ments of Voit, Huppert, Briicke, and others, who found 
 that both uric and hippuric acids existed in combination, 
 the former as a urate and the latter as a hippurate. 
 
 The degree of acidity varies considerably at the different 
 hours of the day, and particularly with the length of time 
 before or after taking food. Usually, a specimen of urine 
 passed at any time of day is acid, excepting after a meal, 
 when it may be temporarily neutral or alkaline from fixed 
 alkalies — alkaline carbonates — which are derived from the 
 salts ingested with the food. This temporary change in 
 the reaction is sometimes called the alkaline tide, beginning 
 with a gradual diminution of the acidity, then becoming 
 neutral or alkaline, reaching its height in from two to four 
 hours, and finally becoming acid again. This is a physi- 
 ologic condition occurring in individuals who are perfectly 
 healthy. Such a urine is generally turbid from the deposit 
 of earthy phosphates ; the addition of a few drops of acetic 
 acid to the urine wall readily cause the turbidity to disappear 
 entirely. The urine may be highly acid, especially after 
 a fast, — for instance, before breakfast, — when it is usually 
 found to be concentrated, having a high specific gravity and 
 high color. Under normal conditions the freshly passed 
 urine may be faintly acid, normally acid, or strongly acid, 
 and in a general way it may be said that, with the excep- 
 tion of the after-meal urine, the degree of acidity depends 
 largely upon the concentration — that is, if dilute, it is faintly 
 acid, and if highly concentrated, strongly acid. 
 
 A urine that is acid when passed, upon standing exposed 
 to the air for from six to twelve hours often becomes more 
 acid ; this phenomenon has been termed acid fcrnientatioji. 
 This increased acidity has been ascribed by Sherer to the 
 presence of lactic and acetic acids, formed by the decompo- 
 sition of the coloring-matters of the urine ; the decompos- 
 ing element being mucus, which acts as a ferment. This 
 explanation has not been satisfactorily proved, however, 
 while the increased acidity is by no means constant. A 
 urine that has undergone this so-called acid fermentation 
 is usually higher in color than when it was passed, and is 
 very likely to contain crystals of acid urates or uric acid. 
 If such a urine is allowed to stand a longer time, it begins 
 to lose its acidity and finally becomes alkaline. 
 
 The alkalinity of the urine is due either to fixed alkalies, 
 — sodium or potassium carbonates, — as has already been
 
 Plate 2 
 
 Sediment of Alkaline Fermentation (ai^ter Hofmann and 
 Ultzmann).
 
 REACTION. 33 
 
 shown, or to the product of alkahnc decomposition — 
 ammonium carbonate formed from the decomposition of the 
 urea. When the urea is acted upon by the iiira ferment, it 
 takes up two equivalents of water, and results in ammonium 
 carbonate. Thus : 
 
 CII,\./) -f 2H,0 = (NII,)j,CO,. 
 
 Such a urine has an ammoniacal or "urinous" odor, 
 giving off free ammonia, in contradistinction to one alka- 
 hne from fixed alkahes in which no ammonia is evolved. 
 A urine that has undergone alkaline decomposition is 
 usually very turbid, partly from the large number of 
 bacteria present, and partly from the deposit of amor- 
 phous phosphates of calcium and magnesium, and crystal- 
 line elements — notably ammonio-magnesium phosphate 
 (triple phosphate), and frequently ammonium urate. (See 
 Plate 2.) If the urine is allowed to stand undisturbed, its 
 surface may be covered with a film, composed of bacteria 
 and a xegetable growth, in which crystals of ammonio- 
 magnesium phosphate and ammonium urate are often en- 
 tangled. Although this alkaline decomposition is most 
 often seen after the urine has been allowed to stand in the 
 air (natural decomposition), it may be found to have taken 
 place inside the body, particularly in certain chronic inflam- 
 matory processes in the bladder, into which the urea fer- 
 ment has gained access ; the freshly passed urine then has 
 a strong ammoniacal odor and alkaline reaction. 
 
 Normal urine may have an amphoteric reaction, — /. e., 
 the same urine may change blue litmus paper red, and red 
 litmus paper blue, — because of the simultaneous presence 
 in the urine of variable proportions of acid and neutral 
 salts. 
 
 Causes of Diminished Acidity. — i. After a full meal, 
 and particularly following the ingestion of a vegetable diet. 
 In vegetarians, as in herbivora, the food contains an excess 
 of alkaline salts with vegetable acids, such as tartaric, malic, 
 citric, succinic, etc. These acids are converted to carbon- 
 ates, which, passing into the urine, give it a neutral or alka- 
 line reaction. 
 
 2. Following the discharge of the gastric juice from the 
 stomach, as by vomiting or through a gastric fistula. 
 
 3. After the administration of considerable quantities of 
 alkaline carbonates, alkaline phosphates, or caustic alkalies. 
 
 3
 
 34 CONSTITUENTS OF NORMAL URINE. 
 
 4. Decomposition of the urine (alkaline fermentation), 
 the urea being converted into ammonium carbonate. 
 
 Causes of Increased Acidity. — i. Exclusive meat diet. 
 
 2. After hot baths and free perspiration. 
 
 3. Excessive muscular exercise with free perspiration. 
 
 4. Internal administration of acids, such as benzoic or 
 boric acids. 
 
 5. The presence of free fatty acids resulting from patho- 
 logic conditions. 
 
 Specific Gravity. — The specific gravity of normal urine 
 is 102 1 for an average amount of 1500 c.c. in the twenty- 
 four hours. This means that, taking distilled water at 15.5° 
 C. (60° F.) as I, each cubic centimeter of the urine weighs 
 1.02 1 grams ; or taking distilled water as looo, each cubic 
 centimeter of the urine weighs 1021 grams. The specific 
 gravity gives the relative proportion of solid matter in the 
 urine ; then, by knowing the total twenty-four-hour quan- 
 tity of urine, an approximate idea of the absolute solids is 
 obtained by multiplying the last two figures of the specific 
 gravity by 2.33. (See p. 40.) Under normal conditions 
 the specific gravity may vary between 1018 and 1025, such a 
 variation being dependent chiefly upon the total twenty- 
 four-hour amount of urine, the quantity and character of 
 the food ingested, and the rapidity of tissue waste. Thus, 
 a urine dilute from taking a large quantity of liquid may 
 have a specific gravity of 10 18, or as low as 1012 ; and, on 
 the other hand, a concentrated urine following copious per- 
 spiration may have a specific gravity of 1025, or as high as 
 1030, and be passed by a perfectly healthy individual. 
 Such variations from the normal are usually temporary ; 
 if permanent, they are usually pathologic. Nitrogenous 
 food, such as meat, increases the solid matter in the urine, 
 and hence raises the specific gravity to a greater or less 
 degree. 
 
 Under pathologic conditions there is a marked variation 
 in the specific gravity, particularly in diseases of the kid- 
 neys, but also frequently in diseases in other parts of the 
 body ; for example, in chronic interstitial nephritis and in 
 diabetes insipidus the specific gravity may be as low as 
 1 00 1 or 1002 ; and, again, in diabetes mellitus it may go 
 as high as 1050. In most diseases of the kidney there 
 is a tendency toward a low specific gravity, although it 
 may be normal or even high. If a normal or pale colored
 
 SPECIFIC GRAVITY. 35 
 
 urine has a specific t^ravity of 1030 or more, the presence 
 of sugar is strongl}' suggested ; but, on the other hand, 
 sugar may be present with a low specific gravity (as low as 
 10 10) ; hence the importance of testing every specimen of 
 urine for sugar, regardless of the specific gravity. 
 
 In albuminous urines, especially those containing one- 
 eighth of one per cent, or more, the specific gravity is always 
 more or less affected by the albumin in solution — that is, it 
 is raised higher than it would be if only normal urinary 
 constituents were present. 
 
 The specific gravity of the urine is also influenced by 
 certain drugs : for example, following the administration of 
 large doses of potassium acetate, the specific gravity may 
 be 1020, the total twenty-four-hour quantity increased to 
 2000 c.c. or more, and the normal urinary constituents not 
 increased. In such a case it is the presence of the 
 increased amount of the potassium salts that affects the 
 specific gravit^^ 
 
 The urinometer is undoubtedly the most convenient 
 means of determining the specific gravity of the urine. 
 This instrument is less accurate than the balance (Westphal 
 or Mohr) and pycnometer, although for practical purposes 
 it is sufficiently accurate if it is properly constructed. 
 Every urinometer should be carefully tested with distilled 
 water at 60° F. (15.5° C), in which it should read o or 
 1000. A large number of urinometers are on the market, 
 some .of which vary several points from the standard, but 
 those constructed by E. R. Squibb & Sons, of Brooklyn, 
 New York, are among the most accurate. (Fig. i.) They 
 are very carefully standardized at "jy^ F. (25° C), — a tem- 
 perature much more usual than 60° F. (15.5° C), — and 
 with each urinometer a thermometer is furnished for tem- 
 perature corrections. In ordinary work the use of the 
 thermometer is unnecessary, since the variations by changes 
 in temperature are usually only slight (a variation in the 
 reading of four is the maximum error which can occur at any 
 temperature at which urine is likely to be tested — Tyson). 
 
 A urinometer-glass should be used whenever the specific 
 gravity is to be taken. Such a glass is usually supplied 
 with each urinometer, but the one used by the author (Fig. 
 2) is strongly recommended. ^ This urinometer-glass has the 
 
 ' Manufactured by Richard Briggs & Co., 287 Washington St., Boston.
 
 36 
 
 CONSTITUENTS OF NORMAL URINE. 
 
 advantage of having a wide foot, perfectly parallel sides, 
 and a well-formed lip, not usually found in the ordinary 
 urinometer-glass. The glass made by E. R. Squibb & 
 Sons has the added advantage of being fluted on the 
 sides. 
 
 In case the specimen of urine is too small for the specific 
 gravity to be taken in the urinometer-glass a sufficiently 
 large test-tube may be used, but such a tube should not be 
 too small in relation to the urinometer ; nor should the 
 latter be allowed to impinge against one side of the glass, 
 lest, in consequence of the capillary attraction between the 
 
 Fig. I. — Squibb's urinometer. 
 
 Fig. 2.— Urinometer and urinometer-glass 
 (slightly smaller than one-half actual size). 
 
 tube and the urinometer, the latter should not sink to the 
 proper level. The urinometer should be introduced into 
 the tube containing the urine, allowed to find its proper 
 level, and the reading taken; the urinometer should then 
 be forced down into the urine, allowed to rise until it again 
 reaches its proper level, and a second reading taken. The 
 two readings should be exactly the same. Any discrepancy 
 in the readings shows that in either one or the other obser- 
 vation the urinometer impinged against one side of the 
 tube, from which it is readily freed by moving it gently from 
 side to side.
 
 SPECIFIC GRAVITY. 37 
 
 Method of Taking Specific Gravity by the Urinome- 
 ter. — Fill the urinometer-glass three-fourths full of urine ; 
 introduce the urinomcter, pushing it down into the urine so 
 that it just touches the bottom of the urinometer-glass, 
 then release it and wait until it finds the correct level ; when 
 it comes to a rest, the scale is read off through the fluid 
 from below upward, the last mark seen below the surface 
 (at the meniscus) being the correct specific gravity. The 
 reading should )iot be taken from above the surface of the 
 fluid, since the capillary attraction of the fluid on the shaft 
 of the urinometer causes an error of from one to two grad- 
 uations on the scale. 
 
 If the quantity of urine is too small to fill sufficiently the 
 cylinder, it may be diluted with enough distilled water to 
 fill the cylinder to the required height, noting the volume 
 added. From the specific gravity of this mixture may be 
 calculated that of the urine. Thus, suppose it is necessary 
 to add four times as much water as urine to enable us to 
 use the urinometer — that is, to make five volumes — and 
 the specific gravity of the mixed fluid is 1004, then that of 
 the urine will be looo + (4x5)= 1020. Although the 
 principle of this method is correct, — and the results must 
 be if the data are, — the urinometers in use are not usually 
 so finely graduated that absolute accuracy in reading is 
 secured, while any error in reading is multiplied by the 
 number of volumes used. Hence, it is desirable to use this 
 method as rarely as possible, especially with urine of low 
 specific gravity. 
 
 Solids. — The term "solids," as ordinarily applied, refers 
 to the normal constituents of the urine present in solution, 
 such as urea, chlorides, uric acid, phosphates, sulphates, 
 ethereal sulphates, and various other constituents present 
 in smaller quantities. 
 
 " Relative " and " Absolute " Solids. — The term rela- 
 tivc solids applies to the proportion of solid matter to that 
 of the water which contains it : for example, the relative 
 quantity of urea is normally tzvo per cent. — that is, two 
 parts of urea in one hundred parts of urine. The absolute 
 solids are the solids contained in the total twenty-four-hour 
 urine, calculated in grams or grains : for example, the 
 absolute quantity of urea is normally thirty-three grams — 
 that is, the total quantity of urea in twenty-four hours. 
 
 The specific gravity of the urine affords a general idea of
 
 38 CONSTITUENTS OF NORMAL URINE. 
 
 the total solids present, but that in itself is not sufficient. 
 It is therefore necessary, first, to obtain the relative propor- 
 tion of the most important constituents, — as Tjrea, chlorides, 
 phosphates, sulphates, uric acid, etc., — and, second, to de- 
 termine the absolute quantities of these solids, before infer- 
 ences can be deduced therefrom. Observations concerning 
 the solids of the urine should be made upon a sample of 
 the mixed twenty-four-hour secretion, and not on the urine 
 of a single micturition. 
 
 Under normal conditions the total solids amount to from 
 seventy to seventy-three grams in twenty-four hours, of 
 which urea constitutes nearly one-half, the chlorides about 
 one-fifth, and the phosphates about one-twenty-fifth. The 
 absolute quantity of urea, being the most abundant solid 
 of the urine, is of the greatest importance in judging of the 
 capability of the kidneys for work, and also the extent of 
 tissue metabolism in both health and disease. The abso- 
 lute quantities of chlorine and phosphoric acid are also 
 important in some cases in completing the picture of the 
 urine. 
 
 The actual quantity of solids in the urine, particularly 
 the total quantities of each of the most important constitu- 
 ents, having been ascertained, in order to make valuable 
 deductions therefrom in health or disease it is necessary to 
 take into consideration the weight, age, habits, diet, sur- 
 roundings, and the nature of the disease in each individual 
 case before deciding as to the extent of the increase or 
 diminution of the solids for a given individual. For ex- 
 ample, on an average mixed diet, a large adult male nor- 
 mally excretes a larger quantity of solids than a small adult 
 male (the average for a person of 66 kilograms being 
 from 66 to 75 grams, of which urea equals from 35 
 to 40 grams) ; and a large adult female, a larger quantity 
 than a small adult female (the average for a person of 55 
 kilograms being from 60 to jo grams, of which urea 
 equals from 25 to 35 grams). In persons between fifty and 
 seventy years of age the total solids fall materially in health. 
 In healthy children, although the total solids are far below 
 the average for an adult, they are larger in proportion to 
 the height, age, and weight than in the adult. Much de- 
 pends also on the diet — that is, a person ingesting an 
 abundance of nitrogenous food will excrete larger quanti- 
 ties of solids, especiall}' urea. On the other hand, when a
 
 TOTAL SOLIDS. 3i) 
 
 meager diet, or one consisting chiefly of milk, is takcMi, the 
 soHds arc usually diminished. 
 
 In most chronic diseased conditions the solids are more or 
 less diminished, whether the disease be in the kidneys or in 
 some other organ or organs of the body, and particularly 
 when the patient is not capable of taking or assimilating a 
 mixed diet. The total solids are notably diminished in ad- 
 vanced chronic diseases of the kidney, in which the functions 
 of these organs are greatly interfered with on account of the 
 diseased epithelium lining the renal tubules. A marked 
 reduction of the solids in renal disease often indicates a 
 tendency to uremia, although this dangerous complication 
 may arise when the solids are normal or only slightly dimin- 
 ished. In the early stages of acute fevers the solids may, 
 for a short period, be normal or increased, but usually at 
 the expense of the tissues (increased metabolism), whereas, 
 later, they are markedly diminished. During the conva- 
 lescence, however, they usually reach the normal, or are 
 increased. In diabetes mellitus and insipidus the total 
 solids (aside from the sugar in the former disease) are gen- 
 erally increased. 
 
 Determination of Total Solids. — The total solids of the 
 urine may be determined in the following ways : 
 
 1. Take five cubic centimeters of the mixed twenty-four- 
 hour urine in a previously dried and weighed platinum or 
 porcelain dish. Evaporate it in a vacuum over sulphuric acid. 
 After twenty-four hours remove this sulphuric acid and re- 
 place by fresh acid ; exhaust again, and weigh after an- 
 other twenty-four hours. Deduct the weight of the dish, 
 and the remainder gives the solids in five cubic centimeters 
 of" urine. From this the solids in the whole volume of 
 urine are readily calculated. This method is one of the 
 most accurate for the determination of the solids of the 
 urine. 
 
 2. A quicker method is to evaporate to dryness over a 
 water-bath a given quantity of urine — say twenty-five cubic 
 centimeters — in a previously dried and weighed porcelain 
 dish. Dry the residue by placing the dish in an oven at i io° 
 C. (230° F.) for a few hours ; cool and weigh. This should 
 be repeated several times until no further loss of weight 
 occurs from drying. Subtract the weight of the dish, and 
 the remainder will represent the solids in twenty-five cubic 
 centimeters of the urine. This method, however, is not
 
 40 CONSTITUENTS OF NORMAL URINE. 
 
 very accurate, as some of the compounds in the urine are de- 
 composed at a temperature of iio° C. (230° F.). 
 
 J. To Determine the Solids in the Tiventy-fotir-hour Urine 
 by Means of the Specific Gravity. — Knowing the quantity of 
 urine passed in twenty-four hours and its specific gravity, an 
 approximate estimation of the total quantity of sohd matter 
 may be readily obtained by multiplying the last two figures 
 of the specific gravity by the arbitrary coefficient of 
 Haeser, 2.33. This will give the approximate number of 
 grams of solids in 1000 c.c. of the urine. For example, 
 suppose the twenty-four-hour urine to be 1350 c.c, and 
 the specific gravity to be 1024, then 
 
 24 X 2.33 = 55.92 grams in looo c.c. 
 
 Since the total quantity of urine in twenty-four hours is 
 1350 c.c, it will contain 
 
 55.92 X 1350 
 
 1000 : 1350 : : 55.92 : x, = ^^^ = 75.49 
 
 grams in twenty -four hours. This result indicates that a 
 trifle more than the average normal quantity of solids has 
 been excreted. 
 
 While this method of arriving at the quantity of solids is 
 not sufficiently accurate for scientific purposes, it is often of 
 considerable value for clinical purposes. It should be borne 
 in mind, however, that if the urine contains solid matter other 
 than the normal constituents, the solids obtained by this 
 method will often be found to be very high. For example, 
 in case of diabetes mellitus they will be found to be above 
 the normal, due to the presence of the sugar ; highly 
 albuminous urines may have increased total solids, due to 
 the quantity of albumin present. So also, after the use of 
 certain drugs, such as the potassium salts, — viz., acetate, 
 citrate, bitartrate, etc., — the solids will be considerably 
 above the normal, because of the presence of these salts.
 
 CHAPTER II. 
 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 UREA. 
 CH4N0O. 
 
 Urea is the chief organic constituent of the urine. It is 
 isomeric with ammonium cyanate, from which it was first 
 prepared synthetically by Wohler. It may also be prepared 
 by the action of ammonia on carbonyl chloride, by hydra- 
 tion of cyanamide, and from ammonium carbonate. 
 
 Urea is readily soluble in alcohol and water, but insoluble 
 in ether. It is odorless, has a salty taste, and its solution 
 has a neutral reaction. Urea crystallizes in colorless four- 
 or six-sided prisms with oblique ends, or, when rapidly crys- 
 tallized, in delicate, white, silky needles. When treated 
 with nitric acid, nitrate of urea — C0N,H^,HN03 — is formed, 
 which crystallizes in octahedral, hexagonal, or lozenge- 
 shaped plates. These plates are usually arranged in strata, 
 although occasionally seen singly (Fig. 3), and are less 
 soluble in water than urea crystals. With oxalic acid urea 
 unites to form oxalate of urea, — (CON^H^)^, H2C20^ + H^O, 
 — which is in the form of flat or prismatic crystals. 
 
 Other compounds of urea with acids have also been de- 
 scribed ; thus, phosphate of urea, CON^H^, HgPO^, was 
 said by Lehmann ^ to occur in small quantities in urine ; a 
 compound of urea with uronitrotoluolic acid — with the 
 formula C,^Hj,,N.^O,„ — was found by Jaffe ^ in dogs' urine 
 after the administration of orthonitrotoluol ; the greater 
 part of the urea in urine is, however, free. 
 
 Urea also forms compounds with salts, the most impor- 
 tant being with mercuric nitrate. With this substance it 
 forms a white precipitate having the formula CON„H^ . Hg- 
 (NO3)., . 3HgO. This compound is important, as Liebig's 
 
 1 " Cheinische Centralblatt," 1866, S. 1119. 
 
 2 " Zeitschrift fur physiologische Chemie," II, 50. 
 
 41
 
 42 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 volumetric process for the estimation of urea is based on 
 its formation. 
 
 There is also a crystalline compound of urea with sodium 
 chloride, CON2H^ . NaCl + H2O, which may be obtained 
 by evaporating to dryness a solution of these two sub- 
 stances, such as occurs, for instance, in ordinary urine. 
 Urea may be decomposed in various ways : 
 I. When heated to from 150° to 170° C, it melts and 
 gives off ammonia ; the substance which remains is termed 
 
 biuret. 1 
 
 2CON.,H^ — NH3 = Cp.NjHj. 
 Urea. Biuret. 
 
 Biuret with caustic potash and copper sulphate gives a 
 
 Fig, 3.— Crystals of nitrate of urea (upper half) and oxalate of urea (lower half) 
 
 (after Funke). 
 
 characteristic rose-red solution. When biuret is heated, it 
 gives off ammonia, and cyanuric acid is left — 
 
 3C.,0,,N3H, - 3NH3 = 2C3H3N3O,. 
 
 Biuret. Cyanuric acid. 
 
 Cyanuric acid gives a violet solution with caustic potash 
 and copper sulphate. 
 
 2. By means of an organized ferment, the torula, or micro- 
 coccus ureae (which grows readily in stale urine), urea takes 
 up water, and is converted into ammonium carbonate — 
 CON^H, + 2H,0 = (NHJ.COg. 
 
 1 "Poggendorfs Annalen," Lxxiv, 67.
 
 UREA. 43 
 
 3. By means of nitrous acid urea is broken up into car- 
 bonic acid, water, and nitrogen — CON,H^ ~\- N,03 = CO2 
 -f 2H2O + 2N,. 
 
 4. Chlorine water causes a somewhat similar decomposi- 
 tion— COK,H, + HP + 3CI, -= CO2 + N^ + 6HC1. 
 
 5. Hypochlorite or hypobromite of soda decomposes 
 urea in the following way : CON2H^ -f 3NaOBr = CO, 
 -f- Ng -|-2H.,0 + 3NaBr. This reaction is important, as 
 upon it is based one of the best methods of estimating the 
 quantity of urea in urine. (See p. 50.) 
 
 Since urea is the chief organic constituent of the urine, 
 it is a fair index of the excretion of nitrogenous matter from 
 the body. Not all of the nitrogen, however, is excreted as 
 urea, as very small amounts of it go out as uric acid, 
 xanthin, hypoxanthin, sarkin, kreatinin, allantoin, etc. 
 
 Much discussion has arisen in the past in relation to the 
 formation of urea — especially where it is formed and from 
 what it is formed. As first pointed out by Meissner,i urea 
 is probably formed chiefly in the liver. This view has 
 been confirmed by the more recent experiments of Brou- 
 ardel,2 Roster,^ Schroeder,^ and Minkowski.^ It is also 
 probable that the spleen and lymphatic and secreting glands 
 participate in the formation of urea. The urea passes into 
 the blood, and is carried to the kidneys, where it is excreted. 
 Contrary to the early belief, urea is not formed in the kid- 
 neys, or, if at all, only in minute quantities, as was first 
 demonstrated by Prevost and Dumas, ^ who found that the 
 formation of urea continued, accumulating in the blood and 
 tissues, even after the complete extirpation of the kidneys. 
 Similarly, in extensive disease of the kidneys in which 
 there is almost complete suppression of urine, urea con- 
 tinues to be formed and collects in the organism. Further- 
 more, in support of this view w^e find that in extensive de- 
 generative changes in the liver, as in acute yellow atrophy, 
 the formation of urea is greatly diminished. On the other 
 hand, in those diseases of the liver in which the activity of 
 the liver-cells is greatly increased, as in diabetes mellitus, 
 the urea formation is increased. 
 
 1 "Zeit. f. rat. Med.," N. F., xxxi, 234. 
 
 2 " Archiv de physiol. norm, et pathol.," [2] III, 373, 551. 
 
 3 Quoted by Hoppe-Seyler, " Physiol. Chem. ," S. 807. 
 * "Lud wig's Festschrift," 1887, .S. 89. 
 
 5 "Ann. de Chim. et de Physiol.," xxiii, 90.
 
 44 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 The quantity of urea eliminated in twenty-four hours 
 varies considerably, the chief cause of variation being the 
 amount of proteid food ingested, together with the rapidity 
 of tissue metabolism in health or disease. In a man who 
 is in a state of equilibrium, and on an ordinary mixed diet, 
 the quantity of urea excreted daily is between 25 and 40 
 grams, the average being about 33 grams (500 grains). On 
 a diet poor in nitrogenous matter it may fall to from 1 5 to 
 20 grams ; and, on the other hand, on a diet rich in nitrogen 
 it may rise to from 60 to 80 grams per diem. The per- 
 centage of urea varies considerably ; it may be roughly 
 said that the average relative quantity in health is two per 
 cent. ; but the percentage usually varies with the concentra- 
 tion of the urine. 
 
 Women excrete rather less urea than men ; children less, 
 absolutely, than adults, but more in proportion to their 
 weight. Uhle gives the following table, which represents 
 the quantity of urea excreted in twenty -four hours per kilo- 
 gram of body-ivcigJit at different ages : 
 
 From 3-6 years, about I gram. 
 
 " 8-11' " "0.8 
 
 " 13-16 " " 0.4-0.6 " 
 
 Adults, " 0.37-0.6 " 
 
 From this it is seen that, per kilogram weight, children up 
 to eleven years of age excrete about twice the quantity of 
 urea that adults do, and after eleven years practically the 
 saine as adults. 
 
 An Increased Quantity of Urea. — (a) In health the 
 absolute quantity of Jitea may be increased by__^i)_^5__ 
 hearty mixed diet. \2) ^trenuous exeTcrsc causing in- 
 creased metabolism ; and-it is for this reason that the quan- 
 tity of urea is greater during the day than during the night : 
 the average proportion, ,of the day to the night urea being 
 as three is to two. 1(3) \y the ingestion of ammonium 
 compounds, particularly ammonium chloride, it having been 
 found that practically nine-tenths of the mfacQgen in the 
 ammonium chloride is eliminated as urea. i(4)\By the in- 
 gestion of large quantities of water, the metkbblism being 
 increased thereby, especially when an abundance of water is 
 taken for a short time. If this ingestion is continued for a 
 long time, the metabolism is diminished, and hence there is 
 a diminution in the urea. if5)NFollowing hot baths the urea 
 may be increased.
 
 UREA. 45 
 
 (b) In disease the absolute quantity of urea is in- 
 creased (i) in the early stages of acute febrile diseases, the 
 increase being due largely to the increased metabolism of 
 the tissues, which, together with the ingestion of very little 
 food, results in emaciation. One notable exception to this, 
 however, is in acute diseases associated with increasing 
 dropsy, as in acute nephritis ; also those accompanied by 
 exudations into other parts of the body, as in cholera ; and 
 other acute intestinal diseases in which there is marked 
 diarrhea. (2) During the convalescence from acute dis- 
 eases associated with dropsy the urea may be increased 
 during the time that the dropsical fluid is being reabsorbed. 
 Such an increase, however, is usually only temporary, 
 and after all of the dropsical fluid has been absorbed the 
 urea falls below the normal, as is the rule in convalescence 
 from other acute diseases. (3) In intermittent fever the 
 urea is increased before the patient has a chill, but dimin- 
 ished afterward. (4) In diabetes insipidus the urea is much 
 increased absolutely (may go as high as 130 grams), the 
 twenty-four-hour quantity of urine being very large, but 
 the specific gravity very low. (5) In diabetes mellitus, on 
 account of the increased metabolism, the total urea is 
 usually above the normal. (6) In chronic interstitial neph- 
 ritis, although the absolute quantity of urea is usually 
 diminished, it may, in rare instances, be absolutely in- 
 creased. This has been occasionally observed in children 
 by the writer, where, at the autopsy, the disease was found 
 to exist to a marked degree. (7) In chronic gout the urea 
 may be increased to fifty or sixty grams in twenty-four 
 hours. 
 
 A Diminished Quantity of Urea. — (a) In health the^. 
 urea is diminished absolutely (i) whenever very little nitro- 
 genous food is taken — seen especially in vegetarians ; also 
 in those instances in which the individual takes very little 
 food of any kind. (2) Sometimes, following very free per- 
 spiration, the urea is diminished absolutely on account of 
 the elimination of a certain amount of this substance by 
 the sweat-glands. (3) In many instances of normal preg- 
 nancy the total urea is diminished. This is explained on 
 the ground that the nitrogenous elements ingested go to 
 nourish the fetus. The average amount of urea in normal 
 pregnancy is about twenty grams in twenty-four hours. 
 (4) Following the administration of small doses of quinine
 
 46 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 (Oppenheim) the urea is low, although not markedly dimin- 
 ished. (5) The long-continued ingestion of excessive 
 quantities of water results in more or less reduction in the 
 total quantity of urea. 
 
 (b) In disease the urea is generally diminished, the ex- 
 tent of the diminution being usually dependent upon, first, 
 the degree of diminished metabolism, and, second, the capa- 
 bility of the kidneys to excrete the urea, (i) In most diseases 
 of the kidneys — especially the advanced chronic forms, such 
 as chronic interstitial, chronic diffuse, and subacute glomer- 
 ular nephritis — the urea is usually markedly diminished. 
 In amyloid infiltration it may be normal or diminished, but 
 usually not so much diminished as in chronic interstitial 
 nephritis, since in the former disease the infiltration takes 
 place about the blood-vessels, and consequently does not 
 interfere with the secreting structure of the kidney until very 
 late. On the other hand, in chronic interstitial nephritis the 
 secreting portion of the kidney is affected much earlier in 
 the disease. Not infrequently a determination of the abso- 
 lute amount of urea is of considerable aid in the differential 
 diagnosis of these two forms of Bright' s disease. In the 
 first two stages of acute nephritis the urea, absolutely, is 
 much below the normal, especially in the first stage or at 
 the time when the dropsy is increasing. (2) In the func- 
 tional disturbances of the kidneys — active and passive 
 hyperemias — the urea is frequently diminished, the extent 
 of the diminution being largely dependent upon the cause 
 of the disturbance. (3) In acute febrile diseases following 
 the acme of the disease the quantity of urea is low, and 
 likewise during the convalescence from these diseases, since 
 the nitrogenous elements go to build up the tissues. (4) In 
 all diseases attended with extensive dropsy the urea is dimin- 
 ished up to the time the effusion begins to be reabsorbed, 
 when it gradually increases. (5) Shortly before death from 
 any cause the urea is usually markedly diminished (five to 
 six grams in twenty-four hours), more especially in chronic 
 kidney diseases. In those cases in which the degeneration 
 of the renal tissue is very extensive and the kidneys are 
 not capable of excreting the urea, the elimination may 
 take place through other glands, notably the sweat-glands. 
 In such instances the skin, especially in the axillae and 
 groins, has been found to be covered with a coating of 
 crystallized urea. (6) Extensive vomiting, and (7) marked
 
 DETFXTION OF UREA. 47 
 
 cases of diarrhea cause a diminution in the amount of the 
 urea eHminated ; this is particularly true in connection with 
 extensive renal disease, a portion of the urea being elim- 
 inated by these channels. (8) In all degenerative changes in 
 the liver, as in acute yellow atrophy, there is very low urea, 
 it apparently being replaced by leucin and tyrosin. 
 
 Detection. — The presence of urea may be detected in 
 the following ways : 
 
 1. Place a drop of the urine on a watch-glass or glass 
 slide, add one drop of pure nitric acid (the yellow nitric 
 acid should be avoided), and allow the mixture to evapo- 
 rate spontaneously in the air. If urea be present, crystals 
 of nitrate of urea will be seen when examined with the 
 microscope. 
 
 2. To a drop of the urine add a drop of a saturated solu- 
 tion of oxalic acid. If urea be present, crystals of oxalate 
 of urea form, which, under the microscope, appear in the 
 form of rhombic plates, or short, thick, rhombic prisms. 
 
 3. To the urine add an equal volume of sodium hypo- 
 bromite or hypochlorite, and if urea be present, the evolu- 
 tion of nitrogen gas takes place. 
 
 4. Place a few crystals of urea in a test-tube, and heat to 
 melting; then add a few drops of sodium or potassium 
 hydrate and a drop or two of a dilute solution of sulphate 
 of copper. The biuret reaction occurs, which consists of a 
 violet or a rose-red color. 
 
 5. To a crystal of urea about the size of the head of a 
 pin add one drop of a moderately concentrated solution 
 of furfurol, and then a drop of concentrated hydrochloric 
 acid, and heat. A play of colors results : a yellow, green, 
 blue, violet, and, finally, in the course of a few minutes, a 
 purple-violet (furfurol reaction of Schiff i). 
 
 Quantitative Determination of Urea. — Various \ 
 methods have been suggested for the quantitative determina- 
 tion of urea. Of these, the three following are most suit- 
 able : (rt) The mercuric nitrate or Liebig's method ; {/>) 
 the hypobromite or hypochlorite method ; (r) Fowler's 
 hypochlorite method (differential density). 
 
 (a) Liebig's Method. — If albumin be present, it must first ^ 
 be removed by coagulation (heat). The combination between 
 urea and mercuric oxide, which is (CON2Hj2Hg(N03)2 . 3HgO, 
 
 1 " Berichte d. chem. Gesellsch.," x, 773, 1887.
 
 48 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 results in a white precipitate, insoluble in water and weak 
 alkaline solutions. It is, therefore, necessary to prepare a 
 standard solution of mercury, and to have an indicator by which 
 to detect the point when all the urea has entered into combina- 
 tion with the mercury, and the latter slightly predominates. 
 This indicator is sodium carbonate, which gives a yellow color 
 with the excess of mercury, owing to the formation of hydrated 
 mercuric oxide. 
 
 Theoretically, loo parts of urea should require 720 parts of 
 mercuric oxide; but practically, 772 of the latter are necessary 
 to remove all the urea, and at the same time show the yellow 
 color with alkali; consequently, the solution of mercuric nitrate 
 must be of empiric strength in order to give accurate results. 
 
 The following solutions must be prepared : 
 
 1. Standard Mercuric Nitrate Solution: Dissolve 77.2 grams 
 of red oxide of mercury (weighed after it has been dried over 
 a water-bath), or 71.5 grams of the metal itself, in dilute nitric 
 acid. Expel the excess of acid by evaporating the liquid to a 
 syrupy consistence. Make up to 1000 c.c. with distilled water, 
 adding the water gradually. This solution is of such strength 
 that 19 c.c. will precipitate 10 c.c. of a 2 per cent, urea solu- 
 tion. Add 52.6 c.c. of water to the liter of the mercuric nitrate 
 solution, and shake well ; then 20 c.c. (instead of 19) = 10 c.c. 
 2 per cent, urea solution — /. ^. , i c.c. = o.oi of urea. 
 
 2. Baryta Mixture: This is a mixture of two volumes of 
 solution of barium hydrate with one of solution of barium 
 nitrate, both saturated in the cold. 
 
 Analysis. — Take 40 c.c. urine; add to this 20 c.c. of baryta 
 mixture, and filter off the precipitate of baryta salts (phosphates 
 and sulphates); take 15 c.c. of the filtrate (this corresponds to 
 10 c.c. of urine) in a beaker. Run into it the mercuric nitrate 
 solution from a burette, until, on mixing a drop of the mixture 
 with a drop of a saturated solution of sodium carbonate on a 
 white tile, a pale lemon color appears. Then read from the 
 burette the amount used, and calculate from this the percentage 
 of urea. 
 
 Corrections. — This method approaches accuracy only when 
 the quantity of urea present is about 2 per cent., which is about 
 the normal percentage of urea in urine. The chlorine in the 
 urine must also be estimated, and the quantity of urea indicated 
 reduced by the subtraction of i gram of urea for every 1.3 
 grams of sodium chloride found. If the urine contains less 
 than 2 per cent, of urea, o.i c.c. of mercuric nitrate solution 
 must be deducted for every 4 c.c. used; if more than 2 per 
 cent, of urea, a second titration must be performed with the 
 urine diluted with half as much water as has been needed of 
 the mercurial solution above 20 c.c. Suppose, then, 28 c.c.
 
 QUANTITATIVE DETERMINATION OF UREA. 49 
 
 have been used in the first titration, the excess is 8 c.c; there- 
 fore 4 c.c. of water must be added to the urine before the 
 second titration is made. When ammonium carbonate is present, 
 first estimate the urea in one portion of urine, and the ammonia 
 by titration with normal sulphuric acid in another; 0.017 gram 
 of ammonia = 0.030 of urea. The equivalent of ammonia in 
 terms of urea must be added to the urea found in the first 
 portion of urine. 
 
 Modifications. — Rautenberg and Pfliiger have devised modifi- 
 cations of Liebig's original method. Rautenberg's method 
 consists in maintaining the urea solution neutral throughout by 
 successive additions of calcium carbonate. Pfluger's method is 
 as follows: A 2 per cent, solution of urea is prepared ; 10 c.c. 
 of this are placed in a beaker, and 20 c.c. of the mercuric nitrate 
 solution are run into it in a continuous stream ; the mixture is 
 then brought under a burette containing normal sodium car- 
 bonate, and this is added with constant agitation until a per- 
 manent yellow color appears. The volume so used is noted as 
 that necessary to neutralize the acidity produced by 20 c.c. of 
 the mercurial solution in the presence of urea. A plate of glass 
 is then laid on a black cloth, and some drops of a strong solu- 
 tion of sodium bicarbonate (free from carbonate) are placed 
 upon it at convenient distances. The mercurial solution is 
 added to the urine in such volume as is judged appropriate, and 
 from time to time a drop of the white mixture is placed beside 
 the bicarbonate, so as to touch but not mix completely. A 
 point is at last reached when the white gives place to yellow ; 
 both drops are then quickly mixed with a glass rod, and the 
 color disappears ; further addition of mercury is then made to 
 the urine until a drop mixed with the bicarbonate remains per- 
 manently yellow. Now is the time to neutralize by the addition 
 of the normal sodium carbonate to near the volume found neces- 
 sary in the preliminary experiment. If this is quickly done, a 
 few' tenths of a cubic centimeter of mercuric nitrate will be 
 found sufficient to complete the reaction. If, however, much 
 time has been lost, it may happen that, notwithstanding the 
 mixture is distinctly acid, it gives, even after the addition of 
 sodium carbonate, a permanent yellow, although no more mer- 
 curic nitrate be added. Under those circumstances the analysis 
 must be repeated, taking the first titration as a guide to the 
 quantities that are necessary. Pfluger's correction for concen- 
 tration of urea is different from Liebig's, and is as follows: 
 
 V^ = volume of urea solution -f- volume of sodium carbonate 
 solution -(- volume of any other fluid free from urea that may 
 be added. 
 
 V2 = volume of mercuric nitrate solution used. 
 
 C = correction = — (V^ — V2) x 0.08. 
 4
 
 50 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 This formula holds good for cases in which the total mixture 
 is less than three times the volume of mercuric nitrate solution 
 used ; with more concentrated solutions the formula gives results 
 too high. 
 
 Pfliiger and Bleibtreu ^ have, recently, in a series of papers, 
 introduced fresh methods of urea analysis of so complex a 
 nature that they are quite unsuitable for ordinary clinical work. 
 
 Liebig's method is by far the most accurate for the quantita- 
 tive determination of urea, but it is too long and complicated 
 for clinical purposes. 
 
 (b) The Hypobromite or Hypochlorite Method. — 
 
 The principle upon which this method is based is that urea, 
 when brought in contact with sodium hypobromite or 
 sodium hypochlorite, is decomposed into nitrogen, carbon 
 dioxide, and water. Thus : 
 
 CH.Np + jNaOBr =. aNaBr + CO^ + N, + 2U,0, 
 
 the volume of nitrogen disengaged being the measure of 
 the urea. The carbon dioxide set free immediately com- 
 bines with the excess of sodic hydrate in the hypobromite 
 mixture used, and forms sodium carbonate, which remains 
 in solution. 
 
 All quantitative determinations by this method are de- 
 pendent upon the fact that one cubic centimeter of nitrogen 
 gas at the standard temperature and pressure is equivalent 
 to 0.0027 gram of urea ; or, on the other hand, that one 
 gram of urea at 0° C. furnishes 370 c.c. of nitrogen. 
 
 Various forms of apparatus for the application of this 
 process have been devised, among which are those of 
 Hiifner, Gerrard, Dupre, W. H. Greene, Charles A. Dore- 
 mus, E. R. Squibb, and others. In the use of these vari- 
 ous forms only approximate results are obtained, but the 
 one devised by E. R. Squibb is by far the most satisfactory 
 for clinical purposes. 
 
 Sqiiibli's Apparatus'^ (^ig- 4)- — This apparatus consists 
 of two two-ounce bottles, a and h, each being supplied with 
 a double-bored rubber stopper and connected by means of 
 a rubber tube, <r; a 2 c.c. pipette that is closed at its 
 upper end by a nipple ; a 30 c.c. graduate, g, into which a 
 
 ^ "Pfliiger's Archiv," XLiv, S. i. 
 
 2 This apparatus can be purchased of E. R. Squibb & Sons, Brooklyn, 
 N. Y., or of Messrs. Eimer & Amend, 205-211 Third Avenue, New York 
 city, at a moderate cost.
 
 QUANTITATIVE DETERMINATION OF UREA. 
 
 51 
 
 rubber tube, d, extends from bottle b ; and a small glass 
 plug, c. 
 
 Reagents. — Among the reagents that may be used for decom- 
 posing the urea in urine by this apparatus, the following are the 
 most convenient and the best : 
 
 I. The Solution of Chlorinated Soda of the United States 
 Pharmacopeia of 1840 to 1870 inclusive, but the solution of the 
 U. S. P. of 1880 must be avoided, as it will not answer the pur- 
 pose at all. If this solution of 1870 is not accessible when this 
 apparatus is to be used, it may be extemporaneously made by 
 the following formula and process from the chlorinated lime 
 
 Fig. '4. — Squibb's urea apparatus, for the approximate estimation of urea in urine. 
 
 supplied with the apparatus, or from any other source. Fifteen 
 or twenty cubic centimeters of this solution are sufficient for each 
 assay. 
 
 2. Extemporaneous Solution of Chlorinated Soda: Take of 
 chlorinated lime (chloride of lime or bleaching powder) 20 
 grams, or 318 grains ; and sodium carbonate (common washing 
 soda, or "sal soda"), 40 grams, or 636 grains. Shake the 
 chlorinated lime in a bottle with 45 c.c. or i^/^ fluidounces 
 of water until thoroughly disintegrated. Allow the mixture 
 to settle for a minute or two, and pour the thin portion 
 upon a paper filter in a funnel, filtering into a bottle of about 
 100 c.c. capacity. Shake the thick residue remaining in
 
 52 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 the bottle with 30 c.c. or i fluidounce more water, and when 
 the first portion on the filter has drained through, pour the 
 whole of the second portion on the filter and allow this to drain 
 through. Then dissolve the sodium carbonate in 30 c.c, or i 
 fluidounce, of hot water, and add this solution to the filtrate in 
 the first bottle. Shake the solutions well, and if the mixture 
 gelatinizes, warm the bottle and shake until it liquefies, and 
 then pour it upon a new filter-paper, filtering off the clear solu- 
 tion into a bottle marked at 100 c.c. When the filtrate has 
 drained through, pour water into the filter until the filtrate 
 reaches the 100 c.c. mark on the bottle. This solution is about 
 equivalent to that of the U. S. P. of 1870 for this assay, and 
 when recently made, 10 c.c. of it are sufficient for each assay, but 
 when old or made from old chlorinated lime, 15 c.c. are a safer 
 quantity. 
 
 3. Solution of Chlorinated Lime : Take of chlorinated lime 
 (" chloride of lime ") 40 grams, or 617 grains ; water, a suffi- 
 cient quantity. Shake the chlorinated lime well with 120 c.c, 
 or 4 fluidounces, of water, and after the mixture has settled for 
 a minute or two pour off the thinner portion on to a filter-paper, 
 and filter into a bottle marked at 200 c.c, or 6fi fluidounces. 
 Add 80 c.c. more water to the thick residue of the chlorinated 
 lime, again shake well, and pour the whole upon the filter after 
 the first portion has nearly all drained through. When the 
 second portion has drained through, pour water on the residue 
 in the filter until the filtrate reaches the 200 c.c. mark on the 
 bottle. Then cork the bottle and shake it, label it, and date 
 the label. 
 
 For the decomposition of urea this solution is the best of all 
 reagents yet tried. It is very efficient when a month old, but 
 how much longer it will retain its efficiency is not known. Its 
 reaction with the urea is very prompt, and is divided into two 
 stages of very active reaction, which are usually from one to 
 three minutes apart. Then the end reaction is fairly sharp. 
 The whole time of shaking is usually not over six minutes, and 
 a warm bath is not needed. Even when made from 18 per 
 cent, chlorinated lime, 10 c.c of this solution are quite sufficient 
 for an assay, and, therefore, the foregoing formula yields enough 
 for 20 assays ; the bottle of chlorinated lime supplied with the 
 apparatus contains about enough to make solution for 40 assays 
 before it will need replenishing. 
 
 4. Solution of Sodium Hypobromite: This, as applied by 
 the improved process of Dr. Charles Rice, is kept in two sepa- 
 rate solutions, which are mixed shortly before using them. 
 
 {a) The solution of caustic soda is made by dissolving 100 
 grams of caustic soda in 250 c.c. of water, the resulting solution 
 measuring about 284 c.c.
 
 UREA. 53 
 
 (^b) The solution of bromine is made as follows : Bromine 
 is commonly sold in one-ounce glass-stoppered vials, which, 
 on an average, contain less than an ounce ; the quantity must 
 be ascertained by weighing the vial and contents after the 
 stopper is loosened, pouring the contents into a bottle of about 
 300 c.c, or 10 fluidounces, capacity, and then weighing the 
 empty vial, and subtracting its weight. Then add to the 
 bromine in the bottle an equal weight of either sodium bromide 
 or potassium bromide, and as many cubic centimeters of water 
 as eight times the nmiiber of grams of the bromine, and shake 
 until the bromine is dissolved, when the solution is ready for 
 use. 
 
 For the assay this and the soda solutions are taken in equal 
 measures, and are mixed, near the time of using, in any desired 
 quantity. If but one or two assays are to be made, they may 
 be measured directly into bottle a, and be mixed there, using 
 the measuring jar for the purpose. While 2.5 c.c. of each solu- 
 tion with 5 c.c. of water, or 3.5 c.c. of each solution with 3 c.c. 
 of water, are sufficient for an assay, it is better to take 5 c.c. of 
 each solution for safety, and not dilute with water. The reaction 
 is very prompt, and the end reaction is fairly definite and sharp, 
 and there is no perceptible double reaction with an interval 
 between them, as in the chlorinated lime solution, unless there 
 is a larger dilution. So long as these solutions are not mixed 
 they will keep indefinitely, and, therefore, when the trouble of 
 making them is over, they are very convenient for use, the results 
 being more uniform, but a trifle lower, than those from the solu- 
 tion of chlorinated lime. 
 
 Process. — i. Provide a vessel containing enough water to im- 
 merse bottle a, the water being at room-temperature, — or about 
 18° C- (64.4° F. ), — to be used as a cold bath. 
 
 2. Put one end of the short rubber tube d on the bent glass 
 tube of the stopper of the bottle b, and slip it on the glass tube 
 just 'SO far that when the bottle b is laid on its side on its sup- 
 port, the free end of the rubber tube will just clear the bottom 
 of the measuring jar, as shown in the cut. 
 
 3. Fill the bottle b with water at room-temperature, and put 
 the stopper firmly in place, allowing the displaced water to 
 escape through the tubes. Then, taking the bottle in the right 
 hand with the forefinger over the end of the straight glass tube 
 of the stopper, incline the bottle toward the bent glass tube, 
 and relax the pressure of the forefinger on the end of the 
 straight tube so that water enough may escape to completely fill 
 the rubber tube d. Then with the left hand put the little glass 
 stopper e in the free end of ^ and lay bottle /^ thus filled, on its 
 support ; this requirement may be fulfilled by the lid of the 
 box.
 
 54 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 4. Next, put one end of the long piece of rubber tubing {c) 
 on the bent glass tube of the stopper of the bottle a. 
 
 5. Measure out in the graduate the quantity of the reagent to 
 be used, and having poured it into bottle a, rinse out the grad- 
 uate-glass. 
 
 6. Dip the stopper of bottle a into water, and put it loosely 
 in its place. 
 
 7. Dip the mouth of the rubber bulb of the pipette in water 
 for lubrication, and put the bulb on the pipette nearly as far as it 
 will go. Compress the large part of the bulb upon the pipette, 
 and having dipped the point in the urine, relax the compression 
 entirely. The expansion of the bulb will cause the urine to 
 rise and fill — or nearly fill — the body of the pipette. Then, tak- 
 ing the body of the pipette between the left thumb and fingers 
 while the point is still immersed in the urine, with the right 
 thumb and forefinger applied to the rubber ring at the mouth of 
 the bulb, screw the bulb upward on the pipette so that the urine 
 may slowly rise to the mark until the lower limb of the menis- 
 cus lies just above the mark. Now, when the point of the pipette 
 is raised out of the urine, the meniscus will fall a little, and lie 
 exactly on the mark. Then screw the bulb a little higher, so 
 that a very little air may enter the point of the pipette, to prevent 
 loss of the measured urine. 
 
 8. Pass the lower end of the charged pipette through the 
 vacant hole in the stopper of bottle a, and then screw the stop- 
 per into its place by holding the stopper firmly, and turning the 
 bottle upon it. 
 
 9. Then put the free end of the long rubber tube c on the 
 end of the straight glass tube of the stopper of bottle b, thus 
 connecting a and b. 
 
 10. Next, take out the little glass stopper e from the free 
 end of the short rubber tube d, and allow the few drops of water 
 that will flow to escape, seeing that the flow ceases completely. 
 
 11. Then put the empty measuring jar in its place under the 
 tube d, to receive the displaced water of the process, when the 
 preparation for the process will be complete. 
 
 12. Take the bottle a by the neck, between the right thumb 
 and forefinger, and take the upper part of the pipette with the 
 left thumb and fingers, in readiness to compress the rubber bulb, 
 shaking the lower part of the bottle from side to side, and not 
 up and down. During this gentle shaking compress the bulb, 
 so as to force all the urine out of the pipette into the bottle 
 with the reagent. Active effervescence will soon commence, 
 and while it is active relax the compression of the bulb gradu- 
 ally and completely. If this be properly done, no liquid — or 
 but a drop or two — will get into the rubber tube to be carried 
 over into bottle b. Continue the shaking as long as bubbles of
 
 UREA. 55 
 
 gas pass over into bottle b. If chlorinated soda solution be 
 used as the reagent and without a warm bath, the shaking will 
 require from twenty to thirty minutes; but with the warm bath, 
 not more than from six to eight minutes. 
 
 13. Bottle a is then immersed in the cold bath, at about 18° 
 C. (64.4° F.), for about four minutes. During this immersion 
 the contraction in bottle a will draw water from bottle b into a 
 and from the measuring jar back into bottle b, and when there 
 is no longer any change in tlie measuring jar, the contraction is 
 finished. 
 
 14. The bottles are removed and set aside to be prepared 
 for a new assay ; and the contents of the measuring jar are 
 carefully read off to half a cubic centimeter, and the quantity 
 thus obtained is noted and referred to the first column of the 
 urea table. There the proportion of urea present is found 
 calculated in percentage, and in grams and grains for various 
 measures of urine. For example, if the graduate-glass contains 
 16 c.c. of displaced water, from the urea table it will be found 
 that the urine contains 2.02 percent, of urea, or 0.621 2 grams in 
 30 c.c. of urine, (^d) If the twenty-four-hour quantity of urine be 
 
 1 1 1 • r 1 ISOO V 2.02 
 
 1500 c.c, then calculating from the percentage — — — = IP -IP 
 
 grams, which represents the app7'oximate number of grams of 
 urea in twenty-four hours, {b') Or, calculating from the third 
 
 1 -1 11 o.62i2Vi';oo r , . , 
 
 column in the table, — S^-oo grams, which represents 
 
 the accurate number of grams of urea in twenty-four hours. 
 
 TABLE OF APPROXIMATE PROPORTIONS OF UREA IN 
 URINE, FOR CLINICAL USE. 
 
 One cubic centimeter of nitrogen gas at 0° C. (32° F.) equals 0.0027 grana 
 of urea. 
 
 Assumed room- temperature for measurements, 18° C. (64.4° F.). 
 
 Rate of expansion, 0.003663 times the volume for each I°C. Correction 
 applied for 18° C. (64.4° F.) is 0.003663 X 18 =0.0659 subtracted for each 
 I. c.c. as read off from the measuring jar, and the percentage is calculated from 
 the corrected reading. 
 
 Thirty cubic centimeters are assumed as equal to one fluidounce, but in con- 
 verting any considerable quantities from one measure to the other 29.52 c.c. 
 should be taken as one fluidounce. 
 
 In converting measures to weights, and in using measures and weights to- 
 gether, an assumed specific gravity for abnormal urine is taken — namely, 1025 
 at 25° C. (77° F. ) ; and 30 c.c. of urine of such specific gravity weigh 30.75 
 grams, and one fluidounce weighs 467.4 grains. 
 
 Four hundred and seventy-three cubic centimeters are as.suined as equal to 
 one pint, or sixteen fluidounces, and when these measures are used for urine, 
 they are assumed as weighing 484.83 grams (1025 x 473) and 7478.4 grains 
 (467.4 X 16) respectively. 
 
 The seventh and eighth columns must not be taken as having any definite 
 relation to, or bearing upon, the assay, excepting when the total twenty-four-
 
 56 
 
 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 hour excretion amounts to just Il8l c.c, or 40 fluidounces, or very near to this 
 measure, as the calculations are based upon this arbitrary quantity. 
 
 E< 
 
 
 
 U 
 
 Urea Con- 
 
 Urea 
 
 CON- 
 
 Urea Con- 
 
 Hi2 
 
 a 
 
 tained IN 30 
 
 TAINED 
 
 IN 473 
 
 tained IN II8I 
 
 to Q .-^ 
 
 fc <J , 
 
 u 
 
 c.c, OR I Fluid- 
 
 c.c, OR 
 
 I Pint, 
 
 C.C, 
 
 OR 40 
 
 ^ f? u . W 
 
 ZO J « J 
 
 z 'J 
 
 (J 
 
 < < 
 
 ounce, OF 
 
 OF URINR. 
 
 Fluidounces, 
 
 Offish" 
 
 o2u 
 
 U 
 
 Uri 
 
 NE. 
 
 
 
 OF Urine. | 
 
 SS^; 
 
 OS 
 
 a: 
 
 U 
 
 (d 
 
 
 
 
 
 
 
 m CS Q 
 H ^ . < a: 
 
 5; (fl ^ 
 5 < 
 
 05^ 
 
 In 
 
 In 
 
 In 
 
 In 
 
 In 
 
 In 
 
 
 0. 
 
 Grams. 
 
 Grains. 
 
 Grams. 
 
 Grains. 
 
 Grams. 
 
 Grains. 
 
 jwS 
 
 4 c 
 
 c. 
 
 0.50 
 
 0.1538 
 
 2.34 
 
 2.425 
 
 37-44 
 
 6.055 
 
 93.60 
 
 
 5 ' 
 
 
 0.63 
 
 0-1937 
 
 2.94 
 
 3-054 
 
 47.04 
 
 7.625 
 
 117.60 
 
 
 
 6 ' 
 
 
 0.76 
 
 0-2337 
 
 3-55 
 
 3-685 
 
 56.80 
 
 9.200 
 
 142.00 
 
 
 
 7 
 
 
 0.88 
 
 0.2706 
 
 4-11 
 
 4.267 
 
 65.76 
 
 10.653 
 
 164.40 
 
 
 
 8 ' 
 
 
 1. 01 
 
 3106 
 
 4.72 
 
 4.897 
 
 75-52 
 
 12.227 
 
 188.80 
 
 
 
 9 ' 
 
 
 1-13 
 
 0.3475 
 
 5-28 
 
 5-479 
 
 84.48 
 
 13.680 
 
 211.20 
 
 
 
 10 ' 
 
 
 1.26 
 
 0-3875 
 
 5-89 
 
 6. no 
 
 94-24 
 
 15 255 
 
 235.60 
 
 
 
 II ' 
 
 
 1-39 
 
 0.4274 
 
 6.50 
 
 6-739 
 
 104.00 
 
 16.825 
 
 260.00 
 
 
 
 12 ' 
 
 
 I-5I 
 
 0.4643 
 
 7.06 
 
 7-321 
 
 112.96 
 
 18.278 
 
 282.40 
 
 
 13 ' 
 
 
 1.64 
 
 0-5043 
 
 7.67 
 
 7951 
 
 122.72 
 
 19.853 
 
 306.80 
 
 Lowest. 
 
 14 ' 
 
 
 1-77 
 
 0.5443 
 
 8.27 
 
 8.582 
 
 132-32 
 
 21.427 
 
 33080 
 
 
 15 ' 
 
 
 1.89 
 
 0.5812 
 
 8.83 
 
 9.164 
 
 141.28 
 
 22.880 
 
 353-20 
 
 
 16 ' 
 
 
 2.02 
 
 0.6212 
 
 9-44 
 
 9-794 
 
 151.04 
 
 24.455 
 
 377-60 
 
 
 17 ' 
 
 
 2.14 
 
 0.6581 
 
 10.00 
 
 10.376 
 
 160.00 
 
 25.907 
 
 400.00 
 
 
 18 ' 
 
 
 2.27 
 
 0.6980 
 
 10.61 
 
 11.005 
 
 169.76 
 
 27.478 
 
 424.40 
 
 
 19 ' 
 
 
 2.40 
 
 0.7380 
 
 11.22 
 
 11.636 
 
 179-52 
 
 29-053 
 
 448.80 
 
 
 20 ' 
 
 
 2.52 
 
 0.7749 
 
 11.78 
 
 12.218 
 
 188.48 
 
 30-505 
 
 471.20 
 
 Normal. 
 
 21 ' 
 
 
 2.65 
 
 0.8149 
 
 12.39 
 
 12.849 
 
 198.24 
 
 32.080 
 
 495-60 
 
 
 .22 ' 
 
 
 2.77 
 
 0.S518 
 
 12-95 
 
 13-430 
 
 207.20 
 
 33-533 
 
 518.00 
 
 
 23 ' 
 
 
 2.90 
 
 0.8918 
 
 13-55 
 
 14.061 
 
 216.80 
 
 35-107 
 
 542-00 
 
 
 24 
 
 
 3-03 
 
 0-9317 
 
 14.16 
 
 14.690 
 
 226.56 
 
 36.678 
 
 566.40 
 
 
 25 ' 
 
 
 3-15 
 
 0.9686 
 
 14.72 
 
 15.272 
 
 235-52 
 
 38-131 
 
 58S.80 
 
 . . . 
 
 26 
 
 
 3-28 
 
 1.0086 
 
 15-33 
 
 15-903 
 
 245.28 
 
 39.706 
 
 613.20 
 
 
 27 
 
 
 340 
 
 1-0455 
 
 15-89 
 
 16.484 
 
 254.24 
 
 41.158 
 
 635.60 
 
 Highest. 
 
 Dorenius Urcovictcr. — The apparatus as represented in 
 figure 5 was devised by Dr. Charles A. Doremus, of New- 
 York. It is much used for rapid chnical purposes, and 
 consists of a bulb with an upright graduated tube, and a 
 small nipple-pipette to hold one cubic centimeter of urine. 
 The tube is so graduated that each of the small divisions 
 represents o.OOl gram of urea. The bulb is filled with 
 the sodium hypobromite solution, and the apparatus in- 
 clined sufficiently to fill the upright graduated tube, and 
 then water is added to fill the remainder of the tube and 
 lower part of the bulb. The pipette is filled with urine to 
 the one cubic centimeter mark, and the point carefully in- 
 troduced into the bend as far as it will go, holding the 
 graduated tube perpendicularly. The nipple is then slowly 
 compressed to expel all of the urine, care being taken not 
 to force air into the tube after the urine has been expelled. 
 The pipette is then withdrawn, and after the evolution of gas 
 is complete the number of cubic centimeters of nitrogen
 
 UREA. 
 
 57 
 
 gas is read off, and the result multiplied by lOO in order to 
 obtain the percentage of urea. Two forms of this appa- 
 ratus are obtainable — one graduated to read fractions of a 
 gram per cubic centimeter of urine, and the other gradu- 
 ated to read the number of grains of urea per fluidounce 
 of urine. 
 
 The Dorcnius urcomctcr as modified by Professor J. D. 
 Hinds (Fig. 6) has many advantages over the original form 
 of apparatus. This instrument consists of a bulb with an 
 upright graduated tube («), the same as the original ; near 
 the lower portion of this tube is a horizontal glass connec- 
 
 Fig. 5. — Doremus ureometer. 
 
 Fig. 6. — Hinds' modification of the Dore- 
 mus ureometer. 
 
 tion, which is provided with a ground glass stop-cock {S), 
 and wdiich supports another upright graduated tube (r) 
 with a capacity of two cubic centimeters. The bulb and 
 upright tube {a) are filled with the sodium hypobromite solu- 
 tion in precisely the same manner as previously described. 
 The upright tube {c) is then filled to the zero mark with 
 the urine to be tested. The stop-cock (^) is then turned, 
 and exactly one cubic centimeter of the urine allowed to 
 enter tube a with the reagent. As soon as the evolution 
 of nitrogen gas is complete, the number of cubic centi-
 
 58 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 meters of the gas is read off, and the result multiplied by 
 lOO in order to obtain the percentage of urea. 
 
 This form of apparatus ^ gives more exact results than the 
 original form, since the one cubic centimeter of urine re- 
 quired for the test is delivered with greater accuracy, and 
 no nitrogen gas is lost by its escape from the bulb. 
 
 (c) Fowler's Hypochlorite Method (Differential 
 Density).'^ — This method is based upon the fact that there 
 is a difference in the specific gravity of urine before and 
 after the decomposition of its urea by the hypochlorites ; 
 and that such difference bears a definite relation to the 
 quantity of urea present. Dr. Fowler found that every 
 degree of density lost corresponds to 0.77 of one per cent., 
 or about 3 1^ grains per fluidounce. The hypochlorite 
 solution employed is Squibb's solution of chlorinated soda, 
 or Labarraque's solution, of which seven parts will decom- 
 pose the urea in one part of urine, unless the amount is 
 very large, in which event the urine should be diluted by an 
 equal bulk of water, and the result multiplied by 2. The 
 presence of albumin and sugar does not interfere with this 
 test. 
 
 Process. — i. Add to i volume of the urine 7 volumes 
 of the hypochlorite solution ; effervescence due to the liber- 
 ation of nitrogen will immediately take place. Shake the 
 jar containing the mixture occasionally, and stand it aside 
 for two hours, when the urea will have been decomposed. 
 Now take the specific gravity of the quiescent fluid. 
 
 2. Ascertain the specific gravity of the mixed urine and 
 hypochlorite solution before decomposition. To do this, 
 multiply the specific gravity of the pure hypochlorite solu- 
 tion by 7, add this to the specific gravity of the pure urine, 
 and divide by 8. The result is the specific gravity of the 
 mixed fluid. From this subtract the specific gravity of the 
 quiescent mixture after decomposition of the urea, multiply 
 the difference by 0.77, and the result is the percentage of 
 urea ; or by 3 ^, which gives the quantity of urea in grains 
 per fluidounce. 
 
 1 This instrument, as well as the original Doremus ureometer, can be ob- 
 tained at a moderate cost from Messrs. Eimer & Amend, 205 to 211 Third 
 Ave., New York city. 
 
 2 Fowler, " Prize Essay to the Alumni Association of the College of Physi- 
 cians and Surgeons," New York. Published in the "New York Medical 
 Journal," July, 1887.
 
 URIC ACID. 59 
 
 As changes of temperature affect the specific gravity 
 and volume of hquids, the hypochlorite solution and urine 
 should be mixed, and the jar set aside along with a bottle 
 of the urine and the hypochlorite solution in the same 
 place, subject to the same temperature. When decomposi- 
 tion is complete, the specific gravities can be taken, and the 
 calculation made. 
 
 Example. — Suppose the specific gravity of the urine is 
 loio, and that of the hypochlorite solution is 1045, that 
 of the mixed fluid will be 
 
 1045 X 7 + loio 
 
 3 = 1040. 
 
 Now suppose the specific gravity of the decomposed fluid 
 is 1038, then (1040 — 1038) X 0.77 = 1.54, the percent- 
 age of urea. 
 
 URIC ACID. 
 
 CjHiNiOs. 
 
 Uric acid (H2U, expressed also U) is, in mammals, next 
 to urea, the medium by which the largest quantity of nitro- 
 gen is excreted from the body. It is, however, in birds 
 and reptiles the principal nitrogenous constituent of the 
 urine. 
 
 Until recently, the theory of the formation of uric acid 
 was that it was a product of the metabolism of the nitro- 
 genous material ingested, and that it represented an inter- 
 mediate product between the nitrogenous substances and 
 the final product, urea. The researches of Horbaczewski,! 
 Hopkins and Hope,^ Jerome,^ and others tend to show 
 that uric acid has an entirely different origin. It is now 
 believed that uric acid is at least partly derived from the 
 nucleins that form a constituent of all cell-nuclei, and which 
 are taken into the body as food. The nucleins are capable 
 of being split up into an albumin and nucleic acid, and it is 
 thought that the uric acid is formed in the body from the 
 nucleic acid through the oxidation of the xanthin or alloxur 
 groups contained in a molecule of nucleic acid. It has 
 been demonstrated that the ingestion of food that is rich in 
 nucleins results in the formation and elimination of a much 
 
 1 " Monatsh. f. Chem.," S. 624, 1889. 2 " Journ. of Physiol.," XXIII, p. 271. 
 3 "Journ. of Physiol.," xxil, p. 146.
 
 60 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 larger quantity of uric acid than the ingestion of an equal 
 amount of food that is poor in nucleins. The chief evi- 
 dence, however, in favor of the view that nucleins play a 
 role as precursors of uric acid is based upon the results of 
 thymus feeding. The experiments of Hopkins and Hope, 
 however, show that extracts of the thymus gland may be 
 prepared which contain only traces of nucleins and nucleic 
 acid, but which, when ingested, produce the characteristic- 
 ally large excretion of uric acid. It, therefore, appears 
 that some more soluble constituent of the diet acts either 
 as a direct precursor, or as a factor in the formation of 
 uric acid. 
 
 Our knowledge of this subject is yet too meager to war- 
 rant the conclusion that this new theory fully explains the 
 formation of uric acid, but there can be no doubt that the 
 nucleins (nucleic acid) play an important part in its forma- 
 tion. 
 
 When uric acid is referred to as a constituent of normal 
 urine, it is never to its free state that allusion is made, but 
 to its combinations chiefly with potassium, sodium, and 
 ammonium, and also with calcium and magnesium ; such 
 combinations being usually known as mixed urates. 
 
 Under ordinary conditions uric acid exists in the urine in 
 the form of urates. Since uric acid is dibasic, — that is, has 
 two replaceable atoms of hydrogen, — two forms of salts 
 exist — i. e., acid urates of potassium, sodium, and ammo- 
 nium, in which only one atom of the hydrogen is replaced 
 by the positive elements or radicles ; and normal (neutral) 
 salts of the same substances, in which both atoms of hydro- 
 gen are replaced. According to Neubauer and Vogel, 
 there are two forms of acid urates — monacid urates (bi- 
 urate), and triacid urates (quadriurate or tetraurate). The 
 normal salts are readily soluble in water at 70° F., but the 
 acid urates are only feebly soluble, while uric acid itself is 
 almost insoluble in water. Hence, the precipitation of the 
 acid urates or uric acid often occurs w^hen the urine cools, 
 or is allowed to stand in a cold place. A urine containing 
 a deposit of acid urates (amorphous urates) is usually more 
 or less concentrated, and always contains a relative excess 
 of the acid urates. If a strong acid be added to a urine 
 that contains a relative excess of urates, they are precipi- 
 tated on account of the feeble solubility of the acid urates 
 and the almost insoluble uric acid. Also, if the urine con-
 
 URIC ACID. 61 
 
 tains an excess of normal urates, they are partially decom- 
 posed by the acid, which chemically unites with the excess 
 of the base to form acid urates, hence their precipitation. 
 Thus, in the nitric-acid test for albumin (performed accord- 
 ing to instructions given on p. 122) a white zone of acid 
 urates is frequently seen above the zone of albumin (Fig. 
 I 5), or above where the zone of albumin would be if pres- 
 ent. It should be borne in mind that a zone of urates may 
 be present when albumin is absent. 
 
 Pure uric acid is soluble in 16,000 parts of cold water 
 and in 1600 parts of boiling water; impure uric acid is 
 more readily soluble in water than the pure. Its cold solu- 
 tions do not show an acid reaction with litmus paper. Uric 
 acid is insoluble in alcohol and ether, but dissolves in warm 
 glycerin, from which, on cooling, it separates in crystalline 
 form. It is insoluble in strong mineral acids, but is soluble 
 in alkaline hydrates as well as in alkaline carbonates, phos- 
 phates, lactates, and acetates. It is more soluble in solu- 
 tions of urea than in water (Riidel). 
 
 On boiling, uric acid reduces alkaline solutions of copper ; 
 before reduction occurs, however, a white precipitate, con- 
 sisting of cuprous urate, is formed. 
 
 When uric acid is artificially decomposed, an interesting 
 series of products results, the most important of which is 
 urea. Whether similar changes take place in the body is 
 still a matter of doubt. 
 
 The following is a list of the principal changes which 
 may be brought about by various reagents : 
 
 1. When uric acid is reduced with weak sodium amalgam, 
 two substances — xanthin (C^H^N^O^) and hypoxanthin or sar- 
 kin (CjH^N^O) — may be obtained. Their formulas differ from 
 that of uric acid in containing one or two atoms less oxygen re- 
 spectively than that substance. 
 
 2. When uric acid is heated in a closed tube with hydro- 
 chloric acid, it is decomposed into glycocoll, carbolic acid, and 
 ammonia: 
 
 C,U,^fi, + 5H,0 = C3H.NO, + 3CO, -f- 3NH3. 
 
 3. By the action of cold, concentrated nitric acid, uric acid 
 takes up water and oxygen, forming alloxan and urea : 
 
 2CjH,N,03 4- 2H,,0 -f O, = 2C,H„N,0^ -}- aCON^H^. 
 Uric acid. Alloxan. Urea.
 
 62 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 Alloxan, when boiled with a strong alkali, takes up water and 
 is decomposed, forming mesoxalic acid and urea: 
 
 2C,H,N,0, + 4H,0 = aCgH.O, ^ 2CON,H,. 
 
 Alloxan. Mesoxalic Urea, 
 
 acid. 
 
 On oxidation, mesoxalic acid forms oxalic and carbonic acids : 
 
 2C3H2O5 + O2 = 2C.,H.,0^ ^ 2CO,. 
 
 Thus, it is seen that in three steps the ultimate products of 
 uric acid are urea, oxalic acid, and carbonic acid. 
 
 4. There is another way in which the same three ultimate 
 products are obtained, but the intermediate step in the process 
 is not the formation of alloxan, but of another somewhat similar 
 substance called allantoin. This process is interesting, as allan- 
 toin is in fetal life one of the products of nitrogenous metabol- 
 ism, and it is thus possible that some sort of change, such as 
 can be produced artificially, occurs in embryonic life. 
 
 Uric acid when oxidized with potassium permanganate (care 
 being taken that the temperature does not rise) takes up water 
 and oxygen, forming allantoin and carbonic acid : 
 
 2C5H,N,0, + 2H.,0 + O2 = 2C\HgN,0, + 2CO,. 
 Uric acid. Allantoin. 
 
 The allantoin crystallizes out in about twenty-four hours. By 
 subjecting allantoin to the action of baryta water, hydrolysis 
 and oxidation again take place, and urea and oxalic acid are 
 formed : 
 
 2C,HgNp3 ^ 4H,0 + O., = 4CON2H^ -f 2C2HJO,. 
 
 Allantoin. Urea. Oxalic acid. 
 
 5. The following decompositions are interesting, as the 
 murexide test is the chief characteristic test for uric acid. 
 
 By oxidation with nitric acid, alloxan and urea are formed : 
 
 2C5H^Np3+2H20+02 = 2C4H2N2O, -u 2C0N,H,. 
 
 By heating or by electrolysis, alloxan splits into alloxantin, 
 parabanic acid, and carbonic acid : 
 
 3C,H,N.p, = C«H,N,0, + C3H.,N,03 + CO, ; 
 
 Alloxan. Alloxantin. Parabanic 
 
 acid. 
 
 and on treating alloxantin with ammonia the purple color due 
 to murexide or purpurate of anmionia appears: 
 
 C,H,N,0, + 2NH3 = CgH^N.O, + H,0. 
 Alloxantin. Murexide. 
 
 Since uric acid exi.st.s in combination as urates, it is not 
 ordinan'l)' found in a free state. It may, however, be de-
 
 URIC ACID. 
 
 63 
 
 posited in the urine in crystalline form, either while in the 
 body or after the urine has been voided. It may then be 
 seen as a deposit of minute reddish crystals, or, more 
 rarely, as reddish sand or gravel. 
 
 Uric acid crystallizes in the form of yellow or yellowish- 
 red crystals of a variety of shapes — -rhombic and rectangular 
 prisms, whetstone-, barrel-, wedge-, club-, diamond-shaped, 
 and as rosettes. (Plate 3.) The diamond-shaped ciystals 
 usually either have a very faint yellow tint or are, not in- 
 frequently, perfectly colorless. 
 
 Crystals of uric acid and those of its salt, — ammonium 
 urate, — together with those of hippuric acid and leucin, 
 
 Fig. 7. — Uric acid and urates (Funke). 
 
 constitute the only crystalline sediments of the urine col- 
 ored yellow or yellowish-red. 
 
 There are certain conditions of the body in which, as a 
 result of overfeeding and consequent sedentary habits, and 
 in some cases from hereditary influences, the oxidation 
 changes in the body are lessened, and uric and oxalic acids 
 are formed in greater proportion to urea than under normal 
 conditions. 
 
 Where is Uric Acid Formed ? — Two different views upon 
 this subject have been advanced : ( i ) That it is formed in the 
 tissues, especially in the liver and spleen, and merely ex- 
 creted by the kidneys ; (2) that the kidneys not only excrete, 
 but also constitute the seat of formation of, uric acid. The
 
 64 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 former view (i) is most generally held, and is supported by 
 the following facts : [a) Under normal conditions uric acid 
 is found in traces in the blood. ((^) After extirpation of 
 the kidneys it continues to be formed, (c) The secretion 
 of uric acid is greatest during the period of digestion — that 
 is, at a time when the liver and spleen are most active, (d) 
 In gout and in anemic conditions, ^ where the excretion of 
 uric acid is diminished, it accumulates in the blood and tissues. 
 
 The chief advocate of the second view (2) is Garrod, who 
 bases his conclusions on the fact of the small amount of uric 
 acid in the blood of reptiles, and also on the fact that he 
 was unable to find a larger quantity of uric acid in the 
 liver and spleen of birds than in those organs in mammals. 
 
 Horbaczewski ^ claims that uric acid is formed as a re- 
 sult of the disintegration of the tissues containing nuclein, 
 especially the leucocytes ; that the amount of uric acid 
 excreted increases when the number of leucocytes in the 
 blood is increased. He also claims that this is the explana- 
 tion of the large amount of uric acid in the urine of chil- 
 dren, especially the new-born, the small amount in hunger, 
 and the larger quantity following the ingestion of a meat diet. 
 
 The investigations of Schroder ^ and Minkowski "* justify 
 the conclusion that uric acid is formed chiefly in the liver, 
 where it appears as a result of the synthesis of ammonia 
 and lactic acid, which, after the removal of the liver, and 
 also in extensive degenerative changes of this organ (cirrho- 
 sis, acute yellow atrophy, etc.), appear in the urine in equiv- 
 alent quantities. Further, that small quantities of uric acid 
 following extirpation of the liver are formed from xanthin 
 and similar substances. 
 
 The quantity of uric acid eliminated in twenty -four hours 
 under normal conditions ranges between 0.2 and i gram, the 
 average being about o. 5 gram. According to Neubauer and 
 Vogel,^ the twenty-four-hour quantity may, normally, go as 
 high as 1.25 grams. In rare instances, especially in disease, 
 the total quantity of uric acid may exceed this figure. The 
 proportion of uric acid to urea is normally about as i : 45. 
 
 The quantity of uric acid in the urine is not necessarily 
 excessive when a deposit of uric acid crystals takes place 
 
 ^ Von Jaksch, *' Deutsche med. Wochenschr.," 1890, No. 23. 
 2 " Monatsh. f. Chemie," Bd. xn, 232, 189I. 
 » " Lud wig's Festschrift," 1887, S. 89. * Loc. cit. 
 
 5 "Analyse des Hams," Bd. i, 1898, S. 312.
 
 Pl.ATK 3 
 
 Uric-acid Crystals ; Normal Color (after Peyer).
 
 URIC ACID. 65 
 
 in the urine upon cooling. As a matter of fact, such a de- 
 posit may, and very often does, occur when the quantity 
 of uric acid is both relatively and absolutely diminished. 
 The separation of uric acid cr^'stals from the urine is 
 usually dependent upon one of three conditions : 
 
 1. A high degree of concentration of the urine, too 
 little water being present to keep the uric acid in solution. 
 
 2. Marked acidity of the urine, the salts of uric acid 
 being deprived of a part of the alkali ; the larger the pro- 
 portion of alkali combined with the uric acid, the more 
 soluble it becomes. 
 
 3. A high percentage of uric acid. Any condition 
 that results in an increased formation of uric acid in the 
 body causes its increase in the blood, and hence an 
 increased amount in the urine, with, usually, a resulting 
 deposition of the crystals. 
 
 When urine habitually contains a deposit of uric acid, an 
 alkali or some substance with which the uric acid will com- 
 bine should be administered, in order to prevent an irrita- 
 tion or inflammation of the urinary tract by the crystals. 
 
 In the consideration which follows the writer refers to the 
 uric acid in solution (as urates) and not to a deposit of uric 
 acid crystals. 
 
 Clinical Significance. — Uric acid is absolutely in- 
 creased (i) by an abundant meat diet, especially when 
 combined with a limited amount of outdoor exercise : in 
 other words, increased metabolism together with limited 
 oxidation. (2) In most of the acute diseases. (3) In 
 acute diseases of the lung, as in pneumonia, or by any dis- 
 ease that interferes with respiration, as hydrothorax and 
 pneumothorax, also by the upward pressure of abdominal 
 tumors, marked ascites, etc. (4) In chronic heart disease 
 or in any condition that interferes with the circulation. (5) 
 In liver disease. (6) In disease of the spleen. (7) In vari- 
 ous forms of anemia, especially splenic leukemia, in which 
 case the proportion of uric acid to urea may be as high as 
 I : 15, or even more. (8) In gout folloiving the par- 
 oxysm. (9) In diabetes mellitus. ^ (10) Following the 
 administration of nuclein.^ 
 
 ^ The question as to whether uric acid is actually increased in diabetes 
 mellitus has given rise to much controversy. It is probable that the increase, 
 if any, is not marked. 
 
 2 " Monatsh. f. Chemie," Bd. xil, 234, 1891, 
 S
 
 66 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 Uric acid is absolutely diminished (i) by low nitrog- 
 enous diet. (2) By the habitual ingestion of large quan- 
 tities of water (long-continued use). (3) In most forms of 
 advanced disease of the kidneys. (4) In gout during the 
 paroxysm. (5) Following the administration of large 
 doses of quinine. (6) In most of the general chronic dis- 
 eases. 
 
 Detection. — i. The Murexide Test. — A small portion 
 of urinary sediment is evaporated to dryness on a porcelain 
 plate or capsule, and a drop or two of nitric acid is added to 
 dissolve it. The mixture is then stirred thoroughly with 
 a glass rod, and carefully evaporated to dryness over a 
 spirit or a small Bunsen flame. When dry and cool, add 
 one or two drops of ammonic hydrate, and if uric acid 
 or urates are present, a beautiful purple-red color promptly 
 appears, gradually diffusing itself over the bottom of the 
 plate or capsule as the ammonia spreads. 
 
 2. Strongly acidulate the urine with concentrated hydro- 
 chloric acid, and allow the mixture to stand from eighteen 
 to twenty-four hours. Usually, a deposit of uric acid crys- 
 tals appears. 
 
 3. Uric acid may be detected in the urine and other 
 fluids, when traces of the acid or of urates are present, by 
 a method suggested by Garrod. A small portion of the 
 suspected fluid is treated on a watch-glass with a few drops 
 of glacial acetic acid. A few filaments of tow or very thin 
 silk are placed in the mixture, and the whole is set aside 
 under a bell-jar in a warm place for from twenty -four 
 to forty-eight hours. Gradually, crystals of uric acid sepa- 
 rate and are deposited upon the filaments. Their character 
 may be readily recognized by microscopic examination. 
 
 4. When a solution of uric acid or of a urate is boiled 
 with an alkaline solution of copper (Fehling's solution), a 
 yellowish-red or reddish precipitate of suboxide of copper 
 occurs. 
 
 Quantitative Determination of Uric Acid. — Heintz's 
 Method. — Take 200 c.c. of filtered urine that is free from 
 albumin, and add 10 c.c. of concentrated hydrochloric acid. 
 Let this stand for twenty-four hours in a cool place, then 
 collect the separated uric acid crystals on a previously dried 
 and weighed filter-paper, and wash once or twice with cold 
 distilled water. Dry the filter-paper holding the uric acid 
 crystals at about 100° C; cool and weigh. By subtracting
 
 URIC ACID. 67 
 
 the weight of the filter-paper, the result will be the weight 
 of the uric acid in 200 c.c. of urine. 
 
 This process can be considered only approximate, and 
 should not be relied upon for accurate results. It fre- 
 quently happens that urines containing uric acid do not give 
 a precipitate by this method ; it then becomes necessary to 
 employ other longer and, probably, more accurate methods. 
 
 Fokker-Salkowski Method.^ — Of the several gravi- 
 metric methods which have been suggested, this is perhaps 
 the most reliable. It depends upon the precipitation of 
 uric acid as ammonium urate, which, on account of its diffi- 
 cult solubility, can be easily handled, and with compara- 
 tively little loss. 
 
 Process. — Take 200 c.c. of urine, render alkaline with 20 
 c.c. of sodic hydrate, allow it to stand an hour, and to the 
 filtered mixture add 10 c.c. of a solution of ammonium 
 chloride (i : 5). Let this stand for forty-eight hours. 
 Transfer the precipitate to a previously dried and weighed 
 filter-paper, and wash two or three times with distilled 
 water. Then treat the precipitate several times with dilute 
 hydrochloric acid (i : 10) until all of the ammonium urate 
 has been decomposed. This leaves on the filter all of the 
 uric acid except what has been dissolved and carried 
 through into the filtrate. This filtrate is, therefore, saved 
 and allowed to stand six hours, after which any separated 
 uric acid crystals are thrown on to the weighed filter-paper. 
 The precipitate, which represents the total uric acid in 200 
 c.c. of urine, is washed twice with water (30 c.c), then with 
 alcohol until the acid reaction has disappeared, and finally 
 the filter-paper is dried and weighed. The difference in 
 weight plus 0.03 gram (correction for solubility) gives the 
 quantity of uric acid in 200 c.c. of urine. From this cal- 
 culate the amount for twenty -four hours. 
 
 If the urine is dilute, it should be concentrated so as to 
 have a specific gravity of from 1017 to 1020 before the fore- 
 going test is applied. The presence of albumin in the urine 
 does not interfere with the test. 
 
 Hopkin's Method. — In this process the uric acid and all 
 of the urates are precipitated by saturating the urine with 
 ammonium chloride, which converts all into ammonium 
 urate. This is then filtered out, and the uric acid separated 
 
 1 " Pfliiger's Archiv," Bd. X, 157, 1875 ; " Virchow's Archiv," Bd. LXVIII, 
 401, 1876.
 
 68 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 by the action of hydrochloric acid. The final estimation 
 is then made by titrating with a standard solution of potas- 
 sium permanganate, which Hopkins has found to be more 
 accurate than weighing. Exceedingly accurate results are 
 claimed for this process, and it has the advantage of being 
 conducted with ease and comparative rapidity. 
 
 The following solution is required : A twcnticth-nonnal 
 sobition of potassium pcnnangaiiatc. This solution is pre- 
 pared by dissolving 1.577 grams of pure crystals of potas- 
 sium permanganate in about 900 c.c. of distilled water. A 
 portion of this solution is then placed in a burette and 
 titrated against a decinormal solution of oxalic acid as fol- 
 lows : Take 10 c.c. of the decinormal oxalic acid solution 
 in a beaker, add some dilute sulphuric acid, and heat this 
 mixture to 60° C. To this hot mixture add the solution 
 of potassium permanganate until a faint but permanent pink 
 color is produced. Note the number of cubic centimeters 
 of the permanganate solution used, and then dilute the 
 remainder so that 20 c.c. of it will exactly correspond to 
 10 c.c. of the decinormal solution of oxalic acid. 
 
 Each cubic centimeter of the twentieth-normal solution 
 of potassium permanganate corresponds to 0.00375 gram of 
 uric acid. 
 
 The permanganate solution will usually retain its strength 
 for several weeks, but it should always be restandardized 
 by titration with oxalic acid before it is used. 
 
 The process, as applied to all urines, normal and patho- 
 logic, is as follows : 
 
 I. In Normal Urine zvithont Deposit. — [a) To 100 c.c. 
 of the urine is added ammonium chloride until practically 
 saturated ; about 3 5 grams are necessary. When a small 
 quantity of the chloride remains undissolved, even after 
 brisk stirring at intervals of a few minutes, saturation 
 is nearly complete. As the temperature of the urine again 
 rises, from the depression due to the process of solution, 
 any residual crystals will, for the most part, dissolve ; but 
 there is no necessity for adding more. 
 
 {b) After having stood for two hours or longer, — better 
 with occasional agitation to promote subsidence, — the pre- 
 cipitate produced is filtered through a thin filter-paper, 
 and washed three or four times with a saturated solution 
 of ammonium chloride. The filtrate should remain per- 
 fectly clear.
 
 URIC ACID. 69 
 
 (c) With a jet of hot distilled water the urate, which will 
 be somewhat pigmented, is now washed off the filter into a 
 small beaker, and heated just to boiling with an excess of 
 hydrochloric acid. It is then allowed to stand, in order 
 that the uric acid may separate completely. Two hours are 
 sufficient if the liquid be cooled. The acid is then filtered 
 off and washed with cold distilled water. The filtrate 
 should be measured before the washing is begun, and one 
 milligram added to the final result for each 15 c.c. of liquid 
 present. This need never be more than from 20 to 30 c.c. 
 
 {li) The acid is now again washed off the filter with hot 
 water, sodium carbonate is added, it is warmed until dis- 
 solved, and the solution then made up to 100 c.c. Being 
 transferred to a flask of sufficient capacity, it is mixed with 
 20 c.c. of concentrated pure sulphuric acid, and immediately 
 titrated with the twentieth-normal potassium permanganate 
 solution. The latter should be added slowly toward the 
 end of the reaction, the close of which is marked by the first 
 approach of a pink color, which is permanent for an appre- 
 ciable interval. The flask should be agitated throughout 
 the titration. 
 
 Since each cubic centimeter of the potassium perman- 
 ganate solution is equal to 0.00375 gram of uric acid, the 
 number of cubic centimeters of permanganate solution multi- 
 plied by 0.00375, P^us the correction of one milligram for 
 each 15 c.c. of liquid present, will give the amount of uric 
 acid in the 100 c.c. of urine used. From this the quantity 
 of uric acid in the twenty-four-hour urine can be readily 
 calculated. 
 
 2. Acid Urines Containing Cystin. — The author recom- 
 mends the addition of a small amount of amnionic lu'drate ; 
 heat and filter. The ammonium chloride may be added 
 while the urine is still warm. 
 
 J. Alkaline Urines ivitli an Abundant Deposit of Phos- 
 phates. — Filter off the phosphates after complete precipita- 
 tion by heat. The ammonium urate separates more rapidly 
 in alkaline than in acid urine. The only objection to adding 
 ammonic hydrate in all cases is its tendency to precipitate 
 the phosphates. 
 
 4. Albuminous Urines. — Albumin does not interfere with 
 the accurate determination of uric acid by this method, but 
 requires a little longer digestion with an excess of hydro- 
 chloric acid, in order to form the soluble acid-albumin.
 
 70 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 5. HigJily Pigvioited Urhw. — The pigment should be 
 removed from the urate precipitate by treating thoroughly 
 with alcohol, and after acidulation the filtrate is gradually 
 heated to boiling and then digested for some time on a 
 water-bath. The separated crystals are then thoroughly 
 washed. 
 
 In a urine containing bile the biliary pigment may come 
 down in considerable quantity ; but despite this, the ultimate 
 error is small. 
 
 Folin's Method.^ — This process depends upon the pre- 
 cipitation of uric acid as ammonium urate, by means of 
 ammonium sulphate, and is conducted as follows : 
 
 Process. — To 100 c.c. of filtered urine add 10 grams of 
 ammonium sulphate ; allow it to stand two hours, filter, 
 and wash the urate precipitate with a ten per cent, solution 
 of ammonium sulphate until it is free from chlorine. Dis- 
 solve the entire urate precipitate in hot distilled water, add 
 to this solution i 5 c.c. of concentrated sulphuric acid, and 
 then titrate, while hot, with a twentieth-normal solution of 
 potassium permanganate, each cubic centimeter of which 
 corresponds to 0.00375 gram of uric acid. Read off the 
 number of cubic centimeters of permanganate solution 
 used, multiply by 0.00375, and to the result add one milli- 
 gram for correction. This equals the amount of uric acid 
 in 100 c.c. of urine. From this calculate the quantity for 
 twenty-four hours. 
 
 According to Hofmeister,- neither albumin nor globu- 
 lin are precipitated by a ten per cent, solution of ammonium 
 sulphate. 
 
 Quantitative Estimation of Uric Acid by the Centri- 
 fuge. — The following method, devised by Dr. R. Harvey 
 Cook,^ promises excellent results and has the advantages of 
 being rapid and quite accurate. It is based, chemically, 
 on the method of Haycraft, in that the uric acid is pre- 
 cipitated as urate of silver. 
 
 The follow'ing apparatus are necessary : a centrifuge, four 
 graduated tubes of a capacity of 15 c.c. each, and a pipette 
 holding one cubic centimeter. 
 
 Process. — Place 10 c.c. of urine in the graduated tubes, 
 add to this from 0.5 to i gram of crystals of sodium car- 
 
 ^ "Zeitschr. f. physiol. Chemie," Bd. xxiv, 3, S. 224. 
 
 2 " Archiv f. exp. Pathol, u. Pharm.," Bd. XXV, 247, 1888. 
 
 3 " Medical Record," March 12, 1898, p. 373.
 
 XANTHIN BASES. 71 
 
 bonate, and i or 2 c.c. of ammonium hydrate. Shake 
 until the sodium carbonate is dissolved; this precipitates 
 the earthy phosphates. Separate this precipitate in the 
 centrifuge, and decant all of the supernatant clear urine 
 into another graduated tube. To the clear urine, now 
 free from phosphates, add 2 c.c. of ammonic hydrate and 
 2 c.c. of an ammoniacal solution of silver nitrate made by 
 dissolving 5 grams of silver nitrate in 100 c.c. of distilled 
 water, and adding ammonic hydrate until the solution be- 
 comes clear. 
 
 The addition of the silver solution causes the uric acid to 
 be precipitated as the urate of silver — a translucent, slimy 
 substance. Separate this precipitate in the centrifuge, pour 
 off the supernatant urine, and add to the precipitate an 
 excess of ammonic hydrate — at least 5 c.c. — and mix thor- 
 oughly. By this last step any of the chlorides that may 
 have been precipitated are redissolved, leaving only pure 
 urate of silver. Lastly, centrifugalize again until the silver 
 urate precipitate has fallen as low as it will go. 
 
 Each 3V <^^ ^ ^^^^^ centimeter as marked on the gradu- 
 ated tube is equivalent to 0.00 1 176 gram of uric acid in 10 
 c.c. of urine. For example : if 0.5 be the lowest reading 
 obtainable, then 5 X 0.001176 = 0.00588 gram of uric 
 acid in 10 c.c. of urine. In order to obtain the per- 
 centage, multiply this result by 10 ; if the twenty-four- 
 hour quantity of urine be known, the total uric acid can be 
 easily calculated. 
 
 XANTHIN BASES. 
 
 •A number of xanthin bases have been found in urine : 
 Xanthin, C.H.N.O^ ; Heteroxanthin, CgHgN^ ; Paraxan- 
 thin, C.HgNp, ; Guanin, C.H,Np ; Hypoxanthin (sarkin), 
 QH.Np ; Adenin, CH.N, ; Episarkin, C.HgN,© ; Carnin, 
 qHsNPj; Epiguanin, Ci^Hj^NgO^ ; and, finally, an un- 
 known base discovered by Kriiger. 
 
 The xanthin bases have also been called nuclein bases (Kos- 
 sel) and alloxur bases (Kossel and Kriiger). The alloxur bases, 
 together with uric acid, have been given the names alloxur 
 bodies (Kossel and Kruger) and purin bodies (E. Fischer). 
 
 Kruger and Salomon ^ have recently made an extensive study 
 of the alloxur bases. From 10,000 liters of urine they obtained 
 
 1 "Zeitschr. f. physiol. Chemie," Bd. xxvi, 1898, S. 350.
 
 72 
 
 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 the following: Xanthin, lo.ii gm.; heteroxanthin, 22.345 
 gm.; l-methylxanthin, 31.285 gm.; paraxanthin, 15.31 gm.; 
 hypoxanthin, 8.50 gm.; adenin, 3.54 gm.; and epiguanin, 
 3.4 gm. The bases adenin, hypoxanthin, and xanthin, due 
 to the breaking down of nuclein, occur in smaller quantities 
 than the homologues of xanthin which are probably derived 
 from the theobromin, caffein, and theophyllin introduced into 
 the system by the use of tea and coffee, paraxanthin being 
 obtained from caffein, heteroxanthin from theobromin, and 
 l-methylxanthin from theophyllin. 
 
 A brief consideration of the most important of the 
 xanthin bases follows.^ 
 
 Xanthin (QH^N^O,). — When pure xanthin is dissolved 
 in a weak alkali with the aid of heat, strongly diluted 
 
 pig._ g. — Xanthin crystals (after the drawings of Horbaczewski, as represented in 
 Neubauer and Vogel). 
 
 (i : 2000), and then saturated with acetic acid, it crystallizes 
 in macroscopic, colorless, glistening, rhombic plates, ar- 
 ranged in groups. (Fig. 8.) Xanthin, which is separated 
 from its concentrated aqueous solution by boiling, is amor- 
 phous, but on standing soon collects in flakes, films, or crusts. 
 Xanthin is soluble in 13,000 to 14,000 parts of cold 
 water, and in 1300 to 1400 parts of hot water; it is diffi- 
 cultly soluble in dilute alcohol and dilute acids, but much 
 more soluble in amnionic hydrate than in water. On 
 cooling, xanthin separates from its warm saturated solution 
 
 1 For details see Neubauer and Vogel, Bd. I, 1898, S. 331.
 
 HETEROXANTHIN. 73 
 
 in ten per cent, ammonia in the form of fine needles of 
 xanthin-ammonium. If xanthin be dissolved in very weak 
 sodic hydrate, on standing small crystals of xanthin-sodium, 
 CjHgNaN^Og . H.,0, separate. A solution of xanthin 
 in ammonia gives, with an ammoniacal solution of zinc 
 chloride, a white precipitate which is soluble in an excess 
 of ammonia. Xanthin in crystalline form contains one 
 molecule of water of crystallization ; when amorphous, it is 
 water-free. If xanthin is heated in a closed tube, it sub- 
 limes without melting, and results in a decomposition with 
 the evolution of hydrocyanic acid. 
 
 Xanthin is a constituent of normal urine, but is present 
 only in traces. Kriiger and Salomon ^ found only 13 grams 
 in 10,000 liters of normal human urine. Stadthagen was 
 able to isolate from the twenty-four-hour quantity of urine 
 of a healthy individual on a mixed diet 0.032 and 0.025 
 gram. 
 
 Xanthin contains one atom less of oxygen than uric acid, 
 to which it is closely allied. It has rarely been encountered 
 as a constituent of the urinary sediment. It has been found 
 as a constituent of a very rare form of calculus, and in those 
 cases reported, was always observed in children. 
 
 Xanthin is increased in leukemia (as high as 0.028 gram 
 in 100 c.c.) ; Stadthagen found 0.07 gram in the twenty-four- 
 hour urine as an average of seven determinations. Pouchet^ 
 found it in unusual quantities in fever, and particularly in 
 affections of the nervous system — pachymeningitis cervicalis 
 hypertrophica and tabes dorsalis. 
 
 Detection. — (i) When a solution of xanthin in a fixed 
 alkali is added to sodium or calcium hypochlorite, nitrogen 
 gas is evolved and the solution becomes green, changing to 
 a brown and finally to a yellow. (2) When xanthin is 
 heated to 200° C. with fuming hydrochloric acid, it is de- 
 composed into glycocoll, ammonia, carbonic acid, and formic 
 acid. (3) When evaporated to dryness with nitric acid, a 
 yellow residue remains, which becomes violet on the addi- 
 tion of potassium hydrate, the violet color increasing upon 
 the application of heat. (See Murexide Test for Uric Add.) 
 
 Heteroxanthin (C.HgNp, . CH3). — Heteroxanthin, 
 when pure, crystallizes from its hot aqueous solution in 
 
 i"Zeitschr. f. physiol. Chemie," Bd. xxi, 169, 1895. 
 2 "Thesis," Paris, 1880.
 
 74 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 glossy needles about a half centimeter in length, also in 
 thorn-like spheres, and in thick columns which have a fan- 
 like arrangement. It is soluble in 1592 parts of water at 
 18° C, in 109 parts of boiling water, and is sparingly 
 soluble in absolute alcohol. When pure, it is insoluble in 
 ether and chloroform ; but when impure, it is sparingly 
 soluble in chloroform. It is readily soluble in ammonia and 
 other alkalies. Heteroxanthin combines with sodium to 
 form a double salt, prepared by the addition of sodic hydrate 
 to its concentrated solution. 
 
 Heteroxanthin is a constituent of normal urine, but is 
 present only in minute quantities. Salomon found only i 
 gram in looo liters ; Kriiger and Salomon isolated 7.5 
 gram from 10,000 liters of normal human urine. 
 
 Clinically, it is increased in leukemia, in phosphorus- 
 poisoning, and following the ingestion of theobromin and 
 caffein. 
 
 Detection. — Heteroxanthin does not respond to the 
 tests for xanthin. It gives an intense Weidel's reaction 
 with hydrochloric acid and a trace of potassium chlorate ; 
 the red residue changes to a violet on the addition of potas- 
 sium hydrate. 
 
 Hypoxanthin (C.H^N^O). — Hypoxanthin, also termed 
 sarkin, is present in normal urine, but only in minute quan- 
 tities. Pure hypoxanthin does not crystallize in the form of 
 needles, but always appears on the bottom and sides of the 
 glass or on the surface of the fluid in the form of a film, as 
 oval kernels with sharp angles. Like xanthin and hetero- 
 xanthin, when heated in a closed tube it sublimes and 
 evolves hydrocyanic acid. It is soluble in 300 parts of cold 
 water and in 78 parts of hot water, also in 900 parts of hot 
 alcohol. It is more readily soluble in ammonia than in 
 water. It is not precipitated by saturating its solution with 
 ammonium chloride. Hypoxanthin is precipitated from its 
 solution in alkalies by carbonic acid. It combines with 
 the salts of sodium, zinc, and calcium to form double 
 salts. 
 
 Hypoxanthin has been found in the normal urine of man 
 by Salomon, Salkowski, and others. It is most abundant 
 after a hearty meat diet (in dogs). It appears to be in 
 larger quantities in the urine of leukemia than in that of 
 health (Stadthagen isolated an average quantity of 0.009 
 gram — as high as 0.027 gram — from leukemic urine), also
 
 PARAXANTHIN. 75 
 
 in diseases of the liver and kidneys (Thudichum), and in 
 fever and diseases of the central nervous system (Pouchet). 
 
 Detection. — When hypoxanthin is treated with zinc 
 and dikite hydrochloric acid, and then sodic hydrate is 
 added, a red or reddish-brown color appears, the result of 
 the absorption of oxygen from the air. Hypoxanthin does 
 not give a green color with sodic hydrate and calcium 
 hypochlorite as does xanthin. 
 
 Paraxanthin (C5H.,Np^(CH3y.— Paraxanthin is iso- 
 meric with theobromin and theophyllin. It crystallizes 
 in colorless, glossy, six-sided plates. It is difficultly solu- 
 ble in cold water, but dissolves much more readily in hot 
 water, its solutions having a neutral reaction. It is insolu- 
 ble in alcohol and ether. It combines with sodium to form 
 a double salt, which has much the same general properties 
 as the compound of sodium with heteroxanthin. 
 
 Paraxanthin has been detected in the urine of man by 
 Thudichum and Salomon. Like the other bases of this 
 group, it was found in unusual quantities in leukemic urines. 
 Comparatively little is known of the clinical significance 
 of this substance. 
 
 Detection. — Paraxanthin gives the Widal reaction, but 
 does not respond to the tests for xanthin. 
 
 The isolation of the xanthin bases is accomplished in four 
 ways: (i) Precipitation with ammoniacal solution of silver 
 nitrate ; (2) with copper suboxide ; (3) with phosphotungstic 
 acid ; (4) with cupric acetate. ^ 
 
 NUCLEIC AQD. 
 
 This acid has been found by Morner in very small 
 quantities in the urine. It appears, however, in large 
 amounts in combination with albumin as nucleo-albumin. 
 (See p. 140.) The nucleic acids are compounds of phos- 
 phoric acid, xanthin bases, and a nitrogen-free substance. 
 Some of these compounds have been recognized as pentose 
 and hexose. The amount of phosphorus in the nucleic 
 acids varies, but may reach as high as 9 or 10 per cent. 
 They zx^ amorphous, have an acid reaction, are soluble in 
 ammonia, in alkaline hydrates, or in distilled water holding 
 a small amount of alkali, and are precipitated from their 
 
 ' See Neubauer and Vogel, "Analyse des Hams," Bd. i, 1898, S. 362.
 
 76 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 solutions by a small amount of hydrochloric acid, but 
 not by acetic acid. They are, however, precipitated by an 
 excess of glacial acetic acid. They are completely precipi- 
 tated by alcohol in the presence of hydrochloric acid. Ac- 
 cording to Kutscher, nuclein is precipitated from a neutral 
 solution of the salts of nucleic acid by an aqueous solution 
 of albumose. Noll ^ has recently succeeded in forming 
 levulinic acid from nucleic acid by heating with thirty per 
 cent, sulphuric acid for two hours. 
 
 Nucleic acid is not precipitated by the reagents used for 
 the precipitation of proteids, and does not give the color 
 reactions of proteids. When some of the nucleic acids are 
 boiled with dilute mineral acids, a substance (carbohydrate) 
 is produced which reduces alkaline solutions of cupric 
 oxide. 
 
 The detection of the nucleic acids depends upon the iso- 
 lation of their chief constituents — phosphoric acid and xan- 
 thin bases. 
 
 ALLANTOIN. 
 C4H8N4O3. 
 
 This substance has been found in the urine of infants 
 within the first eight days after birth, in new-born calves 
 (Wohler), and in the urine of man (Ziegler and Hermann). 
 
 Allantoin, when pure, crystallizes in large monoclinic 
 prisms with hexagonal bases, often arranged in star-like 
 groups ; when impure, in warty and granular particles. It 
 has a neutral reaction, is difficultly soluble in cold water 
 (160 parts), more readily in hot water (30 parts), very sol- 
 uble in alkaline hydrates, and, according to Salkowski, 
 more readily soluble in a solution of piperazin than in 
 water. It is insoluble in alcohol and ether. It combines 
 with acids and bases to form salts. The compounds with 
 silver oxide and mercuric oxide are particularly serviceable 
 for the detection of allantoin. 
 
 When a freshly prepared solution of allantoin in sodic or 
 potassic hydrate is supersaturated with acetic acid, it is 
 immediately precipitated. It then contains allantoic acid. 
 
 Allantoin is obtainable from uric acid by oxidation with 
 potassium permanganate : 
 
 aCjH^N^Os + 2H2O + 02 = aC^HgNPs + 2C0,j. 
 Uric acid. Allantoin. 
 
 i*'Zeitschr. f. physiol. Cheniie," Bd. xxv, S. 430.
 
 ALLANTOIN. 77 
 
 Allantoin is decomposed by heating with hydrochloric 
 acid into allanturic acid and urea : 
 
 QIIeN.Oj + H,0 = CgH.Np, + CH,N,0. 
 Allantoin. Allanturic acid. Urea. 
 
 When allantoin is boiled with an alkali or baryta water, 
 it furnishes first, as in the decomposition with acids, allan- 
 turic acid and urea ; but the allanturic acid is further decom- 
 posed into hydantoic and parabanic acids : 
 
 2C.,H,N,03 = 
 
 ^. CgHgN.Oj + CgH^N^Oj. 
 
 Allanturic 
 acid. 
 
 Hydantoic Parabanic 
 acid. acid. 
 
 and the parabanic acid is finally decomposed into oxalic 
 acid and urea : 
 
 C3H,N,03 + 2H,0 = C,H,0;+ CH,N,0. 
 
 Oxalic Urea, 
 
 acid. 
 
 Allantoin reduces Fehling's solution on boiling. It is 
 not precipitated by lead acetate or phosphotungstic acid, 
 and does not give the murexide reaction. 
 
 Allantoin is present in normal urine in mere traces, ex- 
 cept directly after birth. It has been found to be increased 
 by a meat diet, and by the administration of tannic acid. 
 Pouchet found allantoin considerably increased in the urine 
 of a case of diabetes insipidus and in a case of hysteria 
 with convulsions. 
 
 Detection. — In order to detect allantoin, it must first 
 be separated from the urine. The following method of G. 
 Meissner ^ best serves this purpose : Precipitate the urine 
 with, baryta water, exactly neutralize the filtrate with sul- 
 phuric acid, filter at once, and evaporate to beginning 
 crystallization. The fluid, while still warm, is treated with 
 sufficient alcohol to completely precipitate (this precipitate 
 should be saved). The alcoholic solution is then decanted 
 from the precipitate or filtered off, and completely precipi- 
 tated with ether. Both precipitates, especially the one ob- 
 tained with the ether, contain the allantoin together with 
 other substances. The precipitates are then extracted with 
 a little cold water or with hot alcohol, the allantoin remain- 
 ing undissolved. Characteristic crystals of allantoin are 
 then obtained by recrystallizing the residue from hot water. 
 
 i"Zeitschr. f. rat. Med.," [3] Bd. xxiv, 104, u. Bd. xxxi, 297.
 
 78 
 
 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 KREATIN AND KREATININ. 
 
 CiHgNaOa— CiHjNaO. 
 
 These two substances are constituents of normal urine. 
 They differ chemically in that kreatinin contains one mole- 
 cule less of H2O than kreatin, as seen by the foregoing 
 formulae. Kreatin, which is constantly present in muscle 
 tissue, is in all probability the antecedent of kreatinin, so 
 that two sources of this substance must be recognized — /. c, 
 the muscle tissue of the body and the muscle tissue taken 
 as food. Kreatin is more abundant in alkaline urine than 
 kreatinin, while in a strongly acid urine the reverse is the 
 case. Since the urine is generally acid, kreatinin is the pre- 
 
 Fig. 9. — Crystals of kreatinin-zinc chloride (Salkowski). 
 
 dominating constituent of normal urine, and will be further 
 considered. 
 
 Kreatini)i crystallizes without water of crystallization in 
 colorless, glistening prisms of the monoclinic system ; some- 
 times these crystals, when found lying on their sides, appear 
 in the form of whet-stones. Kreatinin is readily soluble in 
 hot water and quite soluble in cold water ; it is very solu- 
 ble in hot alcohol, but more difficultly so in cold alcohol 
 and ether. It reduces alkaline solutions of copper (Feh- 
 ling's solution) upon boiling. It forms salts with the acids, 
 and double salts with some of the salts of the heavy metals. 
 Among these may be mentioned kreatinin chloride or
 
 KREATININ. 79 
 
 hydrochlorate, which is easily soluble in water and crystal- 
 lizes in the form of transparent prisms or rhombic plates. 
 One of the most important of the double salts is the com- 
 pound of kreatinin with zinc chloride (C^H^N^O)^ . ZnCl2, 
 produced by treating an aqueous or alcoholic solution of 
 kreatinin with zinc chloride. If the kreatinin is pure, the com- 
 pound crystallizes in the form of fine needles grouped together 
 in rosettes or sheaves. (Fig. 9.) Kreatinin-zinc chloride 
 is very slightly soluble in water and insoluble in alcohol. 
 
 Kreatinin is a constituent of normal human urine. Ac- 
 cording to the determinations of Neubauer, a healthy man 
 on a well-mixed diet eliminates from 0.6 to 1.3 grams of 
 kreatinin in twenty-four hours. As indicated, the quantity 
 of kreatinin appears to vary according to the disintegration 
 of muscle tissue in the body and the amount of meat 
 ingested with the food. 
 
 Clinically, it is excreted in increased quantity in acute dis- 
 eases, such as typhoid fever, pneumonia, etc. It is diminished 
 in hunger, in convalescence from acute diseases, in advanced 
 degeneration of the kidneys, and in wasting diseases. 
 
 Detection of Kreatinin. — i. JVej/'s Test. — To a {&\n 
 cubic centimeters of the urine add a few drops of a very 
 dilute solution of sodium nitroprusside, and render alkaline 
 with sodic hydrate. If kreatinin be present, the mixture 
 assumes a ruby-red color, which disappears in a few minutes 
 and is replaced by an intense yellow color, which, on 
 w^arming with glacial acetic acid, gives rise to a green color. 
 The presence of albumin and sugar does not interfere with 
 the reaction. 
 
 2. To a solution of kreatinin add a small quantity of an 
 aqueous solution, of picric acid, and then a few drops of 
 dilute sodic or potassic hydrate. An intense red color ap- 
 pears. This red color is apparent (only less intense) when 
 kreatinin is present in the proportion of i : 5000 ( Jaffe). 
 
 3. When a solution of kreatinin is acidulated with nitric 
 acid and treated with phosphomolybdic acid, a yellow, 
 crystalline precipitate is produced, which is soluble in hot 
 nitric acid. 
 
 4. The double compound of kreatinin and zinc chloride 
 shows, microscopically, characteristic cr^^stals. (Fig. 9.) 
 This test is used for the quantitative estimation of kreatinin. ^ 
 
 ^ See Neubauer and Vogel, "Analyse des Hams," Bd. I, 1898, S. 396.
 
 80 ORGANIC CONSTITUENTS OF NORMAL URINE, 
 
 THE AROMATIC SUBSTANCES IN URINE. 
 
 The aromatic substances that occur in urine belong to 
 four classes : 
 
 1. Hippuric acid, and similar aromatic compounds of 
 glycocoll. 
 
 2. Combinations of glycuronic acid with aromatic sub- 
 stances. (See p. 169.) 
 
 3. Aromatic oxyacids. 
 
 4. Ethereal sulphates. 
 
 Hippuric Acid (CgHgNO,). — Hippuric acid is a constitu- 
 ent of the urine of man in both health and disease. The 
 twenty-four-hour quantity of urine contains between o.i 
 and I gram It is very abundant in the urine of herbivora, 
 
 Fig. 10. — Hippuric acid crystals. 
 
 and in man the quantity varies largely according to the 
 amount of vegetable food ingested. It is absent from the 
 urine of carnivora. 
 
 Hippuric acid crystallizes either in the form of fine 
 needles or four-sided prisms and pillars, the ends of which 
 terminate in two or four planes. (Fig. 10.) At times these 
 resemble the crystals of ammonio-magnesium phosphate, 
 with which they should not be confounded. Typically, the 
 crystals of hippuric acid are in the form of vertical rhombic 
 prisms. 
 
 Hippuric acid is soluble in 600 parts of water at 0° C, 
 and much more soluble in hot water and alcohol. Its solu- 
 tions have a strongly acid reaction. It combines with bases 
 to form salts. Its compounds with the alkalies and alkaline 
 earths are soluble in water and alcohol, but the silver, cop- 
 per, and lead salts are difficultly soluble in water. Strong 
 acids precipitate the hippuric acid from its salts, and it
 
 HIPPURIC ACID. 81 
 
 reappears in crystalline form. When hippuric acid is boiled 
 with an alkaline hydrate or with mineral acids, it takes up 
 a molecule of water and is decomposed into benzoic acid 
 and glycocoll : 
 
 CgHj . CO — HN . CH, . COOH + Hfi = 
 Hippuric acid. 
 
 CgHs . COOH + HjN . CH2 . COOH. 
 Benzoic acid. Glycocoll. 
 
 This same decomposition takes place during the alkaline 
 fermentation of the urine, especially of urine containing 
 albumin, the hippuric acid being acted upon by the micro- 
 coccus ureae. No hippuric acid, therefore, is found in 
 decomposing urine, benzoic acid taking its place. Hippuric 
 acid reduces alkaline solutions of cupric oxide (Fehling's 
 solution) on boiling. 
 
 The experiments of Meissner and Shepard, and of 
 Schmiedeberg and Bunge show that hippuric acid is prob- 
 ably formed by the union of benzoic acid and glycocoll, 
 and that this union takes place in the kidneys, as they 
 failed to find that the synthesis occurred after the removal 
 of the kidneys. 
 
 As previously indicated, the amount of hippuric acid in 
 the urine of man is dependent chiefly upon the character 
 and quantity of food ingested, being increased by a vege- 
 table diet, especially by certain fruits, as prunes, mulberries, 
 cranberries, blueberries, or by any substance containing the 
 benzoic acid radicle. It is increased by the administration 
 of benzoic acid, cinnamic acid, oil of bitter almonds, salicylic 
 acid, toluol, etc. ; also in acute febrile diseases, hepatic dis- 
 eases, diabetes mellitus, and cholera. It is diminished by 
 an exclusive meat diet, although generally it does not dis- 
 appear entirely from the urine upon such a diet. It is an 
 interesting fact that, in accordance with Bunge's experi- 
 ments on dogs, the elimination of hippuric acid appears to 
 be wholly suspended in ca.ses of acute and chronic paren- 
 chymatous nephritis, following the ingestion of benzoic acid, 
 which reappears in the urine unchanged. 
 
 Detection.— When urine containing hippuric acid or one 
 of its salts is evaporated to dryness with concentrated nitric 
 acid, and the residue is heated in a test-tube, the odor of 
 bitter almonds is noticed, due to the formation of nitro- 
 benzol (benzoic acid gives the same result). 
 6
 
 82 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 Hippuric acid may be separated from urine containing an 
 excess of it by evaporating the urine to one-fourth of its 
 volume and acidulating with hydrochloric acid. In a few 
 hours characteristic crystals of hippuric acid will be found 
 in the deposit, when examined microscopically. 
 
 Quantitative Kstimation. — Ma/iod. — From 500 to 
 1000 c.c. of fresh urine are evaporated to a syrupy con- 
 sistence on a water-bath, care being taken to keep the urine 
 neutral by the addition of sodium carbonate. The residue is 
 extracted with cold alcohol (ninety to ninety-five per cent.), 
 taking a quantity about half as great as that of urine em- 
 ployed, and setting aside the mixture for twenty-four hours. 
 The alcohoHc filtrate, which contains the salts of hippuric 
 acid, is then freed from alcohol by distillation. The remain- 
 ing solution is strongly acidulated with acetic acid, in order 
 to liberate the lactic acid, and extracted with at least five 
 times its own volume of alcoholic ether (one part of alcohol 
 to nine parts of ether). From the combined extracts the 
 ether is distilled off and the remaining solution evaporated 
 on a water-bath. The resinous residue is boiled with 
 water, set aside to cool, and filtered through a well-moist- 
 ened filter. The hippuric acid, which is easily soluble in 
 boiling water, is thus separated from constituents that are 
 soluble in alcohol and ether. The filtrate is rendered alka- 
 line with a little milk of lime, any excess of calcium hydrate 
 being removed by passing carbon dioxide through the mix- 
 ture. This mixture is then brought to the boiling-point and 
 filtered. Any impurities present are removed by shaking 
 with ether. The calcium salts remaining in solution are 
 decomposed by means of an acid, and the solution is again 
 extracted with ether. The remaining solution is evaporated 
 to a few cubic centimeters, when the hippuric acid will sepa- 
 rate on standing. The crystals are dried on plates of plaster- 
 of- Paris ; they are then shaken with benzol or petroleum 
 ether to remove any benzoic acid, and finally weighed. 
 These crystals may be shown to be hippuric acid by their 
 microscopic appearance, their solubility in alcohol, and 
 their behavior when evaporated with concentrated nitric 
 acid, as previously indicated. 
 
 Aromatic Oxyacids. — Two of these, hydroparacumaric 
 acid and paraoxyphenyl-acetic acid, are found in the urine 
 in small quantities in combination with potassium. They 
 apparently are derived from the decomposition that takes
 
 ETHEREAL SULPHATES. 83 
 
 place in proteids in the intestine ; tryosin is probably an 
 intermediate product (Baumann) ; 
 
 CgH„N03 + H, = C^HioOj + NH3. 
 
 Tyrosin. Hydropara- 
 
 cumaric acid. 
 
 C,H,„0, = C,Hi„0 + CO,. 
 
 Hydiopara- Paraethyl 
 
 cumaric acid. phenol. 
 
 C«H,„0 4- O3 = CgHgOs + H,0. 
 Paraethyl Paraoxy- 
 
 pheiiol. phenyl-acetic 
 
 acid. 
 
 Ethereal Sulphates. — A few of the products of decom- 
 position are of especial interest because of their behavior 
 within the body, and because after their absorption they 
 appear in the urine in the form of ethereal or conjugate sul- 
 phates of sodium and potassium. A few, such as the oxy- 
 acids, pass unchanged into the urine ; others, such as 
 phenols, are changed into ethereal sulphates by synthesis, 
 and are eliminated by the urine. Still others, such as indol 
 and skatol, are converted into ethereal sulphates only after 
 oxidation. The quantities of these bodies in the urine vary 
 largely with the extent of the putrefaction that is constantly 
 taking place in the intestine. 
 
 The earliest information bearing upon this subject was 
 furnished in 185 i by Stadeler, who found that on distilling 
 the urine of oxen and of men with dilute sulphuric acid, he 
 obtained in the distillate small amounts of phenol. It was 
 not, however, until 1875 that Baumann discovered that 
 phenol existed in an ethereal combination with sulphuric 
 acid. He also determined the presence of other ethereal 
 sulphates, all of which were found to be compounds of the 
 radicle HSO.,. 
 
 The ethereal sulphates appear to have one or both of two 
 origins: (i) From the aromatic substances in the food; 
 hence their greater abundance in the urine of herbivora. 
 (2) From the intestine as a result of putrefaction. They 
 are absorbed from the intestine, pass into the blood, and 
 are eliminated in the urine in combination with potassium 
 and sodium as ethereal sulphates. 
 
 A large number of determinations have been made rela- 
 tive to the proportion of the ethereal sulphates to the 
 ordinary (alkaline) sulphates in the urine of man, and the 
 normal proportion may be stated as about i : 10.
 
 84 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 In disease, whenever the putrefaction in the intestine or 
 in other parts of the body is increased, the proportion of 
 ethereal sulphates rises. The investigations of G. Hoppe- 
 Seyler are noteworthy, his results being summarized as fol- 
 lows : 
 
 1. Deficient absorption of the normal products of digestion, 
 such as occurs in peritonitis and tubercular disease of the intes- 
 tine, leads to an increase of the ethereal sulphates in the urine, 
 because the products of digestion undergo putrefactive changes, 
 and the putrefactive products are absorbed. 
 
 2. Diseases of the stomach, in which the food lies in the 
 stomach a long time and undergoes fermentative changes, 
 always lead to an increase of the ethereal sulphates in the urine. 
 
 3. Simple constipation and typhoid fever do not produce this 
 result. 
 
 4. Putrefactive processes outside the alimentary canal, putrid 
 cystitis, putrid abscesses, putrid peritonitis, etc., have the same 
 result as putrefactive processes within the intestine. The amount 
 of the ethereal sulphates is, moreover, in all cases proportional 
 to the degree of the putrefaction, and is increased by the reten- 
 tion and diminished by the discharge of putrid matter. 
 
 It has been conclusively shown b)- these and other obser- 
 vations that the best criterion of the occurrence and amount 
 of putrefaction in the body is the relation of the ethereal 
 sulphates to the total sulphates. 
 
 Indoxyl-potassium Sulphate (C^H^.NO . SO^ . OK), In- 
 doxyl — Indican (/) — This substance is formed from indol, 
 — CgH^N, — which is a product of the putrefaction of 
 albuminous substances in the intestine. The indol is then 
 absorbed from the intestine and enters the blood, where 
 it becomes oxidized to indoxyl, — C^H^jNO, — which imme- 
 diately combines with potassium (and to a slight extent 
 with sodium) sulphate to form indoxyl-potassium sulphate, 
 in which form it is eliminated in the urine. 
 
 By the oxidation of indoxyl-potassium sulphate indigo- 
 blue is formed : 
 
 zCgHgNKSO^ -(- O, = aC.HjNO + 2HK . SO,. 
 
 Indoxyl-potassium Indigo-blue. Potassium hy- 
 
 sulphale. drate sulphate. 
 
 Indigo-red, which has the same elementary composition 
 as indigo-blue, is also one of the products of the oxidation 
 of indoxyl sulphate. 
 
 Indoxyl is a constituent of normal human urine, as a
 
 INDOXYL-POTASSIUM SULPHATE. 85 
 
 result of the natural intestinal putrefaction. It is absent 
 from tiie urine of the new-born. 
 
 Under ordinary conditions indoxyl does not contribute to 
 the color of freshly passed urine. It may, however, become 
 partially oxidized in the body, especially in disease, or oxida- 
 tion may take place outside of the body during the am- 
 moniacal decomposition of the urine, when it probably 
 furnishes some color to the urine. In rare instances the 
 indoxyl sulphate is completely oxidized within the body, 
 and a blue color is imparted to the urine, due to the deposit 
 of indigo-blue. Furthermore, indigo calculi have been 
 found in the urinary tract following the long-continued 
 separation of indigo from the urine, but such instances are 
 of very rare occurrence. 
 
 The quantity of indoxyl separated from the urine as in- 
 digo-blue has been found to be between 0.005 ^''"'^1 0.025 
 gram in the twenty-four-hour secretion of a healthy indi- 
 vidual on a mixed diet (Neubauer and Vogel). The largest 
 quantities excreted in health are observed after a liberal in- 
 gestion of a meat diet, particularly the so-called red meats, 
 while the smallest quantities have been found during the 
 ingestion of a milk diet. 
 
 Clinical Significance. — The clinical importance of in- 
 doxyl rests chiefly upon its increased elimination, its dimi- 
 nution having little or no importance. Indoxyl is increased : 
 (i) In all cases of increased intestinal putrefaction, espe- 
 cially that taking place in the small intestine. Thus, in 
 diarrhea it is increased, whereas in dysentery (disease of 
 the large intestine) no such increase takes place. It is in- 
 creased in typhoid fever and in cholera, also in some forms 
 of Bright's disease, notably chronic diffuse, chronic inter- 
 stitial, and subacute glomerular nephritis. Simon has ob- 
 served an increase in cases in which the gastric juices 
 contained an abnormally small amount of free hydrochloric 
 acid or in which it was absent entirely, notably carcinoma of 
 the stomach, and he believes that it is possible to form a 
 fairly accurate idea of the amount of free hydrochloric acid in 
 the stomach by examining the urine for indoxyl. There are 
 exceptions to this, however, to explain which he grants is im- 
 possible at the present time. Indoxyl is also increased in 
 acute, subacute, and chronic gastritis of whatever origin ; in 
 acute peritonitis (marked increase), cancer of the mesentery, 
 appendicitis, diseases of the liver and pancreas, especially
 
 86 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 those accompanied by an acute peritonitis ; in Addison's 
 disease, lead colic, and, in short, in any disease of the ab- 
 dominal viscera accompanied by an increase in the intestinal 
 putrefaction. It is also increased in acute diseases elsewhere 
 in the body, as in pneumonia, pleurisy, meningitis, acute 
 articular rheumatism, etc. 
 
 (2) The indoxyl is increased by any condition that pre- 
 vents the passage of fecal matter through the small intes- 
 tine, as in intussusception, twists, new growths, and the like. 
 In diseases of the large intestine an increase of indoxyl is 
 never seen ; thus, the tests for indoxyl in the urine are of 
 decided value in the differential diagnosis. In simple, un- 
 complicated constipation the indoxyl is not increased. 
 
 (3) An increase in the indoxyl is also seen when albu- 
 minous putrefaction takes place in other parts of the body, 
 as in cases of empyema, putrid bronchitis, gangrene of the 
 lungs, advanced phthisis, etc. 
 
 There can be no doubt of the clinical significance of the 
 test for indoxyl in the urine, for points of decided importance, 
 not only in diagnosis, but also in prognosis and treatment, 
 can thus be gained. 
 
 Detection. — (i) The following color reaction depends 
 upon the decomposition and oxidation of the indoxyl-sul- 
 phate of potassium by means of hydrochloric acid, the 
 oxidation being accelerated by the use of nitric acid. The 
 color that results usually consists of a mixture of indigo- 
 blue and indigo-red (amethyst). 
 
 Take 15 c.c. of strong hydrochloric acid (C. P.) in a wine- 
 glass, add one or two drops of strong nitric acid (C. P.), 
 stir, then add thirty drops of the urine to be tested, and 
 stir immediately. An amethyst color soon makes its ap- 
 pearance, reaching its greatest intensity in from five to 
 twenty minutes. The amount of color obtained at the point 
 of greatest intensity furnishes some data as to the amount 
 of indoxyl present. If normal, a distinct but not intense 
 amethyst color appears ; if increased, the color is decided 
 and often very deep ; and if diminished, there will be but 
 very little color, and rarely an entire absence of color. 
 
 The reaction can also be obtained by using hydrochloric 
 acid alone, but has the disadvantage of requiring a longer 
 time for the greatest color to appear. It is, therefore, ad- 
 visable to add one or two drops of nitric acid in order to 
 hasten oxidation, care being taken not to add more, or the
 
 SKATOXYL-POTASSIUM SULPHATE. 87 
 
 oxidation will be so rapid that the amethyst color can not 
 be seen, only a yellow color resulting. ^ 
 
 The thirty drops of urine added should always be uni- 
 form in size, and such as are obtained when the urine is 
 dropped from the lip of a urinometer-glass. (Fig. 2.) It 
 is, therefore, advisable to have a pipette for the perform- 
 ance of the test, made by dropping thirty drops of urine 
 into a wine-glass, then drawing it up into the pipette, and 
 indicating the level of tlie urine by means of a scratch on 
 the glass. 
 
 In urine containing potassium iodide the test for indoxyl 
 can not be satisfactorily applied, particularly if hydrochloric 
 acid containing free hydrochloric-acid gas be used, or if 
 nitric acid be added to the hydrochloric acid. This is 
 because of the oxidizing action of the iodine that is set 
 free. Under such circumstances a yellow color imme- 
 diately results ; in other words, the oxidation is so rapid 
 that the amethyst color can not be seen. 
 
 (2) Take about 10 c.c. of the urine in a test-tube, add an 
 equal volume of hydrochloric acid and a few drops of a 
 freshly prepared saturated solution of sodium hypochlorite, 
 calcium hypochlorite, or common saltpeter, and then i or 2 
 c.c. of chloroform. The mixture is thoroughly agitated and 
 set aside. The indigo that has been set free is taken up 
 by the chloroform, coloring this to a greater or less extent, 
 the degree of increase as compared with the normal being 
 determined by the intensity of color. 
 
 Albumin does not interfere with these two tests. Bile 
 pigment, which interferes with the reaction, may be removed 
 by the addition of a solution of basic acetate of lead, care- 
 fully avoiding an excess. Urines presenting a very dark 
 color may be freed from the greater part of their coloring- 
 matter in the same manner. If potassium iodide be present, 
 the chloroform will be colored more or less of a carmine, 
 owing to the liberation of free iodine. 
 
 Skatoxyl-potassium Sulphate (C„H^NO . SO^K ).— 
 This substance is formed from skatol, which, like indol, is a 
 product of the putrefaction of proteids in the intestine. 
 Some of it is absorbed by the blood, where it combines 
 w^ith potassium sulphate, in which form it is eliminated in 
 
 1 If hydrochloric acid containing much free hydrochloric-acid gas be used 
 for the test, nitric acid should not be added, since the oxidation is effected by 
 the free gas present.
 
 88 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 the urine as a colorless compound, and when it is oxidized, 
 it yields a red color. 
 
 Skatoxyl-potassium sulphate is a constituent of normal 
 urine, but is usually present in smaller quantities than the 
 indoxyl sulphate. 
 
 Clinically, this substance is of little interest except in 
 connection with indoxyl, and since both the skatoxyl and 
 indoxyl sulphates are, clinically, considered as one, it is not 
 necessary here to enter into the consideration of its proper- 
 ties or modes of detection further than to state that the 
 indigo-red oxidation products obtained in the tests for 
 indoxyl are probably partly due to the presence of skatoxyl- 
 potassium sulphate. 
 
 Phenol-potassium Sulphate (C,.H.O SO.j . K). — Phenol, 
 C^^HyO, is one of the products of intestinal putrefaction. 
 The production of phenol probabh' takes place lower down 
 in the small intestine than indol, but higher up in the intes- 
 tine than skatol. It is absorbed from the intestine, and, 
 entering the blood, combines with potassium sulphate to 
 form the ethereal or conjugate sulphate, phenol-potassium 
 sulphate. According to Baumann, some of the sulphate 
 comes from tyrosine, which passes through the stages of 
 parakresol and paraoxybenzoic acid before conversion into 
 the phenol salt. This substance is the form in which all 
 of the phenol or carbolic acid of the body exists. It is a 
 constituent of normal urine, and is present in amounts vary- 
 ing between 0.017 and 0.5 gram — an average of about 0.03 
 gram — for twenty-four hours. Phenol sulphuric acid is 
 abundant in the urine of herbivora. 
 
 A urine rich in indoxyl usually contains an excess of 
 phenol, but one rich in phenol does not always contain an 
 excess of indoxyl. In those cases in which an increased 
 elimination of ethereal sulphates is due to albuminous putre- 
 faction in other parts of the body than the intestine, as in 
 empyema, pulmonary gangrene, putrid bronchitis, etc., an 
 increased elimination of phenol alone may be noted, the 
 amount of indoxyl being about normal. 
 
 Clinical Significance. — The use internally or externally 
 of large amounts of carbolic acid, lysol, salol, and other 
 phenol compounds results in an increase in the amount of 
 phenol sulphate and a corresponding diminution in the ordi- 
 nary sulphates, the latter being taken up by the excess of 
 phenol in the blood. Two substances, pyrocatechin and
 
 PHENOL-POTASSIUM SULPHATE. 89 
 
 hydrochinon, are formed as a result of the splitting up of 
 carbolic acid. Urines containing these substances, although 
 usually normal in color when voided, become smoky, dark 
 brown, or black on standing exposed to the air. This dark 
 color is often more pronounced after alkaline decomposition 
 begins, and is, in all probability, due to the oxidation pro- 
 ducts of hydrochinon. 
 
 The phenol sulphate is increased in those conditions that 
 cause increased putrefaction in the lower part of the small 
 intestine and upper portion of the large intestine. In other 
 words, most of the conditions that cause an increase in 
 the indoxyl sulphate also cause an increase in the phenol 
 sulphate. Its increase is especially marked in peritonitis, 
 pyemia, and in phosphorus-poisoning. 
 
 Detection. — Distil the urine with sufficient sulphuric 
 acid to make a five per cent, mixture, (i) To a portion of 
 the distillate add bromine water, which gives a yellow pre- 
 cipitate of tribromphenol. (2) To another portion add Mil- 
 Ion's reagent, and heat. A beautiful red color results. 
 (3) Saturate still another portion of the distillate with sodic 
 carbonate in the cold, and shake with ether in order to 
 remove salicylic acid and other substances that give a ferric 
 chloride reaction. Evaporate the ether, and to an aqueous 
 solution of the residue add ferric chloride, which gives a 
 deep violet color. 
 
 Determination. — The following procedure may be ap- 
 plied for the determination of phenol in urine : Take 500 to 
 lOOO c.c. of the urine, treat with sufficient sulphuric acid to 
 represent five per cent, of the mixture, and distil as long as 
 a specimen of the distillate is rendered cloudy by bromine 
 water (i : 30), the specimens used for this purpose being 
 carefully preserved. The total quantity of the filtered dis- 
 tillate, together with the specimens that have been set 
 aside, is now treated with bromine water, shaking the mix- 
 ture after each addition of the reagent until a permanent 
 yellow color results. After two or three days the precipi- 
 tate of tribromphenol that forms is collected on a filter that 
 has been previously dried and weighed, washed with water 
 containing a trace of bromine, and then dried over sulphuric 
 acid and weighed. One hundred parts of tribromphenol 
 correspond to 28.4 parts of phenol. 
 
 The urine contains small quantities of two other ethereal 
 sulphates : i. c, kresol-potassiuin sulphate and katccJiol-potas-
 
 90 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 stwn sulphate. These have practically the same significance 
 as those already considered, so that only mere mention here 
 is necessary. For a detailed consideration of these sub- 
 stances see Neubauer and Vogel, " Analyse des Hams," 
 Bd. I, 1898, S. 156 and 158. 
 
 URINARY COLORING-MATTERS. 
 
 Urobilin (CgjH^gN^O^). — Normal urobilin was first isolated 
 from the urine by Jaffe (1868). Although this substance 
 has for a long time been considered the chief coloring- 
 matter of the urine, it probably contributes very little to the 
 color of the freshly passed urine of a healthy individual. 
 Normal urobilin is present in the urine chiefly as a chro- 
 mogen, — urobilinogen, — and it is not until this chromogen 
 is decomposed that its color is set free. In many pathologic 
 conditions, on the other hand, there appears to be a larger 
 amount of free urobilin than normally, and to this MacMunn 
 has given the name "pathological urobilin." This can be 
 artificially prepared from normal urobilin by the action of 
 reducing agents. 
 
 Normal urobilin is amorphous and not deliquescent. Its 
 color varies according to the method of isolation : that pre- 
 cipitated by means of ammonium sulphate is brown ; that 
 precipitated upon the addition of an acid to its alkaline 
 solution is red ; and that obtained by the evaporation of its 
 alcoholic solution is reddish-brown. It is readily soluble in 
 alcohol and chloroform, also in ether, acids, and amnionic 
 hydrate. It is very sparingly soluble in water. Neutral 
 salts increase its solubility in water, but by saturating its 
 solution with some of these salts it is more or less com- 
 pletely precipitated. It combines with alkalies to form 
 salts, and is precipitated from solutions of these salts upon 
 the addition of acids. 
 
 When an acid solution of normal urobilin is examined 
 with the spectroscope, it shows a broad absorption band to 
 the right of E, the left border of which reaches nearly to 
 b, while the right border incloses F. In alkaline solu- 
 tion it shows a less broad absorption band between E and F, 
 inclosing/;. (Fig. 11.) 
 
 The origin of urobilin has been the subject of much dis- 
 cussion. Two theories have been advanced: (i) That 
 urobilin is formed from the bilirubin which enters the in-
 
 UROBILIN. 
 
 91 
 
 testine with the bile, is there acted upon by the nascent 
 hydrogen resulting from fermentation, a reduction product 
 being formed which is absorbed and eliminated by the kid- 
 neys ; (2) that urobilin is formed rather as the result of oxi- 
 dation processes by means of the nascent oxygen in the 
 intestine, or elsewhere in the body, than by a process of 
 reduction. This theory was originally advanced by Mac- 
 Munn, who based his view chiefly on the fact that by the 
 action of hydrogen peroxide on acid hematin he was able 
 to prepare an artificial product which showed the same 
 spectroscopic appearances as normal urobilin. Hoppe- 
 Seyler had previously prepared an artificial urobilin from 
 hemoglobin, and also from hematin, by the action of tin 
 
 Fig. II. — I, Acid urobilin ; 2, alkaline urobilin (after Neubauer and \'ogel). 
 
 and hydrochloric acid. Whether stercobilin and urobilin 
 are'to be looked upon as products of reduction or oxidation 
 must, therefore, still be regarded as unsettled. The most 
 important point to notice, however, is that urobilin may 
 originate either from bile pigment or from blood pigment. 
 It has been conclusively proved that the bile pigment is 
 formed from hemoglobin ; and that in nearly all diseases of 
 the liver accompanied by jaundice, urobilin is largely in- 
 creased in the urine. Furthermore, that those conditions 
 which are attended with a destruction of the blood-corpus- 
 cles are accompanied by an increased amount of urobilin in 
 the urine. It is, therefore, safe to infer that the amount of 
 urobilin in the urine is a measure of the destruction of the 
 hemoglobin, or blood pigment.
 
 92 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 The average quantity of urobilin in the twenty-four-hour 
 urine, under normal conditions, is 123 milligrams; in dis- 
 ease the quantity may reach 800 milligrams. The excre- 
 tion of urobilin is greater in the tropical than in the temper- 
 ate climates (Lawson). 
 
 Clinical Significance. — Urobilin is increased in acute 
 infectious diseases, such as scarlet fever, pneumonia, erysip- 
 elas, malaria, typhoid fever (moderately increased) ; also in 
 acute sepsis, lymphangitis, acute articular rheumatism, appen- 
 dicitis, atrophic cirrhosis and carcinoma of the liver, catarrhal 
 icterus, lead colic, and pernicious anemia. It is also in- 
 creased in cases of poisoning by potassium chlorate, anti- 
 pyrin, antifebrin, and pyridin. On the other hand, it is 
 nearly absent from the urine in phosphorus-poisoning. 
 
 Detection.! — Urobilin is best detected by means of the 
 spectroscope: (i) Take from 10 to 20 c.c. of the urine, 
 acidulate with a few drops of hydrochloric acid, and shake 
 with from 6 to 10 c.c. of amyl alcohol. On spectroscopic 
 examination the clear amyl-alcohol solution of urobilin 
 shows a characteristic absorption band of acid urobiHn. 
 (Fig. II.) (2) If to a small portion of this amyl-alcohol 
 solution be added a few drops of a clear solution of i gram 
 of zinc chloride in 100 c.c. of alcohol that has been ren- 
 dered strongly alkaline with ammonia, a beautiful green 
 fluorescence appears. This solution shows the spectrum of 
 alkaline urobilin. (Fig. 1 1 .) 
 
 For the isolation of urobilin the reader is referred to more 
 extensive works on urinary analysis. 
 
 Urochrome. — This substance is the chief coloring-matter 
 of normal and pathologic urine, and imparts a yellow, orange, 
 and even a brownish color to the urine. According to 
 Garrod,^ a urate sediment always contains some urochrome, 
 
 1 An old test, and one frequently applied for the detection and approximate 
 estimation of urobilin, is the so-called urophaein test (^Heller) : Take about 
 seven cubic centimeters of concentrated sulphuric acid in a wine-glass, and add 
 twice the quantity of urine, which is poured into the acid from a height of 
 about four inches. A garnet-red color appears which, if normal in amount, 
 is so intense that only a little light can be seen through the mixture. If 
 increased, the mixture is opaque, and if diniinished, it is transparent. This 
 test is most unsatisfactory, as normal coloring-matters other than urobilin are 
 set free by the acid. Tliis test is also modified by the presence of abnormal 
 constituents, .such as bile, sugar, etc. The test, therefore, is of very little, if 
 of any, importance for the detection or approximate determination of urobilin 
 in urine. 
 
 ">■ " Journ. of Physiol.," xvii, 441, 1^95.
 
 UROCIIROME. 93 
 
 either alone or with urocrythrin and other coloring-matters. 
 The name urochromc was first applied in 1 864 by Thudichum, 
 who then considered it the chief coloring-matter of the 
 urine. Urochrome is thought by some to consist of impure 
 urobilin. It probably does contain some urobilin, but that 
 it is an independent substance has been satisfactorily demon- 
 strated by Thudichum, Garrod, and others. 
 
 Urochrome contains nitrogen, but is free from iron. Its 
 solutions have an amphoteric reaction. In a dry state it is 
 amorphous, and has a brown color. It is odorless in the 
 cold, but w hen heated over the water-bath it has a faint 
 odor of urine. It is very readily soluble in water and alco- 
 hol ; only sparingly soluble in acetic ether, amyl alcohol, 
 and acetone ; and is insoluble in ether, chloroform, and 
 benzol. Its solution, on the addition of an acid, shows 
 only a diffused absorption of the spectrum at the violet end. 
 According to Thudichum, the acid alcoholic solution shows 
 a faint, narrow absorption band between F and G, its left 
 edge bordering on F. The neutral and alkaline solutions 
 do not show absorption bands. It is precipitated by phos- 
 photungstic and phosphomolybdic acids, acetate of lead, 
 silver nitrate, mercuric acetate, and also by saturating its 
 solution with ammonium sulphate. 
 
 When uric acid is precipitated from a solution that has 
 been treated with urochrome, the crystals are of a yellow or 
 even brown color, and of the whetstone shape, the same as 
 when they crystallize from the urine spontaneously. When 
 uric acid is precipitated by an acid from a solution con- 
 taining urochrome, the crystals are colored brown, the same 
 as when they are precipitated from the urine by an acid. 
 
 Detection. — Urochrome is recognized by the fact that it 
 is precipitated from its solutions by ammonium sulphate, 
 and that when it is decomposed by acids, it furnishes a 
 brown or black substance. It is also distinguished by its 
 color and spectrum. 
 
 Urochrome is isolated, according to Garrod, by saturating 
 the urine with ammonium sulphate, and extracting the pre- 
 cipitate with absolute alcohol. According to Thudichum, 
 it is best isolated by first precipitating the urine with a mix- 
 ture of barium hydrate and acetate, and then treating the 
 filtrate with lead acetate and ammonia. ^ 
 
 1 See Neubauer and Vogel, "Analyse des Harns," Bd. I, 1898, S. 508.
 
 94 
 
 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 Uroerythrin. — This substance is a constituent of normal 
 urine, and is usually present only in small quantities. It 
 has been termed rosacic acid by Prout, and piirpiirin by 
 Golding Bird. 
 
 Uroerythrin is free from iron, and when isolated, is amor- 
 phous and of a brick-red color. It is soluble in amyl alco- 
 hol, slightly soluble in acetic ether and absolute alcohol, 
 and very difficultly soluble in water. Its solution in alco- 
 hol soon decomposes. It is also decomposed by both oxi- 
 dizing and reducing agents. Uroerythrin does not occur 
 in the urine as a chromogen. When a urine is saturated 
 with ammonium sulphate or chloride, uroerythrin is pre- 
 cipitated with the ammonium urate. Its solutions are not 
 fluorescent. It is extracted from a reddish urate sediment 
 by boiling alcohol. 
 
 Uroerythrin in dilute solutions shows two ill-defined ab- 
 
 C I> £ b 
 
 /O iO 30 W ^p eO 70 80 90 (00 ffO 
 
 'JO m /so m m 
 
 Fig. 12. — Spectrum of uroerythrin (after Neubauer and Vogel). 
 
 sorption bands, one with its left border midway between D 
 and E, its right border inclosing E {JD yo E — E 1 3 E), and 
 the other band with its left border to the right of b, and its 
 right border inclosing F {E 44 E — E 9 G). (Fig. 12.) 
 The right band is somewhat darker than the left, the light 
 space between the two being rather ill defined. 
 
 Uroerythrin, for the most part, exists in the urine in 
 chemic combination with uric acid. It not only gives a 
 yellow, or yellowish-red, color to uric acid crystals, but 
 also colors a urate sediment pink or brick-red. 
 
 Clinically, uroerythrin is increased in acute febrile dis- 
 eases, such as pneumonia, influenza, typhoid fever, malaria, 
 acute articular rheumatism, etc. ; in diseases of the liver, 
 especially those in which there is a disturbance in the circu- 
 lation ; in cirrhosis of the liver following the excessive use
 
 UROROSEIN. 95 
 
 of alcohol ; and in chronic diseases of the heart and lungs. 
 An increase of uroerythrin is usually accompanied by an 
 increase of urobilin. 
 
 Detection. — A deposit of amorphous urates having a 
 pink or reddish color shows the presence of uroerythrin. 
 On the addition of an alkaline hydrate its solution is imme- 
 diately colored dark green. An amyl-alcohol solution of 
 uroerythrin, obtained by shaking the urine with amyl alco- 
 hol, shows the characteristic absorption bands. It is iso- 
 lated by saturating the urine with ammonium chloride. 
 
 Urorosein. — Urorosein does not occur in the urine as 
 such, but as a chromogen, which, upon the addition of 
 mineral acids, is gradually broken up, a rose-red color re- 
 sulting. According to Robin, this substance is present in 
 very small amounts in every normal urine, and in much 
 larger quantities in certain diseased conditions. 
 
 Urorosein dissolves in water with a resulting red color ; 
 also in dilute mineral and many of the organic acids ; in 
 alcohol and amyl alcohol. It is extracted from its aqueous 
 solution by amyl alcohol, but not by ether, chloroform, 
 benzol, or carbon disulphide. Its alcoholic solution shows 
 a sharp and narrow absorption band between D and E [D 
 48 E). Ammonia, hydrates of the fixed alkalies, and alka- 
 line carbonates immediately decolorize the red solution. 
 
 The chromogen, according to Robin, crystallizes in color- 
 less transparent needles when its concentrated alcoholic 
 solution is precipitated with ether. These crystals are 
 readily soluble in alcohol and water, but not in ether or 
 chloroform. It is incompletely precipitated by lead acetate. 
 
 Clinically, urorosein is increased in the urine in diseases 
 of the lungs (tuberculosis), pernicious anemia, and in cases 
 of marked chlorosis. It is also increased in diabetes mel- 
 litus, osteomalacia, typhoid fever, carcinoma of any of the 
 abdominal viscera, appendicitis, nephritis, and especially 
 in diseases of the stomach. It is increased by vegetable 
 food. 
 
 Detection. — (i) To 10 c.c. of the urine add 15 drops 
 of concentrated hydrochloric acid, and if the urine be rich 
 in urorosein, a rose-red color appears in the cold in about 
 ten minutes ; the color appears more quickly when the 
 mixture is heated to 70° C. (Robin). (2) Take from 50 to 
 100 c.c. of the urine and add from 5 to 10 c.c. of 25 per 
 cent, sulphuric acid. A reddish or rose-red color appears
 
 96 ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 in a few minutes. If this colored mixture is then shaken 
 with amyl alcohol, the coloring-matter is removed (Nencki 
 and Sieber). 
 
 The spectroscopic examination of the amyl-alcohol ex- 
 tract is indispensable for the certain detection of urorosein. 
 
 OTHER ORGANIC CONSTITUENTS OF THE URINE. 
 
 A number of organic constituents, in addition to those 
 already described, may occur in small quantities in the urine. 
 We may divide these into the following groups : 
 
 1. Nonnitrogenous acids : oxalic, lactic, and succinic 
 acids. 
 
 2. Fatty acids. 
 
 3. Glycerophosphoric acid (?). 
 
 4. Carbohydrates : dextrose (see p. 145) and animal gum. 
 
 5. Ferments : pepsin, trypsin. 
 
 6. Mucin. 
 
 Oxalic Acid (QH^OJ. — Oxalic acid is usually, and per- 
 haps always, a constituent of the urine in health, but is 
 present in very small amounts (as high as 0.02 gram in 
 twenty -four hours). Under pathologic conditions it appears 
 in increased quantities in diabetes mellitus, organic diseases 
 of the liver, and, indeed, in all conditions in which the oxi- 
 dizing power of the system is decidedly interfered with, as 
 in various diseases of the heart and lungs. 
 
 Oxalic acid crystallizes with two molecules of H,0 in 
 colorless, rhombic prisms, which are readily soluble in water 
 and alcohol. 
 
 The greater part of the oxalic acid taken into or formed 
 in the body exists in the form of a salt of calcium — calcium 
 oxalate. 
 
 Calcium Oxalate. — This salt crystallizes in two different 
 forms according" to the number of molecules of water it 
 contains — /. c, crystals belonging to the monoclinic system 
 — C2CaO^, H,,0 (small plates) — and those belonging to the 
 tetragonal system — C2CaO^,3H.,0 (octahedra, etc.). The 
 monoclinic crystals are seen when the salt rapidly separates 
 from a concentrated solution ; the amorphous precipitate of 
 calcium oxalate apparently has the same chemic composi- 
 tion. The tetragonal crystals are seen when the salt slowly 
 separates from dilute acid solutions. 
 
 For a further consideration of this subject see page 217.
 
 FERMENTS. 97 
 
 Lactic Acid (C^HgOj,) is not a constituent of normal urine. 
 Liebig was unable to detect the slightest trace of it in 41, 42, 
 and 56 liters of healthy urine. It does not appear in the urine 
 after the administration of sodium lactate (Nencki and Sieber). 
 It has been found in the urine in combination with bases in cases 
 of acute yellow atrophy and marked cirrhosis of the liver, trichi- 
 nosis, phospliorus-poisoning, and after severe muscular exertion. 
 According to Colasanti and Moscatelli, it occurs in the urine as 
 sarcolactic acid. 
 
 Sarcolactic acid consists of a colorless, odorless, syrupy fluid, 
 soluble in water, alcohol, and ether; it is nonvolatile. The free 
 acid rotates the plane of polarizedlight slightly toward the right, 
 while solutions of its salts rotate the plane slightly toward the 
 left (Wislicenus). Lactic acid is monobasic; it combines with 
 bases to form salts, of which zinc lactate is the most important. 
 Nearly all of its salts are soluble. 
 
 For the detection of lactic acid see Neubauer and Vogel, 
 " Analyse des Harns," Bd. i, 1898, S. 183. 
 
 Succinic Acid (C^HgO^) has been occasionally found in the 
 urine. Under ordinary conditions it probably exists in the 
 urine chiefly in combination with sodium — sodium succinate. 
 Succinic acid has been found in the urine especially after the 
 ingestion of asparagus and asparagin. Baumann failed to find 
 it after the ingestion of sodium succinate. 
 
 Fatty Acids. — These consist of acetic, butyric, formic, and 
 propionic acids. They are apparently free in the urine, and 
 present only in mere traces (0.008 gram per diem). They can 
 be increased to 0.9-1.5 gram by treating the urine with oxidiz- 
 ing agents (v. Jaksch^). The amount of fatty acids also 
 increases during the period of the ammoniacal fermentation 
 (Salkowski 2). In certain febrile conditions they are increased 
 to 0.6 gram, and in certain liver diseases may go as high as one 
 gram per diem. This condition is called lipaciduria by v. Jaksch. 
 
 Ferments. — Pepsin. — Several observers (Briicke, Sahli, 
 Leo, and others) have found pepsin in the urine. The fol- 
 lowing is an alDstract of Leo's ^ work on the subject : 
 " Small pieces of fibrin soaked in the urine absorb the pep- 
 sin, and on removing them to o. i per cent, hydrochloric 
 acid, they are rapidly digested. Control experiments with 
 fibrin not previously soaked in urine gave negative results. 
 The morning urine was found to be richest in pepsin." 
 
 Neumeister and Stadelmann have both shown that the 
 ferment in the urine is true pepsin. 
 
 1 "Zeitschr. f. physiol. Chem.," X, 536. 2 Ibid., xni, 264. 
 
 3 "Pfliiger's Archiv," xxxvn, 223, and xxxix, 246. 
 7
 
 98 ■ ORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 Trypsin. — This ferment is probably absent from normal urine, 
 although Sahli claims to have found it. 
 
 Mucin. — Much, discussion has arisen as to whether the sub- 
 stance that is nearly always present in very minute quantities in 
 the urine is mucin or really nucleo-albuniin. It is considered 
 by some observers to be the chief constituent of the mucus de- 
 rived from the muciparous glands of the urinary tract below the 
 kidneys. Further, that it occurs in normal urine as a viscid, 
 slimy substance, which is precipitated by the vegetable acids, 
 especially acetic acid ; also by alcohol ; that it is free from 
 phosphorus, and, when boiled with dilute acids, yields a sub- 
 stance that reduces alkaline solutions. More recent observers 
 consider it to be nucleo-albumin, and at the present time this 
 theory is most tenable. (Seep. 140.) The question, however, 
 is unsettled, and needs further investigation.
 
 CHAPTER III. 
 
 INORGANIC CONSTITUENTS OF NORMAL 
 URINE. 
 
 The principal inorganic constituents of the urine are the 
 chlorides, phosphates, and sulphates, which are in combina- 
 tion with sodium, potassium, ammonium, calcium, and mag- 
 nesium ; also traces of carbonates of the alkalies. There 
 are also traces of iron, fluorine, and silicic acid, as well as 
 free gases, including carbonic acid, nitrogen, and oxygen. 
 
 The combined quantities of these various substances 
 amount to between nine and twenty-five grams in twenty- 
 four hours. 
 
 CHLORIDES. 
 
 Chlorine exists in the urine chiefly as sodium chloride, 
 although small amounts are in combination with potassium 
 and ammonium. The chlorides, next to urea, constitute 
 the chief solid constituent of the urine. They are derived 
 from the food, — that is, the sodium chloride ingested with 
 the food, — and under normal conditions practically all of 
 this salt ingested is eliminated in the urine in an equivalent 
 amount. 
 
 The quantity of sodium chloride in the twenty-four-hour 
 urine is normally between lo and 20 grams, and, calculated 
 as chlorine, amounts to between 8 and 1 2 grams. A person 
 ingesting food unusually rich in sodium chloride may elimi- 
 nate more than 20 grams (NaCl), and the quantity may 
 even reach 40 or 50 grams in the twenty-four hours. On 
 the other hand, if the amount of nourishment is diminished, 
 a decrease in the elimination of the chlorides is observed. 
 If this is carried to the point of starvation, the chlorides 
 almost entirely disappear from the urine, the traces remain- 
 ing being derived from the tissues and fluids of the body. 
 The latter retain tenaciously a certain amount of sodium 
 
 99
 
 100 INORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 chloride, and if, following a period of starvation, food con- 
 taining sodium chloride is again taken, not all appears in 
 the urine, but a portion is retained in the body until the 
 original equilibrium is restored. A similar retention may 
 be observed for a few days following the ingestion of large 
 quantities of water, which, under ordinary conditions, causes 
 an increased elimination of chlorides. 
 
 An incrc(7scd quantity of chlorine is due to an abundance 
 of NaCl in the food, and is of no clinical importance. In 
 diabetes insipidus, however, the increase of chlorine, which 
 may reach thirty grams or more, is obtained at the expense 
 of the body-fluids, and is, therefore, associated with marked 
 emaciation. A dhni)mtio)i in the quantity of chlorine is in 
 many instances of the greatest clinical importance. Such a 
 diminution is often the result of disease, and not dependent 
 entirely on a diminished quantity of salt ingested, although 
 a low diet, naturally, has some effect on the quantity of 
 chlorine eliminated. 
 
 Clinical Significance. — The chlorides are diminished in 
 the acute stage of all acute diseases, and especially those 
 associated with a serous exudation or transudation (dropsy), 
 vomiting, or diarrhea. One of the most important examples 
 of this is pneumonia, in the acute stage of which, on 
 account of the serous exudation, the chlorine is very low or 
 may even be entirely absent from the urine. As soon as 
 convalescence commences and the serous exudation begins 
 to be absorbed, the chlorine reappears or gradually increases 
 until it may, in a few days, exceed the normal temporarily. 
 The test for chlorides is, therefore, of definite clinical value 
 in determining the progress of the pneumonic process. The 
 quantity of chlorine in the urine is very important in the 
 differential diagnosis between acute meningitis and typhoid 
 fever, the former being attended with a serous exudation, 
 and hence a inm-kcd diminution in the chlorides, while in 
 the latter they are only moderately diminished. The chlorine 
 is markedly diminished or absent in cholera, pyemia, and 
 puerperal fever, and also much diminished in acute articular 
 rheumatism. 
 
 In the convalescent stage of most acute diseases the 
 chlorine gradually rises to normal, but is dependent chiefly 
 on the appetite. 
 
 The chlorides are diminished in all chronic diseases, more 
 particularly in those attended with dropsy, when they may
 
 CHLORIDES. 101 
 
 be absent from the urine. In the chronic diseases without 
 exudation or transudation the diminution in the amount of 
 chlorine is in proportion to the amount of sodium chloride 
 taken with the food — in other words, the quantity of 
 chlorine may be looked upon as a measure of the appe- 
 tite. If at any time during the course of a chronic disease 
 accompanied by dropsy the fluid be absorbed, the quantity 
 of chlorine in the urine slowly rises to near the normal, but 
 only rarely does it exceed the normal, since the absorption 
 of the serous fluid is usually very gradual. 
 
 Detection. — The following test, which depends upon the 
 precipitation of the chlorine by nitrate of silver, can be 
 readily applied for the detection and approximate estimation 
 of chlorides in the urine : 
 
 Take one-half of a wine-glass of urine, underlie with a 
 third as much concentrated nitric acid in the same manner 
 as in the nitric acid test for albumin. (See p. 122.) Then 
 add one drop of a solution of silver nitrate, — one part of 
 silver nitrate and eight parts of water, — and if chlorides be 
 present, a precipitate of silver chloride is formed. If the 
 relative proportion of chlorides is normal or increased, a 
 solid compact ball of silver chloride is obtained, which falls 
 to the surface of the nitric acid. If the relative proportion 
 is diminished, however, instead of forming a solid ball the 
 silver chloride precipitate spreads out or becomes diffused to 
 a greater or less extent through the layer of urine. 
 
 This same test can also be applied by adding to one-half 
 of a wine-glass of urine one or two drops of concentrated 
 nitric acid, stirring the mixture, and adding one drop of the 
 solution of silver nitrate (prepared as directed). If the result- 
 ing precipitate quickly falls to the bottom of the glass in a 
 solid, flaky mass and does not tend to diffuse through the 
 urine, the chlorides are normal or increased ; if diffused, 
 they are diminished. 
 
 If the urine contains more than a trace of albumin, it 
 must be removed by heat before the test is applied, for the 
 following reasons: (i) The precipitate or ball of silver 
 chloride can not be distinctly seen because of the cloud of 
 precipitated albumin ; (2) the silver and albumin combine to 
 form the albuminate of silver, thus modifying the inferences 
 to be deduced from the test. 
 
 Quantitative Tests. — (a) Mohr's Method. — Precipita- 
 tion by silver nitrate.
 
 102 INORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 The following solutions are necessary : 
 
 1. Standard Silver Nitrate Solution: Dissolve 29.075 
 grams of fused silver nitrate in distilled water, and make 
 the whole quantity up to exactly one liter (1000 c.c). One 
 cubic centimeter of this solution is equivalent to o.oi gram 
 of sodium chloride, or 0.006065 gram of chlorine. 
 
 2. A solution of neutral potassium chromate, made by dis- 
 solving one part of the chlorine-free salt in five parts of water. 
 
 Process. — Take 10 c.c. of urine ; dilute with 50 c.c. of 
 distilled water ; add to this 8 or 10 drops of potassium 
 chromate solution. Drop into this mixture from a burette 
 the standard nitrate of silver solution. The chlorine com- 
 bines with the silver to form silver chloride — a white precip- 
 itate. When all the chlorine is precipitated, silver chro- 
 mate (red in color) forms, but not while any chloride 
 remains in solution. The silver nitrate solution must, there- 
 fore, be added until a pink tinge appears. Read off the 
 quantity of standard solution of silver used, subtract i c. c. 
 for correction (see below), and calculate therefrom the 
 quantity of chlorine, or sodium chloride, in the 10 c.c. of 
 urine tested. From this deduce the percentage, or the 
 total number of grams in the twenty-four-hour urine. For 
 example, suppose that, after deducting i c.c. for correction, 
 exactly 10.5 c.c. of the standard silver nitrate solution 
 were used. Since i c.c. of this solution is equivalent to 
 0.006065 gram of chlorine, 10.5 X 0.006065 =0.0636825 
 gram, or the amount of chlorine in the 10 c.c. of urine 
 used. Then the twenty-four-hour urine — say 1500 c.c. — 
 
 contains 0.0636825 X -^=9-55 grams. 
 
 Precautions and Corrections. — If the urine contains al- 
 bumin, it must be removed by means of heat and acetic 
 acid. 
 
 The phosphate of silver is not precipitated in this test, as 
 the silver salts of hydrochloric, chromic, and phosphoric 
 acids are precipitated in the following order : chloride, 
 chromate, and, finally, the phosphate. 
 
 A highly colored urine may give rise to difficulty in de- 
 tecting the pink tinge of the chromate of silver. This is 
 overcome by diluting the urine to a greater extent than in 
 the directions given. It is not always necessary to dilute 
 a pale-colored urine to the extent previously stated, the addi- 
 tion of 20 to 30 c.c. of water often being sufficient.
 
 CHLORIDES. 103 
 
 One cubic centimeter should always be subtracted from 
 the total number of cubic centimeters of silver nitrate solu- 
 tion used, as the urine contains small quantities of certain 
 compounds more easily precipitable than the chromate of 
 silver. To obviate this error, Sutton lias advised the foi- 
 lenving modification of Alohr's test : Take lo c.c. of urine 
 in a thin porcelain dish, and add i gram of pure ammonium 
 nitrate. The whole is then evaporated to dryness, and 
 gently heated over a small flame to low redness until all 
 vapors are dissipated and the residue becomes white. It is 
 then dissolved in a small quantity of water, and the carbon- 
 ates produced by combustion of the organic matter neutral- 
 ized by dilute acetic acid. A few grains of pure carbonate 
 of calcium are added to remove all free acid, and then one or 
 two drops of a solution of potassium chromate. The mix- 
 ture is then titrated with decinormal silver solution (16.966 
 grams of silver nitrate to the liter) until the pink color 
 appears. Since each cubic centimeter of the silver solution 
 represents 0.005837 gram of sodium chloride, the quantity 
 of sodium chloride, or chlorine, can be readily calculated. 
 
 The results obtained by direct titration of the urine with 
 a standard solution of silver nitrate can not be considered 
 absolutely accurate, since uric acid, xanthin bases, sulpho- 
 cyanides, sulphites, coloring-matters, etc., are precipitated 
 with the silver chloride before the end-reaction appears. 
 To obviate such errors, Neubauer and Salkowski have ad- 
 vised the following process : 
 
 Neubauer-Salkowski Method. — The necessary solu- 
 tions are to be prepared according to the directions given 
 under Mohr's method. 
 
 Take 10 c.c. of urine in a small platinum or porcelain 
 crucible ; add one gram of sodic carbonate that is free from 
 chlorine, and i or 2 grams of chlorine-free potassium nitrate, 
 and evaporate to dryness at 100° C. Heat over a free 
 flame — at first gently, later strongly — until the molten mass 
 is perfectly white. Dissolve the white residue in distilled 
 water, and transfer the solution to a small flask. To this 
 alkaline solution add dilute nitric acid, drop by drop, until 
 faintly acid, and then neutralize again with chlorine-free 
 sodic carbonate. Add a few drops of the solution of potas- 
 sium chromate to the mixture, and allow the standard solu- 
 tion of silver nitrate to flow from a burette into the mixture 
 in the flask, until the first appearance of a permanent pink
 
 104 INORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 tinge (end-reaction). Read the number of cubic centimeters 
 of standard solution of silver used, and calculate therefrom 
 the quantity of chlorine or sodium chloride in the lo c.c. 
 of urine tested. 
 
 Volhard and Falck Method. — This method depends 
 upon the action of soluble sulphocyanides with solutions of 
 silver and ferric salts. Soluble sulphocyanides produce in 
 silver solutions a white precipitate of sulphocyanide of silver, 
 which is insoluble in dilute nitric acid. A like precipitate 
 of sulphocyanide of silver with a solution of nitrate of silver 
 is given by the blood-red solution of sulphocyanide of iron, 
 and the color of the latter at last completely disappears. 
 If, therefore, a solution of sulphocyanide of potassium be 
 added to an acid solution of nitrate of silver to which a 
 little ferric sulphate has been added, every drop of the 
 sulphocyanide solution at first produces a blood-red cloud, 
 which, however, quickly disappears on stirring, while the 
 fluid becomes milk-white. It is not until all the silver is 
 precipitated that the red color of the sulphocyanide of iron 
 remains permanent and the end of the process is reached. 
 
 The following solutions are necessary : 
 
 /. Standard solution of sil^'cr nitrate, made according to 
 directions given under Mohr's method. One cubic centi- 
 meter is equivalent to 0.006065 gram (6.065 milligrams) 
 of chlorine, or 0.0 10 gram (10 milligrams) of sodium 
 chloride. 
 
 2. Solution of Ferric Oxide. — A cold, saturated solution 
 of ciystallized ferric alum free from chlorine, or a solution 
 of ferric sulphate that contains 50 grams of oxide of iron 
 to the liter. 
 
 J. Standard Solution of Potassium Sidphocyanide. — Since 
 potassium sulphocyanide can not be accurately weighed, 
 because of its hygroscopic property, it is necessary to stand- 
 ardize by titrating with a standard solution of silver nitrate. 
 Dissolve 10 grams of potassium sulphocyanide in a little 
 less than a liter of distilled water, and place a portion of 
 this in a burette. Take 10 c.c. of the standard silver solu- 
 tion, place in a beaker, add 5 c.c. of the iron solution, and 
 then pure nitric acid, drop by drop, until the mixture is 
 colorless. Then allow the sulphocyanide solution to flow 
 in from the burette until the fluid has a permanent red color, 
 the first appearance of which indicates the end-reaction — 
 that is, when all of the silver is precipitated as silver sulpho-
 
 CHLORIDES. 105 
 
 cyanide, the next drop gives a permanent red color, due to 
 the precipitation of the sulphocyanide of iron. If, for ex- 
 ample, to lo c.c. of the silver solution 9.6 c.c. of the potas- 
 sium sulphocyanide solution have been used before the red 
 color is permanent, 960 c.c. are measured off, and diluted 
 with 40 c.c. of distilled water to make a liter. Titrate once 
 more, in order to be sure that the strength of the two solu- 
 tions — standard silver and potassium sulphocyanide solu- 
 tions — is equivalent. 
 
 Process. — Take 10 c.c. of urine, add i or 2 grams of 
 potassium nitrate free from chlorine, and evaporate to dr>'- 
 ness on a water-bath. The residue is then heated over a 
 free flame — at first gently, afterward strongly — until the 
 carbon is completely oxidized and the residue is a white 
 mass. Since the nitrous acid formed in this process pre- 
 vents the end-reaction, the fused mass is dissolved in water, 
 acidulated with nitric acid, and then the chlorine precipi- 
 tated with an excess of the standard solution of silver. 
 After this mixture has been warmed on a water-bath for a 
 time to remove completely the nitrous acid, it is allowed to 
 cool. Then 5 c.c. of the iron solution are added ; and, 
 finally, the potassium sulphocyanide solution, until the ex- 
 cess of the silver added is precipitated, which is known by 
 the permanent red color of the mixture. The difference be- 
 tween the number of cubic centimeters of the silver and 
 sulphocyanide solutions corresponds to the chlorine con- 
 tained in the urine. If, for instance, at first 15 c.c. of the 
 silver solution were added to 10 c.c. of urine, and 5 c.c. of 
 the sulphocyanide solution were required to titrate back the 
 excess, the amount of chlorine in the urine would corre- 
 spond to 15 — 5 = 10 c.c. of the silver solution. 
 
 (b) Purdy's Method, by the Electric Centrifuge. — 
 The percentage tubes of the Purdy electric centrifuge are 
 filled to the lo-c.c. mark with the urine to be tested; 
 fifteen (15) drops of nitric acid are added to prevent precipi- 
 tation of the phosphates (if the specific gravity be very high, 
 20 to 30 drops should be added), and then the tubes are 
 filled to the 15-c.c. mark with a strong solution of nitrate 
 of silver ( i : 8). The tubes are next closed, and inverted 
 several times, until the urine and the reagents are thoroughly 
 mingled. The tubes are then placed in the centrifuge, and 
 revolved at the rate of 1000 revolutions a minute for 
 three successive periods of five minutes each, when the
 
 106 INORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 quantity in bulk percentage may be read off from the grad- 
 uated scale on the sides of the tubes. Purdy has found 
 that the bulk percentage of chlorides in normal urine thus 
 obtained ranges from lo to 12 per cent. 
 
 By a comparison of the bulk percentages of chlorides 
 Avith the volumetric determinations of the same the author 
 has been able to obtain, from a large number of observa- 
 tions, a standard of percentage by weight. He has found 
 that each ^ of a c.c. of precipitate, calculated as chlorine, 
 is equivalent to 0.123 P^^' cent, by weight. 
 
 PHOSPHATES. 
 
 Phosphoric acid in the urine occurs in the form of two 
 classes of phosphates : 
 
 1 . Earthy Phosphates : phosphates of calcium and mag- 
 nesium, the former being the more abundaht. 
 
 2. Alkaline Phosphates : phosphates of sodium and po- 
 tassium, the former being the more abundant. 
 
 The earthy phosphates, which consist of the phos- 
 phates of the alkaline earths, — calcium and magnesium, 
 — are insoluble in water, but soluble in acids. In an acid 
 urine they are in the form of acid phosphates, which are 
 in solution. Occasionally, a crystalline deposit of acid 
 calcium phosphate (see p. 216) having the composition 
 CaHPO^ + 2H2O (Hassal, Stein) separates from a faintly 
 acid urine. 
 
 In an alkali)ic urine the acid phosphates of magnesium 
 and calcium are converted to normal phosphates, and are 
 precipitated as a heavy, whitish sediment, frequently termed 
 anwrpJioiis phosphates. A similar phosphatic precipitate is 
 often obtained when a faintly acid, neutral, or alkaline urine 
 is heated, owing to the conversion of the acid phosphate to 
 normal phosphate, which is precipitated, and the superphos- 
 phate, which remains in solution : / 
 
 / 
 4CaHPO, = CaH^2PO^ + Ca32PO,. 
 
 This phenomenon is a frequent source of error in testing 
 for albumin in urine by heat. If, upon heating, such a pre- 
 cipitate appears, it may be readily distinguished from the 
 precipitate of albumin by the addition of a few drops of 
 acetic acid, which quickly dissolves the earthy phosphates. 
 When a urine becomes aininoniacal, the phosphate of mag-
 
 PHOSPHATES. 107 
 
 nesium combines chemically with ammonia to form the 
 aviuio)iio-)iicxgiicsium plwspJiatc , or " triple phosphate," which 
 is in crystalline form. (See p. 215.) 
 
 The alkaline phosphates consist chiefly of the phos- 
 phates of sodium and potassium, which, unlike the earthy 
 phosphates, are soluble in water and alkalies. The sodium 
 salt — monosodic acid phosphate (the disodic acid phosphate 
 is also sometimes present) — is much more abundant than 
 the potassium salt, and, as previously stated, it is to this com- 
 pound that the acidity of the urine is chiefly due. The 
 alkaline phosphates form the chief bulk of the phosphates 
 of the urine, being in excess of those combined with the 
 alkaline earths, the proportion being between i ^ and 2 of 
 the former, to i of the latter. 
 
 The phosphoric acid of the urine is derived partly from 
 the food and, apparently, partly from the decomposition 
 products of phosphorus-containing organic substances such 
 as nuclein and lecithin. 
 
 The average quantity of phosphoric acid in the twenty- 
 four-hour urine, calculated as phosphoric anhydride (P.,0.), 
 is from 2.5 to 3.5 grams. This quantity is subject to much 
 variation in health, and on a diet rich in earthy salts may 
 fall to only a fraction of a gram, owing to the fact that the 
 phosphoric acid combines with the earthy salts, and is thus 
 prevented from being absorbed. 
 
 Clinical Significance. — Undei^ pathologic conditions the 
 phosphoric acid is largely increased in the urine in ex- 
 tensive diseases of the bones, as rickets, osteomalacia, dif- 
 fuse periostosis, etc.; in destructive diseases of the lung, as 
 in pulmonar}^ tuberculosis, particularly in the early stages ; 
 in extensive diseases of the nervous tissue, diseases of the 
 brain, in chorea, etc. ; in acute yellow atrophy of the liver ; 
 after sleep produced by potassium bromide, or chloral hy- 
 drate (Mendel) ; and it is temporarily increased after copious 
 drafts of water. 
 
 Phosphoric acid is diminished in acute diseases, probably 
 because only a small amount of food is taken ; and most of 
 the chronic diseases, excepting those previously mentioned ; 
 in all diseases of the kidney ; in gout ; in pregnancy, prob- 
 ably due to the formation of the fetal bones ; and also after 
 large doses of chalk, ether, or alcohol. 
 
 The term phosphaturia should be restricted to indicate 
 a constant increase in the total quantity of phosphoric acid
 
 108 INORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 in solution in the urine. The term is frequently incorrectly 
 applied to urine that has, constantly, a deposit of amor- 
 phous or crystalline phosphates. Those pathologic con- 
 ditions in which the urine contains an abnormally large 
 excess of phosphates in the twenty-four-hour urine may be 
 said to be attended with " phosphaturia." 
 
 A condition of so-called phosphatic diabetes has been 
 described by a few writers, in which the urine is free from 
 sugar, but contains a continued large excess of phosphates. 
 The symptoms are not unlike those of diabetes : /. r., large 
 daily quantity of urine, emaciation, aching pains in the 
 lumbar region, morbid appetite, dry, harsh skin, etc. Not 
 infrequently this condition seems to alternate with diabetes 
 mellitus : that is, the symptoms of diabetes continuing, the 
 sugar disappears from the urine, and is apparently re- 
 placed by a ver>' large excess of the phosphoric acid — as 
 much as lO grams. If the sugar reappears, the quantity 
 of phosphoric acid falls to normal or even below the 
 normal. 
 
 Detection.— I. Earthy Phosphates. — The following 
 test serves for the detection and appro.ximate estimation of 
 the earthy phosphates : Take a half test-tube of filtered 
 urine, and add sufficient amnionic hydrate to render it 
 alkaline. Upon warming the mixture the earthy phosphates 
 separate, and soon begin to settle at the bottom of the 
 tube. If, after eighteen to twenty-four hours, the deposit 
 thus formed is from % to ^ of an inch deep, the relative 
 proportion may be said to be within normal limits ; if less 
 than % of an inch, diminished ; and if more than i^ of an 
 inch, increased. 
 
 2. Alkaline Phosphates. — The following test may be 
 applied for the detection and approximate estimation of the 
 alkaline phosphates : After having separated the earthy 
 phosphates as directed, the mixture is filtered. Take the 
 entire filtrate in another test-tube, and add about one finger- 
 breadth of magnesia mixture. ^ Upon warming the mixture 
 a white precipitate, representing the alkaline phosphates, 
 occurs, which, if normal, settles down to between i^ and 
 'i/^ of an inch after eighteen to twenty -four hours ; if less 
 than )4, o( an inch, diminished ; and if more than ^ of an 
 inch, increased. 
 
 1 Magnesia Mixturf. — Magnesium sulphate, amnionic hydrate, am- 
 monium chloride, of each, i part ; water, 8 parts.
 
 PHOSPHATES. 109 
 
 Determination of Total Phosphoric Acid. — The follow- 
 ing test is based upon the facts that (i) when a solution of a 
 phosphate acidulated with acetic acid is treated with a solu- 
 tion of uranium nitrate or acetate, a precipitate falls that is 
 composed of uranium phosphate ; (2) when a soluble salt 
 of uranium is added to a solution of potassium ferrocyanide, 
 a reddish-brown precipitate, or color, is developed. 
 
 Prepare the following solutions : 
 
 {a) A Standard Solution of Uj'aninni Nitrate or Acetate. — 
 Dissolve exactly 35.5 grams of pure uranium nitrate or ace- 
 tate in distilled water sufficient to make 1000 c.c; i c.c. 
 of this solution corresponds to 0.005 gi'am of phosphoric 
 anhydride (Pp,). 
 
 Oftentimes it is not safe to use these salts of uranium, 
 since they are frequently contaminated with uranic oxides. 
 It then becomes necessary to prepare the standard solution 
 in the following manner : 
 
 1. Make a standard solution of sodium phosphate by dis- 
 solving 10.085 grams of the well-crystallized salt in dis- 
 tilled water, and dilute to a liter ; 50 c.c. then contain o. I 
 gram of PgO.. 
 
 2. To prepare the uranium acetate or nitrate solution, 
 dissolve 20.3 grams of yellow uranic oxide in pure strong 
 acetic acid to make the acetate, or in pure concentrated 
 nitric acid to make the nitrate, and dilute with distilled water 
 to nearly a liter. To determine the strength of this solu- 
 tion, take 50 c.c. of the standard solution of sodium phos- 
 phate, in a glass evaporating dish, add 5 c.c. of the sodium 
 acetate solution (given below), and proceed exactly as with 
 urine (process, see below). The quantity of uranium solu- 
 tion used is then read off, being that which is necessary to 
 decompose the sodium phosphate, corresponding to o.i 
 gram of P.,0.. Then calculate the amount of distilled 
 water to be added to make i c.c. correspond to 0.005 gram 
 of phosphoric anhydride. 
 
 {b) Acid Solution of Sodium Acetate. — Dissolve 100 
 grams of sodium acetate in 800 c.c. of distilled water ; add 
 100 c.c. of 30 per cent, acetic acid, and finally dilute with 
 distilled water to 1000 c.c. 
 
 {c) A saturated solution of potassium ferrocyanide, to be 
 used as an indicator. 
 
 Process. — Take 50 c.c. of the urine in a glass evapo- 
 rating dish, add 5 c.c. of the sodium acetate solution, and
 
 110 INORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 heat the mixture to 80° C. over a water-bath. From a 
 burette, run into the hot urine, drop by drop, the standard 
 solution of uranium, as long as a precipitate forms or until 
 a drop of the mixture, removed by means of a glass rod 
 and placed on a porcelain plate or slab, gives a distinct 
 brown color with a drop of the potassium ferrocyanide solu- 
 tion. When this point is reached, the quantity of uranium 
 solution used from the burette is read off. The number of 
 cubic centimeters used multiplied by 0.005 ^^'^^^ gi^^ ^^^^ 
 quantity of phosphoric acid (calculated as phosphoric anhy- 
 dride) in 50 c.c. of urine, and from this is calculated the 
 quantity in twenty-four hours. 
 
 The reddish-brown color which takes place with the 
 solution of potassium ferrocyanide and the mixture, first 
 makes its appearance at the time when the uranium solution 
 has precipitated all of the phosphoric acid, and the mixture 
 contains free uranium. 
 
 CocJiiiieal tinctia^e is highly recommended by Malot and 
 Mercier as an indicator, instead of the potassium ferro- 
 cyanide. The tincture is prepared by digesting a {q.\n grams 
 of cochineal with a 250-c.c. mixture of one part of alcohol 
 and three or four parts of water, in the cold. After several 
 hours the solution is filtered and it is then ready for use. In 
 the phosphoric acid test a few drops of this tincture are 
 added to the urine, or phosphate solution, in the evaporat- 
 ing dish ; the heat is then applied, and the standard uranium 
 solution added until a faint but distinct permanent green 
 color appears. The green color begins to appear as soon 
 as there is the slightest excess of uranium in the solution — 
 in other words, as soon as the phosphoric acid has been 
 entirely precipitated. 
 
 Quantitative Estimation of Phosphoric Acid Com- 
 bined with Calcium and Magnesium (Earthy Phos- 
 phates). — Process. — Take 200 c.c. of urine, precipitate 
 with ammonic hydrate with the aid of gentle heat, allow 
 to stand from twelve to twenty-four hours, then filter and 
 wash with ammonia water. The filter-paper is then pierced 
 at the point and the precipitate washed through into a 
 beaker with a stream of hot water, and dissolved while warm 
 in as little acetic acid as possible. Add 5 c.c. of the 
 sodium acetate solution, dilute to 50 c.c, and proceed as 
 previously indicated. The difference between the total 
 amount of phosphoric acid and that in combination with
 
 SULPHATES. Ill 
 
 calcium and magnesium — earthy phosphates — also repre- 
 sents the quantity combined with the alkalies — alkaline 
 phosphates. 
 
 Purdy's Centrifugal Method for Total Phosphoric 
 Acid. — Fill the percentage tubes to the lo-c.c. mark with 
 the urine to be tested, and add magnesia mixture (formula, 
 see p. 1 08) to the 15-c.c. mark. The tubes are then closed 
 and inverted several times, until the urine and reagent are 
 thoroughly mixed. The tubes are next placed in the cen- 
 trifuge and revolved for three successive periods of five 
 minutes each at the rate of looo revolutions a minute. 
 The volume percentage is then read off In normal urine 
 this will be found to be in the neighborhood of 8 per cent. 
 
 The author has obtained, from a large number of obser- 
 vations, a standard of percentage by weight, by a com- 
 parison of the volume percentages with the volumetric 
 determinations. He has found that each -j^ of a c.c. of 
 precipitate calculated as PjO. is equivalent to 0.0225 per 
 cent, by weight. 
 
 SULPHATES. 
 
 Sulphuric acid is present in the urine in two forms — as 
 ordinary alkaline sulphates of potassium and sodium (pre- 
 formed sulphuric acid), and as ethereal sulphates ^ (conjugate 
 sulphuric acid). The sulphates are derived partly from the 
 food and partly from the chemic changes of proteids in the 
 tissues. The albuminous substances taken as food contain 
 sulphur, which becomes oxidized in the economy and re- 
 sults in sulphuric acid, some of which, in turn, immediately 
 combines with a portion of the sodium and potassium to 
 forrn ordinary sulphates, and a small portion to form the 
 ethereal sulphates by pairing. 
 
 The total quantity of sulphuric acid in the twenty-four- 
 hour amount of urine of an adult taking a mixed diet is 
 from 1.5 to 3 grams, or an average of 2 grams. About 
 one-tenth of the total sulphuric acid is in the form of ethe- 
 real sulphates. The quantity of sulphuric acid is subject 
 to considerable variation, being largely dependent upon the 
 amount of proteid food ingested. 
 
 The sulphates are never found in the urine as a deposit, 
 owing to the fact that they are very soluble compounds. 
 
 1 See p. 83.
 
 112 INORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 Clinical Significance. — The sulphates are increased in 
 acute fevers, probably due to the markedly increased met- 
 abolism. According to Bence Jones, they are especially 
 increased in acute inflammatory diseases of the brain and 
 spinal cord and in delirium. 
 
 The sulphates are diminished in all diseases, especially 
 the chronic forms, and during the convalescent stage of 
 acute diseases, when the metabolism and appetite are much 
 diminished. They are notably diminished in cases of car- 
 bolic acid poisoning, or following the internal or external 
 use of large amounts of any phenol compound, such as 
 salol, lysol, etc ; under such circumstances, however, the 
 diminution of the ordinary sulphates is attended with a 
 corresponding increase of the ethereal sulphates (phenol- 
 potassium sulphate). 
 
 In general, it may be stated that the variation in the 
 quantity of ordinary sulphates eliminated in the urine runs 
 parallel to that of urea. 
 
 Detection. — The following test serves for both the de- 
 tection and approximate estimation : Take one-half test-tube 
 of filtered urine and add from one to two fingerbreadths 
 of barium solution. ^ A white precipitate occurs which, if it 
 fills one-half the concavity of the test-tube in from eighteen 
 to twenty -four hours, may be considered normal in quantity ; 
 if less than one-half the concavity, diminished ; and if more 
 than one-half the concavity, increased. 
 
 Quantitative Determination. — i. Total Sulphuric 
 Acid. — For the determination of the total amount of sul- 
 phuric acid (SO3) — /. e., preformed and conjugate sulphuric 
 acid together — one of two methods is adopted : {a) Gravi- 
 metric method and {h) volumetric method. 
 
 {a) Gravimetric MctJiod. — This method consists in weighing 
 the precipitate of barium sulphate obtained by adding barium 
 chloride to a known volume of urine ; 100 parts of sulphate 
 of barium correspond to 34.33 parts of sulphuric acid (SO3). 
 
 Method [Sa/koivski). — Take 100 c.c. of urine in a beaker, 
 and acidulate with 5 c.c. of pure hydrochloric acid. This 
 mixture is then boiled, and chloride of barium added to the 
 boiling fluid until no more precipitate occurs. 
 
 The precipitate is collected on a small filter of known 
 ash, and washed with hot distilled water until no more 
 
 1 Barmm Solution — Barium chloride, 4 parts ; concentrated hydrochloric 
 acid, I part ; distilled water, 16 parts.
 
 SULPHATES. 113 
 
 barium chloride occurs in the filtrate : /. c, until the filtrate 
 remains clear after the addition of a few drops of sul- 
 phuric acid. Then wash with hot alcohol and afterward 
 with ether. Remove the filter, and place it with its contents 
 in a platinum crucible. Heat to redness. Cool over sul- 
 phuric acid in an exsiccator ; w^eigh, and deduct the weight 
 of the crucible and filter ash. The remainder is the weight 
 of barium sulphate formed, from which the SO3 is calcu- 
 lated — 100 parts of barium sulphate corresponding to 34.33 
 parts of SO3. 
 
 Correction. — When the experiment is carried out as above, 
 there is a slight error from the formation of a small quan- 
 tity of sulphide of barium. This may be corrected as fol- 
 lows : After the platinum crucible has cooled, add a few 
 drops of pure sulphuric acid, which converts into a sulphate 
 any sulphide present. The contents of the crucible are 
 again heated to redness to drive off any excess of sulphuric 
 acid, cooled and dried over sulphuric acid, and weighed. 
 
 {b) Volumetric Method. — This process is conducted by 
 adding a standard solution of barium chloride to a given 
 quantity of urine as long as a precipitate occurs. 
 
 The following solutions are necessary : 
 
 1. A standard solution of barium chloride made by dis- 
 solving 30.54 grams of pure crystallized barium chloride in 
 water, and diluting to exactly one liter ; i cubic centimeter 
 corresponds to 0.0 10 gram of SO3. 
 
 2. An aqueous solution of potassium sulphate so made 
 that one liter will contain 21.775 grams of the salt. 
 
 Process. — Place 50 c.c. of the urine in a flask or small 
 beaker, and add from 5 to 10 c.c. of pure hydrochloric 
 acid. The mixture is then boiled over a free flame for fif- 
 teen minutes, or heated on a water-bath for one hour. To 
 the hot fluid the standard barium chloride solution is added, 
 I c.c. at a time, until a precipitate fails to occur. After 5 
 to 8 c.c. of the standard solution have been added, filter a 
 small portion of the mixture through a very small filter- 
 paper, and to the filtrate add a few^ drops of the standard 
 solution. If a precipitate occurs, return the whole to the 
 flask, add more barium solution, and test as before. Con- 
 tinue until no more precipitate is formed on the addition of 
 the barium chloride solution. Any excess of barium (that 
 uncombined with sulphuric acid) is show^n by placing a drop 
 or two of the filtrate on a glass plate over a dark back- 
 8
 
 114 INORGANIC CONSTITUENTS OF NORMAL URINIi 
 
 ground, and adding a drop or two of the solution of potas- 
 sium sulphate, when a decided cloudiness appears. This 
 excess of barium must be avoided, and, therefore, in the 
 test with potassium sulphate only the slightest cloudiness 
 should appear, which shows that just the right amount of 
 barium has been added ; if an excess of barium is present, 
 the entire analysis must be repeated. 
 
 The quantity of sulphuric acid is calculated from the 
 amount of barium chloride solution used — one cubic centi- 
 meter of which corresponds to o.oio gram of SO3. 
 
 2. Conjugate Sulphuric Acid (Ethereal Sulphates). — 
 Salkinvski's Method. — One hundred cubic centimeters of 
 clear, filtered urine are mixed with 100 c.c. of an alkaline 
 solution of barium chloride (saturated solution of barium 
 chloride, i part ; and a saturated solution of barium hydrate, 
 2 parts, both saturated in the cold), the mixture being 
 thoroughly stirred. After a few minutes this is filtered 
 through a dry filter into a dry graduate up to the loo-c.c. 
 mark. This portion, corresponding to 50 c.c. of urine, is 
 now strongly acidulated with 10 c.c. of hydrochloric acid, 
 boiled, kept at 100° C. on the water-bath for an hour, and 
 then allowed to stand until the precipitate has completely 
 settled : if possible, it should remain undisturbed for twenty- 
 four hours. The further treatment of this precipitate (con- 
 jugate sulphates) is then carried out as in the above- 
 described gravimetric process. (See (rt).) 
 
 Calculations. — The molecular weight of BaSO^ being 
 232.82 ; that of SO3, 79.86 ; of HgSO^, 97.82 ; and of S, 
 32, the figure expressing the amount of H2SO^, SO3, or S, 
 corresponding to i gram of BaSO^, is found according to 
 the following equations : 
 
 232.82 : 79.86 : : I : .\ , and .r = 0.34301. . ■. I gram of BaSO^ = O.3430I 
 
 gram of SO.,. 
 232.82 : 97.82 : : I : x, and jr = 0.42015. . •. I gram of BaSO^ = O.42015 
 
 gram of H.^SO^. 
 232.82 : 32 : : I : x, and x -0. 13744. .". I gram of BaSO^ ;= 0. 1 3744 
 
 gram of S. 
 
 To calculate results, it is only necessary to multiply the 
 weight of BaSO^ found by 0.34301, 0.42015, or 0.13744, 
 in order to ascertain the amount of sulphuric acid contained 
 in 50 c.c. of urine in terms of SO,, H^SO^, or S, respectively. 
 This method of calculation applies to the gravimetric esti-
 
 CARBONATES. 115 
 
 mation of both the total sulphates and the combined sul- 
 phates. 
 
 To obtain the amount of preformed sulphuric acid, or 
 that in combination with the alkalies, subtract the amount 
 of combined SO., from the total amount of SO3. The dif- 
 ference is the preformed SO3. 
 
 Example : One hundred cubic centimeters of urine gave 
 0.5 gram of total barium sulphate. Then 0.5 multiplied by 
 0.34301 =0.171 gram of total SO.^. Another 100 c.c. of 
 the same urine gave 0.05 gram of barium sulphate from the 
 ethereal sulphates ; then 0.05 multiplied by 0.34301 = 
 0.017 gram of combined SO3. The difference between the 
 total and the combined 803 = 0.171 — 0.017 = 0.154 
 gram of SO3 in combination with the alkalies. 
 
 CARBONATES. 
 
 A freshly passed urine of alkaline reaction generally con- 
 tains small quantities of carbonates and bicarbonates of 
 sodium, magnesium, calcium, and ammonium, all of which 
 arise in the economy from the carbonates of the food, or 
 from salts of malic, tartaric, lactic, succinic, and other vegeta- 
 ble acids ingested with the food. They are, therefore, most 
 abundant in the urine of herbivora, whose urine is thus 
 rendered alkaline. A urine containing carbonates is either 
 turbid when passed, or soon becomes so on standing. The 
 deposit, if allowed to settle, will, on examination, be found 
 to consist of calcium carbonate mixed with phosphates. 
 
 According to Wurster and Schmidt,^ a liter of normal 
 human urine of a specific gravity of 1020, if acid in reac- 
 tion, contains, on an average, from 40 to 50 c.c, and if 
 neutral or alkaline, over 100 c.c. of carbonic acid, which is 
 capable of being expelled by a current of air. The amount 
 of carbonic acid per 100 c.c. varies between 17 c.c. (urine 
 of low specific gravity) and 294 c.c. (urine of high specific 
 gravity). 
 
 Carbonic acid forms neutral (normal) and acid salts. Of 
 the alkaline carbonates, both the acid and the normal are 
 soluble, but the acid is considerably less soluble than the 
 normal. The normal carbonates of calcium and magnesium, 
 on the other hand, are ver\' slightly soluble, but the acid is 
 
 ' "Centralbl. f. Physiologie," 1887, 421.
 
 116 INORGANIC CONSTITUENTS OF NORMAL URINE. 
 
 more soluble than the normal. The carbonate of ammo- 
 nium is volatile at ordinary temperature. 
 
 For the detection and quantitative determination of car- 
 bonic acid, both free and combined, see Neubauer and 
 Vogel, "Analyse des Harns," Bd. i, 1898, S. 37 u. 735. 
 
 IRON. 
 
 Iron is found only in minute traces in the residue of the 
 urine after ignition. According to Magnier, the amount of 
 iron in a healthy man of medium weight varies between 0.003 
 and 0.0 1 1 gram in a liter. The coloring-matter, which is 
 precipitated with the uric acid on the addition of concen- 
 trated hydrochloric acid, according to Kunkel, contains 
 iron. 
 
 Detection. — The ash of the residue of urine is always 
 used for the isolation and detection of iron. It is dissolved 
 in a little hydrochloric acid, and the solution divided into 
 two parts. The first part is boiled with a drop of nitric 
 acid and treated with a solution of potassium sulphocyanide 
 which, if ferric oxide be present, produces a red or blood- 
 red color. If potassium ferrocyanide is added to the other 
 half of the solution, after boiling with nitric acid and dilut- 
 ing, flocculi of Prussian blue separate after standing a time. 
 
 For the quantitative determination of iron and further 
 information regarding this substance the reader is referred 
 to Neubauer and Vogel, " Analyse des Harns," Bd. i, 
 1898, S. 47 u. 750. 
 
 HYDROGEN PEROXIDE. 
 
 This substance was first detected in the urine by Schonbein. ^ 
 The most reliable reaction that serves for its recognition depends 
 upon the power it possesses of bleaching a dilute tincture of 
 indigo. The urine to be tested must be perfectly fresh. 
 
 The relative unimportance of this substance in the urine for- 
 bids more than a mere mention here. ^ 
 
 1 " Joum. f. prakt. Ch.," xcii. i68, 1864. 
 
 2 See Neubauer and Vogel, " Analyse des Harns," 1898, S. 39.
 
 CHAPTER IV. 
 
 ABNORMAL CONSTITUENTS OF URINK 
 
 PROTEIDS. 
 
 Under pathologic conditions urine may contain a number 
 of proteids — /. r., serum albumin, serum (or para-) globulin, 
 albumose, peptone, hemoglobin and methemoglobin, and 
 fibrin and fibrinogen. Egg-albumin is occasionally found, 
 especially after the liberal ingestion of eggs as a food. 
 Several of these proteids may be present iii the urine at the 
 same time, or, on the other hand, only a limited number 
 present, such as albumin and globulin, albumin and hemo- 
 globin, etc. 
 
 General Reactions of the Proteids. 
 A. Color tests. 
 
 1. Xanthoproteic Reaction. — Heat the solution of the 
 proteid with concentrated nitric acid. There results a yellow 
 color, which, on the addition of an alkaline hydrate, changes 
 to a deep orange. If ftiuch proteid, except albumose and pep- 
 tone, be present, a yellow precipitate is obtained at the same 
 time; with less proteid, its solution merely turns yellow on 
 boiling, and orange on the addition of an alkali ; if only a trace 
 is present, no yellow color is observed until after the addition 
 of the alkali. 
 
 2. Millon's Reaction. — With Millon's reagent ^ proteids, 
 when present in sufficient quantity, give a precipitate that turns 
 red on heating. If only present in traces, no precipitate is ob- 
 served on heating, but merely a red colorization of the solution. 
 
 3. Piotrowski's Reaction. — If a solution of the proteid be 
 mixed with an excess of a concentrated solution of sodic hy- 
 drate, and one or two drops of a dilute solution of sulphate of 
 copper be added, a violet color is obtained, which deepens on 
 boiling. Albumoses and peptones give a rose-red color {Jniiret 
 reaction) ; care must be taken in the addition of the cupric 
 sulphate solution, since an excess gives a reddish-violet color 
 
 ^ See foot-note, p. 168. 
 117
 
 118 ABNORMAL CONSTITUENTS OF URINE. 
 
 somewhat similar to that obtained in the presence of other pro- 
 teids. 
 
 The foregoing tests serve to detect the smallest traces of pro- 
 teids. 
 
 B. General Precipitants. — Solutions of proteids are pre- 
 cipitated by the following reagents (peptones are exceptions 
 in most cases) : 
 
 1. Render the solution strongly acid with acetic acid, and 
 add a few drops of a solution of potassium ferrocyanide. A 
 precipitate shows the presence of proteids, except true peptone 
 and some forms of albumose. 
 
 2. Render the fluid as before strongly acid with acetic acid, 
 add an equal volume of concentrated solution of sodium sul- 
 phate, and boil. A precipitate forms if proteids, except pep- 
 tone, are present. This test is particularly useful, since the 
 reagents used do not produce any decomposition of other 
 substances that may be present, and do not interfere with cer- 
 tain other tests that may be applied after the removal of the 
 proteids by filtration. 
 
 3. Completely saturate the fluid with ammonium sulphate, 
 having previously neutralized and then rendered /i?/////)' acid with 
 acetic acid ; this precipitates all proteids except peptones. 
 
 4. Alcohol, tannic acid, phosphotungstic acid, and potassio- 
 mercuric iodide are also general precipitants, the last two being 
 particularly useful for delicate tests. 
 
 The term " albumin," in its ordinary clinical use, includes 
 not only serum albumin, but also serum globulin, and, in 
 rare instances, albumose. It should be remembered that 
 these proteids differ in many respects, and, so far as is pos- 
 sible, should be separately identified. 
 
 ALBUMIN. 
 
 Serum albumin is doubtless the most important proteid 
 found in the urine. It can safely be considered an abnor- 
 mal constituent when present in amounts capable of being 
 detected by the tests that are ordinarily used. Whether 
 or not albumin is present in minute traces in the urine in 
 health — such traces being incapable of detection by the 
 tests generally employed — is still a debated question. From 
 a practical point of view this question can be disregarded. 
 
 Albuminuria is not necessarily an indication of renal dis- 
 ease, for albumin may be present in the urine without the 
 slightest alteration in the renal structure. In general, the 
 presence of albumin indicates a disturbance or disease in
 
 ALBUMIN. 119 
 
 some part of the genito-urinar}' tract, and with one exception 
 — /. c, " functional albuminuria" — is always accompanied 
 by formed physiologic or pathologic elements in the urinary 
 sediment. 
 
 Albumin is not capable of ciystallization ; it is soluble in 
 water, in dilute saline solutions, and in saturated solutions 
 of sodium chloride and magnesium sulphate. It is, how- 
 ever, precipitated by saturating with sodium or ammonium 
 sulphate. It is coagulated by heat, usually at from 70° to 
 73° C, particularly in the presence of sodium chloride. It 
 is not precipitated by ether, in which respect it differs from 
 egg-albumin. Under ordinary conditions it does not pass 
 through animal membranes. 
 
 Causes of Albuminuria. — In general, the causes of 
 albumin in the urine are: (i) Changes in the kidney structure, 
 which, on account of its abnormal state, allows the albumin 
 to transude ; (2) alterations in the blood pressure in the 
 kidneys ; (3) abnormal changes in the quality of the 
 blood entering the kidney, thus rendering its serum albu- 
 min more diffusible ; and (4) disturbances or diseases of 
 the urinary tract below the kidneys — /. e., renal pelvis, 
 ureters, bladder, prostate gland, and urethra. Under this 
 heading may be included, also, albuminous elements enter- 
 ing from the genital tract. 
 
 Clinical Importance. — i. Albuminuria due to patho- 
 logic changes — inflammatory and degenerative — in the 
 kidneys is without doubt the most important, and often the 
 most serious, form. These changes include the variety of 
 diseases commonly grouped under the term of Bright' s 
 disease. Not only do we have to deal with these extensive 
 diseases of the kidney, but also with certain disturbances 
 of the renal function that are accompanied by the pres- 
 ence of albumin. 
 
 The quantity of albumin in the urine in various renal af- 
 fections may vary between the slightest possible trace and 
 from three to four per cent. From the quantity of albumin 
 alone it is impossible to judge in all cases of the nature or 
 severity of the renal changes. For instance, the grave con- 
 dition — chronic interstitial nephritis — may exist with only 
 the slightest possible trace of albumin in the urine. On the 
 other hand, a simple renal congestion may, for a short 
 time, be accompanied by from y^ to y^ of one per cent, of 
 albumin. In certain conditions — for example, an acute
 
 120 ABNORMAL CONSTITUENTS OF URINE. 
 
 nephritis in which the diagnosis has already been estab- 
 Hshed — very general information concerning the progress 
 of the disease may be gained by examining the urine daily 
 for albumin. Such information, however, is unsafe if not 
 accompanied by a complete chemic and microscopic exam- 
 ination of the twenty-foiu'-hour secretion. 
 
 2. The second form — alterations in the blood pressure 
 in the kidneys — is a common cause of albuminuria. It is 
 always the result of circulatory disturbances that include 
 the renal vessels. There is usually more or less structural 
 change in the kidneys, and, besides albuminuria, a greater 
 or smaller number of formed pathologic elements in the 
 sediment. There may be an increase in the arterial pres- 
 sure, as in certain affections of the nervous system in which 
 there is an interference with the vasomotor regulation of the 
 coats of the blood-vessels ; also in sudden exposure to cold 
 and zvct, in which case the internal organs become ab- 
 normally filled with blood ; and in arteriosclerosis. On 
 the other hand, the blood pressure may be diminished, as 
 in certain forms of cardiac disease, which results in a back 
 pressure in the renal veins (passive cogestion), and hence 
 albuminuria. The pressure of tumors or of the pregnant 
 uterus on the abdominal veins will often cause albuminuria, 
 but soon after the cause is removed the albumin disappears 
 from the urine. 
 
 So-called" Functional or Physiologic Albuminuria." 
 — The most marked condition in which this occurs is after 
 prolonged muscular exertion. A study of this condition 
 was made by Leube,i who found albumin in the urine in i6 
 per cent, of soldiers after a prolonged march; Oertels^ found 
 it in 3 per cent, of the cases examined. 
 
 3. This form, which causes albuminuria by changes in 
 the quality of the blood entering the kidney, is notably 
 seen in cases of anemia (this is perhaps partially explained by 
 the lessened nutrition of the renal cells), and in the first stage 
 of the convalescence from cholera. In phosphorus-poison- 
 ing and hemoglobinemia, also in carbon monoxide poison- 
 ing and after the excessive use of morphine, the blood 
 is probably so altered as to permit the transudation of the 
 serum albumin into the renal tubules. In some of these 
 
 1 *' Virchow's archiv," Lxxii, 145 ; i.xxix. 
 
 2 " Ziemssen's Handbucli der allgcmein. Therapie," IV.
 
 ALBUMIN. 121 
 
 cases of poisoning the kidneys are simultaneously affected, 
 so that the cause of the albuminuria may be partly ex- 
 plained by the renal disturbance. 
 
 4. This form of albuminuria has been variously termed 
 false, adventitious, or cxceidoital. Under this class are in- 
 cluded a large number of urines that contain comparatively 
 small amounts of albumin. The quantity of albumin usually 
 depends upon the amount of blood and pus coming from 
 the diseased area, and, therefore, may be abundant if much 
 blood is present. In many instances, particularly when the 
 disturbance or disease is located in the bladder or urethra, 
 the kidney is not affected at all by the condition, the urine 
 being normal until it reaches the affected area. On the 
 other hand, in cases of pyelitis and prostatitis, the function 
 of the kidneys is very apt to be secondarily disturbed by 
 the local disease, and consequently more or less albumin 
 of renal origin. Albumin not infrequently gets into the 
 urine from the genital tract : in the female, from the vagi- 
 nal discharge, consisting of a mixture of more or less pus, 
 blood, and epithelium, also, occasionally, menstrual fluid ; 
 in the male, from seminal fluid. As a rule, the source of 
 albumin in such cases may be determined by both chemic 
 and microscopic investigation, together with the local symp- 
 toms. It is important that this variety of albuminuria be 
 borne in mind by the student in order to avoid error. 
 
 Albuminuria of Adolescence and Cyclic Albumin- 
 uria. — These forms may, or may not, be accompanied 
 by a renal disturbance : in other words, renal casts and 
 cells may or may not be present in the sediment. A 
 large proportion of these cases occurs in youths and young 
 adults. The quantity of albumin usually varies between a 
 slightest possible trace and one -half of one per cent., gener- 
 ally averaging one-eighth of one per cent., or less. The 
 quantity often varies as the time of day — /. c., being less (or 
 sometimes absent) at night during the hours of rest, appear- 
 ing in the morning, especially upon exercising, increasing 
 during the day, and diminishing toward evening. In some 
 of these cases the amount of albumin is fairly constant, day 
 and night, particularly in cases of albuminuria of adoles- 
 cence. The presence of albumin may continue for weeks, 
 months, or even years, and then finally disappear. Little 
 can be said concerning the causes of these forms of albu- 
 minuria. There are often circulatory changes that appear
 
 122 
 
 ABNORMAL CONSTITUENTS OF URINE. 
 
 to be functional in character, and the individual is generally 
 found to be somewhat below the standard of vigorous 
 health. An abnormal increase in the blood pressure or 
 changes in the quality of the blood have been suggested as 
 the possible explanation of this form of albuminuria. 
 
 It is safe to conclude from the foregoing consideration 
 that the presence of albumin in the urine is to be regarded 
 merely as a " danger signal," and that when it is present, a 
 further chemic and microscopic study of the urine is neces- 
 sary before deciding as to the existing condition. Albu- 
 minuria in itself can not be considered diagnostic. 
 
 Detection of Albumin in Urine. — Nitric Acid Test. 
 — Alzvays filter the urine to be tested. This is an important 
 step, even though the urine appears 
 to be perfectly clear, since all urines 
 contain a certain amount of sus- 
 pended matter, which must be re- 
 moved in order to detect the smallest 
 traces of albumin. 
 
 Take a perfectly clear and dry wine- 
 glass (Fig. 13),! and one-half fill with 
 the filtered urine. Incline the glass 
 so that the urine reaches nearly the 
 edge, and then underlie zvitJi concen- 
 trated nitric acid (C. P.), pouring it 
 from the bottle as slozvly as possible 
 (Fig. 14), until the acid equals ap- 
 proximately onc-thij'd the volume of 
 urine used. If albumin be present, a 
 more or less distinct white band or 
 zone of coagulated albumin will be 
 seen just abov^e the junction of the 
 acid and urine. This zone will var>' in thickness according 
 to the quantity of albumin present, the rapidity with which 
 the acid is poured, or, in other words, the extent to which 
 the acid and urine are mixed, and, lastly, the amount of 
 effervescence that follows the addition of acid (decomposi- 
 tion of carbonate, and in case yellow nitric acid is used, the 
 decomposition of the urea and uric acid, with effervescence). 
 
 Fig. 13. — Wine-glass (one- 
 half actual size). 
 
 1 The wine-glass here represented is perhaps best suited for the satisfactory 
 performance of the nitric acid test. It is made of clear white glass, and is 
 free from defects. It was formerly manufactured by the Sandwich Glass Co,, 
 under the name of " CoUamore Wine Glass."
 
 ALBUMIN. 
 
 123 
 
 Approximate Estimation of Albumin. — If in every case 
 the proportion of urine and acid is as previously indicated, 
 and the nitric acid is poured from the bottle as slowly as 
 possible, much can be told concerning the approximate 
 quantity of albumin present by the appearance of the zone 
 obtained. It is very difficult, and, indeed, practically impos- 
 sible, to give the percentage of albumin as judged from the 
 zone, if the quantity is less than a trace ; if more than a 
 trace, a general idea as to the percentage can be given. 
 
 {li) Slightest Possible Trace. — This is, naturally, the 
 smallest amount of albumin capable of being detected by 
 ordinary tests, and can certainly be considered an entity in 
 connection with the nitric acid test. These slightest traces, 
 I regret to say, are often overlooked, especially by the 
 inexperienced, because the proper means for their detection 
 
 Fig. 14. — Method of performing the nitric acid test for albumin. 
 
 are not employed. It is important, first of all, that the 
 wine-glass be perfectly clean, and, secondly, that a dark 
 background be adjusted obliquely in front of, or a little 
 to one side of, the glass, between the source of light and 
 the glass, but not so placed as entirely to cut off the light. 
 (See Fig. 15.) In this way the merest haze of albumin, 
 which is usually a rather wide, hazy band, approximately 
 -jlg to "I" of an inch in width, and not a sharp and narrow 
 band, is discernible. A clear, but usually narrow, layer of 
 clear urine can frequently be seen between this haze or 
 cloud of albumin and the zone of acid urates that forms 
 higher up in the layer of urine. The slightest possible 
 trace can not be seen without the use of a dark back- 
 ground.
 
 124 
 
 ABNORMAL CONSTITUENTS OF URINE. 
 
 {b) Very Slight Trace. — This is a faint zone which is best 
 seen by using a dark background. If the wine-glass is 
 held between the eye and the light, a very faint cloud 
 may be seen, but the observer will often be in doubt as to 
 the presence of albumin until a dark background is used. 
 This zone can not be discerned as the observer looks down 
 on to the surface of the urine : that is, the bottom of the 
 wine-glass can be distinctly seen. 
 
 ic) Slight Trace. — This is a distinct white zone which 
 can readily be seen from the side without a dark back- 
 ground. In looking through the urine from above down- 
 ward, a very faint cloud can be made out, although the 
 bottom of the wine-glass can be distinctly seen. 
 
 ^H 
 
 i 
 
 1 
 
 
 9 
 
 ^ 
 
 rife 
 
 ,^ 
 
 £ 
 
 jffB 
 
 fc 
 
 
 felfemr 
 
 V ■> 
 
 ^1 
 
 H^ 
 
 ^^ 
 
 fcff 
 
 Fig. 
 
 15. — Method for llie detection of minute quantities of albumin. Lower zone, 
 alljumin ; upper zone, acid urates. 
 
 (d) Trace. — A trace of albumin is a zone which is dis- 
 tinctly seen without a dark background, when viewed from 
 the side. In looking through the urine from above down- 
 ward a decided cloud is seen, but this cloud is usually not 
 so dense as to prevent one's seeing the bottom of the 
 wine-glass. 
 
 {e) Large Trace (including -^ of i per cent.). — A zone 
 which, seen from the side, is very evident, but not granular 
 (flocculent). When viewed from' above downward, it is 
 found to be quite dense, although not so dense as to 
 obstruct entirely the transmission of a little light. (The
 
 ALBUMIN. 125 
 
 light can be cut off by placing the hand between the source 
 of Hght and the glass.) 
 
 (/) Onc-ciglitJi of One Per Cent. — A marked zone which 
 is not flocculcnt. The bottom of the glass can not be 
 seen, although a faint ray of light can usually be seen 
 coming through the zone. 
 
 (^) One-fonrth of One Per Cent. — A zone which is 
 quite flocculent when viewed from the side. No light can 
 be seen through the band in looking from above downward. 
 
 {]l) One-half of One Per Cent, or More. — When the quan- 
 tity of albumin reaches one-half of one per cent, or more, 
 a dense, very floeen lent h?in6. forms; light can not be seen 
 through it. Above one-half of one per cent, it is difficult 
 to estimate the approximate quantity present ; a quantita- 
 tive test should then be made according to the instructions 
 given on page 131. 
 
 If the proper appliances are at hand, it is advisable to 
 make a quantitative determination of the albumin in all 
 cases in which the amount is a traee or more. 
 
 In the nitric acid test practically nothing can be deter- 
 mined from the width of the zone of albumin. In dealing 
 with the smaller quantities the width of the band will 
 depend largely on the rapidity with which the nitric acid is 
 poured, and also upon the amount of effervescence that 
 follows the addition of the acid. The bands will usually 
 vary in width from about ^-^ of an inch to \ of an inch or 
 more. Usually in the presence of the large quantities of 
 albumin the band is quite narrow, but exceedingly dense. 
 
 Heat Test. — The heat test for albumin depends upon 
 the separation (coagulation) of this proteid from fluids which 
 are faintly acid, preferably with acetic acid, by heating at a 
 temperature of about 75° C. 
 
 It is essential that the urine should have a faintly acid 
 reaction ; for, if the urine is alkaline, the albumin is in the 
 form of alkali albumin, which is not coagulable by heat. 
 Again, if too strongly acidulated, the albumin is in the form 
 of acid albumin, which is likewise incapable of being coagu- 
 lated by heat. 
 
 /. If the urine is acid, take one-half test-tube of the filtered 
 urine, add one drop (not more) of 10 per cent, acetic acid, 
 and mix thoroughly ; hold the test-tube by the lower portion, 
 and boil the upper one-third of acidulated urine. If a cloud 
 forms, it consists of either albumin or earthy phosphates.
 
 126 ABNORMAL CONSTITUENTS OF URINE. 
 
 Add another drop or two of acetic acid, boil again, and if 
 the cloud remains, albumin is present ; if the cloud disap- 
 pears, the precipitate is phosphatic. 
 
 2. If the urine is alkaline, take one-half test-tube of the 
 filtered urine, add two or three drops of lo per cent, acetic 
 acid, and boil the upper one-third of the urine as directed. 
 If the urine has not yet been rendered faintly acid, a pre- 
 cipitate or coagulum of albumin will not appear until 
 sufficient acetic acid has been added, drop by drop, to 
 the hot urine, to faintly acidulate. As soon as the proper 
 reaction has been reached, a precipitate will appear if albu- 
 min be present. As stated previously, the further addition 
 of one or two drops of acetic acid will help to determine 
 whether the precipitate is phosphatic or is a coagulum 
 of albumin. 
 
 It scarcely ever happens that a urine, when voided, is 
 too acid for the successful application of the heat test, and 
 even in a strongly acid urine it is often necessary to use 
 one drop of acetic acid in order that the examiner may be 
 satisfied of the presence or absence of albumin. 
 
 Nitric acid, which is often used for acidulation instead of 
 acetic acid, is liable to lead to serious error in judging of 
 the presence of albumin by the heat test. This is espe- 
 cially so if the albumin is present in small amount, since 
 the addition of so strong an acid converts the albumin to 
 acid albumin, — syntonin, — which is soluble and not coag- 
 ulated by boiling. Less danger exists in the use of acetic 
 acid (lo per cent.), providing, however, that an excess of the 
 acid is avoided. Nitric acid should, therefore, not be used 
 in connection with the heat test. 
 
 The approximate estimation of the quantity of albumin 
 from the density of the coagulum of albumin by heat is not 
 always a simple matter in the hands of most observers, 
 since a standard for comparison can not be easily fixed. 
 On the other hand, those who prefer to use the heat test 
 instead of the nitric acid test for routine work can learn to 
 estimate the approximate quantity in a general way. 
 
 The Potassium Ferrocyanide and Acetic Acid Test. 
 — This test may be applied in two ways : i. e., (a) by actual 
 mixture and {b) by the contact method. 
 
 {a) To a half test-tube of urine add from three to five 
 cubic centimeters of a solution of potassium ferrocyanide 
 (i : lo), and from one to three cubic centimeters of 50 per
 
 ALBUMIN. 127 
 
 cent, acetic acid ; the rea^jents and urine should be thor- 
 oughly mixed. If albumin be present, a white, finely divided 
 precipitate will appear within half a minute or a minute. 
 
 (/») Take a mixture of one part of 50 per cent, acetic acid 
 and two parts of potassium ferrocyanide solution in a wine- 
 glass, and carefully overlay with the urine to be tested. If 
 albumin be present, a narrow, sharply defined, white zone 
 will appear just above the junction of the two flluids. The 
 urine to be tested must be acid in reaction in order to 
 obtain a satisfactory test. This reagent does not precipi- 
 tate peptones, alkaloids, or phosphates, but may precipitate 
 acid urates. It has been found to react slightly with 
 artificial solutions of nucleo-albumin. 
 
 A comparative experimental study of the three tests 
 described convinces the writer of the following order 
 of delicacy : (i) nitric acid test; (2) heat test; (3) potas- 
 sium ferrocyanide and acetic acid test. 
 
 Other Tests for Albumin. — It has long been known 
 that albumin is coagulated or precipitated by other agents 
 than nitric acid, heat, and potassium ferrocyanide and acetic 
 acid. Some of these tests have claimed much attention, 
 and have been found to be extremely delicate, but it is safe 
 to say that their delicacy is often at the expense of accuracy. 
 The chief objection to many of the tests is that they pre- 
 cipitate other substances than albumin, and although these 
 substances are distinguished from albumin by taking certain 
 precautions, or by the application of other tests, the ob- 
 server is either misled, and considers that albumin is present, 
 or he is left in a confused state of mind. While, doubtless, 
 it is desirable that we should possess tests for albumin 
 which are very sensitive, yet extreme delicacy of re- 
 action is of secondary consideration and not of clinical 
 importance. Such tests should, therefore, not enter into 
 the routine examination of the urine, thus avoiding unneces- 
 sary confusion. 
 
 Picric Acid Test. — This test has been strongly advised by 
 Dr. George Johnson. 1 The test is applied as follows: Into a 
 test-tube six inches long pour a four-inch column of filtered 
 urine. Then, holding the test-tube in a slanting position, pour 
 gently an inch of a saturated solution of picric acid (made by 
 adding six or seven grains of picric acid to a fluidounce of boil- 
 
 * "Albumin and Sugar- testing," London, 1884.
 
 128 ABNORMAL CONSTITUENTS OF URINE. 
 
 ing distilled water) over the surface of the urine ; the reagent 
 thus mixing with only the upper layer of the urine. As far as 
 the yellow color of the reagent extends, the coagulated albumin 
 renders the liquid turbid, contrasting with the clear urine below. 
 In order to obtain a satisfactory reaction there must be an actual 
 mixture and not a mere surface contact. When the quantity of 
 albumin is small and the turbidity is slight, the application of 
 heat to the upper part of the turbid mixture increases it. This 
 reagent also precipitates urates, peptone, albumose, vegetable 
 alkaloids, and mucin, all of which, except mucin, are dissolved 
 by a degree of heat much below that of the boiling-point. 
 
 The Potassio-7nercuric-iodide Test. — This test was sug- 
 gested by M. Charles Tanret. The reagent (double iodide of 
 mercury and potassium, acidulated with acetic acid) is prepared 
 as follows: Bichloride of mercury, 1.35 grams; potassium 
 iodide, 3.32 grams; acetic acid. 20 c.c. ; distilled water, suf- 
 ficient to make 100 c.c. The bichloride of mercury and the 
 potassium iodide should be dissolved separately in water, and 
 the two solutions mixed ; the acetic acid is then added, and 
 the whole mixture made up to 100 c.c. The contact method is 
 used, and since the reagent is heavier than the urine, the latter 
 is carefully poured on to the surface of the reagent in a test- 
 tube or wine-glass. If albumin be present, a white, sharply de- 
 fined band appears at the junction of the two fluids. This test 
 precipitates the same substances as picric acid, including nucleo- 
 albumin. All of these precipitates except albumin are dissolved 
 by gentle heat, the precipitate reappearing upon being cooled. 
 According to Oliver, the precipitate of nucleo-albumin is not 
 dissolved by heat if a large excess of reagent is used, the mer- 
 curic salt apparently preventing solution. This test is exceed- 
 ingly delicate. 
 
 Trichloracetic Acid Test. — This test is applied by means of 
 the contact method. The reagent is prepared by dissolving 
 15 grams of the crystals of trichloracetic acid in about 10 c.c. 
 of distilled water, making a saturated solution. Delicate results 
 are claimed for this test, but, from the fact that it precipitates 
 mucin and nucleo-albumin, it can not be regarded as a reliable 
 test for albumin. 
 
 Sodium Tungstate. — This test was suggested by Dr. George 
 Oliver as a very sensitive reagent for albumin. The reagent is 
 prepared by mixing equal parts of a saturated solution of sodium 
 tungstate (1:4) and a saturated solution of citric acid. The 
 contact method is used, and since the reagent is heavier than 
 urine, it is best applied by the overlaying method. The reagent 
 precipitates, in addition to albumin, acid urates, peptone, and 
 mucin. It gives no reaction with the alkaloids, and all precipi- 
 tates, except albumin and mucin, are readily dissolved by heat.
 
 ALBUMIN. 129 
 
 A large number of other so-called ' * delicate tests ' ' have been 
 suggested for the detection of albumin, only a few of which are 
 worthy of mention: Acidulated brine test (Roberts), nitric- 
 magnesium test (Roberts), phenic acid test (Millard), Heiden- 
 lang'stest, Heynsius'stest, acetic acid and sodium sulphate, etc. 
 
 Albumin- test Papers. — According to the suggestion of Dr. 
 George Oliver, a number of the tests named have been prepared 
 and used in paper form. This is accomplished by using chem- 
 ically inert filter-paper, some of which is to be saturated with 
 solutions of the albumin reagents, and some with citric acid, 
 and then drying. The papers are then cut into slips of con- 
 venient size for testing, and may be carried about in the pocket- 
 case for use at the bedside of the patient. In testing, the follow- 
 ing method is followed : Into a small test-tube containing 5 c.c. 
 of distilled water are dropped a reagent paper and one charged 
 with citric acid. After agitation for a minute or so the test- 
 papers are removed, and the solution is ready for testing. The 
 urine is now added ; the test may be conducted either by a mix- 
 ture of the two or by the contact method, of which Dr. Oliver 
 advises the latter. 
 
 Dr. Oliver now recommends the use of two reagents only for 
 albumin — viz., the potassium ferrocyanideand potassio-mercuric- 
 iodide papers. The former of these will be found trustworthy, 
 and of very great convenience at the bedside. 
 
 The potassio-mercuric-iodide test must, in all cases, be con- 
 trolled by heating, otherwise it may be misleading. 
 
 The Removal of Albumin by Heat. — If the urine to be 
 examined contains more than a trace of albumin, it should 
 be removed before testing for chlorides, sulphates, and 
 sugar, since the albumin either enters into combination 
 with the reagents or. reacts with them in such a manner as 
 to render the tests unreliable. The best method for the 
 removal of albumin is to coagulate it by heat ; this should 
 be applied in connection with both qualitative and quanti- 
 tative analyses. 
 
 I. For Qualitative Tests. — Take one-third of a test- 
 tube of urine, add one drop of dilute acetic acid, and boil the 
 whole mixture thoroughly. If a flocculent precipitate does 
 not form, add at intervals, drop by drop, more acetic acid, 
 heating the mixture after each addition until a distinct floc- 
 culent coagulum forms. Filter ; the filtrate should be per- 
 fectly clear and practically free from albumin. 
 
 ■2. For Quantitative Analysis. — Take a definite 
 quantity of the urine, say 50 c.c, place in a porcelain evap- 
 9
 
 130 ABNORMAL CONSTITUENTS OF URINE. 
 
 orating dish, add two or three drops of dilute acetic acid, 
 and boil thoroughly. If a flocculent coagulum of albumin 
 does not appear, add a few more drops of the acetic acid, 
 drop by drop, stirring constantly and continuing the heat 
 until such a flocculent coagulum forms. Filter, — the filtrate 
 should be free from precipitate, — and wash once or twice 
 with water. Allow the filtrate and wash-water to run into 
 a graduate, and add sufficient water to make the original 
 volume (50 c.c). Mix the contents of the graduate thor- 
 oughly, and use for the quantitative tests. 
 
 In removing albumin by heat a flocculent coagulum 
 should be obtained in all cases, and this is accomplished 
 when the urine has a faintly acid reaction (preferably with 
 acetic acid). In case a flocculent coagulum is not obtained, 
 the filtrate will be more or less turbid, the turbidity being 
 due to the finely divided precipitate of albumin. Such a 
 turbid filtrate is unfit for further tests. 
 
 Quantitative Estimation of Albumin in Urine. — Ex- 
 pression of Quantity of Albumin Found in Urine. — In 
 referring to the quantity of albumin found in the urine the 
 author, in all cases, means the quantity by iveigJit, and not 
 the bulk measure ; thus, if the expression "^ of i per 
 cent." be used, it is ^^ of i per cent, by weight that is 
 intended. We not infrequently read that urines contain 25, 
 50, and even 75 per cent, of albumin. The quantity by 
 bulk is, of course, intended, since 3 to 5 per cent, by 
 w^eight is probably the maximum amount of albumin that 
 urine can contain. Much greater care should be exercised 
 in speaking of the quantity of albumin present, using the 
 terms percentage by zveiglit or percentage by bulk, according 
 to the meaning of the writer. Attention given this matter 
 will be the means of avoiding much confusion, particularly 
 to students. 
 
 The term "i per mille," or "i p. m.," refers to the num- 
 ber of grams of albumin contained in i liter of urine ; 
 thus, the foregoing expression equals i gram of albumin in 
 1000 c. c. of urine, or ^ of i per cent, by weight ; 2 p. m. 
 equals 2 grams in looo c. c, or -^-^ of i per cent. ; 5 p. m. 
 equals 5 grams in 1000 c. c, or i of i per cent., etc. 
 
 Gravimetric Process. — This process for the quantita- 
 tive estimation of albumin gives accurate results, but is 
 unsuitable for clinical purposes on account of the length of 
 time and the apparatus required for its completion.
 
 ALBUMIN. 
 
 131 
 
 1f?ifl 
 
 Take lOO c.c. of the urine, place in a beaker or glass 
 evaporating dish, and heat on a water-bath. A two per 
 cent, solution of acetic acid is then added, drop by drop, 
 until, upon boiling, a flocculent precipitate of albumin 
 separates. This is then filtered through an 
 ash-free filter which has been previously 
 dried and weighed. The precipitate is 
 washed successively with water, alcohol, 
 and ether, and dried at a temperature of 
 120° to 130° C. After cooling the filter 
 is again weighed, and the difference in 
 weight due to the precipitate represents the 
 quantity of albumin in the 100 c.c. of 
 urine used. 
 
 Devoto^ recommends the following pro- 
 cedure : Take a definite quantity of urine, 
 precipitate the albumin with ammonium 
 sulphate, heat on a water-bath, and wash 
 the precipitate with boiling water until the 
 filtrate no longer becomes cloudy on stand- 
 ing, or upon the addition of sodium chloride. 
 The precipitate is then washed with alcohol 
 and ether, and the remainder of the process 
 conducted as previously directed. 
 
 Esbach's Method. — This test is made 
 by means of a standard graduated glass 
 tube or albuminometer,^ as shown in figure 
 16. The process is as follows : The fol- 
 lowing solution is prepared : Picric acid, 
 10 grams ; citric acid, 20 grams ; distilled 
 water, to lOOO c.c. (i liter). Fill the 
 albuminometer tube with the urine to the 
 letter U, then add the reagent to R, close 
 the tube with the stopper, and invert several 
 times, until the urine and the reagent are 
 thoroughly mixed. Stand the tube in a 
 rack for twenty-four hours, and then read 
 off the number of grams of albumin to the liter, as will be 
 indicated by the number on the side of the tube on a level 
 where the albumin settles. If it is desired to know the 
 
 Fig. 16. — Esbach's 
 albuminometer. 
 
 1 Devoto, " Zeitschr. f. physiol. Ch.," xv, 474, 1891. 
 ^ Esbach's tubes are supplied by Eimer & Amend, of Third Avenue, New 
 York, at a moderate cost.
 
 132 ABNORMAL CONSTITUENTS OF URINE. 
 
 percentage of albumin in the urine instead of the number 
 of grams per hter, remove the decimal point one figure 
 to the left; thus, 5 grams per liter would be 0.5 per cent, 
 of albumin. It will be observed that Esbach's albumin- 
 ometer tubes are so graduated that their highest range is 
 7 grams per liter — 0.7 per cent, of albumin. If, therefore, 
 the urine be highly albuminous, it should be diluted with 
 one or two volumes of water before testing, and the pro- 
 duct multiplied by two or three, according as the volume 
 is doubled or trebled. 
 
 Centrifugal Method — Potassium Ferrocyanide and 
 Acetic Acid. — Albumin can be readily precipitated by 
 means of a mixture of potassium ferrocyanide and acetic 
 acid, and quantitated by using the graduated tubes of a 
 centrifugal apparatus. 
 
 Process. — Take 10 c.c. of filtered urine, add 3.5 c.c. of a 
 solution of potassium ferrocyanide (i : 10), and 1.5 c.c. 
 of acetic acid (U. S. P.) ; close the tube with the thumb, 
 and invert several times in order to mix thoroughly. The 
 tubes are then placed in the centrifuge, which is revolved 
 until the precipitate of albumin has been completely set- 
 tled and the supernatant fluid is perfectly clear. The cen- 
 trifuge should be run at the speed of lOOO revolutions per 
 minute and for from three to five minutes. According to 
 Purdy, each -^-^ c.c. of precipitate represents i percent, hulk 
 incasiire, or volume per cent, of albumin. 
 
 In order to determine the percentage of albumin by 
 weight in the use of the above method the writer, a few 
 years ago, made a series of experiments which led to the 
 following conclusion : each -^ c.c. of precipitate represc?its 
 ■^ of I per cent, of albumin by zveigJit. 
 
 This method furnishes a very rapid, accurate, and con- 
 venient means of quantitating albumin, and is subject to 
 only very- slight sources of error. The most important 
 part of the test is to thorougJily settle the precipitate. 
 
 GLOBULIN. 
 
 Serum globulin, also termed paraglobulin, is a proteid 
 which is usually associated with serum albumin, and is fre- 
 quently found in the urine. Globulin is insoluble in water 
 and soluble in dilute (i per cent.) solutions of sodium chlo- 
 ride. It is also soluble in dilute acids or alkalies, being 
 changed into acid- and alkali-proteid respectively, unless
 
 GLOBULIN. 133 
 
 the acids and alkalies are exceedingly dilute and their action 
 is not prolonged. It is precipitated by saturating its solu- 
 tions with magnesium sulphate, with sodium chloride, and 
 by half-.saturation with ammonium sulphate. Globulin can 
 be quantitated by saturating its neutral solution with magne- 
 sium sulphate, since the other proteids are not precipitated 
 by it. It is partially precipitated from its solution by 
 carbonic acid gas. When its solutions are dialyzed, it is 
 precipitated, owing to the fact that the percentage of salt is 
 so far reduced by dilution that it is no longer sufficient to 
 hold the globulin in solution. Its dilute saline solutions 
 coagulate on heating to 75° C. (Halliburton). 
 
 Normal urine is free from globulin, but this proteid may 
 be found in the urine under pathologic conditions. 
 
 Clinical Significance. — The clinical significance of the 
 presence of globulin is much the .same as that of albumin. 
 It has been found in abundance in amyloid infiltration of 
 the kidneys (in much larger quantities than in other forms 
 of Bright's disease — Senator), acute nephritis, chronic cys- 
 titis, pyonephrosis ^ following deranged digestion, and in 
 the severe hyperemia following cantharides poisoning. 
 Although globulin is usually present in the urine in much 
 smaller quantities than albumin, it may equal or even exceed 
 it in amount. It is occasionally found in the urine when 
 albumin is absent. In severe organic disease of the kidneys 
 and in the albuminuria that occurs in diabetes, Maguire ^ 
 found that the proportion of albumin to globulin was as 
 2.5 : I (normal in the blood, L5 : i). 
 
 Detection. — Saturate the urine, which has been pre- 
 viously neutralized and filtered, with magnesium sulphate ; 
 a white precipitate results if globulin is present. 
 
 When a few drops of the globulin-containing urine are 
 allowed to fall into a large volume of distilled water, a tur- 
 bidity appears (nucleo-albumin gives a similar turbidity) ; 
 when much globulin is present, the water assumes a milky 
 opalescence. 
 
 Quantitative Estimation of Globulin. — Take 100 cc. 
 of the urine-containing globulin, render neutral or faintly 
 alkaline with amnionic hydrate, and remove the precipitated 
 phosphates by filtration ; then completely saturate with 
 magnesium sulphate ; filter, and wash with a saturated solu- 
 
 ' " Boston Medical and Surgical Journal," March 3, 1898, p. 197. 
 2 " British Medical Journal," vol. II, l886, p. 543.
 
 134 ABNORMAL CONSTITUENTS OF URINE. 
 
 tion of magnesium sulphate. The entire precipitate on the 
 filter-paper is then dissolved in water or a weak solution 
 of sodium chloride, and the globulin coagulated by boil- 
 ing, the solution having been previously faintly acidu- 
 lated with acetic acid. The coagulation must be com- 
 plete. Filter through a previously dried and weighed 
 filter-paper. The filter containing the precipitate is then 
 dried at a temperature of i io° to 120° C, cooled, and 
 weighed. The difference between the filter-paper and 
 filter-paper plus precipitate equals the quantity of globulin 
 in 100 c.c. of urine. 
 
 This test is probably not perfectly accurate, since small 
 amounts of other proteids, notably some forms ofalbumose,^ 
 are precipitated by magnesium sulphate. 
 
 ALBUMOSES. 
 
 This proteid belongs to the general class of proteoses. 
 The albumoses, together with another proteose, — glohulose, 
 — are absent from normal urine (except perhaps in the 
 slightest traces), but are occasionally found under patho- 
 logic conditions. Up to the present time very little, if any- 
 thing, is known of the clinical significance of the globu- 
 loses, so that they will not be considered here. 
 
 The albumoses are formed by the action of the gastric 
 and pancreatic juices on proteid material, and appear as 
 intermediate products between the proteid material and the 
 final product, peptone. 
 
 Varieties. — According to Kiihne, there are at least two 
 albumoses — autialdionose, the forerunner o( antipeptone, and 
 Jiemialbiimose, the forerunner of heinipeptone. Of these two 
 forms he^nialbiimose is the more important. Kiihne and 
 Chittenden, in their earlier work,^ at first distinguished 
 between a soluble and insoluble form, but more recently 
 they have described four closely allied, though dis- 
 tinct forms of albumose. ^ (i) Protalbimiose , soluble in 
 hot and cold water and precipitated by saturation with 
 sodium chloride and magnesium sulphate. (2) Hetcro- 
 albiunose, insoluble in hot and cold water, soluble in dilute 
 (0.5 per cent.) and in more concentrated (15 per cent.) 
 
 1 Halliburton, "Text-book of Cheni., Physiol., and Pathol.," p. 783. 
 
 2 "Zeitschr. f. Biol.," Bd. xix, 1883, S. 174. 
 
 3 Ibid., Bd. XX, S. II.
 
 ALBUMOSES. 135 
 
 solutions of sodium chloride, but precipitated from these by 
 saturation with the salt. It is precipitated by alcohol, 
 when it is partly converted into (3) dysalbumose, which is 
 insoluble in saline solutions. (4) Dciitcro-albiimosc soluble 
 in hot and cold water, not precipitated by saturating with 
 sodium chloride or magnesium sulphate, unless an acid be 
 added at the same time, but is precipitated by saturating 
 with ammonium sulphate and by nitric acid, if an excess is 
 not added. 
 
 Clinical Significance. — Albumose was first discovered 
 in the urine by Bence Jones ^ in a case of osteomalacia. 
 It has since been found in this disease by Kiihne ^ and 
 others. Virchow ^ has found albumose in the bone-marrow 
 in cases of osteomalacia ; Hoppe-Seyler ^ found it in several 
 cases of atrophy of the kidneys ; Lassar ^ found it in the 
 urine of people who had been rubbed with petroleum, and 
 Oertel ^ in a few cases after severe exertion. Senator has 
 found albumose in the urine in croupous pneumonia, diph- 
 theria, tertiary syphilis, carcinoma, hemiplegia, and muscu- 
 lar atrophy. It has been found by a number of observers 
 in sarcomata of the bones of the trunk, especially of the 
 ribs and sternum. Fitz '^ has reported a case of myxedema 
 in which albumosuria was a prominent feature. 
 
 H. Senator ^ has recently reported a case of multiple 
 sarcomatosis of the ribs in which albumosuria was a promi- 
 nent feature. His patient also suffered from chronic paren- 
 chymatous nephritis with amyloid infiltration of the kidneys, 
 fibrinous pleurisy, bronchopneumonia, and gangrene in 
 the region of the left trochanter. 
 
 The quantity of albumose found in the urine of croupous 
 pneumonia, diphtheria, tertiary syphilis, carcinoma, muscu- 
 lar atrophy, after severe exertion, etc., is usually very small, 
 it being present only in traces ; in cases of sarcomata of 
 the bones of the trunk the quantity may reach as high as 
 ^ of I per cent. 
 
 1 "Phil. Trans. Roy. Soc," vol. i, 1848. 
 
 2 " Zeitschr. f. Biol.," xix, S. 209. 
 •* " Virchow's Archiv," iv, S. 309. 
 *" Physiol. Chem.," S. 858. 
 
 5 "Virchow's Archiv," Lxxvil, S. 164. 
 * " Ziemssen's Handbuch d. Therapie," 1884. 
 '" American Jour. Med. Sciences," July, 1898. 
 ' " Berliner klin. Wochenschr. ," Feb. 20, 1899.
 
 136 ABNORMAL CONSTITUENTS OF URINE. 
 
 Although the condition of albumosuria has been 
 thoroughly studied by a number of able chemists and clin- 
 icians, its true clinical significance, up to the present time, 
 is very indefinite. The fact that albumose has been so fre- 
 quently found in bone diseases would suggest a possible 
 cause of the condition. 
 
 Detection. — From a clinical point of view it is not essen- 
 tial to distinguish between the various forms of albumose ; 
 the following reactions suffice for its detection : 
 
 1. Take a small portion of the urine in a test-tube, and 
 warm gently. A precipitate appears which is redissolved 
 on boiling and reappears on cooling. 
 
 2. Acidulate the urine with acetic acid, and add a few 
 drops of a saturated solution of sodium chloride. A pre- 
 cipitate is formed which disappears on heating and reap- 
 pears on cooling. 
 
 3. Add a few drops of nitric acid to the urine in a test- 
 tube. If the acid is not in excess, a precipitate is formed 
 which disappears on boiling and reappears on cooling. 
 
 4. Add acetic acid, avoiding an excess, and then a few 
 drops of a solution of potassium ferrocyanide (i to 10). A 
 precipitate is formed which disappears on boiling and reap- 
 pears on cooling. 
 
 5. Completely saturate the urine (preferably, according 
 to Kiihne, at boiling temperature) with neutral ammonium 
 sulphate. Filter and wash the precipitate with a saturated 
 solution of ammonium sulphate. Dissolve the precipitate 
 in water or dilute sodium chloride solution, and, if albumose 
 be present, its solution will give the biuret reaction. This 
 method separates the albumoses from the peptones, the 
 former being precipitated, the latter remaining in solution 
 and appearing in the filtrate from the ammonium sulphate 
 precipitate. 
 
 PEPTONE. 
 
 Peptones are the final products of gastric and pancreatic 
 digestion of albuminous bodies, in so far as these final 
 products are still true albuminous substances. When, 
 however, the digestion (hydration) is continued, the pep- 
 tones split up into simpler bodies, which are no longer 
 proteid in character. Peptones are, furthermore, products 
 of pathologic changes in the blood-corpuscles. They may 
 also be produced from albumin by the continued action of
 
 PEPTONE. 137 
 
 acids and alkalies, and it is said, also, by the decomposin<j 
 action of bacteria, as well as the long-continued operation 
 of a temperature of 130° to 143° C. 
 
 Peptones are not coagulated by heat. They are not 
 precipitated by nitric acid, ammonium sulphate, potassium 
 ferrocyanide and acetic acid, but are thrown down by a 
 mixture of picric and citric acids, tannic acid, phospho- 
 molybdic acid, phosphotungstic acid, potassio-mercuric 
 iodide (Tanret's reagent), mercuric chloride, and Millon's 
 reagent. They are precipitated, but not coagulated, by 
 alcohol. Peptone is very soluble in water, and is readily 
 diffused through animal membranes ; albumoses are only 
 slightly diffusible. 
 
 Peptones exist in two forms: (i) Hcinipcptoiic, which is 
 obtained by the action of trypsin on hemialbumose. When 
 purified and digested with trypsin it yields much leucin and 
 tyrosin, and in this respect alone does it differ from anti- 
 peptone. (2) Antipcpt07ie is formed as the result of 
 digestion of antialbumose, but is not capable of yielding 
 leucin and tyrosin when purified and subjected to the most 
 prolonged action of the pancreatic juice. It, moreover, 
 does not yield leucin and tyrosin when treated with 
 sulphuric acid, and does not react with Millon's reagent. 
 Peptone is not present in healthy blood or normal urine. 
 
 Clinical Significance. — Peptone was first described in 
 the urine by Gerhardt. ^ Up to the publication of the very 
 able researches of Kiihne and Chittenden, most of the 
 proteids clas.sed as peptones were probably albumoses, or 
 mixtures of albumoses and peptones, so that the early data 
 concerning peptonuria are far from reliable. The proteid 
 most liable to be mistaken for peptone is deutero-albumose. 
 According to Maixner, peptone is always present in the 
 urine when pus is forming in any part of the body. For 
 this reason peptonuria is often present in septicemia, and can 
 thus be distinguished from other conditions that are not pyo- 
 genic. Likewise, in acute inflammatory diseases, the pres- 
 ence of peptone in the urine usually indicates that suppura- 
 tive changes have been established, other known causes of 
 peptonuria being absent. Destruction of the corpuscular 
 blood elements in some of the acute infectious diseases 
 seems to be a cau.se of peptonuria. According to v. 
 
 ' •' Deutscli. Arclii\. f. klin. Med.," v, 215.
 
 138 ABNORMAL CONSTITUENTS OF URINE. 
 
 Jaksch, peptonuria is a constant accompaniment of epidemic 
 cerebrospinal meningitis, and is absent in tubercular menin- 
 gitis. This furnishes an important means of distinguishing 
 between these two diseases, providing suppurative conditions 
 elsewhere are excluded. 
 
 A number of observers have described peptonuria in a 
 variety of pathologic conditions : Suppurative diseases, em- 
 pyema, croupous pneumonia, gangrene of the lung, small- 
 pox, erysipelas, scarlet fever, typhoid fever, tuberculosis, 
 acute rheumatism, cancer of the gastro-intestinal tract and 
 liver, cerebral hemorrhage, phosphorus-poisoning, typhus, 
 etc. Naturally, the accuracy of observation in connection 
 with some of the above-mentioned diseases is doubted, 
 since, previous to the work of Kiihne and Chittenden, 
 nothing was known of the means of distinguishing between 
 peptone and other proteids. 
 
 Detection. — The accurate detection of peptone depends 
 upon its separation from albumose, and this is accomplished 
 as follows : The urine, first faintly acidulated with acetic 
 acid, is completely saturated with ammonium sulphate, and 
 filtered. The precipitate may consist of albumin, globulin, 
 or albumose. The only proteid in the filtrate, however, is 
 peptone, which can be detected by the biuret reaction, or 
 by precipitation with tannic acid, potassio-mercuric iodide, 
 picric acid, phosphotungstic acid, or phosphomolybdic acid. 
 According to Kuhne, in order to separate completely the 
 albumoses from the peptones the saturation with ammonium 
 sulphate should be conducted at the boiling temperature. 
 Furthermore, a single saturation with ammonium sulphate 
 should not be depended upon for the removal of all of the 
 albumose, but saturation should be repeated until precipita- 
 tion fails to occur. 
 
 Separation. — Chittenden recommends the following pro- 
 cess for the separation of the peptone from the ammonium 
 sulphate saturated solution. The fluid is concentrated 
 somewhat, and set aside in a cool place for the crystalliza- 
 tion of a portion of the ammonium salt. The fluid is then 
 mixed with about one-fifth of its volume of alcohol, and 
 allowed to stand for some time, when it separates into two 
 layers, an upper one rich in alcohol, and a lower one rich 
 in salts. The latter is again treated with alcohol, by which 
 another separation of the same order is accomplished. The 
 lighter alcoholic layers containing the peptone are united
 
 PEPTONE. 139 
 
 and exposed to a low temperature until considerable of the 
 contained salt crystallizes out. The fluid is then concen- 
 trated, and after the addition of a little water is boiled with 
 barium carbonate until the fluid is entirely free from ammo- 
 nium sulphate. Any excess of baryta in the filtrate is 
 removed by the cautious addition of sulphuric acid, after 
 which the concentrated fluid, reduced almost to a syrupy 
 mass, is poured into absolute alcohol for the precipitation 
 of the peptone. 
 
 Biuret Reaction. — Take a small portion of the fluid to be 
 tested in a test-tube, add an excess of sodic hydrate, and then add, 
 drop by drop, a dilute solution of copper sulphate. The charac- 
 teristic reaction is the appearance of a rose-red color. Great care 
 must be exercised in the addition of the copper solution, since an 
 excess of it gives a reddish-violet color, which is often misleading. 
 
 The substances in the urine which give the characteristic 
 biuret reaction are albiimoses, peptones, and tirobilin. Since 
 more or less urobilin is present in every urine, it must be 
 thoroughly removed before this test can be satisfactorily applied 
 for the detection of albumoses and peptone. 
 
 METHOD OF SEPARATION AND IDENTIFICATION OF 
 PROTEIDS. 
 
 The following table, proposed by Halliburton, ^ gives the 
 method for separating serum albumin, serum globulin, 
 albumoses, and peptone, should they happen to be present 
 together in the urine. This is a very rare occurrence, but 
 in doubtful cases it is best to test for every one in the list : 
 
 1. If the urine gives no precipitate on boiling after 
 faintly acidulating with acetic acid, albumin and globulin 
 are absent. If a precipitate occurs, albumin or globulin or 
 both are present. 
 
 2. If the urine after neutralization gives no precipitate on 
 saturation with magnesium sulphate, globulin and hetero- 
 proteose are absent. If such a precipitate occurs, one or 
 the other is present. 
 
 3. If the urine be saturated with ammonium sulphate 
 and filtered, and the filtrate gives no xanthoproteic or biuret 
 reaction, peptone is absent. 
 
 4. If the urine gives no precipitate on boiling after acidu- 
 lation, no precipitate with nitric acid, and no precipitate on 
 
 ^ "Text-book of Chem., Physiology, and Pathology," p. 788.
 
 140 ABNORMAL CONSTITUENTS OF URINE. 
 
 adding ammonium sulphate to saturation, peptone can be 
 the only proteid present. Confirm this by the biuret reac- 
 tion. 
 
 5. If all proteids are present, they may be separated as 
 follows : 
 
 Saturate the urine (faintly acidified with acetic acid) with 
 ammonium sulphate. A precipitate is produced. Filter. 
 
 (") Precipitate. . (^^ Filtrate. 
 
 Contains albumin, globulin, het- Contains peptone, 
 
 and deuteropioteose. Collect 
 
 the precipitate on a filter, wash it with saturated solution of ammonium sul- 
 phate, and redissolve it by adding a small quantity of water. To this solution 
 add ten times its volume of alcohol ; a precipitate is formed ; collect this, and 
 let it stand in absolute alcohol for from seven to fourteen days. Then filter 
 off the alcohol, dry the precipitate at 40° C, extract it with water, and filter. 
 An insoluble residue is left. 
 
 (<?) Residue. I [h) Extract. 
 
 This consists of albumin and glob- This contains the proteoses in solu- 
 
 ulin coagulated by the alcohol. tion. 
 
 Heterocaseose is precipitated by heating the solution to 65° C, or by satu- 
 rating a portion of the extract with magnesium .sulphate. Deuteroproteose 
 remains in solution. 
 
 Take another portion of urine, neutralize it, and saturate with magnesium 
 sulphate. A precipitate is produced. Filter. 
 
 (rt) Precipitate. I {b) Filtrate. 
 
 This consists of globulin and het- j This contains albumin, deutero- 
 
 eroproteose, which may be separated proteose, and peptone. Add alcohol 
 by the prolonged use of alcohol, as | as above ; albumin is rendered in.solu- 
 above. 1 ble in water in from .seven to ten days. 
 
 The deuteroproteose and peptone are 
 soluble, and may then be separated 
 I by ammonium sulphate. 
 
 NUCLEO-ALBUMIN (MUCIN?) 
 
 A true nucleo-proteid, or nucleo-albumin is a combination 
 of a nuclein with more albuminous matter. ^ This form of 
 proteid formerly known as mucin is probably not true 
 mucin. The presence of small quantities of nucleo-albumin 
 in the urine occurs under normal conditions, it being a pro- 
 duct of the secretion of the cells lining the urinary tract. 
 This substance is probably identical with the nucleo-albu- 
 min of bile. 
 
 ^ A nuclein is a combination of some form of proteid matter with a nucleic 
 acid (Chittenden).
 
 NUCLEO- ALBUMIN. 141 
 
 Native nuclco-albumins contain approximately 1.5 per 
 cent, of phosphorus, are amorphous, and insoluble in water, 
 but they dissolve in weak solutions of the neutral salts. 
 They are completely precipitated by saturating their solu- 
 tions with ammonium sulphate, and only incompletely pre- 
 cipitated when their solutions are saturated with magnesium 
 sulphate, or sodium chloride. They are soluble in alkaline 
 hydrates and carbonates, and are readily precipitated from 
 these alkaline solutions by means of strong mineral acids. 
 They are, however, soluble in acetic acid and dilute mineral 
 acids, and in this respect they differ from the nucleins. 
 
 When nucleo-albumin is dissolved in a solution of so- 
 dium chloride and boiled, a precipitate separates. It is 
 precipitated by all of the reagents used for the precipita- 
 tion of albuminous bodies, and gives all of the color reac- 
 tions of proteid substances. When nucleo-albumin is 
 repeatedly dissolved and precipitated, it becomes decom- 
 posed, with the separation of a portion, which is rich in 
 phosphorus. When it is subjected to the action of pepsin- 
 hydrochloric acid, it furnishes a proteid and insoluble nu- 
 clein. When some of the nucleo-albumins are boiled with 
 moderately dilute mineral acids, a substance is produced 
 which reduces an alkaline solution of cupric oxide with a 
 resulting brown color. 
 
 Clinical Significance. — Nucleo-albumin has been repeat- 
 edly found in increased proportion in the urine of women, 
 in which case it is derived chiefly from the genital tract. It 
 is also found in increased amounts in urine that has passed 
 over the irritated mucous membrane of some portion of the 
 urinary tract. Such a urine is usually turbid when passed, 
 and in a short time deposits a bulky cloud, usually found 
 to contain a small, and sometimes a large, number of 
 leucocytes, red blood-globules, and epithelial cells. It was 
 first found in large quantities by Miiller in the urine of 
 leukemia, and afterward by Malfutti and others in diphtheria, 
 scarlatinal nephritis, cystitis, and after the use of pyrogallic 
 acid, naphthol, and corrosive sublimate. It was also 
 observed by Obermayer in the urine of a case of acute 
 atrophy of the liver. Ott found it in abnormal quantities 
 in the urine during high fever. Nucleo-albumin is always 
 present in increased quantities in urine that contains bile. 
 
 Detection. — For the detection of nucleo-albumin the 
 urine is treated with an excess of acetic acid, when it is
 
 142 ABNORMAL CONSTITUENTS OF URINE. 
 
 rendered turbid if much of this proteid be present. In 
 testing a concentrated urine for nuclco-albumin it is advis- 
 able to dilute it before acidulating, on account of the high 
 proportion of salts, which retain nucleo-albumin in solution 
 even in the presence of an excess of acetic acid. In testing 
 for the presence of nucleo-albumin in an albuminous urine 
 it is necessary first to remove, by boiling, the great bulk 
 of the serum albumin, and any serum globulin present. 
 The fluid is then filtered, and allowed to cool before testing 
 with acetic acid. 
 
 Ott's method for the detection of nucleo-albumin is 
 very serviceable : To the urine add an equal quantity of 
 saturated salt solution (NaCl), and then Almen's tannin 
 solution 1 is slowly added. If nucleo-albumin be present, 
 even in small amounts, an abundant precipitate will fall. 
 
 Von Jaksch recommends for the precipitation of nucleo- 
 albumin a solution of acetate of lead. 
 
 HEMOGLOBIN. 
 
 Hemoglobin is the pigment of the red blood-corpuscles. 
 It gives the reactions of a proteid, but differs from proteids 
 in containing iron and in being crystallizable. It belongs 
 to the group of compound proteids, and yields as cleavage 
 products, besides very small amounts of volatile fatty acids 
 and other bodies, chiefly /n^toV/ (96 per cent.) and a color- 
 ing-matter, licnwchroDwgen (4 per cent.) containing iron, 
 which in the presence of oxygen is readily oxidized into 
 hcniatiii (Hammarsten). 
 
 Hemoglobin is found in two forms — /. c. {a), oxyhemo- 
 globin, that charged with oxygen and found in arterial 
 blood, and presenting, in dilute solutions, two absorption 
 bands between Frauenhofer's lines D and E ; and {b), reduced 
 licjnoglobin, that deprived of its oxygen and found in venous 
 blood, and presenting a single absorption band between 
 D and E, occupying a space about midway between the two 
 bands of oxyhemoglobin. 
 
 For further details concerning this subject see page 230. 
 
 ^ Aln!en''s iannin solution consists of: Tannin, 5 grams; 25 per cent, 
 acetic acid, loc.c. ; 40 to 50 per cent, methylated spirit, 250 c.c.
 
 FIBRIN. 143 
 
 FIBRIN. 
 
 Fibrin is the albuminous body that separates on the 
 so-called spontaneous coagulation of blood, lymph, and 
 transudations, as also on the coagulation of a fibrin- 
 ogen solution after the addition of blood-serum or the 
 fibrin ferment. It is an elastic, white, stringy substance, 
 which is insoluble in water, ether, and alcohol. It is sol- 
 uble with difficulty in solutions of sodium chloride (5 to 15 
 per cent.), in solutions of potassium nitrate (6 per cent.), 
 and in solutions of magnesium sulphate (5 to 10 per cent.). 
 The substance that goes into solution when fibrin is dis- 
 solved in saline solutions is undoubtedly a proteid of the 
 globulin class. It is coagulated by heat, precipitated from 
 its solutions by saturating them with magnesium sulphate, 
 and also by dialyzing away the salt from such solutions. 
 The temperature of coagulation is 60° to 75° C. in a 
 sodium chloride solution, and y^° to 75° C. in a magnesium 
 sulphate solution. Weak hydrochloric acid (0.2 per cent.) 
 causes fibrin to swell up into a transparent jelly. Fibrin is 
 slowly dissolved by the strong acids, with the formation of 
 acid albumin or syntonin, and albumoses. Fibrin is readily 
 digested by pepsin in the presence of hydrochloric acid 
 (0.2 per cent.), and by the pancreatic juice, with the result- 
 ing formation of albumoses and peptone. Fibrinogen, 
 which has also been found to have the properties character- 
 istic of globulin, is the fibrin-precursor in blood plasma. 
 
 Clinical Significance. — Fibrin most commonly appears 
 in the urine as an accompaniment of blood, whether the 
 blood comes from the kidneys or some other part of the 
 urinary tract. Usually, if there is an extensive hemorrhage 
 into the urinary tract, fibrin is abundant, and, on the other 
 hand, if only little blood is present, the quantity of fibrin is 
 small. But fibrin may be present in the urine when blood- 
 corpuscles are absent ; thus, the so-called coagnlable tirinc, 
 which, upon standing some time, forms the fibrinous 
 coagula. The extent of coagulation depends upon the 
 quantity of fibrin present ; sometimes only a sticky sedi- 
 ment forms in the bottom of the sediment-glass ; more 
 rarely, the urine is converted into a gelatinous mass. 
 
 Detection, — Fibrin is insoluble in water ; it is also insol- 
 uble in sodic hydrate, in which respect it differs from albu- 
 minous substances. If washed, fibrin is dissolved in a solu-
 
 144 ABNORMAL CONSTITUENTS OF URINE. 
 
 tion of sodic carbonate (one per cent.) with the aid of gentle 
 heat, and its solution gives the xanthoproteic and Millon's 
 reaction for proteids. It is readily digested by artificial 
 gastric juice. 
 
 Fibrin should not be mistaken for the grayish, ropy mass 
 that usually forms in purulent, alkaline urines, alkaline 
 from the ammonia and ammonium carbonate resulting from 
 the decomposition of the urea. (See p. 237.)
 
 CHAPTER V. 
 
 CARBOHYDRATES. 
 
 The carbohydrates, which are either normally or abnor- 
 mally present in urine, resemble one another in a few of 
 their chemic characteristics. All are hydrocarbons con- 
 taining six atoms of C, or a multiple thereof; excepting 
 inosite, all have a strong rotary power over polarized light, 
 are soluble in water, and have a neutral reaction. 
 
 Normal urine under physiologic conditions contains a 
 small amount of carbohydrates, among which are animal 
 gum and also grape-sugar, but in amounts which can 
 not be recognized by the ordinary sugar reactions. The 
 glucoside — mucin — increases the proportion of carbohy- 
 drates in the urine. 
 
 Glucose, lactose, levulose, cane sugar, inosite, glyco- 
 gen, and the like are not infrequently found abnormally in 
 amounts sufficient to respond to certain chemic tests, and 
 under such circumstances they are of pathologic interest. 
 The most important of these, from a clinical point of view, 
 isglucose. 
 
 GLUCOSE. 
 
 CoH].,Oa. 
 
 (Diabetic Sugar, Dextrose, Grape-sugar.) 
 
 Careful chemic examinations have shown it to be highly 
 probable that normal urine contains traces of sugar. ^ 
 Under pathologic conditions glucose is present either 
 temporarily — glycosuria — or permanently — diabetes mej- 
 litus. (See Diabetes Mellitus, p. 368.) 
 
 Glucose crystallizes in colorless, transparent prisms, 
 which collect in bundles or in hard, tenacious crusts. It is 
 soluble in its own weight of water, slightly soluble in cold 
 
 ^ Neubauer and Vogel, " Analyse des Hams," Bd. i, 1898, S. 62. 
 10 145
 
 146 ABNORMAL CONSriTUENTS OF URINE. 
 
 alcohol, more readily in hot alcohol, and insoluble in ether. 
 Animal charcoal extracts it from its solutions (Bence Jones ^ 
 and Seegen^). Solutions of glucose turn the rays of polar- 
 ized light to the right (dextrose), and, according to the last 
 accurate determinations of ToUens, ^ the specific rotation of 
 the aqueous solution was found to be + 52.5°. In alka- 
 line solutions it reduces the salts of copper, bismuth, 
 mercury, and silver ; in the copper tests the cupric oxide 
 is reduced to cuprous oxide (suboxide of copper). Glu- 
 cose forms an osazone with phenylhydrazin, — phenylgluco- 
 sazone (Plate 4), which crystallizes in highly characteristic 
 groups of yellow needles. 
 
 Isolation. — Grape-sugar may be separated from the 
 urine in a number of ways, but the most practical method 
 is that advised by Salkowski.^ 
 
 Salkowskis Method. — Take 20 c.c. of urine and add 
 10 c.c. of a 1.6 normal solution of copper sulphate (with 
 199.52 grams of copper sulphate to the liter), and 17.6 c.c. 
 of normal sodic hydrate. After twenty to thirty minutes, 
 dilute with 100 c.c. water, and filter. When the fluid has 
 passed through, the filter-paper is immediately placed on 
 bibulous paper and entirely freed from the rest of the fluid. 
 The precipitate is then dissolved in 50 c.c. of dilute hydro- 
 chloric acid (i of hydrochloric acid, specific gravity 1 120, to 
 10 of water), the copper removed by sulphureted hydro- 
 gen, the filtrate exactly neutralized with sodic carbonate, 
 and evaporated to 20 c.c. This fluid is then to be tested 
 for sugar, either qualitatively or quantitatively. Salkowski 
 claims that 0.5 per cent, of sugar can be detected in urine 
 in this way. Einhorn has detected as little as 0.05 per cent, 
 of sugar by this method. 
 
 Detection of Sugar in Urine. — The copper tests, which 
 depend upon the power that grape-sugar possesses in alka- 
 line solution of reducing the oxide of copper to lower 
 oxides, are perhaps more commonly used than all others 
 for the detection of sugar in the urine. It is safe to say 
 that they are the most convenient and rapid of all tests that 
 are capable of being applied by the student and practitioner 
 of medicine. 
 
 1 '• Lancet," I, l86l, No. 3. 
 
 2 "Pfiuger'.s Archiv," V, 375, 1872. 
 
 3 " BericlUe der chem. Gesell.sch.," xvu, 2234, 1884. 
 *"Zeitschr. f. physiol. Ch.," \\\, 96, 1879.
 
 GLUCOSE. 147 
 
 The oldest of the copper tests is Trommer's, in which 
 the hydrate of copper is set free at the time of its apphca- 
 tion by an excess of sodic or potassic hydrate. 
 
 Trommer's Test. — i. Take a third of a test-tube of 
 urine, render alkahne with sodic or potassic hydrate. To 
 this mixture then add, drop by drop, a weak solution (five 
 per cent.) of sulphate of copper, shaking the mixture after 
 each addition, until a deep-blue solution is obtained, or until 
 the cupric hydrate, which forms as the copper is added, fails 
 to dissolve. The upper one-half of the mixture is then 
 boiled, and if sugar be present, a yellow precipitate of sub- 
 oxide of copper soon forms. 
 
 2. A second similarly prepared mixture of these ingre- 
 dients may be made and set aside for from six to twenty- 
 four hours without the addition of heat. If sugar be 
 present, a similar precipitate of cuprous oxide will take 
 place. If the reaction, with heat, is at all doubtful, it is 
 important that this control-test should be made, since, as 
 Neubauer has pointed out, most of the organic substances 
 that reduce copper do so only when heated or after pro- 
 longed boiling. 
 
 Fehling's Test. — This test is performed by the use of 
 Fehling's solution, which is prepared according to the 
 original fonmila, as follows : Pure crystallized cupric sul- 
 phate, 34.639 grams ; a solution of caustic soda, — specific 
 gravity 1120, — about 500 c.c. ; chemically pure crystallized 
 neutral sodic tartrate, 173 grams. Prepare by dissolving 
 the sulphate of copper in 100 c.c. of distilled water; next 
 dissolve the neutral sodic tartrate in the solution of caustic 
 soda, and add the copper solution, little by little ; finally, 
 bring the whole volume to 1000 c.c. (i liter) with distilled 
 water. Ten cubic centimeters of this solution require 50 
 milligrams of sugar to completely reduce it. 
 
 It is a well-known fact that Fehling's solution prepared 
 in the manner described soon decomposes on standing, 
 and therefore becomes unfit for use. Furthermore, it has 
 been found (Soxhlet) that the solution as previously given is 
 too concentrated to obtain a delicate reaction. The folloiv- 
 ing modificatioi of Fchling' s solution is tJwrcfore nroiu- 
 mendcd for the purpose of obtaining a permanent solution, 
 and one which also furnishes a rapid and yet delicate reac- 
 tion. The solution is divided into two parts — viz., copper 
 solution (A) and alkaline tartrate solution (B).
 
 148 ABNORMAL CONSTITUENTS OF URINE. 
 
 A. Cupric sulphate 34.639 grams. 
 
 Distilled water ad 1000 c.c. 
 
 B. Sodio-potassium tartrate (Rochelle salt) . 173 grams. 
 Sodic hydrate (specific gravity Il20)i . . 500 c.c. 
 Distilled water ad 1000 '• 
 
 These solutions — A and B — are to be kept in separate 
 bottles and in a dark place. Equal parts of the two solu- 
 tions produce diluted Fehling's solution. It will be seen 
 that the combined volume of the two solutions amounts to 
 2000 c.c, or one-half the strength of the solution of the 
 original formula. Therefore, 20 c.c. of the combined mix- 
 ture (10 c.c. of each) require 50 milligrams of sugar to 
 completely reduce it. 
 
 Process. — Qualitative Test. — Take equal parts of the 
 two solutions — A and B, about one fingerbreadth of 
 each — in a test-tube, and boil. If the Fehling's solution 
 remains clear on boiling, then add 20 to 30 drops of the 
 suspected urine which is free from albumin. Do not boil 
 after the addition of the urine. If much sugar be pres- 
 ent, a yellow or red precipitate of suboxide of copper 
 readily appears. In case the quantity of sugar in the urine is 
 less than i per cent, the reduction will not appear until after 
 several minutes — five to thirty. If a reduction does not 
 take place in thirty minutes, it is advisable to let the test 
 stand for from eighteen to twenty -four hours, since traces 
 of sugar show evidence of a reduction of the copper only 
 after several hours, when a small amount of the suboxide 
 will be found in the bottom of the test-tube. Less time is 
 required for the test if the urine is gently heated previous 
 to its being added to the boiling Fehling's solution. The 
 nonappearance of a suboxide precipitate shows that the 
 urine is free from sugar. 
 
 In the hands of the author Fehling's test, performed in 
 the manner previously indicated, is one of the most delicate 
 and reliable tests available for routine work. The phenylhy- 
 drazin test is more delicate than Fehling's, but is less suit- 
 able for routine examinations on account of the length of 
 time required for the performance of the test. (See p. 
 150.) 
 
 If the two solutions, which constitute Fehling's solution, 
 are kept in separate bottles and mixed at the time they are 
 
 ^ Sodic hydrate, having a specific gravity of 1 120, is prepared as follows: 
 Caustic soda, 52.727 grams ; distilled water, sufficient to make 5cx) c.c.
 
 GLUCOSE. 149 
 
 to be used, there need be no fear that the solutions will 
 decompose, even after keeping them several months. 
 
 Professor Haines, of Chicago, has advised a modification 
 of Fehling's solution,^ and claims that the solution prepared 
 according to his formula is stable, and, although kept on 
 hand indefinitely, it may always be depended upon to be 
 in good order for testing. 
 
 Haines' Test {Simplified Foruiuhx). — Take pure copper 
 sulphate, 30 grains ; distilled water, ^^ of an ounce ; make a 
 perfect solution, and add pure glycerin, y^ of an ounce ; 
 mix thoroughly, and add 5 ounces of liquor potassse. In 
 testing with this solution take about i dram and gently boil 
 it in an ordinary test-tube. Next add 6 to 8 drops (not 
 more) of the suspected urine, and again gently boil. If 
 sugar be present, a copious yellow or yellowish-red precipi- 
 tate separates ; if no such precipitate appears, sugar is absent. 
 
 On account of the decomposition of Fehling's solution 
 on standing, Schmiedeburg has suggested the substitution 
 of I 5 grams of pure maiinite for the neutral sodic tartrate 
 of Fehling's solution. The mannite should first be dis- 
 solved in 100 c.c. of distilled water, then 500 grams of the 
 solution of caustic soda, specific gravity 1 140, should be 
 added, and the solution completed according to the original 
 formula for Fehling's solution. 
 
 With the same end in view 173 grams of pure glycerin 
 have likewise been substituted for the neutral sodic tartrate 
 of Fehling's solution. 
 
 When the proper precautions are observed, reliable re- 
 sults may be expected with Fehling's solution, with saccha- 
 rine urine which contains about -^-^ of i per cent, of sugar. 
 
 Precautions and Errors. — These are applicable to all cop- 
 per tests : 
 
 1. If the urine contains more than a trace of albumin, it 
 must be removed, as it interferes with the reduction of the 
 oxide of copper. 
 
 2. When the mixture of urine and reagent is allowed to 
 stand several hours without boiling, a considerable quantity 
 of sugar is necessary before a satisfactory reaction occurs. 
 
 3. The mixed urine and reagent should never be heated 
 or boiled, since, as already stated, there are often organic 
 substances other than sugar in the urine, which have, in the 
 
 ^ Purely, " Practical Urinalysis," p. 103.
 
 150 ABNORMAL CONSTITUENTS OF URINE. 
 
 presence of heat, a reducing; action on an alkaline solution 
 of cupric oxide. These substances are uric acid, urates, 
 kreatinin, hippuric acid, mucin, hypoxanthin, glycuronic 
 acid, alcapton, alkaloids, arsenic, and carbolic acid. Uric 
 acid is the chief source of error, and should always be 
 b(jrne in mind in the use of the copper tests. 
 
 4. The flocculent precipitate of earthy phosphates that is 
 thrown down by the alkaline hydrate should not be mis- 
 taken for the suboxide of copper. Such a precipitate is 
 either colorless or of a greenish hue. 
 
 5. Decolorization of the reagent by the urine should not 
 be mistaken for a reduction of the copper. There must be 
 an actual yellow or red precipitate. Any highly acid 
 normal or pathologic urine may have a decolorizing action 
 on the copper reagent. 
 
 6. Too strong a solution of copper should not be used, 
 since, in the presence of heat, a yellow or greenish-yellow 
 color is often produced. This color may not appear until 
 the mixture has cooled. 
 
 Phenylhydrazin Test- — The phenylhydrazin test for 
 sugar is applied as follows : To 50 c.c. of the suspected 
 urine add i or 2 grams of hydrochlorate of phenyl- 
 hydrazin, 2 grams of sodium acetate, and heat on a 
 water-bath for one hour ; or add 10 to 20 drops of pure 
 phenylhydrazin and an equal number of drops of 50 per 
 cent, acetic acid, and heat as before. On cooling, if not 
 before, pJioiylghicosazonc separates out as a crystalline or 
 amorphous precipitate. If upon microscopic examination 
 the precipitate is found to be amorphous, it is dissolved in 
 hot alcohol, and the solution diluted with water, and boiled 
 to expel the alcohol, whereupon the compound is obtained 
 in the characteristic form of yellow needles. It is claimed 
 that by this method it is possible to obtain the crystals from 
 a urine that contains only o. 5 gram of sugar per liter, or 
 0.05 per cent. 
 
 Williamson has modified the phenyl h)'drazin test for 
 sugar, as described in the work on urinary analysis by 
 Hoffmann and Ultzmann, and has found it very useful. 
 
 Williamson's Test.^ — "A test-tube of ordinary size is 
 filled for about half an inch with hydrochlorate of phenyl- 
 hydrazin (in powder) ; then acetate of soda in powder (or 
 
 1 Williamson," Diabetes Mellitus and its Treatment," 1898, p. 25.
 
 Plate 4 
 
 Crystals of PiiKNYLGLacosAZONE (after vonJaksch).
 
 GLUCOSE. 151 
 
 small crystals) is added for another Jialf-iiicJi. Tlie test- 
 tube is then half filled with urine, and boiled over a spirit- 
 lamp. In performing the test I have not attempted to dis- 
 solve the salts by shaking the tube, but have simply applied 
 the flame of the lamp to the bottom of the tube, and the 
 powders have soon passed into solution. After the urine 
 has reached the boiling-point I have always continued to 
 boil for about tzvo viimitcs. The tube is then left in the 
 test-stand, and examined again some time afterward." 
 
 If sugar be present, a yellowish deposit forms at the 
 bottom of the tube, and on microscopic examination it is 
 seen to consist chiefly of beautiful needle-shaped crystals 
 of a bright sulphur-yellow color. If no sugar is present, 
 only brownish amorphous globules or yellow scales are 
 found in the deposit. By performing the test in this simple 
 manner Williamson ha-s never obtained any ciystals of 
 phenylglucosazone in normal urine. 
 
 Much discussion has arisen concerning the proper method of 
 performing this test for sugar. According to Hirschl,^ if a mix- 
 ture be left on a water-bath for a shorter time than one hour, a 
 glycuronic acid compound (melting-point, 150° C.) is formed, 
 which is liable to be mistaken for phenylglucosazone. On the 
 other hand, it has been pointed out by a number of observers 
 that if the mixture be kept on a water-bath for as long a period 
 as one hour, a small deposit of the crystals may be obtained in 
 many normal urines. These crystals are frequently of a doubt- 
 ful nature, even after they have been dissolved in hot alcohol 
 andrecrystallized. 
 
 According to Fisher, the reaction which takes place be- 
 tween phenylhydrazin and glucose is represented by the 
 following equation : 
 
 CeHpPe + 2CeH5 . N2H3 = CiaH^.N^O, + 2H,0 + 2H. 
 
 A great advantage of the phenylhydrazin test for sugar 
 is that it gives no reaction with uric acid, kreatinin, hip- 
 puric acid, pyrocatechin, etc., while wath Fehling's test, as 
 ordinarily applied (boiling the urine and F"ehling's solution 
 together), these substances are often a source of fallacy. 
 
 Plicnylglucosazone (C^H.^N^O^) cr>'stallizes in bright, fine, 
 yellow needles (see Plate 4), which are arranged singly 
 or in stellate groups. They are almost insoluble in water, 
 
 1 " Zeitschr. f. physiol. Ch.," xiv, 377.
 
 152 ABNORMAL CONSTITUENTS OF URINE. 
 
 but dissolve in boiling alcohol, and melt at 204° to 
 205° C. 
 
 Fermentation Test. — The fermentation test is an excel- 
 lent and reliable one for the detection of sugar (glucose) in 
 all cases in which the urine contains more than ^ of i 
 per cent, of sugar. The test depends upon the fermenta- 
 tion of the sugar by means of yeast, yielding alcohol, car- 
 bon dioxide, and various other less important substances, 
 vi'ith a resulting decrease in the specific gravity. The fol- 
 lowing equation represents the reaction which takes place : 
 
 C6H,A = 2C2H,0 + 2CO,. 
 
 The most convenient method of applying this test is as 
 follows : Take a test-tube, preferably one of large diameter, 
 introduce into it a piece of compressed yeast about the 
 size of a pea, and fill the test-tube to the top with the 
 urine to be tested. Stopper tightly with a rubber cork 
 having a single perforation, through which a glass tube is 
 passed so that it reaches nearly to the bottom of the test- 
 tube. Above the cork the glass tube is bent at right 
 angles to the perpendicular of the test-tube, and some four 
 inches from this bend the tube is again given a right- 
 angled bend downward. A receptacle is then placed 
 under the end of the glass tube. 
 
 If sugar is present, evidences of fermentation will pre- 
 sent themselves, generally within twelve hours, by the for- 
 mation of carbon dioxide which rises to the surface of the 
 urine, but, being held in by the cork, forces the urine out 
 through the bent glass tube into the receptacle at the end 
 of the tube. Sufficient carbonic acid gas is usually obtained 
 from highly saccharine urines to force out all of the urine 
 in the test-tube. The test should be subjected to a tem- 
 perature of 80° to 90° F. 
 
 This test can not be relied upon if less than j^ per cent, 
 of sugar is present, since a small quantity of carbon dioxide 
 is likely to be absorbed by the urine (water will absorb an 
 equal volume of carbonic acid gas). 
 
 In the performance of this test it should be borne in 
 mind that some specimens of yeast spontaneously evolve 
 gas, and it is, therefore, best to perform with each urine 
 tested a control experiment with yeast mixed with water 
 instead of urine, in order to judge of the amount of gas in 
 the yeast itself.
 
 GLUCOSE. 153 
 
 The chief disadvantage of the fermentation test is that it 
 requires several hours for its completion, and it is therefore 
 not practical for routine work. 
 
 Bismuth Tests. — These tests depend upon the power 
 that sugar (glucose) possesses of reducing the salts of 
 bismuth, with a resulting black precipitate of metallic 
 bismuth. 
 
 (a) Botiger's Test. — Take one-fourth of a test-tube of the 
 suspected urine, add an equal volume of potassic hydrate 
 (liquor potassae, U. S. P.), or a solution of sodic carbonate 
 (i part of crystals to 3 parts of distilled water), mix, and 
 add a small amount of subnitrate of bismuth. Shake, and 
 boil the whole mixture, and if sugar be present, a black 
 precipitate appears, which clings to the sides of the test- 
 tube. A gray, instead of a black, precipitate is obtained if 
 the quantity of sugar is small, in which case a smaller 
 amount of bismuth should be used in making the test. 
 According to Tyson, this gray precipitate, said to be char- 
 acteristic of small quantities of glucose, sometimes presents 
 itself when no sugar is present. 
 
 The urine to be tested should be free from albumin and 
 other substances containing sulphur, since traces of sulphur 
 combine with the bismuth salts to form bismuth sulphide, 
 which is likely to be mistaken for metallic bismuth. To 
 obviate this difficulty, Brijcke has suggested the following : 
 
 {6) Bruckc's Alodification of Bottgcr' s Test. — Frohn's 
 reagent ^ is recommended for the removal of the sulphur 
 compounds in the following way : Pour into a test-tube a 
 certain quantity of water, say 10 c.c, and fill another tube 
 to the same level with the suspected urine. To the first 
 add a drop of Frohn's reagent, which will cause a pre- 
 cipitate. Then add, drop by drop, concentrated hydro- 
 chloric acid until the precipitate is redissolved. In this 
 way the approximate quantity to be added to the suspected 
 urine is ascertained. Acidulate the urine in the other test- 
 tube with the same quantity of hydrochloric acid ; treat it 
 with the reagent until precipitation is complete, and filter. 
 The filtrate, which should not be rendered turbid on the 
 further addition of hydrochloric acid or the reagent, is 
 thoroughly boiled with an excess of sodic or potassic 
 
 1 Frohn's reagent : 1. 5 grams of freshly precipitated bismuth subnitrate are 
 mixed with 20 grams of water, and heated to boiling ; then 7 grams of potas- 
 sium iodide and 20 drops of concentrated hydrochloric acid are added.
 
 154 ABNORMAL CONSTITUENTS OF URINE. 
 
 hydrate, as in Bottger's test. If a gray or black precipitate 
 or color is formed, sugar is present. Brucke claims that 
 this test will detect 0.4 per cent, of glucose in water. 
 
 (r) Ny lander's Test. — Almen's fluid is used. It consists 
 of 4 grams of Rochelle salt (sodio-potassic tartrate), dis- 
 solved in 100 c.c. of a 10 per cent, solution of caustic soda. 
 The fluid is warmed, and 2 grams of subnitrate of bismuth 
 are added. One volume of this fluid is added to 10 volumes 
 of urine, and the mixture heated. In a few minutes (three 
 to five) it will become black if sugar be present. The reac- 
 tion will indicate the presence of at least o. i per cent, of 
 sugar. This test is not applicable to albuminous urines, and 
 the reaction occurs in the presence of melanin or melanogen, 
 or when the fluid is rich in reducing substances other than 
 sugar. 
 
 Methylene-blue Test. — Methylene-blue is decolorized 
 by glucose in a warm alkaline solution. In performing 
 the test the diabetic or suspected urine is diluted (i part to 
 9 of water). Of this diluted urine 2 c.c. are mixed with 
 6 c.c. of a I : 3000 solution of methylene-blue, and 2 c.c. 
 of potassic hydrate are then added. The mixture is boiled 
 for one or two minutes, when the blue color disappears if 
 sugar be present. Care must be taken that the fluid is 
 shaken as little as possible, since the blue color returns 
 easily, owing to the action of the oxygen in the air. It is 
 important to dilute the urine, as all undihitcd urine dis- 
 charges the blue color ; but normal urine diluted i : 9 of 
 water does not decolorize methylene-blue. 
 
 Williamson has found that a distinct reaction is obtain- 
 able by this method when diabetic urine is diluted until the 
 percentage of sugar is only 0.07, but when further diluted, 
 until it is 0.014, "o reaction is obtained. Urines rich in 
 urates give a doubtful reaction when diluted i : 9. Since 
 urine often contains reducing substances other than sugar, 
 Frohlich ^ recommends that it be treated first with 5 c.c. 
 of a concentrated solution of lead acetate, and with 5 c.c. 
 of a solution of basic acetate of lead ; then take an equal 
 quantity of the filtrate and a concentrated solution of 
 methylene-blue (i : 300), add potassic hydrate, and boil, as 
 previously indicated. This test is not so satisfactory as the 
 phenylhydrazin or the P'ehling test. 
 
 1 "Centralbl. f. inn. Med.," 1898, No. 4.
 
 GLUCOSE. 155 
 
 Numerous other tests have been suggested for the de- 
 tection of sugar in urine. The following may be men- 
 tioned : Diazobenzolsulphonic acid (Penzoldt), picric acid 
 (Johnson), sodium or potassium hydrate and heat (Moore), 
 acetate of lead and ammonia (Rubner), alpha-naphthol and 
 thymol (Molisch), and indigo-carmine (Mulder). Most of 
 the above-named tests are greatly inferior to those that 
 have been described. 
 
 Quantitative Determination of Sugar in Urine. — A 
 quantitative determination of the sugar should be made in 
 all cases in which it has been detected. It is only by a 
 knowledge of the quantity of sugar present that a diag- 
 nosis of the condition can be made, the severity of the dis- 
 ease ascertained, and the results of treatment judged. The 
 twenty-four-hour quantity of urine should be accurately 
 kept, and while it is being collected, put in a cool place to 
 prevent fermentation. The entire secretion for the twenty- 
 four hours should then be thoroughly mixed and measured, 
 and a sample of this taken for the determination. The 
 urine obtained at a single micturition should not be used 
 for the quantitative test, for the reason that there is consid- 
 erable variation in the quantity of sugar eliminated : ac- 
 cording to the time of day, and the length of time after a 
 meal. 
 
 The total quantity in grams should in every instance be 
 calculated. A knowledge of the percentage of sugar alone 
 is never sufficient, for the percentage in itself means little if 
 the total quantity is not determined. In routine work the 
 percentage is usually obtained, but only for the sake of 
 convenience in figuring the total number of grams of sugar. 
 ' Fehling's Test. — This is one of the most practical 
 quantitative tests for sugar in urine, and is conducted by 
 the titration method, using the modified Fchling s solution, 
 the formula of which is given on page 148. 
 
 The process depends upon the fact that the blue color 
 disappears, and that the copper is completely precipitated 
 from a definite quantity of Fehling's solution by a given 
 amount of grape-sugar ; thus, every 20 c.c. of the Fehling's 
 solution used require 50 milligrams of sugar to completely 
 reduce it. 
 
 Necessary Apparatus (Fig. 17). — A Florence flask of 
 250 c.c. capacity ; a common retort-stand with a burette- 
 holder attachment, and with a piece of copper- or iron-wire
 
 156 
 
 ABNORMAL CONSTITUENTS OF URINE. 
 
 gauze that is large enough to cover one of the rings of 
 the stand (a tripod, the top of wjiich is covered with cop- 
 per-wire gauze, may be conveniently used) ; a 25- or 50-c.c. 
 burette, which is graduated to tenths of a cubic centimeter ; 
 a lo-c.c. pipette; a loo-c.c. glass-stoppered graduate; and 
 a Bunsen burner or a large spirit-lamp. 
 
 
 
 Fig. 17. — Apparatus for the quantitative estimation of sugar : wi, Meniscus. 
 
 The analysis should be conducted as follows : First take 
 the specific gravity of the urine to be tested, then test for 
 albumin, — preferably by the nitric acid test, — and if more 
 than a trace be present, remove it according to the directions 
 given on page 129.
 
 GLUCOSE. 157 
 
 If the specific gravity of the urine is more than 1030, dilute 
 it I : 10 witii distilled water (urine, i ; water, 9) ; \i less than 
 1030, dilute it I : 5 (urine, i ; water, 4). Mix thoroughly, 
 and pour the diluted urine into the burette, filling it to the 
 zero mark, care being taken to expel all air from below the 
 stop-cock. Next take 10 c.c. of each of the solutions A 
 and B by means of the lO-c.c. pipette, and place in the 
 250-c.c. flask. Add 60 c.c. of distilled water, making the 
 entire volume amount to 80 c.c. Place the flask on the 
 wire gauze, and boil the mixture. After the diluted Feh- 
 ling's solution has boiled for a short time, — say for two or 
 three minutes, — and it is found that the solution does not 
 show evidences of reduction, the diluted urine is added, 
 drop by drop, from the burette into the Fehling's solution, 
 which is kept boiling. When, on removing the flame, after 
 a series of observations, it is found that the meniscus has 
 lost its blue color and has become colorless, ^ the reaction 
 is complete. 
 
 The inenisais (Fig. 17, ;//), which is seen as a clear line 
 (blue at first and later colorless), is best detected by plac- 
 ing the flask between the eye and the light. As the eye is 
 raised and lowered, this clear line will be seen just beneath 
 the surface of the fluid. 
 
 The blue color having disappeared from the mixture, the 
 number of cubic centimeters of diluted urine employed is 
 read off. Since it takes just 50 milligrams (0.050 gram) 
 of sugar to completely reduce the cupric oxide in the 20 
 c.c. of Fehling's solution used, the percentage of sugar in 
 the urine may be readily calculated, and from the per cent., 
 the number of grams of sugar eliminated in twenty-four 
 h,ours. 
 
 Example : If 15 c.c. of diluted urine were necessary to 
 complete the test, and the urine was originally diluted i : 
 10, then 15 H- 10= 1.5 c.c. of undiluted urine. Since 1.5 
 c.c. of undiluted urine reduced the copper, and 50 milli- 
 grams of sugar accomplish the same end, then 1.5 c.c. of 
 urine must contain 50 milligrams of sugar. The percent- 
 age is obtained according to the following proportion : 
 
 1.5 : 0.050 : : ICO : x 
 X ---= 3 yi per cent. 
 
 ' When the test solution is allowed to stand for a short time after the test has 
 been completed, it again becomes blue, due to the reoxidation by the oxygen 
 from the air. This should not be mistaken for an incomplete reduction.
 
 158 ABNORMAL CONSTITUENTS OF URINE. 
 
 Suppose the total quantity of urine in twenty-four hours 
 amounted to 2000 c.c, then ^^ = 66.6 grams, ^ the 
 
 ' 100 O ' 
 
 quantity of sugar in twenty-four hours. 
 
 Precautions : i. The urine should be added to the boil- 
 ing Fehling's solution, drop by drop, in order to obtain a 
 suboxide precipitate that will settle in a very short time. 
 If a considerable quantity of the urine is added at a time, 
 the precipitate will not settle well, and the meniscus can 
 not be distinctly seen. 
 
 2. A yellow color to the meniscus or to the body of 
 the solution, besides that produced by the suboxide pre- 
 cipitate, indicates that too much of the saccharine urine 
 has been added, and that the end reaction has passed. A 
 new titration is then necessary. 
 
 3. The Fehling's solution should be kept at the boiling 
 temperature, except during the time required for observing 
 the meniscus. As soon as the solution cools, reoxidization 
 of the copper begins, and consequently the blue color 
 reappears. 
 
 Purdy's Method. — The following modification of Feh- 
 ling's method is advised by Dr. Purdy, who claims that by 
 the use of his solution various defects of Fehling's method 
 are overcome : 
 
 Take of pure cupric sulphate, 4.752 grams; potassium 
 hydroxide, 23.5 grams ; strong ammonia (U. S. P. — specific 
 gravity 0.9) 350 c.c. ; glycerine (C.P.), 38 c.c. ; distilled 
 water, to make lOOO c.c. 
 
 Prepare by dissolving the cupric sulphate and glycerine 
 in 200 c.c. of distilled water with the aid of gentle heat. 
 In another 200 c.c. of distilled water dissolve the potassium 
 hydrate, mix the two solutions, and, when cool, add the 
 ammonia. Finally, with distilled water bring the volume 
 of the whole to exactly lOOO c.c. Thirty-five cubic centi- 
 meters of this solution are reduced, upon boiling, by 
 exactly 2 centigrams (0.02 gram) of grape-sugar. 
 
 Proceed by accurately measuring 35 c.c. of the solution 
 into the flask, dilute with about two volumes of distilled 
 
 ' .Since this iiielluxl of lii;uring is based on the supposition tlmt i c.c. is 
 equal to i gram, the same as distilled water, it can not rightly be applied to 
 urine, l c.c. of which weighs more than I c.c. of distilled water ; therefore, the 
 figures 66.6 represent only the approximate quantity of sugar. Accurate figures 
 may be obtained by correcting for the difference between the specific gravity 
 of the urine tested and that of distilled water.
 
 GLUCOSE. 159 
 
 water, and bring the whole thoroughly to the boiling-point. 
 Fill the burette to the zero mark with the urine to be tested, 
 and slowly discharge the urine into the boiling test solution, 
 drop by drop, until the blue color begins to fade ; then, 
 still more slowly, three to five seconds elapsing after each 
 drop, until the blue color completely disappears and the 
 test solution is left perfectly colorless and transparent. The 
 number of cubic centimeters required to discharge the blue 
 color in 35 c.c. of the test solution contains exactly 2 centi- 
 grams (0.02 gram) of sugar. 
 
 If 35 c.c. of the test solution are reduced by 2 c.c. of 
 urine, then i : 0.02 : : 100 : x, and x = i per cent, of 
 sugar; reduced by i c.c, 2 per cent.; reduced by ^ of a 
 cubic centimeter, 3 per cent. ; reduced by ^ of a cubic 
 centimeter, 4 per cent. ; reduced by ^ of a cubic centimeter, 
 8 per cent. 
 
 If absolute accuracy of results is desired, it is better to 
 dilute the urine to be tested with 2 volumes of distilled 
 water, and divide the product by 3 ; especially if the per- 
 centage of sugar is high. 
 
 The advantages claimed by Purdy for this test are (i) 
 its perfect end-reaction ; (2) the stability of the solution ; 
 (3) its rapidity of application, only requiring about five 
 minutes, and (4) its accuracy. 
 
 Fermentation Test. — The fermentation test for sugar 
 can not be considered an accurate quantitative test, although 
 it may be used with advantage for determining the approxi- 
 mate quantity of sugar present. The method suggested by 
 Roberts is as follows : Four ounces of the saccharine 
 urine are placed in a twelve-ounce bottle, and a piece of 
 cornpressed yeast is added. The bottle is then stoppered 
 with a nicked cork to permit the escape of the carbonic acid 
 gas, and set aside in a warm place to ferment. Beside it 
 is placed a tightly corked four-ounce bottle filled with the 
 same urine, but without any yeast. In from eighteen to 
 twenty-four hours fermentation will have ceased. The fer- 
 mented urine is then decanted into a urinometer-glass, and 
 the specific gravity taken. The specific gravity of the un- 
 fermented urine in the other bottle is taken at the same 
 time, and the loss of density ascertained. Roberts has 
 shown that every degree in the specific gravity lost in 
 fermentation corresponds approximately to ojie grain of 
 sugar per Jluidounce. Thus, if before fermentation the
 
 IGO ABNORMAL CONSTITUKNTS OF URINE. 
 
 specific gravity was 1040 and after feriiientation it is 
 1020, it will have contained 20 grains of sugar to the 
 fluidounce of urine. The two portions of urine in the 
 bottles should be subjected to exactly the same tempera- 
 ture. 
 
 The percentage of sugar may be roughly ascertained by 
 multiplying the number of degrees lost in the specific grav- 
 ity by the arbitrary coefficient 0.23. 
 
 In the hands of the writer the fermentation test yields 
 results which are in the neighborhood of one-half per cent, 
 below those obtained by using Fehling's solution. A 
 decided objection to this method is that it requires from 
 eighteen to twenty-four hours for the completion of the 
 analysis. 
 
 Einhorn has devised a fermentation apparatus that 
 gives only approximate results. Two specially con- 
 structed and graduated tubes are used, one of which is 
 filled with a mixture of the suspected urine and a small 
 quantity of yeast, and the other with a mixture of normal 
 urine and yeast, as a control. The tubes are then set aside 
 at a temperature of from 30°-34° C. (86°-93° F.), and left 
 until fermentation has ceased. The percentage of sugar is 
 then read off from the column of carbon dioxide present. 
 If the second tube also shows a small amount of gas, the 
 figure corresponding to the amount is deducted from the 
 reading in the first tube. 
 
 By Polarization. — Glucose, or grape-sugar, rotates the 
 plane of polarized light toward the right, and upon this 
 fact a quantitative test for that substance is based. 
 Although a quantitative deterniination of grape-sugar by 
 this method is theoretically accurate, when applied to urine 
 it is open to fallacy, since the urine is apt to contain other 
 substances such as laivulose, ;5-oxybutyric acid, etc., which 
 rotate the plane of polarized light in the opposite direction. 
 As pointed out by v. Jaksch, Hoppe-Seyler, and others, it 
 is advisable to apply the test both before and after fermen- 
 tation, and the difference in the results w'ill represent the 
 quantity of grape-sugar in solution. 
 
 A large variety of polariscopes have been constructed 
 for this purpose, among the best of which are those of 
 Soleil, Laurent, Lippich, Ultzmann, Misterlich, v. Fleischl, 
 and Schmidt & Haensch. In recent years the use of the 
 half-shadow polariscope has rendered this quantitative test
 
 GLUCOSE. 
 
 161 
 
 more reliable, on account of the accuracy with which the 
 extent of rotation is determined. 
 
 The polariscope manufactured by Schmidt & Haensch, 
 of Berlin, is one of the best. ^ It is a half-shadow instru- 
 ment, being so made that gas or petroleum light can be 
 used instead of a sodium light. It determines direct per- 
 centages of sugar, and is not only accurate, but its operation 
 is quick and simple. 
 
 Fig. i8. — The Schmidt & Haensch polariscope. 
 
 In the Schmidt & Haensch apparatus, as represented in 
 figure 1 8, O is the ocular ; S, the ivory scale with vernier ; 
 L, the ocular by means of which the scale is read ; K, the 
 screw-head by which the quartz wedge is moved ; B, the 
 glass tube for holding the suspected fluid ; and P, the 
 receptacle for the glass tube. 
 
 1 This instrument can be obtained of Messrs. Eimer & Amend, 205-211 
 Third Avenue, New York city. 
 II
 
 162 ABNORMAL CONSTITUENTS OF URINE. 
 
 The source of light is a well-constructed lamp, with a 
 flat burner, for either gas or petroleum ; a special lamp can 
 be constructed so as to use electric light. The lamp should 
 be removed about 30 cm. from the apparatus, and so 
 adjusted that the illuminating lens in the chimney of the 
 lamp shall be exactly central to the optical axis of the 
 apparatus. In looking through the instrument a clear 
 circular field should be seen, with a sharp perpendicular 
 line between the two halves of the field. If the field is not 
 perfectly distinct, the ocular (O) should be drawn out until 
 the perpendicular line and the circular outline of the field are 
 sharply defined. This adjustment should be made without 
 the glass tube — that is, the receptacle should be empty and 
 its cover closed. 
 
 The delicate scale (/^), on which are found numbers cor- 
 responding to the principal lines, is read through the 
 ocular (L). The zero point on the vernier (5) should be made 
 to correspond exactly with that on the scale (F) by means 
 of the adjustment-screw (AT). When the zero point on the 
 vernier is opposite that on the scale, the two halves of 
 
 the field of the apparatus 
 should exactly correspond — 
 that is, they should be equally 
 lighted. (See ^, Fig. 19.) If, 
 however, the two halves of 
 the field should not receive 
 an equal amount of light, 
 they should be made to correspond exactly by the use of the 
 adjustment-screw {-fC). The vernier (S) is then moved to 
 the side corresponding by means of a micrometer-screw, 
 until its zero point is opposite that on the scale (F). 
 
 Having adjusted the apparatus, the glass tube is then 
 filled with the suspected urine, and placed in the receptacle. 
 The two halves of the field, which are then found to 
 receive an 7/ ncqua/ amount of light, are made to correspond 
 by means of the adjustment-screw (A'), and the rotation to 
 the right or to the left read on the scale. The result is the 
 percentage of sugar in the fluid. Every interval on the 
 scale corresponds to ^ per cent., and between these inter- 
 vals are lines which are equivalent to -^-^ per cent. 
 
 Example. — If the scale is moved toward the left, the 
 number of scale intervals that have been passed is reckoned 
 from the zero point on the vernier. Suppose that the
 
 GLUCOSE. 163 
 
 number of scale-intervals passed is 7, and that the zero 
 point of the vernier stands between 7 and 8 and at the 
 mark corresponding to 0.3 per cent., then 
 
 7 half per cent. = 3.5 -|- 0.3 = 3.8 per cent. 
 
 A similar reading is made when the scale is moved 
 toward the right. In order to read direct percentages of 
 sugar on the scale the 200-mm. tube should always be 
 used. If it should be necessary, on account of the turbidity 
 of the urine, to use the 100- or 50-mm. tubes, the reading 
 in every instance should be multiplied by either 2 ( loo-mm. 
 tube) or 4 (50-mm. tube). 
 
 Grape-sugar rotates the plane of polarized light toward 
 the right ; albumin rotates toward the left. Consequently, 
 in a urine containing both albumin and sugar the degi'ee 
 of rotation to the right or to the left will depend upon the 
 predominance of one or the other of these substances. 
 
 Prccautio)is. — The urine must be clear ; if it is turbid, it 
 should be filtered as rapidly as possible through a plaited 
 filter of soft filter-paper. If the urine is then so highly 
 colored that when the long glass observation tube (200 
 mm.) is used the line of separation between the two halves 
 of the field can not be distinctly seen, the shorter glass 
 observation tube (100 or 50 mm.) should be used. If the 
 field is still indistinct, the urine should be shaken in a flask 
 with pure, dry, animal charcoal, or decolorized by add- 
 ing to the urine one-tenth of its volume of basic acetate of 
 lead, and then filtered. In the latter instance the results 
 obtained by polarization must be multiplied by ■^, on 
 account of the dilution. 
 
 The temperature of the urine must be from 15° to 20° C. 
 If the urine is free from albumin, the percentage of sugar is 
 obtained directly by the use of the 200-mm. tube, in the 
 manner mentioned. If, on the other hand, the urine con- 
 tains albumin, a second polarization is necessary after the 
 removal of the albumin. The albumin is removed as fol- 
 lows : Take 100 c.c. of the urine in an evaporating dish, 
 and place on a water-bath. Add acetic acid, drop by drop, 
 continuing the heat until a flocculent precipitate appears. 
 Filter as quickly as possible, cool, and add sufficient dis- 
 tilled water to the filtrate to make 100 c.c. The result of 
 the second polarization will represent the exact percentage 
 of sugar.
 
 164 ABNORMAL CONSTITUENTS OF URINE. 
 
 LACTOSE. 
 
 (MiLK-SUCAR.) 
 
 Lactose, C,2H220ii' ^^ ""^ infrequently found in small 
 amounts in the urine of women (the maximum being about 
 one per cent.) near the end of gestation, but more especially 
 in nursing women in whom the flow of milk has become 
 impeded, as in cases of mastitis. Lactose is also frequently 
 seen in the urine of women who have weaned their children. 
 Its presence may continue for from three to four days, and 
 even a week, particularly in those in whom the secretion 
 of milk is copious. Whereas lactose, when present, is an 
 abnormal constituent of the urine, its presence can not be 
 considered of pathologic significance. Its chief importance 
 lies in the fact that it should, in all cases, be distinguished 
 from glucose. 
 
 Lactose crystallizes in colorless, four-sided prisms, with 
 acuminated ends, bounded by four angles. The specific 
 rotary power of lactose is -|- 52.5°, and is independent of 
 the concentration in solutions that contain up to 56 per 
 cent, at ordinary temperatures. It reduces the salts of 
 copper upon boiling in alkaline solution, but more feebly 
 than grape-sugar. It does not undergo alcoholic fermenta- 
 tion with yeast ; is quite soluble in cold, and freely soluble 
 in hot, water ; insoluble in alcohol and ether. It is pre- 
 cipitated by acetate of lead and ammonia (Briicke). 
 
 Isolation. — According to F. Hofmeister, the following 
 process serves for the isolation of milk-sugar : Since evapo- 
 ration of the urine is liable to decompose the lactose, it is 
 directly precipitated by a solution of acetate of lead and 
 ammonia, and the precipitate is washed. The filtrate and 
 wash-water should again be precipitated with lead acetate 
 and ammonia, and the process repeated until the filtrate 
 shows no more rotation. The washed precipitate is then 
 suspended in cold water, and decomposed with sulphureted 
 hydrogen. The solution is freed from the greater part of 
 the hydrochloric acid by shaking with silver oxide, and 
 from the remainder of the HCl by neutralizing the filtrate. 
 The solution is once more treated with H.,S, and the mix- 
 ture evaporated after the addition of barium carbonate. Be- 
 fore the residue becomes syrupy it should be treated with a 
 sufficient amount of 90 per cent, alcohol to produce a 
 flocculent, rapidly settling precipitate. The filtrate, placed
 
 LEVULOSE. 165 
 
 in a desiccator, yields cr>'stals of lactose, which should be 
 washed with dilute alcohol, then recrystallized from water 
 after decolorizing with animal charcoal, and finally freed 
 from adhering substances by boiling with 60 to 70 per cent, 
 alcohol. These crystals are then subjected to the tests 
 for lactose, including that with Barfoed's reagent. 
 
 Detection. — If the urine reduces Fehling's solution 
 feebly, does not ferment with yeast, and rotates the polar- 
 ized light strongly to the right, lactose is probably present, 
 especially if the urine is that of a pregnant or nursing 
 woman. A confirmatory test may be made by using the 
 phenylhydrazin test, which, in the presence of lactose, forms 
 an osazone. Phenyl-lactosazone crystallizes in the form of 
 yellow needles, which are usually aggregated in clusters, 
 and melts at 200° C, with the evolution of gas. Lactose,' 
 unlike glucose, does not reduce Barfoed's reagent, 1 but 
 this test can not be applied to urine, since Barfoed's re- 
 agent is reduced to a slight extent by normal urine. 
 
 The certain detection of lactose is secured only by iso- 
 lating it from the urine. 
 
 LEVULOSE. 
 
 (Fruit Sugar.) 
 
 Levulose, C,.Hj,0^, is only rarely found to be a con- 
 stituent of the urine. When present, it is usually found 
 associated with grape-sugar, and is rarely, if ever, found 
 alone. In such instances it usually happens that consider- 
 ably more sugar is found in diabetic urine by titration than 
 by polarization, thus showing the presence of a substance 
 that rotates to the left. The diminution in the optical 
 activity of the urine is not necessarily caused by a sugar 
 that rotates to the left, but may be produced in the absence 
 of albuminous substances (albumin, globulin, albumose, 
 and peptone) by other bodies, especially /5-oxybutyric acid, 
 glycuronic acid, cystin, and other compounds. 
 
 It is characterized by being noncrystallizable when 
 impure (although it crystallizes in long, wavy needles 
 when pure), and by turning the plane of polarized light to 
 
 1 Barfoed's Reagent: Dissolve one part of cupric acetate in 15 parts of 
 water; to 200 c.c. of this solution add 5 c.c. of acetic acid containing 38 per 
 cent, of glacial acetic acid ("Journ. f. prakt. Chem." [2], Bd. vi (1872) 
 S. 344)- \ / /'
 
 166 ABNORMAL CONSTITUENTS OF URINE. 
 
 the left instead of to the right. Its rotary power dimin- 
 ishes as the temperature rises, while that of grape-sugar 
 is independent of the temperature. Levulose reduces the 
 salts of copper, although much more feebly than grape- 
 sugar. 
 
 There is no sure process known for the isolation of 
 levulose. 
 
 Detection. — Levulose is best detected by means of the 
 polariscope, since it rotates the plane of polarized light to 
 the left. It yields with phenylhydrazin an osazone (phenyl- 
 levulosazone) that crystallizes in yellow needles whose 
 melting-point is 150° C, while those formed from grape- 
 sugar have a melting-point of 204° C. 
 
 If the left-handed rotation is caused by substances other 
 than levulose, by subjecting the urine to alcoholic fermen- 
 tation the left-handed rotation disappears if due to this form 
 of sugar, and persists if caused by other bodies. 
 
 LAIOSE. 
 
 (Leo's Sug.a.r.) 
 
 Laiose, CgHj^Og, was first discovered by Leo,^ who found 
 it in the urine of 3 out of 21 severe cases of diabetes mellitus. 
 These urines gave 1.2 to 1.8 per cent, more sugar by titration 
 than by polarization. This sugar could not be isolated from 20 
 liters of normal urine. 
 
 Laiose is closely allied to levulose in that it rotates the plane 
 of polarized light to the left, reduces alkaline solutions of the 
 cupric salts, and combines with phenylhydrazin. It is not fer- 
 mentable and does not have a sweet taste. The neutral pale- 
 yellow syrup does not crystallize if kept for a year. It is 
 readily soluble in water, moderately in methyl alcohol, spar- 
 ingly in ethyl alcohol, and insoluble in ether and chloroform. 
 It is completely precipitated by basic acetate of lead and 
 ammonia. 
 
 Isolation. — The urine is precipitated with basic acetate of 
 lead, and the filtrate with ammonia. The second precipitate 
 contains the laiose together with the dextrose. The precipitate 
 is washed and decomposed with sulphureted hydrogen. Since 
 the filtered fluid becomes dark by evaporating in the air, Leo 
 concentrated it by distilling in a vacuum, and finally drying 
 over sulphuric acid. The syrupy residue is then dissolved in 
 methyl alcohol, and the grape-sugar that has dissolved with it is 
 
 1 Han.s Leo, " Virchow's Archiv," cvn, 108, 1887.
 
 INOSITE. 167 
 
 precipitated by a solution of baryta in metliyl alcohol, sufficient 
 to give a strongly alkaline reaction. It is quickly filtered, and 
 the filtrate allowed to stand over sulphuric acid to remove the 
 ammonia, by which procedure, besides the baric carbonate, the 
 remainder of the barium compound of sugar is precipitated. 
 Carbonic acid gas is passed through the filtrate to remove the 
 excess of baryta, and the methyl alcohol is distilled off in a 
 vacuum, the residue dissolved in water, and the baryta in solu- 
 tion precipitated by sulphuric acid. 
 
 Detection. — Urines that do not contain any more sugar by 
 titration than by polarization need not be tested for this form 
 of sugar. If the isolated substance is a reducing body, it is 
 probably laiose. 
 
 SUBSTANCES ALLIED TO SUGAR. 
 
 INOSITE. 
 
 (Muscle Sugar.) 
 
 Inosite, CgH^p^ + 2U.p, is a rare constituent of the 
 urine. It has occasionally been found in small quantity in 
 diabetes mellitus, as an accompaniment of grape-sugar ; in 
 the last stages of certain forms of chronic disease, particu- 
 larly subacute glomerular and chronic diffuse nephritis ; 
 and also after the ingestion of large quantities of water 
 (Kulz). It has also been found in phthisis, syphilis, and 
 typhus fever. 
 
 According to Neubauer and Vogel, inosite is not a 
 sugar ; but from the experiments of Maquenne i it should 
 be grouped among the compounds of the fat series, mannite. 
 
 Inosite forms in cauliflower groups of crystals, and, at 
 times, in single crystals that are three or four lines in length. 
 It has a sweet taste, dissolves in 7. 5 volumes of cold water 
 at 17° to 20° C, readily in hot water, and is slightly sol- 
 uble in alcohol. It is very .soluble in dilute or concen- 
 trated acetic acid, and crystallizes more readily from these 
 solutions than from water (Maquenne). It is insoluble in 
 absolute alcohol and in ether. Its solutions are optically 
 inactive, and it does not combine with phenylhydrazin, and 
 is not fermentable by yeast ; it, however, undergoes lactic- 
 and butyric-acid fermentation. Inosite does not reduce the 
 cupric salts when boiled in the presence of an alkaline 
 
 1 " Bull, dela Soc. Chim." [2], xi.vii, 290; XLvni, 58, 1887 ; " Comptes 
 Rendus," civ, 225, 297, and 1719.
 
 168 ABNORMAL CONSTITUENTS OF URINE. 
 
 hydrate, but not infrequently gives a greenish precipitate, 
 which redissolves on cooling. 
 
 Isolation. — The urine to be tested for ino.site, after any 
 albumin present has been removed, is first concentrated to 
 one-fourth of its bulk, then completely precipitated with a 
 solution of neutral acetate of lead, avoiding an excess, or 
 with baryta water, filtered, and the warmed filtrate treated 
 with subacetate of lead as long as any precipitate occurs. 
 After twelve hours the subacetate precipitate that contains 
 the inosite, together with lead oxide, is collected on a filter- 
 paper, and after washing is suspended in water and decom- 
 posed with sulphureted hydrogen. After standing a while 
 a little uric acid first separates from the filtrate ; the fluid is 
 filtered from it, then concentrated as much as possible, and 
 while boiling treated with three or four times its volume of 
 alcohol. If a heavy precipitate results that rapidly settles, 
 the hot alcoholic solution is simply poured off, but if a floc- 
 culent nonadhesive precipitate occurs, the hot solution is 
 filtered through a heated funnel and allowed to cool. If, 
 after twenty-four hours, groups of inosite crystals have de- 
 posited, they are filtered and washed with a little cold alco- 
 hol. In this case it is advisable to dissolve the precipitate 
 once more in as little boiling water as possible, and precipi- 
 tate it a second time with three or four volumes of alcohol 
 in order to avoid any loss of the inosite. If, however, no 
 crystals of inosite have separated, ether is gradually added 
 to the clear, cold, alcoholic filtrate until a milky cloudiness 
 results on shaking thoroughly, and it is then allowed to 
 stand twenty-four hours. Almost all of the inosite present is 
 separated in the form of shining, pearly leaflets if too small 
 an amount of ether has not been used (an excess does no 
 harm). The separated inosite is recognized by the reactions 
 I and 2, given below. 
 
 Detection. — The urine should be free from albumin. 
 The following tests (i and 2) depend upon the action of 
 concentrated nitric acid which oxidizes inosite to rhodizonic 
 acid. The carbohydrates do not give these reactions. 
 
 I. If a fluid containing inosite is evaporated in a porce- 
 lain dish to a few drops, and a small drop of Millon's 
 reagent ^ is then added, a yellow precipitate is soon formed. 
 
 * Millon's Reagent : Dissolve one part of metallic mercury in two parts of 
 ordinary nitric acid, evaporate to one-half volume, and add I ^'^ parts of water. 
 After twenty-four hours the clear supernatant fluid is decanted from the basic salt.
 
 GLYCURONIC ACID. 169 
 
 If this is spread out as much as possible on the edge of the 
 dish and again gently warmed, there remains, as soon as the 
 fluid is all evaporated, first a yellowish residue, which 
 soon becomes red providing too much of the reagent has 
 not been added. The color disappears on cooling, but re- 
 appears upon the application of gentle heat. Starch, lactose, 
 mannite, glycogen, uric acid, urea, taurin, and cystin do not 
 give this red color ; albumin is colored red, and therefore, 
 if present, must be previously separated. 
 
 2. Evaporate the fluid containing inosite with concentrated 
 nitric acid nearly to dryness, on a platinum dish, moisten 
 the residue with a few drops of ammonic hydrate and a 
 solution of calcium chloride. Then evaporate the mixture 
 to dryness, and there appears a vivid rose-red color, which, 
 according to Scherer,^ appears with even one milligram of 
 inosite. 
 
 GLYCURONIC ACID. 
 
 Glycuronic acid, CgHj^jO,, is sometimes found in the urine, 
 and is, above all, most likely to be mistaken for sugar. It 
 probably occurs normally in very small amounts in the urine as 
 cojubined glycuronic acid, coupled with potassium sulphate. 
 It may appear in the urine in much larger quantities, particu- 
 larly after the administration of chloral, butyl-chloral, chloro- 
 form, turpentine, camphor, morphine, naphthalene, curare, and 
 nitrobenzol, when it also exists in combination. After the ad- 
 ministration of chloral it appears as urochloralic acid ; after cam- 
 phor, as campho-glycuronic acid ; after turpentine, as turpen- 
 glycuronic acid ; after naphthalene, as naphthol-glycuronic 
 acid, etc. It is said to occur in considerable quantities in the 
 urine of apparently healthy people who have not a diabetic 
 history. 
 
 Glycuronic acid, when pure, is not crystalline, but is ob- 
 tained only as a syrup. It dissolves in alcohol, is readily solu- 
 ble in water, but insoluble in ether. Glycuronic acid itself is 
 dextrorotatory, but when in combination, turns the plane of 
 polarized light to the left. It is converted into saccharic acid 
 by the action of bromine, and seems to occupy an intermediate 
 position between this acid and gluconic acid, CgHj^O,, obtained 
 by the oxidation of glucose or cane sugar with chlorine or bro- 
 mine. It reduces the salts of copper, bismuth, silver, and 
 mercury, and does not undergo alcoholic fermentation with 
 yeast. It gives a crystalline compound with phenylhydrazin. 
 
 1 "Ann. d. Cheni. u. Pharni.," LXXXI, 375.
 
 170 ABNORMAL CONSTITUENTS OF URINE. 
 
 Isolation. — Glycuronic acid is best isolated from the urine 
 by the method of Schmiedeberg and Meyer, ^ as follows : 
 
 Take a large quantity of urine and decolorize by means of 
 animal charcoal. Then evaporate it to a syrup, and treat with 
 a large quantity of damp barium hydrate, heating for some 
 time over a water-bath. Extract with absolute alcohol, which 
 leaves glycuronic acid and various other substances undissolved ; 
 mix the residue with water and filter. Add more baryta to the 
 filtrate, again filter, and evaporate the filtrate to a small volume 
 over a water-bath. An amorphous barium precipitate separates, 
 which is washed with water, and then decomposed by sulphuric 
 acid. The barium sulphate is then filtered off, the filtrate evapo- 
 rated down and dried in a vacuum, when crystals of the anhy- 
 dride will be obtained. 
 
 Detection. — If the urine reduces the salts of copper, and 
 does not undergo alcoholic fermentation with yeast, and is 
 dextrorotatory, glycuronic acid is probably present. 
 
 CANE SUGAR. 
 (Saccharose.) 
 
 Cane sugar, Cj^H^^Oj^, is a very uncommon constituent of the 
 urine. It has been found after the ingestion of large quantities 
 of cane-sugar, but only in rare instances, and, therefore, is of no 
 practical importance from a clinical standpoint. It occasionally 
 appears in the urine from extraneous sources, particularly when 
 the urine is transported in a bottle that is not clean or has con- 
 tained simple syrup. It is sometimes added to the urine by the 
 insane, or those persons who are disposed to deceive the physi- 
 cian or chemist. 
 
 Cane sugar, when pure, does not reduce the salts of copper, 
 but, on account of the fact that the commercial article contains 
 traces of glucose as an impurity, a reduction of the cupric oxide 
 may follow the test. It crystallizes in prismatic form, and its 
 aqueous solutions rotate the polarized light strongly to the right, 
 -(- 73.8. When boiled with dilute hydrochloric or sulphuric 
 acids, it undergoes the process of ^Hnversion^^ — that is, it takes 
 up a molecule of water and is converted into dextrose and levu- 
 lose, according to the following equation : 
 
 ^12^220,1 f H2O = CgH,20g -f CpHjjOfi. 
 
 Dextrose. Levulose. 
 
 On account of the strong rotation of levulose the solution 
 now rotates to the left instead of to the right ; hence the term 
 inversion. 
 
 1 " Zeitschr. f. physiol. Ch.," in, 422, 1879.
 
 ACETONE. 171 
 
 Detection. — Traces of cane sugar may be overlooked in the 
 ordinary analysis of the urine. When present in larger quanti- 
 ties, the specific gravity is usually very high, even though the 
 normal solids are not increased ; any glucose present is usually 
 found to be in small quantities. The dextrorotatory polarization, 
 which, after inversion, becomes levulorotatory, indicates the 
 presence of cane sugar. 
 
 ACETONE. 
 
 Acetone is a volatile compound frequently found in large 
 amounts in the urine under certain diseased conditions. 
 According to v. Jaksch, de Boeck, and A. Slosse, normal 
 urine contains traces of acetone (o. i gram in twenty -four 
 hours — "physiological acetonuria "). Le Noble claims, 
 however, that this body is only found in the urine of 
 healthy persons after the use of alcohol and food rich in 
 proteid matter. 
 
 Acetone, CgHgO, is the typical member of the group 
 known as ketones, and may be prepared artificially by the 
 dry distillation of calcium or barium acetate. It may be 
 obtained in considerable quantities by distillation of the 
 urine or the blood of certain diabetic individuals. The 
 peculiar fruity, sweet odor frequently noticed in the breath 
 and in the urine of diabetic subjects is due to acetone. It 
 is a volatile, colorless liquid, of a specific gravity of 0.792, 
 boiling at 56.5° C, soluble in water, and characterized by 
 an ethereal or fruity odor. The principal source of acetone 
 is the decomposition of the proteids of the body as well 
 as those taken as food (v. Jaksch). 
 
 Clinical Significance. — The condition of acetonuria is 
 divided by v. Jaksch, according to cause, into : (i) Febrile ace- 
 tonuria (scarlet fever, typhoid fever, pneumonia, measles, 
 smallpox, etc.) ; (2) diabetic acetonuria ; (3) acetonuria 
 accompanying certain forms of cancer independent of inani- 
 tion ; (4) acetonuria of starvation ; (5) the production of 
 acetone in psychoses ; (6) acetonuria as an expression of 
 autointoxication ; (7) acetonuria in derangements of diges- 
 tion ; (8) acetonuria in chloroform narcosis. The most 
 common of these forms is febrile acetonuria. It is seen in 
 children as well as in adults, and does not belong to any 
 particular fever. In diabetes the appearance of acetone in 
 the urine indicates an advanced stage of the disease. The 
 ingestion of an abundance of nitrogenous food tends to the
 
 IT> AI5NOKMAI, (( )NSTn"UKNTS OK URINK. 
 
 production of acctonuria. riius it is that tlic urine of dia- 
 betics often contains a larger amount of acetone after elimi- 
 nating starches and sugars from the diet, and restricting it 
 chiefly to nitrogenous substiuices. Acctonuria existing 
 alone (autointoxication with acetone) tends to a favorable 
 termination. Of greater importance are those cases in 
 which much acetone is found as an accompaniment of grave 
 symptoms of cerebral irritation. 
 
 Detection. — Legal's Test. — This is a rough test, but is 
 of sei"vice on account of being easy of application. 
 
 One-fourth of a test-tube of urine is treated with a few 
 drops of a freshly {prepared and somewhat concentrated 
 solution of sodium nitroprusside, a few drops of acetic 
 acid are added to prevent the reaction with kreatinin, and 
 the mixture is then rendered alkaline with ammonic or sodic 
 hydrate. The mixture gradually develops a red color, 
 which increases to a deep purple-red color. In the ab.sence 
 of acetone the red or purple-red tint does not form. 
 
 For purposes of greater accuracy it is necessary to distil 
 the urine (500 to lOOO c.c), after the addition of a little 
 phosphoric acid (i gram per liter), to prev^ent the evolution 
 of gases ; the first 10 to 30 c.c. of the distillate are used 
 for the following tests : 
 
 Lieben's Test. — A few cubic centimeters of the distillate 
 are treated with several drops of a dilute solution of iodo- 
 potassic iodide and sodic hydrate. In the presence even 
 of traces of acetone, a precipitation of iodoform in crys- 
 talline form occurs, which may be readily recognized by 
 its odor. 
 
 Quantitative Estimation of Acetone. — The method of 
 Messinger, as modified by Huppert, is best adapted to the esti- 
 mation of acetone in urine, and is based upon the observation 
 of Lieben, that acetone gives rise to the formation of iodoform 
 when treated with iodine in an alkaline solution. If, then, a 
 solution of acetone be treated with a known amount of iodine, 
 the quantity present is determined by retitrating the iodine that 
 was not used in the formation of iodoform. 
 
 Solutions Required. — (i) Acetic acid (50 per cent, solution) ; 
 (2) sulphuric acid (12 per cent, solution); (3) sodic hydrate 
 solution (50 per cent.) ; (4) a decinormal solution of iodine ; 
 (5) a decinormal solution of sodium thiosulphate. 
 
 Process. — One hundred cubic centimeters of urine, or less if 
 much acetone be present as determined by Legal's test, are
 
 ACETONE. 173 
 
 treated with 2 c.c. of the acetic acid solution, and distilled until 
 seven-eighths of the total amount has passed over. The dis- 
 tillate is received in a retort that is connected with a bulb appa- 
 ratus filled with water. As soon as seven-eighths of the urine 
 has distilled over, a small amount of the distillate of the 
 remainder is tested for acetone by Lieben's method. Should a 
 positive reaction be obtained, it will be necessary either to 
 repeat the entire process with less urine, diluted to about 200 
 c.c, or to add about 100 c.c. of water to the residue and to 
 distil until all the acetone has been driven over. The distillate 
 is then treated with i c.c. of the sulphuric acid, and redistilled. 
 The addition of the acetic acid and of the sulphuric acid, respect- 
 ively, serves the purpose of holding back the phenol and the 
 ammonia. Should the first distillate contain nitrous acid, 
 which may be recognized by the addition of a little starch-paste 
 containing a trace of potassium iodide, when the solution will 
 turn blue, this is removed by adding a little urea. The second 
 distillate is received in a bottle provided with a well-ground 
 glass stopper, and holding about one liter. To prevent the 
 escape of acetone, the glass stopper is replaced by a doubly per- 
 forated cork, through which two glass tubes pass, one to the 
 distilling apparatus, the other to the bulb apparatus. The dis- 
 tillate is then treated with a carefully measured quantity of the 
 decinormal solution of iodine — about 10 c.c. for each 100 c.c. 
 of urine used — and sodic hydrate solution, which should be 
 added drop by drop until the blue color has disappeared and 
 the iodoform separates out. To this end a slight excess of the 
 solution must be added. Should ammonia be present, a blackish 
 cloud will be observed at the zone of contact of the .sodic hydrate 
 and the iodine solution, and it will be necessary to repeat the 
 entire process. The bottle is closed and shaken for about one 
 minute. The solution is then acidulated with concentrated 
 hydrochloric acid, when the mixture assumes a brown color if 
 io-dine be present in excess. If this does not occur, more of the 
 iodine solution must be added, and the process repeated until 
 an excess is present. The excess is then retitrated with the 
 thiosulphate solution until the solution presents a faint yellow 
 color. A few cubic centimeters of starch solution are then 
 added, and the titration continued until the last trace of blue 
 has disappeared. The number of cubic centimeters employed 
 in the titration is finally deducted from the total amount of the 
 iodine solution added, and the result multiplied by 0.967. 
 The figure thus obtained will then indicate, in terms of milli- 
 grams, the amount of acetone contained in the 100 c.c. of urine, 
 as I c.c. of the thiosulphate solution is equivalent to i c.c. of 
 the iodine solution, or to 0.967 milligrams of acetone.
 
 174 ABNORMAL CONSTITUENTS OF URINE. 
 
 DIACETIC ACID. 
 
 Diacetic acid, also termed aceto-acetic or ethyl-diacctic 
 acid, CgHjp03, sometimes appears in the urine. Its pres- 
 ence must always be regarded as abnormal. Urine con- 
 taining diacetic acid is always rich in acetone, for which 
 diacetic acid is often mistaken. These two bodies e.xist in 
 the urine independently, although by the action of alkalies 
 diacetic acid is readily converted to acetone, alcohol, and 
 COg, as shown by the following : 
 
 C6H10O3 -f H,0 = CjH.O + C,Hp + CO, . 
 
 Diacetic acid. Acetone. Alcohol. 
 
 Whether a similar decomposition takes place in the blood 
 remains still an open question. 
 
 Diacetic acid is a colorless liquid, which gives a charac- 
 teristic Bordeaux-red color with a solution of ferric chloride. 
 But this color with ferric chloride may be produced by the 
 presence of other substances in the urine, such as salicylic 
 acid, carbolic acid, antipyrin, thallin (Legal and Hammar- 
 sten) ; also acetic and formic acids, sulpho- (thio-) cyanates, 
 and /5-hydroxybutyric acid. Diacetic acid is distinguished 
 from these substances by the fact that, if the urine be pre- 
 viously boiled, diacetic acid does not give the ferric chloride 
 reaction, while the other substances continue to give the 
 Bordeaux-red color as before. Furthermore, that salicylic 
 acid, carbolic acid, etc., are not extracted from the urine by 
 ether, whereas diacetic acid is soluble in ether. 
 
 Clinical Significance. — As already mentioned, the pres- 
 ence of diacetic acid in the urine (diaceturia) is always 
 pathologic, and should in general be considered a serious 
 symptom. Diacetic acid is frequently found in the urine in 
 diabetes mellitus, in fevers, and also idiopathically as a form 
 of autointoxication (diacetemia). It is of common occur- 
 rence in the urine of children as a concomitant of fever 
 (v. Jaksch), and is then generally devoid of serious impor- 
 tance ; but in children or adults suffering from diabetes it is 
 a symptom of grave import. Diaceturia is most common 
 in the advanced stages of diabetes mellitus, and particularly 
 in children and persons under the age of thirty. The oc- 
 currence of this symptom may be looked upon as a very 
 probable forerunner of diabetic coma and rapid death. The 
 author's experience has led him to make an unfavorable prog-
 
 BILE. 175 
 
 nosis in all cases of diabetes mellitus (under thirty years of 
 age) in which the urine contains diacetic acid. 
 
 The form of autointoxication of which diaceturia is the 
 chief index is usually rapidly fatal, being accompanied by 
 such symptoms as vomiting, dyspnea, jactitation, and coma, 
 without evidence of any other pathologic process. 
 
 Detection. — The process suggested by v. Jaksch is most 
 reliable, and is as follows : To the urine a fairly concen- 
 trated solution of perchloride of iron is cautiously added, 
 and if a phosphatic precipitate forms, this is removed by 
 filtration, and more of the perchloride of iron solution sup- 
 plied. If the Bordeaux-red color appears, one portion of 
 the urine is boiled, while another portion is treated with 
 sulphuric acid and extracted with ether. If now the urine 
 that has been boiled gives no reaction with the perchloride 
 of iron solution, while the ethereal extract shows a claret- 
 red color with the iron solution, diacetic acid is probably 
 present, particularly if, at the same time (on testing the 
 urine directly and its distillate), it is found to be rich in 
 acetone. 
 
 The urine to be tested should be perfectly fresh, for the 
 reason that in a urine that has begun to decompose the 
 diacetic acid takes up a molecule of water and splits into 
 acetone, alcohol, and carbon dioxide. 
 
 BILE. 
 
 Of the constituents of bile, the biliary pigments and 
 acids chiefly concern us here. Another constituent of bile 
 — viz., cholesterin — has never yet been found in the urine 
 in" jaundice, but has been met with in considerable quantities 
 in other connections. 
 
 BILIARY PIGMENTS. 
 
 A urine containing bile is always abnormally colored. 
 The chief unaltered biliary pigment is bilirubin, which is an 
 intermediate product in the body between hemoglobin and 
 urobilin. (See p. 91.) When bilirubin (orange-yellow) 
 becomes oxidized, either by exposure to the air or by re- 
 agents, the first and most important oxidation product is 
 biliverdin (green) ; then follow the less important products, 
 bilicyanin (blue), bi/ifnscin, hiliprasiii , and finally cJiolctelin (.^). 
 Bilirubin is in the urine in a free state ; but in biliary calculi,
 
 176 ABNORMAL CONSTITUENTS OF URINE. 
 
 in which it is often present in abundance, it exists as a cal- 
 cium compound — bilirubin caiman. 
 
 The color of a bile-containing urine is either greenish-yel- 
 low, yellowish-brown, deep brown, greenish-brown, or, on 
 standing exposed to the air, may be nearly pure green. On 
 shaking the urine it gives a persistent greenish-yellow or yel- 
 low froth or foam. Furthermore, if a piece of filter-paper or 
 linen be moistened with such urine, it retains a permanent 
 yellow color on drying. A jaundiced urine almost invari- 
 ably contains an excess of urobilin and indoxyl. A urine 
 from which the bile has recently disappeared is usually 
 highly colored, due to the large excess of urobilin. 
 
 A bile-containing urine is always albuminous. The 
 chief proteid appears to be nucleo-albumin, which is 
 usually accompanied by traces of serum albumin. In this 
 connection it is noteworthy that the nitric acid test for 
 albumin can not be satisfactorily used for the detection of 
 slight traces, on account of the amount of coloring-matter 
 set free by the acid, thus obscuring a faint zone of albumin. 
 For this reason, therefore, in a urine containing much bile, 
 the heat test for albumin is preferable. The sediment 
 usually contains a large number of renal epithelial cells, 
 which are more or less colored by the bile pigment. Not 
 infrequently, they have attached to their surfaces stellate 
 clusters of bilirubin crystals, which have a yellowish-brown 
 color ; also small, irregular, brown, bilirubin granules. (See 
 p. 224.) The sediment also contains renal casts and abnor- 
 mal blood globules, free and adherent to casts, the result of 
 the irritation of the kidneys by the bile. If more than a 
 mere trace of bile pigment be present in the urine, the organ- 
 ized elements of the sediment are invariably stained yellow 
 or yellowish-brown. 
 
 Clinical Significance. — Bile pigments occur in the urine 
 in every case of jaundice — in other words, in every case in 
 which there is an obstruction to the outflow of bile from 
 the bile-ducts {Jtepatogenous icterus). Thus they are found 
 in a variety of pathologic conditions of the liver, of which 
 the most common are catarrhal jaundice, obstruction in the 
 common bile-duct by biliary calculi, cancer, and cirrhosis 
 of the liver. They may also appear in the urine incases 
 of destruction of the red blood globules, as in severe infec- 
 tious conditions, phosphorus-poisoning, etc. {Jiematogcnous 
 icterus ). Bile pigments often make their appearance in the
 
 BILE. 177 
 
 urine before there is much coloration of the conjunctivje, or 
 any yellow color in the skin. 
 
 Detection. — Marechalt's Test. — Take about one finger- 
 breadth of an alcoholic solution of iodine (not too strong) 
 in a test-tube, and underlie with urine by allowing it to flow 
 down the side of the inchned test-tube from a pipette placed 
 above the level of the iodine. If biliary pigments are 
 present, a green color appears just below the point of con- 
 tact of the two fluids, and remains for some time, even for 
 twenty-four hours. In this test the possibility of confound- 
 ing with indoxyl is said to be excluded. 
 
 Gtnelin's Test. — This test is performed in two ways : 
 
 1. A quantity of urine is placed in a wine-glass, and a 
 small quantity of concentrated nitric acid is allowed to flow 
 carefully down the side of the wine-glass to underlie the urine, 
 as described in the nitric acid test for albumin. If bihaiy 
 coloring-matters are present, at the point of union between 
 the urine and the acid a play of colors will very soon 
 appear, which, if typical, should be green, blue, violet, red, 
 and yellow or yellowish-green, in the order named. Often, 
 however, one or more colors are wanting. The green is 
 most constant, the first green being indispensable to prove 
 the presence of bile ; but violet, shading into red and yellow, 
 is also very constantly seen. The other colors may be pro- 
 duced by other coloring-matters, especially indoxyl. 
 
 2. The test can also be applied by placing a drop of the 
 suspected urine on a porcelain plate, and allowing a drop 
 of the fuming nitric acid, which has been placed adjacent, to 
 gradually mingle with the urine. The same play of color 
 occurs. 
 
 Another method consists in precipitating the urine with 
 a small amount of milk of lime. A small portion of this 
 precipitate is then treated with a drop of concentrated nitric 
 acid, and if bile pigments are present, a play of colors, like 
 that seen in Gmelin's test, occurs. 
 
 The two tests for biliary pigments just described are quite 
 satisfactory, providing the urine contains a large amount of 
 bile, but they are far from conclusive when the urine con- 
 tains minute traces of biliary pigments. Various other tests 
 for bile pigments have been advised, but all possess greater 
 shortcomings than Marechalt's or Gmelin's tests, and many 
 of them are valueless. In the hands of the writer Mare- 
 chalt's test is the most serviceable of all tests, especially
 
 178 ABNORMAL CONSTITUENTS OF URINE. 
 
 when applied in the manner previously outlined. It is to be 
 said, however, that a normal urine often reacts with iodine 
 so as to suggest a trace of bile when it is evident that no 
 bile pigments are present. It is certain that this subject 
 needs further investigation in order to be able to demon- 
 strate satisfactorily the presence of traces of bile pigments 
 in urine. 
 
 BILIARY AQDS. 
 
 Any interference with the discharge of bile from the liver 
 or common bile-duct results in the passage of the bile con- 
 stituents into the blood and their elimination by the urine 
 {liepatogcnous icterus). But bile pigments may also pass into 
 the urine under other circumstances, especially when there 
 is destruction of the red blood-corpuscles through poisoning 
 by ether, chloroform, arseniureted hydrogen, phosphorus, 
 and in grave infectious diseases. In this second form of 
 icterus the blood coloring-matter appears to be transformed 
 into bile pigment elsewhere than in the liver, possibly in the 
 blood, and thus it is that we have the so-called licniatogcnous 
 icterus. Only the bile pigments appear in the urine in these 
 cases, while in hepatogenous icterus the urine contains the 
 bile pigments and bile acids at the same time (Leyden). 
 This arbitrary distinction, however, can not be fully main- 
 tained in all cases. It is certainly true that the presence 
 of more than mere traces of bile acids in the urine indicates 
 the existence of hepatogenous jaundice, but cases of absorp- 
 tion icterus undoubtedly occur in which no bile acids can be 
 detected in the urine. 
 
 According to Dragendorf, Vogel, and Oliver, traces of 
 bile acids occur in normal urine, but Hoppe-Seyler and 
 Udranszky both hold the opposite view. This question 
 must be considered unsettled until confirmatory evidence 
 bearing upon one or the other view is at hand. 
 
 All bile acids can be conveniently divided into two groups 
 — the glycocholic and the taurocJiolic acid groups. The glyco- 
 cholic acids contain nitrogen, but are free from sulphur, 
 and can be split, with the addition of water, into glycocoU 
 and an acid free from nitrogen — cholic acid. The tauro- 
 cholic acids contain nitrogen and sulphur, and are split, 
 with the addition of water, into taurin, which contains sul- 
 phur and cholalic acid. The existence of different glyco- 
 cholic and taurocholic acids depends on the fact that there
 
 BILE. 179 
 
 are several cholalic acids. These two groups of acids exist 
 in the urine chiefly as salts of sodium. 
 
 Clinical Significance. — As already intimated, bile acids 
 are most commonly found in the urine in cases of obstruc- 
 tive jaundice — that is, in the Jiepatogcnous form, and not gen- 
 erally present in the Iieviatogeiious form of icterus. This very 
 general rule, however, is subject to much variation, and, 
 therefore, the determination of the presence of bile acids 
 can not be considered especially diagnostic of the existence 
 of hepatogenous jaundice. They are present in the urine 
 of hepatic congestion, cirrhosis, and hepatic tumors ; also 
 in carcinoma and severe acute bilious attacks. They have 
 also been found in anemia, hemoglobinuria, scurvy, and 
 splenic leukemia. They are much less common in the 
 urine in amyloid infiltration of the liver. 
 
 Tests for bile acids are not usually made in the routine 
 analysis of urine. In fact, for purposes of diagnosis, the 
 detection of bile pigments is generally sufficient. It is impos- 
 sible to apply satisfactorily the ordinary test — Pettenkofer's 
 — for bile acids directly to the urine ; they must, therefore, 
 be isolated. 
 
 Isolation. — The simplest method of obtaining the biliary 
 acids is the one suggested by Dr. Tyson, ^ and is as fol- 
 lows : " Six or eight ounces (i8o to 240 c.c.) of the sus- 
 pected urine are evaporated to dryness over a water-bath. 
 The residue thus obtained is treated with an excess of abso- 
 lute alcohol, filtered, and the filtrate treated with an excess 
 of ether (12 to 24 times its bulk), by which the bile acids, if 
 present, are precipitated. These are then removed by fil- 
 tration, and redissolved in distilled water. The solution is 
 then decolorized by passing through animal charcoal, and 
 the resulting colorless fluid subjected to Pettenkofer's test." 
 
 According to Hoppe-Seyler, the bile acids can be sepa- 
 rated from the urine in the following manner : Render 
 the urine alkaline with ammonic hydrate, and precipitate 
 directly with basic acetate of lead ; wash the precipitate 
 with water, dry by gentle heat, heat several times with 
 absolute alcohol, and filter while hot. To the alcoholic 
 solution of lead salts of the bile acids add a few drops of 
 sodic hydrate and evaporate to dryness. Extract the 
 residue with absolute alcohol by the aid of heat ; evapo- 
 
 1" Philadelphia Medical Times," July 5, 1873.
 
 180 ABNORMAL CONSTITUENTS OF URINE. 
 
 rate the solution to a small volume, and shake vvitii an 
 excess of ether, whereby the biliary salts are separated 
 as an amorphous precipitate. Filter, dissolve the precipi- 
 tate in distilled water, and apply Pettenkofer's test. 
 
 Dragendorff has shown that the bile acids can be extracted 
 from urine that has been acidulated with hydrochloric acid 
 by shaking with chloroform. 
 
 If ox bile be added to urine, Pettenkofer's reaction can 
 generally be demonstrated without separating the bile salts 
 as just indicated, providing, however, the color of the urine 
 used is normal or pale, and not high. 
 
 Detection. — Pettenkofer's Test for Bile Acids. — The 
 test, as usually applied, is as follows : 
 
 Process. — Bile, which may be considerably diluted, or a 
 dilute solution of bile salts or acids, is mixed in a porce- 
 lain dish with a iQ\N drops of a lo per cent, solution of 
 cane sugar. Concentrated sulphuric acid is then added to 
 the mixture, with constant stirring, to an extent not ex- 
 ceeding two-thirds of its volume, the addition of the acid 
 being so regulated that the temperature of the mixture is 
 not allowed to rise abov^e 70° C. A brilliant cherry-red 
 changing to a reddish-purple color soon makes its ap- 
 pearance. On standing for some time the color becomes 
 darker and assumes more of a blue tint. The reaction 
 may also be obtained by the addition of first the acid and 
 then the sugar solution. The success of the test depends 
 upon keeping the temperature of the mixture below 70'^ C. 
 (a cold water-bath may be used), and the avoidance of any 
 excess of sugar, which, by being charred by the acid, gives 
 a brown color and masks the typical purple. To avoid 
 this, Drechsel recommends the use of phosphoric acid 
 (5 of the glacial acid to i of water) instead of sulphuric acid. 
 In this case the solution must be heated by immersion in 
 boiling water. 
 
 According to Schenk,^ if the typical purple solution is 
 diluted with alcohol, it shows with the spectroscope a char- 
 acteristic absorption spectrum, consisting of two absorption 
 bands, one between D and E, bordering on E, and a second 
 between E and F, adjoining F. 
 
 Pettenkofer's reaction depends upon the presence of 
 cholalic (or cholic) acid, a constituent of the bile acids ; also 
 
 ^ " Jahresber. f. ThierCh.," II, 232.
 
 BILE. 181 
 
 upon the formation of /w/z/'/yV (also known as furfuralde- 
 hyde) which results from the action of the sulphuric acid 
 upon the sugar, the characteristic color arising from the in- 
 teraction of the furfurol with the cholalic acid. 
 
 This test is far from satisfactory when applied directly to 
 the urine, even when the bile acids are present in consid- 
 erable amount, since, on the one hand, urinary pigments 
 and other substances are charred by the sulphuric acid, 
 thus interfering with the brilliancy of the reaction ; and, 
 secondly, if the urine contains proteids, cholesterin, amyl 
 alcohol, and various other substances, a purple color is pro- 
 duced which closely resembles that due to bile acids. 
 
 Oliver's Peptone Test. — This test is based on the physi- 
 ologic fact that, when the products of gastric digestion, pep- 
 tone and parapeptone, which pass from the stomach in an acid 
 medium, meet with the bile in the duodenum, they are precipi- 
 tated. So, too, albuminous urine, or urine charged with pep- 
 tone, is precipitated by a solution of bile salts, — sodium glyco- 
 cholate or taurocholate. Thus an acid solution of peptone is 
 recommended and is prepared as follows : 
 
 Pulverized peptone (Savary and Moore), 30 grains; salicylic 
 acid, 4 grains; acetic acid, 30 minims; and distilled water up 
 to 8 fluidounces. Filter until a clear filtrate is obtained. 
 
 Process. — To 60 minims of this test solution add 20 minims 
 of perfectly clear urine which has been previously rendered nor- 
 mally acid if alkaline, and which has been reduced to a specific 
 gravity of 1008. If the proportion of bile salts be normal or 
 subnormal, no immediate reaction occurs, but in a short time a 
 mere tinge of milkiness appears. If in excess, a distinct tur- 
 bidity promptly appears, becoming more intense in a minute or 
 twQ, the degree of opacity being directly proportionate to the 
 amount of bile acids present. On agitation the opalescence 
 diminishes, and may finally disappear, but is restored on adding 
 more of the test solution. 
 
 Approximate Quantitative Test. — This is based upon a 
 permanent standard of oi)acity provided by mixing equal pro- 
 portions of the test solution and normal urine reduced to the 
 specific gravity of 1008. To 60 minims of the test solution 
 add the suspected urine diluted to a specific gravity of 1008, 
 usually 10 to 20 minims at a time, allowing a minute to elapse 
 after each addition, until the opacity induced is exactly equal 
 to or slightly exceeds that of the standard, the tubes being held 
 to the light, shaded by a dark background. If 50 or 60 minims 
 bring up the opacity to that of the standard, the proportion of 
 bile salts does not exceed the normal. Any smaller quantity
 
 182 ABNORMAL CONSTITUENTS OF URINE. 
 
 required indicates an excess, while the smaller the amount 
 needed, the larger the proportion of bile salts present. 
 
 OLIVER'S STANDARD TABLE. 
 
 Minims. 
 
 Urine. 
 
 Drops. 
 
 Percentage of Increase over 
 the Normal Standard. 
 
 I 
 
 or 
 
 2 
 
 =: 
 
 6000 
 
 2 
 
 or 
 
 4 
 
 = 
 
 3OCX) 
 
 3 
 
 or 
 
 6 
 
 = 
 
 2000 
 
 4 
 
 or 
 
 8 
 
 = 
 
 1500 
 
 5 
 
 or 
 
 10 
 
 = 
 
 1200 
 
 lO 
 
 or 
 
 20 
 
 =r 
 
 600 
 
 15 
 
 or 
 
 30 
 
 = 
 
 400 
 
 20 
 
 or 
 
 40 
 
 = 
 
 300 
 
 25 
 
 or 
 
 50 
 
 = 
 
 240 
 
 30 
 
 or 
 
 60 
 
 = 
 
 100 
 
 35 
 40 
 
 or 
 or 
 
 70 
 80 
 
 = 
 
 83 
 
 66 
 
 45 
 
 or 
 
 90 
 
 = 
 
 50 
 
 This test, according to Dr. Oliver, is so delicate that one 
 part of bile salts can readily be detected in 18,000 to 20,000 
 parts of a solution of sodium chloride. An increase over 700 
 per cent, beyond the normal is rarely encountered. Oliver has 
 yet to find anything that interferes with this test for bile acids 
 in the urine. 
 
 Dr. Oliver has also devised a peptone test-paper that he con- 
 siders permanent, reliable, and convenient for use. 
 
 EHRLICH'S DIAZO REACTION. 
 
 This reaction was first described by Ehrlich ^ in 1882. 
 It depends upon the peculiar color produced in the urine 
 (and more particularly in the foam) by the action of diazo- 
 benzol-sulphonic acid upon certain unknown substances in 
 the presence of an excess of ammonic hydrate. 
 
 The following- solutions are neces.saiy for the reaction : 
 
 Solution A. 
 
 Sulphanilic acid (.saturated aqueoi:s solution) . 200 c.c. 
 Hydrochloric acid (concentrated) 10 " 
 
 Solution B. 
 
 Sodium nitrite i " 
 
 Distilled water 200 " 
 
 These solutions {A and E) are to be kept separate, in 
 well-.stoppered bottles, and preferably in a dark place. It 
 is necessary to have the sodium nitrite solution as fresh as 
 possible, and, since it decomposes in the course of a few 
 
 ' "Zeitschr. f. klin. Med.," IV, 285-288.
 
 EHRLICH'S DIAZO REACTION. 183 
 
 weeks, it is advisable to keep only a small quantity of it 
 
 on hand. . , , 
 
 Method of Applying Test.-Take in a test-tube a mix- 
 ture of 40 parts of solution A and i part of solution i> ; 
 add an equal volume of urine; shake the whok mixture 
 thoroughly, and allow an excess of amnionic hydrate to 
 run slowly down the side of the tube. If the diazo reac- 
 tion be present, the foam will be colored pink, and tha 
 portion which is acted upon by the amnionic hydrate will 
 have a crimson color. When the test-tube is inverted, the 
 entire column of liquid in the tube will be found to have a 
 crimson color, while the foam still remains pink. 
 
 Ehrlich found that this reaction was almost constantly 
 present in the urine of typhoid fever. He also obtained 
 the reaction in the urine of a variety of other diseases, 
 mostly acute febrile diseases, but in these its occurrence 
 was not constant. He. therefore, called attention to the 
 value of the diazo reaction as an aid in the diagnosis of 
 
 typhoid fever. • • ^u 
 
 Since the discovery of this peculiar reaction m the urine 
 considerable discussion has arisen as to its clinical value in 
 connection with the diagnosis of typhoid. It is sate to 
 sav that the reaction, as ordinarily applied, has met 
 with much disfavor, owing partly to the fact that it is 
 frequently obtained in the urines of a number of other dis- 
 eases such as pulmonary phthisis, pneumonia, pleurisy, 
 scarlet fever, diphtheria, measles, erysipelas, acute miliary 
 tuberculosis, syphilis, carcinoma, puerperal septicemia and 
 other septic conditions, acute and chronic rheumatism, etc., 
 and partly on account of the failure of some observers to 
 follow the methods laid down by Ehrlich. 
 
 Dr Charles L. Greene, of St. Paul, Minn., who has 
 made a very careful study ^ of this subject, has found 
 that much more satisfactory results are obtained by 
 modifying the proportions of solutions A and i>. Me, 
 therefore recommends the use of a test solution, which 
 shall consist of 100 parts of solution A and i part ot 
 solution B, instead of 40 parts of A and i part of B as 
 ordinarily used. In a study of 3 1 5 cases representing 
 many of the common forms of disease he obtained by 
 means of this modified test solution characteristic reactions 
 
 1 " Medical Record," Nov. 14, i J
 
 184 ABNORMAL CONSTITUENTS OF URINE. 
 
 in only five diseases : i. c, typhoid fever, 95 per cent. ; 
 pneumonia, 9 per cent. ; carcinoma, 50 per cent. ; pulmon- 
 ary phthisis, 12.5 per cent.; and septicemia, 75 percent. 
 He firmly believes that all cases of severe typhoid will 
 show a diazo reaction if the test is properly applied during 
 the height of the disease — that is, between the tenth and 
 eighteenth days. 
 
 Von Jaksch,! on the other hand, believes that the so- 
 called diazo reaction is always due to the presence of ace- 
 tone, and he considers the reaction rather an uncertain test 
 for acetone than a test for anything else. 
 
 The author can recommend Greene's modified test solu- 
 tion, since by its use positive reactions are obtained in a 
 much smaller number of diseases than by the use of the 
 original Ehrlich solution. However, he can not agree with 
 Greene as to its diagnostic value in typhoid, owing to the 
 fact that in some cases of this disease, especially the milder 
 forms, no characteristic reactions can be obtained at any 
 time during the disease. It is certain that many of the 
 urines that show this reaction contain acetone, but further 
 investigation is necessary to prove that the so-called diazo 
 reaction is directly or indirectly due to acetone. 
 
 VARIOUS METALLIC SUBSTANCES. 
 
 Various metallic substances, notably lead, arsenic, and 
 mercury, are eliminated in the urine, and, when suspected, 
 should be carefully sought for. 
 
 Arsenic may be absorbed in either small or large amounts, 
 and is quite readily eliminated in the urine without the aid 
 of drugs. It is, to a slight degree, cumulative — that is, 
 sufficient arsenic may be absorbed in three or four days' 
 time to require from sixty to ninety days for its complete 
 elimination. 
 
 Lead is usually absorbed in very small quantities, and 
 the cause of its ver)-- slow elimination from the body is 
 probably its accumulation in the system as a fixed con- 
 stituent of the tissues. The natural channel of elimination 
 is by way of the kidneys, and in order that it should become 
 a constituent of the urine it must first be converted into a 
 soluble salt of lead. This is best effected by giving potas- 
 
 ' Von Jaksch, "(!liiiical Diagnosis," 1897, p. 375.
 
 METALLIC SUBSTANCES. 185 
 
 sium iodide, which combines with the lead, forming iodide 
 of lead, and is ehminated by the kidneys. Even after 
 giving potassium iodide, and under the most favorable 
 conditions, only minute traces of lead are eliminated in 
 twenty-four hours. Therefore, a large quantity of urine 
 is required for the analysis, and every precaution taken to 
 prevent accidental contamination. 
 
 Analysis. — The first step in the analysis for either ar- 
 senic or lead is (i) the destruction of the organic matter of 
 the urine, and the addition of sulphuric acid for the purpose 
 of driving off the nitric acid, thus leaving the residue in the 
 form of sulphates ; and (2) the application of independent 
 tests for either lead or arsenic as the case may be. 
 
 /. Destnictioji of Orgatiic Matter. — Take at least one 
 liter of urine in an evaporating dish, and evaporate to dr)^- 
 ness over a water-bath. Add to this residue about 100 c.c. 
 of concentrated nitric acid (C. P.), and continue the heat 
 until the acid has evaporated, when a yellow cake remains. 
 Transfer this yellow mass — nitrates and nitro-compounds — 
 to a crucible by means of a porcelain spatula, heat with a 
 Bunsen flame until the mass ignites, and continue the heat 
 until a white residue remains. Cool ; add 10 to 20 c.c. of 
 concentrated sulphuric acid (C. P.), anti heat until all of the 
 nitric acid has been expelled — that is, until the red fumes 
 disappear and dense white fumes are evolved. Cool, and 
 then add from 25 to 50 c.c. of distilled water, and filter, 
 reserving the filtrate for the test for arsenic. The precipitate 
 on the filter is washed several times with distilled water in 
 order to remove all soluble sulphates, and the final residue 
 on the filter reserved for the test for lead. 
 
 2. {a) Process for Arsenic. — The filtrate from the insolu- 
 ble sulphates, which contains any arsenic that may be 
 present, is then introduced into a Marsh apparatus that has 
 been previously tested and found to be free from arsenic. 
 The approximate quantity of arsenic can be judged from the 
 intensity of the mirror of metallic arsenic obtained in the 
 delivery tube, and should be expressed in hundredths of a 
 milligram. 
 
 Great care should be taken to expel all of the nitric acid 
 by means of the sulphuric acid, otherwise an explosion will 
 ensue when the solution is put into the Marsh apparatus. 
 
 (^) Process for Lead. — The residue on the filter-paper, 
 which consists of insoluble sulphates, including lead sul-
 
 186 ABNORMAL CONSTITUENTS OF URINE. 
 
 phate, is thoroughly extracted with hot dilute ammonium 
 acetate containing an excess of acetic acid, and then filtered. 
 A current of sulphureted hydrogen is passed through the 
 filtrate for about an hour, the lead acetate being precipi- 
 tated as lead sulphide. Filter, dissolve the residue in hot 
 dilute nitric acid, run into a watch-glass, and evaporate to 
 dryness over a water-bath. A preliminary test for lead 
 may be made at this time, by drawing through the residue 
 a drop of a moderately strong solution of potassium 
 iodide, and thoroughly drying. If lead be present, the 
 yellow iodide of lead will be obtained. ^ The residue on 
 the watch-glass is then dissolved in hot dilute acetic acid 
 and filtered. The filtrate, which contains the lead in the 
 form of an acetate, is then treated with either a few drops 
 of a saturated solution of potassium chromate, or a few 
 cubic centimeters of dilute sulphuric acid, and allowed to 
 stand twenty-four hours. The solution that contains the 
 lead chromate or sulphate is then filtered, and the precipi- 
 tate, which is usually exceedingly slight, is washed a few 
 times with distilled water. Sulphureted-hydrogen water, 
 which has been previously filtered, is allowed to pass 
 through the filter-paper holding the precipitate, and the 
 filter then carefully dried. If lead be present, a slight black 
 precipitate will be seen adhering to the surface of the filter- 
 paper near its center. 
 
 Mercury. — This substance appears in the urine follow- 
 ing the external or internal use of its various compounds. 
 The test is applied in the following manner : 
 
 Acidulate a portion of the urine with hydrochloric acid, 
 then add copper filings, and heat to from 50° to 60° C. for 
 about five minutes ; let stand until cool. Wash the cop- 
 per filings, place them in a shallow dish, and at one side of 
 the dish, or on a watch-glass that is to be inverted over 
 the filings, place one drop of a i per cent, solution of gold 
 chloride ; heat over a low flame. The mercuiy that is 
 deposited on the copper will be volatilized and will redden 
 the solution of gold chloride. According to Brugnatelli,^ 
 this test is capable of detecting -^^ of a milligram of mer- 
 cury in one liter of urine. 
 
 Chloral. — A simple test for chloral in the urine is the 
 
 ^ This is not a reliable test, as a trace of iron, which is oftpn present, will 
 give the same reaction. 
 
 ^ "Journ. de Pharm.," April, 1890, p. 367.
 
 HEMATOPORPHYRIN. 187 
 
 so-called isocyanplioiyl test. The principle of the test de- 
 pends upon the fact that an alkali decomposes the chloral 
 into formic acid, which immediately unites with the alkali 
 to form a formiate and chloroform, which in the presence of 
 aniline results in a characteristic volatile compound. 
 
 Test. — Take one-third of a test-tube of urine, and add 
 one drop of pure aniline (aniline oil), and about one finger- 
 breadth of an alcoholic solution of sodic hydrate, — or an 
 equal amount of a strong aqueous solution of sodic hydrate 
 and alcohol may be used, — and heat. If chloral be present, 
 a volatile compound, having a very disagreeable odor, is 
 evolved. 
 
 In many instances this test is very unsatisfactory ; it is, 
 therefore, necessary to resort to other more complicated 
 methods, the one proposed by Duroy ^ being advised. 
 
 Iodides and Bromides. — Iodides and bromides make 
 their appearance in the urine after their administration. The 
 presence of iodides is frequently observed in the nitric acid 
 test for albumin. Iodine is set free by the nitric acid, and 
 appears as a reddish-brown color-zone at the juncture of the 
 urine and acid, the color usually becoming gradually diffused 
 through the column of acid. When the presence of an iodide 
 is suspected, the following test may be readily applied : 
 
 Test. — Take one-half test-tube of urine, add a small 
 amount of chloroform, — about one fingerbreadth, — then 
 add a few drops of yellow nitric acid, and shake. The 
 chloroform takes up the iodine, which is set free by the 
 nitric acid, and assumes a pink or purple-red color. 
 
 The presence of bromides is determined in the following 
 manner : 
 
 'Test. — Proceed exactly as in the test for iodine, care 
 being taken to add more of the yellow nitric acid than in 
 the test for iodine, in order to completely set free the 
 bromine. The chloroform takes up the bromine, and 
 assumes an Indian-red color — a mixture of red, yellow, and 
 brown. 
 
 HEMATOPORPHYRIN. 
 
 Hematoporphyrin, CjgHj^NjOg, is a coloring-matter de- 
 rived from the blood, and normally present in the urine, 
 but only in traces. It was discovered in 1871 by Hoppe- 
 
 1 WTiarton and Stille, 1884, p. 395.
 
 188 
 
 ABNORMAL CONSTITUENTS OF URINE. 
 
 Seyler, who found that by treating hematin with concen- 
 trated sulphuric acid and heating, there resulted a com- 
 pound whose acid and alkaline solutions showed unusual 
 spectral bands. To this new compound he gave the name 
 " hematoporphyrin." Since its discovery, it has been recog- 
 nized by a number of observers and under a variety of cir- 
 cumstances. 
 
 Hematoporphyrin is identical with iron-free hematin 
 (Nencki). A urine containing this coloring-matter, when 
 viewed by reflected light, is opaque and almost black ; or, in 
 a thin layer, it is reddish-brown. In an isolated form 
 
 m m m m no 
 
 a /3 \ ^- (5" I ^ \ 
 
 Fig-. 20. — Hematoporphyrin spectra ; i,.\cid; 2, alkaline; 5, neutral. 
 
 hematoporphyrin is nearly insoluble in water, in dilute 
 acetic acid, benzol, and nitrobenzol ; it is slightly solu- 
 ble in ether, chloroform, and amyl alcohol, and readily 
 soluble in alcohol, alkaline hydrates, and carbonates, as 
 well as in dilute mineral acids. 
 
 Spectra. — The acid alcoholic solution shows (Fig. 20, 
 i) two absorption bands : one rather dark, situated between 
 Frauenhofer's lines C and D, with its right border over- 
 lapping D ; and the second, sharpl}- defined, nearly inter- 
 mediate between D and E. 
 
 The a/kaline solution presents (Fig. 20, 2) a four -banded
 
 HEMATOPORPHA'RIN. 189 
 
 spectrum as follows : A faint and very narrow band about 
 midway between C and D ; two between D and E, one 
 with its left border near D, the other including E ; the 
 fourth band, which is the darkest of all, but which, how- 
 ever, is not well defined, includes nearly all of the space 
 between b and F, and incloses F. 
 
 The neutral and victallic spectra are represented in the 
 accompanying illustration (Fig. 20, 3) ; they are less char- 
 acteristic than the acid and alkaline spectra, and therefore 
 will not be described here in detail. 
 
 Clinical Significance. — Since urine normally contains 
 traces of hematoporphyrin, its presence becomes of im- 
 portance only when it is present in large amounts. It was 
 first discovered in the urine by Baumstark (1874) in a case 
 of leprosy, and then by MacMunn, le Nobel, and others in 
 acute articular rheumatism. Neusser found this pigment 
 in cases of phthisis pulmonalis, and pleurisy with effusion. 
 Perhaps its most frequent appearance in large amounts is fol- 
 lowing the prolonged use of sulphonal, trional, or tetronal ; 
 it is only rarely found after one or two doses of any one 
 of these three drugs. ^ It is conmionly found in cases 
 of lead-poisoning, of which Nakarai has reported six ; the 
 author has met with it in cases of lead-poisoning, but 
 never in large quantities. This coloring-matter has also 
 been observed in cases of intestinal tuberculosis (Nakarai). 
 The bearing of nervous phenomena upon the production 
 of hematoporphyrin uria is a subject that requires further 
 study. In two cases reported by Rankin and Partington 
 and one by the author, obscure nervous symptoms were 
 prominent, and possibly had some bearing on the cause of 
 the hematoporphyrinuria. 
 
 Salkowski's Method for the Separation of Hemato- 
 porphyrin. — "Take about 30 c.c. of urine, add baryta 
 mixture (equal parts of a 10 per cent, solution of 
 barium chloride and a saturated solution of barium hy- 
 drate), until it is completely precipitated. Wash once with 
 water, and once with absolute alcohol, using the latter 
 drop by drop. Transfer the precipitate to an evaporating 
 dish, add from 6 to 8 drops of concentrated hydrochloric 
 acid and sufficient absolute alcohol to make a thin pap, 
 then stir thoroughly. Heat over a water-bath, filter through 
 
 1 Ogden, " Boston Medical and Surgical Journal," Feb. 24, 1898.
 
 190 ABNORMAL CONSTITUENTS OF URINE. 
 
 a dry filter-paper, and finally add sufficient absolute al- 
 cohol to make from 8 to lo c.c. of filtrate." 
 
 This solution (acid) may be examined directly with the 
 spectroscope for the bands of acid hematoporphyrin, or it 
 may be rendered alkaline, preferably with amnionic hy- 
 drate, and examined for the characteristic bands of alkaline 
 hematoporphyrin. 
 
 The spectroscopic examination of this alcoholic solution 
 must be made within a few hours after its preparation, since 
 the solution readily decomposes, after which it is useless 
 for observation. 
 
 Detection. — This coloring-matter can only be detected 
 with certainty by means of 'the spectroscope. The four 
 spectral bands of the alkaline solution are most charac- 
 teristic. 
 
 MELANIN. 
 
 Melanin is a pigment that is sometimes found in the 
 urine of persons suffering from pigmented tumors. It is 
 usually found in solution in the urine, and more rarely in 
 the form of small black granules which are in suspension. 
 Freshly voided urine containing melanin is usually trans- 
 parent and of a normal color. When, however, the urine 
 is allowed to stand exposed to the air, the color changes to 
 a brown, and finally to a black. Only in rare instances is 
 the urine black when it leaves the body. 
 
 Melanin is eliminated in the form of a chromogen, — nicla- 
 nogcn, — which becomes oxidized in the air or by oxidizing 
 agents, with a resulting dark or black color due to a de- 
 posit of the pigment, melanin. Just where this pigment 
 is converted into a chromogen in the body has not yet been 
 determined. Ganghofner and Pribram claim that the change 
 takes place in the liver, but this is still a matter of doubt. 
 
 Melanin is insoluble in water, ether, amyl alcohol, and 
 dilute acids. It is readily soluble in sodic and ammonic 
 hydrates, sodic carbonate, and monosodic phosphate ; hence 
 it is not precipitated carbon. It contains iron, sulphur, 
 and nitrogen. The chromogen, melanogen, is readily oxi- 
 dized by potassium bichromate with sulphuric acid, a five 
 per cent, solution of chromic acid, fuming nitric acid, 
 potassium permanganate, and potassium chlorate with 
 hydrochloric acid, with a resulting black color.
 
 PTOMAINES AND LEUCOMAINES. 191 
 
 Litten observed that urine containing melanin did not 
 undergo ammoniacal fermentation, but, instead, became 
 more acid than normally with the formation of a thick 
 fungus-growth on its surface. He also found that the 
 urine often contained a reducing substance similar to 
 glucose ; such a reaction, however, has not been reported 
 by other observers. 
 
 Clinical Significance. — Melanuria is most commonly 
 seen in case of melanotic sarcoma in some part of the 
 body, not necessarily in the kidneys. It has, very rarely, 
 been observed to a marked degree in severe wasting dis- 
 eases, and has also been observed in persons suffering from 
 repeated attacks of intermittent fever. The urine of indi- 
 viduals suffering from melanotic new growths may be en- 
 tirely free from melanin while the growth is actively pro- 
 gressing. 
 
 Detection. — i. The most sensitive test for the presence 
 of melanin is the addition of bromine water, which causes 
 a yellow precipitate that gradually blackens (Zeller). 
 
 2. A few drops of a fairly concentrated solution of ferric 
 chloride will cause the urine to turn gray : if more be added, a 
 precipitate of phosphates falls, carrying the coloring-matter 
 with it, and again dissolves with an excess of the iron solu- 
 tion (v. Jaksch, Pollak). 
 
 3. Sodium nitroprusside with caustic potash and acetic 
 acid gives a deep-blue color, probably due to the formation 
 of soluble and insoluble Prussian blue (v. Jaksch). This 
 test, however, can not always be obtained with melanin 
 that has been isolated from the urine, and the reaction must 
 not be regarded as a test for melanin, or only when other 
 tests have shown the presence of melanin or melanogen. 
 
 Morner separated the coloring-matter that was in the 
 form of a chromogen in the urine by precipitating with 
 baryta water, and then purifying. 
 
 PTOMAINES AND LEUCOMAINES.— TOXICITY OF URINE. 
 
 Ptomaines may be defined as organic chemic com- 
 pounds, basic in character, and formed by the action of 
 bacteria on nitrogenous matter. On account of their basic 
 properties, in which they resemble the vegetable alkaloids, 
 ptomaines may be called putrefactive alkaloids. They have 
 also been called animal alkaloids, but this is a misnomer,
 
 192 ABNORMAL CONSTITUENTS OF URINE. 
 
 because, in the first place, some of them are formed in the 
 putrefaction of vegetable matter, and, in the second place, 
 the term " animal alkaloids " is more properly restricted 
 to the leucomaines, — those basic substances which result 
 from tissue metabolism in the body. 
 
 While some of the ptomaines are highly poisonous, this 
 is not an essential property, and others are wholly inert. 
 Indeed, the greater number of those which have been iso- 
 lated up to the present time do not, when employed in single 
 doses, produce any apparent harmful effects. Brieger re- 
 stricts the term ptomaine to the nonpoisonous basic pro- 
 ducts, and designates the poisonous ones as "toxines." 
 
 Since all putrefaction is due to the action of bacteria, it 
 follows that all ptomaines result from the growth of these 
 organisms. The kind of ptomaine formed will, therefore, 
 depend upon the individual bacterium engaged in its pro- 
 duction, the nature of the material being acted upon, and 
 the conditions under which the putrefaction goes on, such 
 as the temperature, the amount of oxygen present, and the 
 duration of the process. 
 
 All ptomaines contain nitrogen as an essential part of 
 their basic character. In this they resemble the vegetable 
 alkaloids. Some of them contain oxygen, while others do 
 not. The latter correspond to the volatile- vegetable alka- 
 loids, nicotine and coniine, and the former correspond to 
 the fixed alkaloids. 
 
 It was formerly supposed that putrefaction was simply 
 oxidation, but the researches of Pasteur and others have 
 demonstrated the fact that countless myriads of minute 
 organisms are engaged constantly in transforming matter 
 from organic to the inorganic form. Hermetically seal the 
 organic matter and it will remain unchanged indefinitely. 
 
 According to Pouchet, healthy urine contains traces of 
 certain toxic substances of an alkaloidal nature ; and accord- 
 ing to the researches of Bouchard, Lepine, and Guerin, 
 these bodies are more abundant under diseased conditions. 
 They were found by A. Villiers as an invariable manifesta- 
 tion in measles, diphtheria, and pneumonia. Pouchet found 
 in the urine of cholera an alkaloid which was not identical 
 with that observed by him in the feces of the same disease. 
 Feltz found similar bodies in the urine of cancer patients, 
 and Lepine in that of pneumonia. Toxines have been 
 found in the urine of scarlet fever and pneumonia (Albu) ; in
 
 PTOMAINES. 193 
 
 carcinoma of the stomach, and in Addison's disease (Ewald, 
 Jacobsen). Bouchard discovered that human urine acted 
 as a poison when injected into the veins of a rabbit, and he 
 referred the toxic effects to various substances, among which 
 were animal alkaloids. 
 
 A. B. Griffiths has published a series of alkaloids which 
 he has isolated from the urine in several diseases. They 
 are as follows : 
 
 Parotitis. — CgHj^N^O^ (isomeric with lysatin), white prisms, 
 soluble in water, ether, and chloroform ; is neutral, and has a 
 bitter taste. Gives a bright yellow precipitate with phospho- 
 tungstic acid, a white precipitate with phosphomolybdic acid, 
 and a brown precipitate with tannin. On boiling with mercuric 
 oxide it furnishes, first, kreatin, then methylguanidin, then 
 oxalic acid, and finally the base, propylkreatin. It is very 
 poisonous, producing in the cat excitement, a stoppage of the 
 flow of saliva, convulsions, coma, and death, ^ 
 
 Scarlet Fever. — C^H^^NO^, a white, crystalline substance, 
 soluble in water with a faint alkaline reaction. It gives a 
 crystalline compound with chloral hydrate and gold chloride, a 
 yellowish-white precipitate with phosphotungstic acid, a white 
 precipitate with phosphomolybdic acid, and a yellow precipitate 
 with picric acid. It is also precipitated by Nessler's reagent. ^ 
 
 Diphtheria. — Gj^H^^N^Og, a white, crystalline substance 
 which gives a yellow precipitate with tannin, a white precipitate 
 with phosphomolybdic acid, and a yellow precipitate with 
 Nessler's reagent. It appears in cultures of the diphtheria 
 bacillus.^ 
 
 Measles. — CjH.NjQ (glycocyamidin), in the form of white 
 plates, whose solution in water has an alkaline reaction. The 
 compound with platinic chloride is in the form of microscopic 
 needles, and that with HgGl^, nearly insoluble prismatic needles. 
 It is precipitated by picric, phosphomolybdic, and phospho- 
 tungstic acids. It is very poisonous to the cat, causing fever 
 and death in about thirty-six hours. ^ 
 
 Pertussis. — Cj.HjgNO^, a white, crystalline substance, soluble 
 in water, and forms a compound with chloral hydrate, and one 
 with chloride of gold. It gives a white precipitate with phos- 
 phomolybdic acid, a yellow precipitate with picric acid, and a 
 brown precipitate with tannin. It also appears in the cultures 
 of the pertussis bacilli of Afanasieff. '' 
 
 Glanders. — G,.HjgNjOg, a white, crystalline substance, which 
 is soluble in water and has an alkaline reaction. The pre- 
 
 1 "Comptes Reiidiis," cxiii, 656. 2 /_„,_ ^-// 3 /„,■ ,,/_ 
 
 * Loc. cit., cxiv, 497, 1892. 5 j^g^^ ^-ji 
 
 13
 
 194 ABNORMAL CONSTITUENTS OF URINE. 
 
 cipitates with chloral hydrate, chloride of gold, and chloride of 
 platinum are crystalline. It gives a greenish precipitate with 
 phosphotungstic acid, a brownish-white precipitate with phos- 
 phomolybdic acid, a yellow precipitate with picric acid, and 
 is precipitated by Nessler's reagent. It also appears in cul- 
 tures of the bacilli of glanders. When it is injected sub- 
 cutaneously into a rabbit, it causes an abscess at the seat of 
 inoculation, specific nodes in the lungs and spleen, metastatic 
 abscesses, and death. ^ 
 
 Pneumonia. — Cj^^Hj^N^O,, in the form of white, oblique 
 prisms, which are soluble in water ; its solution has an alkaline 
 reaction. It gives a white precipitate with phosphotungstic 
 acid, a yellowish-white precipitate with phosphomolybdic acid, 
 a brownish precipitate with Nessler's reagent, and a yellow pre- 
 cipitate with picric acid. Its solution rotates the plane of 
 polarized light to the right [aj^ = 23. 5°. 2 
 
 Epilepsy. — Cj^H^jN^O,, white, oblique prisms, which dis- 
 solve in water; its aqueous solution has an alkaline reaction. 
 The precipitate with mercuric chloride is greenish white; with 
 silver nitrate, yellowish; with phosphotungstic acid, white; 
 with phosphomolybdic acid, brownish-white; and with tannin, 
 yellow. When injected into animals, it causes tremor, dilatation 
 of the pupils, convulsions, and death.'' 
 
 Erysipelas. — CjjHjgNOj, orthorhombic plates, which are sol- 
 uble in water. It gives a white precipitate with HgCI^; with 
 ZnCljj, a granular precipitate, which, upon heating, dissolves 
 with a resulting decomposition ; with Nessler's reagent a green 
 ])recipitate, with picric acid a yellow precipitate, and with gold 
 chloride, a yellow precipitate, which is soluble in water. The 
 compound with platinic chloride is in the form of prismatic 
 needles. It is also precipitated by phosphotungstic and phos- 
 phomolybdic acids and tannin. It is very poisonous, causing 
 in animals high fever, and death in about eighteen hours.* 
 
 Puerperal Eever. — C^^H^gNO^, a white, crystalline substance, 
 soluble in water and with an alkaline reaction. It gives a 
 red precipitate with tannin, a yellow precipitate with picric 
 acid, and a brownish-white precipitate with phosphomolybdic 
 acid. It is also precipitated by Nessler's reagent. It is very 
 poisonous, killing a dog in about twelve hours. '^ 
 
 Eczema. — C^H,j.NO, a white, crystalline substance, soluble 
 in water and with an alkaline reaction. The compounds with 
 chloral hydrate, gold chloride, and platinic chloride are crystal- 
 line. With phosphotungstic acid it gives a brownish precipitate, 
 with phosphomolybdic acid a yellow precipitate, with picric acid 
 
 1 Loc. lit., cxix, 1382. 1892. 2 /(,j-_ ^if^ 3 1^0^^ cit., cxv, 185, 1892. 
 
 ■* Loc. cit., cxv, 667. * Loc. cit.y cxv, 668.
 
 PTOMAINES. 195 
 
 a yellow precipitate, with AgNOj a yellowish precipitate, and 
 with HgClj a greenish precipitate ; it is also precipitated by 
 Nessler's reagent. When a solution of this substance in steril- 
 ized water is injected subcutaneously into a rabbit, it causes a 
 marked inflammation at the point of inoculation, high fever, and 
 death. ^ 
 
 Influenza.— CgYl^l<iO^, white, prismatic needles, which have 
 a faintly alkaline reaction. The precipitate with phosphotungstic 
 acid is brownish ; with phosphomolybdic acid, yellowish ; with 
 picric acid, yellow ; with tannin, red ; with HgCl^, white ; and 
 with Nessler's reagent, brown ; it is not precipitated by ZnCl . 
 It produces a high fever, and death in eight hours. This 
 ptomaine differs from that of pneumonia. 2 
 
 Carcinoma of the Uterus. —Q^^O^, a white substance in 
 the form of microscopic needles, soluble in water and with 
 an alkaline reaction. It gives a yellow precipitate with phos- 
 photungstic acid, a brownish precipitate with phosphomolybdic 
 acid, a red precipitate with AgNOj, a gray precipitate' with 
 HgCl^, and a brownish precipitate with Nessler's reagent. It 
 causes fever, and death in three hours. ^ ' 
 
 P/eur/t/s.—C.Up^. When precipitated from chloroform, it 
 appears as colorless, right-angled plates with two axes; when 
 separated from hot water, it is in the form of feathery aggrega- 
 tions. With Nessler's reagent it gives a bright yellow precipi- 
 tate, which, upon standing, becomes brownish, while the solu- 
 tion has a reddish color. This precipitate is dissolved, and the 
 solution rendered colorless by heat. It is not precipitated by 
 potassium ferrocyanide in the cold, but when the mixture is 
 heated, it gives a white or bright yellow precipitate, which be- 
 comes green upon standing. Ferric chloride gives a white pre- 
 cipitate ; iodide of potassium and cadmium a red, and iodide 
 of potassium and bismuth a green precipitate. It is poisonous. * 
 Angina Pectoris. — Cjj,HgNO^. A white crvstalline sub- 
 stance, soluble in water, and faintly alkaline! It gives a 
 yellowish precipitate with phosphotungstic acid; a yellow pre- 
 cipitate with phosphomolybdic acid ; a red precipitate with 
 tannin; a green precipitate with AgNOg , a green precipitate 
 with HgCl^ ; and a brown precipitate with Nessler's reagent. 
 It causes fever, and death in two hours. •' 
 
 The experiments of Albu « have, in many in.stances. con- 
 firmed tho.sc of Griffiths. Albu found alkaloids in the 
 
 J Loc. cit., ex VI. 1205, 1893. 1 Loc. at., cxvii, 744, 1893. 
 
 ^ Loc. cit., cxviii, 1350, 1894. 
 
 *"Chem. News," lxx, 109; " Chem. Centralbl.," 1894, 11. icx)0. 
 
 * '^Comptes Rendus," cxx, 1128, 1895. 
 
 8 A. Albu, " Berliner klin. Wochenschr.," xxi, 8 u. 1081, 1894.
 
 196 ABNORMAL CONSTITUENTS OF URINE. 
 
 urine of cases of scarlet fever, measles, pneumonia, diph- 
 theria, phthisis with hectic fever, sepsis accompanying car- 
 cinoma of the uterus, erysipelas, Basedow's disease, tetanus, 
 pernicious anemia, autointoxication with urticaria following 
 acute gastric catarrh, and in diabetic coma. 
 
 Leucomaines are those basic substances which arc found 
 in the living tissues, either as the products of fermentative 
 changes other than those of bacteria, or of retrograde 
 metamorphosis. The first attempt at the systematic study 
 and generalization of these basic substances was made by 
 Gautier, who included under this subject all of those 
 substances which are formed in animal tissues during 
 normal life, in contradistinction to the ptomaines or basic 
 products of putrefaction. The distinction between vege- 
 table and animal alkaloids is not well defined. Vegetable 
 tissues are known to contain not only what are ordinarily 
 designated as ptomaines, such as choline, but also leuco- 
 maines, such as hypoxanthin, xanthin, etc. Under this head 
 must also be placed, on account of their relationship to 
 xanthin, those well-defined alkaloidal bases, caffein and 
 theobromin. 
 
 The leucomaines proper may be divided into two distinct 
 and well-defined groups — (i) the uric acid group, and (2) 
 the kreatinin group. 
 
 The first of these groups contains a number of well- 
 known bases, w'hich are closely related to uric acid. They 
 are as follows : Adenin, hypoxanthin, guanin, xanthin, 
 (uric acid), heteroxanthin, methylxanthin, paraxanthin, 
 carnin, episarkin, pseudoxanthin, cytosin, gerontin, sper- 
 min. 
 
 The members of the kreatinin group have all been dis- 
 covered by Gautier, and by him are regarded as allied to 
 kreatin and kreatinin. They are as follows : Kreatinin and 
 kreatin, crusokreatinin, xanthokreatinin, amphikreatin, and 
 two unknown bases. 
 
 Toxicity of Urine. — The question of the toxicity of 
 normal urine has been the subject of much controversy. 
 From the experiments of Feltz and Ritter, Astaschewsky, 
 Schiffer, Bouchard, Lepine, Stadthagen, Gautier, Guinard, 
 and others, it can now be positively stated that normal 
 urine does possess a certain degree of toxicity. It is more 
 difficult to decide upon the nature of this poison. 
 
 Feltz and Ritter, and, independenth', Astaschewsky,
 
 TOXICITY OF URINE. 197 
 
 arrived at the opinion that the toxicity was chiefly due to 
 the potassium salts of the urine. Although Schiffer ac- 
 knowledged the presence and action of the inorganic salts, 
 he maintained that the urine contained a definite organic 
 poison for the reason that the concentrated aqueous solu- 
 tions from alcoholic extracts of the urine-residue killed 
 large rabbits in doses corresponding to from i to i }4 liters 
 of urine deprived of inorganic salts. 
 
 Bouchard has shown that from 30 to 60 c.c. of normal 
 urine, injected intravenously, will kill a rabbit weighing one 
 kilogram. Hence a man weighing 60 kilograms, and ex- 
 creting 1200 c.c. per diem, would, if 50 c.c. are necessary 
 to kill one kilogram of living matter, secrete enough poison 
 to kill 24 kilograms of animal. Bouchard claims that 
 there are five different poisons that may be met with in the 
 urine, each one of which produces a definite symptom : 
 viz., narcosis, salivation, mydriasis, paralysis, and convul- 
 sions. He found that the day-urine, which is chiefly nar- 
 cotic, is from two to four times more toxic than that 
 secreted during sleep, and that the latter induces convulsions 
 and is antagonistic to the former. Further, that the toxicity 
 is independent of the density, since night-urine is denser 
 than that secreted during the day. Bouchard also claims 
 that the greater part of the toxicity of urine is due to 
 organic poisons, especially to coloring-matters ; and that the 
 potassium salts are regarded as the cause of only a small 
 fraction of the toxicit^^ 
 
 Lepine also found that about 60 c.c. of urine were suffi- 
 cient to kill I kilogram of animal. To the inorganic salts, 
 however, he ascribed a much greater importance, inasmuch as 
 he estimates that 85 per cent, of the intoxication is due to 
 this cause. Stadthagen has also arrived at practically the 
 same conclusion, that from 80 to 85 per cent, of the tox- 
 icity^ is due to the inorganic constituents. A part of the 
 toxic matter — i 5 to 20 per cent. — is therefore due to organic 
 substances. No one organic substance in the urine, such 
 as urea, kreatin, kreatinin, etc., possesses this toxicit)^ 
 
 It is now a well-established fact that the urine of certain 
 infectious diseases, such as cholera (Bouchard) and septi- 
 cemia (Feltz), is far more poisonous than normal urine. 
 That the poisons, basic or otherwise, which are generated 
 within the body by the activity, of bacteria can be excreted 
 in the urine is seen in the fact that immunitv to the action
 
 198 ABNORMAL CONSTITUENTS OF URINE. 
 
 of bacillus pyocyaneus has been conferred on animals by 
 previous injection of urine taken from animals inoculated 
 with that bacillus (Bouchard), or with filtered cultures of 
 the same (Charrin and Ruffer). 
 
 Furthermore, the excretion of the tetanus and diphtheria 
 poisons by the urine has been shown to take place. Thus, 
 Brunner demonstrated the tetanus poison in the urine of 
 experimental animals, but failed with the urine of the dis- 
 ease in man. Bruschettini, however, with the urine of a 
 tetanus patient, produced tetanic symptoms in mice by the 
 injection of from 3 to 10 c.c. subcutaneously. In the urine 
 from diphtheria patients Roux and Yersin demonstrated the 
 presence of the diphtheritic poison by inducing paralysis in 
 animals. Although basic substances are not present in the 
 urine of cholera, they are present in the intestinal discharges 
 (putrescin in only one of four cases — Roos). From cholera 
 feces Pouchet extracted an oily fluid very poisonous to 
 frogs ; whereas Villiers obtained a base which produced 
 convulsions in guinea-pigs. 
 
 In the consideration of the toxines in the urine of infec- 
 tious diseases it must not be forgotten, as pointed out by 
 Jawein, that the poison as well as the specific germ may be 
 present in the urine. Thus, in rabbits that died as a result 
 of infection with anthrax bacillus, erysipelas streptococcus, 
 Eberth's bacillus, and Frankel's diplococcus, the urine 
 was found to contain these organisms.
 
 CHAPTER VI. 
 
 URINARY SEDIMENTS. 
 
 It has already been stated that strictly normal, freshly 
 passed urine of acid reaction contains no sediment except 
 faint flocculi of mucus, which gradually subside toward 
 the bottom, and entangle a few mucus-corpuscles and an 
 occasional epithelial cell. Should the urine, however, be 
 alkaline, as is frequently the case three or four hours after 
 a meal, it may be more or less cloudy at the moment it is 
 passed, and quickly deposit a flocculent precipitate of earthy 
 phosphates, which may occupy considerable bulk. Upon 
 microscopic examination the sediment will be found to con- 
 sist of amorphous granules, which will quickly disappear on 
 the addition of a few drops of acetic acid. 
 
 When a normal urine without sediment has stood for 
 some time, especially at a moderate or low temperature, 
 there is frequently observed a deposit of amorphous gran- 
 ular matter, usually of a pink color, and sometimes it is 
 almost colorless. It is readily soluble by heat,^ and is 
 composed of amorphous urates — a mixture in varying pro- 
 portions of acid urates of potassium, sodium, and ammo- 
 nium, with which urates of calcium and magnesium are 
 occasionally commingled. Such a deposit of urates may 
 also contain crystals of uric acid or octahedral crystals of 
 calcium oxalate. Bacteria from the air and other sources 
 frequently make their appearance in the sediment ; also, 
 often, spores of torula cerevisiae — the yeast fungus — and 
 spores of penicillium glaucum are found. 
 
 When a urine becomes alkaline as a result of the de- 
 composition of the urea into ammonium carbonate, it has 
 an entirely different appearance, and it is at this time that 
 we find myriads of bacteria, together with a deposit of 
 phosphates, both amorphous and crystalline. At the very 
 beginning of the reaction, when the urine may still be 
 
 199
 
 200 URINARY SEDIMENTS. 
 
 neutral or even faintly alkaline, any crystals of uric acid that 
 may be present begin to dissolve and to change their form 
 so as to become more or less unrecognizable, while on their 
 fragments may often be seen to adhere prismatic crystals of 
 urate of sodium and dark spheres of urate of ammonium. 
 As the reaction becomes more strongly alkaline the uric 
 acid disappears altogether, and the field becomes crowded 
 with granules of amorphous phosphate of lime, beautiful 
 triangular prisms (" coffin-lid " shaped crystals) and irregu- 
 larly shaped crystals of ammonio-magnesium phosphate, 
 and the dark spheres of urate of ammonium which are often 
 beset with spiculae. (Fig. 28.) 
 
 The methods used for the examination of urinary sedi- 
 ments are both microscopic and chemic. By means of the 
 microscope various deposits are recognized by characteris- 
 tics that are in themselves diagnostic. But the micro- 
 scope does not in all instances reveal the exact nature of 
 certain substances, and then it becomes necessary to resort 
 to chemic tests, which, together with the microscope, afford 
 reliable data concerning the substances examined. 
 
 METHODS OF OBTAINING URINARY SEDIMENTS. 
 
 Two methods are in common use for obtaining urinary 
 sediments — /. e., {a) centrifugal victJwd and {Ji) gravity 
 mctliod. 
 
 (a) Centrifugal Method. — More recent experience has 
 demonstrated the immense advantages of the centrifugal 
 method of obtaining urinary sediments for purposes of 
 microscopic examination. The principle of this method de- 
 pends upon the fact that when the urine is placed in tubes 
 and revolved at a high speed upon horizontal rotating arms, 
 a centrifugal force is exerted upon all solid particles in the 
 urine, hundreds of times greater than gravity, and, conse- 
 quently, the urinary sediment is deposited in the bottom of 
 the tubes almost immediately, irrespective of the specific 
 gravity of the urine or the character of the sediment. 
 Some of the advantages of this method are as follows : 
 
 1. Centrifugal sedimentation of the urine permits of an 
 immediate microscopic examination, instead of waiting for 
 from twelve to twenty-four hours as by the old method of 
 gravity. 
 
 2. The centrifugal method secures more completely con-
 
 CENTRIFUGAL METHOD. 
 
 201 
 
 centrated sedimentation, and, therefore, it is better suited 
 for purposes of microscopic diagnosis. 
 
 3. Microscopic examination of freshly voided urine may- 
 be made before casts or morphologic elements have had 
 time to undergo maceration or solution in the urine, and 
 before the appearance of large numbers of bacteria, which 
 always greatly obscure the microscopic field. 
 
 4. It affords the only positive means of distinguishing 
 between primary and secondary crystalline elements in 
 the urine, since by this method only can the urine be 
 
 Fig. 21. — The Purdy electric centrifuge. 
 
 examined microscopically as soon as voided, and, there- 
 fore, before the formation of those crystals that are de- 
 posited in nearly all normal urines that are left standing 
 for several hours. 
 
 5. By the old method of gravity, it sometimes happens 
 with urines of high specific gravity that the lighter casts 
 (such as those of the narrow, hyaline order) fail to settle, 
 and thus elude detection. The centrifuge precipitates all 
 casts without delay, irrespective of the above-named condi- 
 tions.
 
 202 
 
 URINARY SEDIMENTS. 
 
 It will, therefore, be readily seen that the centrifuge is 
 destined to supersede the old method of gravitation for all 
 purposes of urinary sedimentation. 
 
 Of the various number of centrifugal machines on the 
 market the electric centrifuge devised by Dr. Purdy, of 
 Chicago, is undoubtedly the most serviceable. 
 
 The Purdy electric cenfrifnjj^e,'^ shown in figure 21, can 
 be operated on the interrupted incandescent illuminating 
 current, on the constant illuminating current, on the storage 
 
 c.c.\ 
 
 Fig. 22. — Tubes for the Purdy centrifuge : a, Percentage tube ; b, sediment tube. 
 
 current, and on the galvanic current (sulphuric cell) ; and 
 is suitably adjusted for operation at any voltage from 10 to 
 120 volts, providing the nature and strength of the current 
 be specified. 
 
 The apparatus is capable of all grades of speed from 500 
 to 10,000 revolutions per minute, according to the strength 
 of the current used and the resistance of the arm. When 
 the sediment tubes (Fig. 22), each with a capacity of 15 
 
 ^ The Purdy electric centrifuge is manufactured by Williams, Brown and 
 Earle, 918 Chestnut St., Philadelphia.
 
 CENTRIFUGAL METHOD. 
 
 203 
 
 c.c, are filled and introduced into the aluminium shields of 
 the apparatus, it is capable of sustaining a speed of from 
 2000 to 2500 revolutions per minute, the tips of the tubes 
 at the same time describing a circle, the diameter of which 
 is 13^ inches. The centrifugal force is from two to three 
 thousand times greater than gravity, so that all the elements 
 of a sediment — organized and nonorganized — are in from 
 three to five minutes forced to the extreme tips of the tubes, 
 where they may at once be utilized for microscopic purposes. 
 Concerning the Jiand centrifuge, of which there are a large 
 
 1/ 
 
 Fig. 23. — The Bausch and Lomb spiral-gear urinary centrifuge with tubes (one-fourth 
 
 actual size). 
 
 number on the market, it is to be said that only a compara- 
 tively {q.v^ are of practical value. The spiral-gear' centri- 
 fuge, manufactured by The Bausch & Lomb Optical Co., 
 of Rochester, N. Y., has been extensively used by the 
 author, and can be highly recommended. 
 
 The centrifuge proper (Fig. 23) consists of a small circu- 
 lar case containing a train of gears made of extra hardened 
 bronze, and having teeth spirally cut, three of which are 
 engaged at all times. This form of gearing runs easier and
 
 204 
 
 URINARY SEDIMENTS, 
 
 is more durable than any of the straight gear machines, as 
 it prevents backlash or lost motion. The centrifuge is very- 
 small, yet it is strong and capable of a high rate of speed — 
 3000 revolutions per minute. 
 
 The glass tubes used for holding the urine are both gradu- 
 ated and plain, and have practically the same shape as 
 those already described in connection with the electric 
 
 centrifuge. These tubes are car- 
 ried in aluminium shields, and are 
 supported on elastic cushions to 
 prevent breakage during rotation. 
 (b) Gravity Method.— The old 
 so-called gravity method of obtain- 
 ing a sediment, and one that is not 
 without advantages at the present 
 time, consists in placing the urine 
 in a urine glass (Fig. 24) having 
 parallel sides and a concave- bot- 
 tom, ^ then covering with a piece of 
 filter-paper, a glass plate, or other 
 convenient article, in order to keep 
 out dust and other foreign matter. 
 Allow the glass to stand, prefer- 
 ably in a dark and moderately cool 
 place, until the urine is well settled. 
 The time required for a sediment 
 that is suitable for microscopic ex- 
 amination is from one to twenty- 
 four hours ; usually a satisfactory 
 sediment is obtained within twelve 
 hours. Occasionally, in a normal 
 urine or one of high specific grav- 
 ity, the sediment does not fall to 
 the bottom of the glass, but, instead, is suspended in the 
 column of urine ; this cloud is sometimes termed the 
 " nubecula." 
 
 The chief objection to the use of this method is the 
 length of time required for the urine to settle. Further- 
 
 Fig. 24. — Urine or sediment 
 glass. 
 
 ^ The urine glass, also sometimes termed sediment glass, should be made 
 of perfectly clear, smooth glass which is free from air-bubbles. The bottom 
 of the glass should be concave and without the objectionable upward, nipple- 
 like projection so often found in the ordinary sediment glass. These glasses 
 can be obtained of The Richard Briggs Co., 287 Washington Street, Boston.
 
 GRAVITY METHOD. 
 
 205 
 
 more, unless preservatives are used, the urine often un- 
 dergoes alkaline decomposition before a sediment settles, 
 when it becomes unfit for microscopic examination. But 
 preservatives may be used without altering the sediment or 
 otherwise interfering with the microscopic examination. 
 Whenever this method is used, it is the habit of the writer 
 to add to that portion of the urine that is set aside for 
 sediment from 15 to 30 c.c. of a saturated 
 (4 per cent.) solution of boric acid, which, 
 under ordinary conditions, preserves the 
 urine until the sediment is satisfactorily 
 settled. A drop or two oi formalin (for- 
 maldehyde gas in water) may be added to 
 the urine, but not always with satisfactory 
 results, since a peculiar crystalline (?) pre- 
 cipitate is often deposited, especially if too 
 much is added, which seriously interferes 
 with the examination of the sediment. 
 Other preservatives, such as chloral, sali- 
 cylic acid, chloroform, etc., may be used, 
 but with even less satisfactory results. 
 
 There can be no question of the many 
 advantages of the centrifugal method over 
 the gravity method for obtaining sediments, 
 and the writer strongly recommends its use 
 for both the practitioner and the student. 
 There are, however, two disadvantages : 
 viz., (i) by the use of the centrifuge the 
 proportion of abnormal elements, such as 
 casts, blood globules, pus-corpuscles, etc., 
 may be very large, since the greater part ot 
 the sediment is included in a drop or two 
 of fluid, whereas the sediment obtained by 
 gravity might really contain very few ab- 
 normal elements ; the examiner is thereby 
 misled as to the extent of the pathologic 
 process. This is particularly the case in judging of the 
 amount of pus which a given urine contains, also the pro- 
 portion of crystalline elements in a urine. (2) The drop or 
 two of sediment obtained by the use of the centrifuge may 
 contain so much pus, so many crystals, or epithelial cells 
 as to obscure any renal casts that would otherwise be 
 readily detected in a sediment obtained by gravity. 
 
 Fig. 25. — Pipette for 
 sediments.
 
 206 URINARY SEDIMENTS. 
 
 THE PREPARATION OF SEDIMENTS FOR MICROSCOPIC 
 EXAMINATION. 
 
 Having obtained a well-settled sediment, either by the 
 use of the centrifuge or by allowing the urine to stand in a 
 urine glass to settle by gravity, the examiner should supply 
 himself with a suitable pipette, slides, and cover-glasses, 
 and a microscope of the best make. 
 
 1. Pipette. — Great care should be used in making a 
 pipette, for unless the drawn-out tip is of the proper shape 
 and the opening of the proper size, a suitable sediment can 
 not be obtained. The pipette shown in figure 25 repre- 
 sents the approximate size of the glass tubing that should 
 be used, and the shape of the drawn-out, or, what may be 
 termed the proximal, end. If the proximal tip be abruptly 
 drawn to nearly a point, and the opening be too small, a 
 good sediment can not be obtained. The other end, or 
 distal end, of the glass tube should be rounded off in the 
 flame so as to prevent cutting the finger, and the opening 
 should be nearly as large as the diameter of the tubing. 
 
 2. Slides and Cover-glasses. — These should be free 
 from scratches and be perfectly clean. The No. 2 square or 
 oval cover-glass is perhaps best suited for the examination 
 of urinary sediments. 
 
 3. Microscope. — It will not be necessary here to give a 
 detailed description of the microscope or to refer to its use. 
 The instrument should be one of the best : viz., the Leitz 
 or Zeiss microscope made in Germany, or the Bausch & 
 Lomb microscope made by the Bausch & Lomb Optical 
 Co., of Rochester, N. Y. For the examination of urinary 
 sediments the Abbe condenser can not be satisfactorily 
 used, since too much light is furnished thereby, the ordinary 
 diaphragm supplied with each instrument being most ser- 
 viceable. 
 
 Method. — The pipette, held between the thumb and 
 middle and ring-fingers, is carried to the bottom of the 
 sediment glass with the index-finger (which should be per- 
 fectly dry) pressed upon the distal end. When the pipette 
 has reached the heaviest portion of the sediment, it is gently 
 rotated between the thumb and fingers without removing 
 the index-finger from the distal end, and a small amount of 
 the sediment allowed to enter slowly. The pipette is with- 
 drawn from the urine and carefully zviped from end to end
 
 CLASSIFICATION OF SEDIMENTS. 
 
 207 
 
 to remove all fluid from its outer surface. Two or three 
 slides are then placed on the table, and a drop of the sedi- 
 ment placed on each and covered with the cover-glasses. 
 The preparations are then ready for microscopic examina- 
 tion. The writer, who uses a Leitz microscope, is in the 
 habit of examining the specimen first with a low power, — 
 No. 5 objective and No. i eye-piece, — and then with a 
 higher power — 7 objective and i or 3 eye-piece. Having 
 carefully searched the three preparations, it is probable that 
 most or all of the elements have been seen. 
 
 It' is sometimes necessary, especially if the sediment is 
 bulky, to first take a sediment from the upper layer, and 
 then one from the bottom layer, in order to be able to 
 detect the lighter elements (casts, etc.) and the heavier sub- 
 stances (crystals). 
 
 It sometimes happens that casts and cells do not settle, 
 but are held in suspension in a cloud near the top of the col- 
 umn of urine. When such a cloud is present, a drop of 
 sediment from it should alwa\'s be examined. 
 
 URINARY SEDIMENTS. 
 
 The urinary sediments are best classified, for the purpose 
 of study, into two groups — i. e., nonorganized or chemic, 
 and organized or anatomic deposits, as follows : 
 
 I. NONORClAMZEl). 
 
 I. 
 
 Uric acid 
 
 (cr\-stalline). 
 
 2. 
 
 Urates 
 
 (amorphous or crystalline). 
 
 3- 
 
 Hippuric acid 
 
 (crystalline). 
 
 4- 
 
 Calcium oxalate 
 
 (crystalline). 
 
 5- 
 
 Calcium phosphate 
 
 (amorphous or crystalline). 
 
 6. 
 
 Ammonio-magnesium 
 
 phosphate — triple phosphate 
 (cr}^stalline or amorphous). 
 
 7- 
 
 Calcium carbonate 
 
 (crystalline or amorphous). 
 
 8. 
 
 Cystin 
 
 (cry.stalline). 
 
 9- 
 
 Cholesterin 
 
 (crj'stalline). 
 
 10. 
 
 Leucin 
 
 (crystalline). 
 
 II. 
 
 Tyrosin 
 
 (crystalline). 
 
 12. 
 
 Hematoidin — bilirubin 
 
 (crystalline). 
 
 13- 
 
 Xanthin 
 
 (crystalline or amorphous). 
 
 14. 
 
 Indigo 
 
 (crystalline).
 
 208 URINARY SEDIMENTS. 
 
 
 II. ORGANIZED. 
 
 I. 
 
 Epithelium. 
 
 2. 
 
 Nucleo-albumin (mucin). 
 
 3- 
 
 Blood. 
 
 4- 
 
 Pus. 
 
 5- 
 
 Renal casts. 
 
 6. 
 
 Spermatozoa. 
 
 7- 
 
 Fat. 
 
 8. 
 
 Fibrin. 
 
 9. Fungi and infusoria. 
 
 10. Morbid growths. 
 
 1 1 . Parasites. 
 
 III. EXTRANEOUS SUBSTANCES. 
 
 NONORGANIZED SEDIMENTS. 
 
 The nonorganized or chemic sediments of the urine are 
 usually crystalline, although in a few instances they are 
 amorphous, and are to be distinguished from the organized 
 sediments described under a separate heading. 
 
 Uric Acid.i — Uric acid crystals are frequently found as 
 constituents of the urinary sediment. They always occur 
 in an acid urine, and usually in one that is strongly acid. 
 They appear in normal as well as in pathologic urine. The 
 crystals are usually colored a deep yellow or orange-red, 
 sometimes a pale yellow, and sometimes brown, and occa- 
 sionally they are colorless. Pure uric acid is very difficultly 
 ciystallizable ; therefore, the crystals of uric acid found in 
 the sediment are those of the impure acid. 
 
 Uric acid crystallizes in a variety of shapes, but the 
 typical shape may be said to be the rhombic plate. It is, 
 however, comparatively rare to find these typical forms in 
 the sediment, the great majority of the ciystals found being 
 modifications of this form. (Fig. 26.) Thus we find the 
 rectangular prisms, the barrel, whetstone, club, spear, 
 wedge, dumb-bell, and diamond shapes ; also the crystal 
 resembling a comb with teeth on two sides, the rosette 
 (coalescence of crystals of varying shapes) and irregularly 
 shaped crystals, all of which have a more or less yellow 
 color, except the diamond form, which is not infrequently 
 
 1 For General Consideration, Properties, and Tests for Uric Acid see pages 
 59 to 71.
 
 URIC ACID. 
 
 209 
 
 nearly colorless. There are many more forms of uric acid 
 crystals than those mentioned, and practice soon teaches 
 one to recognize these varied forms, even though they may 
 deviate much from the typical shape. The rosette form 
 (Plate 5) may at times be fan shaped ; and, again, the indi- 
 vidual crystals may have coalesced so as to form a large, 
 solid, compact spherule, often with sharp spicules projecting. 
 These large rosettes and spherules of uric acid frequently 
 have the appearance of particles of sand, hence the term 
 uric acid sand. Occasionally, the coalescence of the uric 
 
 Fig. 26. — Forms of uric acid : i, Rhombic plates ; 2, whetstone forms ; 3, 3, quadrate 
 forms ; 4, 5, prolonged into points ; 6, 8, rosettes ; 7, pointed bundles ; 9, barrel forms 
 precipitated by adding hydrochloric acid to urine. 
 
 acid cr>^stals results in much larger bodies, which have been 
 termed wic acid gravel, and still larger, uric acid calculi. 
 Ultzmann claims that the irregular forms of uric acid, espe- 
 cially the rough and pointed forms, are almost always an 
 accompaniment of uric acid calculi. 
 
 Uric acid crystals may be either primary (those separating 
 from the urine inside the body) or secondary (those separating 
 from the urine outside the body), but the author knows of 
 no certain means from the appearance of the crystals them- 
 selves of distinguishing between the two. The only certain 
 14
 
 210 URINARY SEDIMENTS. 
 
 means of determining the presence of the primary crystals 
 is to obtain a freshly passed specimen and, after thoroughly 
 agitating, centrifugalize while still warm — it may be neces- 
 sary to centrifugalize several portions in order to obtain the 
 crystals, if present. With these precautions, any crystals 
 found are primary ; such crystals are usually highly col- 
 ored, compact, and in the form of the rosette or spiculated 
 spherule, although other forms may be primary. 
 
 All acid urines tend to deposit their uric acid sooner or 
 later. The time of on. set of precipitation varies from a 
 few hours to five or six days, or even longer. It possesses 
 a strong tendency to crystallize upon contact with any 
 organic or inorganic substances ; thus, upon standing the 
 crystals often cling to the sides of the glass or to threads 
 or specks suspended in the urine. This fact renders it 
 more liable than any other crystalline deposit to form about 
 
 / 
 
 Fig. 27. — Acid sodium urate crystals. 
 
 a nucleus in the urinary tract and result in gravel or cal- 
 culi. 
 
 Urates. — (a) Acid Sodium Urate. — This salt of uric 
 acid occurs in urine of acid, neutral, or faintly alkaline reac- 
 tion, and is generally amorphous, but sometimes crystalline. 
 When amorphous, it forms a predominant part of the de- 
 posit of amorphous or mixed urates, seen in the bottom of the 
 vessel after the urine cools. It crystallizes in colorless, 
 prismatic, needle-like crystals, which are usually arranged in 
 stellate (star-like) clusters. (Fig. 27.) Occasionally, the 
 needle crystals are found alone. Sometimes the clusters 
 have a dumb-bell appearance, each half of which is striated 
 and broad at the extremities ; one-half of one of the 
 dumb-bell-like clusters, viewed from above, would be fan 
 shaped. 
 
 Acid sodium urate is very insoluble in cold water (1200 
 parts) but quite soluble in hot water.
 
 Plate 5 
 
 Uric- ACID Crystals with Amorphous Urates (after Peyer).
 
 URIC ACID AND URATES. 
 
 211 
 
 (b) Acid Ammonium Urate. — This is crystalline and 
 occurs in the urinary sediment as yellowish-red or dark- 
 brown spherules, which are studded with fine, sharp-pointed 
 spicules. To these the terms " thorn-apple crystals " and 
 "hedge-hog crystals" have been given. These spicules 
 may be short or long, sometimes branched, curved, or 
 bent. (See Plate 6.) It also frequently crystallizes in 
 fine needles, which are in clumps, having a sheaf-of-wheat 
 arrangement ; and sometimes in the center of a clump a 
 small spherule may be found embedded. These crystals 
 are also colored dark-brown, and should not be mistaken 
 for tyrosin crystals or the groups of colorless crystals of 
 
 
 
 Fig. 28.— Deposits in amnioniacal urine (alkaline fermentation) : A, Acid amnnmium 
 urate; B. ammonio-magnesium phosphate ; C, bacterium ureae. 
 
 acid sodium urate, although by some they are considered 
 identical with the latter. 
 
 The crystals of acid ammonium urate are soluble in iiot 
 water, and dissolve in hydrochloric acid and other acids, 
 with the subsequent precipitation of uric acid crystals. 
 When they are treated with potassic hydrate, the odor of 
 ammonium is evolved. 
 
 The crystals often occur in acid urine with a deposit of 
 amorphous urates. They are very frequently deposited 
 during the alkaline fermentation of the urine, and are found, 
 along with amorphous earthy pho.sphates and crystals of 
 ammonio-magnesium phosphate. (Fig. 28.) It is, in fact, 
 the only urate found in strongly alkaline urine.
 
 212 URINARY SEDIMENTS. 
 
 (c) Acid Potassium Urate. — This exists in acid urine, 
 is amorphous, and forms a part of a deposit of amorphous 
 urates. Like acid sodium urate, it is very insoluble in cold 
 and quite soluble in hot water. 
 
 (d) Acid calcium urate is a constituent of acid urine, 
 but occurs only rarely and usually in small quantity in a 
 deposit of amorphous urates. It is an amorphous white 
 powder, difficultly soluble in cold water, faintly soluble in 
 hot water, and is known to have calcium for its base, since, 
 upon incineration, it leaves a residue of calcium carbonate. 
 
 Amorphous or Mixed Urates. — These consist, as 
 mentioned, of acid sodium urate, acid potassium urate, 
 ammonium urate, and sometimes acid calcium and mag- 
 nesium urates. A deposit of amorphous urates frequently 
 occurs in urine, more especially in concentrated urine, 
 upon cooling to the room-temperature, and particularly if 
 subjected to a low temperature. The deposit usually 
 falls rapidly to the bottom of the urine glass, and when 
 settled, has a pink or yellowish-red color due to uroery- 
 thrin ; it may rarely be colorless. Occasionally, a portion 
 of the deposit is so finely divided that it will not settle, the 
 urine remaining turbid throughout ; but even under such 
 circumstances the greater part settles, forming a heavy 
 deposit. 
 
 Detection of Amorphous Urates. — First determine the 
 reaction of the urine, and if acid, pour a small portion of 
 the turbid urine into a test-tube and heat gently, but avoid 
 the boiling temperature. If amorphous urates are present, 
 they are dissolved by the heat, and the urine becomes clear. 
 They are dissolved by an alkaline hydrate, but with the 
 simultaneous precipitation of the earthy pho.sphates. When 
 amorphous urates are treated with acetic acid or any of the 
 strong mineral acids, they are dissolved, with the subse- 
 quent crystallization of uric acid. They also respond to 
 the murexide test. 
 
 Treatment of a Sediment Containing Amorphous 
 Urates. — It is obvious that when a sediment consists chiefly 
 of amorphous urates, most of the formed elements will be 
 obscured by the abundance of urate granules ; it, therefore, 
 becomes necessary to get rid of the amorphous urates be- 
 fore a satisfactory microscopic examination can be made. 
 This is best accomplished in the following manner : 
 
 Fill a urine glass with the urine, allow the sediment to
 
 Plate 6 
 
 Ammonium Urate, showing Spherules and Thorn-apple-shaped 
 Crystals (after Peyer).
 
 URIC ACID AND URATES. 213 
 
 settle thoroughly ; decant the supernatant urine, and then 
 add warm water to the sediment, using an amount of water 
 equal to the quantity of urine originally taken. The warm 
 water dissolves the urates and, at the same time, dilutes the 
 urine so that they will not reform. Then allow the sedi- 
 ment to settle again, or centrifugalize, and examine in the 
 usual way. 
 
 Aside from the solution of the urates, the addition of 
 warm water modifies the sediment in only one particular — 
 /. e., any normal blood present will become swollen and lose 
 its color (abnormal blood). 
 
 Care should be taken to avoid the use of boiling water, 
 or water having a high temperature, else any albumin 
 present will be coagulated, rendering the sediment unfit 
 for examination. 
 
 Clinical Significance. — /. Uric Acid : Uric acid crys- 
 tals are frequently found in the urine of persons who are in 
 perfect health, especially when the urine is concentrated or 
 unusually acid. As has been mentioned, a deposit of uric 
 acid crystals does not necessarily indicate an increase of uric 
 acid in the urine, for, as a matter of fact, a deposit may 
 occur even when the uric acid is much diminished. Any 
 urine upon standing for several hours is apt to deposit 
 crystals of uric acid. Under such circumstances crystals of 
 uric acid are of no clinical importance. 
 
 A deposit of uric acid is often the result of a hearty meat 
 diet, especially when coupled with sedentary habits of life 
 and faulty digestion. Likewise, a deposit is frequently a 
 result of increased tissue metabolism and, consequently, an 
 increased formation of uric acid, attended with emaciation, 
 headaches, and nervous debility. An increased formation 
 of uric acid is sometimes the result of conditions in which 
 the oxidizing power of the system is seriously impaired, as 
 in diseases of the respiratory tract and circulatory organs. 
 
 Uric acid sediments are often met with in acute febrile 
 conditions, in which there is a marked diminution in the 
 aqueous element and an increased acidity. A deposit of 
 uric acid is of frequent occurrence in gout, especially fol- 
 lowing a paroxysm ; also in the early stages of chronic 
 interstitial nephritis, particularly when the disease is the 
 result of gout. Given, then, a patient with gouty ten- 
 dencies, who has habitually taken a hearty meat diet, and 
 whose urine shows a constant deposit of uric acid cr>'stals
 
 214 URINARY SEDIMENTS. 
 
 and evidences of more or less renal disturbance, an early- 
 stage of chronic interstitial nephritis should be strongly 
 suspected. Crystals of uric acid are frequently seen tem- 
 porarily in the sediment during the convalescent stage of 
 an acute diffuse nephritis. 
 
 In the urine of children who are convalescing from scarlet 
 fever or other acute exanthem, uric acid deposits are very 
 apt to occur, and even uric acid gravel may be found under 
 such circumstances. 
 
 Primary uric acid, or that formed inside the body, is 
 always of importance. It is frequently accompanied by 
 evidences of marked irritation of the kidney or other por- 
 tion of the urinary tract. The primary crystals should in 
 all instances be distinguished from those that are secondarily 
 formed. (See p. 209.) 
 
 2. Urates : A deposit of amorphous urates, like uric acid, 
 often occurs in any urine that is concentrated or unusually 
 acid, seen especially in acute febrile diseases. In diseases 
 of the liver and heart, also in subacute glomerular (paren- 
 chymatous) nephritis, a deposit of amorphous urates often 
 takes place. A primary deposit of acid ammonium urate 
 is of frequent occurrence in the kidneys of the new-born, 
 and crystals of the same may be found in the urine. 
 Further than this, the clinical importance of urates is much 
 the same as that of uric acid. It should be borne in mind 
 that urines that are allowed to stand in a cold place are very 
 apt to deposit amorphous urates. 
 
 Phosphates. — The earthy phosphates are the only salts 
 of phosphoric acid that appear in the urinary sediment. 
 They consist of (^) auunonio-niagnesijini pJiospJiate or triple 
 phosphate, and {b) calcium pJiosphate. These deposits are 
 found only in very feebly acid, neutral, or alkaline urine, and 
 are most abundant following the alkaline fermentation. 
 They appear to the naked eye as bulky, opaque, white de- 
 posits, unless they are accompanied by blood, with which 
 they are then more or less tinged. The urine itself is likely 
 to be turbid from the presence of amorphous phosphate of 
 calcium in suspension, especially after a vegetable diet. It 
 often has an ammoniacal and sometimes a fetid odor, though 
 not necessarily. Phosphatic deposits are especially abun- 
 dant in the urine of some affections of the bladder, and often 
 attend diseases of the spinal cord, because of paralysis of 
 the bladder and consequent retention of urine.
 
 PHOSPHATES. 
 
 215 
 
 (a) Ammonio-magnesium phosphate, MgNH^PO^.- 
 6H./J, or triple phosphate, is a crystalline deposit occurring 
 in two forms : 
 
 1. The triangular prism with beveled edges is most 
 typical and frequent. (Fig. 29.) There are many modifi- 
 cations of this type, one of the most common being the so- 
 called " cofifin-lid " crystal, which is the triangular prism with 
 one of the three angles wanting. Frequently, the crystals 
 are shortened so as to form squares, and these are the ones 
 already referred to as being possibly mistaken for the octa- 
 hedral crystals of calcium oxalate. 
 
 2. The stellate or feathery crystals of triple phosphate 
 (Fig. 29) are less commonly seen. They predominate in 
 
 Fig. 29. — Triple-phosphate crystals. 
 
 the precipitate that follows the addition to the urine of 
 ammonic hydrate. These crystals gradually undergo con- 
 version into the prismatic form. 
 
 (b) Calcium phosphate is either amorphous (normal 
 salt, Ca^{VO^).^ or crystalline (acid salt, CaHPOJ. (i) 
 The aniorpJunis form is most frequently found as a whitish 
 flocculent deposit ^ in the after-meal urine. It is often 
 precipitated from the urine by heat, and constitutes an 
 important source of error in testing for albumin by heat ; 
 this precipitate is readily dissolved by acetic acid. This 
 form of calcium phosphate sometimes occurs in a very 
 feebly acid urine as minute, pale, highly refractive granules. 
 
 ^ This deposit usually consists partly of magnesium phosphate.
 
 216 URINARY SEDIMENTS. 
 
 which are arranged in irregular clumps, and often adherent 
 to renal casts or other organized elements of the sediment. 
 Amorphous phosphate of lime is a frequent accompaniment 
 of triple phosphate in a neutral or alkaline urine. 
 
 (.?) Acid calcium pJwsphate, or the crystalline form, is fre- 
 quently found in urinary deposits, and is often mistaken for 
 the crystals of acid urate of sodium. Crystals of acid 
 phosphate of calcium sometimes occur alone, sometimes with 
 crystals of triple phosphate, and not infrequently with the 
 amorphous form of calcium phosphate. They are also met 
 with in a urine of weak acid reaction, but one that is about 
 to undergo the alkaline fermentation. Acid calcium phos- 
 phate crystallizes in the form of prisms that are found either 
 singly or in stellate groups. (Fig. 30.) Frequently, the 
 groups have a fan-like, and sometimes a club-like, arrange- 
 
 Fig. 30.— Acid calcium phosphate crystals. 
 
 ment. Usually, the individual crystals are small, but may 
 be large and thick, with one end beveled to a sharp point, 
 with cutting-edges on each side. 
 
 It is often impossible to decide from the microscopic 
 appearance of these crystals whether they are acid calcium 
 phosphate or acid sodium urate, especially when found in 
 a faintly acid urine. These two forms of crystals are dis- 
 tinguished by treating them with acetic acid, which rapidly 
 dissolves the phosphate crystal, while that of acid sodium 
 urate is more slowly dissolved, and is subsequently replaced 
 by crystals of uric acid. The crystals of acid calcium phos- 
 phate are often accompanied by crystals of calcium oxalate. 
 
 Clinical Significance. — It has already been shown (p. 
 29) that a deposit of amorphous phosphates may occur in 
 health in a urine alkaline from fixed alkalies, notably two 
 or three hours after a hearty meal. If this deposit be tem-
 
 CALCIUM OXALATE. 217 
 
 porary, it is of no clinical importance ; if, however, it be 
 permanent, and the twenty-four-hour urine contain a heavy 
 deposit of amorphous phosphates, it becomes of pathologic 
 importance, and in most instances indicates a low general 
 metabolism. Ordinary tonic treatment usually results in a 
 complete disappearance of the deposit. 
 
 Crystalline phosphates when deposited zvithiii tlic body, 
 often cause much damage to the urinary tract. Such de- 
 posits consist chiefly of crystals of ammonio-magnesium 
 phosphate formed as the result of the presence of a vola- 
 tile alkali — ammonia which arises from the decomposition 
 of the urea in the urinary passages. This is most com- 
 monly encountered in cases of chronic cystitis, chronic pye- 
 litis, and pyelocystitis, in which the clinical symptoms are 
 mostly irritant in character. The mechanical irritation by the 
 crystals, ////.y the irritating effect of the ammonia, adds much 
 to the distress of the patient. The most frequent causes of 
 this condition of the urine are obstructive diseases of the 
 lower urinary tract. Likewise, those diseases that affect 
 the contractile power of the muscles of the bladder. Thus, 
 in enlarged prostate, diseases of the spinal cord, paraplegia, 
 etc., the urine is retained, and soon undergoes ammoniacal 
 fermentation with a resulting deposit of triple phosphate. 
 This condition of the urine nearly always precedes the so- 
 called " surgical kidney " and other dangerous septic con- 
 ditions that also often result from the introduction of un- 
 clean instruments into the bladder. 
 
 Calcium Oxalate.^ — Crystals of oxalate of calcium are 
 found in either acid or alkaline urine, but most commonly 
 in acid urine ; they are frequently associated with crystals of 
 uric acid. When present in an alkaline urine, they are 
 usually found along with crystals of ammonio-magnesium 
 phosphate, for which they are frequently mistaken. 
 
 When crystals of calcium oxalate are constantly present 
 in the urine, the condition is termed oxahtria. 
 
 Calcium oxalate crystallizes in two typical forms — the 
 octalicdral and dumb-bell crystals. There are, however, 
 various modifications of these two forms, according to the 
 positions of the crystals. (Fig. 31.) 
 
 I. The octahedral crystals are made up of two four- 
 sided pyramids, placed base to base, and when viewed from 
 
 1 For the properties of Calcium Oxalate see p. 96.
 
 218 URINARY SEDIMENTS. 
 
 the side, their characteristic appearance is that of a square 
 crossed obhquely by two bright lines, forming the so-called 
 " envelop " crystal. If, however, the octahedron be turned 
 with one of its long axes toward the observer while the 
 other is held upright, the short axis will necessarily be 
 transverse, and the crystal will appear as a long and very 
 acute octahedron. 
 
 Frequently, the octahedra coalesce in such a way as to 
 have the appearance of an open umbrella, constituting the 
 so-called "umbrella" crystals. Sometimes each half of 
 an octahedron is connected by a short quadrilateral prism, 
 and such have been called " prismatic " crystals of calcium 
 oxalate. A kw other irregular forms are occasionally 
 found, but most of them, if not all, are modifications of the 
 typical octahedron. Occasionally, a number of the octa- 
 
 o ry " ^ 
 
 Fig. 31. — Various forms of calcium oxalate crj'stals. 
 
 hedral crystals are found intimately adherent, forming 
 larger or smaller microscopic concretions. Isolated crystals 
 are not infrequently found adherent to renal casts. 
 
 2. The dumb-bell and oval crystals of calcium oxalate 
 are more rarely found in the urinary sediment than the 
 octahedral forms, but when thus met with, are highly char- 
 acteristic. The dumb-bell crystals are always associated 
 with a larger or smaller number of oval or circular forms, 
 which have bright centers showing their biconcavity. In 
 addition to these are found allied forms, especially those 
 with partial concavities at the sides. Frequently, two dumb- 
 bells are found crossed at their centers, forming a double 
 dumb-bell crystal. These colorless dumb-bell crystals of 
 calcium oxalate should not be mistaken for the yellowish-red
 
 CALCIUM OXALATE. 219 
 
 or brown dumb-bells of uric acid and of ammonium urate. 
 The dumb-bells of uric acid and of ammonium urate are 
 readily soluble in alkaline hydrates, while those of calcium 
 oxalate are difficultly soluble ; the dumb-bells of uric acid 
 are insoluble in dilute hydrochloric acid, while those of 
 calcium oxalate are soluble. The dumb-bell or oval crys- 
 tals of calcium oxalate are, like the octahedral forms, quite 
 often found adherent to renal casts, and a number of them 
 may be joined together to form microscopic concretions. 
 
 The small circular ciystals are sometimes mistaken for 
 normal blood globules. They are readily distinguished by 
 the fact that the oxalate, although biconcave, is very highly 
 refractive, colorless, and insoluble in acetic acid, whereas 
 the normal blood globule has a pale-yellow color, and is 
 rendered abnormal by acetic acid. 
 
 Primary and Secondary Crystals of Calcium Oxalate. 
 — The primary crystals, or those formed inside the body, 
 are generally the large octahcdra, and also most of the oval 
 2ir\d dumb-bell forms. Secondary crystals, or those formed 
 after the urine has been passed, are usually the small 
 oetahedra and perhaps some of the very small oval, circular, 
 and dumb-bell forms. These secondary crystals are most 
 commonly found in a urine that has been allowed to stand 
 for some time, when they are frequently accompanied by 
 uric acid. Only rarely are the large crystals deposited 
 secondarily ; they may, however, be deposited following the 
 addition of acetic acid to the urine. 
 
 Distinction Betiveen Crystals of Calcium Oxalate and 
 Those of Ammonio-magnesium Phosphate. — The fact that, at 
 times, some of the crystals of ammonio-magnesium phos- 
 phate (triple phosphate) closely resemble the octahedral 
 form of calcium oxalate often leads to much confusion. 
 These are the small crystals of triple phosphate, modifica- 
 tions of the typical triangular prism, with its beveled ends, 
 in which the body of the prism, instead of being a parallelo- 
 gram, is nearly square, and in which the line connecting the 
 beveled ends is exceedingly short, but rarely so short as 
 not to be seen by careful focusing. The nature of the crys- 
 tals may, however, be determined by the characteristic 
 shape of the larger crystals about them, for they never 
 occur alone. As previously mentioned, the octahedron of 
 calcium oxalate is usually a square crossed by two diagonal 
 lines, and therefore has the appearance of an envelop. The
 
 220 URINARY SEDIMENTS. 
 
 phosphate crystals are promptly dissolved by acetic acid, 
 while those of the oxalate of lime are insoluble in this acid. 
 
 Clinical Significance. — Crystals of calcium oxalate may 
 be found in the urine of persons who are typically healthy, 
 as well as in certain diseased conditions. In licalth the 
 presence of an oxaluria is dependent upon the character of 
 the food ingested. Thus, it often follows the ingestion of 
 rhubarb, onions, sorrel, tomatoes, grapes, and the like, 
 because of the amount of oxalic acid contained in these 
 substances. It is of frequent occurrence in various dis- 
 turbances of digestion. It often follows the abundant 
 ingestion of carbohydrates, and the use of an excessive 
 meat diet ; this is especially the case when there is any 
 interference with the oxidizing power of the system. We 
 know that oxalic acid is formed as an intermediate product 
 of the metabolism between uric acid and urea ; that the 
 process of formation appears to be one of oxidation which, 
 if diminished, results in an oxaluria. Thus, in diseases of the 
 heart a7id lungs an oxaluria is of frequent occurrence. It 
 is commonly seen in diseases of the nervous system, and it 
 is claimed by some that the oxalic acid present in the 
 blood, on account of its poisonous action, causes a certain 
 train of symptoms of which nervous phenomena are espe- 
 cially prominent. This constitutes the theory of so-called 
 '' oxalic-acid diathesis." It is true that oxalic acid, when 
 taken internally in considerable amount, exerts a poisonous 
 action upon the organism, not only locally on the digestive 
 tract, but upon the heart and nervous system. However, 
 further evidence is necessary to prove that the symptoms 
 of the so-called " oxalic-acid diathesis " are directly due to 
 an increased formation of oxalic acid, or its retention in the 
 blood. 
 
 The primary crystals of calcium oxalate often set up a 
 more or less marked irritation of the urinary tract, espe- 
 cially if they separate from the urine in the kidney or renal 
 pelvis ; the mechanical action is usually much less severe 
 if the crystals separate in the bladder. The irritation 
 thereby may be very severe and even be accompanied by 
 abundant hemorrhage. Such a severe mechanical disturb- 
 ance is invariably accompanied by pain, often frequent and 
 painful micturition, and usually by a more or less concen- 
 trated urine. If the separation of these primary crystals con- 
 tinues for some time, the tendency to a calculus-formation
 
 CYSTIN. 221 
 
 in the pelvis of the kidney or bladder is very great, and 
 especially in those cases in which there is more oi less 
 hemorrhage. 
 
 In the more severe forms of oxaluria the condition has 
 been incorrectly termed " false Bright's disease," owing to 
 the extreme nervous symptoms, emaciation, dry skin, con- 
 stant pain or a sense of weight across the loins, frequency 
 of micturition, and other symptoms similar to those that 
 accompany a nephritis. 
 
 Cystin.' — Cystin, (CjHgNSO,),, is an amido-acid, and con- 
 stitutes one of the rarer forms of abnormal urinary sedi- 
 ments. It crystallizes in the form of colorless hexagonal 
 plates (Fig. 32), the angles of which measure 120 degrees. 
 The sides of these plates are usually equal, although rarely 
 two sides are found to be longer or shorter than the other 
 
 O 
 
 O 
 
 O 
 
 <2) 
 
 Fig. 32. — Cystin cn-stals. 
 
 four. It also crystallizes in quadrilateral prisms or groups 
 of prisms. Crystals of cystin have an opalescent luster, 
 and are often arranged in rosettes. 
 
 Cystin is insoluble in water, alcohol, and ether; also in 
 -acetic and tartaric acids. It is soluble in mineral acids and 
 oxalic acid, in amnionic hydrate and other alkaline hydrates 
 and carbonates, but is insoluble in ammonic carbonate. It 
 is readily precipitated from, its alkaline solution by acetic 
 acid. Its solutions rotate the plane of polarized light 
 strongly toward the left. 
 
 Cystin contains 26 per cent, sulphur, the odor of sul- 
 phureted hydrogen being evolved when a urine containing 
 cystin undergoes ammoniacal fermentation. 
 
 Cystin is probably not a normal constituent of the urine, 
 although Goldmann and Baumann claim to have isolated 
 a substance resembling cystin, in very small quantities as
 
 222 URINARY SEDIMENTS. 
 
 a benzoyl compound from normal urine. Under pathologic 
 conditions the quantity of cystin in the urine undergoes 
 considerable variation at different times, and it may tem- 
 porarily disappear. The daily quantity may reach as high 
 as 1.5 grams (Toel) ; ordinarily, however, it varies between 
 a few milligrams and one gram. 
 
 Cause of Cystimiria. — Until recently the cause of cystin - 
 uria was thought to be due to abnormal processes of oxida- 
 tion in the liver, since, in some respects, cystin resembled 
 taiirin. Marowski ^ considered it a vicarious elimination 
 of taurin because in his case there was an absence of bile 
 in the intestine. 
 
 The experiments of Baumann and v. Udranszky, Brieger, 
 and others, threw new light on the causation of this condi- 
 tion. They found that certain products of intestinal putre- 
 faction, called diamines, were eliminated in the urine and 
 feces of persons afflicted with cystin uria. Baumann and 
 V. Udranszky ^ made frequent examinations of the urine of 
 a case of cystinuria for diamines, and found them regularly. 
 They were isolated in the form of a benzoyl compound, 
 which varied in amount from 0.2 to 0.4 gram in twenty- 
 four hours. Approximately, one-third to one-fourth of 
 these substances existed as tetramethylendiamine, and the 
 remainder as pentamethylendiamine. ^ According to Brie- 
 ger, since these diamines arise only as a result of putre- 
 factive processes due to specific bacteria, cystinuria can be 
 considered the result of a specific infection of the intestine. 
 In Baumann's case both diamines were invariably found in 
 the feces as well as in the urine, and he observed that the 
 relative amounts of these substances in the feces, especially 
 the cadaverin, varied inversely as those in the urine. 
 Neither Brieger nor Baumann was able to discover these 
 diamines in the feces of healthy individuals, or in those 
 suffering from other diseases.* 
 
 So far as has yet been determined, no definite relation 
 exists between the formation of cystin and the diamines, 
 
 ' " Deutsches Archiv f. klin. Med.," iv, S. 449. 
 
 2 "Zeitschr. f. physiol. Chem.," 1889, xiil, S. 562. 
 
 •' Brieger gave new names to these two substances, calling the first " pu- 
 trescin," and the latter "cadaverin." 
 
 * According to Neubauer and Vogel, these diamines have been found in the 
 intestinal discharges of patients with Asiatic cholera.
 
 CYSTIN. 223 
 
 although the same conditions that produce diaminuria 
 usually also produce cystinuria. 
 
 Clinical Significance. — Hereditary predisposition certainly 
 appears to have some bearing as a cause, since so many 
 cases have been reported of the existence of the affection 
 in several members of the same family. It is difficult, 
 however, to explain the hereditary transmission of cystin- 
 uria by the theory of Brieger, unless we assume that such 
 individuals are more susceptible to the action of the " spe- 
 cific bacteria" that produce the intestinal putrefaction than 
 others. 
 
 Cystin is met with in the urine of both infants and adults, 
 but only rarely occurs in old age. It does not appear to 
 be connected with any local or constitutional disease. It 
 may be present and continue for years without any notice- 
 able impairment of health, although, as a result of its sepa- 
 ration from the urine, there is usually more or less irritation 
 of the urinary tract. It has been occasionally observed in 
 cases of liver disease, and Ebstein has noted the presence 
 of cystin in the urine of cases of acute articular rheumatism. 
 The danger of a calculus-formation always attends the 
 separation of cystin from the urine inside the body. Where 
 a concretion exists, it is usual to find few (sometimes many) 
 isolated crystals of cystin. 
 
 Detection. — The detection of cystin is based chiefly on the 
 recognition of the characteristic crystals in the urinary 
 sediment ; also their solubility in weak ammonic hydrate, 
 and their recrystallization upon the evaporation of the 
 ammonic hydrate. 
 
 It is always important to distinguish between the crystals 
 of cystin and other like crystalline elements. Cystin can be 
 differentiated from the pale, six-sided cr>'stals of uric acid 
 by allowing a drop of weak ammonic hydrate to mingle 
 with the deposit on a glass slide, when either form of crys- 
 tal will disappear ; evaporate, and if cystin be present, the 
 crystals reappear ; if uric acid be present, crystals of ammo- 
 nium urate will be found, instead of those of uric acid. 
 Another simple method consists in treating the crystals 
 with hydrochloric acid, which readily dissolves the cystin, 
 but leaves uric acid unchanged. Cystin is distinguished 
 from triple phosphate by its behavior with acetic acid, which 
 quickly dissolves the phosphate crystals while those of cys- 
 tin remain unchanged.
 
 224 URINARY SEDIMENTS. 
 
 The evolution of sulphurctcd hydrogen from the urine 
 should always lead to an examination for cystin, although 
 HjS is by no means ahvays due to the presence of cystin. 
 Frequently, silver coins carried in the pockets of persons 
 suffering from cystinuria are blackened by the sulphureted 
 hydrogen evolved, owing to the fact that cystin is some- 
 times eliminated by the skin, where it decomposes and fur- 
 nishes H2S. ^ 
 
 Bilirubin and Hematoidin. — Bilindnu is frequently de- 
 posited in a urine containing bile in an amorphous or crys- 
 talline form. The crystals of bilirubin (Plate 7) have two 
 forms — (i) clusters of needles arranged as stellates, occur- 
 ring either free in the urinary sediment or found attached to 
 cells ; and (2) minute rhombic tablets or plates which vary 
 in color from a yellow to a beautiful ruby red. 
 
 They are soluble in caustic soda, and on the application 
 of a drop of nitric acid a green rim forms about them. 
 
 Hematoidin, a derivative of hematin, was first discoxered 
 by Virchow in extravasated blood. It resembles bilirubin 
 as closely in appearance as in its chemic properties. The 
 crystalline formation of the two is identical. (Plate 7.) 
 According to Hoppe-Seyler, \^ Jaksch, and others, the}' 
 are in all respects indistinguishable, and it is, therefore, safe 
 to say that they are one and the same substance occurring 
 under vaiying conditions. 
 
 As previously stated, these crystals are very commonly 
 found in urine containing bile ; it is not uncommon to find 
 them in the urinary sediment following an extensive hemor- 
 rhage, or the evacuation of an abscess, or pyonephrosis in 
 which there has been hemorrhage. Leyden found these 
 crystals in nephritis gravidarium ; Foltanek and Rosenheim 
 in acute yellow atrophy ; and v. Jaksch in phosphorus- 
 poisoning, cirrhosis of the liver, as well as in severe jaun- 
 dice of the most distinct types. The author has occasion- 
 ally met with these crystals in hemorrhage from the pros- 
 tatic region, once in cancer of the bladder, and once follow- 
 ing a traumatic hemorrhage from the kidneys, as well as 
 in jaundice from various causes. 
 
 Leucin. — Leucin, C^.H^gNO.,, — amidocaproic acid, — is 
 one of the products of decomposition of proteid bodies or 
 of their derivatives, and is formed by the activity of certain 
 
 ^ For the quantitative determination of cystin see Neubauer and V'ogel, 
 "Analyse des Harns," Bd. i, 1898, S. 807.
 
 Plate 7 
 
 ^ m 
 
 Hematoidin (Bilirubin) Crystals.
 
 LEUCIN. 225 
 
 ferments, especially trypsin. As a urinary deposit it is of 
 very rare occurrence. It is usually accompanied by crys- 
 tals of tyrosin. 
 
 Leucin occurs as highly refractive spherical crystals, 
 which are usually marked with radiating and concentric 
 striae. (Fig. 33.) When pure, it crystallizes in very delicate, 
 small plates, often of irregular shapes and with a greasy 
 feel, and are usually arranged in groups or found lying one 
 upon another. When very impure, they appear as yel- 
 lowish, highly refractive globules, apparently without crys- 
 talline structure. In this form they may be mistaken for 
 oil-drops, but by careful study it will be found that they 
 are less highly refractive than oil-drops — i. e., not possess- 
 ing quite so wide a dark border. 
 
 Leucin, when pure, is difficultly soluble in cold, but more 
 
 Fig- 33- — Leucin crystals. 
 
 readily soluble in hot, water; it is only sparingly soluble in 
 alcohol ; readily soluble in acids and alkaline hydrates, and 
 insoluble in ether. When impure, its solubility is distinctly 
 increased. Leucin sublimes without melting when heated 
 to 170° C. ; at a higher temperature it is decomposed into 
 carbonic acid and amylamin. It combines with bases and 
 acids to form salts. It can be obtained artificially by decom- 
 posing proteids with acids. 
 
 Detection. — Leucin may be recognized by the character- 
 istic microscopic appearance of its crystals. Having found 
 crystals resembling leucin, confirmatory tests should always 
 be employed. 
 
 I. When leucin is evaporated on a platinum foil with 
 nitric acid, a colorless residue remains, which, if treated 
 15
 
 226 URINARY SEDIMENTS. 
 
 with a few drops of sodic hydrate and heated, furnishes, 
 according to the purity of the leucin, a watery, or more or 
 less colored, fluid. If this fluid be concentrated, there re- 
 mains an oily fluid that does not adhere to the platinum, 
 but collects in drops of varying size (Scherer). 
 
 2. On the addition of a trace of chinon and a few drops 
 of sodic hydrate to a cold aqueous solution of leucin a 
 marked violet color appears. Other amido-acids, as well 
 as certain proteid bodies, give this reaction (Wurster). 
 
 3. Leucin does not give a color reaction with furfurol, 
 but tyrosin, on the other hand, gives a decided reaction 
 with an aqueous solution of this substance. 
 
 Since leucin nearly always accompanies tyrosin, its 
 clinical importance will be considered under the subject of 
 tyrosin. 
 
 Tyrosin. — Tyrosin, CgHj^NOg, like leucin, is one of the 
 products of the decomposition of proteid substances. It 
 crystallizes in the form of exceedingly fine needles, which 
 are arranged in sheaf-like collections, often crossing each 
 other, and intersecting at their constricted middle portions. 
 It also crystallizes in rosettes with the needles radiating from 
 their centers (Fig. 34), especially if crystallized from an 
 alkaline solution. 
 
 The crystals are colorless, but when arranged in masses, 
 often look dark, especially near the central portions, because 
 of the compact arrangement of the needles. They are 
 tasteless and odorless, very sparingly soluble in cold water 
 (i : 2000 at 20° C), but much more soluble in boiling 
 water (i : 150). They are almost insoluble in strong alco- 
 hol (i : 135,000), quite insoluble in ether, and readily solu- 
 ble in acid, alkalies, and solutions of the alkaline salts. 
 Tyrosin readily combines with bases and acids to form dis- 
 tinct compounds. (For details see Neubauer and Vogel, 
 "Analyse des Harns," Bd. i, 1898, S. 281.) 
 
 Tyrosin that has been isolated from the urine or other 
 fluids is readily recognized, even when present in very small 
 amounts, by means of Hoffmann's and Piria's tests. 
 
 Hoffmann' s Test. — When a solution of tyrosin or a sus- 
 pected deposit that has been boiled with an excess of water 
 Ls heated with Millon's reagent, a bright crimson or pink 
 color is produced. If much tyrosin be present, a similarly 
 colored precipitate forms, while the supernatant fluid remains 
 red, or sometimes a purple-red.
 
 TYROSIN. 
 
 227 
 
 Piria's Test. — If ty rosin be treated on a watch-glass with 
 a Httle concentrated sulpiiuric acid, and heated on a water- 
 bath for from five to ten minutes, there results a compound 
 — tyrosin-sulphuric acid — which has a pink color. This 
 pink solution is then diluted with water, warmed, neutral- 
 ized with barium carbonate, and filtered while hot. The 
 colorless and neutral filtrate is then treated with a few drops 
 of a very dilute solution of perchloride of iron, which pro- 
 duces a violet color. An excess of the iron salt should be 
 avoided, as it readily destroys the color. 
 
 According to v. Udranszky,i a characteristic reaction is 
 obtained when an aqueous solution of furfurol is added to a 
 solution of tyrosin. 
 
 Fig. 34.— Tyrosin crystals. 
 
 Furfurol Reaction. — Dissolve a small crystal of tyrosin 
 in I c.c. of water, add one drop of a 0.5 per cent, solution of 
 furfurol, and then underlie with concentrated sulphuric acid ; 
 the fluid is colored rose-red. The mixture should not have 
 a temperature above 50° C. 
 
 The foregoing tests for tyrosin can not be applied directly 
 to the urine with satisfactory results, since various urinary 
 constituents either give the same reactions or obscure the 
 tests. It is, therefore, necessary to isolate the tyrosin, which, 
 according to Blendermann,^ can be accomplished in the fol- 
 lowing manner : 
 
 Precipitate the urine with basic acetate of lead, filter, and 
 
 ^ "Zeitschr. f. physiol. Chem.," xii, 355, 1888. 
 '^ "Zeitschr. f. physiol. Chem.," vi, 260, 1882.
 
 228 URINARY SEDIMENTS. 
 
 remove the lead from the filtrate by passing sulphureted 
 hydrogen through it. Filter, and evaporate this filtrate to 
 a very small volume, and allow it to stand several hours to 
 crystallize. Filter, dissolve the crystals in boiling water, and 
 apply the tests as directed. 
 
 If the urinary sediment contains crystals that resemble 
 tyrosin, their presence should always be confirmed as fol- 
 lows : Filter off the sediment, wash with water, dissolve 
 while still on the filter in hot ammonic hydrate to which 
 some ammonium carbonate has previously been added, evap- 
 orate the filtrate to crystallization, and examine microscop- 
 ically. 
 
 Care should be taken not to mistake the large hedgehog 
 and sheaf-like crystals of acid urate of ammonium, also 
 the sheaf-like crystals of acid sodium urate, for the rosettes 
 and sheaves of tyrosin. 
 
 Clinical Significance. — Leucin and tyrosin are constantly 
 formed as products of the digestion of proteids, particularly 
 by the action of trypsin, and usually, if not always, occur 
 together. The presence of these substances in the urine is 
 of very rare occurrence. It is claimed by some observers 
 that they are present in minute traces in normal urine. 
 This, however, is still an unsettled question, as certain reli- 
 able observers have been unable to confirm such claims. 
 
 Leucin and tyrosin have been found in the urine in con- 
 siderable amounts in acute yellow atrophy of the liver and 
 in acute phosphorus-poisoning. They have also been ob- 
 served in the urine in cases of severe typhus fever, severe 
 smallpox, and diseases of the intestines. The appearance 
 of these two substances in disease is invariably accompanied 
 by a very marked reduction in the quantity of urea. 
 
 Cholesterin. — Cholesterin, C.,^H,,0, is a monatomic 
 alcohol that is normally present in nervous tissue, blood- 
 corpuscles, bile, and elsewhere. It occurs pathologically 
 in gall-stones, as well as in atheromatous cysts, in pus, in 
 tubercular masses, old transudations, excrements, and 
 tumors. 
 
 Cholesterin is probably not a constituent of the urine 
 in health, and only occurs in this fluid under pathologic 
 conditions. It crystallizes in large, colorless, transpar- 
 ent plates (Fig. 35), whose angles and sides frequently 
 appear broken, and whose acute angles are often from jd 
 to 87 degrees. In large quantities it appears as a mass
 
 CHOLESTERIN. 
 
 229 
 
 of white plates having a luster resembling mother-of-pearl, 
 and a greasy feel. 
 
 Cholesterin is insoluble in water, dilute acids, and alkalies. 
 It is easily soluble in boiling alcohol, and recrystallizes 
 on cooling. It is readily soluble in ether, chloroform, 
 and benzol, and also in the volatile and fatty oils. It is 
 dissolved to a slight extent b\^ alkaline salts of the bile 
 acids. > 
 
 Cholesterin crystals are only found in the urinary sedi- 
 ment in cases of extensive fatty degeneration of some part 
 of the urinary tract, as, rarely, in cases of subacute glomer- 
 ular nephritis and chronic diffuse nephritis, and still more 
 rarely during the fatty stage of an acute nephritis ; also in 
 case of the evacuation of an abscess into the urinary tract. 
 
 Fis- 35- — Cholesterin crystals. 
 
 Detection. — If a mixture of five parts of sulphuric acid 
 arid one part of water acts on a cholesterin crystal, first a 
 bright carmine-red and then a violet color appears. This 
 fact is u.sed in the microscopic detection of cholesterin. 
 Another test consists in treating the crystal first with dilute 
 sulphuric acid and then with a solution of iodine. The 
 cr\'stals will be gradually colored violet, bluish-green, and 
 finally a beautiful blue. 
 
 Sa/kcnvski' s Reaction. — Cholesterin is dissolved in chloro- 
 form, and then treated with an equal volume of concen- 
 trated sulphuric acid. The cholesterin solution becomes 
 first bluish-red, then gradually violet-red, while the sul- 
 phuric acid appears dark red with a greenish fluorescence. 
 
 Cholesterin is readily detected in the urinary sediment by 
 means of the microscope.
 
 230 URINARY SEDIMENTS. 
 
 ORGANIZED SEDIMENTS. 
 
 The organized or anatomic sediments consist of formed 
 elements coming from various parts of the urinary tract. 
 Some of these elements are present in the urine under 
 normal conditions, while others are found only as the result 
 of functional disturbance or disease. 
 
 Blood. — Red blood-corpuscles in the urinary sediment 
 are always abnormal constituents, and indicate a pathologic 
 condition in some portion of the urinary tract. Not infre- 
 quently, in the female, blood enters the urine from the 
 genital tract ; under such circumstances it is quite unim- 
 portant. 
 
 Blood -corpuscles vary in their microscopic appearance 
 according to the character of the urine in which they are 
 found, the length of time they have been in the urine, and 
 the location of the urinary tract from which they come. 
 Red blood-corpuscles are conveniently divided, for the pur- 
 pose of urinary examination, into two classes — /. c, (a) 
 normal and {li) abiioniial blood globules. 
 
 (a) Normal Blood. — This refers to the unaltered blood- 
 corpuscles, which are so characteristic in appearance that 
 there is very little, if any, danger of mistaking them for other 
 elements in the sediment. They consist of biconcave discs, 
 which ahuays have a yellow color. (Fig. 36, left half) They 
 are smaller than a leucocyte, being about g-^-Vo" ^^ '^'^ '\nc\v 
 (between 7 and 8 micromillimeters) in diameter, free from 
 nuclei, and perfectly homogeneous — that is, free from gran- 
 ules and other visible cell-contents. These biconcave discs 
 undergo a reversal of light and shadow on careful focusing, 
 the center and periphery alternating in brightness or shadow 
 as the objective is approximated to the slide or removed from 
 it. Normal blood globules that have been in the urine for 
 some time begin to undergo a change. Their edges often 
 become irregular and crenated, — the so-called crcnatcdblood- 
 corpiisclc, — found particularly in urines that contain a rela- 
 tively large proportion of sodium chloride. This form still 
 has more or less color, and belongs to the class of normal 
 blood. In fact, any blood-corpuscle that has the slightest 
 yellowish tint can be considered a normal blood-corpuscle. 
 Within a few hours after the blood enters the urine the cor- 
 puscle begins to swell and lose its color and density, and 
 it is then that we have the —
 
 BLOOD. 231 
 
 (b) Abnormal Blood Globules. — These are merely 
 blood rings or shadows. (Fig. 36, right half.) _ The blood 
 globule that was formerly biconcave is now biconvex — in 
 other words, is swollen and has become a sphere, devoid of 
 color or, if any color, the slightest tint of brown at the 
 margin. The corpuscle has also become reduced in diam- 
 eter, being only about two-thirds of the diameter of the 
 normal blood-corpuscle. There are various forms of cor- 
 puscles in the change from normal to abnormal blood, but, 
 since the color is the criterion, any blood-corpuscle that has 
 lost its yellow color is abnormal. 
 
 A urine containing normal blood is usually more or less 
 reddish in color, depending upon the quantity present. If 
 the amount of blood is excessive, it produces in alkaline 
 urine a bright-red color (oxyhemoglobin), and in highly 
 acid urine more of a brownish-red color (oxy- and methe- 
 
 ° ^000 
 
 o 
 
 
 o 
 o C) ° 
 
 ° o 
 
 o 
 
 Fig. 36.— Blood-corpuscles : a, Normal; 6, abnormal. 
 
 moglobin). Abnormal blood, when present in considerable 
 quantity, imparts a brownish or smoky color (methemoglo- 
 •bin and hematin) to the urine. If present in large amounts, 
 the color is usually very dark and may be black. If 
 the quantity of either normal or abnormal blood in the 
 .urine be small, the color may give no indication of its 
 presence, and under such circumstances is not usually de- 
 tected until the sediment is examined microscopically. 
 
 A distinct reaction for albumin is always obtainable in a 
 urine containing blood, even though the quantity of blood 
 be extremely small. 
 
 Treatment of a Sediment Containing Blood. — The presence 
 of a large amount of blood in the urinary sediment gener- 
 ally completely obscures other formed elements ; on this 
 account the blood globules must be destroyed. The de- 
 struction of blood is best accomplished in the following 
 way :
 
 232 URINARY SEDIMENTS. 
 
 Allow the urine to settle thoroughly in a urine glass, then 
 decant the supernatant bloody fluid, and to the sediment re- 
 maining in the glass add a large volume of lukewarm water 
 and a few drops of dilute acetic acid. Stir thoroughly with 
 a glass rod, breaking up all clots, and allow the fluid to 
 settle again. Repeat this process until the wash-water is 
 practically free from blood pigment. Finally, settle and 
 examine. The blood pigment will be found to have been 
 washed from the blood-corpuscles, leaving a very fine net- 
 work of abnormal blood globules and fibrin, in which other 
 formed elements, such as casts, epithelium, etc., are capable 
 of detection. 
 
 The fact that a urine containing a large quantity of blood 
 always contains a considerable number of leucocytes should 
 be borne in mind, especially in drawing inferences as to the 
 presence or absence of a suppurative process that is associ- 
 ated with hemorrhage. If the leucocytes are numerous — 
 in fact, abundant — and more or less arranged in clumps, 
 suppuration in some part of the urinary tract is highly 
 probable. 
 
 " Hematuria " is the term applied to a urine that contains 
 blood, — that is, the blood-corpuscles together with the 
 blood pigment, — and should not be confounded with the 
 term " hemoglobinuria," which applies to a urine containing 
 blood pigment witJiont blood-corpuscles. (See p. 362.) 
 
 Clinical Significance. — The first interest in connection 
 with a hematuria is to locate the source of the hemorrhage. 
 Blood in the urine may come from the kidney, pelvis of 
 kidney, ureter, bladder, prostate, or urethra. Blood com- 
 ing from the genital tract of the female should in all cases 
 be distinguished from that coming from the urinary tract. 
 
 From the Kidney. — In fresh urine blood from the kidney 
 is usually abnormal in character, and therefore imparts a 
 more or less smoky color to the urine. Such urines after 
 standing deposit a brown or coffee-colored sediment. But 
 the blood may be normal, especially if from the straight 
 tubules or in case of abundant renal hemorrhage when the 
 urine is generally of a bright-red or brownish-red color, and 
 upon standing furnishes an abundant blood-red sediment. 
 Urines containing blood from the kidneys are generally 
 acid in reaction, although if the amount of blood be very 
 large, the reaction may be alkaline. Blood from the kidney 
 is usually accompanied by renal casts, which often have the
 
 BLOOD. 233 
 
 blood adherent ; and even blood-casts may be found. This 
 fact constitutes an important element in diagnosis, since the 
 only positive evidence of renal hemorrhage is the presence 
 of blood on casts and true blood-casts. Blood-clots, usually 
 of small size, are not infrequently found in the sediment in- 
 cases of abundant hematuria of renal origin. Large clots, 
 however, are generally absent from the sediment unless they 
 be of the long, slender, rod-like variety, which have been 
 molded in passing through the ureters. In case the hemor- 
 rhage is very slight blood-clots are usually not found in the 
 sediment. 
 
 The most frequent causes of blood from the kidney are 
 the acute diseases and disturbances of this organ, such as 
 active hyperemia (little blood), severe active hyperemia (con- 
 siderable blood), and acute nephritis (large amount of 
 blood). A ve/y small amount of blood is sometimes found 
 in the various chronic diseases of the kidney, but is generally 
 so slight that it is unimportant. In all of the above-men- 
 tioned kidney affections the blood is usually abnormal. In 
 an exacerbation of an acute or an acute exacerbation of a 
 chronic kidney disease the blood is generally abundant and 
 normal in character, this condition being characterized by 
 the sndden appearance of normal blood and a rapid fall in 
 the twenty-four-hour quantity of urine. (See p. 298.) 
 This form of renal hemorrhage is most common in the 
 parenchymatous forms of renal disease, such as acute 
 nephritis, subacute glomerular nephritis, and chronic diffuse 
 nephritis. Hematuria is not uncommon in chronic inter- 
 stitial nephritis as the result of vascular changes, including 
 cardiac disease and atheromatous arteries. It is by no 
 means rare in amyloid infiltration of the kidneys, on ac- 
 count of the extensive infiltration about the smaller blood- 
 vessels. 
 
 In tuberculosis of the kidney hemorrhage is a common 
 symptom. The attacks are usually intermittent, although 
 at times constant for a long period. An abundance of pus 
 frequently accompanies a hematuria of this origin. A v&ry 
 thorough search for tubercle bacilli in the urinary sediment 
 should always be made before eliminating this possibilit\' 
 of hemorrhage. New growths of the kidney also give rise 
 to repeated attacks of hematuria, and at times the quantity 
 of blood is profuse. There is generally more or less pus in 
 the sediment, and also an abundance of small round and
 
 234 URINARY SEDIMENTS. 
 
 degenerated cells. Such cases are to be recognized by- 
 renal tumor, more or less pain, and general cachexia of the 
 patient. 
 
 A calculus in the substance of the kidney or in the renal 
 pelvis of the kidney is a frequent cause of hemorrhage. 
 The blood is generally accompanied by more or less pus. 
 There is usually pain in the region of the affected kidney, 
 tenderness on deep pressure, and pain extending down the 
 leg or into the testicle. There may be renal colic when 
 there is a small stone in the renal pelvis, the blood often 
 being accompanied by small caudate cells from the super- 
 ficial layer of the pelvis. In the light of these symptoms a 
 hematuria resulting from a calculus should be suspected. 
 The sediment should be carefully searched for crystalline 
 deposits, which may or may not be present. 
 
 The ingestion of certain drugs such as cantharides, tur- 
 pentine, as well as certain other poisonous substances, may 
 give rise to renal hematuria. It may also be due to trauma 
 involving the kidneys, either directly as by wounds or 
 blows, or indirectly from concussion. In tropical countries 
 renal hematuria is frequently the result of an invasion of the 
 kidney by a minute parasite — distoma haematobium. (See 
 p. 267.) Of the various other causes of hemorrhage of renal 
 origin, renal embolism, purpura haemorrhagica, hydatids, 
 abscess, and cystic disease of the kidneys may be mentioned. 
 
 From the Lnver Urinary Passages. — Abundant hemor- 
 rhage from the bladder is not uncommon, and is most liable 
 to be the result of one of three abnormal conditions — /. c., 
 vesical calculus, tuberculosis, or new growth. A moderate 
 amount of blood usually accompanies all acute and chronic 
 inflammations of the bladder. Blood from the bladder is 
 generally normal in character, but if present in small 
 amounts, may be abnormal, particularly if the urine in 
 which it is contained be highly acid or strongly akaline. The 
 quantity of blood may be so abundant as to cause coagula- 
 tion within the bladder or, as is more frequent, shortly after 
 the urine has been voided. Blood-clots are more common in 
 vesical hematuria than in other forms of hemorrhage, and 
 are invariably associated with profuse bleeding. The clots 
 are usually small and irregular in shape, but may be large 
 and regular. A clot in the bladder may completely ob- 
 struct the outflow of urine. Rarely, long, smooth, cord- 
 like blood-clots are passed by the urethra. One instance
 
 BLOOD. 235 
 
 of this was observed by the author, the clot being seventy- 
 two inches in length. 
 
 Blood of vesical origin is generally accompanied by more 
 or less pus, and in cases of long-standing cystitis the urine 
 is frequently alkaline, although not invariably so. For 
 purposes of diagnosis the blood must be destroyed before 
 microscopic examination is undertaken, and then a search 
 made for characteristic cells of new growth, or crystalline 
 elements ; or the sediment prepared, and carefully examined 
 for tubercle bacilli. 
 
 Hemorrhage from the neck of the bladder is probably 
 most commonly the result of tuberculosis, although it may 
 be due to various other pathologic conditions of this region. 
 In most respects it resembles hemorrhage from the fundus 
 of the bladder, although accompanied by symptoms sug- 
 gestive of neck-of-bladder trouble. 
 
 Hematuria of urethral origin may arise from traumatism, 
 acute gonorrhea, urethral chancre, or following surgical 
 operations on strictures of the urethra. The blood is gen- 
 erally normal in character, and precedes the flow of urine, 
 and also oozes from the meatus between the acts of mic- 
 turition. 
 
 TeicJiniaiDi' s Test for Blood Pigment. — In the application 
 of this test to urine it is necessary to coagulate the albu- 
 min, which carries down with it the blood pigment. This is 
 best accomplished for the purpose of this test (i) by 
 strongly acidulating the urine with acetic acid, and then 
 adding a saturated solution of sodium tungstate also acidu- 
 lated with acetic acid. Upon heating this mixture a brown- 
 ish precipitate of albumin and blood pigment is obtained, 
 which is collected on a filter and dried. (2) The albumin 
 can also be coagulated by boiling the urine, which has been 
 faintly acidulated with acetic acid, as described on page 
 129. This precipitate is placed on a filter, washed, and 
 dried. 
 
 Method. — A small portion of the dried and powdered pre- 
 cipitate containing the blood pigment is placed on a micro- 
 scopic slide, and moistened with a weak solution of potas- 
 sium iodide or sodium chloride, and evaporated to dryness. 
 The residue is covered with a cover-glass, and glacial 
 acetic acid allowed to flow underneath in contact with the 
 powder. This preparation is then gently heated until the 
 acid begins to boil, when it is cooled, and examined
 
 236 URINARY SEDIMENTS. 
 
 by means of the microscope. If blood pigment be pres- 
 ent, brown rhombic plates (Fig. ^y) of iodide or chh^ride 
 of hematin (also known as hemin crystals) will be found. 
 These rhombic crystals are generally isolated, but they 
 occasionally cross each other to form more or less charac- 
 teristic groups. 
 
 This test affords one very important means of determin- 
 ing the presence of blood or blood pigment in the urine 
 and other fluids of the body. It is also of great import- 
 ance in distinguishing between the dark or black urines due 
 to hemoglobin (see Hemoglobinuria, p. 362) and those 
 that are dark or black from other pigments. Further- 
 
 Fig. 37. — Teichmann's hemin cr>'Stals. 
 
 more, this test is of great practical value in the medicolegal 
 detection of blood. 
 
 Pus. — Pus-corpuscles, also termed leucocytes, are round, 
 well-defined bodies, which are usually extremely gran- 
 ular. (Fig. 38, «.) They vary a little in size, but are 
 usually quite constant and a trifle less than twice the size of 
 the average normal blood globule. Although generally 
 round, they vary somewhat in shape according to the age 
 of the pus, the reaction of the urine, and the pathologic 
 process that they accompany. Pus-corpuscles usually con- 
 tain two or three nuclei, — polymorphonuclear leucocytes, 
 — which constitute the chief characteristic of the typical 
 pus-corpuscle. There is also the moiiomiclcar leucocyte, 
 which is less common in the urinary sediment, and not 
 easily distinguished from the small round cell.
 
 PUS. 237 
 
 The nuclei of the pus-corpuscle are not usually distinct, 
 on account of the very granular character of the body, but 
 if the corpuscle be not decomposed or disintegrated, two 
 or more nuclei can be made out upon focusing closely. 
 The distinctions of the nuclei, and, in fact, the general 
 appearance of the pus-corpuscle, depend largely upon the 
 reaction of the urine in which they are contained and the 
 age of the pus. 
 
 In Acid Urine. — Fresh pus in an acid urine is very 
 dense and the nuclei are seen with difficulty, if at all ; this 
 constitutes the so-called " normal pusy On the other 
 hand, pus which has been suspended in the urine for some 
 period, either within or outside the body, has a different 
 appearance ; the body of the corpuscle becomes less distinct 
 and the nuclei more prominent ; this is sometimes termed 
 
 ® ® ® 
 
 ® 
 © 
 
 Fig. 38— a, Pus-corpuscles as ordinarily seen ; 3, ameboid pus-corpuscles ; c, pus-cor- 
 puscles showing the action of acetic acid. 
 
 ^' abnormal pus'' or '' %vaslied-oiit pits." In the abnormal 
 pus-corpuscle the nuclei, instead of being separate bodies, 
 are often fused, forming a single horseshoe-shaped nucleus, 
 .which is not so dense as the individual nuclei of the nor- 
 mal pus-corpuscle. These abnormal pus-corpuscles may 
 come from any part of the urinary tract, and are most com- 
 mon in cases of long-continued chronic inflammation. 
 
 In Alkaline Urine. — When a urine containing pus be- 
 comes alkaline by a volatile alkali or alkaline hydrate, such 
 as ammonium carbonate or hydrate resulting from the 
 decomposition of the urea, the pus-corpuscles become de- 
 stroyed. By the action of the alkali the pus becomes 
 converted into a gelatinous, tenacious mass (see Donne's 
 Test for Pus), which in many respects resembles white of 
 &%g. If a portion of this mass be examined microscopi-
 
 238 URINARY SEDIMENTS. 
 
 cally, the pus-corpuscles will be found to have been de- 
 stroyed, while only a dense mucus-like mass with adherent 
 amorphous phosphates, crystals of triple phosphate, and 
 bacteria remains. Some of the nuclei of the pus-corpus- 
 cles may still be found. 
 
 Pus-corpuscles are practically indentical with the white 
 corpuscles of the blood and lymph. In a fresh state they 
 often present protoplasmic processes, — ameboid move- 
 ments, — and under such circumstances should not be mis- 
 taken for small caudate cells. 
 
 It is very important to determine the exact nature of all 
 small, round, or irregular bodies whose nuclei are not dis- 
 tinct, to distinguish between leucocytes and small round 
 cells, and also between ameboid leucocytes and small cau- 
 date cells. This is best accomplished by treating the urin- 
 ary sediment with dilute acetic acid, as follows : Moisten 
 the microscopic slide with a fraction of a drop of the acid, 
 then place a drop of the sediment on the drop of acid ; 
 mix thoroughly by means of a glass rod, and cover with 
 a cover-glass. 
 
 Action of Acetic Acid. — When dilute acetic acid (20 per 
 cent.) is added to a fluid containing pus, the changes in the 
 corpuscles are very rapid ; the first effect being to cause them 
 to swell up, and next to dissolve the granules, the body of 
 the corpuscle becoming smooth and the nuclei very distinct. 
 In a short space of time the body of the corpuscle becomes 
 almost invisible, while the nuclei remain a much longer 
 time. 
 
 Epithelial cells are affected by acetic acid in much the 
 same manner as leucocytes, but to a less marked degree. 
 The first effect is a solution of the granules, making the 
 nucleus very prominent, and, finally, after prolonged action 
 of the acid, the cell begins to swell. The body of the cell 
 does not usually become faint or invisible by the action of 
 this acid. 
 
 The action of water on the pus-corpuscle and epithelial 
 cell is identical with that of acetic acid, except that it is 
 very much slower and the stage of distinct nuclei is reached 
 much later. 
 
 Characteristics of Uri)ie Containing Pits. — An acid urine 
 containing pus is turbid except when the corpuscles are 
 only few in number. It very soon deposits an opaque 
 white sediment, which rapidly settles to the bottom of the
 
 PUS. 239 
 
 sediment glass. This deposit should not be mistaken for a 
 deposit of amorphous urates or phosphates. The distinc- 
 tion is easily made by means of the microscope, also by 
 the fact that the phosphatic deposit is readily dissolved by 
 acetic acid, while the deposit of pus undergoes the changes 
 already described. On the other hand, a deposit of amor- 
 phous urates is readily dissipated by gentle heat. 
 
 A purulent urine that has undergone alkaline fermenta- 
 tion is invariably turbid and often contains a large, ropy 
 mass, consisting of decomposed pus, etc., as previously 
 mentioned. 
 
 Donne' s Test for Pus. — This depends upon the reaction 
 that takes place between alkalies and the pus, and consists 
 in the addition of an alkaline hydrate — potassic, sodic, or 
 ammonic hydrate — to the suspected urine, or its sediment 
 after the supernatant urine has been poured off. If pus 
 be present, the urine becomes viscid, or the sediment is 
 promptly converted into a viscid, gelatinous, mucus-Hke 
 mass, which adheres to the bottom and sides of the test- 
 tube. If some of this viscid substance be examined under 
 the microscope, the pus-corpuscles will be found to have 
 been destroyed or, rather, converted into the substance it- 
 self. If the action has not been very long or the propor- 
 tion of the alkali to the pus is small, the outline of the pus- 
 corpuscles may still be seen ; so, also, the nuclei of the 
 corpuscles may still be discernible, embedded in the mucus- 
 like mass. 
 
 According to v. Jaksch, leucocytes are stained a deep 
 rhahogony-brown (glycogenic reaction) by a solution of 
 potassic iodide. This serves to distinguish them from 
 small round cells, which are stained a light yellow color. 
 ' A. Vitali recommends the following test for pus : The 
 suspected urine, if alkaline, is acidulated with acetic acid, 
 and filtered through a thick filter. The deposit on the 
 filter is then treated with a little guaiacum tincture, which 
 has been kept in the dark. If pus be present, the inner 
 surface of the filter takes a blue tint. The result is ob- 
 tained even with a small number of leucocytes. 
 
 Clinical Significance. — A perfectly normal urine may con- 
 tain isolated leucocytes. It is only when they occur in 
 considerable numbers or in conjunction with other formed 
 elements (casts, etc.) that their presence becomes important. 
 
 Pus is one of the most common elements found in the
 
 240 URINARY SEDIMENTS. 
 
 urinary sediment. It may be derived from the .sub.stancc of 
 the kidney or pelvis of the kidney, the ureters, the bladder, 
 the prostate gland, the urethra, or from the rupture of an 
 abscess into some part of the urinary tract. Given, then, a 
 urine containing pus, the first effort should be directed 
 toward determining its source. The character of the ele- 
 ments (cells, casts, etc.) that accompany the pus is of the 
 utmost importance in locating the suppurative process. 
 
 Pus coming from the kidney is found in cases of chronic 
 suppuration in the tulnilcs, such as may result from the 
 presence of a calculus, the existence of a tubercular pro- 
 cess, or the extension of an inflammation from the pelvis 
 of the kidney into the renal tubules. In these conditions 
 the pus is usually present in large quantity, and is some- 
 times accompanied by a few or numerous renal casts, 
 including pus-casts, which come from the suppurating area 
 or the neighborhood of the diseased area in the kidney. In 
 acute nephritis and following acute exacerbations of chronic 
 renal diseases pus is usually present in greater or smaller 
 quantities, and often found adherent to casts, but in these 
 conditions true pus-casts are only rarely found. 
 
 The diagnosis of abscess of the kidney can not be posi- 
 tively determined until the abscess has evacuated its con- 
 tents into the urinary passages. Previous to rupture of 
 the abscess the urine usually presents evidences of a renal 
 congestion — active hyperemia — that is going on in the renal 
 tissue around the abscess pocket. A urine that suddenly 
 contains a large quantity of greenish pus strongly suggests 
 abscess of the kidney. 
 
 In chronic pyelitis the urine is generally acid in reaction ; 
 the pus is not only free, but is often arranged in clumps, and 
 is mixed with small round cells from the deep layer of the 
 pelvis of the kidney. Any obstruction to the outflow of 
 pus causes a pyonephrosis ; if the back pressure becomes 
 sufficient to force an opening, a sudden gush of greenish 
 pus follows. So far as the author is aware an abundant 
 deposit of greenish-colored pus is indicative only of abscess 
 of the kidney, the evacuation of an abscess into the urinary 
 tract, or pyonephrosis. 
 
 Numerous leucocytes usually accompany an acute pye- 
 litis, but ordinarily they are insignificant as compared with 
 the other formed elements, which are, in themselves, diag- 
 nostic.
 
 EPITHELIUM. 241 
 
 Acute and chronic inflammations of the bladder — cystitis 
 — are always associated with purulent urine. In acute cys- 
 titis the urine is generally acid, but in chronic inflammation 
 of this membrane the urine is often alkaline — ammoniacal 
 — when voided. This is by no means true of every chronic 
 inflammation of the bladder, since in tubercular cystitis and 
 also in some cases of calculous cystitis the urine is acid in 
 reaction. Purulent urines in general, and especially those 
 from the bladder, readily become alkaline upon standing 
 exposed to the air, if not already alkaline when voided. In 
 cystitis the ropy, glairy mass consisting of decomposed pus, 
 amorphous and crystalline phosphates, as well as epithelial 
 cells, is not infrequently found. 
 
 Pus from the neck of bladder or prostatic region is often 
 found free, and arranged in clumps and mixed with neck- 
 of-bladder cells. Oftentimes spermatozoa are found free 
 and mixed with the pus in shreds. 
 
 In urethritis the pus is usually very dense, and found 
 chiefly in long threads or shreds, mingled with urethral 
 cells, especially when of gonorrheal origin. When the 
 amount of pus is abundant, it is generally free, no shreds 
 being found. In acute gonorrhea the pus is usually yel- 
 lowish in color. If any doubt exists as to the exact source 
 of this pus, the question is often settled by directing the 
 patient to pass the first portion of his urine into one ves- 
 sel and the last portion into another ; if urethral, the first 
 portion will contain much pus, while the second will be 
 practically free from it. 
 
 - Pus from the uterus or vagina is usually accompanied by 
 an abundance of squamous epithelium. If, in the case of 
 a female, there is any doubt as to the source of the epi- 
 thelium and pus, — whether bladder or vaginal, — a catheter 
 specimen or one voided after a thorough vaginal douche 
 should be procured. If pus be present in such a specimen, 
 it must have originated in some portion of the urinary tract ; 
 but if no pus be present, then it must have come from the 
 genital tract. In blennorrhea a considerable quantity of pus 
 may find its way into the urine. 
 
 Epithelium. — Epithelial cells from various parts of the 
 
 urinary tract usually form a part of the sediment of every 
 
 normal and pathologic urine. Epithelium is the normal 
 
 product of the mucous membrane, and represents the 
 
 " wear and tear " of such surfaces. In disease the desqua- 
 i6
 
 242 URINARY SEDIMENTS. 
 
 mation is usually much increased ; the recognition of the 
 cells from the various parts of the urinary passages is, 
 therefore, of the greatest importance, for it is often only by 
 this means that abnormal processes can be located. The 
 student should familiarize himself, as far as possible, with 
 the cells that are characteristic of certain areas, before 
 drawing inferences as to pathologic states ; he should also 
 bear in mind that every normal urine contains a certain 
 number of cellular elements. 
 
 The epithelial cells found in the urinary sediment coming 
 from a given part of the tract usually have entirely different 
 shapes from those found in prepared histologic specimens 
 of that part. For example, some of the renal epithelium 
 /// situ is cuboid in shape, while that found in the urine is 
 usually round. Other similar examples could be cited in 
 which the shapes of the original cells have become changed, 
 apparently by the action of the urine. 
 
 In the detailed study of the cells that follows, the 
 leucocyte ivill be used as a standard for comparison, since 
 this body is nearly constant in size. (Fig. 39, a.) 
 
 Renal Epithelium. — These are epithelial cells from the 
 tubules of the kidney. They are essentially small round 
 cells, which are usually more or less granular, and present 
 a single nucleus. (Fig. 39, b.^ There are three sizes of 
 renal cells : /. ^., the first, which is smaller than a leucocyte, 
 and probably comes from the smaller tubules in the cortical 
 portion of the kidney ; the second, which is about the same 
 size as the leucocyte, and constitutes the average renal cell, 
 which is probably from the convoluted tubules ; and the 
 third, which is larger than the leucocyte, and probably comes 
 from the straight or collecting tubules. Renal cells are 
 frequently adherent to casts and, when practically covered 
 with them, form the so-called epithelial cast. Renal cells 
 are often very granular, and sometimes much distorted, as a 
 result of degenerative processes in the kidney ; such are 
 seen especially in cases of advanced chronic interstitial 
 nephritis. 
 
 Fatty renal cells ^XQ those which contain fat-drops (Fig. 
 39, <?), and are the result of degenerative processes in the 
 tubules of the kidney. Such cells may contain only one or 
 two fat-globules, or they may be entirely fatty degenerated. 
 They do not usually differ in size from the renal cells 
 already mentioned, and are not to be mistaken for the
 
 PELVIC EPITHELIUM. 243 
 
 larger, so-called compound granule cell, to be described 
 later. Not infrequently some or all of the fat is washed 
 out of the cell, when it will be found to contain one or more 
 vacuoles. Fatty renal cells are found in the urinary sedi- 
 ment in cases of subacute glomerular nephritis, chronic 
 diffuse nephritis, during the fatty stage of acute nephritis, 
 and not infrequently in the severer forms of renal congestion.' 
 Renal cells always accompany renal casts, although at 
 times they are present only in small numbers. Any small 
 round cell that is adherent to a cast can be safely considered 
 a renal epithelial cell. 
 
 Pelvic Epithelium. — Epithelial cells from the pelvis of 
 the kidney vary in shape according to the parts from which 
 they come, (a) Those from the supa-jicial layer of the 
 pelvis are small caudate cells. (Fig. 39, c.) The tails are 
 often curved and at times are bifurcated. The body is the 
 same size or perhaps a little larger than that of the leuco- 
 cyte, and usually has a distinct nucleus, a brown color, 
 and is quite granular. These cells are sometimes arranged 
 in groups, overlapping "like shingles on a roof," but are 
 usually found singly. They are invariably accompanied 
 by more or less blood, and indicate either a simple irritation 
 of the renal pelvis or a more extensive inflammatory process 
 — an acute pyelitis. They are of frequent occurrence, and 
 often occur in very large numbers in cases of acute pyelo- 
 nephritis, especially those cases that are of toxic origin. (/;) 
 The cells from the deep layer of the pelvis of the kidney 
 are merely small round cells (Fig. 39, d), usually about • 
 the size of the leucocyte, and having much the same appear- 
 ance as the renal cells, although frequently not quite so 
 dense. These cells are often arranged in clumps, and are 
 always accompanied by pus which is both free and mixed 
 with the cells in clumps. Deep pelvic cells are always 
 found in cases of chronic pyelitis. (.) The cells from the 
 caliccs of the kidney (Fig. 39, e) are only rarely found in the 
 sediment. They belong to the class of small round cells, 
 but are considerably larger than the deep pelvic cells. They 
 are also somewhat larger than the cells from the straight 
 tubules of the kidney, and are generally found in clunips, 
 overlapping one another. These cells have large, roundi 
 prominent nuclei, and are less granular than the cells from 
 the deeper layer of the pelvis. They are usually found in 
 cases of acute pyelitis.
 
 244 
 
 URINARY SEDIMENTS. 
 
 Ureteral Epithelium. — The author has had exceptional 
 opportunities for the study of cells from the ureter in speci- 
 mens obtained by the ureteral catheter. EpitheHal cells 
 from the ureter are of two forms (Fig. 39,/) — i. e., (i) 
 small caudate cell, which is somewhat larger and denser 
 than the cell from the superficial layer of the pelvis of the 
 kidney, also with a larger and more prominent nucleus and 
 a somewhat larger tail ; and (2) a small spindle cell, which 
 is generally very narrow and with a small nucleus. These 
 two forms of cells are usually quite granular and small, and 
 
 Fig. 39. — Epithelium from various parts of the urinary tract : a, Leucocyte (for 
 comparison); b, renal cells; c, superficial pelvic cells; rf, deep pelvic cells; ^, cells 
 from calices ; /", cells from ureter ; g, g, g, g, g, squamous epithelium from the blad- 
 der ; h, /i, neck-of-bladder cells ; z, epithelium from prostatic urethra ; k, urethral cells ; 
 /, /, scaly epithelium ; m, m', cells from seminal passages ; n, compound granule cells ; 
 o, fatty renal cell. 
 
 should not be confounded with similar cells of larger size, 
 which come from the bladder. The diagnosis of an inflam- 
 matory process in the ureter is generally not easily made 
 from the urinary sediment, since the number of cellular 
 elements from this membrane is often small, and the in- 
 flammatory condition is usually accompanied by either a 
 pyelitis or a cystitis. In case there is marked irritation of 
 the mucous membrane of the ureter by crystalline elements 
 or small calculi, ureter cells may be found in large numbers, 
 and the diagnosis more easily determined.
 
 BLADDER EPITHELIUM. 245 
 
 Bladder Epithelium. — The epithelial cells from the 
 fundus of the bladder are, for the most part, of the squamous 
 or pavement variety. They are large, flat, thin, polygonal 
 cells (Fig. 39, g), having a distinct and usually a central 
 nucleus, which is prominent without the aid of acetic acid. 
 When arranged in groups, the cells are frequently found 
 joined by their edges and not overlapping, although at times 
 they are found overlapping to a slight extent. Squamous cells 
 from the bladder are generally moderately granular, but may 
 be entirely free from granules. Those cells that come from 
 near the openings of the ureters are usually large, thin, and 
 circular in shape. Epithelial cells from the month are not 
 unlike those from the fundus of the bladder, but differ by 
 having small nuclei and containing small particles of carbon. 
 Cells from the mouth are generally clumped, and accom- 
 panied by a large amount of mucin in which they are en- 
 tangled, and often by particles of food. 
 
 Epithelial cells from the neck of the bladder (in the male) 
 are thicker, smaller, and much denser than those coming 
 from the fundus. They are generally round or oval, and 
 have a small, prominent nucleus. (Fig. 39, h.) They are 
 usually not granular, and are from three to five times the 
 size of a leucocyte. Cells from the neck of the bladder 
 are often arranged in clumps of three or five, but are usually 
 not found overlapping. An occasional cell from this region 
 may be found in a perfectly healthy urine, but when found 
 in excess with leucocytes, they indicate an irritation, and 
 when mixed with pus. an inflammatory process at the neck 
 of the bladder. 
 
 Prostatic Cells. — Epithelial cells from the prostatic 
 ducts are small round cells, which are not unlike renal cells 
 in- size. They are usually less granular and somewhat 
 denser than renal cells, and present a single distinct nucleus. 
 They are often adherent to long shreds of mucin, — so-called 
 "prostatic casts,'' — and are generally accompanied by leuco- 
 cytes and often by spermatozoa. 
 
 Seminal Cells. — These are cells from the seminal 
 passages, and are medium round cells, which are highly 
 granular, rather dense, and contain an ill-defined nucleus. 
 (Fig. 39, ;;/, ;//.) Spermatozoa are often found within the 
 body of the cell or projecting from it. These cells are in- 
 variably accompanied by free spermatozoa. 
 
 Urethral Cells. — Epithelial cells from the urethra vary
 
 246 URINARY SEDIMENTS. 
 
 in shape according to the portion from which they come. 
 Those from the prostatic portion are usually dense, pyriform, 
 round, or irregular cells with a single distinct nucleus. 
 (Fig. 39, /.) They are smaller than those from the neck of 
 the bladder, and from one and one-half to twice the size of 
 a leucocyte. They are usually not clumped unless en- 
 tangled in shreds of mucin with pus, as is often the case in 
 stricture of this portion of the urethra. Cells from the 
 pendulous portion of the urethra are either small round or 
 small caudate in shape (Fig. 39, k), but somewhat denser 
 than renal and superficial pelvic cells, but not so dense as 
 those from the prostatic urethra. These cells are most 
 frequently seen in the discharge that results from a gonor- 
 rheal inflammation, and are usually intimately mixed with 
 mucin and pus. The recognition of the cells from this 
 portion of the urethra is of no great consequence, as the 
 diagnosis of a urethritis is generally made by other means. 
 
 Vaginal Epithelium. — The urine of the female nearly 
 always contains more or less epithelium from the genital 
 tract — that is, the vaginal secretion, generally consisting 
 chiefly of epithelium with a greater or smaller number of 
 pus-corpuscles, is washed from the vulva and often causes 
 a very abundant sediment. Vaginal epithelium consists 
 chiefly of the squamous or pavement form, although many 
 other varieties of cells are usually present, such as the spin- 
 dle, large and medium round, large and small caudate, and 
 irregular cells. These cells are mononuclear, and usually 
 only slightly granular, and generally somewhat larger than 
 the average sized bladder cell. Vaginal cells are often 
 arranged in large clumps, and on careful focusing will be 
 found to be overlapping, " like shingles on a roof," and often 
 several layers in depth. Very often the so-called scaly epi- 
 thelial cell (Fig. 39, r) is found, which represents the old 
 epithelium from the vulva, and is a very thin, degenerated 
 cell, containing only a remnant of a nucleus, if any nucleus 
 at all. A urine holding a large amount of squamous epi- 
 thelium and only a few leucocytes generally contains a 
 vaginal secretion, which, in the majority of instances, is not 
 abnormal. 
 
 Compound Granule Cells. — These are medium and 
 large round cells that have undergone complete fatty degen- 
 eration. They are entirely filled with fat globules of vary- 
 ing size, and do not show a nucleus. (Fig. 39, ;/.) Com-
 
 RENAL CASTS. 247 
 
 pound granule cells should not be mistaken for fatty renal 
 cells, the former being always larger than the latter, and 
 usually more completely degenerated. Not infrequently 
 they have prismatic or long hair-like crystals of the fatty 
 acids protruding from them. They may be found free in 
 the sediment, or adherent to casts. Compound granule 
 cells are the result of extensive fatty degeneration, and 
 come not only from the urinary tract but from other mucous 
 membranes as well, especially those that are chronically 
 diseased. When of renal origin, they are found in the 
 sediment during the fatty stage of an acute nephritis, also 
 in subacute glomerular and chronic diffuse nephritis, and 
 rarely in active hyperemia. They may be found in the 
 sediment in chronic pyelitis, chronic cystitis, chronic pros- 
 tatitis, and in urethritis ; also as a result of ulcerations in any 
 part of the urinary tract, and often in large numbers in the 
 contents of an abscess or cyst cavity that has evacuated 
 into the urinary passages. They are sometimes found in 
 vaginal secretions, and also in expectorated matter that has 
 been introduced into the urine. Compound granule cells 
 are, therefore, of no great practical importance unless found 
 in the presence of, and adherent to, renal casts. 
 
 Renal Casts. — Renal casts, also termed "tube-casts" 
 and "cylinders," are molds of the uriniferous tubules. 
 They are produced by the admission into the tubules of a 
 coagulable (?) substance, which there solidifies, and, en- 
 tangling whatever it may have surrounded in its liquid 
 state, subsequently contracts, and is forced from the renal 
 tubules by the urine. It is then carried into the pelvis of 
 the kidney, thence into the bladder, and voided with the 
 urine. 
 
 The origin of renal casts has been the subject of much 
 discussion and must still be considered an unsettled question. 
 
 Three theories have been advanced as to their probable 
 nature and mode of formation : 
 
 («) That they are composed of coagulable elements of 
 the blood that have transuded into the renal tubules through 
 pathologic lesions of the latter, and have there solidified, 
 to be later voided with the urine as molds of the tubules. 
 
 {b') That they consist of a secretion of the pathologic 
 epithelium lining the renal tubules, this secretion solidifying 
 to form molds or tube-casts, which are forced out by the 
 urine.
 
 248 URINARY SEDIMENTS. 
 
 (r) That they are the direct result of the disintegration 
 of the renal cells, whose products become formed into casts 
 of the tubules in which they are formed, and being forced 
 out by the urine make their appearance in the sediment. 
 
 The first theory {a) is the most plausible of the three ; 
 at least, it is applicable to the nature and mode of formation 
 of most of the casts found in the urinary sediment. 
 
 Renal casts have been variously classified, but the 
 simplest division is the following, which is based upon their 
 microscopic appearance : 
 
 I. Hyaline (transparent) casts-/ (2 
 
 1(3 
 
 Pure hyaline. 
 
 Fibrinous. 
 
 Waxy. 
 
 Fine. 
 
 Coarse. 
 
 Brown. 
 
 II. Granular " < 
 
 III. Epithelial 
 
 IV. Blood 
 V. Fatty 
 
 VI. Pus 
 
 r(i) Urate. 
 VII. Crystalline " < {2) Oxalate. 
 
 I (3) Cystin. 
 VIII. Bacterial 
 IX. " Mucous " (nucleo-albumin) casts, also termed 
 fa/si' casts. 
 
 I. Hyaline Casts. — Hyaline^ casts are of three varie- 
 ties : (i) Pure hyaline, (2) fibrinous, and (3) waxy casts. 
 
 (/) Pure liyaline casts are pale, transparent, homogeneous 
 cylinders, generally with rounded ends. (Fig. 40.) They 
 may be short or very long, even extending through six or 
 more fields of the microscope. ^ They are found of vary- 
 ing diameters, some narrow and others wide, but always 
 presenting a cylindric appearance. Their sides are usually 
 parallel and straight, but they may be indented, presenting 
 a scalloped appearance. They are often twisted upon them- 
 selves, and not infrequently have a serpentine shape. One 
 end of the cast may be ragged and irregular, showing that 
 the original cylinder has been divided, and occasionally a 
 
 ^ The term hyaline is here used in the broad sense of transparent. 
 2 Leitz microscope. No. i eye-piece and No. 7 objective.
 
 HYALINE CASTS. 249 
 
 segment is seen with both ends ragged. Pure hyaHne casts 
 are free from granules, and are therefore often very difficult 
 to detect in the sediment. They are best discovered by 
 reducing the amount of light entering the microscope, 
 either by manipulating the mirror, or by interposing the 
 hand between the source of light and the mirror, thus shading 
 the microscopic field. As a rule, the casts of large diameter 
 are somewhat more refracting, and thus more readily de- 
 tected than the small narrow casts. 
 
 Not infrequently hyaline casts contain a few very fine 
 granules of a pale color. They sometimes exhibit here and 
 there upon their surfaces a renal cell or a blood globule or 
 droplet of oil. Such casts are considered strictly of the 
 
 Fig. 40. — Pure hyaline casts. 
 
 hyaline order, and are referred to as hyaline casts with a 
 renal cell or a blood globule or fat-drops adherent, as the 
 case may be. 
 
 The narrow hyaline casts doubtless have their origin in 
 the smaller undenuded tubules, while those of large diameter 
 come chiefly from the large straight, or collecting tubules of 
 the kidney. In advanced disease of the kidney, notably 
 chronic interstitial nephritis, we find an exception to the 
 rule — /. e., the majority of the casts emanating from high up 
 in the kidney are of large diameter, while those from the 
 collecting tubules are very large. Such casts are from ex- 
 tensively denuded tubules, the result of the advanced 
 disease.
 
 250 URINARY SEDIMENTS. 
 
 Hyaline casts are common to all diseases and disturbances 
 of the kidney, and not pathognomonic of any one abnormal 
 condition. They are, however, predominant in the sedi- 
 ment in cases of chronic interstitial, chronic diffuse nephritis, 
 amyloid infiltration, and in passive hyperemia ; while their 
 relative proportion is much smaller in comparison with the 
 other forms of casts present in active hyperemia, acute 
 nephritis, and subacute glomerular nephritis. 
 
 [2) Fibrinous Casts. — These are very dense or JiigJdy 
 refractive casts, usually of the transparent variety and ahuays 
 of a yellozvish color, which ranges between a pale yellow 
 and a deep brown. (Plate 8.) 
 
 Fibrinous casts are, however, sometimes granular, and 
 often have renal epithelial cells and blood globules, and, 
 not infrequently, oil-drops adherent. Like the pure hya- 
 line casts, they are of various shapes and sizes, but being 
 heavier and denser than the hyaline form, show a greater 
 tendency to crack and break, thus becoming divided into 
 rather short segments, the ends of which are usually thick 
 and ragged. They are also frequently found of moderate 
 length, with rounded ends ; they are, as a rule, of larger 
 diameter than the average hyaline cast found in the sedi- 
 ment. Fibrinous casts sometimes have so little color as to 
 be distinguished with difficulty from the waxy cast that is 
 always perfectly colorless. If any doubt exists in the mind 
 of the observer as to their true character, the term " highly 
 refractive casts " should be used, until, upon further study, 
 the observer is convinced that they are fibrinous and not 
 waxy casts. The bearing of this suggestion is seen in the 
 following paragraph : 
 
 Fibrinous casts usually accompany blood in the sedi- 
 ment — in other words, are found in acute diseases or dis- 
 turbances of the kidney, such as acute nephritis, and some- 
 times active hyperemia ; also in acute exacerbations of 
 either acute or chronic renal diseases. The fibrinous cast 
 is simply one of the elements of an acute condition, and as 
 this condition subsides, it disappears from the sediment. 
 Fibrinous casts do not, therefore, indicate an unfavorable 
 prognosis. Waxy casts, on the other hand, are practically 
 unheard of in active hyperemia and acute nephritis, but are 
 most often found in the sediment in the advanced forms of 
 kidney disease, their presence being always an unfavorable 
 prognostic sign.
 
 Plate 8 
 
 ^^^12~i<^ 
 
 P"i URINOUS Casts.
 
 HYALINE CASTS. 
 
 251 
 
 The Xqxtcl Jibri7io2is as applied to these casts is inappro- 
 priate, as they do not consist of fibrin, nor do they have 
 any relation to it, only resembling fibrin in their yellow or 
 brownish color. 
 
 (j) Waxy Casts. — These, like the fibrinous casts, are 
 very higJdy refractive casts of the transparent variety, and 
 are always perfectly colorless. (Fig. 41.) They are usu- 
 ally of large diameter and often very long, and their sur- 
 faces may be marked by indentations showing imperfect 
 vertical segmentations ; they often have a serpentine appear- 
 ance. Not infrequently, waxy casts are coarsely granular, 
 the granules apparently having the same composition as 
 the cast itself (Fig. 41.) They may have fat-drops, or fatty 
 
 Fig. 41. — Waxy casts. 
 
 renal cells, or compound granule cells adherent to them. 
 On account of their thickness and density, waxy casts are 
 often found with cracks on their surfaces, also frequently 
 found in segments, with one or both ends rough and irrep-- 
 ular, showmg that the long casts have become broken into 
 several small pieces. 
 
 Waxy casts should, in all instances, be distinguished from 
 fibrinous casts, since, as has already been explained, they 
 have an entirely different significance. 
 
 Waxy casts are found in the sediment in the advanced 
 stages of all chronic diseases of the kidney, such as chronic 
 interstitial, chronic diffuse, and subacute (parenchymatous) 
 nephritis, and are of bad omen, indicating that death will
 
 252 URINARY SEDIMENTS. 
 
 probably occur within a comparatively short time, usually a 
 year. This rule, however, is not invariable, as was well 
 demonstrated by a case that the author observed for a 
 period of over two years, in which waxy casts were con- 
 stant, and, as was shown at the autopsy, there existed a 
 marked chronic diffuse nephritis of the parenchymatous 
 variety. Waxy casts are a frequent accompaniment of 
 amyloid infiltration of the kidneys, in which they appear 
 earlier than in other chronic renal diseases, and arc of de- 
 cided diagnostic value. They are of much less importance 
 as a prognostic sign than in other chronic renal affections. 
 
 The term waxy, as applied to these casts, is a misnomer. 
 It was formerly supposed that waxy casts were characteristic 
 of amyloid infiltration of the kidneys, but, as has been 
 shown, they are often found in other chronic diseases of the 
 kidney. These cacts rarely show the amyloid reaction with 
 methyl-violet and with iodopotassic-iodide solution, even 
 when amyloid disease of the kidneys is present. 
 
 The hyaline cast constitutes the basis or groundwork of 
 all other casts to be described, each cast being named 
 according to the elements adherent to or embedded in it. 
 Thus, a cast covered with granules is called a granular cast ; 
 with epithelium, an cpitliclial cast ; with blood, a blood-cast, 
 etc. 
 
 II. Granular Casts. — These casts consist of a hyaline 
 basis in which granules are embedded. Various terms are 
 applied to these casts — i. e., when covered with fine granules, 
 finely granular ; with coarse granules, coarsely granular ; 
 and when the granules are colored so as to give the cast a 
 brown color, broivn granular, etc. (Fig. 42.) 
 
 The granules found on these casts probably come from 
 the renal tubules, and are the result of the degeneration and 
 disintegration of the renal epithelium. At times, these 
 granules appear to result partly from the destruction of 
 blood-corpuscles and leucocytes. This is particularly the 
 case in connection with the brown granular casts, which 
 appear to derive their color from the blood pigment. Bile 
 naturally stains granular casts yellow or it may give them a 
 brown color. Brown granular casts nearly always accom- 
 pany blood-casts. 
 
 Granular casts, like the hyaline forms, have a variety of 
 shapes, and may be of small, medium, or large diameter. 
 They are usually rather short and have rounded ends ; not
 
 EPITHELIAL CASTS. 
 
 253 
 
 infrequently, however, fragments of granular casts are found 
 with rough and irregular ends. They may have renal epi- 
 thelium, blood globules, fat, or leucocytes adherent to their 
 surfaces or embedded in them. 
 
 Finely granular casts are found in ever}^ disease or dis- 
 turbance of the kidney ; they, therefore, can not be con- 
 sidered pathognomonic of any one disease or class of dis- 
 eases. 
 
 III. Epithelial Casts. — These are casts that are prac- 
 tically covered with renal epithelium. (Fig. 43, i.) The 
 renal cells may be embedded in, or firmly adherent to, 
 either hyaline or granular casts. A hyaline cast that holds 
 one, two, or three renal cells is best termed a hyaline cast 
 
 Fig. 42— a, Hvaline and finely granular cast ; b, finely granular cast ;<:, coarsely 
 granular cast ; d, brown granular cast ; e, granular cast with normal and abnormal 
 blood adherent ; /, granular cast with renal cells adherent ; g, granular cast with fat 
 and a fatty renal cell adherent. 
 
 with a retial cell or cells adherent ; the same applies to a 
 granular cast. This term serves to distinguish such casts 
 from those that are covered with renal cells and properly 
 called epithelial casts. Renal cells on casts are usually 
 more or less granular and swollen, and sometimes they are 
 so firmly embedded in the cast that their outlines are ill 
 defined. The nuclei of the cells often stand out prominently, 
 although at times the cells are so granular as partially or 
 entirely to obscure the nuclei. These cells may also con- 
 tain fat globules. In an epithelial cast leucocytes are 
 frequently found mixed with the epithelial cells ; such a 
 cast, which consists chiefly of epithelium, should not be 
 mistaken for a true pus-cast.
 
 254 
 
 URINARY SEDIMENTS. 
 
 Epithelial casts are most commonly found in those path- 
 ologic conditions that cause an exfoliation of the renal 
 epithelium, such as severe active hyperemia, acute nephritis, 
 and subacute glomerular nephritis. They are only rarely 
 found in the urine of chronic interstitial nephritis and amy- 
 loid infiltration of the kidneys. In cases of extreme renal 
 irritation and congestion the epithelial lining of the tubules 
 is sometimes thrown off intact for short distances, an epi- 
 thelial cylinder possessing a lumen resulting. 
 
 IV. Blood-casts. — These are of two kinds — i.e., {a) a 
 hyaline or granular cast, which is practically covered with 
 blood globules ; and (/;) the cylinder, which consists of 
 coagulated blood — fibrin with blood globules firmly em- 
 bedded. 
 
 Blood-casts are found in the urine in those conditions in 
 
 Fig. 43.— I, Epithelial cast; 2, blood-cast; 3, pus-cast; 4, fatty cast; 5, fatty cast 
 with a compound granule and fatty renal cell adherent (crystals of the fatty acids 
 protruding). 
 
 which there is more or less hemorrhage into the renal 
 tubules. In the majority of instances the blood-cast is 
 made up of abnormal blood (Fig. 43, 2), in which case the 
 inference is that either the blood comes from high up in 
 the kidney or the hemorrhage into the tubules is very slow. 
 In casts of this kind the blood-corpuscles are unusually 
 distinct, but, at times, indistinct, requiring careful focus- 
 ing in order to make out the faint, deeply embedded 
 globules. Not infrequently blood-casts consist of nonnal 
 blood ; under such circumstances the hemorrhage is usuall}' 
 either from the pyramidal portion of the kidney — straight 
 tubules — or is very abundant and from higher up in the 
 kidney. These normal blood-corpuscles, which still have 
 their pale-yellow color, are often observed agglutinated,
 
 FATTY CASTS. 255 
 
 at times forming a solid mass on the cast. Ordinarily, 
 however, they are not so agglutinated but that the outlines 
 of the individual corpuscles can be readily seen. Blood- 
 casts are generally short, of medium diameter, and quite 
 uniform throughout, usually having rounded ends. One 
 portion of the cast may be hyaline or granular, and the re- 
 mainder covered with blood. 
 
 Blood-casts are found in the urine in hematuria of renal 
 origin, acute diffuse nephritis, acute renal congestion, and 
 hemorrhagic infarctions of the kidneys. Blood-casts do not 
 in themselves furnish positive evidence of organic renal dis- 
 ease, since any hemorrhage from the kidney may be asso- 
 ciated with blood-casts in the urine. On the other hand, it 
 may be stated that the presence of blood-casts constitutes the 
 only positive evidence of the existence of renal hemorrhage. 
 
 V. Fatty Casts. — These are casts that are thickly 
 studded with fat drops. (Fig. 43, 4.) It has already been 
 stated that a hyaline or granular cast may have oil globules 
 attached, but the term fatty cast only applies to those that 
 are practically covered with fat. At times, fine needle- or 
 hair-like crystals of the fatty acids are found protruding 
 from these casts, and they may have fatty renal cells and com- 
 pound granule cells embedded in or attached to them. (Fig. 
 43 » 5-) Generally, the fat-drops are small and appear as 
 glistening points ; such should not be mistaken for the less 
 highly refracting granules not fat. Sometimes the globules 
 are large, when they are easily recognized. Fatty casts indi- 
 cate that a fatty degeneration of the kidney is in progress, 
 since the fat is probably the result of extreme degeneration 
 of the renal cell protoplasm. They are not necessarily in- 
 dicative of a chronic kidney disease, although most common 
 in , subacute glomerular (chronic parenchymatous) and 
 chronic diffuse nephritis. They are also found during the 
 fatty stage of an acute nephritis, and occasionally in severe 
 renal congestion. 
 
 VI. Pus-casts. — Pus-casts are tho.se that are covered 
 with pus-corpuscles or leucocytes. (Fig. 43, 3.) The cor- 
 puscles are generally highly granular, and often so much so 
 that their nuclei are entirely obscured. Under such cir- 
 cumstances, because of failure to make out the nuclei, casts 
 that are covered with pus-corpuscles are often considered 
 to be epithelial casts. Such inference should not be drawn 
 without first thoroughly treating the sediment with dilute
 
 256 URINARY SEDIMENTS. 
 
 acetic acid, which dissolves the granular matter, thus caus- 
 ing the nuclei of the leucocytes and the nucleus of the 
 cell to stand out prominently. 
 
 Hyaline or granular casts with one, two, or three leuco- 
 cytes adherent are frequently found in acute diseases and 
 disturbances ; also in acute exacerbations occurring during 
 the course of a chronic disease of the kidneys. True pus- 
 casts, on the other hand, are quite uncommon, and, when 
 present, indicate a chronic suppurative process in some 
 portion of the kidney. Pus-casts may be formed in case 
 there is an abscess of the kidney or tuberculosis of this 
 organ ; also in cases of chronic pyelitis with extension into 
 the straight tubules, in which instance they are usually of 
 large diameter. 
 
 Bacterial Casts. — True casts when covered with bacteria 
 have received the name " bacterial casts." Accidental 
 aggregations of bacteria that closely resemble renal casts in 
 shape and size, and seen particularly in urines that have 
 been exposed to the air for a long time, should not be mis- 
 taken for bacterial casts. True bacterial casts closely 
 resemble the brown granular casts, and are distinguished 
 from the latter by their resistance to certain chemicals, such 
 as acetic acid, mineral acids, and strong alkalies. It is 
 almost impossible to distinguish between them by means of 
 the microscope, particularly if the bacteria belong to the 
 class of micrococci as is usually the case. Bacterial casts 
 are very uncommon, and are chiefly found in the septic 
 forms of renal disease, especially those accompanied by 
 embolism, and are therefore a grave prognostic sign. They 
 are sometimes found in the ascending form of chronic pyelo- 
 nephritis or "surgical kidney." 
 
 VII. Crystalline Casts. — These are of three kinds, and 
 are named according to the form of crystal adherent to or 
 embedded in them. Thus, a urate cast is one that is 
 covered with crystals of ammonium urate, usually the 
 hedgehog crystals ; the cystin cast, covered with hexagonal 
 crystals of cystin, as seen rarely in cases of cystinuria ; and 
 the calcimn oxalate cast, covered with the octahedral, oval, 
 or dumb-bell crj^stals of calcium oxalate. As a rule, 
 cr}'stalline casts show that the cr}^stals deposited thereon 
 were separated in the kidney, and therefore primary. Occa- 
 sionally, crystals are deposited on casts secondarily — that 
 is, after the urine has been voided.
 
 FALSE CASTS. 257 
 
 False Casts. — False casts, also termed mucin casts, 
 shreds, or cyllndroids, are not infrequently found in the sedi- 
 ment. They are long, flat structures, usually with fine, 
 wavy, longitudinal striations, and long tapering ends. (Fig. 
 44.) They are colorless, often twisted or folded, and 
 usually free from adherent elements, although they may 
 have cells, leucocytes, and blood globules adherent. False 
 casts are usually longer than the true renal casts just 
 described, and appear to be flat and not cylindric. It is 
 probable that these structures consist only of coagulated 
 nucleo-albumin or mucin, although the subject requires 
 further investigation in order to determine their true nature. 
 It is sufficient to say that they are, apparently, not true 
 casts, that they are frequently present in a urine that is free 
 from albumin, and that they are of little clinical importance. 
 
 False casts may originate in the kidney, but they are 
 most commonly found in the sediment in connection with 
 
 Fig- 44-— False casts or cylindroids (after von Jaksch). 
 
 irritation or inflammation of the lower urinary passages, 
 particularly of the bladder, prostatic region, and urethra. 
 They may be found in the prostatic ducts as a result of mild 
 or severe inflammatory processes, when they are usually 
 accompanied by a large number of mucin (nucleo-albumin) 
 threads or shreds. It is often exceedingly difficult to dis- 
 tinguish these so-called prostatic casts from true renal casts ; 
 in fact, these two structures may exist in the same urinary 
 sediment. 
 
 Prostatic Plugs. — These bodies, occasionally found in 
 the urinary sediment, are evidently formed in the prostatic 
 ducts. They appear to be cylindric, often with rounded 
 ends, and are usually of large diameter, but may be of 
 irregular shape, as from a dilated duct or cavity. They are 
 either colorless or colored yellow, when they have much 
 the appearance of fibrinous casts. Prostatic plugs usually 
 have spermatozoa embedded in them, and, at times, leuco- 
 17
 
 258 
 
 URINARY SEDIMENTS. 
 
 cytes or epithelial cells from the prostatic ducts are firmly- 
 adherent to them. 
 
 These bodies are found most commonly in mild inflam- 
 matory processes that involve the region of the neck of the 
 bladder and the prostatic ducts. 
 
 Spermatozoa. — Spermatozoa are frequently found in the 
 urine of healthy men. They are bodies about 50 // in 
 length, and consist of an oval head, or body, about 4.5 // 
 in length, to which is attached a long, tapering whip-like 
 tail of extreme delicacy. (Fig. 45.) When freshly ejected, 
 they exhibit active eel-like movements, strongly suggestive 
 
 
 
 C 
 
 
 
 
 
 
 '" 
 
 % 
 
 
 ^'' 
 
 
 
 
 
 L 
 
 
 
 c 
 
 ' 
 
 
 
 < 
 
 Q 
 
 
 d) 
 
 '■7 
 
 c 
 
 
 
 
 'J 
 
 
 H " 
 
 
 
 
 
 
 
 i 
 
 
 c 
 
 
 
 
 6 
 
 
 Oo 
 
 
 ■ V 
 
 y 
 
 
 
 
 ? ^ 
 
 
 
 
 
 
 
 
 6 
 
 \ 
 
 
 <y 
 
 
 
 Fig. 45. — Spermatozoa. 
 
 of volition ; but as seen in the urine they are always 
 motionless. The cause of the movements in spermatozoa 
 is unknown, although Roberts claims that they are floating 
 cilia and resemble the oscillating sperm-cells of the anther- 
 idae of mosses. Their movements are arrested by water, 
 alcohol, ether, drying, etc. They resist putrefaction, and 
 when once dried, may, after years, be restored to their 
 original form by moistening them with a weak solution of 
 sodium chloride or potassium acetate. Spermatozoa are 
 usually accompanied by medium-sized, highly granular 
 cells ; also by finely granular cells with one or more nuclei ; 
 more rarely, by lecithin corpuscles and spermatic crystals.
 
 CORPORA AMYLACE/E. 259 
 
 Clinical Significance. — A certain number of spermatozoa 
 necessarily find their way into the urine of both sexes after 
 coitus ; also into the urine of men after involuntary nocturnal 
 emissions. The persistent absence of spermatozoa from 
 the seminal fluid indicates sterility. The recognition of 
 spermatozoa is most important in connection with medico- 
 legal cases — cases of suspected rape. Their presence in 
 vaginal secretion soon after coition and in stains upon linen 
 is easy of demonstration. Spermatozoa are sometimes 
 found in the urine in cases of severe acute febrile disease, 
 such as typhoid fever, pneumonia, and acute septic condi- 
 tions, also following convulsions. They are of frequent 
 occurrence in cases of acute or chronic prostatitis or irrita- 
 tion in the prostatic region. The condition of spermator- 
 rhea is characterized by the constant presence of sperma- 
 tozoa. 
 
 Detection. — Spermatozoa are best detected by their char- 
 acteristic appearance under the microscope. Florence,^ of 
 Lyons, has recently described a characteristic reaction that 
 takes place between iodine-potassium iodide and seminal 
 fluid. 
 
 Florence Reaction. — The reagent is prepared as follows : 
 
 Potassium iodide, 1.65 giams. 
 
 Iodine, 2.54 " 
 
 Distilled water, 30 " 
 
 The iodine-potassium iodide in this mixture corresponds to 
 the formula KI3. 
 
 A small portion of the suspected seminal fluid is treated 
 with a drop of the foregoing reagent. If semen be present, 
 small, dark, rhombic crystals appear, which are very simi- 
 lar in their general appearance to the hemin crystals ob- 
 tained in Teichmann's test for blood. So far as is known, 
 no other secretion of the body gives this reaction. 
 
 Corpora Amylaceae. — The so-called amyloid bodies, or 
 corpora amylaceae, have somewhat the appearance of starch 
 granules, but they differ from starch in their chemic re- 
 actions. They are microscopic, spheroid, homogeneous, 
 or lamellated bodies (Fig. 46), usually containing within 
 them a core, which is also frequently lamellated and some- 
 times colored. They do not swell when soaked in hot 
 
 1 Florence, " Du Sperme et des Taches de Sperme en Medecine Legale," 
 1897.
 
 260 URINARY SEDIMENTS. 
 
 water, and are not split up by boiling with dilute mineral 
 acids ; they are not dissolved by fuming nitric acid. Amy- 
 loid bodies are colored red by methyl-violet, while starch 
 is colored blue. When the former are treated with iodine 
 or iodine-potassium-iodide solution, they not infrequently 
 show a violet to a blue color, which becomes distinctly 
 blue by the subsequent action of sulphuric acid. These 
 bodies seem to have no connection with amyloid infil- 
 tration, although they sometimes resemble its products. 
 They may occur normally as well as under pathologic con- 
 ditions, and are apparently of little clinical importance. 
 
 Corpora amylacese are frequently found in the acini of 
 the prostate gland, from which they may find their way 
 into the urine, sometimes in large numbers. They are also 
 found in the ependyma of the ventricles of the brain and in 
 
 Fig. 46.— Corpora amylaceae. 
 
 areas of sclerosis of the brain and cord ; also in extravasa- 
 tions of blood in various other situations. The amyloid 
 bodies represented in figure 46 were found by the author in 
 the urine of a man who, several days before, had had an 
 extensive hemorrhage from the prostatic region. At the 
 time these bodies were found the urine was, however, free 
 from blood. In the experience of the writer these so-called 
 amyloid bodies are a rare constituent of the urinaiy sedi- 
 ment. 
 
 Amyloid Concretions. — These are frequently found in 
 the prostate gland of old people. They are sometimes 
 large enough to be detected with the naked eye, and are 
 usually hard, and often have a dark color due to the depo- 
 sition of pigment. (See Prostatic Concretions, p. 280.)
 
 EXTRANEOUS SUBSTANCES. 261 
 
 EXTRANEOUS SUBSTANCES FOUND IN URINE. 
 
 These are very numerous, and include, indeed, all sub- 
 stances that are liable to get into vessels containing the 
 urine. The most common of these are fibers of cotton and 
 linen, hair of blankets, worsted, wool, human hair, cats' 
 hair, splinters of wood, oil globules, starch granules, lyco- 
 podium and other pollen, tea leaves, bread crumbs, particles 
 of glass, dust, etc. It is a common custom with some 
 persons to expectorate into the vessel that is to contain 
 the urine or into the urine after it has been voided, hence 
 pavement epithelium containing pigment granules, particles 
 of food, free oil, etc., will be found. It is very important 
 that the student should become familiar with the microscopic 
 appearances of all these extraneous elements before he be- 
 gins the examination of urinary sediments. 
 
 PRESERVATION OF URINARY SEDIMENTS. 
 
 In order to preserve urinary sediments it is necessary to 
 treat the urine and its sediment in such a way as to prevent 
 subsequent changes, of which the most common are ammon- 
 iacal decomposition and the formation of vegetable growths. 
 To accomplish this end, the coloring-matters and the salts 
 of the urine must be remov^ed by washing with those media 
 that will take up the soluble urinary constituents and, at the 
 same time, leave the sediment — cells, casts, crystals, etc. — 
 in the same condition as found in the fresh urine. 
 
 Epitliclial cells, renal casts, blood, pus, fat, and fibrin, 
 are best preserved in the following manner : Allow the 
 urine to settle thoroughly in a urine glass, or centrifugalize, 
 and wash by decantation twice with a saturated aqueous 
 solution (4 per cent.) of boric acid, and then three times 
 with an aqueous solution of potassium acetate (specific 
 gravity, 1030) containing y^ of i per cent, of formalin. 
 The sediment is left in the last washing of potassium acetate 
 and formalin, and is then placed in a tightly stoppered bottle, 
 where it will keep for months and years. By this process 
 the sediment suffers very little, if any, change, excepting 
 that any blood that was originally in the sediment as 
 normal blood will be changed to abnormal blood. 
 
 Crystalline sediments on account of their solubility in the 
 media already given require different treatment, the pre-
 
 262 URINARY SEDIMENTS. 
 
 servative used varying with the form of crystal to be pre- 
 served. 
 
 Uric acid, calcium oxalate, hippuric acid, cystin, and 
 cholcsicrin crystals should be washed, by decantation, several 
 times with a small volume of very dilute acetic acid (i to 2 
 per cent.), and, finally, after all of the soluble urinary salts 
 have been removed, left in the last washing. This is then 
 placed in a perfectly clean, tightly stoppered bottle. 
 
 Acid amjnonitim urate and acid sodium urate crystals 
 should be washed, by decantation, several times with a small 
 volume of 33 per cent, alcohol, and, after all of the soluble 
 urinary salts have been removed, left in the last washing, 
 and then placed in a clean, tightly stoppered bottle. 
 
 Triple phosphate and acid calcium phospJiatc crystals should 
 be washed, by decantation, several times with a small wo\\xvc\q 
 of very dilute ammonic hydrate (i to 2 per cent.), finally 
 left in the last washing, and placed in a clean, well-stoppered 
 bottle. 
 
 Some of these crystals, such as the oval and dumb-bell 
 forms of calcium oxalate, cystin, triple phosphate, and acid 
 calcium phosphate, frequently undergo partial solution in 
 their respective media, particularly when kept in the bottle 
 for several months or years. All crystalline sediments keep 
 better when mounted on glass slides ; it is, therefore, advis- 
 able to mount them as soon as possible after washing. 
 
 The washing can be done by the centrifugal or the 
 gravity methods, the former having the advantage of com- 
 pleting the washing in a few hours and before bacteria or 
 other foreign substances enter the fluid. 
 
 The Mounting of Urinary Sediments. — After the sedi- 
 ments have been prepared in the manner described they 
 can be mounted on glass slides, and thus preserv^ed for 
 years. 
 
 Method. — Place a glass slide on a turn-table and make a 
 cell by the use of Bell's cement and a camel's-hair brush. 
 Allow the cement to dry thoroughly. Place a drop of the 
 prepared sediment within the cell, and cover with a circular 
 cover-glass of such a size that its margin rests well on the 
 ring of cement. Take up the excess of fluid from around 
 the cover-glass by means of a piece of filter-paper, care being 
 taken not to admit air to the cell, and also to remove all air- 
 bubbles that may be present. Return the slide to the turn- 
 table, and carefully cover the margin of the cover with Bell's
 
 MICRO-ORGANISMS. 263 
 
 cement so as to make the cell air-tight. Allow this layer of 
 cement to dry, and in two or three days apply another coat. 
 Mounts prepared in this manner will in most instances keep 
 several years, and are very useful for purposes of demon- 
 stration or for reference. 
 
 MICRaORGANISMS. 
 
 The micro-organisms that are found in the urine belong to 
 the following different classes : Bacteria (nonpathogenic and 
 pathogenic),' molds, and yeasts, all of which properly belong 
 to one general class called f2iiigi. 
 
 Fresh normal urine is free from bacteria or other micro- 
 organisms, and, as has been repeatedly demonstrated, is a 
 sterile fluid. Numerous investigations have shown that 
 bacteria are usually, if not always, present in the urethra of 
 both the male and female, particularly near the meatus ; 
 therefore urine that was sterile intra vesicam becomes con- 
 taminated as it passes through the urethra. 
 
 Bacteria, being vegetable in their nature, belong to the 
 class of fungi, and for purposes of study are more conven- 
 iently divided into two classes : {a) nonpathogenic or those 
 that are innocuous, and {b) pathogenic forms or those that 
 are pyogenic in their nature. 
 
 (a) Nonpathogenic Forms. — As already stated, fresh 
 normal urine is free from bacteria, but when such urine is 
 allowed to stand exposed to the air for some time, it soon 
 becomes crowded with micro-organisms of various kinds, 
 rendering the urine turbid and, for the most part, unfit for a 
 satisfactory examination. 
 
 The microscopic appearance of fermenting normal urine 
 is' subject to much variation. The conversion of urea into 
 ammonium carbonate is probably effected through the 
 agency of several forms of micro-organisms (Leube, C. 
 Fliigge, v. Jaksch, v. Limbeck), of which the micrococcus 
 iirece (Fig. 47) is the most prominent, and at times may be 
 seen in almost pure culture upon the surface of the decom- 
 posing fluid. These micrococci form in long chain-like 
 series, although they may occur as free, round, highly re- 
 fracting dots ; they are usually of comparatively large size, 
 and are constant inhabitants of the air. Of the other micro- 
 organisms that have a part in the decomposition of urea, the 
 staphylococcus urecB candidus and staphylococcus Jirece lique-
 
 264 
 
 URINARY SEDIMENTS. 
 
 facials (Lundstrom), bacillus iirccc (Leube), iirobacilhis 
 Frciidcnrcichii, and the urobacillits Maddoxii should also be 
 mentioned. It is claimed that the urobacillus Maddoxii is 
 the micro-organism that renders the urine viscid and 
 stringy. A number of other bacteria have been isolated 
 from decomposing urine, but little is yet known of their 
 importance. Occasionally, long spiral bacilli with large 
 
 Fig. 47. — Micrococcus ureae (after v. Jaksch). 
 
 spores, and cocci that group themselves in globular masses 
 of varying sizes are met with in the urine. 
 
 Molds are, under normal circumstances, a very rare mani- 
 festation in decomposing urine. In diabetic urine, however, 
 they not infrequently make their appearance, especially after 
 the alcoholic fermentation has ceased. They are then found 
 floating in a layer on the surface of the urine. The urine 
 is at the same time more or less turbid with bacteria and 
 yeast fungi. 
 
 Fig. 48. — Sediment from fermenting diabetic urine with casts of micrococci : 
 a, b, c. Various forms of uric acid ; d, micrococci in form of casts ; e, molds ; jT, yeast 
 fungi ; g, bacilli and micrococci (after v. Jaksch). 
 
 The yeast fungus of the urine (saccharomyces urinae) 
 consists, in the sporule stage, of transparent oval cells, which 
 are seen both singly and in rows of two, three, or more. 
 (Fig. 48, f.) They are found in saccharine urine, and are 
 identical with the yeast fungus (saccharomyces cerevisiae). 
 They grow in acid urine, but cease to multiply as soon as 
 the urine becomes alkaline.
 
 MICRO-ORGANISMS. 265 
 
 Yeast spores are distinguished from normal blood-corpiis- 
 clcs by the fact that the former are smaller, perfectly color- 
 less, and have usually a focal point. They differ from 
 abnormal blood-corpuscles in having an oval shape, a focal 
 point seen especially in the larger sporules, and a cell-body, 
 the abnormal blood globule appearing simply as a ring 
 — that is, apparently without a cell-body. (Compare p. 
 
 231-) 
 
 The presence of the yeast fungus in the urine is always 
 suggestive of the presence of sugar, but in the experience 
 of the writer this rule is by no means invariable. It occa- 
 sionally happens that the urine to be examined is placed in 
 a bottle containing a mere trace of syrup ; in such a urine 
 the yeast fungus grows rapidly. 
 
 Penicilli2im glaucnm is not infrequently met with in acid 
 urine with or without sugar or albumin. The sporule stage 
 furnishes cells very similar to those of the yeast fungus, 
 but later the penicillium multiplies by linear division of 
 cells, forming threads that have a characteristic appearance. 
 
 The sarcina nrince is a fungus only occasionally seen in 
 the urine. It is smaller than that which forms in the 
 stomach (sarcina ventriculi), being in point of size compar- 
 able to the sarcina of the lung. They are cubes, each 
 group of eight cells being so arranged as to resemble a 
 " bale of goods." 
 
 (b) Pathogenic Forms. — The pathogenic micro-organ- 
 isms found in the urine may be divided into two classes — 
 i. e., micrococci and bacilli. Of the micrococci the strepto- 
 coccus pyogenes, the staphylococcus pyogenes albus, citrcus, 
 and aureus, and the gonococcus of Neisser are the most im- 
 portant. The most common bacilli found in the urine are 
 the bacillus coli communis, the urobacillus liquefaciens scpti- 
 cus, and the tubercle bacillus. 
 
 When recently voided urine is found to contain patho- 
 genic micro-organisms, the condition becomes serious on 
 account of the marked tendency to decomposition of the 
 urine within the bladder. These micro-organisms occur in 
 the freshly voided urine in connection with certain specific 
 diseases, such as typhoid fever, erysipelas, relapsing fever, 
 ulcerative endocarditis, glanders, malignant pustule (bacillus 
 of anthrax), septic processes, and tuberculosis. The spirilla 
 of relapsing fever occur very rarely and only when hemor- 
 rhage takes place in the kidney during an exacerbation (v.
 
 266 URINARY SEDIMENTS. 
 
 Jaksch). According to Horton-Smith,i the freshly voided 
 urine of typhoid fever is usually turbid from the presence 
 of the typhoid bacilli. Richardson ^ has recently shown 
 that the virulence of these bacilli is destroyed by the inges- 
 tion of urotropin (a formaldehyde compound). Actinomyces 
 may also occur in the urine in instances in which the genito- 
 urinary tract is infested with it, or in those cases in which 
 it enters this tract from other parts (Braatz). Lustgar- 
 ten and Mannaberg have found cocci in the urine in acute 
 nephritis ; and Letzerich has found bacilli in the " primary 
 nephritis " of children. Mircoli also determined the pres- 
 ence of pneumococci-like forms in the urine of children 
 suffering from acute nephritis. Schweiger has demonstrated 
 that in scarlet fever the urine is distinctly contagious; and 
 he claims that all renal lesions arising in the course of in- 
 fectious fevers are caused by micro-organisms. 
 
 In recent years the recognition of the tubercle bacillus in 
 the urine or urinary sediment has been attended with great 
 pathologic interest. A detailed consideration of this sub- 
 ject, together with the method best adapted to the detec- 
 tion of tubercle bacilli, will be found on page 323. It is of 
 great importance to differentiate the tubercle bacillus from 
 the smegma bacillus, which is frequently present in the urine. 
 
 Gonococci consist of diminutive kidney-shaped cocci 
 aggregated in large groups. They are, for the most part, 
 diplococci with the flattened surfaces of the kidney-shaped 
 cocci presenting to each other. They are often found in 
 abundance in the gonorrheal discharge from the urethra, 
 within the pus-corpuscles and exfoliated epithelial cells, as 
 well as free in the shreds of mucin. It has been satisfac- 
 torily demonstrated that diplococci, in all respects resem- 
 bling gonococci, exist in the genital tract. It is, therefore, 
 exceedingly important from a diagnostic point of view to 
 distinguish the gonococci from those that closely resem- 
 ble them. This is best accomplished in the following way : 
 First, stain a preparation with Loeffler's solution of methyl- 
 ene-blue. If the characteristic groups of diplococci are 
 found in the cells and pus-corpuscles, then stain a new 
 preparation by Grain's method, as follows : (i) Cover the 
 preparation with aniline-gentian-violet solution (without 
 
 ^ "Transactions of the Medical and Surgical Society," London. 
 *" The Journal of Experimental Medicine," vol. iv, No. I, 1899.
 
 PARASITES. 267 
 
 heat) for thirty seconds ; (2) wash in water for two or three 
 seconds ; (3) cover the preparation with Gram's solution 
 of iodine (iodine, i part ; potassium iodide, 2 parts ; water, 
 250 parts) for thirty seconds ; (4) wash with 95 per cent, 
 alcohol until the color ceases to come out of the prepara- 
 tion ; (5) wash in water for two or three seconds ; (6) 
 counterstain with saturated aqueous solution of Bismarck 
 brown ten seconds ; (7) wash in water, mount, and examine. 
 Gonococci are stained brown, while other diplococci are 
 stained blue by this method. 
 
 PARASITES. 
 
 Filaria Sanguinis Honiinis. — This is the parasite that 
 causes the condition of chyluria. This parasite was first dis- 
 
 Fig. 49. — Eggs of distoma hsematobimn in sediment (after v. Jaksch). 
 
 covered and described by Lewis, of Calcutta, who found 
 them in large numbers in the urine and blood of persons 
 who were passing milk)- or chylous urine. ^ 
 
 Distoma Hcematobinni. — The eggs of this parasite are 
 often found both in the urinary passages and in the urine 
 of inhabitants of tropical climates. This worm infests the 
 north and east coasts of Africa, and, according to Brock, is 
 found also in South Africa. The eggs are oval, slender 
 bodies, about o. 1 2 mm. long and 0.04 mm. broad, and fur- 
 nished with a small spike, which projects from the ex- 
 
 1 A detailed account of this parasite, together with an illustration of the 
 same, will be found under the subject of Chyluria, p. 360.
 
 268 
 
 URINARY SEDIMENTS. 
 
 tremity or from the side. (Fig. 49.) Both the male and 
 female parasites have been found in the branches of the 
 portal vein, the splenic vein, the vesical plexus, etc., and 
 are nourished by the blood. The male is from 1 2 to 14 mm. 
 long, and the female is from 16 to 20 mm., and nearly 
 cylindric in shape. (Fig. 50.) In case the individual is 
 infested with this parasite the most prominent symptom is 
 
 Fig. 50. — Distoma haematobium ; male and female, with eggs (after v. Jaksch). 
 
 severe burning pain during micturition. The pain is usu- 
 ally momentary, and caused by the passage of the eggs 
 along the urethra, which they irritate by their sharp angles. 
 The urine usually contains blood- and pus-corpuscles, with 
 eggs of the parasite, and sometimes a considerable quantity 
 of fat. There are often marked cystitis, pyelitis, sometimes 
 nephritis, and septic processes. 
 
 Echinococci. — Echinococcus cysts have been found in 
 
 '^ 
 ^ 
 
 Fig. 51.— Echinococcus scolices and hooklets (after Heller). 
 
 the kidney, although rarely. Usually, only one kidney is 
 affected. The hydatid growth is made up of an outer cap- 
 sule, within which the mother cysts are found. Within 
 the mother cysts are the daughter cysts. Both the large 
 mother cysts and the smaller daughter cysts float freely in 
 the liquid contents of the capsules holding them. This 
 peculiar growth is caused by a very small tapeworm, — the
 
 PARASITES. 
 
 269 
 
 tcenia cchinococciis, — whose natural size is about that of a 
 millet seed, (Fig. 52.) This worm consists of a head 
 much like that of the ordinary tapeworm, four mouths or 
 suckers, and a double row of booklets. 
 
 The scolices and booklets (Fig. 5 i) occasionally find their 
 way into the urine, either from the cysts in the kidney or 
 from some neighboring organ, as the result of rupture. The 
 booklets are usually accompanied by 
 more or less blood, leucocytes, and at 
 times shreds of membrane forming the 
 hydatid cyst. The diagnosis of echino- 
 coccus growth of the kidney is only 
 made with certainty by finding charac- 
 teristic booklets in the urinary sediment. 
 
 Hydatid disease of the kidney in man 
 is most commonly contracted from the 
 dog, whose intestinal tract is often in- 
 fested with large numbers of echinococci. 
 The eggs that are passed with the stools 
 find their way into the food, thence to 
 the stomach of man ; as the embrj'o 
 hatches it enters the blood, is carried to 
 the liver or kidneys, where it forms the 
 hydatid cyst. This disease is most com- 
 mon in the arctic regions, where the 
 natives live with their dogs, and it is 
 said that in Iceland approximately one- 
 seventh of the mortality is due to hydatid 
 disease. 
 
 Ejistrongylus Gigas. — The presence of 
 this parasite in the urine is a very rare oc- 
 currence. According to the researches 
 of 'Leuckart.i the existence of this para- 
 site in man is a matter of some doubt. 
 
 Ascaridcs. — In rare instances ascarides 
 have been found in the urinary passages 
 in the urine is usually explained by an abnormal communi- 
 cation between the intestine and the urinary tract. Scheiber ^ 
 reports having found in the urine of a woman worms that he 
 considered had been derived from the genital organs, and he 
 has named them rliabditis o-cnitalis. 
 
 »w4'> 
 
 \--m 
 
 Fig. 52. — Taenia 
 echinococcus, enlarg- 
 ed. Above, at the 
 right, echinococcus 
 of natural size (after 
 Heller). 
 
 Their presence 
 
 1 Leuckart, " Deutsche med. Wochenschr.," xni, S. 390. 
 
 2 Scheiber, " Virchow's Archiv," Lxxxn, 161, 1884.
 
 CHAPTER VII. 
 
 URINARY CONCRETIONS, 
 
 Urinary concretions or calculi consist of an aggregation 
 of solid matter that has becorne separated or precipitated 
 from the urine. They may form in any part of the urinary 
 tract, from the tubules of the kidney to the meatus urina- 
 rius. They vary very much in their composition, but in- 
 variably consist of certain constituents of the urine — either 
 normal or pathologic — that have separated or become pre- 
 cipitated from it. The nucleus may, however, consist of a 
 foreign body that has been introduced into the urinary pas- 
 sages, or of certain substances that have their nativity in 
 the body, such as mucous or blood coagula, or fragments 
 of morbid tissue that have become detached. Of the for- 
 eign substances that have been found to form the nucleus 
 of urinary calculi may be mentioned peas or beans that 
 have been introduced into the urethra by the insane or by 
 children, pieces of catheters or bougies that have been acci- 
 dentally broken off in the urethra or bladder, pieces of soap 
 or candles, hanpins, pins, needles, and bullets that have 
 lodged in some portion of the urinary tract. From this 
 it is seen that the nucleus of a urinary calculus may be any 
 substance that has its origin in the body and that exists in 
 solid form in the urinary passages, or a foreign body that 
 may have been accidentally or intentionally introduced into 
 them. 
 
 The conditions of the urine favoring the growth of calculi 
 are variable. Among the causes may be mentioned (i) a 
 diminution in the amount of water excreted ; (2) a change 
 in the reaction of the urine, whether abnormally acid or 
 alkaline ; (3) an increased formation of some of the less 
 easily soluble constituents of the urine. Changes in the 
 
 270
 
 URINARY CONCRETIONS. 271 
 
 reaction embrace hyperacidity, which favors the deposition 
 of uric acid and urates and of calcium oxalate by diminish- 
 ing the solvent action of the urine over these substances ; 
 and an alkaline condition of the urine, which causes the 
 separation of the phosphates and carbonates of calcium 
 and magnesium and of ammonium urate. The chief effect 
 of an increased acidity of the urine is to lessen the solu- 
 bility of the uric acid by diminishing the amount of alkali 
 with which it may enter into combination. Uric acid is 
 usually present in the urine in solution in the form of nor- 
 mal urate of sodium or potassium, which is very soluble in 
 water. In case the uric acid is deprived of a part or the 
 whole of its base, either the acid urate of potassium or 
 sodium or uric acid is the result. These substances, being 
 much less soluble in water than the normal urates, separate 
 from the urine, and tend to become aggregated in the form 
 of concretions. An alkaline reaction of the urine may be 
 due to the presence of either a fixed alkali or to free am- 
 monia and ammonium carbonate. It rarely happens that a 
 calculus forms as a result of a deposition of the earthy 
 phosphates by a fixed alkali, as is well demonstrated in 
 those cases in which alkaline remedies are given for a long 
 time, as in the treatment of acute rheumatism, and also in 
 those cases in which the urine is habitually alkaline, as in 
 some cases of faulty metabolism. 
 
 Of much greater importance is an ammoniacal reaction 
 that frequently results in a calculus formation by the de- 
 position of triple phosphate, amorphous phosphates, and 
 ammonium urate. (See Reaction, p. 31.) Concretions from 
 this cause are quite commonly met with in cases of irritation 
 or inflammation of the bladder, the change from a normally 
 acid to an alkaline reaction being due to the presence of the 
 urea ferment that decomposes the urea. A deposit of phos- 
 phates always tends to increase the size of any calculi that 
 may already exist. 
 
 A diminution in the amount of water excreted, particu- 
 larly when coupled with an increased formation of any of 
 the slightly soluble constituents of the urine, such as uric 
 acid and acid urates, calcium oxalate, cystin, and very rarely 
 xanthin, favors the tendency to the formation of concretions 
 within the urinary passages, since these substances do not 
 find a sufficient amount of urine to hold them in solution.
 
 272 URINARY SEDIMENTS 
 
 CONSTITUENTS OF URINARY CALCULI. 
 
 These are either organic or inorganic or a mixture of 
 the two. They are conveniently divided into two classes, 
 as follows: (i) Primary coistitiioits, or those which sepa- 
 rate from the urine without any material change in the 
 character of the urine, other than changes referable to 
 altered metabolism ; and (2) secondary constituents, or those 
 which separate' from the urine as a result of ammoniacal 
 fermentation. 
 
 ' Primary Constituents. Secondary Constituents. 
 
 ! sodium, 
 ammonium, 
 potassium. Calcium phosphate, 
 calcium, 
 magnesium. 
 Calcium oxalate. Calcium carbonate. 
 
 Calcium phosphate, both crystalline Ammonio-magnesium phosphate 
 
 and amorphous. (triple phosphate). 
 
 Calcium carbonate. Ammonium urate. 
 
 Cystin. 
 Xanthin. 
 Indigo. 
 
 Urostealith (Heller). 
 Silica. 
 Albuminous substances (blood, pus, 
 
 etc.). 
 Bilirubin (hematoidin). 
 
 Urate of ammonium, calcic carbonate, and calcic phos- 
 phate may, therefore, be either primary or secondary con- 
 stituents. 
 
 Urinary concretions are most commonly found in the 
 pelvis of the kidney and in the bladder, but they may form 
 in any part of the urinary tract. In the Warren Museum 
 at the Harvard Medical School is a rare specimen showing 
 a number of medium-sized concretions in the pelves of both 
 kidneys and in both ureters, also a large calculus in the 
 bladder. Calculi are also sometimes formed in sinuses con- 
 necting the urinary passages with the intestines, uterus, or 
 vagina. 
 
 The nnniber of concretions that may be present in the 
 urinary passages is almost unlimited ; often there is only a 
 single stone, but there may be several hundreds. 
 
 Urinary concretions vary in size from that of a pinhead 
 to that of an orange or even larger. Those of small size
 
 CONSTITUENTS OF URINARY CALCULI. 273 
 
 have been somewhat arbitrarily termed sa)id or gravel, 
 while those of large size are called stones or calculi. The 
 size of a calculus is limited only by the dimension of the 
 cavity in which it is formed. The smaller concretions 
 usually emanate from the kidney or pelvis of the kidney, 
 while those of large size generally come from the bladder. 
 Concretions vary in weight from a few milligrams to .several 
 grams ; in the Dupuytren Museum, at Paris, is a calculus 
 weighing i 596 grams. 
 
 T\\& surf ace of a urinary calculus varies with its composi- 
 tion and its location in the urinary tract. Those consisting 
 of uric acid, phosphates, and cystin are usually smooth, 
 while those made up of calcium oxalate are generally 
 rough and lobulated — vmlberry calculi. In case several 
 concretions occupy a single cavity — for example, the 
 bladder — their surfaces are often polished in those portions 
 that rub against each other during the natural movements 
 of the bladder wall or during the changes in position of the 
 body. The smooth or polished surfaces are termed facets. 
 
 The shape of urinary calculi varies as the location. Those 
 in the kidney proper are generally very irregular ; they 
 often have small projections that have extended into cavities 
 formed by the destruction of the renal tissue. Calculi in 
 the pelvis of the kidney when large usually assume the 
 form of that cavity, projections taking place into the calices, 
 and giving the calculus in some cases a shape not unlike 
 that of an elephant ; small concretions in the pelvis are 
 generally round or oval. Calculi in the bladder vary 
 greatly in shape. If only a single concretion be present, it 
 is usually round, oval, or sometimes flat. If numerous 
 calculi are present, their form may be modified by constant 
 pressure against each other. Occasionally, a calculus 
 becomes partially encysted in the bladder, so that the 
 deposit takes place only upon one portion, thereby causing 
 the growth of the calculus to take place in one direction 
 only, and giving it a very irregular shape. Those that 
 have formed in the urethra are generally oblong or cylindric 
 in shape, and when there are several, the ends of those that 
 are adjacent are often highly polished. 
 
 The color of calculi varies with their composition and the 
 
 admixture of organic subtsances such as blood, pus, fibriri, 
 
 etc. Those consisting of uric acid and urates are always 
 
 colored, varying between a pale straw and a dark brown, 
 
 18
 
 274 URINARY SEDIMENTS. 
 
 the coloring-matter being derived chiefly from the urine. 
 Calculi consisting of calcium oxalate are often of a dark- 
 brown color due chiefly to the presence of decomposed 
 blood and of fibrin. Phosphatic calculi are generally gray- 
 ish or white, while those made up of cystin are usually yellow 
 in color. 
 
 The composition of urinaiy calculi may be simple, con- 
 sisting of only one constituent of the urine, such as uric 
 acid or calcium oxalate, or it may be compoiind, with two 
 or more primary deposits occurring in separate and alternate 
 layers, the most common of these constituents being uric 
 acid and calcium oxalate. Several of the constituents may 
 be mixed in any portion of the stone. It is not uncommon 
 to find a calculus with a central portion composed of alter- 
 nate layers of two or more of the primary constituents and 
 an outer layer of some one of the secondary constituents. 
 
 Most urinary calculi consist of three distinct parts — i. e., 
 the nucleus ; the body ; and the crust. The nucleus occu- 
 pies the center and may have the same composition as the 
 rest of the concretion, but it often consists of some albu- 
 minous body, such as a coagulum of fibrin, or mucus or 
 pus mixed with uric acid, urate, or calcium oxalate crystals 
 about which are deposited other similar or perhaps entirely 
 different urinary constituents. A concretion may have 
 several nuclei, as, for example, when two or more small 
 calculi become united to form a single stone ; these nuclei 
 are readily seen when a section is made through the calcu- 
 lus. The nucleus varies much in size and usually occupies 
 the center of the concretion, but it may be excentrically 
 placed especially if the growth of the calculus is only in 
 one direction. 
 
 The body comprises the greater part of the calculus and 
 surrounds the nucleus ; it may or may not have the same 
 composition as the nucleus. The body may consist of 
 concentric layers of two or more urinary constituents, such 
 as a layer of uric acid and urates, another of calcium oxa- 
 late, and so on for several layers. The several layers of the 
 body may be differently colored ; even those having the 
 same composition may be variously colored. 
 
 The crust or external envelop of the calculus is deposited 
 upon the body, and always consists of one or more of the 
 secondary constituents of the urine, the phosphates usually 
 predominating ; in other words, the crust is always found
 
 URIC ACID AND URATE CONCRETIONS. 275 
 
 after ammoniacal fermentation of the urine has taken place, 
 and it usually forms upon v^esical calculi. Concretions that 
 have formed in an acid urine do not, therefore, have a crust. 
 Calculi that have smooth surfaces like the uric acid and 
 urate may not havx a crust formation even when present in 
 an ammoniacal urine, but calculi consisting of calcium oxa- 
 late, on account of their rough surfaces, usually have a crust 
 formation and sometimes the deposit begins while they are 
 quite small. As a rule, the time required for the beginning 
 of formation of a crust depends largely upon the time nec- 
 essary for the calculus to produce a cystitis. 
 
 URIC AQD AND URATE CONCRETIONS. . 
 
 Calculi consisting partly or entirel}- of uric acid and 
 urates comprise the great majority of concretions found 
 in the urinary tract. They are very common as renal 
 calculi in children, especially those consisting chiefly of 
 ammonium urate. They are generally smooth, oval, or 
 round and of a yellow or brown color. When such con- 
 cretions are formed in the kidney or pelvis of the kidney, 
 they may be washed out with the urine singly or in num- 
 bers, and are then found to vary in size from a pinhead to 
 that of a kernel of wheat, or to that of a pea. Their pas- 
 sage down the ureter is accompanied by more or less pain, 
 so acute at times as to cause the symptoms of renal colic. 
 If these small concretions are retained in the bladder, they 
 usually grow more or less rapidly, and then instead of being 
 perfectly smooth are often irregular, and vaiy in weight from 
 a few grains to several ounces. When uric acid and urate 
 concretions are forming, the urine is usually found to be 
 concentrated, highly colored, of strongly acid reaction, and 
 of high specific gravity. The sediment generally contains 
 crystals of uric acid or the hedgehog forms of acid ammo- 
 nium urate, or the stellate groups of sodium urate ; there is 
 usually also evidence of more or less irritation of the kid- 
 neys and frequently signs of mechanical irritation of the 
 bladder that has been set up by the crx^stalline elements. 
 
 Concretions that consist chiefly of urates do not usually 
 attain the large size of the mixed uric acid and urate calculi, 
 rarely being found larger than an average sized marble. 
 They are usually lighter in color and not so hard as the
 
 276 URINARY SEDIMENTS. 
 
 mixed concretions. When .some of the powdered calculus 
 is heated on platinum foil, it chars and completely disap- 
 pears if uric acid or ammonium urate be the only constituent ; 
 but if sodium urate be present, there remains a residue that 
 is soluble in water and has an alkaline reaction (carbonate 
 of the alkali). 
 
 CALCIUM OXALATE CONCRETIONS. 
 
 These are met with most often as medium or large, dark 
 brown, rough, trabeculated bodies having a mulberry-like 
 surface, hence the name " inidbcrry calculi.'" They are very 
 hard and can be crushed only with difficulty. Calcium oxa- 
 late concretions are composed chiefly of calcium oxalate 
 which is mixed with more or less organic matter. Occasion- 
 ally the body of the calculus consists of alternating layers 
 of calcium oxalate and uric acid. The nucleus often consists 
 of uric acid and urates, or a coagulum of blood or mucus ; 
 it may, however, be made up entirely of calcium oxalate. 
 As previously stated, calcium oxalate concretions are very 
 apt to have a crust consisting chiefly of phosphates. 
 
 The characteristics of the urine from which oxalate con- 
 cretions are being deposited are very much the same as 
 when uric acid and urate concretions are forming. The 
 sediment will contain crystals of calcium oxalate and evi- 
 dences of a more or less marked irritation of the kidneys 
 and bladder. If the stone is forming in the bladder, a 
 typical chronic cystitis may exist. When some of the pow- 
 dered calculus is heated on platinum foil, it chars slightly, 
 on account of the organic matter that is mixed with it ; there 
 remains a white residue of calcium oxide or calcium car- 
 bonate, according to the amount of heat used. If the 
 former, it will be found to be only slightly soluble in a 
 drop of water, which will have an alkaline reaction ; if the 
 latter, it will dissolve with effervescence in a drop of acetic 
 acid. 
 
 PHOSPHATIC CONCRETIONS. 
 
 \ These always form in neutral or alkaline (ammoniacal) 
 urine and originate chiefly in the bladder. They are usually
 
 CALCIUM CARBONATE CONCRETIONS. 277 
 
 white or of a grayish color, quite soft and easily crushed. 
 They are often covered on their surface with bright, glisten- 
 ing points representing large crystals of triple phosphate. 
 The surface may be smooth or rough ; if it is smooth it 
 frequently has the feeling of chalk. Phosphatic concre- 
 tions having a grajash color are usually harder than the 
 white or chalky calculi. The former consist chiefly of cal- 
 cium phosphate, while the latter are composed chiefly of 
 triple phosphate. Concretions that consist solely of cal- 
 cium phosphate, or triple phosphate are very uncommon, the 
 mixed phosphatic calculus being the one met with most fre- 
 quently. 
 
 If some of the powdered calculus be heated on platinum 
 foil it does not char or burn, but a bulky residue remains 
 which dissolves in acetic acid without effervescence, as does 
 the original powder. 
 
 CALCIUM CARBONATE CONCRETIONS. 
 
 Concretions composed of calcium carbonate are very rare 
 in man, very few cases having been reported. They are not 
 uncommon in the herbivora. They are usually small, of a 
 grayish color, of smooth surface and very hard. Calcium 
 carbonate concretions are generally spherical in shape, and 
 on section they present concentric lines. When some of 
 the original powder is treated with a drop of acetic acid it 
 dissolves with effervescence ; when the powder is heated on 
 platinum foil to a white heat it is converted into calcium 
 oxide, which is but slightly soluble in a drop of water, the 
 solution having an alkaline reaction. 
 
 CYSTIN CONCRETIONS. 
 
 These are among the rarer forms of calculi. They are 
 quite soft and of a pale-yellow color. As a rule, they are 
 oval or cylindric in shape with a rough — finely granular — 
 surface. They may form in the kidneys or bladder, the 
 latter location being perhaps the more common. 
 
 Cystin calculi when taken from the body usually have a 
 yellow color not unlike beeswax, but after being exposed
 
 278 URINARY SEDIMENTS. 
 
 to the light for a long period the color changes to a green. 
 They are generally of light weight and vary much in size. 
 
 Probably the largest cystin calculus in existence is the 
 one reported by Dr. E. S. Wood.^ It was removed from 
 the bladder by Dr. J. C. Warren, and weighed, after drying, 
 101.883 grams. It was in the form of a flattened oval, and 
 measured 2^X2^X1^ inches. 
 
 Upon section they are found to be crystalline and present 
 a radiating appearance. When some of the powdered cal- 
 culus is heated on platinum foil it burns with a blue flame, 
 and the odor of burning sulphur is evolved ; no residue 
 remains after ignition. Cystin is recognized by its solubility 
 in alkaline hydrates and in strong acids, also by its insolu- 
 bility in acetic acid. If some of the powder be treated w^ith 
 a drop of ammonic hydrate on a glass slide, it will dissolve ; 
 and if the mixture be allowed to stand until the ammonia 
 has escaped, the residue will be found to consist of the 
 colorless hexagonal cr^^stals of cystin. 
 
 XANTHIN CONCRETIONS. 
 
 These are very rare, being probably the rarest of all of 
 the urinary calculi. They may consist entirely of xanthin, 
 or the xanthin may be mixed with uric acid and urates. 
 The cases of xanthin calculi thus far reported have occurred 
 in children. Xanthin concretions vaiy in color from a white 
 or pale yellow to a brown, and they range in size from a 
 bean to a hen's egg. 
 
 When some of the powdered calculus is heated on plati- 
 num foil, it chars and entirely disappears ; in this respect it 
 resembles uric acid. But xanthin can readily be distin- 
 guished from uric acid by a modification of the murexide 
 test (see p. 66). If some of the powdered calculus be 
 treated with a drop of nitric acid on a porcelain surface 
 and evaporated to dryness, and the residue treated with a 
 drop of potassic hydrate, a pinkish tint appears which, if 
 xanthin be present, deepens to a violet on warming. Uric 
 acid gives a violet with potassic hydrate, the color disap- 
 pearing on w^arming. 
 
 1 " Journ. Boston Soc. Med. Sciences," Feb., 1898, p. 82.
 
 INDIGO CONCRETIONS. 279 
 
 INDIGO CONCRETIONS. 
 
 These are also exceedingly rare. Ord ^ has reported a 
 case in which an indigo calculus was found in the pelvis of 
 the right kidney of a woman whose left kidney was de- 
 stroyed by sarcoma. The stone weighed 40 grams, and 
 had a nucleus consisting of a coagulum of blood and a 
 deposit of calcium phosphate. Indigo derived from a de- 
 composition of the indican of the urine was deposited upon 
 one side of the calculus. Forbes 2 has also reported an 
 indigo calculus w^hich was found in the pelvis and a calyx 
 of one kidney. The stone weighed 147 grains ; its greatest 
 thickness, fore and aft, was if of an inch ; it measured 
 across its base i ^ inches, and from base to apex i y. inches. 
 It was dark brown in color ; and when it was drawn across 
 white paper, it left a rough, blue mark. The specimen can 
 be seen in the Museum of Jefferson Medical College, Phila- 
 delphia. 
 
 So far as the author is aware these two cases of indigo 
 calculus are the only ones that have thus far been recorded. 
 
 UROSTEALITH CONCRETIONS. 
 
 Urostealith, or fatty concretions, are very rare. They are 
 soft and elastic when fresh ; but when dry they are hard 
 and brittle. They are generally of a yellowish or brown- 
 ish color, and are frequently enclosed within a phosphatic 
 crust. When some of the calculus is heated on platinum 
 foil it burns with a yellow flame and gives off an odor not 
 unlike that of benzoin or shellac. 
 
 FIBRIN OR BLOOD CONCRETIONS. 
 
 These are formed as a result of the coagulation of blood 
 in the urinary tract. They are commonly found as nuclei 
 of other calculus growths, and not infrequently contain a 
 deposit of uric acid, calcium oxalate, or phosphates. When 
 
 1 Ord, "Influence of Colloids upon Crystalline Form and Cohesion in 
 Urinary and Other Calculi," London, 1879, p. 144. 
 
 2 "Medical News," Aug. 18, 1894.
 
 280 URINARY SEDIMEN'JS. 
 
 portions of calculi containing a large proportion of organic 
 matter are heated on platinum foil, they give off the odor 
 of burnt horn and burn with a yellow flame. 
 
 Concretion? containing crystals of Jicuiatoidin are occa- 
 sionally seen. These crystals are most commonly seen in 
 fibrin concretions, or in those calculi that have formed in 
 the presence of a considerable amount of blood. 
 
 PROSTATIC CONCRETIONS. 
 
 Concretions emanating from the follicles of the prostate 
 are occasionally discharged with the urine. They usually 
 have a laminated nucleus consisting of amyloid bodies {cor- 
 pora ainylacecB) about which is deposited a mixture of 
 ammonio-magn.esium phosphate and calcium phosphate. 
 They do not, as a rule, produce symptoms until they have 
 attained a large size ; prostatic concretions of large size are, 
 however, rare. 
 
 CHEMIC EXAMINATION OF URINARY CALCULI. 
 
 Before beginning the chemic examination of a calculus, 
 its size, shape, color, and density should be observed, as 
 these properties often suggest the probable composition of 
 the concretion. Since a calculus may consist of alternate 
 layers of two or more substances, it is first necessary to 
 make a section through the center of each layer of the 
 stone by sawing, in order to determine the composition of 
 each layer. If several different layers are found, it is essen- 
 tial that a portion of each layer be subjected to chemic ex- 
 amination ; that portion to be tested should always be in 
 the form of a fine powder, which can be obtained by scraping 
 a very small amount of the stone from its cut surface by 
 means of a knife-blade, or by placing small particles of the 
 calculus in a mortar and grinding them to a powder with a 
 pestle. If the section of the stone is found to have a 
 homogeneous appearance, it is only necessary to examine 
 the sawdust ; it is, however, advisable to make a separate 
 examination of the nucleus in every instance, since this por- 
 tion of a concretion is subject to marked variation. 
 
 The chemic examination is best conducted in the follow- 
 ing manner :
 
 CHEMIC EXAMINATION OF URINARY CALCULI. 281 
 
 1. Preliminary Examination. — Heat on platinum foil : 
 Albumin = a flame with odor of burnt horn. 
 Urostealith =; a flame with odor of shellac and benzoin. 
 Cystin ^= a blue flame with odor of SO^. 
 
 Xanthin and uric acid = char without a flame. 
 
 Alkaline urates ::= alkaline residue soluble in H^O. 
 
 Earthy phosphates = a residue soluble in acetic acid with- 
 out effervescence. 
 
 Calcium oxalate and calcium carbonate = a residue soluble 
 in acetic acid zvith effervescence. 
 
 Calcium carbonate = original powder soluble in acetic 
 acid with effervescence. 
 
 Calcium oxalate =^ox\g\\\z\. powder insoluble in acetic acid. 
 
 Silica ^ residue insoluble in HCl. 
 
 Murexide Test for Uric Acid. — Original powder -f HNO^ 
 and evaporate = pink residue -f- NH^OH = purple 
 color = uric acids and urates. 
 
 Original powder + HNOj and evaporate -)- KOH 
 = violet color, which disappears on heating = uric 
 acid. Violet increases on heating = xanthin. 
 
 2. Systematic Examination. — Presence of uric acid 
 
 shown by ( i). Boil in H^O and filter. 
 
 A. Filtrate -[- HCl. Let stand 24° = crystals of uric 
 
 acid. Bases in solution. Concentrate. 
 
 Calcium urate = one drop of solution -f- solution ammo- 
 nium oxalate = crystals calcium oxalate. 
 
 Magnesium urate = one drop of solution -|- NH^OH -j- 
 Na^HPO^ :^ crystals ammonio-magnesium phosphate. 
 
 Sodium urate = one drop of solution -(- Pt.Cl^ = after 
 concentrating, prisms of sodioplatinic chloride. 
 
 Potassium urate a.nd ammonium urate = one drop of solu- 
 tion -f- Pt.Cl^ := dodecahedra of potassioplatinic 
 chloride and ammonioplatinic chloride. 
 
 Potassium Urate. — Evaporate solution and igniteon mica. 
 Residue -|- HCl -)- Pt. Cl^= potassioplatinic chloride. 
 
 A?nmotiium Urate. — Evaporate solution and ignite on 
 mica. Residue = no crystals with Pt. CI^. 
 
 B. Portion insoluble in H^O. Add HCl. 
 Uric acid = insoluble. 
 
 Calcium carbonate = soluble with effervescence. Filter + 
 NH^OH 1= precipitate of calcium oxalate, calcium 
 phosphate, and ammonio-magnesium phosphate. 
 Wash. Calcium oxalate = insoluble in acetic acid. 
 Filter + ammonium oxalate to filtrate. Calcium 
 phosphate gives precipitate of calcium oxalate. Fil- 
 ter -f- NH^OH to filtrate = precipitate of ammonio- 
 magnesium phosphate.
 
 PART II. 
 DIAGNOSIS. 
 
 CHAPTER VIII. 
 
 DISTURBANCES AND DISEASES OF THE 
 KIDNEYS. 
 
 ACTIVE HYPEREMIA. 
 
 Active hyperemia — active congestion — is essentially not 
 a disease of the kidneys, but a disturbance of the functions 
 of these organs. This condition is invariably due to the 
 presence of some irritant that is within or is passing through 
 the kidneys, or to some alteration in their circulation — in 
 other words, it is always secondary in its nature. 
 
 Causes. — The causes of active hyperemia may be divided 
 into three general classes : 
 
 I. Any general disease or disturbance, which is not 
 primarily renal, but which may cause a change in the 
 renal circulation, as in severe nervous diseases, notably 
 delirium tremens and acute mania ; also in other serious 
 affections that act by causing a change in the pressure of 
 the blood in the renal vessels. 
 
 Exposure to cold and wet may set up an active hyperemia 
 of the kidneys or an acute nephritis. The reason for a 
 renal disturbance under such circumstances probably is that 
 the superficial blood-vessels and the capillaries of the skin 
 suddenly contract, due to vasomotor changes, congesting 
 the internal organs, and, since the function of the skin is 
 interfered with, the renal congestion is augmented by the 
 necessity for increased activity of the kidneys. 
 
 II, Irritants \A^ithin or Passing Through the Kid- 
 neys. — These may be divided into two distinct classes — 
 viz., insoluble and soluble. 
 
 282
 
 ACTIVE HYPEREMIA. 283 
 
 (a) Insoluble Irritants. — These are cr)'stalline substances 
 that may be separated from the urine in the kidneys, and 
 may set up a mechanical disturbance in the renal tubules — 
 c. g., uric acid, acid ammonium or sodium urate, calcium 
 oxalate, acid calcium phosphate, and cystin. 
 
 [b) Soluble Irritants. — Of these there are — 
 
 /. The toxines, which are soluble poisons formed and 
 eliminated during the progress of disease. Their irritating 
 effect is especially seen in the acute diseases — viz., pneu- 
 monia, typhoid fever, erysipelas, measles, scarlet fever, diph- 
 theria, acute rheumatism, acute miliary tuberculosis, cere- 
 brospinal meningitis, malaria, etc.; and not infrequently in 
 chronic diseases, such as pulmonary tuberculosis, chronic 
 rheumatism, chronic malaria, etc. Irritant toxines may also 
 be formed in the intestines as a result of faulty processes 
 going on there. These are absorbed by the blood and 
 eliminated by the kidneys, causing an active hyperemia. 
 This is especially seen in children who are suffering from 
 diarrhea or an enterocolitis. 
 
 Toxines may also be formed in those acute and chronic 
 local diseases that are attended with suppuration, notably 
 urethritis, prostatitis, vesiculitis, bone diseases, abscesses 
 (from which there is absorption), and diseases of the female 
 genitalia, the disturbing element being a toxine that is ab- 
 sorbed from the seat of the disease by the blood and elimi- 
 nated by the kidneys. 
 
 2. Drtigs. — The elimination of any irritating drug, such 
 as arsenic, lead, mercury, cantharides, salicylic acid, po- 
 tassium chlorate, phenol and its compounds, volatile oils, 
 etc. 
 
 J. Coricentrated Urine. — Not infrequently the passage of 
 a concentrated urine sets up an active hyperemia that varies 
 in intensity from a very mild condition to one that is quite 
 severe. It is especially seen if the urine has been in a state 
 of concentration for a long time. An active hyperemia 
 from this cause rapidly disappears when the patient is given 
 plenty of diluent drinks, the urine becoming diluted and 
 less irritating. 
 
 ^. Bile. — This substance acts as an irritant in its way 
 through the kidney. It is obvious that the merest trace of 
 bile would not, as a rule, produce more than the slightest 
 active hyperemia, whereas larger amounts generally set up 
 a more marked form of this disturbance.
 
 284 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 5. Sugar. — What has been said of bile may also be 
 credited to sugar. The author has yet to see a urine con- 
 taining bile or sugar — especially if one or the other were 
 present for more than a day or two and in more than the 
 slightest trace — where there was not evidence of an irrita- 
 tion of the kidneys. 
 
 III. Irritants Extending Upward from the Lower 
 Urinary Tract. — It is not uncommon to have a gonorrheal 
 inflammation extend upward from the urethra and bladder, 
 and involve the straight or collecting tubules of the kidney. 
 The same danger exists in an inflammation of the bladder 
 from any other cause. 
 
 In case there is some obstruction to the outflow of urine, 
 as by a urethral stricture or an enlarged prostate, the col- 
 lecting tubules may dilate, and finally result in a "surgical 
 kidney." 
 
 Various bacteria, more especiall}' tubercle bacilli, whether 
 coming from the lower urinary passages by extension or 
 by way of the blood-vessels, may set up a focal active 
 hyperemia of the kidneys. The disturbance is principally 
 confined to the pyramidal portion with more or less evi- 
 dence of extension into the cortical portion of the kidney. 
 Reference will again be made to this under the heading of 
 Tuberculosis of the Kidney. 
 
 Character of the Urine. — This varies as the cause : 
 i\ g., if the hyperemia is due to the elimination of toxines 
 that are produced in the course of an acute febrile dis- 
 ease, we will generally find a highly colored, concentrated 
 urine, whereas if the cause of the irritation is not accom- 
 panied by fever, the urine may have about a normal con- 
 centration, or it may be dilute. 
 
 It is, of course, impossible to give the characteristics of 
 the urine that will apply in every case of active hyperemia, 
 yet a few general rules may be laid down concerning the 
 average urine in this disturbance. 
 
 Quantity in Twenty-four Hours. — Usually less than 
 1500 c.c. ; average, from 800 to 1200 c.c. It may be as 
 low as 300 or 400 c.c, and may exceed 1500 c.c, but only 
 for a short time. 
 
 Color. — Normal or high. Not infrequently it is paler 
 than normal. It may be slightly smoky (usually seen, 
 however, in severe active hyperemia, or catarrhal nephritis). 
 (See p. 286.)
 
 ACTIVE HYPEREMIA. 285 
 
 Reaction. — Almost always acid, and frequently strongly 
 acid. 
 
 Specific Gravity. — This varies according to the metab- 
 olism and quantity of urine ; it is generally normal or high 
 (to 1 8 to 1030), sometimes less than normal. It usually 
 bears an inverse relation to the quantity of urine passed — 
 e.g., quantity of urine in twenty-four hours 800 c.c, spe- 
 cific gravity 103O; or quantity 2000 c.c, specific gravity 
 1014. This, however, is not always the case, for both the 
 quantity and specific gravity may be below the normal at the 
 same time — i\ ^., quantity 1200 c.c, specific gravity 1012. 
 
 Normal Solids (Urea, Uric Acid, Chlorides, Phosphates, 
 and Sulphates). — Absolutely, about normal or slightly di- 
 minished, depending upon the metabolism. In case the 
 metabolism is much reduced, as by an acute infectious dis- 
 ease, the solids may be found, absolutely, very much dimin- 
 ished. In diabetes mellitus they are usually absolutely 
 increased. They are r'datively increased if the urine is 
 concentrated ; and relatively diminished if the twenty-four- 
 hour quantity is near the normal and the metabolism is low. 
 
 Albumin. — The quantity varies as the cause and the 
 severity. If the irritation is slight, there may not be more 
 than the slightest possible trace or a slight trace. On the 
 other hand, if the hyperemia is severe, as following expo- 
 sure to cold and wet, the quantity of albumin may go as 
 high as ^ of I per cent., but such an amount rarely con- 
 tinues for more than a day or two, when it will fall to a trace, 
 slight trace, or even the slightest possible trace. (See Severe 
 Active Hyperemia.) Very soon after the removal of the 
 cause of the irritation the albumin entirely disappears, but 
 not' until all of the renal epithelium that has been denuded 
 by the irritant or other active process has been restored to 
 the -tubules. 
 
 Sediment. — Usually considerable in quantity, and in the 
 average mild case consists of an occasional (or few) hyaline 
 and finely granular cast, with blood and renal cells adherent. 
 An occasional (or few) free renal cell and blood globule. 
 
 If crystalline elements, such as uric acid or calcium 
 oxalate, are the cause of the disturbance, they will generally 
 be found in the sediment, and occasionally embedded in the 
 casts. Normal blood also is very apt to be found under 
 these circumstances, as a result of the mechanical irritation 
 by the crystals.
 
 286 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 Long-continued Active Hyperemia. — If the source of 
 irritation has not been removed, and the hyperemia con- 
 tinues for months or years, fatty elements, such as fatty renal 
 cells, fat drops adherent to the casts, compound granule cells, 
 and rarely a small fatty cast, may be found in the sediment. 
 These fatty changes evidently result from the interference 
 with the nutrition of the renal epithelium. Besides the fatty 
 elements there is not infrequently a little more abnormal 
 blood than in the average mild hyperemia of short duration. 
 
 The solids will usually be found to be absolutely more 
 diminished than in the average temporary irritation. 
 
 Severe Active Hyperemia (" Catarrhal Nephritis"). — 
 A mild active hyperemia may gradually or suddenly become 
 intensified, especially during the progress of acute infectious 
 diseases, and a mild but true inflammatory process exist. 
 A severe irritation of the kidneys may, however, be severe 
 from the start, as is sometimes seen in cases of exposure to 
 cold and zvct. 
 
 Causes. — Any of the causes of an active hyperemia 
 already enumerated may result in a severe renal congestion ; 
 toxines are especially liable to produce this condition. 
 
 Character of the Urine in the Acute Stage. 
 
 Quantity. — Usually below the normal — 600 to looo c.c. 
 
 Color. — Smoky, because of the altered blood pigment 
 (methemoglobin or hematin). If there is very much nor- 
 mal blood present, the urine may have a blood-red color. 
 
 Reaction. — Generally strongly acid. It may, however, 
 have the normal acidity. 
 
 Specific Gravity. — This varies from 1018 to 1025 — in 
 other words, not far from the normal. Of course, if the 
 metabolism is much diminished, it may be as low as 1012 
 to 1015. 
 
 Solids. — Absolute. — The absolute solids are usually some- 
 what below the normal, but dependent upon the metabolism. 
 In pneumonia they may be high during the first fev/ days 
 of the acute stage, but later on they may be very low, when 
 not only the metabolism is low, but there is a serous exuda- 
 tion or effusion, into which to a greater or less extent the 
 chlorides and urea go. Relative. — As a rule, the relative 
 solids are about normal. They may be a little high or even 
 below normal, depending upon the degree of concentration 
 of the urine. 
 
 Albuviin. — This varies in quantity from a slight trace to
 
 ACTIVE HYPEREMIA. 287 
 
 i^ of I per cent. The large quantity of albumin, however, 
 is usually present only for a short period (a day or two), 
 and then falls to about a trace. The comparatively small 
 quantity of albumin (slight trace or trace) is one of the 
 important elements in the diagnosis of a catarrhal nephritis 
 as distinguished from an acute nephritis, which is character- 
 ized by a large amount of albumin (i^ to i ^^ per cent.). 
 
 Sediment. — Usually considerable in quantity and consists 
 chiefly of abnormal blood (possibly some normal blood if the 
 irritation is at its height) ; few (or numerous) granular and 
 brown granular, an occasional blood, epithelial, and fibrin- 
 ous cast ; numerous renal epithelial cells, often colored 
 brown, and a few leucocytes. 
 
 Frequently there is evidence of a coexisting acute in- 
 flammation of the pelvis of the kidneys, in which case 
 small caudate cells from the superficial layer of the pelvis 
 and clumps of cells from the caHces will be found. 
 
 Convalescence from a Severe Active Hyperemia. — In 
 the severe forms of active hyperemia or catarrhal nephritis 
 there is frequently a distinct convalescent stage, especially 
 in those cases in which the source of irritation has been partly 
 or entirely removed by natural means or by treatment. 
 
 Character of the Urine. — Quantity. — The quantity is 
 usually found to be above the average normal (1500 c.c), 
 varying from 1600 to 2000 c.c. 
 
 Color. — Slightly smoky or pale. 
 
 Reaction. — Usually acid, unless mild diuretics, such as 
 potassium acetate, may have been taken, when the reaction 
 will be found alkaline from fixed alkalies. 
 
 Specific Gravity. — This varies as the twenty-four-hour 
 quantity. It is generally between 10 12 and 10 18. 
 
 Normal Solids. — Absolute . — The solids, especially the 
 urea, are absolutely about normal. If for any reason the 
 patient be kept on a low diet, of course the solids will be 
 absolutely lower than when a liberal amount of nitrogenous 
 food is given. Relatively, the solids are diminished. 
 
 Albumin. — This varies from the slightest possible trace 
 to a large trace, usually the former. If the process be still 
 rather active, the albumin may reach a large trace (about 
 yV of I per cent.). 
 
 Sediment. — A few (sometimes numerous) abnormal blood 
 globules. An occasional (or few) hyaline, finely granular, 
 and brown granular casts, some with a little blood and fat,
 
 288 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 and a few with renal cells adherent. Few free renal cells, an 
 occasional one slightly fatty. 
 
 If there was a mild pyelitis during the acute stage of the 
 disturbance, evidence of it may still be found — viz., little 
 pus, free and in clumps ; small round cells, free and in the 
 clumps of pus ; and, possibly, an occasional small caudate 
 cell from the superficial layer of the pelvis of the kidney. 
 In such a case leucocytes may be found on an occasional 
 cast, especially those coming from the straight tubules. 
 
 If the irritant has been entirely removed, the quantity of 
 urine gradually falls to the normal, the casts disappear and 
 finally the blood, at which time the urine will be found free 
 from albumin — in other words, complete recovery. 
 
 A circumscribed inflammation of one or both kidneys 
 may take place, especially as a result of the extension of a 
 gonorrheal or tubercular inflammation or other bacterial 
 infection of the bladder and lower urinary passages to the 
 renal pelvis, and then to circumscribed areas of the kidney. 
 A circumscribed inflammatory process may also be set up 
 around a crystalline deposit or morbid growth in the kid- 
 ney. Ijnder these circumstances the urine has the usual 
 features of an active hyperemia, and not those of acute 
 nephritis. • 
 
 There are very few clinical symptoms aside from the 
 abnormal features of the urine, which are directly referable 
 to this disturbance of the kidneys. In the majority of in- 
 stances of mild active hyperemia renal symptoms are entirely 
 wanting. Since an active hyperemia is ahvays secondary, 
 it may be stated in general that the symptoms encountered 
 are those of the disease or abnormal condition that causes 
 it, and not those that are referable to the kidneys them- 
 selves. 
 
 In the severer forms of this condition, particularly when 
 due to mechanical irritants (crystals), pain in the loins is 
 not uncommon. When due to cxposzire to cold and ivct, 
 pain in the loins, languor, headache, neuralgic pains in va- 
 rious parts of the body, and more or less frequency of mic- 
 turition are sometimes present. 
 
 It is probable that an active hyperemia or active conges- 
 tion of the kidneys always becomes a part of the initial 
 stage of an acute nephritis. 
 
 Dropsy never exists as a rcstdt of an active hyperemia of 
 the kidneys, even zvhen it is severe.
 
 PASSIVE HYPEREMIA. 289 
 
 Differential Diagnosis. — From the urine alone it is 
 often difficult, if not impossible, to distinguish between a 
 severe active hyperemia (during its height) and an acute 
 nephritis, owing to the fact that the albumin may be tem- 
 porarily high, and the amount of blood and number of 
 renal elements (casts and renal cells) abundant. By ob- 
 serving the urine for a period of a few days, if a severe 
 hyperemia, the amount of albumin and blood and the 
 number of casts will be found to diminish rapidly. The 
 urine will then have the characteristics of an ordinary 
 active hyperemia, or the convalescent stage of this disturb- 
 ance. In case the condition is one of acute nephritis the 
 changes in the urine will be more gradual, and the three 
 stages — /". I'., acute, fatty, and convalescent, are easily dis- 
 tinguished. The albumin will be abundant usually for a 
 period of ten days or two weeks, and the amount of blood 
 and the number of casts and renal cells will remain large. 
 
 A urine secreted just before the fatal termination of a 
 chronic interstitial nephritis may have all of the characteris- 
 tics of a mild active hyperemia. The only features of such a 
 urine pointing to a chronic nephritis are the low quantity 
 of urine and the very low total solids. A consideration of 
 the clinical history and the symptoms is of the greatest 
 importance in differentiating between these two conditions. 
 
 PASSIVE HYPEREMIA. 
 
 Passive hyperemia of the kidneys, also termed chronic 
 passive congestion, is, like active hyperemia, not a disease 
 of the kidneys, but a disturbance that is always secondary 
 to some obstruction to the venous circulation. As a result 
 of this, the kidneys are engorged with blood, and the 
 urine becomes modified to a greater or less extent. 
 
 Causes. — (i) Disease of the heart accompanied by ob- 
 struction to the flow of blood through it. (2) Liver disease 
 with obstruction to the passage of blood through the as- 
 cending vena cava, whether due to marked enlargement or 
 extensive atrophy (cirrhosis). (3) Ttinwrs of the abdomen, 
 including the pregnant uterus, may cause sufficient obstruc- 
 tion to the circulation in the kidney to cause a passive hy- 
 peremia. 
 
 Character of the Urine. — Quantity. — In uncomplicated 
 cases the twenty-four-hour quantity of urine is diminished, 
 19
 
 290 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 usually varying from 400 to 1200 c.c, but is largely de- 
 pendent upon the degree of obstruction and the character 
 of the disease producing it. 
 
 Color. — Generally high, especially if due to disease of the 
 liver, or a markedly uncompensated heart. It may be 
 normal or pale if due to a long-standing organic disease, or 
 following treatment by diuretics. 
 
 Reaction. — Usually strongly acid ; when the urine is 
 dilute and of low specific gravity, the reaction is either nor- 
 mal or faintly acid. 
 
 Specific Gravity. — This varies inversely as the quantity, 
 and directly as the metabolism. If the urine is high col- 
 ored and concentrated, it will have a specific gravity varying 
 between 1025 and 1035. On the other hand, if the urine 
 is pale and less concentrated, it will vary between 10 12 
 and 1020. 
 
 Normal Solids. — Absolute. — Usually considerably di- 
 minished, especially if the cause of the disturbance is 
 marked. Since there is more or less dropsy accompanying 
 the heart or liver disease, the chlorides and urea will be 
 found absolutely diminished. (See Effect of Dropsy upon 
 the Solids.) Relative. — Increased, especially the uric acid. 
 In extreme cases accompanied by marked dropsy the urea 
 and chlorides will be relatively diminished. 
 
 Albumin. — This varies between the slightest possible trace 
 and ^ of I per cent, (except in pregnancy, when it may 
 exceed this quantity). The amount of albumin is generally 
 a very slight trace or a trace. 
 
 Sediment. — Frequently there is a deposit of amorphous 
 urates. An occasional (or few) hyaline and finely granular 
 cast of small diameter. Rarely, a renal cell, and voy 
 rarely, a blood globule (blood is often absent). If more 
 than a stray blood globule be present, it is usually either 
 accidental or the result of some slight complication. Fat 
 globules are not found in the cells or adherent to the casts, 
 except in case there is some active parenchymatous change 
 as a complication. 
 
 Not infrequently a passive hyperemia is complicated by 
 an active hyperemia, in which case a few blood globules 
 (abnormal) will be found free and adherent to casts. (See 
 Differential Diagnosis.) 
 
 Passive Hyperemia of Pregnancy. — The urine of a preg- 
 nant woman, especially between the seventh and ninth
 
 PASSIVE HYPEREMIA. 291 
 
 months, will almost invariably show more or less evidence 
 of a passive hyperemia of the kidneys. Most of these 
 cases pass a urine having the characteristics of passive 
 hyperemia already described, except that in pregnancy it is 
 not common to find a highly concentrated or highly colored 
 urine, but rather one having a normal or pale color, and a 
 normal or slightly low specific gravity. 
 
 Occasionally, the renal disturbance is severe, when the 
 albumin usually exceeds -jlg- of i per cent., and may go as 
 high as i of i per cent. 
 
 The renal casts in the sediment are frequently of larger 
 diameter than those found in the sediment of an ordinary 
 passive hyperemia due to heart or liver disease. 
 
 The symptoms encountered in passive hyperemia are 
 those of the disease or disturbance that causes the passive 
 congestion of the kidneys ; there are usually no symptoms 
 that are directly referable to the kidneys themselves. There 
 is generally dropsy, mostly of the feet and legs ; dyspnea ; 
 edema of the lungs, which causes a hacking cough ; and 
 prominence of the veins of the abdomen. 
 
 Differential Diagnosis. — The diagnosis of an uncom- 
 plicated passive hyperemia of the kidneys can usually be 
 made from the urine without a knowledge of the clinical 
 history or physical examination. If, however, the condi- 
 tion is complicated in any way, either by an active hyper- 
 emia, acute nephritis, or by some chronic disease of the 
 kidneys, the diagnosis of passive hyperemia can not be 
 made with certainty from the urine alone. 
 
 In the passiv^e hyperemia of pregnancy a rapid increase in 
 the quantity of albumin and an increase in the number of 
 hyaline and finely granular casts in the sediment are always 
 important, as these changes frequently serve as a " danger 
 signal " to the approach of puerperal eclampsia. It must be 
 borne in mind, however, that puerperal convulsions may 
 occur without there being necessarily any marked change 
 in the quantity of albumin or the appearance of blood. 
 Nevertheless, this fact does not lessen the importance of 
 carefully watching the urine for such changes as may indi- 
 cate the approach of this serious complication. It is a well- 
 known fact that chronic diseases of the kidney do not pre- 
 dispose to the occurrence of puerperal eclampsia, even 
 though a passive hyperemia is superimposed. 
 
 Passive congestion of the kidneys is to be distinguished
 
 292 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 from a chronic interstitial nephritis chiefly by the large quan- 
 tity of urine and the low absolute quantity of urea in the 
 latter disease. Also by the predominance in interstitial dis- 
 ease of the quantity of urine passed at night over that passed 
 during the day, and by the prominent symptoms of intersti- 
 tial nephritis — /. c, a full, hard pulse, cardiac hypertrophy, 
 absence of dropsy until late in the disease, etc. — all of which, 
 except dropsy, are absent in passive hyperemia. In chronic 
 interstitial nephritis near death, when the quantity of urine 
 has fallen to the normal or below, it is frequently impossible 
 to distinguish between these two conditions. 
 
 ACUTE DIFFUSE NEPHRITIS (ACUTE NEPHRITIS). 
 
 This condition consists of an acute inflammation or 
 degeneration of the kidneys ; the pathologic process is 
 usually present in both kidneys, although it may be entirely 
 confined to one of these organs. According to Councilman, ^ 
 an acute diffuse nephritis includes a number of pathologic 
 conditions : /. c. — 
 
 " (a) Acute Degenerative Nephritis. — In this are in- 
 cluded degenerative lesions of the epithelium, embracing 
 cloudy swelling, hyaline, fatty, and dropsical degeneration, 
 and often complete necrosis, without lesions other than 
 degenerative, in the glomeruli or in the interstitial tissue. 
 This occurs chiefly in infectious diseases, in jaundice, in 
 anemia, and as the result of the action of certain poisons. 
 The kidney is slightly swollen or unchanged in size, rather 
 paler and more opaque on section ; the markings may be 
 obscure or more prominent than normal. There is often 
 albuminous exudation in the glomerular capsules and in the 
 tubules. 
 
 (b) Acute Glomerular Nephritis. — The essential 
 changes consist in acute lesions in the glomeruli. There 
 may be acute proliferation of the endothelium of the vascular 
 tufts, hyaline and fibrinous thrombi in the vessels, accumula- 
 tion of leucocytes in the vessels, degeneration of the vessel 
 wall, etc. These changes in the vascular tufts of the glomer- 
 ulus can occur with or without changes in the capsular epi- 
 thelium. The changes in the capsular epithelium consist in 
 degeneration and proliferation. The capsular space may 
 contain an albuminous hemorrhagic or fibrinous exudation. 
 
 ^" Amer. Journ. Med. Sciences," July, 1897.
 
 ACUTE DIFFUSE NEPHRITIS. 293 
 
 The changes in the vascular tufts and in the capsule are so 
 frequently combined in various degrees that they can not be 
 separated into two subclasses. The glomerular lesions are 
 accompanied by degeneration of the tubular epithelium, 
 necrosis, and exfoliation. Often there are dilatation of the 
 tubules and edema and cellular proliferation of the inter- 
 tubular tissue. There may be more or less hemorrhage into 
 the tubules. 
 
 This affection occurs in infectious diseases, notably in acute 
 endocarditis, measles, and diphtheria, or as an independent 
 affection. The kidney is usually increased in size. The 
 capsule easily strips off; the surface is pinkish and mottled 
 with points of ecchymosis. On section the cortex is wide, 
 rather paler and more opaque, markings obscure ; glomeruli 
 pale, enlarged, and prominent. Pyramids often congested. 
 The tissue moist and pits on pressure. While these appear- 
 ances are usually marked, lesions of the glomeruli may be 
 found with but little macroscopic change in the kidney. 
 
 (c) Acute Hemorrhagic Nephritis. — The essential 
 change consists in hemorrhage in the tissue combined with 
 degeneration of the epithelium. The hemorrhage is chiefly 
 found in the capsule of the glomeruli and in the tubules. 
 The degenerative lesions may be extensive and lead to 
 necrosis and exfoliation. Edema, hemorrhage, and cellular 
 infiltration are often found in the intertubular tissue. The 
 kidney is enlarged, hemorrhages are found in the capsule ; 
 the surface is dark red, with numerous ecchymoses. On 
 section the cortex is swollen and sprinkled with dots and 
 streaks of ecchymosis. 
 
 (d) Acute Interstitial Nonsuppurative Nephritis. — 
 The essential lesion consists in acute proliferation of the cells 
 in the intertubular tissue. The proliferation takes place 
 mainly from the vascular endothelium. The cells lie within 
 and without the vessels. They are large and similar to the 
 endothelial cells of young granulation tissue. They are 
 found chiefly in the intermediate zone of the kidney between 
 the pyramids and the cortex. In the cortex they are both 
 generally diffused and in areas chiefly around the glomeruli. 
 There is more or less degeneration and necrosis of the 
 tubules, affecting chiefly those in the areas of cellular infil- 
 tration. Leucocytes in small numbers may be found in the 
 intertubular tissue among the other cells, in the degenerated 
 epithelium, and in the lumen of the tubules. The glomeruli
 
 294 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 are not affected. This affection occurs in acute infectious 
 diseases, notably in diphtheria and scarlet fever. The kidney 
 is large, pale, somewhat mottled ; on section, moist, opaque, 
 markings obscure, and milky fluid can be pressed from it." 
 
 From a clinical point of view we are unable at present to 
 distinguish with certainty between these four forms of acute 
 nephritis, either by the characteristics of the urine or by a 
 consideration of the urine in connection with the clinical his- 
 tory and symptoms. The description that follows applies 
 to an acute nephritis as seen clinically, and is without refer- 
 ence to these different forms of the disease. It is probable, 
 however, that the form which Councilman designates as 
 " acute degenerative nephritis " corresponds to the condition 
 w^hich the author has described as active hyperemia. 
 
 Causes. — An acute nephritis may be caused by any irri- 
 tant or abnormal condition, such as causes an active hyper- 
 emia (see Causes of Active Hyperemia) ; in fact, an active 
 hyperemia from any cause may end in a true acute nephritis. 
 Of the causes exposure to cold and wet is probably the most 
 common. Toxines, notably those of diphtheria and scarlet 
 fever, are very apt to cause acute nephritis. Bacterial in- 
 fection is sometimes a cause, and when present, generally 
 produces the disease in its most virulent form. In preg- 
 nancy there may be an acute nephritis, which is usually ac- 
 companied by puerperal convulsions, and not infrequently 
 this complication proves fatal. 
 
 An acute nephritis may be divided into three stages : First 
 or acute, second or fatty, and thii^d or convalescent stage. 
 
 First or Acute Stage. — 
 
 Character of the Urine. — Quantity. — Much diminished 
 — usually 200 to 400 c.c. There may be almost complete 
 anuria, the patient frequently passing not more than 100 c.c. 
 in forty-eight hours. 
 
 Color. — Very smoky (dark) or, in the first day or two, 
 almost black ; if much normal blood, a blood-red color. 
 
 Reaction. — Usually acid ; sufficient blood may be pres- 
 ent to give a slightly alkaline reaction. 
 
 Specific Gravity. — Generally high, although it may be 
 low. If albumin be present in large amount (and it gener- 
 ally is excessive), it will raise the specific gravity to 1030, 
 even though the normal solids are diminished. 
 
 Normal Solids. — Absolutely, much diminished, espe-
 
 ACUTE DIFFUSE NEPHRITIS. 295 
 
 daily the urea and chlorine. (See Effect of Dropsy on 
 Normal Solids.) If the dropsy is increasing, as is the rule 
 during this stage, the chlorine may be found absent. Rela- 
 tively, diminished, especially the urea and chlorine. 
 
 Albumin. — Generally }^ to }4 of i per cent. It may 
 exceed this quantity, going as high as i ^ per cent. The 
 amount varies with the severity of the disease and the degree 
 of obstruction in the tubules. 
 
 Sediment. — Abundant and of a dark-brown or choco- 
 late color. It consists of a large number of abnormal, and 
 perhaps some normal, blood globules. Many brown 
 granular renal epithelial cells. Many brown granular, 
 epithelial, blood, and fibrinous casts, and perhaps a few 
 hyaline and finely granular casts. A large amount of 
 granular debris from the broken-down renal cells and blood 
 globules. There are usually numerous leucocytes, free, in 
 clumps, and adherent to the casts ; also small caudate cells 
 from the superficial layer of the pelvis, as well as an occa- 
 sional clump of round cells from the calices of the kidney 
 — an acute pyelitis. 
 
 The duration of this stage is usually from five to ten 
 days. The urine then commences to show signs of im- 
 provement, the dropsy begins to diminish, the absolute 
 solids are a little higher, the quantity of urine gradually in- 
 creases, and fatty elements begin to appear or have already 
 appeared. 
 
 Second or Fatty Stage. — 
 
 Character of the Urine. — Quantity. — This varies be- 
 tween 800 and 1500 c.c, according to the amount of im- 
 provement that has taken place. 
 
 Color. — Still very smoky. 
 
 Reaction. — Usually acid. 
 
 Specific Gravity. — This generally ranges between 10 15 
 and 1020. It is still influenced by the considerable amount 
 of albumin that is present. 
 
 Normal Solids. — Absolutely, somewhat diminished, al- 
 though higher than in the first stage. Relatively, dimin- 
 ished. The urea and chlorine w^ill be found relatively 
 higher as the dropsy diminishes. 
 
 Albumin. — This varies between yi and ^ of i per cent. 
 As a rule, the diminution in the quantity of albumin is in 
 inverse proportion to the increase in the twenty-four-hour
 
 296 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 quantity of urine. In the first part of this stage the quan- 
 tity of albumin may exceed ^ of i per cent. 
 
 Sediment. — This is still abundant in quantity, and of a 
 brown color. The elements are practically the same as in 
 the acute stage, but with the addition of fatty renal cells, 
 fatty casts, and compound granule cells. The amount of 
 fat at this time follows quite closely the degree of severity 
 of the disease during the acute stage — that is, if there was a 
 rather mild acute stage, the number of fatty elements and 
 the degree of degeneration will not be extensive ; but if 
 there was a severe acute stage, the quantity of fat will be 
 excessive. Furthermore, from a single examination of the 
 urine at this time, and without a knowledge of the previous 
 history, it may be impossible to determine whether we are 
 dealing with the fatty stage of an acute nephritis or a sub- 
 acute glomerular nephritis that is complicated by an acute 
 process. 
 
 The evidences of a pyelitis seen in the acute stage will 
 probably be present to a greater or less extent in this stage, 
 although it occasionally happens that the acute pyelitis 
 has developed into a subacute or chronic pyelitis. The 
 latter is shown by the presence of a larger quantity of pus, 
 free, arranged in clumps, and adherent to casts of large 
 diameter ; also a large number of small round cells, free 
 and in the clumps of pus. 
 
 The duration of this stage is about the same as that of 
 the first, — viz., five to ten days, — providing there is steady 
 improvement. 
 
 With the favorable progress of the disease the character 
 of the urine gradually changes still more, and we have the 
 third or convalescent stage. The edema has entirely dis- 
 appeared. 
 
 Third or Convalescent Stage. — 
 
 Character of the Urine. — Quantity. — This generally 
 varies between i 500 and 3000 c.c. There is usually a gradual 
 rise in the quantity, as high as 4000 c.c, where it gener- 
 ally remains for a few days or even weeks. As the condi- 
 tion approaches complete recovery, the quantity falls 
 gradually, and in some cases there is a sudden fall to about 
 the normal. 
 
 Color. — Usually, the urine has lost its smoky color and 
 is pale. Occasionally, the smoky color continues, especi-
 
 ACUTE DIFFUSE NEPHRITIS. 297 
 
 ally in the early part of this stage, and as long as the urine 
 contains a large amount of abnormal blood. As the amount 
 of blood diminishes, the color becomes pale. 
 
 Reaction — Faintly acid. 
 
 Specific Gravity. — This varies as the quantity — /. c, if 
 the twenty-four-hour amount is between 3000 and 4000 c.c, 
 it will be not far from 1008 to 1010. On the other hand, 
 if the quantity is between 1800 and 2500 c.c, it will be be- 
 tween 1012 and 10 1 8. 
 
 Normal Solids — These are absolutely normal. They may 
 be increased for a time, especially the urea and chlorides, 
 due to their reabsorption from the serous transudations and 
 their elimination in the urine. They are relatively dimin- 
 ished, the degree of diminution being dependent upon the 
 dilution of the urine. 
 
 Albumin. — This is usually between yi oi \ per cent, and 
 a very slight trace, according to the. extent of the convales- 
 cence and the twenty-four-hour quantity of urine. The 
 larger the quantity of urine, the smaller the amount of al- 
 bumin. The average quantity in this stage will be not far 
 from a trace. 
 
 Sediment — Generally, slight in quantity and colorless, 
 although it may still have a brownish color if much abnor- 
 mal blood be present. It consists of numerous (or few) 
 abnormal blood globules. Few (or occasional) hyaline, 
 granular, and brown granular casts, and rarely a blood, 
 epithelial, and fibrinous cast. Most of the casts with 
 abnormal blood and a little fat adherent. Few renal cells, 
 some fatty. Rarely there may be a small fatty cast. The 
 brown granular and fibrinous casts are the first to disappear. 
 
 If there was a chronic pyelitis in the second stage, evi- 
 dence of it will probably still be found. As the convales- 
 cence advances, the pyelitis usually disappears rather sud- 
 denly, if it has not entirely recovered during the second 
 stage. 
 
 The duration of the convalescent stage is from one to 
 four months, but not infrequently it lasts for a longer period, 
 even from one to two years, followed by complete recovery. 
 
 In a perfectly favorable convalescent stage, without com- 
 plications, after the lapse of a month or two, the quantity 
 of urine falls to the normal, the albumin diminishes to a I'ery 
 slight trace or the slightest possible trace, the quantity of blood 
 diminishes, the brown granular and fibrinous casts disap-
 
 298 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 pear and then the majority of the fatty elements. In well- 
 advanced convalescence, only hyaline and granular casts, an 
 occasional blood globule free and adherent to some of the 
 casts, an occasional renal cell, and rarely a fatty renal cell 
 remain. If the urine is first examined at this time and with- 
 out a knowledge of a previous history of the case, it is often 
 impossible to determine whether the condition is one of 
 active hyperemia or a well-advanced convalescence from an 
 acute nephritis, for the urine is the type of one of simple 
 active hyperemia. When complete recovery has taken 
 place, all abnormal elements disappear from the sediment, 
 and the urine is normal in character. 
 
 The prognosis in a case of acute nephritis is usually 
 good, although there is always a liability that it may result 
 in a chronic disease of the kidneys. It is certainly the ex- 
 ception, and not the rule, for an acute nephritis to run as 
 favorable a course as has just been outlined. 
 
 Exacerbations (relapses) are very liable to occur, espe- 
 cially during the convalescent stage. 
 
 Causes. — Probably the most common cause is exposure 
 — a draft of air on the head and neck, too httle clothing, 
 cold and wet feet, etc. Since the skin is usually veiy active 
 at this time, any sudden exposure stops its action and in- 
 creases the congestion or inflammation of the kidneys. Oc- 
 casionally, the ingestion of highly nitrogenous food (meats, 
 etc.) is apparently an element in causing an exacerbation. 
 Sometimes an exacerbation occurs without a discernible 
 cause, even when the patient has taken every precaution. 
 The onset is usually sudden, and the patient realizes that 
 he does not feel as well as usual, having a recurrence of the 
 symptoms of the acute stage — i. c, diminished quantity of 
 urine, frequent micturition, and generally some headache and 
 pain in the back. There is usually more pallor than before 
 the attack, and often swelling of the face and extremities. 
 
 Cliaractcr of the Urine. — The urine of an exacerbation 
 is characterized (i) by a sudden fall in the quantity, (2) a 
 blood-red color, and (3) the presence in the sediment of a 
 large quantity of normal blood. It may be either mild or 
 severe, and the severity of the attack governs the extent to 
 which the quantity of urine is diminished, and the amount of 
 normal blood found ; in other words, if severe, the quantity 
 of urine is greatly reduced and the amount of normal blood 
 large ; if mild, a moderately diminished quantity and com-
 
 ACUTE DIFFUSE NEPHRITIS. 299 
 
 paratively little blood. The quantity of albumin increases 
 and the normal solids diminish according to the severity. 
 The blood, epithelial, and fibrinous casts are again present in 
 moderately large numbers. In the course of two or three 
 days, possibly a week or ten days, the urine again increases 
 and the normal blood disappears, although the latter may 
 continue in small amount (not sufficient to give the urine a 
 bloody color) for weeks. Following the disappearance of 
 the greater part of the normal blood, the urine generally 
 contains a larger quantity of abnormal blood than before 
 the exacerbation, hence a smoky color again for a few days. 
 After a short time has elapsed the urine again presents the 
 characteristics of the third, or convalescent, stage of an acute 
 nephritis. 
 
 Any number of exacerbations may occur, the average 
 being from one to four, and the larger the number, the more 
 prolonged the convalescence. Likewise, the greater the 
 number of exacerbations, the more extensive the pathologic 
 changes in the kidney, and hence the more unfavorable 
 the prognosis, since the acute nephritis may end in a chronic 
 disease of the kidneys. An unfavorable prognosis is not 
 necessarily warranted, however, as cases of acute nephritis 
 accompanied by frequent exacerbations have recovered after 
 a lapse of two years. 
 
 Symptoms of uremia may appear at the time of a severe 
 exacerbation because of the interference with the elimination 
 of the toxic material from the body ; but, fortunately, this 
 complication is only rarely seen. 
 
 Prominent Symptoms. — The onset of an acute nephritis 
 is usually very rapid and, like other acute processes, is fre- 
 quently ushered in by a chill. There is usually rapid pallor, 
 swelling of the lower eyelids and face, also edema of the legs, 
 and often general dropsy ; intense headache, thirst, nausea, 
 and often vomiting ; pain in the back and limbs, and 
 frequency of micturition. Because of the last-mentioned 
 symptom the patient often has the firm impression that he is 
 passing a large quantity of urine, but when the total 
 quantity is measured, it will be found to be abnormally 
 diminished. There is usually at first some elevation of tem- 
 perature, also a high tension pulse. Acute uremic symp- 
 toms are not uncommon, the most prominent of which are 
 nausea and vomiting, stupor, and sometimes convulsions. 
 Acute visual disturbances are occasionally seen.
 
 300 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 Differential Diagnosis. — The distinction between a 
 severe active J'.ypercDiia and a mild acute nephritis is, in some 
 instances, not easily deduced from the urine alone. How- 
 ever, the history of a sudden onset and the prominent symp- 
 tom of edema, — swelling of the face and legs, — together with 
 the chief characteristics of the urine — viz., the persistence 
 of a considerable amount of albumin, considerable blood, 
 and numerous casts — will serve to distinguish an acute 
 nephritis from a severe form of active hyperemia. 
 
 The urine of the second stage of acute nephritis may not 
 differ materially from one of subacute glomendar nephritis 
 {active stage) complicated by an acute process. In the latter 
 condition the albumin is usually present in larger amounts, 
 and the total quantity of urea is gencrall}^ much lower than 
 in the former disease. In an acute nephritis the clinical 
 symptoms will show that the condition is gradually improv- 
 ing, while in a case of a complicated subacute glomerular 
 nephritis the patient is at his worst. In doubtful cases, 
 however, the urine should be carefully watched for several 
 days ; if an acute nephritis, the third or convalescent stage 
 will appear ; if a subacute glomerular nephritis complicated 
 by an acute process, the acute complication will gradually 
 subside, leaving the disease in its uncomplicated form ; or 
 the patient may have S}'mptoms of uremia and succumb to 
 the disease. 
 
 The urine of the coiivalescent stage of an acute nepJiritis 
 should not be mistaken for the urine of chronic interstitial 
 or cJironic diffuse nepJiritis. The acute histor>', the charac- 
 teristic first and second stages of an acute nephritis, the 
 presence of blood in the sediment, and the normal total solids 
 will serve to distinguish an acute from a chronic form of renal 
 disease. 
 
 SUBACUTE GLOMERULAR NEPHRITIS. 
 
 Subacute glomerular nephritis, also termed " chronic par- 
 enchymatous nephritis," " fatty degeneration of the kid- 
 neys," and " chronic diffuse nephritis of the parenchymatous 
 type," is a disease characterized by marked degenerations 
 of the glomeruli as well as of the epithelial lining of the 
 renal tubules. 
 
 The essential lesions are in the glomeruli. They consist 
 in swelling and nuclear increase in the vascular tufts and 
 obliteration of the vessels by hyaline degeneration, both of
 
 SUBACUTE GLOMERULAR NEPHRITIS. 301 
 
 the cells and the vascular walls. These changes in the tufts 
 are often combined with proliferation and desquamation of 
 the capsular epithelium with connective-tissue ingrowth. 
 There is extensive degeneration, necrosis, and desquamation 
 of the tubular epithelium. The intertubular tissue is the 
 seat of edema and connective-tissue formation. The kidney 
 is enlarged, and the capsules may cling slightly to the sur- 
 face, which is pale and slightly mottled. On section, the 
 cortex is increased in width, pale, opaque, markings obscure, 
 glomeruli pale, and its consistency is increased (Council- 
 man). 
 
 Causes. — This disease is sometimes the result of a pre- 
 vious acute nephritis, during the course of which frequent 
 exacerbations hav^e occurred, and when the convalescence 
 has been extended over a long period (years). It is, per- 
 haps, more common for the disease to accompany chronic 
 wasting diseases, such as phthisis, syphilis, and chronic 
 suppurative bone diseases ; also in cases of prolonged 
 malaria. When the disease is an accompaniment of these 
 conditions, the changes in the kidney are gradual, and the 
 disease appears to be chronic from the beginning. The rea- 
 son for a subacute glomerular nephritis under these circum- 
 stances is not known. 
 
 The disease can be conveniently divided into two stages — 
 /. c, active and inactive stages. 
 
 ACTIVE STAGE. 
 
 This stage is seen at the time when the patient is at his 
 worst. The urine is concentrated and highly characteristic, 
 and there is marked dropsy. 
 
 Character of the Urine. — Quantity. — Very small, vary- 
 ing from 200 to 800 c.c, the average being not far from 
 400 c.c. 
 
 Color. — High, like that of a fever urine, and often turbid 
 because of the presence of amorphous urates. In case of 
 a recent acute exacerbation, the color will be bloody. 
 
 Reaction, — Usually strong acid. 
 
 Specific Gravity. — High — 1026 or 1028, and often as 
 high as 1030 or 1035. 
 
 Normal Solids. — Absolutely, much diminished, especially 
 the urea and chlorides, which are low because of the very 
 extensive and increasing dropsy. The chlorides may be
 
 302 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 nearly absent. Relatively, the uric acid and the urea are in- 
 creased, unless the disease has been going on for a long 
 time, in which case the urea will be relatively diminished. 
 The chlorides are much diminished or nearly absent. 
 
 Albwnin. — In this form of kidney disease, and especially 
 in this stage, the quantity of albumin is the largest ever found 
 in the urine. It varies between y^, of i and 3 or 4 per cent, 
 by weight, but the average quantity is usually from ^ of i to 
 I per cent. The maximum amount ev^er reported was as high 
 as 5 per cent. Upon performing the heat test for albumin 
 it is not very uncommon to find that the urine completely 
 solidifies, in which case the quantity of albumin exceeds 2 
 per cent. The average quantity in this stage is between ^ 
 of I and I per cent., usually nearer the latter figure. 
 
 Sediuteiit. — If a deposit of amorphous urates is present, 
 the sediment will be abundant and usually of a pink or red- 
 dish-brown color. If there is not a deposit of urates, the 
 amount of sediment will be " considerable " and practically 
 colorless. If the disease be complicated by an acute pro- 
 cess, normal blood may be present in sufficient quantity to 
 color the urine and sediment red. The sediment consists of 
 many hyaline, granular, and fatty casts, some of which have 
 fatty renal and compound granule cells adherent ; numer- 
 ous //r^' fatty renal and compound granule cells. Crystals 
 of the fatty acids are often seen projecting from the fatty 
 renal and compound granule cells, and the fatty casts. 
 Cholesterin cr}^stals are occasionally seen, but usually only 
 in the late stages of the disease. If the disease is well ad- 
 vanced, waxy casts may be seen in the sediment. When 
 present, they are of bad omen. In an uncomplicated case the 
 sediment is free from blood and renal blood elements. As a 
 matter of fact, chronic diseases of the kidneys are usually 
 more or less complicated by either a mild or severe acute pro- 
 cess, so that usually an occasional (or numerous) blood 
 globule will be found. If there is very much blood present, 
 a few leucocytes are often found free and adherent to some 
 of the casts. 
 
 With the improvement that usually follows rest in bed, 
 a milk diet, and mild diuretic treatment, providing the dis- 
 ease is not near its termination, there is a distinct change in 
 the character of the urine. The dropsical effusions have 
 diminished, the edema of the extremities has largely disap- 
 peared, although usually not entirely, and the process in the
 
 SUBACUTE GLOMERULAR NEPHRITIS. 303 
 
 kidneys appears to be quiescent. Then we have the inac- 
 tive stage of the disease. 
 
 INACTIVE STAGE. 
 
 Character of the Urine. — Quantity.— Usually, from 
 800 to 1200 c.c. It may exceed the normal quantity for a 
 day or two at the time the edema is being absorbed, but 
 it soon falls to about 1200 c.c. 
 
 Color. — The color is pale and not infrequently the urine 
 has a greenish tint. 
 
 Reaction. — Generally, acid. 
 
 Specific Gravity. — This varies as the twenty-four-hour 
 quantity, but in the early part of the disease it will gen- 
 erally vary between 10 10 and 10 15. 
 
 Normal Solids. — They are both absohitely and relative- 
 ly diminished. The solids may be absolutely somewhat 
 higher than in the active stage, especially at the time of the 
 greatest absorption of the edema, but the increase is usually 
 slight. 
 
 Albumin. — The quantity of albumin is smaller than in 
 the active stage, but it is still present in large amount, gen- 
 erally from % to yi of I per cent. Occasionally, it is a 
 little less than y^ of i per cent., particularly if the twenty- 
 four-hour quantity of urine is about i 500 c.c. 
 
 Sediment. — This is "considerable" in quantity, and 
 colorless. A deposit of amorphous urates is usually not 
 present. It consists of the same elements that were found 
 in the active stage, but they are less in number : numerous 
 hyaline, granular, and fatty casts, fatty renal and compound 
 granule cells. If waxy casts were present in the active 
 stage, they will be found at this time, although fewer in 
 number. Crystals of the fatty acids and cholesterin will 
 also be found if the)^ were present in the active stage. 
 
 ATROPHIC STAGE. 
 
 This stage is only very rarely seen, since death usually 
 occurs before atrophy of the kidneys has taken place. The 
 kidneys become very small, have a yellow color, consist 
 principally of fat, and there is a marked increase in the con- 
 nective tissue. 
 
 Character of the Urine. — The quantity of urine is usually 
 not far from the normal, and it may be slightly increased.
 
 304 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 The specific gravity and the normal solids are very low ; the 
 quantity of albumin falls to about y^ of i per cent, or less ; 
 and the sediment consists of practically the same elements 
 as in the inactive stage of the disease, except a smaller 
 number of fatty elements and a larger proportion of waxy 
 casts. 
 
 A subacute glomerular nephritis is characterized by fre- 
 quent alternations of the active and passive stages, without 
 there being necessarily a true acute exacerbation. But 
 acute exacerbations are as likely to occur in this disease 
 as in an acute diffuse nephritis. When present, the urine 
 has the additional elements of the acute disease, together 
 with the normal blood and renal blood elements — blood- 
 casts, etc. 
 
 Prominent Symptoms. — The patient usually suffers from 
 indigestion (early symptom), often attended with vomiting ; 
 almost constant headache, which gradually increases in in- 
 tensity from month to month ; marked pallor (" pasty") and, 
 usually, swelling of the face ; and invariably marked edema 
 of the extremities, which finally extends and increases to a 
 condition of extreme general dropsy (ascites, pleuritic effu- 
 sion, etc.). There is frequency of micturition, but a small 
 quantity of urine is passed. Palpitation and dyspnea on ex- 
 ertion are often present to a marked degree. The disease 
 is characterized by periods of activity in which the edema 
 is increased, the quantity of urine is very small, and 
 there are uremic symptoms. It is also characterized by 
 quiescent periods, in which the patient improves, the edema 
 diminishes, and the quantity of urine increases, although 
 generally not above the normal except for a day or two. 
 
 The duration of the disease is usually from two to five 
 years, but this depends upon the care of the patient and 
 the hygienic surroundings. If the circumstances are such 
 that he can have the very best care, life may be pro- 
 longed a year or two longer ; on the other hand, an 
 early end is often the fate of such cases among the poorer 
 classes. 
 
 The prognosis is invariably unfavorable. So far as is 
 known, recovery never takes place after the disease has be- 
 come well established. Death may result from uremia or, 
 as is not infrequent, from some secondary acute disease, 
 such as pneumonia, erysipelas, diphtheria, etc. The low 
 physical state of the patient renders him very susceptible
 
 CHRONIC INTERSTITIAL NEPHRITIS. 305 
 
 to other diseases, especially those of an acute infectious 
 nature. 
 
 Differential Diagnosis. — The diagnosis of a subacute 
 glomerular nephritis from the urine alone is generally not 
 difficult, providing the condition is uncomplicated. In case 
 the disease is complicated by an acute process it can not be 
 readily distinguished from the second stage of an acute 
 nephritis. Under these circumstances the history of the 
 case should be considered, and the character of the urine 
 should be carefully watched for several days. If a compli- 
 cated subacute nephritis, the acute process will generally 
 subside in the course of from two to three weeks, when the 
 urine will have the characteristics of an uncomplicated sub- 
 acute nephritis. The edema that was extreme at first 
 usually continues after the acute process has subsided — viz., 
 after the blood has entirely disappeared. On the other 
 hand, if the disease is an acute nephritis passing through the 
 second stage, the third or convalescent stage will soon ap- 
 pear, the edema will entirely subside, and the patient will 
 gradually improve until there is complete convalescence. 
 
 CHRONIC INTERSTITIAL NEPHRITIS. 
 
 This condition has been variously termed chronic neph- 
 ritis, chronic diffuse nephritis of the interstitial type, sclerotic 
 kidney, gouty kidney, small gramdar kidney, chronic diffuse 
 nephritis without exudation, etc. It is a chronic disease of 
 the kidneys, which is characterized chiefly by an increase in 
 the connective tissue of those organs. The disease develops 
 very slowly and insidiously, usually having been in prog- 
 ress for years before it is recognized, and then often only 
 accidentally discovered by the physician who is consulted 
 for the relief of headaches or some annoying stomach diffi- 
 culty ; or perhaps it is first encountered by the life insur- 
 ance examiner or oculist. 
 
 According to Councilman, some of the pathologic pro- 
 cesses found in chronic interstitial nephritis, such as chroidc 
 arteriosclerotic ncpJiritis, and chronic degenerative and inter- 
 stitial nephritis really belong under the heading of chronic 
 diffuse nephritis. 
 
 In chronic arteriosclerotic nephritis the essential lesions 
 occur in the arteries, and consist in those changes known 
 as arterioscleroses. There is degeneration of the epi- 
 20
 
 306 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 thelium of the tubules, with more or less complete de- 
 struction. The degeneration takes place slowly, and at 
 any given time sections may show only a slight degree. 
 Atrophic changes in the epithelium are common. The 
 lesions may affect almost equally all parts of the kidney, or 
 appear in areas corresponding to the vascular territories of 
 those arteries that are most affected. There is a general 
 increase in the connective tissue, though large areas of 
 tubules may be found with no increased tissue between 
 them. This condition of the kidney is found accompany- 
 ing a general arteriosclerosis affecting all the arteries of the 
 body, or the vascular lesions may be most marked in the 
 renal arteries. The kidney varies in size ; it may be 
 slightly larger or of normal size, but is usually very much 
 smaller than normal. The capsule may or may not be 
 adherent. The surface is more or less irregular and granu- 
 lar ; the color is red and often cyanotic. On section, the 
 cortex may be much diminished in size, of a dark-red 
 color, the markings obscure, and the glomeruli injected ; 
 the arteries in the intermediate portion are evident, and often 
 project above the cut surface. The pyramids show venous 
 congestion ; the consistency of the kidney is greatly in- 
 creased. Most of the cases of contracted kidney belong to 
 this class. 
 
 To the class of cJironic degenerative and interstitial neph- 
 ritis belong those cases of contracted granular kidney that 
 occur without primary arterial lesions. It is difficult to give 
 a name to the condition, for there is no single change 
 that predominates. Degeneration, atrophy, and destruc- 
 tion of the epithelium in various degrees are found. There 
 is a general increase in connective tissue more diffuse than 
 in the arteriosclerotic nephritis, but not so diffuse as in the 
 chronic glomerular form. The increase in the connective 
 tissue is most intense where the degeneration of the epithe- 
 lium is most marked. Lines of connective tissue extend to 
 the surface, and by their contraction produce depressions. 
 Very minor degrees of change, which may consist in small 
 areas of cellular infiltration with hyperplasia of the connec- 
 tive tissue extending down from the capsule, are very com- 
 monly found. The essential lesion seems to be a slow 
 degeneration of the epithelium, followed by connective-tis- 
 sue hyperplasia. The microscopic appearances of the kid- 
 ney vary extremely, following the different degrees of the
 
 CHRONIC INTERSTITIAL NEPHRITIS. 307 
 
 lesions. The gross and microscopic condition may be com- 
 plicated by lesions of another character (Councilman). 
 
 Causes. — There are three toxic agents that are probably 
 causes of this disease : 
 
 1. Lead. — Chronic lead-poisoning is usually met with in 
 type-setters, painters, those handling lead, and others ex- 
 posed to its influence. The damage to the kidneys is 
 apparently due to the constant elimination of the lead, which 
 acts as a chemic irritant. The connective -tissue changes 
 do not usually appear until after years of almost constant 
 poisoning. 
 
 2. Alcohol. — Those persons who are addicted to the 
 moderate use of alcohol, especially if continued for years, 
 may have a chronic interstitial nephritis, which may lead to 
 their death or be an accompaniment of some other acute or 
 chronic disease that proves fatal. 
 
 3. Uric Acid. — The gouty individual is often the victim 
 of this disease — the so-called " gouty kidney." The man- 
 ner in which uric acid produces a chronic interstitial nephri- 
 tis can not be well explained unless we assume that it is the 
 result of the constant irritation set up by the elimination of 
 excessive amounts of uric acid and other products of 
 diminished metabolism. 
 
 Arsenic. — Chronic arsenic-poisoning probably leads to 
 this form of disease, especially in those persons who have 
 been exposed to the influence of the substance for a long 
 period of years. 
 
 Syphilis and chronic malaria are also considered 
 causes of this disease. It is certain that these conditions 
 are often accompanied by a chronic interstitial nephritis, but 
 not invariably. It is probable that any long-continued irri- 
 tation of the kidneys gradually results in renal changes 
 that finally terminate in a chronic interstitial nephritis. 
 
 Arteriosclerosis. — There can be no doubt that this dis- 
 ease of the blood-vessels results in those changes that 
 characterize this form of kidney disease. It is common in 
 middle-life, and, as before stated, most of the cases of con- 
 tracted kidney belong to this class. 
 
 Chronic interstitial nephritis can be divided, clinically, 
 into three stages according to the degree to which the urine 
 becomes modified from the normal and the extent of the 
 renal changes : first or early stage, second or advanced 
 stage, and third of late stage.
 
 808 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 FIRST OR EARLY STAGE. 
 
 This stage is seen at the time when the individual is 
 capable of attending to business and, with the exception of 
 headaches and frequent attacks of indigestion, enjoys a fair 
 degree of health. There may not be any noticeable fre- 
 quency of micturition at this time, although the patient will 
 probably find it necessary to urinate once or twice during 
 the night. 
 
 Character of the Urine. — Quantity. — This is a very 
 important element in the diagnosis. It is moderately in- 
 creased above the normal at this time — usually, between 
 1500 and 2000 c.c. Frequently, the quantity of urine 
 passed at night exceeds that passed during the day ; this 
 is much more marked during the advanced stage of the 
 disease. 
 
 Color. — Normal or slightly pale. 
 
 Reaction. — Acid. 
 
 Specific Gravity. — This varies inversely as the quantity 
 of urine, but will usually be found to vary between 1012 
 and 1018. 
 
 Coloring-matters. — All somewhat diminished except 
 the indoxyl, which is generally increased. 
 
 Normal Solids. — The absolute solids are somewhat 
 diminished, although not markedly. The total quantity of 
 urea eliminated by an average-sized adult will be about nor- 
 mal, or it may be higher than normal, especially if the indi- 
 vidual is having a liberal nitrogenous diet. Relatively, they 
 are nearly normal or somewhat diminished, depending on the 
 dilution of the urine. The percentage of urea will probably 
 be found to be not far from 1.5 per cent. 
 
 Albumin. — This varies between the slightest possible trace 
 and a trace. It is at this time that the presence of albumin 
 is sometimes overlooked, because of the failure to detect 
 the slightest possible traces. (See Detection of Albumin.) 
 The author's experience leads him to believe that albumin is 
 ahvays present in the urine of chronic interstitial nephritis, 
 even in the early stages. 
 
 Sediment. — This is usually very slight in quantity and 
 requires very careful sedimentation in order to be able to 
 obtain a satisfactory preparation for examination. Often- 
 times it is necessary to centrifugalize the urine in order to 
 obtain the best results from the microscopic examination.
 
 CHRONIC INTERSTITIAL NEPHRITIS. 
 
 309 
 
 It Will be found to consist of an occasional hyaline and finely 
 granular cast. No excess of renal cells and, unless com- 
 plicated, no blood or fat are present. 
 
 In this stage the diagnosis of chronic interstitial nephritis 
 from the urine alone is usually extremely difficult, but when 
 combined with the clinical history and ph)-sical examination 
 It becomes less difficult, although often doubtful until the 
 case has been carefully watched for some months. 
 
 SECOND OR ADVANCED STAGE. 
 The patient at this time usually finds it necessary to dis- 
 continue business, because of lack of strength, habitual 
 headache, more or less marked gastric disturbance, and 
 perhaps other more serious symptoms ; in other words, the 
 disease is at its height, and the patient requires almost con- 
 stant attention. 
 
 Character of the Urine.— Quantity.— This gradually 
 but steadily increases from 2000 to 3000 or 4000 c.c. 
 Rarel}', it may go as high as 6000 c.c. in twenty -four hours. 
 Color. — Pale and sometimes almost colorless. 
 Reaction — Faintly acid. 
 
 Specific Gravity. — This has fallen from 1012 or 1015 
 to 1 010 or lower. . 
 
 Normal Solids.— ^/7.y^V///^/j/, much diminished. Occa- 
 sionally, if the disease is not very far advanced and the 
 patient is having the best of care and can take a moderately 
 nitrogenous diet, the urea may be nearly or quite normal, 
 but this does not continue for a very long time. Relatively, 
 much diminished. 
 
 Coloring-matters.— These are all diminished, except 
 the indoxyl, which is often normal or increased. 
 
 Albumin. — This has increased, and usually varies be- 
 tween a trace and yi of i per cent. It may rarely reach 
 y^ of I per cent. 
 
 Sediment. — This is much the same as in the early stage, 
 except that the casts are more numerous and usually more 
 granular. The renal cells, which are only few in number, 
 will be found to be quite granular. Oftentimes the abnor- 
 mally formed renal elements are found with some difficulty, 
 since the amount of sediment is so slight. As in the early 
 stage, the urine may require centrifugalization in order to ob- 
 tain a satisfactory sediment for examination.
 
 310 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 THIRD OR LATE STAGE. 
 
 This is at a time when the disease has advanced to a late 
 stage, and the patient is more or less uremic — /. e., suffering 
 from intense headache, nausea, vomiting, and often convul- 
 sions. General weakness is marked. Dyspnea is often a 
 prominent symptom. There is considerable vertigo and 
 disturbance of vision — the so-called albinnimiric retinitis. 
 There may be some edema of the feet at this time, due to 
 an uncompensated heart. 
 
 Character of the Urine. — Quantity. — This has gradu- 
 ally fallen from the large quantity to about 1500 c.c. The 
 quantity of urine passed at night is usually greater than that 
 passed during the day. 
 
 Color. — Veiy pale (watery). 
 
 Reaction. — Faintly acid. 
 
 Specific Gravity. — Usually between 1005 and loio ; 
 even when the twenty-four-hour quantity of urine is much 
 below the normal — e.g., with a quantity of 500 c.c. the 
 specific gravity may be as low as 1005. 
 
 Normal Solids. — Both absolutely and relatively much 
 diminished. 
 
 Albumin. — Usually, a distinct trace ; rarely, the. slightest 
 possible trace. It may, on the other hand, reach as high as 
 ]^ of I per cent. 
 
 Sediment. — This is still slight in quantity, and consists 
 of numerous (or many) hyaline, finely and coarsely granu- 
 lar, and a few waxy casts. Most of the renal cells will be 
 found to be very granular. No fat nor blood unless com- 
 plicated. Often in the late stage a few abnormal blood 
 globules will be found. It, therefore, may be difficult from 
 the urine alone and without a previous knowledge of the 
 case to make a diagnosis of a primary renal disease, espe- 
 cially if the quantity of urine is small and the waxy casts 
 are stained by the blood so as to resemble fibrinous casts. 
 The blood may be due to a slight acute exacerbation, or it 
 may be the result of either a circumscribed acute nephritis or 
 a more or less general active hyperemia. If the disease is 
 the result of some active irritant (lead or arsenic), blood may 
 be found in the sediment in all stages of the disease. 
 
 Prominent Symptoms. — Owing to the latency of the 
 disease, symptoms are frequently not noticed until the 
 occurrence of one of the serious or fatal complications.
 
 CHRONIC INTERSTITIAL NErHRITIS. 311 
 
 Even an advanced grade of chronic interstitial nephritis may 
 be compatible with great mental and bodily activity. There 
 may have been no symptoms whatever to suggest to the 
 patient the existence of a serious disease. In other cases 
 the general health is greatly disturbed. The patient com- 
 plains of lassitude, sleeplessness, has to arise two or three 
 times at night to micturate, the digestion is disordered, and 
 there are complaints of headache, failing vision, and shortness 
 of breath on exertion. The pulse is usually hard, the tension 
 increased, and the vessel-wall, as a rule, thickened. Hyper- 
 trophy of the left side of the heart occurs, to overcome the 
 resistance offered in the arteries ; and in many cases a sys- 
 tolic murmur develops at the apex, probably as a result of 
 relative insufficiency. Bronchitis is a frequent accompani- 
 ment, especially in winter. Sudden attacks of oppressed 
 breathing, particularly at night, are not infrequent. Cheyne- 
 Stokes breathing may be present, most commonly toward 
 the close, but the patient may be walking about and even 
 attending to business. Dyspepsia and loss of appetite are 
 common ; in fact, severe vomiting may be the first symptom. 
 Severe and fatal diarrhea may develop ; the breath is often 
 heavy and urinous. Headache is frequently an early and 
 persistent feature of chronic interstitial nephritis. Hemor- 
 rhages may take place into the meninges or the cerebrum ; 
 such are usually associated with marked changes in the 
 walls of the vessels. Disorders of vision may be one of the 
 first symptoms of the disease, and the oculist may be the 
 first to make the diagnosis of a chronic form of renal 
 disease. Ringing in the ears, with dizziness, is not un- 
 common. 
 
 Edema, except very slight swelling of the ankles, is very 
 uncommon in chronic interstitial nephritis until late in the 
 disease, when it is probably due to an uncompensated 
 heart. The skin is often dry and pale. Epistaxis may 
 occur and prove serious. Uremic symptoms, some of 
 which have been mentioned, are common in the advanced 
 stage of the disease. Uremic convulsions may be frequent 
 and severe. 
 
 Duration. — A chronic interstitial nephritis is usually in 
 progress for many years — from ten to thirty, or a longer 
 time. It is most common in middle life, and if discovered 
 early and the source determined, by good care the patient 
 may have fair health for many years.
 
 312 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 Prognosis. — The prognosis is very unfavorable, although, 
 as has been stated, if the disease is discovered during its 
 early stages, the patient may live many years. Occasion- 
 ally, the patient dies of some intercurrent disease such as 
 pneumonia, or, perliaps more commonly, cerebral hemor- 
 rhage because of the diseased arteries. Frequently, a sud- 
 den attack of uremia results fatally. The appearance of 
 waxy casts usually indicates that the fatal termination will 
 occur within one year, and often within six months. 
 
 Clinically, an uncomplicated case of chronic interstitial 
 nephritis — that is, one that does not present some evidence 
 of a slight parenchymatous change (presence of fat) — is 
 quite uncommon, it being the rule to find rarely a fat 
 globule adherent to an occasional cast. 
 
 Differential Diagnosis. — The diagnosis of an early stage 
 of chronic intei'stitial nepJiritis from the urine alone is often 
 difficult, owing to the fact that the urine is so slightly 
 altered from the normal. It is at this time that a very care- 
 ful consideration of the clinical history and the physical 
 examination are of infinite importance. It is needless to say 
 that an early recognition of this form of nephritis is very 
 important, for if it is the result of some chronic irritation, as 
 by lead or uric acid, the same should be recognized and the 
 irritant removed as early as possible. 
 
 The so-called "cardiac and renal " cases are worthy of 
 consideration here because of the differential diagnosis 
 between a chronic interstitial nepJiritis and passive hyperemia. 
 The latter condition is sometimes superimposed on the 
 former because of an uncompensated heart. From the 
 urine alone it is often impossible to decide which con- 
 dition is the more prominent. A very small twenty-four- 
 hour quantity of urine, a comparatively small amount of 
 albumin (trace), and the presence of marked edema are all 
 against a chronic nephritis. On the other hand, if the sedi- 
 ment contains waxy casts, or casts from extensively denuded 
 tubules, very granular renal cells, and, clinically, a high 
 tension pulse, and other evidences of increased blood pres- 
 sure, the condition may be a chronic interstitial nephritis in 
 a late stage, and at a time in the disease when the edema is 
 the direct result of the secondary disease of the heart. It 
 is sometimes necessary to watch the effect of treatment by 
 digitalis or other drugs that act chiefly on the diseased 
 heart before deciding as to the probability of an underlying
 
 SENILE INTERSTITIAL NEPHRITIS. 313 
 
 chronic interstitial nephritis. If the original abnormal 
 features of the urine were the results of a passive congestion, 
 such abnormalities will usually largely disappear as the con- 
 dition of the heart improv^es by treatment. 
 
 It is often difficult, if not impossible, to distinguish between 
 an active hyperemia attended with low metabolism, and a late 
 stage of a chronic interstitial nephritis attended witli a very 
 slight acute process and without the presence of waxy casts 
 in the sediment. About five years ago the author examined 
 the urine of a man, aged seventy, in which the urinary picture 
 was quite typical of an active hyperemia. Uremic coma 
 developed two da}"s later and death followed. At the 
 autopsy very small, red, granular kidneys were found, 
 indicative of a marked chronic interstitial nephritis. Of 
 course, in such cases, a knowledge of the clinical history 
 and the physical examination are of the greatest importance. 
 
 The usual prominent signs and symptoms of a chronic 
 nephritis will, in most cases, serve to establish the diag- 
 nosis. 
 
 SENILE INTERSTITIAL NEPHRITIS. 
 
 Synonym. — Senile atrophy of the kidneys. 
 
 This form of disease usually occurs in persons after the 
 age of from fifty to sixty ; but the disease is not necessarily 
 present in every elderly person. It is usually a part of the 
 general degeneration of the blood-vessels and sometimes a 
 part of a general arteriosclerosis. 
 
 In the senile kidney the chief lesions are those due to 
 disease of the vessels. These vascular lesions are accom- 
 panied by impairment in the power of regeneration. Pre- 
 vious lesions of the kidney, even though slight in character, 
 may gradually make their influence felt in impairing the 
 resistance of the tissue. The epithelial lesions may consist 
 chiefly in atrophy. Microscopically, the kidney is usually 
 more or less injected and atrophied. On microscopic exam- 
 ination the epithelium of the tubules is degenerated, small, 
 and atrophic. The formation of yellow pigment in the 
 atrophic epithelium is frequently seen. There is some gen- 
 eral increase in the connective tissue, but this is chiefly 
 marked close beneath the capsules, and may extend from 
 here in lines into the cortex (Councilman). 
 
 Character of the Urine. — The urine does not bear the 
 usual characteristics of the typical chronic interstitial
 
 314 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 nephritis, but has more the appearance of a passive 
 hyperemia. 
 
 The quantity is generally not far from i 500 c.c., and may 
 even be considered below the normal. 
 
 The albumin is, ordinarily, from the slightest possible trace 
 to a trace. 
 
 The normal solids are absolutely diminished, but no more 
 than would be expected in a person of advanced years 
 when the metabolism is decidedly low. Relatively, they are 
 about normal. 
 
 The sediment has practically the same appearance as in 
 the early form of chronic interstitial nephritis — an occa- 
 sional hyaline and granular cast and granular renal cell. 
 
 It may be impossible from the urine alone and without a 
 knowledge of the case to make a positive diagnosis of a 
 senile interstitial nephritis. 
 
 CHRONIC DIFFUSE NEPHRITIS. 
 
 Synonym. — Chronic diffuse nephritis with exudation. 
 
 Chronic diffuse nephritis is undoubtedly one of the most 
 common of the chronic diseases of the kidney. 
 
 From a clinical point of view, this form of disease par- 
 takes essentially of two pathologic conditions : ( i) An inter- 
 stitial element, which is generally very prominent and shown 
 by the increased twenty-four-hour quantity, pale color, low 
 specific gravity, increased indoxyl, and relatively and abso- 
 lutely diminished normal solids ; (2) a parenchymatous ele- 
 ment, shown by the comparatively high percentage of albu- 
 min and the presence of fatty renal elements (fatty casts, 
 fatty renal cells, etc.) in the sediment. Usually, the inter- 
 stitial element is predominant, hence the characteristic 
 features of the disease in a general way resemble those of a 
 chronic interstitial nephritis. 
 
 Pathologically, the morbid processes in the kidney may 
 consist of any one, or a combination of any, of the following 
 conditions : Chronic glomerular nephritis, chronic arterio- 
 sclerotic nephritis, chronic degenerative and interstitial neph- 
 ritis. 
 
 In chronic glomerular nepliritis the essential lesions are 
 in the glomeruli, and consist of extensive hyaline degenera- 
 tion of tufts and of entire glomeruli, and obliteration of 
 capillaries. Every transition may be seen between these
 
 CHRONIC DIFFUSE NEPHRITIS. 315 
 
 glomerular lesions and those in the subacute form of neph- 
 ritis. There may be some increase in the capsular epithe- 
 lium and connective-tissue formation within the capsule. 
 The tubular epithelium shows extensive degeneration and 
 destruction. Entire tubules are destroyed, often being rep- 
 resented by the thickened irregular membrana propria. 
 There is a general and diffuse increase of the connective 
 tissue affecting almost equally all parts of the kidney. This 
 condition is usually found as an independent affection, or it 
 may be combined with acute infections of various sorts, 
 when there is often a history that points to a previous acute 
 or subacute affection. The kidney may be slightly larger 
 than normal, of normal size, or considerably smaller than 
 normal. The capsule is often adherent, the surface even, not 
 granular, and pale. On section, the cortex varies in width ; 
 it may be quite small, opaque, whitish, the markings obscure, 
 the glomeruli not visible nor pale, and the consistence of the 
 tissue greatly increased (Councilman). 
 
 (For the pathologic description of chronic arteriosclerotic 
 nephritis and of chronic degenerative and interstitial neph- 
 ritis, see pp. 305, 306.) 
 
 Causes. — The causes of a chronic diffuse nephritis are, 
 in some instances, probably the same as those of chronic 
 interstitial nephritis. The disease sometimes follows an 
 acute nephritis in which the stage of convalescence has been 
 prolonged for many months or years. The author has 
 met with a few cases in which a chronic diffuse nephritis 
 followed an acute nephritis of pregnancy. 
 
 Prominent Symptoms. — In the majority of cases of 
 chronic diffuse nephritis the symptoms are, in many respects, 
 the same as in chronic interstitial nephritis. But in this dis- 
 ease there is constantly more or less edema, which is usu- 
 ally slight during the early stages, becoming more marked 
 as the disease advances, when general dropsy may be 
 extreme. There is usually gastric disturbance and fre- 
 quency of micturition, accompanied by an increase in the 
 daily quantity. Circulatory disturbances are more or less 
 marked, especially when the disease forms a part of a 
 general arteriosclerosis. Anemia, a pasty appearance of 
 the skin, emaciation, and visual disorders are not uncom- 
 mon. Uremic symptoms are frequently met with, especial- 
 ly in advanced cases, or as the result of acute exacerba- 
 tions.
 
 316 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 The characteristics of the urine of the average advanced 
 case of chronic diffuse nephritis are as follows : 
 
 Character of the Urine. — Quantity. — The average 
 quantity is about 2000 c.c. It may be considerably 
 higher — 3000 c.c. — or lower, — 1500 c.c, — and it may oc- 
 casionally be below the normal, but only temporarily. The 
 quantity of urine at night often exceeds that of the day. 
 
 Color. — Pale and sometimes greenish. 
 
 Specific Gravity. — Average loio to 1015. If the 
 twenty-four-hour quantity is unusually high, the specific 
 gravity may be from 1004 to 1008. 
 
 Normal Solids. — Absolutely, diminished and sometimes 
 to a marked degree ; relatively, much diminished. The 
 indoxyl is generally normal or increased. 
 
 Albumin. — This varies between a large trace and 3^ of i 
 per cent., but the average is usually between y^ and J^ of 
 I per cent. The quantity of albumin is much larger than 
 in chronic interstitial nephritis and smaller than in subacute 
 glomerular nephritis. 
 
 Sediment. — This is generally slight in quantity, and con- 
 sists of numerous hyaline and granular casts, mostly with 
 fat adherent ; an occasional (or few) fatty cast ; numerous 
 renal cells, most of which are fatty, and a few compound 
 granule cells. No blood is seen unless complicated. If the 
 disease is far advanced, a few waxy casts will be found ; 
 occasionally, they are present in large numbers. When 
 waxy casts appear in the sediment, the twenty-four-hour 
 quantity of urine will usually be less than normal. 
 
 In case the parenchymatous element predominates the 
 quantity of urine will be not far from the normal (1500 
 c.c), the specific gravity and quantity of albumin will be 
 correspondingly high, and the amount of fat in the sediment 
 will be greater than indicated above. If, on the other hand, 
 the interstitial element predominates, the quantity of urine 
 will be large (2500 to 3000 c.z>^, the specific gravity and 
 quantity of albumin correspondingly low, and the amount 
 of fat comparatively small. 
 
 Differential Diagnosis. — In the diagnosis of chronic 
 diffuse nephritis special attention should be paid to the 
 twenty-four-hour quantity of urine, which, if permanently 
 increased, will usually serve to distinguish it from a subacute 
 glomerular nephritis. In some instances of chronic diffuse 
 nephritis, notably following an acute exacerbation while the
 
 AMYLOID INFILTRATION. 317 
 
 dropsy is still marked, the total quantity of urine is often 
 less than normal, the quantity of albumin is very large, and 
 the amount of fat is excessive. Under these circumstances 
 it is usually impossible from the urine alone to distinguish 
 the condition from a subacute glomerular nephritis, without 
 watching the urine for a considerable period. It is often 
 impossible to differentiate between a chronic diffuse nephritis 
 near death, and a subacute glomerular nephritis also near 
 
 death. , • ■ • ,• • 
 
 An nncomplicatcd chronic interstitial nephritis is distin- 
 guished from a chronic diffuse nephritis by the presence of 
 fat in the sediment, the comparatively high quantity of 
 albumin, and, upon physical examination, the presence of 
 edema in the latter disease. 
 
 The duration of chronic diffuse nephritis will depend 
 largely on whether the interstitial or the parenchymatous 
 element predominates. If the former, the patient may live 
 from ten to fifteen years, providing he has the best of care ; 
 on the other hand, if the parenchymatous element is pre- 
 dominant, the duration of life is usually between five and 
 ten years. As in subacute glomerular nephritis, acute ex- 
 acerbations are very likely to occur, and if they are very 
 numerous, the duration of life may not exceed from five to 
 eight years, and often death occurs within a much shorter 
 
 period. 
 
 The prognosis is, in most cases, grave. The appearance 
 of waxy casts in the sediment is an unfavorable sign ; death 
 will probably occur within one year. 
 
 AMYLOID INHLTRATION. 
 
 Synonyms.— Lardaceous kidney ; waxy degeneration ; 
 chronic depurative disease of the kidneys. 
 
 Amyloid infiltration is a disease that is not confined alone 
 to the kidneys. The lesions are usually prominent in other 
 organs of the body as well— notably the liver and spleen. 
 
 In amyloid infiltration, as the name implies, the character- 
 istic lesion is the amyloid infiltration about the blood-vessels ; 
 consequently, the portion of the kidney that is most seriously 
 affected is the glomerulus. There may be small masses of 
 amyloid along the vascular loops, or the entire glomerulus 
 may be converted into a glassy, homogeneous mass, the 
 result of the deposit of the amyloid material. Usually,
 
 318 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 some of the glomeruli are only moderately affected, hence 
 the functions of the kidneys are maintained for some 
 period. 
 
 The amyloid material is stained a mahogany-brown color 
 by iodine, whereas the unaffected tissue takes a dehcate 
 yellow stain ; and a rose-red color by methyl-violet, the 
 undiseased tissue being stained blue. 
 
 Causes. — Amyloid infiltration is often an accompaniment 
 of syphilis, phthisis, tubercular disease of the joints, chronic 
 suppuration of the bones, and chronic wasting diseases. The 
 exact reason for amyloid infiltration in these conditions is 
 not known. 
 
 Prominent Symptoms. — The features of the urine alone 
 may not definitely indicate the presence of this disease. 
 Usually, the associated conditions (syphilis, tuberculosis, 
 etc.) give hints as to the nature of the process. The liver 
 and spleen are usually enlarged. Diarrhea is a common 
 symptom. Increased arterial tension and cardiac hyper- 
 trophy are not usually present, except in those cases in 
 which amyloid infiltration occurs in the secondary con- 
 tracted kidney. Under these circumstances there may be 
 uremia and retinal changes, which, as a rule, are not met 
 with in uncomplicated amyloid infiltration. Frequency of 
 micturition and the elimination of a large quantity of urine 
 in twenty-four hours are often important and early signs. 
 It is essential that the clinical history, the physical examin- 
 ation, and the urine should receive equal weight in the diag- 
 nosis of amyloid infiltration ; it rarely happens that the urine 
 alone affords sufficient data for an accurate diagnosis. 
 
 Character of the Urine. — The urine of a well-advanced 
 case of amyloid infiltration is as follows : 
 
 Quantity. — Usually, above 1 500 c.c. ; generally, between 
 2000 and 4000 c.c. The quantity of the day urine usually 
 exceeds that of the night. Like the other chronic affec- 
 tions of the kidneys, the quantity generally falls to normal 
 or below the normal a short time before death. 
 
 Color. — Generally, very pale ; the urine often has a 
 greenish tint. 
 
 Specific Gravity. — This is below the normal ; it is usu- 
 ally found to vary between 10 12 and 1018. 
 
 Normal Solids. — Absolutely, normal or slightly dimin- 
 ished, but dependent upon the metabolism. Relatively, 
 much diminished, especially if the Quantity of urine be very
 
 AMYLOID INFILTRATION. 319 
 
 large. The probable explanation of the normal quantity of 
 solids in the urine is the fact that the parenchyma or secret- 
 ing structure of the kidney does not become involved until 
 late in the disease, the principal pathologic changes being 
 about the blood-vessels. Absolutely, the indoxyl may be 
 increased, but it is usually diminished. 
 
 Albumin. — In an uncomplicated case the quantity of 
 albumin varies between a trace and yi of i per cent. ; only 
 rarely does it exceed yi of i per cent. On the other hand 
 it may be less than a trace, particularly if the quantit}^ of 
 urine is in the neighborhood of 4000 c.c. 
 
 Sediment. — This is generally very slight in amount, and 
 consists of a few hyaline, granular, and occasional (or few) 
 waxy casts ; rarely, a renal cell. No fat nor blood, unless 
 complicated. 
 
 The waxy casts appear rather early in this disease, much 
 sooner than in the other chronic diseases of the kidney. 
 The question has often arisen as to whether the waxy casts 
 found in amyloid disease were cylinders of amyloid material 
 or of the same composition as those found near the end of 
 other chronic affections of the kidney ? The quer>' still 
 remains unsettled, for the reason that it is very difficult to 
 satisfactorily stain the waxy casts by the stains ordinarily 
 used for the detection of amyloid material. If the suspected 
 sediment is first washed several times by decantation with a 
 dilute solution of glycerine, and methyl-violet added, some 
 of the casts (both waxy and hyaline) will be found to have 
 a slight reddish tint. Further experiments are, however, 
 necessary before any definite conclusions can be drawn from 
 the use of stains. 
 
 Amyloid disease of the kidney is Axry apt to be compli- 
 cated by parenchymatous degeneration ; such changes are 
 probably secondary to the extensive deposit of amyloid 
 material in the glomeruli and the resulting interference with 
 the nutrition of the renal epithelium. Sometimes this 
 parenchymatous change is very marked, so that the urine 
 will have the characteristics of chronic diffuse nephritis ; or 
 it may predominate to such an extent that the urine will 
 resemble one of subacute glomerular nephritis, the evi- 
 dences of amyloid being thereby obscured. 
 
 Differential Diagnosis. — In the diagnosis between an 
 U7icoinplicated amyloid infiltration and a chronic interstitial 
 nephritis \.\\Q enlarged liver and spleen, an absence of increased
 
 320 DISTURBANCES AND DISEASES OF THE KIDNEYS. 
 
 arterial tension and cardiac hypertrophy, and the history 
 of syphiHs, tuberculosis, etc., will usually indicate amyloid 
 disease. From the urine alone it is impossible to distin- 
 guish with certainty between these two conditions. It 
 should be said, however, that in amyloid infiltration the 
 total solids and the total quantity of urea are usually 
 higher than in chronic interstitial nephritis, but such a rule 
 is by no means invariable, since amyloid disease is often ac- 
 companied by a chronic disease that very much diminishes 
 the metabolism. 
 
 As previously stated, in considering the diagnosis of this 
 disease the physical examination and clinical history should 
 always be carefully weighed along with the characteristics 
 of the urine. 
 
 The duration of this disease is largely dependent on the 
 cause. As a rule, it extends over a period of several years 
 — from ten to fifteen ; sometimes a longer, and occasionally 
 a much shorter, time. 
 
 The prognosis depends rather on the condition with 
 which this renal affection is associated. As a rule, it is 
 erave.
 
 CHAPTER IX. 
 
 DISEASES OF THE KIDNEYS (CONTINUED), 
 
 TUBERCULOSIS OF THE KIDNEYS. 
 
 Primary tuberculosis of the kidneys is not very rare. It 
 occurs in two distinct forms — viz., local caseating tuberculo- 
 sis and acute miliary tuberculosis. The latter form is always 
 associated with tuberculosis in other parts of the body, such 
 as phthisis pulmonalis and tubercular meningitis. This 
 form rarely gives rise to distinct urinary symptoms. Local 
 caseating tuberculosis, on the other hand, usually results in 
 urinary symptoms to a marked degree, and it is this form 
 that deserves special consideration in this connection. 
 
 The substance of the kidney may contain only a few, or 
 there may be a large number of, tubercular nodules. The 
 process very soon involves the pelvis of the kidney, and in a 
 majority of the cases not only the pelvis but the ureter as 
 well, and sometimes the bladder and prostate. It may be 
 difficult to say in advanced cases whether the disease has 
 started in the bladder, prostate, or seminal vesicles, and crept 
 up the ureters, or whether it started in the kidneys and pro- 
 ceeded downward. Osier believes that in the majority of cases 
 the latter is true, and the infection is through the blood. One 
 kidney alone may be involved, and the disease creeps down 
 the ureter and may involve the mucous membrane of the 
 bladder to a greater or less extent. The process is com- 
 mon in the middle period of life, but it may occur in the 
 extremes of age. It is more frequent in males than in 
 females. 
 
 Prominent Symptoms. — The symptoms are usually 
 those of chronic pyelitis. The urine may be purulent for 
 years, and there may be little or no distress. Even before 
 the bladder becomes involved micturition is often frequent, 
 and many instances are mistaken for cystitis. The condJ- 
 21 321
 
 322 DISEASES OF THE KIDNEYS. 
 
 tion may be in progress for many years without marked 
 impairment of health. In cases in which the disease be- 
 comes advanced and both organs are affected, constitutional 
 symptoms are more marked. General tuberculosis is com- 
 mon. Intermittent hematuria is of frequent occurrence, 
 denoting ulcerative changes in the mucous membrane of the 
 tubules of the kidney. 
 
 Physical examination may detect special tenderness on 
 one side, or the kidney may be palpable in front on deep 
 pressure ; but a tuberculous kidney seldom causes a large 
 tumor. Occasionally, the ureter becomes occluded and 
 pyonephrosis results ; but this is rare in comparison with its 
 frequency in calculous pyelitis. 
 
 Character of the Urine. — Early in tuberculosis of the 
 kidney the urine is only slightly altered from the normal. 
 There may be the slightest trace of albumin, and the sedi- 
 ment may contain only a very few leucocytes and an occa- 
 sional blood globule. When, however, the disease becomes 
 more advanced and ulcerative changes have begun, the 
 urine will usually have the following characteristics : 
 
 Quantity. — The total quantity of urine for twenty-four 
 hours is generally increased, although it may be normal or 
 diminished. 
 
 Color. — Pale. The urine is usually more or less turbid, 
 due to the pus, blood, etc., in suspension. 
 
 Reaction. — Generally acid, except when the urine con- 
 tains an abundance of blood, when it may be faintly acid or 
 alkaline. 
 
 Specific Gravity. — Usually below the normal — loio to 
 loi 5, or thereabouts. 
 
 Normal Solids. — Both relatively and absolutely, dimin- 
 ished. If there is general advanced tuberculosis, the solids 
 will be absolutely very low. 
 
 Albumin. — The quantity of albumin is dependent, in the 
 first place, on the amount of destruction of the kidney, and, 
 secondly, on the amount of pus and blood present. If the 
 disintegration of the renal tissue is marked, the albumin is 
 usually high, approximating from ^ to ^ of i per cent. 
 If, on the other hand, the tubercular process is localized and 
 not extensive, the amount of albumin may not exceed a 
 slight ti'ace, or trace. 
 
 Sediment. — Abundant. Chiefly pus, which is usually 
 free, but may be more or less clumped ; the pus may be
 
 TUBERCULOSIS OF THE KIDNEYS. 323 
 
 markedly degenerated. Many small round cells, some of 
 which are usually fatty. Hyaline and granular casts, some 
 of larger diameter, are usually present, but they may be so 
 obscured by the pus as to escape detection. Blood is gen- 
 erally present, but sometimes in small amount ; it may, 
 however, be very abundant, intermittent hematuria being a 
 common symptom of this disease. The sediment also con- 
 tains tubercle bacilli. 
 
 To distinguish the condition from a calculous p)'elitis is 
 often difficult. Hemorrhage may be present in both condi- 
 tions, though not nearly so frequently in the tuberculous 
 disease. The diagnosis rests on three points : ( i ) The 
 detection of some focus of tuberculosis, as in the testes ; (2) 
 the presence of tubercle bacilli in the sediment ; and (3) the 
 use of tuberculin. In women the kidney involved is now 
 easily determined by catheterizing the ureters after the plan 
 introduced by Kelly, of Baltimore. Dr. Edw. Reynolds, 
 has recently reported a case of early tuberculosis of the 
 kidney,^ in which the author had the opportunity of 
 making a careful study of the urine, and in which cathet- 
 erization of the ureters led to the location of the disease. 
 
 Detection of Tubercle Bacilli in the Urinary Sediment. 
 
 Either centrifugalize the urine or allow the sediment to 
 settle by gravity ; decant the supernatant urine, and wash 
 twice by decantation with distilled water. After the second 
 washing, centrifugalize. The sediment is then taken up by 
 means of a pipette and placed on from four to eight cover- 
 glasses, which have been carefully cleansed in nitric acid 
 and then in alcohol. Care should be exercised not to get 
 too much sediment on the cover-glasses, for the layer may, 
 after drying, be too thick, especially if there is much pus in 
 the sediment. These cover-glass preparations are then 
 dried by placing them on an iron or copper plate, under 
 which is placed a very small flame (about y^ of an inch 
 in height will suffice), the main object being to get very 
 gentle heat so that the specimens will be dried slowly 
 and without being charred. Stain the dried preparations 
 with either carbol-fuchsin (Ziehl-Neelson) or aniline water 
 and fuchsin (Koch-Ehrlich) in the usual manner. Decolor- 
 ize in 20 per cent, nitric acid, wash in water, and, finally, still 
 
 1" Johns Hopkins Bulletin," Nov., 1898, p. 253.
 
 324 DISEASES OF THE KIDNEYS. 
 
 further decolorize in jo per cent, alcohol for at least ten 
 minutes. Then stain with an aqueous solution of methylene- 
 blue, mount, and examine. 
 
 It is very important that the preparations should be 
 thoroughly decolorized in alcohol in order to be able to 
 distinguish between tubercle bacilli and smegma bacilli ; 
 the latter being quite readily decolorized by this means, 
 while the former are not affected. A very close resem- 
 blance exists between these two organisms. At times the 
 smegma bacillus appears thicker than the tubercle bacillus, 
 and sometimes the ends have a clubbed appearance, but 
 this is not true in all instances ; consequently, the data thus 
 far at hand are of no differential importance. Smegma 
 bacilli are not uncommon in the urine of both male and 
 female, particularly in the urine of those who are not 
 cleanly. It is obvious that special care should be taken in 
 procuring a specimen that is to be examined for tubercle 
 bacilli. Since in those individuals who are not cleanly the 
 smegma collect about the genitalia, it is essential that these 
 parts be thoroughly cleansed before the urine is voided. A 
 still better procedure is to procure a catheter specimen, if 
 possible. Attention to these details contributes materially 
 to a satisfactory result of the examination. 
 
 Tubercle bacilli in the urine are usually arranged in 
 groups (Plate 9), although they may occur singly. They 
 may be present in large numbers and easily found ; on the 
 other hand, they may be rare and escape detection even after 
 prolonged examination. The fact that tubercle bacilli can not 
 be found in a urinary sediment does not, then, prove their 
 absence. In all suspicious cases a portion of the sediment 
 (^ to I c.c.) should be injected into the peritoneal cavity 
 of a guinea-pig. If the bacilli are present, the animal will 
 develop tuberculosis in from six to eight weeks ; if not 
 present, the animal will not be affected by the inoculation. 
 This constitutes the safest method for the detection of 
 tubercle bacilli in urine. 
 
 RENAL CALCULUS. 
 
 Calculi may originate in the secreting structure of the 
 kidney, — usually in the tubules, — forming cavities for their 
 location in the parenchyma of the organ. 
 
 Renal calculus is usually unilateral, though there are
 
 Plate 
 
 Tubp:rci.e Bacilli in Urinary Sediment 
 Observation.) 
 
 X ^oo. (Personal
 
 RENAL CALCULUS. 325 
 
 many exceptions to this rule. The calculus, when large, is 
 usually single, the smaller ones being more apt to be 
 multiple. 
 
 Renal calculus occurs at all ages, including intra-uterine 
 life. It is, however, most common before fifteen, and after 
 fifty, years of age. In young people and children calculi 
 are most frequent among the poor, while the condition in 
 advancing life is most common in people in comfortable cir- 
 cumstances and of luxurious habits. As a rule, the calculi 
 in infency are composed of ammonium urate ; those in 
 young adults, uric acid ; those after fifty years of age are 
 made up of either uric acid or calcium oxalate. 
 
 Prominent Symptoms. — These consist of dull aching 
 pain situated deeply in the loin, usually unilateral, and 
 often radiating along the ureter toward the testicle or labia, 
 down the thigh, and sometimes extending as far as the 
 foot. The pain may be sharp and lancinating at times. 
 When a stone enters the ureter, intensely severe paroxysms 
 of pain (renal colic) are usually experienced, lasting a few 
 hours and then suddenly subsiding. The ordinary pain of 
 renal calculus is nearly always increased by exercise — walk- 
 ing or riding. There is often tenderness upon deep pressure 
 anteriorly, especially if the calculus has excited much in- 
 flammation. Gastric disturbances are common, includincr 
 nausea, vomiting, and periods of more or less disordered 
 digestion, hyperacidity, flatulence, etc. 
 
 Character of the Urine. — The urine is usually highly 
 concentrated, of high color, high specific gravity, and sharply 
 acid reaction. Sometimes it has a decided smoky color, 
 because of the presence of altered blood pigment. Rela- 
 tively, the solids are generally increased ; absobitely, about 
 normal, providing the patient is in good general condition ; 
 as a rule, the normal solids will depend upon the meta- 
 bolism. 
 
 The amount of albumin depends on the extent of the 
 irritation and the quantity of blood. 
 
 The sediment is usually that of an active hyperemia or 
 irritation of the kidneys. It is not uncommon to find crys- 
 tals or microscopic concretions of the same substance as the 
 calculus that is being formed in the kidney. There may be 
 a considerable quantity of blood, which is usually abnormal 
 in character, providing the hemorrhage is not abundant ; if 
 profuse, there is generally more or less normal blood. The
 
 326 DISEASES OF THE KIDNEYS. 
 
 sediment may or may not contain pus. It is more common 
 perhaps to find only a few leucocytes rather than an abun- 
 dance of pus. If much pus is present, it is probable that 
 either an abscess of the kidney or a chronic pyelitis has been 
 produced by the stone. 
 
 Renal calculi usually consist of either uric acid or urates, 
 calcium oxalate, or cystin. Occasionally, the calculus is 
 the result of a deposit of phosphates in the kidney. Such 
 a deposition is always secondary to an extension upward 
 from the bladder or pelvis of the kidney. In case of a 
 phosphatic calculus in the kidney the urine is usually pale 
 in color, with an alkaline reaction, and an abundant deposit 
 of phosphates in the urinary sediment. 
 
 ABSCESS OF THE KIDNEY. 
 
 Abscess of the kidney is usually due either to injury of 
 the organ, to an encysted concretion that sets up a marked 
 irritation in some portion of the kidney, or to tubercular 
 disease of the organ. 
 
 The condition is accompanied by the usual symptoms of 
 an abscess in any part of the body — viz., fever, localized 
 pain, cachexia, marked languor, nausea and vomiting, etc. 
 On the affected side there may be a distinct tumor, which, 
 on manipulation, is found to be extremely tender ; again, the 
 condition may exist without tumor. 
 
 The abscess usually ruptures into the pelvis of the kidney 
 or into the renal tubules, and the urine that was free from 
 pus will suddenly contain a large amount of it. 
 
 Character of the Urine. — The urine generally has the 
 characteristics of a fever urine — high color, high specific 
 gravity, strongly acid reaction, and containing a very slight 
 trace or a trace of albumin. The sediment usually has the 
 appearance of one of active hyperemia, which may be mild 
 or severe, according to the extent of the inflammatoiy 
 process (circumscribed acute nephritis) about the abscess, 
 and the degree of disturbance that is invariably set up as a 
 result of the elimination of toxines by the healthy kidney. 
 As soon as the abscess evacuates into the urinary tract, 
 the sediment, which is abundant and usually of a greenish 
 color, contains an abundance of degenerated pus, many 
 small round cells, usually a few compound granule cells, 
 and more or less blood. There is frequently hematuria fol-
 
 RENAL EMBOLISM. 327 
 
 lowing the evacuation of the abscess, especially if any of 
 the renal blood-vessels have been ruptured. This hem- 
 orrhage may be slight and of short duration if due to 
 injury of the capillaries, and may be extensive and per- 
 sistent if one or more of the larger vessels have been 
 ruptured. 
 
 The sudden appearance of a large amount of blood and 
 pus in a urine that has previously been clear and free from 
 these elements is strongly suggestive of abscess of the 
 kidney, especially when taken in conjunction with the 
 clinical history and symptoms. A diagnosis of this con- 
 dition can not be made from the urine alone previous to the 
 rupture of the abscess and without a clinical knowledge of 
 the case. 
 
 The prognosis is usually grave when the disease is of 
 tubercular origin. When it is due to trauma or to an 
 encysted concretion, the prognosis is often good if an early 
 diagnosis is made. Occasionally, recovery follows drainage 
 of the pus-sac, and in rare instances spontaneous recovery 
 takes place, particularly when the destructive changes are 
 only slight. In most cases of abscess of the kidney sur- 
 gical interference is necessary. 
 
 RENAL EMBOLISM. 
 
 Renal embolism consists of an impacted thrombus that 
 has formed in some part of the circulatory system, — usually 
 on the valves of the heart, — and is carried by the blood 
 current to the kidney, where it occludes one of the renal 
 ■vessels. The anatomic changes resulting from renal em- 
 bolism are very constant and striking, and the condition is 
 quite commonly found at the autopsy, although only rarely 
 recognized during life. 
 
 Prominent Symptoms. — -A previous history of endo- 
 carditis is generally found. The sudden pain that usually 
 accompanies the occlusion of the renal vessel may be 
 severe, often followed by nausea and vomiting, and some- 
 times by a state of collapse. On the other hand, the pain 
 may be comparatively slight, although usually persistent 
 for some time. Chills and a more or less irregular tem- 
 perature are frequent accompaniments of this condition. 
 
 Character of the Urine. — From the urine alone the 
 diagnosis of a renal embolism is practically impossible.
 
 328 DISEASES OF THE KIDNEYS. 
 
 The urinary changes usually begin abruptly, and the urine 
 suddenly has the characteristics of one accompanying fever. 
 The urine is usually much diminished in quantity, of high 
 color, and high specific gravity — 1025 to 1035. Rela- 
 tively, the normal solids are increased ; absolutely, normal or 
 slightly diminished. The quantity of albumin depends upon 
 the extent of the disturbance in the neighborhood of the area 
 affected by the embolus. The sediment usually has the 
 characteristics of a more or less severe active hyperemia 
 or a circumscribed acute nephritis, which is in progress 
 around the diseased area. 
 
 TUMORS OF THE KIDNEY. 
 
 These are benign or malignant. Of the benign tumors, 
 the most common are the fibromata ; lipoinata, lyjuph- 
 adcnoniata, and angioniata are constantly met with. Adeno- 
 mata may be congenital. Malignant growths — sarco7)ia or 
 carcinoma — may be either primary or secondary. Sarcomata 
 are the more common. 
 
 Tumors of the kidney grow rapidly and may attain a 
 very large size — 12 to 30 pounds. They are often soft, 
 and hemorrhages frequently occur in them. In sarcomata 
 invasion of the pelvis or of the renal vein is common. In 
 almost all instances tumor is present. An increasing tumor 
 in the anterior lumbar region, between the costal arch and 
 the crest of the ilium, is always suggestive of renal tumor. 
 The tumors are usually fixed, although they may be mov- 
 able ; they are frequently lobulated. 
 
 Prominent Symptoms. — Hematuria. — This may be the 
 first indication. The blood is fluid or clotted ; sometimes 
 a blood-clot is passed having the appearance of a cast of 
 the ureter. 
 
 Progressive Emaciation. — Loss of flesh is usually marked 
 and advances rapidly. 
 
 Pain. — This is generally present, and of a dull aching 
 character, situated in the flank and radiating down the thigh. 
 The pressure of the tumor often causes severe and alarming 
 symptoms, such as edema of the feet and legs, ascites, dis- 
 turbances of the stomach, various neuroses, — the result of 
 pressure on the large nerve-trunks, — and anemia. There is 
 often frequent micturition, which may be so marked as to indi- 
 cate a disease of the bladder when only the kidney is involved.
 
 CYSTIC DISEASE OF THE KIDNEYS. 329 
 
 Character of the Urine. — Perhaps the most prominent 
 feature of the urine is the presence of more or less blood — 
 hematuria ; occasionally, the amount of fresh blood is 
 very large, but this is not true in every case. The urine 
 usually shows evidence of a circumscribed inflammation or 
 congestion of the kidney in the neighborhood of the new 
 growth : in other words, the urine presents the picture of a 
 more or less severe active hyperemia of the kidney. Pus is 
 generally absent in the sediment, save in advanced cases 
 attended with decided destructive changes in the kidney or 
 changes in the new growth itself Under such circum- 
 stances the quantity of pus is comparatively small, consider- 
 ing the extent of the necrotic changes. Rarely, cancer 
 elements can be recognized in the urinary sediment. Occa- 
 sionally, the presence of a large number of epithelial cells 
 with large and prominent nuclei and of various shapes is 
 strongly suggestive of new growth, especially if the mucous 
 membrane of the pelvis is involved or has become ulcerated. 
 The presence in the sediment of organized elements, such as 
 renal casts, renal cells, etc., is of little or no diagnostic 
 value in renal cancer. 
 
 A diagnosis of renal cancer from the urine alone is only 
 of the rarest occurrence, and then only in case particles of 
 the morbid growth with a distinct alveolar structure are 
 discovered in the sediment ; but in malignant disease 
 limited to the parenchyma of the kidney the appearance 
 of portions of the growth in the sediment is practically un- 
 known. 
 
 CYSTIC DISEASE OF THE KIDNEYS. 
 
 Cystic disease of the kidneys is probably the result, in 
 most cases, of some obstruction to the outflow of urine 
 through one or more renal tubules. Three varieties of 
 cysts are met with : 
 
 1. Small cysts, seen especially in chronic interstitial neph- 
 ritis, resulting from dilatation of obstructed tubules or Bow- 
 man's capsule. 
 
 2. Solitary cysts, ranging in size from a marble to an 
 orange, or even larger, without evidences of other changes 
 in the kidney. 
 
 J. Congenital cystic kidneys. In this condition the kid- 
 neys are represented by a conglomeration of cysts varying 
 in size from a pea to a marble. The organs are greatly en-
 
 330 DISEASES OF THE KIDNEYS. 
 
 larged, and together may weigh from seven to ten pounds. 
 In the fetus they may attain a size sufficient to impede 
 labor. Little or no renal tissue may be noticeable, although 
 on microscopic examination it is seen that a considerable 
 amount remains in the interspaces. 
 
 The cystic fluid is usually clear, but it may be turbid, and 
 sometimes reddish-brown or even black in color ; occasion- 
 ally, it is viscid. Specific gravity is usually low. Albumin, 
 blood-corpuscles, and sometimes hematoidin crystals, leuco- 
 cytes, cholesterin, triple phosphates, and fat globules are 
 found in the contents. Urea and uric acid are present 
 only in traces. The contents of one cyst may have an 
 entirely different character from those of an adjacent cyst. 
 
 Character of the Urine. — In general the character of 
 the urine is that of a chronic interstitial nephritis. In some 
 instances the urine is not abnormal, especially in those cases 
 in which there are no other changes in the kidney. 
 
 The diagnosis of cystic disease of the kidney can not 
 be made with certainty from the urine alone. The condi- 
 tion, especially the congenital form, may exist unsuspected 
 until found at the autopsy, death being the result of some 
 other disease. Great enlargement of both kidneys, with 
 hypertrophy of the left ventricle and increased arterial ten- 
 sion, would suggest cystic disease. 
 
 Operative interference is not justifiable. It is important 
 to remember that the conglomerate cystic kidney is almost 
 invariably bilateral. Osier cites an instance in w^hich one 
 kidney was removed and the patient died within twenty-four 
 hours from cystic disease of the other kidney.
 
 CHAPTER X. 
 
 DISEASES OF THE URINARY TRACT BELOW 
 THE KIDNEY PROPER, 
 
 The diseases of the urinary tract below the kidney 
 proper have received names according to their location and 
 their duration. They are, for the most part, inflammatory 
 in character, and may be either acute or chronic. In a 
 consideration of the urine of all such diseases, the quantity 
 of albumin, the total amount of urea, and the character of 
 the sediment are of special importance for purposes of 
 diagnosis. 
 
 PYELITIS. 
 
 This is an inflammation of the mucous membrane of the 
 pelvis of the kidney ; it may be either acute or chronic. 
 
 ACUTE PYELITIS. 
 
 An acute inflammation of the pelvis of the kidney may 
 be either mild or severe, and local or general. Primary 
 acute pyelitis is not of common occurrence, but is usually 
 found to exist as an accompaniment or a complication of an 
 acute disease of the kidney proper. 
 
 Causes. — The disease is usually produced in one of 
 three ways : (i) By the extension of an inflammatory 
 process downward from the kidney; (2) by the upward 
 extension of disease of the bladder ; (3) by irritants con- 
 fined within the pelvic cavity itself An acute nephritis 
 is usually accompanied by a more or less severe acute 
 pyelitis (see p. 295) — in other words, the irritant that 
 has set up the nephritis has also had its irritating influ- 
 ence on the mucous membrane of the pelvis by extension 
 downward. Not infrequently an acute pyelitis (together 
 with an acute nephritis) follows exposure to cold and 
 wet, and it may be set up by the irritating action of the 
 
 331
 
 332 DISEASES OF THE URINARY TRACT. 
 
 toxines of certain acute infectious diseases, such as typhoid 
 fever, scarlet fever, diphtheria, and septicemia. A gonor- 
 rheal infection of the lower urinary tract may, by exten- 
 sion, result in an acute pyelitis, and sometimes, later, an 
 acute nephritis. When an acute pyelitis occurs without 
 an accompanying acute nephritis or disease of the lower 
 urinary passages, it is almost invariably due to the irritat- 
 ing action of crystalline elements or to a small concretion 
 within the pelvic cavity. If due to a concretion, the inflam- 
 matory process may be circumscribed. Rarely, the pressure 
 of a new growth, which is located outside of the urinary 
 tract, on the pelvis of the kidney results in an acute pyelitis. 
 
 Prominent Symptoms. — There is usually more or less 
 pain referred to the region of the affected kidney or kidneys, 
 and it is often found radiating along the course of the ureter 
 toward the groin. There is frequently some fever, although, 
 as a rule, the temperature is not high. The disease may, 
 however, be ushered in by a chill or a succession of rigors 
 followed by a high temperature for a day or two. Hema- 
 turia is an early symptom, and usually continues for several 
 days. The patient may suffer from renal colic, caused by 
 the marked irritation of crystalline elements or by a cal- 
 culus or blood-clot obstructing the outflow of urine through 
 the ureter. Rarely, a pyonephrosis results from obstruc- 
 tion in the ureter. Micturition is more frequent than 
 normal. The symptoms of an accompanying acute nephri- 
 tis or a cystitis are often sufficiently prominent to entirely 
 obscure those that are referable to the pelvis itself. 
 
 Character of the Urine. — The urine of a simple acute 
 pyelitis, without much involvement of the kidney proper, 
 usually has the characteristics of a fever urine. 
 
 Quantity. — Considerably diminished — /. e., from 400 to 
 800 or 1000 c.c. 
 
 Color. — High, and frequently smoky, sometimes a blood- 
 red color, depending upon the amount and character of the 
 blood present. 
 
 Specific Gravity. — This is generally higher than normal 
 — 1025 to 1030, or as high as 1035. 
 
 Normal Solids. — Absohitcly, diminished ; relatively, in- 
 creased. 
 
 Albumin. — The quantity of albumin is variable, but in a 
 general way corresponds to the amount of blood and pus 
 present. As a rule, the quantity of albumin is chiefly rela-
 
 CHRONIC PYELITIS. 333 
 
 tive to the amount of blood rather than to the quantity 
 of pus present. The quantity usually varies between a 
 sliglit trace and y^ oi \ per cent. 
 
 Sediment. — Chiefly normal blood. Numerous small 
 caudate cells from the superficial layer of the pelvis of the 
 kidney. Some pus, both free and in clumps. There are, 
 frequently, clumps of small, medium, or large round cells 
 from the calices of the kidney. Since there is nearly always 
 some extension of the inflammatory process into the straight 
 tubules, a few (or occasional) granular and brown granular 
 casts with adherent renal cells from the straight tubules, and 
 abnormal blood will be found. If the tubular involvement 
 is marked, the number of casts will be much larger, and the 
 general characteristics of the urine will approach those of 
 an acute nephritis complicated by an acute pyelitis. The 
 presence of crystals or crystalline fragments should always 
 be noted, for they may be the cause of the pyelitis, or may 
 lead to the diagnosis of a calculus and the probable compo- 
 sition of the same. 
 
 An acute pyelitis as a complication of an acute nephritis 
 or the result of an irritant toxine usually disappears with the 
 subsidence of the primary affection. Sometimes it lasts 
 only a few days and then, quite suddenly, the urine and 
 sediment bear the characteristics of a chronic pyelitis. 
 When the disease is due to the presence of a concretion or 
 to a gonorrheal infection, it very soon becomes chronic, and 
 may continue for months or years as a chronic pyelitis. 
 
 CHRONIC PYELITIS. 
 
 -This is a chronic inflammation of the mucous membrane 
 of the pelvis of the kidney. It may be mild or severe, and 
 local or general. 
 
 Causes. — A chronic pyelitis is induced by a variety of 
 causes, among which the following are the most important : 
 (i) The irritation by crystals or calculi — a very common 
 cause. (2) Tuberculosis. (3) The infectious pyelitis that 
 develops in fevers, in which an acute pyelitis precedes the 
 chronic inflammation. (4) Obstruction to the outflow of 
 urine through the ureter, as by an impacted calculus, blood- 
 clot, stricture or twist of the ureter, etc. (5) The presence 
 of decomposing urine, following pressure upon the ureter 
 by tumors located outside the urinary tract. (6) A frequent 
 cause of a chronic pyelitis is the upward extension of an
 
 334 DISEASES OF THE URIXARY TRACT. 
 
 inflammation of the bladder. (7) Obstruction to the out- 
 flow of urine by a tight stricture of the urethra, a very nar- 
 row prepuce, or tumor of the bladder. (8) Movable kidney. 
 
 Prominent Symptoms. — In the forms of chronic pyelitis 
 associated with the acute febrile diseases symptoms may 
 be wanting. There may be more or less pain in the region 
 of the affected organ. If, at any time, there is retention of 
 the pus as the result of obstruction in the ureter or bladder, 
 chills followed by fever, sweats, and sometimes renal colic 
 ensue. Such symptoms rapidly disappear following an 
 evacuation of the pus, but spontaneous evacuation of the 
 pus cavity (renal pelvis) may not take place ; under these 
 circumstances a true pyonephrosis results. Aside from 
 twists of the ureter, perhaps the most common cause of 
 frequent attacks of retention of pus, followed in a few days 
 by evacuation of the pus cavity, is the presence of calculi 
 in the renal pelvis, the obstruction being removed b)' a 
 change of position or other means. A pyonephrosis with 
 its attending symptoms is not an uncommon outcome of a 
 chronic pyelitis. 
 
 Character of the Urine. — The urine has the general 
 characteristics of one of a chronic disease. 
 
 Quantity. — Usually, less than normal — about 1200 c.c. 
 
 Color. — Pale. The urine is generally ver\- turbid, due to 
 the pus in suspension. 
 
 Reaction. — Usually, faintly acid. The urine readily be- 
 comes alkaline upon standing. 
 
 Specific Gravity. — This is below the normal — loio to 
 1015. 
 
 Normal Solids, — Both absolutely and relatively, dimin- 
 ished. The absolute quantity of urea will usually be found 
 to vary between 15 and 25 grams ; the extent of the dimi- 
 nution will depend upon the metabolism. 
 
 Albumin. — This is relative chiefly to the amount of 
 blood and pus present ; if the kidney proper is only slightly 
 involved, the albumin will generally var}' between a very 
 sligJit trace and a large trace. 
 
 Sediment. — Chiefly degenerated pus, both free and in 
 clumps ; many small round cells, some in the clumps of 
 pus ; a few blood globules. In most cases there is more 
 or less involvement of the straight tubules of the kidney ; but 
 renal casts are often difficult of detection in the sediment, 
 owing to the presence of the pus which obscures them.
 
 CALCULOUS PYELITIS. 335 
 
 In a chronic pyelitis the casts present, are usually of large 
 diameter, and they may have leucocytes adherent to them, 
 or there may be true pus casts. 
 
 A careful search should always be made for crystals or 
 crystalline fragments, and when present the diagnosis of a 
 calculous pyelitis is rendered probable. On the other hand, 
 a concretion may exist in the renal pelvis without the pres- 
 ence of any formed crystals, or crystalline elements, in the 
 sediment. Great care should be taken not to mistake ex- 
 traneous particles of dust, pieces of broken glass, etc., for 
 fragments of a calculus. 
 
 The urinary sediment should in all doubtful cases be 
 examined for tubercle bacilli, for it is only by this means 
 that a tubercular pyelitis can be eliminated. 
 
 The diagnosis of a new growth involving the pelvis of 
 the kidney is very difficult from the urine alone. Rarely, 
 the presence of an unusual number of cellular elements 
 leads to such a diagnosis, but such inferences should be 
 well guarded by clinical signs and symptoms. 
 
 Duration and Prognosis. — A chronic pyelitis usually 
 disappears with the removal of the cause, if su^h is possible. 
 If due to tuberculosis or a new growth of the kidney and 
 its pelvis, surgical interference is usually necessary. 
 
 There is constant danger of disease of the healthy kidney, 
 and when it occurs, there is, unfortunately, little that can be 
 done to relieve the condition. The disease in a mild form 
 may continue for years without causing, in itself, much suf- 
 fering. This is especially the case when the disease is caused 
 by accidental twists of the ureter as in floating kidney, 
 in which instance the urine is retained in the renal pelvis 
 until a time when the pressure of the retained fluid becomes 
 sufficient to force its escape, or until the kidney regains its 
 normal position by a sudden change of position of the 
 patient, or until it is replaced by surgical operation. When 
 the kidney is stitched into position, the chronic pyelitis 
 usually subsides in a short time ; otherwise the disease may 
 continue in a mild form as long as these temporary twists 
 of the ureter occur. 
 
 CALCULOUS PYELITIS. 
 
 Although this subject has been considered in connection 
 with an acute and chronic pyelitis, it deserves special atten- 
 tion because of its importance.
 
 33.6 DISEASES OF THE URINARY TRACT. 
 
 Calculi that cause pyelitis may be large or small, and 
 may be free in the pelvis or become encysted. They 
 often have projections that extend up into the calices and 
 sometimes into the straight tubules ; the tubules thus 
 obstructed become dilated by the purulent urine, and 
 often result in abscesses. When the pressure of the fluid 
 in the abscess sac becomes sufficient to dislodge the 
 obstructing calculus, the urine suddenly contains a large 
 amount of pus, which is almost invariably of a greenish 
 color. Sometimes there is a gradual leakage of pus about 
 the seat of the obstruction, and not infrequently the abscess 
 connects with one or more tubules, so that the urine con- 
 stantly contains pus, and often in enormous quantities. The 
 author has recently seen a case of multiple abscess of the 
 kidney due to a large calculus in the pelvis, in which the 
 pus sacs apparently had a common opening from which an 
 enormous amount of pus was discharged — nearly one-fourth 
 of the twenty-four-hour urine being thick greenish pus. 
 
 In calculous pyelitis there may be only slight tubidity of 
 the mucous membrane, such a condition being sometimes 
 called catarrhal pyelitis. More commonly, the mucous sur- 
 face is roughened, grayish in color, and thick. Under these 
 circumstances there are almost always more or less dilata- 
 tion of the calices and flattening of the papillae. Follow- 
 ing this condition there may be (i) extension of the suppu- 
 rative process to the kidney itself, forming a pyelonephritis. 
 (2) A gradual dilatation of the calices with atrophy of the 
 kidney substance, and, finally, the production of the condi- 
 tion of pyonephrosis in which the entire organ is repre- 
 sented by a sac of pus with or without a thin shell of renal 
 tissue. (3) After the kidney structure has been destroyed 
 by suppuration, if the obstruction at the orifice of the pelvis 
 persists, the fluid portions may be absorbed, and the pus 
 become inspissated, so that the organ is represented by a 
 series of sacculi containing grayish pap-like masses, which 
 have become impregnated with lime-salts. 
 
 Prominent Symptoms. — The symptoms are, for the 
 most part, the same as those in chronic pyelitis. There may 
 be pain in the back or there may be tenderness on deep 
 pressure on the affected side. Before the condition of 
 pyuria is established, besides the attacks of pain, there may 
 be rigors, high fever, and sweats. Pain is often increased 
 by exercise, — walking or riding, — but not in all cases.
 
 HYDRONEPHROSIS. 337 
 
 Coincident with the retention of pus, a tumor may be felt 
 on the affected side. The general condition of the patient 
 usually indicates prolonged suppuration. Occasionally, 
 nervous symptoms, which may be associated with dyspnea, 
 supervene ; or the termination may be by coma. These 
 nervous phenomena have been attributed to the absorption 
 of the decomposed materials from the seat of the disease. 
 
 Character of the Urine. — The urine generally has the 
 characteristics of an acute or a chronic pyelitis. The most 
 predominant element in the sediment is the pus, which is 
 often present in large quantity. There is usually more or 
 less blood, and sometimes it is present in considerable quan- 
 tity. The sediment may, or may not, contain crystalline 
 elements or concretions ; the mere absence of cr}^stals 
 would not be sufficient ground for excluding the condition 
 of calculous pyelitis. 
 
 Usually, the other (unaffected) kidney is more or less 
 congested as a result of the elimination of toxines from the 
 diseased organ. This is especially the case in chronic pye- 
 litis or abscess of the kidney due to a stone, but it is often 
 very difficult to find renal casts in the presence of so much 
 pus. 
 
 Diagnosis. — Between the tuberculous and calculous 
 forms of pyelitis it may be difficult or impossible to distin- 
 guish, except by the detection of tubercle bacilli in the 
 urinary sediment. The examination for tubercle bacilli 
 should be made systematically in all suspicious cases, and 
 if not found by the microscope, guinea-pigs should be in- 
 oculated with a portion of the sediment. 
 
 HYDRONEPHROSIS. 
 
 This is a condition due to an obstruction in the ureter and 
 the retention of 7io7iptirident urine in the pelvis of the kidney. 
 If the obstruction continues, the pelvis of the kidney be- 
 comes extremely dilated, and as a result of the back pres- 
 sure there is a marked dilatation of the straight tubules, and 
 then the smaller tubules. Finally, the kidney and its pelvis 
 are converted into a sac, which may be of sufficient size to 
 produce a tumor on the affected side. The kidney soon 
 loses its function after the urine begins to back up into the 
 small tubules, and, finally, the entire work of secretion and 
 excretion is thrown on the other kidney. 
 
 22
 
 338 DISEASES OF THE URINARY TRACT. 
 
 About from thirty-five to forty per cent, of these cases are 
 congenital, the remainder may be acquired. The congenital 
 causes comprise twists of the ureter upon its axis, undue 
 obliquity of the ureteral opening into the bladder, redupli- 
 cation, valve-like folds of the mucous membrane of the ure- 
 ter, and imperforate ureter. The acquired causes are (i) an 
 impaction of a calculus ; (2) a blood-clot in the ureter; (3) 
 stricture of the ureter, especially following traumatism ; (4) 
 twist of the ureter, particularly in case of " floating kidney," 
 and if due to this cause, the condition usually continues until 
 the pressure becomes sufficient to force an opening and 
 allow the fluid to escape (intermittent hydronephrosis) ; (5) 
 new growth in the pelvis or ureter, or one outside of the 
 urinary tract, causing marked pressure on the ureter. 
 
 Prominent Symptoms. — A dull, aching pain is usually 
 present in the renal region. A tumor is present in most 
 cases, gradually encroaching on the median line and down- 
 ward toward the iliac fossa. A sudden diminution in the 
 size of the tumor coincident with the elimination of an 
 unusual quantity of nonpurulent urine, may be considered 
 diagnostic. Vomiting sometimes occurs during these periods 
 of retention, and occasionally a urinous odor may be observed 
 in the perspiration at such times, especially if both kidneys 
 are involved. Constipation is a frequent result of pressure 
 upon the colon ; more rarely, diarrhea maybe present from 
 the same cause. As long as the hydronephrosis is single 
 and the remaining kidney healthy, there is usually an 
 absence of uremic symptoms. Enlargement of the unaf- 
 fected kidney may compensate for the defective elimination. 
 Hypertrophy of the left side of the heart usually follows. 
 
 Character of the Urine. — Owing to the virtual loss of 
 function of the affected kidney, the entire work of elimina- 
 tion is thrown on the other kidney and, as a result, it is 
 common to find evidence of more or less active congestion 
 of the unaffected organ. (See Active Hyperemia.) The 
 quantity of urine is generally diminished ; the normal solids 
 are absolutely diminished, although not to a marked degree ; 
 and there is usually albumin, varying between the slightest 
 possible trace and a trace. The sediment usually contains 
 an occasional (or {q.\\^ hyaline, granular, and brown granu- 
 lar casts, some of which have renal cells and a little abnor- 
 mal blood adherent ; and a {q.\n free renal cells and blood 
 globules.
 
 PYONEPHROSIS. 339 
 
 In rare instances the urine may be perfectly normal. 
 
 The fluid in the Jiydroncplirotic sac is usually of a pale 
 color, of low specific gravity, and contains only small 
 amounts of the normal urinary constituents, notably urea 
 and uric acid. Albumin is generally present, the quantity 
 being in the neighborhood of a trace. The sediment wswdWy 
 consists of a few blood globules, cells from the pelvis and 
 tubules of the kidney, and a iQ.\N casts of small diameter 
 from the higher tubules. There is no pus, or, at the most, 
 only an occasional leucocyte. 
 
 The outlook in hydronephrosis depends upon the cause. 
 When unilateral, the condition may never produce serious 
 trouble, and the intermittent forms may persist for years and 
 finally disappear. Occasionally, the cyst ruptures into the 
 peritoneum, more rarely through the diaphragm into the 
 pleural cavity and lung. The sac may discharge spontane- 
 ously through the ureter and the fluid never reaccumulate, 
 or the condition may change to one of pyonephrosis. 
 
 PYONEPHROSIS. 
 
 This condition is the result of an obstruction to the out- 
 flow of urine through the ureter, and the retention of piirn- 
 lent urine in the renal pelvis. It usually follows a pre- 
 existing acute or chronic pyelitis, although it may exist 
 primarily as a hydronephrosis, and later become a pyo- 
 nephrosis as a result of the inflammatory process set up by 
 chemic or mechanical irritants in the pelvis — notably crys- 
 talline elements or a calculus. 
 
 "The destruction of the kidney is sometimes very rapid, 
 because of the retained pus-containing fluid and the ex- 
 tension of the inflammatory process to various parts of the 
 kidney proper. As in hydronephrosis, the back pressure 
 of the retained fluid results, first, in a marked dilatation of 
 the renal pelvis ; next, the straight tubules ; then, the smaller 
 tubes, which become atrophied and lose their function ; and, 
 finally, the disorganized kidney and its pelvis constitute a 
 large pus sac. 
 
 Causes. — Any of the causes ascribed to a hydronephrosis 
 may produce a pyonephrosis by partially or entirely oc- 
 cluding the ureter, if a pyogenic organism be present. 
 Of these the most common are impacted calculus, twist 
 of the ureter in case of "floating kidney," and trau-
 
 340 DISEASES OF THE URINARY TRACT. 
 
 matic or inflammatory stricture of the ureter. Marked pres- 
 sure on the ureter or the pelvis of the kidney by new growths 
 that are situated outside of the urinary tract may produce 
 this condition. 
 
 Prominent Symptoms. — The most prominent symptoms 
 of pyonephrosis comprise pyuria with constitutional symp- 
 toms, such as chills, irregular temperature, emaciation, 
 anemia, and prostration. If there is a tumor, it may be 
 elastic and fluctuating, or hard, and extend both forward 
 and downward. Pain is present, varying with the size of 
 the tumor and degree of fluctuation ; it often appears in 
 paroxysms of intensity — renal colic. Pressure over the 
 anterior of the tumor greatly increases the pain, or causes 
 it if not present before. On the other hand, lateral pressure 
 may relieve the pain when present. The bowels are usually 
 disturbed, constipation or diarrhea being frequent. The 
 sudden appearance of a purulent urine that has previously 
 been clear and free from pus is often of great diagnostic 
 value. 
 
 Character of the Urine. — If the pyonephrosis is uni- 
 lateral and the occlusion of the ureter on the affected side is 
 complete, the urine usually shows the existence of a more or 
 less severe active hyperemia of the unaffected kidney. This 
 is undoubtedly due partly to the absorption of toxic prod- 
 ucts from the diseased kidney, and partly to the extra work 
 of elimination. The urine will be free from pus and other 
 evidences of a pyonephrosis, so that the diagnosis of this 
 condition can only be made from the physical examination 
 and the clinical symptoms. 
 
 If by any means the obstruction in the ureter be re- 
 moved, the urine will suddenly become veiy turbid, and 
 when it settles will contain a very abundant sediment hav- 
 ing a decidedly greenish tint. On microscopic examination 
 this sediment will be found to consist of a large quantity 
 of degenerated and disintegrated pus, accompanied by an 
 abundance of small round cells. There may be a small 
 amount of blood in this sediment, but usually blood- 
 corpuscles are difficult to find — or, more properly, difficult 
 to recognize — in the presence of so much pus. 
 
 The odor of the urine containing the pus is generally 
 very offensive, and sometimes the reaction is alkaline. 
 
 The quantity of albumin is usually large, — y% to /^ of i 
 per cent, or more, — and very often the albumin is accom-
 
 URETERITIS. 341 
 
 panied by an abundance of globulin. The author has met 
 with one case in which the quantity of globulin equaled 
 that of the albumin. From a diagnostic point of view the 
 other characteristics of the urine are not especially significant. 
 
 It is often necessary to remove the diseased kidney in 
 order to save the life of the patient. The pus sac thus 
 removed usually contains very little, if any, fluid material, 
 but, instead, a thick, putty-like or cheesy mass of inspis- 
 sated pus, the liquid portion having been previously ab- 
 sorbed. This putt}'-like substance may contain a deposit 
 of lime-salts. 
 
 A pyonephrosis is always attended with danger to life. 
 Perforation into the peritoneal or pleural cavities may 
 occur, or the patient may be worn out by the hectic fever, 
 or amyloid disease may develop. 
 
 URETERITIS. 
 
 An inflammation of the mucous membrane of the ureter 
 may be acute or chronic. The inflammatory process may 
 be local or general, according to the cause. 
 
 A diagnosis of this condition from the urine alone is 
 practically impossible, especially if the urine is voided in 
 the natural way. Since the advent of catheterization of the 
 female ureters, exceptional opportunities have been afforded 
 for studying diseases of this tract, and some instructive 
 observations have been made. 
 
 Causes. — This inflammatory condition may be a part of 
 an acute pyelitis or an acute cystitis, by extension. It is 
 probably more frequent in connection with an acute pye- 
 litis, and often due to the same causes. (See p. 331.) 
 Aside from an inflammatory process due to exposure to 
 cold and wet, perhaps the most common cause is the pas- 
 sage of calculi or microscopic crystals of uric acid or cal- 
 cium oxalate. If the calculus can not be forced through 
 the ureter, it first produces a marked acute ureteritis and 
 later a chronic inflammation at its lodging point, which is 
 frequently at the place where the ureter crosses the brim of 
 the pelvis. The microscopic crystals often produce an irri- 
 tation or inflammation of the mucous membrane through- 
 out the entire length of the tube. Like an acute pyelitis, 
 the acute process in the ureter soon becomes chronic. The 
 inflammation may have the characteristics of a chronic
 
 342 DISEASES OF THE URINARY TRACT. 
 
 ureteritis from the beginning, as in tubercular ulcerations, 
 or a gradual extension upward of a chronic inflammation 
 of the bladder. The pressure on the ureter by new growths 
 located outside of the urinary tract, twists, and strictures of 
 the ureter often produce more or less inflammation. 
 
 Symptoms. — The most prominent clinical feature is the 
 paroxysmal sharp pain — renal colic — that starts in the 
 region of the kidney, follows down the line of the ureter 
 into the testicle, and along the inner side of the thigh. 
 During the paroxysm of pain there is usually nausea and 
 vomiting, marked prostration, and sometimes a little fever. 
 (See Renal Calculus.) On bimanual examination the 
 thickened ureter or impacted calculus can, occasionally, 
 be felt through the abdominal wall. 
 
 Character of the Urine. — The urine usually has the 
 characteristics of the inflammatory process above or below 
 the ureter — acute or chronic pyelitis, and acute or chronic 
 cystitis. The diagnosis of a simple ureteritis, if such exists 
 without a pyelitis or cystitis, can only rarely be made from the 
 urine alone ; even then it is ver}' difficult to distinguish it from 
 an irritation or acute inflammation of the pelvis of the kid- 
 ney. In a simple ureteritis due to an impacted calculus the 
 urine usually has a high color, strongly acid reaction, and 
 high specific gravity. The quantity of albumin commonly 
 varies with the amount of blood. The sediment frequently 
 contains more or less blood, and sometimes the blood is 
 present in abundance. There are usually small caudate 
 and spindle cells from the ureter, and a few (or numerous) 
 leucocytes. 
 
 Catheterization of the ureters may lead to the diagnosis 
 of ureteritis, stricture of the ureter, or the presence of a cal- 
 culus in the ureter. The history of renal colic, or of more 
 or less continuous pain in the region of the ureter, is of 
 importance in the diagnosis. 
 
 CYSTITIS. 
 
 This is an inflammation of the mucous membrane of the 
 bladder ; it may be either acute or chronic. 
 
 ACUTE CYSTITIS. 
 
 Causes. — One of the most common causes of this disease 
 is an infection with micro-organisms, such as the gonococ-
 
 ACUTE CYSTITIS. 343 
 
 cus in cases of backward extension of a gonorrheal ure- 
 thritis ; with the pyogenic staphylococci and other forms of 
 pyogenic bacteria that have been introduced into the bladder 
 by means of an unclean catheter ; and with the tubercle 
 bacillus. It may result from an acute prostatitis ; from in- 
 jury, as with the rough use of sounds ; from extensive ure- 
 thral stricture ; from foreign bodies, such as calculi ; from 
 drugs, such as cantharides and copaiba ; and from new 
 growths. An acute cystitis is not uncommonly seen fol- 
 lowing exposure to cold and wet, sexual .excesses, and 
 simple acute retention of urine. An acute inflammation 
 of the bladder is a frequent complication of acute infec- 
 tious diseases, notably typhoid fever, in which case it is 
 probably the direct result of the action of the typhoid 
 bacillus. 
 
 In the mild cases of acute cystitis the vesical mucous 
 membrane is congested, thickened, and swollen, and the 
 epithelium becomes detached in places, leaving abraded sur- 
 faces. In the severe forms the bladder becomes lined with 
 a tough, tenacious layer of mucin (?) ; there may be ulcera- 
 tions and sloughing. The submucous connective tissue is, 
 in some cases, infiltrated with pus, and hemorrhagic areas 
 are not uncommon. 
 
 Prominent Symptoms. — One of the first symptoms is 
 increased frequency of micturition, which usually becomes 
 more and more prominent, only a very small quantity of 
 urine being voided at each effort at urination. Tenesmus is 
 frequently very severe ; the patient will often lean over the 
 vessel or urinal, quivering with the muscular effort, without 
 relief to the distressing and very urgent desire. The pain, 
 which is likewise extreme, may be referred to the neck of 
 the bladder, to the perineum, to the glans penis, or to the 
 hypogastrium, and may radiate into the loins or down the 
 thighs. There is frequently marked constitutional disturb- 
 ance with more or less elevation of temperature, although in 
 some cases the general disturbance is slight in comparison 
 with the intensity of the local symptoms. 
 
 Character of the Urine.— Quantity. — The twenty-four- 
 hour quantity of urine is usually small, varying from 500 to 
 800 or 1000 c.c. 
 
 Color. — Bloody or smoky, depending upon the amount 
 and character of the blood present. 
 
 Reaction. — Strongly acid.
 
 344 DISEASES OF THE URINARY TRACT. 
 
 Specific Gravity. — Early in the disease the specific 
 gravity is usually high — 1025 to 1030; later, it is normal 
 or slightly diminished — 1015 to 1022. 
 
 Normal Solids. — Relatively, increased ; but absolutely, 
 more or less diminished, depending upon the amount of 
 systemic disturbance set up by the disease. 
 
 Albumin. — The quantity of albumin is variable, but in 
 a general way it is relative to the amount of blood and pus 
 in the urine. It is not uncommon for the quantity of albu- 
 min to reach or even exceed y^ of i per cent., but usually 
 it is less than this figure. 
 
 Sediment. — The sediment, which is generally abundant, 
 consists chiefly of normal blood ; considerable pus, some in 
 clumps, and a large amount of squamous epithelium. 
 Numerous small round cells, perhaps some of them fatty, 
 may be found. 
 
 CHRONIC CYSTITIS. 
 
 Causes. — A chronic cystitis may result from an acute 
 cystitis. In some instances the changes taking place in the 
 mucous membrane of the bladder are so sliijht and fjradual 
 that a chronic process results apparently without a preexist- 
 ing acute stage. In general, the same causes that have 
 been attributed to an acute inflammation of the bladder may 
 be looked for to explain the presence of a chronic cystitis. 
 Among these causes are to be borne in mind infection 
 by micro-organisms, as following the introduction of insuf- 
 ficiently purified and disinfected catheters or bougies, or 
 when the instrument carries into the bladder pus and bacte- 
 ria from an ulcerating surface or a pus pocket in the urethra 
 (stricture). A very frequent cause of this form of cystitis 
 is the enlarged prostate. Owing to the inability of the 
 patient to completely empty his bladder, the residual urine 
 sooner or later decomposes by the rapid development of 
 bacteria, and a general cystitis results. In a similar manner 
 many cases of cystitis arise in patients with nervous disease, 
 who have paralysis of the bladder, as in paraplegia ; also 
 in persons who are severely ill and stupid from some acute 
 disease, such as typhoid fever. In the acute infectious dis- 
 eases a chronic cystitis may appear, either as the result of 
 frequent catheterization, or by the action of the bacteria 
 causing the disease. 
 
 In cases of vesical calculus vesical tuberculosis, and new
 
 CHRONIC CYSTITIS. 345 
 
 growths of the bladder, a chronic cystitis is probably more 
 commonly seen than an acute cystitis, since the disturbance 
 by these agencies is at first slight. The subsequent changes, 
 which are often very gradual, become more pronounced, 
 and finally a well-marked chronic inflammatory process is 
 apparent. 
 
 In women the agents of inflammation may quite easily 
 enter the bladder from the vagina through the short female 
 urethra ; thus arise the frequent cases of cystitis in childbed 
 (usually an acute cystitis). Communications may develop 
 between the bladder and certain neighboring organs, such 
 as vesicorectal or vesicovaginal fistulae, by which, again, 
 access to the bladder is open to the agents of inflammation. 
 
 The pathologic changes in the wall of the bladder may 
 result in atony or atrophy, with thinning of the mucous 
 membrane, fatty degeneration of the muscular fibers almost 
 to the point of disappearance, and great distention of the 
 organ. Again, they may be followed by hypertrophy of 
 the muscular coat, the fibers forming ridges or fasciculi 
 standing out in the interior of the bladder and separated by 
 lozenge -shaped spaces, the organ itself being contracted so 
 that its cavity can contain but a few cubic centimeters of 
 fluid. Sometimes between these muscular bars pouches of 
 mucous membrane protrude, forming distinct sacculi com- 
 municating with the interior of the bladder by narrow 
 mouths and remaining permanently ; occasionally, they 
 contain calculi. In chronic cystitis of long standing the 
 mucous membrane often takes on a slaty, grayish-black 
 color as a result of hemorrhages. The incrustation of the 
 mucous membrane with urinary salts, especially with am- 
 monio-magnesium phosphate, is also frequently found in the 
 chronic form of this disease. 
 
 Prominent Symptoms. — The symptoms of an acute 
 cystitis are present in a modified form. Micturition is not 
 so frequent ; tenesmus is much less or is absent (in mild 
 cases) ; pain is usually very slight, and in mild cases it may 
 be absent ; the constitutional symptoms are comparatively 
 slight, and become marked only when renal changes have 
 occurred or when a general toxemia has followed the 
 absorption of the products of urinary decomposition. 
 
 Character of the Urine. — Quantity. — The twenty-four- 
 hour quantity of urine is usually only moderately diminished 
 — /. c, 800 to 1400 c.c.
 
 346 DISEASES OF THE URINARY TRACT. 
 
 Color. — Generally pale, but it may be normal in color ; 
 it may, however, be tinted with blood to a greater or less 
 extent. The freshly passed urine is generally turbid, due to 
 the presence of pus and epithelium and an abundance of 
 bacteria. 
 
 Reaction. — Frequently alkaline, but it may be acid and 
 sometimes it is strongly acid, especially in the early stages 
 of the disease. The reaction varies according to the pres- 
 ence or absence of urea-decomposing organisms. 
 
 Specific Gravity. — This varies usually between ioi2 
 and I020 ; average about 1015. 
 
 Normal Solids. — Both relatively and absolutely, dimin- 
 ished. 
 
 Albumin. — This varies between the slightest possible trace 
 (mild cases) and ^ of i per cent, (severer forms). It is 
 usually directly dependent upon the amount of pus and 
 blood present. 
 
 Sediment. — Abundant. If the urine be acid, the sedi- 
 ment will consist chiefly of pus and small round cells ; con- 
 siderable squamous epithelium, and generally a small 
 (sometimes a considerable) amount of blood. If the urine 
 be alkaline, — ammoniacal, — the sediment will settle in a 
 viscid, sticky mass, which consists mostly of decomposed 
 pus, amorphous phosphates, crystals of triple phosphate, 
 and often crystals of ammonium urate. The pus corpuscles 
 may be so embedded in the mucin-like substance and so 
 changed as to entirely lose their characteristic appearance. 
 
 There can be no doubt that decomposing alkaline urine 
 acts as a chemic irritant to the mucous membrane of the 
 bladder ; hence, cases of mild cystitis often become inten- 
 sified by the irritation of the ammonia salts that are formed. 
 
 TUBERCULOSIS OF THE BLADDER. 
 
 Tuberculosis of the bladder is not an uncommon condi- 
 tion. The existence of a chronic inflammation of the blad- 
 der, in the absence of tangible evidences of infection from 
 gonorrhea, chronic obstruction, or by instrumentation, 
 should always leave a suspicion of the tubercular nature of 
 the affection. The two places in which tuberculosis of the 
 bladder is most likely to commence are the trigone and 
 ureteral orifices, the latter being the more common. The 
 tubercular process begins with the formation of typical gray
 
 TUBERCULOSIS OF THE BLADDER. 347 
 
 nodules in the mucous membrane ; these nodules become 
 confluent, caseate, soften, and finally produce ulceration. 
 In more acute cases the disease leads to diffuse cheesy infil- 
 tration and general ulceration. 
 
 Vesical tuberculosis is found more frequently in males 
 than in females, and is a disease of early and middle life 
 (seventeen and forty years of age). In the male the disease 
 is frequently associated with tuberculosis of the seminal vesi- 
 cles and of the prostate. The resistance of the mucous 
 membrane of the bladder to tubercle bacilli is quite marked ; 
 in some cases of tuberculosis of the kidney the bladder may 
 be irrigated with urine containing tubercle bacilli for years 
 without becoming tubercular. 
 
 Prominent Symptoms. — The symptoms of vesical tuber- 
 culosis are similar to those of stone in the bladder. The 
 disease is initiated by a frequent desire to urinate, by pain 
 after emptying the bladder, with slight hematuria at longer 
 or shorter intervals. Later in the disease intermittent 
 hemorrhage becomes a conspicuous clinical symptom, but 
 it is never so profuse as in tumor of the bladder. Reten- 
 tion and incontinence of urine are quite common. 
 
 Character of the Urine.— Quantity.— The twenty-four- 
 hour quantity is usually diminished, although it may be 
 slightly increased. 
 
 Color. — Pale ; sometimes bloody. The urine is gener- 
 ally quite turbid from the pus, blood, etc., in suspension. 
 
 Reaction. — Nearly always acid, except when the urine 
 contains a large amount of blood, when it may be neutral 
 or alkaline. 
 - Specific Gravity. — Usually, below the normal — i o i o to 
 
 1015. 
 
 Normal Solids. — Relatively and absolutely, diminished. 
 
 Albumin. — The quantity will depend chiefly on the 
 amount of blood and pus present ; it usually varies between 
 a slight trace and a large trace. In case of abundant hema- 
 turia the quantity of albumin will, of course, be high — }i 
 to 3<( of I per cent. 
 
 Sediment. — Abundant. Chiefly pus, which is generally 
 free, but may be slightly clumped. Considerable squamous 
 epithelium and many small round cells, some of which are 
 fatty ; a few (sometimes numerous) blood globules. The 
 sediment also contains tubercle bacilli. 
 
 As in tuberculosis of other parts of the urinary tract.
 
 348 DISEASES OF THE URINARY TRACT. 
 
 the symptoms are variable and often misleading. Even the 
 presence of tubercle bacilli in the urine, indicating as it 
 does tuberculosis of the urinary system, does not locate the 
 anatomic seat of the disease. The presence of tubercle 
 bacilli and squamous epithelium, which are more or less inti- 
 mately mixed with the pus, makes the diagnosis of vesical 
 tuberculosis probable. 
 
 The prognosis in this condition is usually grave. Spon- 
 taneous recovery is exceedingly rare. If the disease be 
 mild and limited to the bladder, it may remain in a latent 
 condition for years. There is always danger of an exten- 
 sion of the tubercular process to the kidney, which is soon 
 followed by a suppurative pyelonephritis. There can be 
 but little doubt that appropriate general and local treat- 
 ment will prolong life and alleviate the distressing symp- 
 toms. 
 
 In all cases of cystitis in which the cause of the disease 
 is not obvious the urinary sediment should be very care- 
 fully searched for tubercle bacilli. In case the organisms 
 can not be found a guinea-pig should be inoculated with a 
 portion of the sediment (^ to i c.c), and the result of this 
 experiment obtained, before eliminating the diagnosis of 
 tuberculosis. (See Detection of Tubercle Bacilli in the 
 Urinary Sediment, p. 323.) 
 
 TUMORS OF THE BLADDER. 
 
 Tumors of the bladder may be either benign or malig- 
 nant. 
 
 The benign tumors include the fibromata, fibromyx- 
 omata, and papillomata ; of these the latter are by far the 
 most frequent. Fibromata and fibromyxoviata grow from 
 the submucous coat of the bladder ; they are either sessile 
 or pedunculated, and are covered by unaltered mucous 
 membrane or by villi. Papillomata grow from the super- 
 ficial layer of the mucous membrane ; they appear as red 
 vascular masses, usually with long pedicles, and occasion- 
 ally they are sessile. Sometimes the papillae are long and 
 slender and float in the urine in numerous filaments from a 
 common base ; sometimes the mass has a cauliflower ap- 
 pearance, this form of tumor constitutes the so-called villous 
 growtJi of the bladder. (In Fig. 53 the masses represent 
 small portions of very small villi in which characteristic
 
 TUMORS OF THE BLADDER. 
 
 349 
 
 small caudate cells are arranged about a central cone of 
 fibrous tissue, blood-vessels, etc. The caudate cells have 
 prominent and relatively large nuclei, and are somewhat 
 larger than the average cell from the superficial layer of the 
 pelvis of the kidney. In papillomatous disease of the 
 bladder cells of this kind may be found in the sediment 
 singly or in clumps.) Frequently, they undergo ulceration ; 
 
 
 ^»fe 
 
 fe^i^ 
 
 
 ?- % 
 
 W&f/ . 
 
 
 ^ 
 
 
 
 « 
 
 
 
 cv < 
 
 
 b 
 
 "V ' 
 
 
 Fig- 53- — Portions of a villous growth of the bladder: a. Magnified 190 diameters; 
 d, magnified 370 diameters. 
 
 they sometimes bleed very freely. Nearly all vesical 
 growths tend to assume a papillomatous character. When 
 the fibrous elements are numerous, the structure is denser ; 
 this constitutes the fihropapillonia. There is reason to be- 
 lieve that a growth originally purely papillomatous may 
 become malignant in its later stages (" American Text- 
 book of Surgery ").
 
 350 DISEASES OF THE URINARY TRACT. 
 
 Malignant tumors of the bladder, although for the most 
 part papillomatous, belong either to the order of sarcomata 
 or to carcinomata. (See Cancer of the Prostate.) 
 
 The prominent symptoms of tumor of the bladder are 
 those of a chronic cystitis. (See p. 345.) Intermittent 
 hematuria is a common symptom. Pain is usually not so 
 marked as in the average case of chronic cystitis, and it 
 may even be absent, especially if the disease does not in- 
 vade the trigone (Fenwick). Frequency of micturition is 
 an early and constant symptom. 
 
 Character of the Urine. — The urine has much the same 
 characteristics as in chronic cystitis, except that the reaction 
 is generally acid ; there is a bloody or smoky color, and on 
 account of the quantity of blood, a comparatively high 
 percentage of albumin. Blood may be present in large 
 amount ; in fact, the quantity of blood is often greater than 
 in almost any other disease of the urinary tract. Large 
 blood-clots may partially fill the bladder, and not infre- 
 quently they are the cause of retention of urine. The 
 blood is usually not so intimately mixed with the urine as 
 when it comes from the kidney. 
 
 After the urine has settled and the blood has been de- 
 stroyed (see p. 231), shreds are frequently seen floating in 
 the urine. Upon microscopic examination these may be 
 found to consist of pus and cells embedded in mucin, or 
 bits of tissue perhaps resembling the mass represented in 
 figurc 53 (villous growth). Inferences as to the nature 
 of these shreds — whether malignant or benign — can not 
 usually be drawn from a microscopic examination of the 
 sediment. Sometimes, as previously stated, the sediment 
 contains caudate cells, single or in clumps, which will lead 
 to the diagnosis of villous growths. Likewise, medium and 
 small round and irregular cells with prominent and rela- 
 tively large nuclei may be found, suggesting a new growth 
 of the bladder. Usually, the epithelial elements are a pre- 
 dominant feature of the sediment. 
 
 Following the introduction of sounds or bougies into the 
 bladder, the urine often contains cells (caudate, large and 
 small round) that have been mechanically detached from 
 the mucous surface. These cells are found both singly and 
 in clumps ; and care should be taken not to mistake them 
 for cells of a new growth.
 
 ACUTE PROSTATITIS. 351 
 
 PROSTATITIS. 
 
 An inflammation of the prostate gland may be either 
 acute or chronic, and parenchymatous or foHicular. 
 
 In the parciicliymatous form the inflammation afiects the 
 whole substance of the gland, and constitutes the severer 
 acute forms of prostatitis. 
 
 ACUTE PROSTATITIS (PARENCHYMATOUS). 
 
 Causes. — Among the causes of this condition may be 
 enumerated gonorrhea, urethral stricture, extreme and pro- 
 longed sexual excitement, concentrated and highly acid 
 urine, exposure to cold and wet, violence from instruments, 
 fragments of calculi, trauma, etc. It may also result from 
 the action of chemic irritants, strong urethral injections, the 
 internal administration of cantharides, etc. Gonorrheal in- 
 flammation, after the first week, may extend to the prostate, 
 particularly if the patient indulges in liquor, sexual inter- 
 course, or uses strong injections throwing them deep into 
 the urethral canal, or takes violent exercise. Sometimes, 
 during gonorrhea, the prostate becomes inflamed without 
 an exciting cause. The inflammation behind a stricture 
 may extend back and involve the prostate in the same way. 
 Sexual hyperemia, too much prolonged or too often re- 
 peated, may lead to an acute prostatitis. 
 
 Prominent Symptoms. — The organ swells rapidly, put- 
 ting the capsule on the stretch, and often reaches the size of a 
 small orange. The exploring finger in the rectum strikes at 
 once against an unevenly enlarged mass that projects into 
 the cavity of the intestine. It is very tense and hot, ex- 
 tremely tender, and can be felt distinctly to pulsate. The 
 lightest touch, even the presence alone of the finger in the 
 rectum, at once excites a marked desire to micturate ; pres- 
 sure over the pubes has the same result. The patient may 
 have an unnatural desire to defecate ; if he endeavors to 
 do this, he strains ineffectively, causing pain, but getting no 
 relief. There is subjectively a feeling of weight, heat, and 
 throbbing, and sometimes pain in the back and limbs. The 
 stream of urine is usually small, and occasionally there is 
 complete retention of urine as a result of the swelling. 
 Almost invariably there are an associated congestion of the 
 vesical neck and a consequent extreme tenesmus. The urine 
 causes pain in its passage, but the pain is most severe when
 
 352 DISEASES OF THE URINARY TRACT. 
 
 the last drops of urine are being expelled. There is gener- 
 ally febrile disturbance, and the patient is usually irritable, 
 despondent, and suspicious. 
 
 Character of the Urine. — Quantity. — The twenty-four- 
 hour quantity is small — generally between 500 and lOOO c.c. 
 
 Color. — High or bloody. 
 
 Reaction. — Strongly acid. 
 
 Specific Gravity. — Usually high — 1025 to 1035. 
 
 Normal Solids. — Relatively, increased; absolutely, 
 diminished. If the acute process lasts more than two or 
 three days, the solids will be much diminished absolutely. 
 
 Albumin. — Usually between yi and 3^ of i per cent. ; 
 but the quantity is dependent chiefly on the amount of 
 blood and pus present. 
 
 Sediment. — Chiefly normal blood. Considerable pus, 
 both free and in clumps ; many small round cells and a 
 marked excess of cells from the prostatic region (neck of 
 bladder) ; frequently there are spermatozoa and cells from 
 the seminal passages. Occasionally, casts of the prostatic 
 ducts are present, and with difficulty distinguished from 
 casts of the renal tubules, which may also be present as a 
 result of a coincident renal congestion. 
 
 Diagnosis. — The clinical picture of the case is generally 
 sufficient for a diagnosis without an analysis of the urine. 
 In some instances, however, the diagnosis between an acute 
 prostatitis and acute cystitis is not easy, but can often be 
 made by attention to the following points : 
 
 Acute Prostatitis. Acute Cystitis. 
 
 Perineal and rectal pain. Possibly a little tenderness of the 
 
 perineum on pressure, but little or 
 no rectal pain. 
 Pain violent and throbbing, aggra- Pain burning, not especially affected 
 
 vated during defecation. by defecation. 
 
 Stream of urine diminished in size. Size of stream not usually affected. 
 
 Retention of urine common. Retention of urine much less com- 
 
 mon. 
 Rectal examination shows enlarge- No prostatic enlargement or tender- 
 ment and extreme tenderness of the ness recognizable on rectal exam- 
 
 prostate, ination. 
 
 Urinary sediment contains blood, pus. Urinary sediment contains, besides 
 marked excess of epithelium from blood and pus, much squamous 
 
 prostatic region, spermatozoa, and epithelium, usually no marked ex- 
 
 prostatic casts. cess of cells from prostatic region, 
 
 and no spermatozoa nor prostatic 
 casts. 
 
 A greater or less involvement of the neck of the bladder 
 is often an accompaniment of an acute prostatitis.
 
 PROSTATIC ABSCESS. 353 
 
 PROSTATIC ABSCESS. 
 
 An abscess of the prostate is liable to form as the result 
 of a parenchymatous inflammation of the organ. There may 
 be one or more purulent foci, or the whole substance of the 
 prostate contained within its fibrous capsule may suppurate. 
 
 The symptoms are in many respects similar to those of 
 an acute prostatitis. A sharp chill or a series of rigors 
 announces the beginning of suppuration. As the pus 
 forms it presses upon the already narrowed canal of the 
 urethra ; and, finally, unless the abscess is veiy small, 
 obliterates it entirely, causing retention of urine. There 
 are usually local throbbing and lancinating pain. These 
 abscesses, left alone, discharge into the bladder, urethra, 
 rectum, or through the perineum. When such an abscess 
 opens spontaneously, all pain and discomfort are immedi- 
 ately relieved. A small purulent collection in the prostate 
 may empty itself gradually into the urethra by one or 
 more minute openings ; in such cases the diagnosis of a 
 prostatic abscess is not easily made. 
 
 Character of the Urine. — This will vary according to 
 circumstances : If the abscess is forming and has not yet 
 opened, the urine will be concentrated, of high color, and 
 high specific gravity, containing a very small amount of 
 albumin ; the sediment will consist of a few leucocytes, 
 blood globules, and an excess of cells from the neck of the 
 bladder or prostatic urethra — in other words, di fever tirine, 
 in which the sediment presents the evidences of an irrita- 
 tion in the prostatic region. On the other hand, if the 
 abscess has ruptured, the urine, with the exception of 
 the sediment, will present the characteristics of that of 
 severe chronic prostatitis. The sedhncnt, which is abundant 
 and often greenish in color, will consist chiefly of pus, both 
 free and in clumps, that in clumps usually being much 
 degenerated ; many small round cells, some fatty, and 
 generally a few compound granule cells ; and few or num- 
 erous blood globules. There is also an excess of cells 
 from the prostatic region. 
 
 CHRONIC PROSTATITIS. 
 
 Causes. — A chronic inflammation of the prostate gland 
 may be the result of an acute prostatitis. In some in- 
 stances, as following sexual excesses, masturbation, etc., the 
 23
 
 354 DISEASES OF THE URINARY TRACT. 
 
 pathologic process in the organ starts as a sHght irritation 
 that gradually increases, finally becoming a well-marked 
 chronic condition without passing through an acute stage. 
 A chronic prostatitis may result from stricture of the urethra, 
 contracted meatus, phimosis, hypertrophy of the prostate in 
 persons past the age of fifty-five, tuberculosis, trauma, irri- 
 tation by crystalline elements, etc. 
 
 Prominent Symptoms. — Perhaps the most prominent 
 symptom of this condition is frequency of micturition. 
 There are usually some pain and a feeling of uneasiness at 
 the neck of the bladder, especially toward the close of uri- 
 nation, and often pain at the end of the penis and along 
 the under surface of the urethra. There may be a muco- 
 purulent discharge from the urethra, but this is not gen- 
 erally the case. Defecation is sometimes painful. Walk- 
 ing causes pain, and crossing the legs decidedly increases 
 it. As the disease advances, the sitting posture be- 
 comes painful. Retention of urine is common. Constitu- 
 tional disturbance may be absent, particularly in mild 
 cases ; when the disease is marked, however, there may be 
 more or less fever and mental depression. The finger in 
 the rectum may find slight enlargement and at times detect 
 extra sensibility. 
 
 If the disease is the result of Jiypertrophied prostate, not 
 only will the enlargement be apparent to the finger in the 
 rectum, but signs of mechanical obstruction to the outflow 
 of urine will be prominent ; the stream will be interrupted 
 and show a lack of force ; the patient will be unable to 
 completely empty the bladder, only passing that which is 
 in excess. This "residual" urine may remain stationary 
 in amount, but more often it gradually increases until, in 
 some cases in which both hypertrophy of the prostate and 
 atony of the bladder are marked, only an ounce or two of 
 urine can be evacuated voluntarily, although catheterization 
 will show that the bladder contains possibly a pint or more. 
 The decomposition of the retained urine invariably results 
 in a chronic cystitis ; often a pyelonephritis develops ; 
 general sepsis occurs ; and the patient becoming uremic 
 dies during coma. 
 
 Fortunately, a fatal termination is not the outcome of all 
 cases of chronic prostatitis ; some are amenable to treatment 
 and entirely recover, especially the milder cases and those
 
 CHRONIC PROSTATITIS. 355 
 
 which are not tubercular, or those in which an abscess of the 
 prostate lias not developed. 
 
 Character of the Urine. — Quantity. — The total quantity 
 for twenty-four hours is usually between 800 c.c. and 
 1200 c.c. 
 
 Color. — Pale. The urine is generally turbid, due to the 
 presence of a large amount of pus in suspension. 
 
 Reaction. — Usually acid ; if there is an accompanying 
 chronic cystitis, the reaction may be alkaline, especially in 
 cases of hypertrophy of the prostate. 
 
 Specific Gravity. — This will generally be found to vary 
 between 1012 and 1018 — average about 10 15. 
 
 Normal Solids. — Both relatively and absolutely, dimin- 
 ished ; the degree of diminution will depend largely on the 
 amount of constitutional disturbance. 
 
 Albumin. — The quantity of albumin will depend on the 
 amount of pus and blood ; it usually varies between a very 
 slight trace and ^ of i per cent. In case there is an accom- 
 panying disturbance or disease of the kidney the amount of 
 albumin will be proportionately higher. 
 
 Sediment. — This is abundant, and consists chiefly of pus, 
 both free and in clumps ; many small round cells, some of 
 which are fatty ; also an excess of cells from the neck of the 
 bladder and prostatic urethra ; a few (sometimes numerous) 
 blood globules ; and sometimes spermatozoa, and the highly 
 granular cells from the seminal passages. Prostatic plugs 
 (cylinders of long diameter resembling large renal casts or 
 bodies of irregular shapes from dilated ducts or cavities), 
 sometimes with spermatozoa embedded, are of frequent 
 occurrence, especially in the mild (follicular) forms of 
 chronic prostatitis. Frequently, the sediment contains large 
 and small shreds that will be found to consist of pus, small 
 round cells, and dense cells from the prostatic region, which 
 are embedded in mucin (nucleo-albumin). If there is an 
 accompanying chronic cystitis, as is the rule in cases of 
 hypertrophied prostate, the sediment will contain more or 
 less squamous epithelium, and frequently crj^stals of triple 
 phosphate. A renal disturbance that is probably indirectly 
 due to the chronic prostatitis, and perhaps the result of the 
 absorption of toxines, is not uncommon. An occasional or 
 a few renal casts may be found in the sediment, which are 
 sometimes distinguished with difficulty on account of the 
 abundance of pus.
 
 356 DISEASES OF THE URINARY TRACT. 
 
 TUBERCULAR PROSTATITIS. 
 
 This disease of the prostate is almost invariably associ- 
 ated with tuberculosis of some other part of the genito- 
 urinary tract. The disease occurs in tubercular, debilitated 
 subjects, its chief feature being cheesy degeneration, situ- 
 ated for the most part in the ducts and follicles of the 
 organ. True miliary tubercle does not seem to occur in 
 the prostate. 
 
 The symptoms are those of a severe chronic prostatitis. 
 Generally, there is more or less frequency of micturition. 
 The symptoms become spontaneously better or worse, but 
 the general tendency is toward steady aggravation. The 
 cheesy masses ulcerate, form abscesses that break in all 
 directions, leaving open cavities or fistulas. Intermittent 
 hemorrhage from the urethra is quite a constant symptom. 
 The disease is probably more common than has hitherto 
 been supposed. 
 
 Character of the Urine. — Quantity. — The twenty-four- 
 hour quantity is usually not far from looo c.c. 
 
 Color. — Pale. The freshly passed urine is usually tur- 
 bid, and sometimes it is opaque. 
 
 Reaction. — Acid. 
 
 Specific Gravity. — Usually, below the average normal, 
 varying between 1012 and 1018. 
 
 Normal Solids. — Both relatively and absolutely, dimin- 
 ished, but dependent largely on the extent of the constitu- 
 tional disturbance and the appetite. 
 
 Albumin. — This varies as the amount of pus and blood 
 present in the urine ; it is usually from a slight trace to a 
 large trace. 
 
 Sediment. — This is generally abundant and consists 
 chiefly of pus both free and in clumps ; a large number 
 of small round cells, some of which are fatty ; often an 
 excess of dense round cells from the neck of the bladder 
 and prostatic urethra ; and a few (sometimes numerous) 
 blood globules. When the freshly passed urine is examined, 
 the pus is often found to be ameboid. Large clumps of 
 degenerated and disintegrated pus and cells are occasion- 
 ally found. 
 
 A urine having the above characteristics should always 
 be examined for tubercle bacilli, which, however, are usu- 
 ally difficult to find, but occasionally they are present in
 
 CANCER OF THE PROSTATE. 357 
 
 large numbers. (For details concerning the examination 
 for tubercle bacilli, see p. 323.) If the bacilli are not found 
 in the sediment after repeated trials, a guinea-pig should be 
 inoculated with a portion of the sediment in order to deter- 
 mine positively their presence or absence. 
 
 CANCER OF THE PROSTATE. 
 
 Primary cancer of the prostate is exceedingly rare. It is 
 usually secondary to carcinoma or sarcoma elsewhere, es- 
 pecially in the kidney or testicle. The scirrhous, melanotic, 
 and medullary forms have all been noted ; of these the latter 
 is perhaps the most frequent. 
 
 The symptoms at first are those caused by an in- 
 crease in the size of the organ, such as obstruction to 
 the outflow of urine, frequency of micturition, and pain. 
 The early symptoms are not pathognomonic. Later in 
 the disease the cancerous cachexia, glandular enlargement, 
 and the evidences of a cancerous affection elsewhere in the 
 body are usually sufficiently prominent to suggest cancer 
 of the prostate. Rectal examination may be of value in 
 determining the form of cancer that exists. Hematuria is 
 common. 
 
 Urine. — An analysis of the urine is often of but little 
 value in the diagnosis of cancer of the prostate. The charac- 
 teristics of the urine are usually those of chronic prostatitis. 
 The urine may, from time to time, contain a large amount of 
 blood. Occasionally, the presence of a large number of 
 medium and small round cells, with relatively large and 
 prominent nuclei, may suggest the presence of malignant 
 disease of the prostate. 
 
 The diagnosis of cancer of the prostate is very difficult 
 if the disease appears after the organ has from any cause 
 become hypertrophied. 
 
 URETHRITIS. 
 
 Of all the diseases encountered in genito-urinary surgery 
 urethral inflammation is the most common. Although 
 strictly a local affection, and exerting little or no poisonous 
 action upon the blood, it is the most venereal of all venereal 
 diseases, since it is the commonest malady acquired during 
 the copulative act.
 
 358 DISEASES OF THE URINARY TRACT. 
 
 The term nrctJiritis signifies simple inflammation of the 
 urethra. The term gonorrJiea, although etymologically 
 inaccurate, indicating as it does a flow of semen, has been, 
 and is still, universally employed and considered, especially 
 among the laity, to have the same meaning as the term 
 urethritis. But a gonorrhea is in all probability due to a 
 specific organism — the gonococcus. A gonorrhea is a ure- 
 thritis, but the converse is by no means always true, since 
 urethral inflammation may have a variety of causes other 
 than an infection with the gonococcus. For practical pur- 
 poses it is better to retain the two terms, calling that gonor- 
 rhea that has been unmistakably derived from an individual 
 of the other sex with a gonorrhea, and reserving the term 
 urethritis for all inflammatory urethral discharges having 
 another origin. Or the term simple jwcthritis may be used 
 to indicate those conditions in which the gonococcus is 
 absent, and specific Jiretlwitis to indicate those in which the 
 gonococcus is present. 
 
 Causes. — Simple Urethritis. — Authentic cases are on 
 record of well-marked urethritis following exposure to 
 leucorrheal discharges ; to the pus from a healthy abscess, 
 or from a purulent bronchial catarrh ; to the secretion from 
 an endocervicitis or endometritis ; to the discharge result- 
 ing from ulceration or malignant disease of the uterus ; to 
 menstrual fluid or acrid vaginal discharges ; to power- 
 ful injections ; to the irritating influences of crystalline ele- 
 ments or the passage of a calculus ; to catheterization ; to 
 exposure to cold and wet ; to a concentrated urine ; to 
 the action of certain drugs — cantharides ; to the extension 
 of inflammatory diseases from the prostate or bladder ; 
 occasionally, to the free use of alcoholic drinks, especially 
 beer — the so-called " beer clap " ; and to many other non- 
 specific causes. 
 
 Specific Urethritis or Gonorrhea. ^ — There is scarcely 
 a shadow of doubt but that the cause of gonorrhea is the 
 gonococc7is of Neisser. (See p. 266.) The microscopic 
 detection of this micro-organism is, so far as known, the 
 only safe means of distinguishing between specific urethritis 
 and a simple urethritis. 
 
 Prominent Symptoms. — The most constant symptom of 
 a simple urethritis is a urethral discharge. On the first, 
 
 1 For details concerning thi.s disease, see special works on genito-urinary 
 surgery.
 
 URETHRITIS. 359 
 
 second, or third day after having indulged in sexual inter- 
 course, perhaps with a partner having an extensive leucor- 
 rhea, the first symptom noticed is a slight, uneasy sensation 
 at the meatus, a Httle smarting, and a pearly drop of pus at 
 the meatus ; or perhaps the lips of the urethra are glued 
 together in the morning on rising. The inflammation will 
 probably not run high or last long, and upon microscopic 
 examination specific gonococci will not be found. In some 
 instances the discharge is -profuse, the inflammation runs 
 high and continues for weeks, and with the exception of 
 the absence of gonococci the disease can not be distinguished 
 from true gonorrhea. There may be pain all along the 
 pendulous urethra, and the canal is sensitive to pressure ; 
 the meatus feels hot and sore, and urination is frequent and 
 painful. Chordee may be as prominent as in a true gonor- 
 rheal inflammation. An acute prostatitis or cystitis may 
 follow. General systemic disturbance is sometimes marked. 
 Organic stricture may follow a simple urethritis. 
 
 Character of the Urine. — Quantity. — Usually dimin- 
 ished — 800 c.c. to 1200 c.c. 
 
 Color. — Normal or high. The urine is generally more 
 or less turbid owing to the pus and epithelial cells in sus- 
 pension. 
 
 Specific Gravity. — From 1020 to 1030, but dependent 
 on the concentration of the urine. 
 
 Reaction. — Usually, strongly acid. 
 
 Normal Solids. — Relatively, normal or increased ; abso- 
 lutely, normal. In those cases in which marked constitu- 
 tional disturbance exists the solids are generally absolutely 
 diminished. 
 
 Albumin. — Albumin is invariably present ; the quantity 
 is dependent on the amount of blood and pus present ; it 
 usually varies between iht slightest possible trace and a large 
 trace. 
 
 Sediment. — Chiefly dense pus ; many urethral cells 
 and an occasional (or few or numerous) blood globule ; 
 often an excess of mucin (nucleo-albumin). If the inflam- 
 matory process is most marked in the prostatic urethra, 
 cells from that region, as well as cells from the neck of the 
 bladder, will be found with the pus. In case of an organic 
 stricture, or gleet, the pus and cells will be found chiefly in 
 shreds of mucin (nucleo-albumin). 
 
 The urine should be carefully watched for evidences of
 
 360 DISEASES OF THE URINARY TRACT. 
 
 a complicating prostatitis or cystitis, in which case the 
 amount of pus will be larger, and the quantity of blood 
 greater than in a urethritis. There will also be an unusual 
 number of cells from the prostatic region, and, perhaps, 
 casts of the prostatic ducts and spermatozoa ; or, in case of 
 cystitis, an abundance of squamous epithelium. 
 
 In all cases of urethritis of doubtful origin, a thorough 
 search for gonococci should be made. (For method of 
 staining, see p. 266.) 
 
 CHYLURIA. 
 
 This is a condition that results from a pathologic commu- 
 nication between the lymphatic system and the urinary 
 
 o <^>!?<^<^^« *Q^er ^"P^ 
 
 C^°^-^M 
 
 ,'^*v 
 
 
 Fig. 54. — The filaria sanguinis hominis. The head can be seen at the left of cut : 
 the tail, at the right. The parasite is inclosed within a hyaline capsule. Magnified 
 2S0 diameters. 
 
 passages. Under such circumstances the urine has a milky 
 appearance, due to the presence of chyle. The cause of 
 this disease is a parasite — the filaria sangtihds Jiominis (see 
 Fig. 54) — that invades the blood and obstructs the lymph- 
 atic channels, finally resulting in the rupture of a lymph- 
 atic vessel. The disease appears to be confined chiefly to 
 the tropics (India, China, Bermuda, Brazil, Australia, and the 
 West Indies), or to those individuals who have spent much 
 of their lives there. Guiteras has shown that the disease is 
 not uncommon in the Southern States. It is of very rare 
 occurrence in the New England States, the author having 
 met with only one case ; in this case the filaria was readily
 
 CHYLURIA. 361 
 
 found in the blood. Besides the endemic form of this dis- 
 ease, it is very rarely met with following traumatism and 
 disease in which an abnormal communication has formed 
 between the lymphatics and the urinary tract. Osier refers 
 to a nonparasitic form of chyluria. The disease affects alike 
 both males and females, and may occur at any age. 
 
 A peculiar feature of the parasite is that it works at 
 night, or while the patient is in the recumbent position, being 
 quiescent while the patient is up and about. In conse- 
 quence, the night urine is milky, while that passed during 
 the day is clear and usually of normal color ; but if the in- 
 dividual sleeps or reclines during the day, the urine passed 
 at that time is milky. 
 
 Characteristics of the Urine.— The characteristics of a 
 chylous urine are as follows : 
 
 Quantity. — This is usually below the average normal — 
 1500 c.c; it may, however, be normal or slightly increased. 
 
 Color. — Milky. Opaque. Occasionally, the urine is 
 slightly tinged with blood. 
 
 Reaction. — Acid. 
 
 Specific Gravity. — Usually, normal or sHghtly dimin- 
 ished ; it may be as low as 10 10, particularly if the quantity 
 of urine is moderately increased. 
 
 Normal Solids. — Relatively, normal or slightly dimin- 
 ished. Absolutely, slightly diminished, especially the urea 
 and chlorides. The phosphates may be moderately in- 
 creased. 
 
 Albumin. — This will depend chiefly on the amount of 
 blood present in the urine. Usually, the quantity varies be- 
 tween the slightest possible trace and a trace. Owing to the 
 opacity of the urine, the usual tests for albumin can not be 
 satisfactorily applied. It is necessary to first remove the fat 
 in suspension by shaking with ether ; then either the nitric 
 acid or the heat test can be applied to the clear urine in the 
 usual manner. 
 
 Sediment. — Slight ; often no sediment is visible on in- 
 spection. Chiefly fine granular matter, a few leucocytes, 
 and an occasional (or few, and sometimes numerous) blood 
 globule. Perhaps, rarely a hyaHne and granular cast and 
 renal cell may be found. Casts are not always present. No 
 fat globules are discernible by the microscope. Often a few 
 uric acid crystals may be seen. The filaria has been found 
 in the urine, but its presence is, by no means, constant.
 
 362 DISEASES OV THE URINARY TRACT. 
 
 The fat in a chylous urine is in a com[)lcte state of emul- 
 sion, and since it can not be seen microscopically, i/s pres- 
 ence is dcteruiiiicd with certainty only by shaking with ether. 
 The ether takes up the fat and leaves the urine clear and 
 of normal appearance. The fat does not separate from a 
 freshly passed chylous urine, or one that has been hermeti- 
 cally sealed or is sterile — that is, the fat does not rise to 
 the surface as in the case of milk. Dr. E. S. Wood has in 
 his possession a specimen of chylous urine that he sealed 
 up while it was fresh (sterile) in the year 1874. The fat 
 has not separated and the specimen has its original appear- 
 ance. When, however, a urine containin<j chyle is allowed 
 to stand exposed to the air, it undergoes the usual ammo- 
 niacal fermentation and the fat rapidly separates, rising to 
 the surface, as in milk. 
 
 Sometimes a chylous urine undergoes spontaneous co- 
 agulation on standing ; occasionally, coagulation takes 
 place in the bladder, and may give rise to most distressing 
 symptoms until it is broken up and removed. The firm, 
 vibrating, jelly-like clots that form after the urine is voided 
 often resemble corn-starch bianc mange. This characteris- 
 tic of a chylous urine is dependent upon the presence of 
 fibrin, the quantity of which varies considerably ; usually, 
 it is not present in sufficient amount to cause coagulation. 
 
 A chylous urine should always be distinguished from a 
 urine to which milk has been added either accidentally or 
 intentionally. In such a urine the individual globules of 
 fat are readily made out under the microscope, and the fat 
 is not separated from the urine by shaking it with ether. 
 
 HEMOGLOBINURIA. 
 
 Hemoglobinuria is a condition that is characterized by 
 the presence of blood coloring-matter in the 7irine, with very 
 few, if any, of the corpuscidar elements of the blood. This 
 condition should in all instances be distinguished from a 
 hematuria which indicates the presence of both blood pig- 
 ment and corpuscular elements. (See p. 232.) Hemo- 
 globinuria is the result of the destruction of the red blood- 
 corpuscles within the blood-vessels or tissues ; the blood 
 coloring-matter that is then set free finds its way into the 
 urine. The blood pigment, as found in the urine under 
 these circumstances, is generally in the form of oxyhemo-
 
 HEMOGLOBINURIA. 363 
 
 globin and hematin, although, according to Hoppe-Seyler ^ 
 and HalHburton,^ in some instances the pigment may be in 
 the form of methemoglobin (spectroscopic examination). 
 Two cHnical groups of this condition may be distinguished : 
 
 (a) Toxic Hemoglobinuria. — This is induced by poisons 
 that cause rapid destruction of the blood-corpuscles, such 
 as carbon monoxide, arseniureted hydrogen, muscarine, 
 potassium chlorate (in large doses) ; also the poisons of 
 scarlet fever, malaria, yellow fever, typhus fever, purpura 
 hemorrhagica, scurvy, and syphilis. It is quite common 
 following extensive burns. Exposure to cold and violent 
 muscular exercise are stated to produce hemoglobinuria, 
 but such instances have not been observed by the author. 
 Epidemic hcnwglobimiria (Winckel's disease) occurs in the 
 new-born. It begins about the fourth day of life, and is 
 associated with jaundice, cyanosis, and nervous symptoms. 
 This form of disease should be distinguished from sim- 
 ple icterus neonatorum, with which there may be blood and 
 blood coloring-matter. According to Osier, this condi- 
 tion is probably an acute infectious disorder. 
 
 (b) Paroxysmal Hemoglobinuria. — This form of dis- 
 ease has been found in persons subject to various forms of 
 Raynaud's disease. It is also associated with cold and 
 exertion, and has been brought on in susceptible persons 
 by the use of a cold foot-bath. This form of hemoglobin- 
 uria is not infrequent in malaria. According to Bastianelli, 
 it practically never occurs except in infections with the 
 estivo-autumnal parasite. This -condition should not be 
 mistaken for malarial hematuria. 
 
 The attacks may be preceded by chills and fever ; in other 
 instances the temperature is subnormal. There may be 
 vomiting and diarrhea. Pain in the lumbar region is not 
 uncommon. Jaundice has been present in a number of 
 cases. The paroxysms rarely persist for more than a day 
 or two. Paroxysmal hemoglobinuria is more common in 
 males than in females, and occurs chiefly during adult life. 
 
 Character of the Urine. — Quantity. — This is usually 
 below the normal. If much fever, the quantity may not 
 exceed 500 or 800 c.c. 
 
 Color. — Smoky or dark brown. In extreme cases the 
 urine may be black. 
 
 1 Hoppe-Seyler, "Physiol. Chemie.," S. 862. 
 
 2 Halliburton, "Chemical Physiology and Pathology," p. 777.
 
 364 DISEASES OF THE URINARY TRACT. 
 
 Reaction. — Generally acid ; if the urine is highly con- 
 centrated, the reaction may be strongly acid. 
 
 Specific Gravity. — Usually, normal or high — from 1020 
 to 1030. 
 
 Normal Solids, — Absolutely, diminished ; the degree of 
 diminution will depend largely on the disease that causes 
 the hemoglobinuria. Relatively, increased or normal. 
 
 Albumin. — This varies between a trace (mild cases) 
 and y>, of I per cent, (severe cases). The quantity of 
 albumin corresponds to the amount of blood pigment 
 present. 
 
 Sediment. — Chiefly brown granular matter, colored by 
 the hematin. An occasional, or few, brown and fine gran- 
 ular, and often numerous brown granular, casts. Rarely, 
 an occasional blood globule. The number of blood 
 globules bears no proportion whatever to the intensity of 
 the color of the urine. There are usually, also, a {Q.\y 
 brown-stained squamous and renal cells. 
 
 The diagnosis of hemoglobinuria depends upon the dark- 
 brown color, the virtual absence of corpuscular blood ele- 
 ments, the large quantity of albumin, and the detection of 
 blood pigment by means of Teichmann's test (see p. 235) 
 or the spectroscope. Hemoglobinuria should always be 
 distinguished from hematuria ; it should not be confounded 
 with the dark-brown urines seen after the external or inter- 
 nal use of carbolic acid, pyrogallic acid, salol, naphthol, and 
 other petroleum compounds, in which the color deepens as 
 the urine stands exposed to the air, and in which the quan- 
 tity of albumin is small. Hemoglobinuria should not be 
 mistaken for melanuria, or hemotoporphyrinuria. Spectro- 
 scopic examination is usually of value in deciding as to the 
 nature of the pigment present. 
 
 PNEUMATURIA. 
 
 The passage of gas with the urine is not a common con- 
 dition. Gas may gain entrance to the bladder by the fol- 
 lowing means: (i) From mechanical causes, as vesical 
 irrigation or cystoscopic examination in the knee-chest posi- 
 tion. (2) By developing in the viscus, follow^ing the intro- 
 duction of gas-forming organisms in catheterization or other 
 operations. The yeast fungus, the colon bacillus, and the 
 bacillus aerogenes capsulatus have been found. (3) By
 
 UREMIA. S65 
 
 communication with some air-holding viscus, as in cases of 
 vesico-enteric fistula. 
 
 Most cases of pneumaturia occur in old men with enlarged 
 prostates, or in case of obstruction from stricture of the ure- 
 thra. The passage of the gas is usually at the end of mic- 
 turition, and sometimes may be accompanied by a loud 
 sound. The diagnosis is readily made by causing the pa- 
 tient to urinate while bathing or by plunging the end of 
 the catheter in water. 
 
 UREMIA. 
 
 A toxemia developing in the course of nephritis or in 
 conditions associated with anuria, usually results in a train 
 of symptoms that have received the name uremia. The 
 nature of the poison or poisons that produce these symp- 
 toms is as yet unknown. 
 
 Many theories as to the cause of uremia have been ad- 
 vanced. The view most widely held is that the condition 
 is due to the accumulation in the blood of waste substances 
 — body poisons — that should be thrown off by the kidneys. 
 As Carter has said, " If, however, from any cause, these 
 organs [the kidneys] make default, or if there be any pro- 
 longed obstruction to the outflow of urine, accumulation of 
 some or of all the poisons takes place, and the characteristic 
 symptoms are manifested ; but the accumulation may be 
 very slow, and the earlier symptoms, corresponding to the 
 comparatively small dose of poison, may be very slight ; 
 yet they are in kind, though not in degree, as indicative 
 of uremia as are the more alarming symptoms, which ap- 
 pear toward the end, and to which alone the name uremia 
 is often given." 
 
 Another view is that uremia depends on the products of 
 abnormal metabolism. Hughes and Carter concluded, from 
 a careful study of this question, that the poison is of an albu- 
 minous nature ; in fact, quite different from anything found 
 in normal urine. Herter and others have shown that the 
 toxicity of the blood-serum in uremic states is much in- 
 creased. Brown-Sequard suggested that the kidneys have 
 an internal secretion, and it is urged that the symptoms of 
 uremia are due to their disturbance. Traube believed that 
 the symptoms of uremia, particularly coma and convul- 
 sions, were due to localized edema of the brain. 
 
 It is safe to say that we know practically nothing of the
 
 366 DISEASES OF THE URINARY TRACT. 
 
 cause of uremia. Experiments have shown that urea is 
 probably not a causative agent ; but how much the other 
 urinary salts and the nitrogenous extractives have to do 
 with the condition has not yet been determined. Bouchard 
 claims to have separated from the urine no less than seven 
 different substances that play a part in uremia : 
 
 1 . Diuretic substance : fixed, organic, and in reality urea. 
 
 2. Narcotic substance : fixed, and of organic nature. 
 
 3. Sialogenous substance : organic ; chemic nature un- 
 known. 
 
 4 and 5. Two substances causing convulsions : one (4) 
 may belong to the group of coloring-matters ; it is in reality 
 an alkaloid. The other (5) is the potassium salts. 
 
 6. A substance causing contraction of the pupil : fixed, 
 organic, and comparable in many respects to the organic 
 substance that induces convulsions. 
 
 7. A substance that reduces heat : fixed and organic. 
 Bouchard's observations tend strongly to confirm the 
 
 view now generally held that the symptoms are caused by 
 the retention of excretory products of the body. It must 
 be conceded that the nature of these poisonous ingredients 
 is complex. 
 
 Prominent Symptoms. — From a clinical point of view, 
 uremia may be either acute or chronic. The division of the 
 symptoms as given by the French writers is perhaps most 
 practical, and is as follows: (a) cerebral ; {U) dyspneic ; (r) 
 gastro-intestinal . 
 
 Among the cerebral manifestations are (i) mania; (2) 
 delusional insanity; (3) convulsions; (4) coma ; (5) local 
 palsies ; and a variety of nervous phenomena, such as 
 occipital headache, intense itching of the skin, numbness 
 and tingling in the fingers, and cramps in the muscles of 
 the legs. 
 
 Dyspnea. — This may be paroxysmal or continuous, and 
 there may be Cheyne-Stokes breathing. 
 
 The gastro-intestinal manifestations are usually chiefly 
 nausea and vomiting ; the latter may be almost uncontrol- 
 able. Diarrhea may be present ; sometimes it is profuse 
 and associated with an intense catarrhal or even diphtheric 
 inflammation of the colon. 
 
 Urine. — An examination of the urine is of the greatest 
 value in the diagnosis of uremia. The quantity of urine is 
 usually much diminished ; there may be almost complete
 
 UREMIA. 367 
 
 suppression. On the other hand, the quantity may be nor- 
 mal or even increased. In a case of chronic interstitial 
 nephritis studied by the author at the Boston City Hos- 
 pital, uremic symptoms rapidly developed when, for any 
 reason, the quantity fell from 3500 or 4500 c.c. down to 
 2000 c.c. 
 
 The normal solids are usually diminished, especially 
 the urea, but they may be normal or only slightly reduced. 
 As a rule, the activity of the symptoms bears an inverse 
 ratio to the quantity of urea excreted. Albuuiin is always 
 present in the urine in this condition. It may vary be- 
 tween the slightest possible trace and 3 or 5 per cent., but 
 the quantity will depend upon the nature of the associated 
 lesion. The author has not met with a single instance of 
 uremia in which albumin w^as not present, at least, in the 
 slightest possible trace. The sediment invariably contains ab- 
 normally formed elements, particularly renal casts and renal 
 cells. It may contain a variety of other abnormal elements, 
 such as blood, pus, and ciystaUine elements. Waxy casts 
 are very common in the sediment, especially when the 
 condition accompanies advanced chronic disease of the 
 kidneys. 
 
 Uremia may occur during either an acute or chronic 
 kidney disease. An acute exacerbation of a subacute or 
 chronic nephritis is very liable to be followed by uremic 
 symptoms. So far as the author is aware, uremia never 
 occurs during the course of a simple active hyperemia. 
 
 Puerperal eclampsia, a common complication arising 
 before, during, or after confinement, in all probability is 
 identical with uremia. It may occur in the course of an 
 extensive passive hyperemia of pregnancy, or as the result of 
 a sudden acute nephritis. A woman who has had a per- 
 fectly normal pregnancy may suddenly develop uremia 
 (eclampsia) without previous warning either in the urine or 
 by physical signs. No doubt puerperal eclampsia is the 
 result of a toxemia, and it may have the same cause or 
 causes as uremia. 
 
 Diagnosis. — Uremia should, in ever>^ instance possible, 
 be distinguished from cerebral lesions, such as hemorrhage, 
 meningitis, and even tumors; also epilepsy, acute alcoholism, 
 opium-poisoning, and diabetic coma. For information re- 
 garding the differential diagnosis of uremia, the reader is 
 referred to various works on medicine.
 
 368 THE URINE IN GENERAL DISEASES. 
 
 DIABETES MELLITUS. 
 
 Diabetes mellitus is a disease in which grape-sugar or 
 glucose is excreted in the urine for a long period, — often for 
 many months or years, — and excreted in large quantity or 
 in sufficient amount to give a reaction with the ordinary 
 clinical tests for sugar. But the term diabetes mellitus can 
 not be applied to all cases in which sugar is detected in the 
 urine. Glucose is occasionally present in the urine for a 
 short period only, as after febrile attacks, acute diseases, and 
 injuries, and as a result of the action of certain toxic sub- 
 stances. These are cases of tonporaiy glycosuria, and not true 
 diabetes mellitus. Then, again, after a very large quantity 
 of saccharine food has been taken a small amount of grape- 
 sugar may appear in the urine of many apparently healthy 
 persons, or if the sugar in the diet should exceed a certain 
 limit, a small quantity of it will always be found in the 
 urine ; these are instances of temporary alimentary glycosu- 
 ria (Williamson). 
 
 Causes. — Hereditary influences are important ; instances 
 are on record of its occurrence in many members of the 
 same family. Males are more frequently affected than 
 females, the ratio being about three to two ; this is especially 
 true after the age of thirty. In the early period of life, and 
 before the age of thirty, the liability of the two sexes 
 is about equal. The disease may occur in infancy — under 
 one year — or in extreme old age. Hebrews are especially 
 prone to this disease. It is comparatively rare in the 
 colored race (from 8 to lo per cent, Futcher). In most 
 of the cases of diabetes after thirty years of age the subjects 
 have been excessively/"^/ at the beginning of, or prior to, 
 the onset of the disease. The so-called " fat man's diabe- 
 tes " is not of grave significance, since it is usually the 
 result of excesses of starchy and saccharine diet, and is only 
 occasionally followed by true diabetes. Von Noorden has 
 shown that there may be a " diabetogenous obesity," in 
 which diabetes and obesity develop in early life ; such 
 cases are very unfavorable. Gout, syphilis, and malaria 
 have been regarded as predisposing causes. Severe nervous 
 strain and nervous shock precede many cases. In one 
 instance seen by the author a true diabetes followed severe 
 fright at the sight of a snake. The combination of seden- 
 tary life, close application to business, and overindulgence in
 
 DIABETES AIELLITUS. 369 
 
 food and drink seem especially prone to induce the disease. 
 Injury to, or disease of, the brain and spinal cord is not in- 
 frequently followed by diabetes. In an investitjation of 212 
 cases of traumatic glycosuria by Higgins and Ogden ^ the 
 following results were noted : In cases of scalp wounds and 
 minor head injuries glycosuria was found in 5.95 percent.; in 
 scalp wounds with exposure of bone, 9.3 per cent; in con- 
 cussion, 2.5 per cent.; in fractures of the vault of the 
 skull, 20.8 per cent.; and in fractures of the base, 23.8 per 
 cent. From the examination of these 212 cases the follow- 
 ing conclusions were drawn : 
 
 1. That sugar may appear in the urine as early as six 
 hours after a head injury, and disappear within twenty-four 
 hours ; the average time for its appearance being from eight 
 to twelve hours ; the average time for its disappearance 
 being from the fifth to the ninth day. 
 
 2. That a small proportion of cases exhibit a permanent 
 glycosuria from the date of the injury to the head. 
 
 3. That acetone and diacetic acid are rarely, if ever, found 
 in such cases, excepting when the condition becomes a per- 
 manent glycosuria, and even then probably only after a 
 number of months or years. 
 
 Glycosuria may occur during pregnancy. An irritative 
 lesion of Bernard's diabetic center in the medulla is an occa- 
 sional cause. Glycosuria sometimes occurs during the 
 course or following acute infectious diseases. 
 
 Hibbard and Morrissey ^ found in the observations made 
 on 230 diphtheria cases that glycosuria was present in 25 
 per cent, of all cases examined ; in 17 per cent, of the fatal 
 cases, and in 19 per cent, of those that recovered. The 
 quantity of sugar in these cases varied between a mere trace 
 and 3^ per cent. The time of the appearance of the 
 glucose in the urine varied from the second to the eighteenth 
 day, and the duration varied from one day to several weeks. 
 The authors concluded that, in many instances, antitoxine 
 was the probable cause of the glycosuria. 
 
 A glycosuria sometimes makes its appearance just before 
 death in cases of chronic diffuse nephritis and subacute 
 glomerular nephritis. It appears to be in some way con- 
 nected with the extensive dropsy at this time, and is, per- 
 haps, the result of edema of the brain. 
 
 ^ "Boston Medical and Surgical Journal," Feb. 28, 1895. 
 2 "Journal of the Boston Society of Medical Sciences," Feb., 1898. 
 24
 
 370 THE URINE IN GENERAL DISEASES. 
 
 Lesions of the pancreas are met with in about 50 per cent, 
 of the cases (Hansemann). Total extirpation of this organ 
 in dogs has been shown by v. Mering and Minkowski to pro- 
 duce diabetes ; the same result follows the complete removal 
 of the pancreas in man. In disease of the pancreas diabetes is 
 supposed to be caused by the prevention of the formation 
 of the glycolytic ferment. It is believed that this ferment, 
 which emanates from the pancreas, is taken up by the blood, 
 and that it is by its presence alone that the normal assimi- 
 lative processes can take place with the glycogen. 
 
 The nature of diabetes mellitus is unknown. For a sum- 
 mary of the anatomic changes found in this disease, the 
 reader is referred to Saundby's " Lectures on Diabetes," 
 1891. 
 
 Character of the Urine. — Quantity. — This is usually 
 greatly increased, the increase being generally in direct ratio 
 to the quantity of sugar present. In the average case the 
 quantity varies from 3000 c.c. to 6000 c.c. In very severe 
 cases it may go as high as, or even exceed, 10,000 or 
 20,000 c.c, in twenty-four hours. Occasionally, the total 
 daily quantity is less than 1500 c.c. This is particularly 
 true in the very mild forms of temporary glycosuria, or near 
 the fatal termination of cases of true diabetes mellitus. 
 
 Color. — Usually, VQ.xy pale. Watery. Sometimes the 
 urine has a normal, or rarely a high, color. On standing 
 diabetic urine speedily becomes opalescent, owing to the 
 rapid development of yeast spores and other fungi. 
 
 Reaction. — Generally acid. It is often strongly acid, 
 and the acidity increases at the onset of diabetic coma 
 (Williamson). When a diabetic urine is allowed to stand, 
 it remains acid for many days, and it may even increase in 
 acidity, owing to the development of lactic acid by ferment- 
 ation. 
 
 Specific Gravity. — This is increased ; it generally ranges 
 between 1025 and 1050, or it may be higher still. Not in- 
 frequently the specific gravity is below 1020. While the 
 density of the urine is raised if a large quantity of sugar be 
 present, we can not conclude, if the specific gravity be low, 
 that sugar will be absent ; the urine should be tested for sjigar 
 in every instance, tvhether it lias a high or a low specific 
 gravity. 
 
 Normal Solids. — Absolutely, increased, or they may be 
 normal. Occasionally, the total urea goes as high as 60 or
 
 DIABETES MELLITUS. 371 
 
 lOO grams. Owing to the large quantity of urine, the 
 normal solids are relatively diminished. In very mild cases 
 with a small quantity of sugar they may be relatively 
 normal. 
 
 Preceding or during diabetic coma the normal solids are 
 usually both relatively and absolutely diminished. 
 
 Under ordinary conditions the total solids of the urine are 
 high, owing to the presence of the sugar. 
 
 Sugar. — The presence of sugar is, of course, the most 
 important abnormality of the urine in diabetes. The per- 
 centage varies, according to the nature of the case, from 
 0.5 up to 8 or 12. The daily quantity of sugar also varies. 
 It is often from 20 to 60 grams in the twenty -four hours, but 
 may rise to 300 or 500 grams. In rare instances the total 
 quantity of glucose may exceed 750 grams. 
 
 To estimate the amount of sugar, the total quantity of 
 urine for twenty-four hours must be carefully collected and 
 well mixed, and then a sample submitted to examination. 
 The twenty-four-hour excretion of sugar should be calculated 
 in all cases, since it is by this means only that definite infor- 
 mation regarding the effect of treatment is obtained. 
 
 The twenty-four-hour quantity of urine should always be 
 accompanied by a specimen of the fasting urine (early morn- 
 ing urine) ; also by a specimen passed after the heartiest 
 meal. A very small amount, or an entire absence, of sugar 
 in the fasting urine constitutes an important element in the 
 diagnosis between a temporary glycosuria and a true dia- 
 betes mellitus. 
 
 Albumin. — This is usually present, but in very small 
 amount — generally the slightest possible trace. In case there 
 is a coexisting chronic interstitial nephritis, which is not 
 very common, the amount of albumin may reach a trace or 
 large trace. 
 
 Sediment. — An occa.sional hyaline and finely granular 
 cast ; rarely a renal cell and blood globule. There is 
 usually, also, a moderate excess of squamous epithelium 
 and sometimes a slight excess of leucocytes. If the urine 
 has been allowed to stand for some period, an abundance 
 of sugar spores (torula cerevisiae) will be found. 
 
 The nature of the renal disturbance in the majority of 
 cases of diabetes mellitus is a renal congestion (active hy- 
 peremia), which is probably partly caused by the irritating 
 action of the sugar on the renal epithelium, and possibly by
 
 372 THE URINE IN GENERAL DISEASES. 
 
 the ingestion of an unusual amount of nitrogenous food. 
 But a chronic nephritis (usually the interstitial form). is 
 sometimes met with, especially in those cases of permanent 
 diabetes that have been in progress for several years. Un- 
 der these circumstances the quantity of albumin is some- 
 what higher, the number of casts larger, and the normal 
 solids lower than in the average case of diabetes attended 
 with a renal congestion. 
 
 Prominent Symptoms. — In temporary glycosuria symp- 
 toms may be slight or entirely wanting. Usually, polyuria 
 is the most noticeable sign of the condition. A hearty ap- 
 petite and gastric disorders are not uncommon. A craving 
 for sweets is sometimes present. The patients are, as a 
 rule, obese and past the age of thirty. Occasionally, the 
 symptoms in this form quite closely resemble those asso- 
 ciated with true diabetes mellitus, but usually they are 
 milder than in the permanent form of the disease. 
 
 In permanent diabetes the most prominent symptoms are 
 (i) a constant and seemingly unquenchable thirst, (2) poly- 
 uria, (3) hunger, (4) emaciation, (5) general weakness, and 
 (6) a variety of nervous disorders. Although the quantity 
 of water taken is frequently excessive, the tongue and mouth 
 remain dry, parched, and congested. Sometimes the gums 
 are tender and become shrunken so that the teeth loosen ; 
 frequently, the saliva is scanty. The skin is dry and harsh. 
 Eczema and erythema, especially about the genital organs, 
 are frequent and annoying symptoms. Boils and carbuncles 
 are among the most common of the skin lesions in diabetes. 
 They often occur at an early stage, and sometimes are the 
 first symptoms noticed by the patient. 
 
 The temperature may be normal or subnormal. In ad- 
 vanced cases, and especially preceding or during diabetic 
 coma, the temperature may be as low as 95° or 94° F. 
 As a result of the voracious appetite, the digestion sooner 
 or later becomes disordered. Constipation and attacks of 
 diarrhea are not uncommon ; constipation is the rule. 
 
 Various nervous manifestations appear, such as neuralgia, 
 neuralgic pains in the chest, pain and tenderness in the 
 calves of the legs (neuritis), sometimes sufficient to inter- 
 fere with walking. Sensations of abnormal heat of the 
 skin are common. The patient becomes fretful, irritable, 
 and hypochondriacal, and usually there is a marked lessen- 
 ing or a complete loss of sexual power. Gangrene of the
 
 DIABETIC COINIA. 373 
 
 extremities is common, especially in those past the age of 
 from thirty to forty years. Cataract and diabetic retinitis 
 are liable to occur. 
 
 The pronounced and persistent polyuria produces fre- 
 quent micturition, which harasses the patient both day and 
 night. The quantity of urine passed during the day usu- 
 ally exceeds that passed at night. One of the most 
 frequent lung complications is tubercular disease, which is 
 most common in poor, hard-working people. Cardiac 
 weakness and enlargement, sometimes attended by valvular 
 disease or functional disturbances, are not uncommon. 
 
 Diagnosis. — An effort should be made in all cases 
 to distinguish between a permanent diabetes niellitiis and a 
 temporary glycosuria. In both forms the sugar eliminated 
 must be glucose (grape-sugar). In the former the sugar is 
 co7istantly present in the urine, while in the latter the fasting 
 urine (early morning urine) is generally free from sugar, or 
 contains only a very slight trace, and the after-meal urine is 
 highly saccharine. A diet free from carbohydrates will 
 often serve to distinguish between these two forms, since in 
 a temporary glycosuria the urine is usually quite readily 
 rendered sugar-free, while in the permanent form the quan- 
 tity of sugar may be reduced, but the urine is made sugar- 
 free only with great difficulty, or not at all. 
 
 Course and Prognosis. — In children the disease is rapidly 
 fatal. It may be stated that the older the patient at the 
 time of the onset, the slower the course. In fleshy elderly 
 individuals, the disease is much more amenable to treat- 
 ment than in thin persons. Cases without hereditary influ- 
 ences are the most favorable. Persons are met with who 
 have had the disease for fifteen years (Osier). In true dia- 
 betes mellitus instances of cure are rare. Not a few of the 
 cases of reputed cures belong to the class of temporary 
 glycosuria. In cases under thirty to forty years of age the 
 outlook is bad. 
 
 DIABETIC COMA. 
 
 Apart from coma produced by various conditions, such 
 as cerebral hemorrhage, uremia, etc., there is a special group 
 of symptoms ending in coma that is a frequent termination 
 of diabetes. These symptoms are unaccompanied by any 
 gross lesions of the organs, and are apparently due to the 
 toxic condition of the diabetic blood. Generally, the patient
 
 374 THE URINE IN GENERAL DISEASES. 
 
 comes under treatment for other symptoms of diabetes 
 before the onset of the coma ; occasionally, the patient is 
 first seen during the comatose stage. 
 
 Diabetic coma occurs both in the severe and mild forms 
 of diabetes, and rarely, if ever, in a temporary glycosuria. 
 It may occur at any age, but it is very common in young 
 persons and in persons under middle life. 
 
 An exciting cause is sometimes a long railway journey. 
 A sudden change of diet — from a mixed to a rigid nitrog- 
 enous diet — often appears to be an exciting cause of dia- 
 betic coma ; and it is said that a sudden change from a 
 rigid nitrogenous diet to a mixed nitrogenous and carbo- 
 hydrate diet has occasionally been immediately followed by 
 coma. The opinion is gradually gaining ground that a highly 
 nitrogenous diet favors the development of coma, especi- 
 ally in the severe cases in which the urine gives a port- wine 
 color with ferric chloride (diacetic acid reaction). In many 
 instances prolonged constipation has appeared to play some 
 part as an exciting cause, but it is not invariably present. 
 
 Diabetic coma appears to be occasionally precipitated by 
 intercurrent affections or complications, such as bronchitis, 
 pleurisy, pneumonia, tonsillitis, carbuncles, pharyngeal, 
 ischiorectal, or alveolar abscesses. The administration of 
 anesthetics and the performance of surgical operations have 
 also figured occasionally as exciting causes of coma. Rapid 
 and marked loss of weight sometimes precedes the onset of 
 coma. 
 
 The symptoms often begin with lassitude, epigastric 
 pain, nausea, and sometimes vomiting. Frequently, dyspnea 
 and headache are early symptoms. The patient becomes 
 anxious, restless, or excited. Speech becomes thick and 
 incoherent, and finally he becomes drow'sy, and the drowsi- 
 ness gradually develops into coma. The pulse is rapid and 
 the tension is low ; the heart's action is weak, but cardiac 
 murmurs are not usually heard. The tongue is dry and 
 red, and the face becomes pale and cold ; frequently there 
 is slight cyanosis. 
 
 Generally, the breath has a peculiar odor ; the urine also 
 has the same smell. The latter has been variously de- 
 scribed, most frequently perhaps as an odor resembling 
 new-mown hay ; it has been termed the acetone odor. Con- 
 vulsions, as a rule, do not occur, and in this respect diabetic 
 coma differs markedly from uremia.
 
 DIABETES INSIPIDUS. 375 
 
 Bremer's blood test with methylene-blue will often 
 serve to distinguish diabetic coma from other forms of 
 coma. 
 
 Urine. — The urine is diminished in quantity preceding 
 and during diabetic coma, the color is not so pale and the 
 acidity of the urine is increased. There is frequently a 
 marked diminution in the quantity of sugar before the 
 onset and during the coma. Usually, the quantity of 
 albumin increases. The normal solids become absolutely 
 much diminished. The sediment usually contains numer- 
 ous hyaline and finely granular casts ; a few renal cells, 
 which are often quite granular ; and an occasional blood 
 globule. 
 
 The urine almost invariably gives the reactions for ace- 
 tone and diacetic acid. (See pp. 172 and 175.) 
 
 Importance of Acetone and Diacetic Acid in Dia- 
 betic Urine. — Acetone and diacetic acid are most com- 
 monly found in the urine of the advanced cases of true 
 diabetes mellitus. In most instances their presence is an 
 important prognostic element. Although the reactions for 
 both acetone and diacetic acid may be obtained in the urine 
 for weeks or months without any comatose symptoms 
 occurring, they certainly indicate the constant danger of 
 coma. The author's experience leads him to believe that 
 when these reactions are obtained, and especially a marked 
 reaction with ferric chloride (diacetic acid), an unfavorable 
 prognosis is warranted, although in rare instances he has 
 known both acetone and diacetic acid to disappear from the 
 urine as the patient improved under treatment. He has 
 never met with these two substances in cases of temporary 
 glycosuria. 
 
 DIABETES INSIPIDUS. 
 
 This disease is characterized by the elimination of very 
 large quantities of nonsaccharine urine of low specific 
 gravity. Willis, in 1674, first recognized the distinction 
 between the saccharine and nonsaccharine forms of dia- 
 betes. The disease is most common in young persons — 
 between five and thirty years of age. Males are more fre- 
 quently attacked than females. The affection may be con- 
 genital, and in a iew instances a hereditary tendency has 
 been noted. Traumatism, such as injury to the head, 
 trunk, or limbs, has occasionally been the exciting cause.
 
 376 THE URINE IN GENERAL DISEASES. 
 
 The disease has also followed sunstroke, or violent emotion, 
 such as fright ; also intracranial growths or other lesions of 
 the nervous system. It has followed rapidly the copious 
 drinking of cold water, or a drinking-bout ; or has set in 
 during the convalescence from acute disease. Osier has 
 noted it in several cases of tuberculous peritonitis. 
 
 Practically nothing is known of the pathology of this 
 disease. It is, doubtless, of nervous origin. 
 
 Prominent Symptoms. — The most prominent symptoms 
 of this disease are the marked and never-satisfied thirst, 
 the elimination of enormous quantities of urine, marked 
 emaciation, and a dry, pinched, and dusky skin. Excep- 
 tionally, the disease does not appear to interfere in any way 
 with the general health. The appetite is usually not in- 
 creased as in diabetes mellitus. Death may take place from 
 some intercurrent affection. Spontaneous cure may take 
 place. 
 
 Character of the Urine. — Quantity. — This varies be- 
 tween 5000 c.c. and 20,000 c.c. during the twenty-four 
 hours. 
 
 Color. — Very pale. Watery. 
 
 Reaction. — Faintly acid or neutral. Upon standing, the 
 urine soon becomes ammoniacal and turbid, and often has 
 a rather offensive, fish -like odor. 
 
 Specific Gravity. — This is very low — usually betAveen 
 looi and 1005. 
 
 Normal Solids. — Absolutely, verj' much increased ; the 
 total urea may exceed 100 grams, while the chlorides, phos- 
 phates, and sulphates are also ver}' high. Relatively, very 
 much diminished. 
 
 Albumin. — Usually absent ; the urine may, however, 
 contain the slightest possible trace of albumin, particularly in 
 cases of long standing. 
 
 Sediment. — Very slight. Generally, it is necessary to 
 centrifugalize the urine in order to get any visible sediment. 
 It usually consists chiefly of cellular elements — squamous 
 epithelium and small round cells ; sometimes a leucocyte 
 and blood globule are found. In exceptional cases renal 
 casts (pure hyaline) may be found. 
 
 Diagnosis. — Hysteric polyuria may sometimes simulate 
 this disease very closely. The amount of urine excreted 
 may be enormous, but there is never a marked increase of 
 the solids, and often only the development of other hys-
 
 DIABETES INSIPIDUS. 377 
 
 teric manifestations may enable the diagnosis to be made ; 
 a polyuria from this cause is, however, always transitory. 
 
 In certain cases of cJwonic interstitial nephritis a very large 
 quantity of urine of low specific gravity may be passed, but 
 the usual low total solids, the presence of albumin and of 
 hyaline casts, and the existence of heightened arterial ten- 
 sion, stiff arteries, and hypertrophied left ventricle aid ma- 
 terially in the diagnosis. Occasionally, in chronic interstitial 
 nephritis the normal solids as well as the quantity of urine 
 are very high, as in a case seen by the author about four 
 years ago ; a child, age seven ; quantity of urine, from 
 6000 to 7000 c.c. ; specific gravity, from 1002 to 1006 ; urea, 
 45 grams ; chlorine, 13 grams ; PgO., 55 grams. On account 
 of the absence of the usual signs and symptoms of chronic 
 interstitial nephritis the case was supposed to be one of dia- 
 betes insipidus, but at the autopsy very small, red, granular 
 kidneys were found. 
 
 The course of diabetes insipidus depends entirely upon 
 the nature of the primary trouble. Sometimes with organic 
 disease, either cerebral or abdominal, the general health is 
 much impaired, Irt the idiopathic cases the affection has 
 been known to persist for fifty years with a fair degree of 
 health. Death usually results from some intercurrent affec- 
 tion. Recovery may take place.
 
 CHAPTER XI. 
 
 THE URINE IN DISEASES OUTSIDE OF THE 
 URINARY TRACT. 
 
 FEVER URINE. 
 
 In acute febrile conditions the characteristics of the urine 
 become modified from the normal according to the height 
 and character of the fever and the degree of toxemia or 
 altered metabolism. During the early stage of an acute 
 febrile disease the quantity of urine is abnormally small, — 
 from 500 c.c. to loooc.c, — the color is high, there is a high 
 specific gravity, and an intensely acid reaction. There is 
 usually a considerable amount of sediment ; often there is 
 an abundant sediment after the urine cools, due to a deposit 
 of amorphous urates. The normal solids are both relatively 
 and absolutely increased, especially the urea, which has 
 been known to be as high as 85 grams in twenty-four hours. 
 Uric acid is also usually increased, although the extent to 
 which it is increased is largely dependent on the disease that 
 causes the fever. The chlorides are always absolutely dimin- 
 ished. The phosphates are absolutely diminished at first, 
 but later they are increased. In a very mild febrile attack 
 albumin may be absent. In the more severe febrile diseases, 
 with high temperature, albumin is always present, vary- 
 ing in amount from the slightest possible trace to a trace. 
 The sediment usually contains an occasional (or few) gran- 
 ular and brown granular cast, some with blood and renal 
 cells adherent ; a few (or numerous) free renal epithelial 
 cells ; and a i&w blood globules. 
 
 As the fever begins to abate, the quantity of urine in- 
 creases, and frequently there is polyuria during the conva- 
 lescence from the febrile condition. Although during con- 
 valescence the patient may be taking more food than in 
 the early stage of the disease, the normal solids for the 
 twenty-four hours will be diminished, owing to the fact that 
 
 378
 
 URINE OF CHRONIC DISEASE. 379 
 
 the food elements are used to build up those tissues that have 
 been diseased. As complete convalescence approaches, the 
 quantity of urine falls to the normal, and the solids 
 gradually rise to their normal quantities. During conva- 
 lescence the albumin and the other abnormal elements grad- 
 ually disappear from the urine, and the renal tubules become 
 restored to their normal condition. 
 
 In case the acute disease terminates fatally during the 
 acute stage the quantity of urea and other solids, instead of 
 being high, will be found to gradually diminish up to the 
 time of death, and may, on the last day or two of the 
 disease, amount to only 5 or 10 grams in twenty -four 
 hours. 
 
 The characteristics of the urine in acute febrile condi- 
 tions, as a rule, conform to those of an active hyperemia, 
 which may be either mild or severe. Such renal disturb- 
 ance is no doubt partly due to the irritating action of the 
 concentrated urine itself, but is more directly dependent on 
 the elimination of irritating toxines developed during the dis- 
 ease from which the patient is suffering. Although the 
 renal affection usually begins as an active hyperemia, it 
 often becomes intensified, and may result in an acute neph- 
 ritis. The extent of the renal involvement is usually in 
 direct proportion to the degree of toxemia. 
 
 /;/ acute diseases attended with a serous exudation the char- 
 acteristics of the urine differ somewhat from the preceding. 
 The chlorides are diminished to a much greater extent than 
 in an ordinary acute affection without exudation, and, in- 
 deed, they may be absent. The urea is also not so high 
 (although it may still be above the normal) as in acute dis- 
 ease without serous exudation. In rare instances the total 
 urea may be considerably diminished, apparently as a result 
 of the exudation. (See Pneumonia, p. 383.) 
 
 URINE OF CHRONIC DISEASE (NOT RENAL). 
 
 In many chronic affections of the body in which fever is 
 absent, such as cancer, tuberculosis, etc., the urine gener- 
 ally has an entirely different appearance from that found in 
 acute febrile diseases. 
 
 The quantity is slightly below the normal — 1000 c.c, or 
 1200 c.c. ; the color is usually pale, but it may be normal 
 or, rarely, slightly high ; the reaction is faintly acid, or it
 
 380 DISEASES OUTSIDE OF THE URINARY TRACT. 
 
 may be alkaline. The normal solids arc both relatively and 
 absolutely diminished, the amount of diminution being depen- 
 dent largely upon the appetite, which is generally more or 
 less disturbed. Albumin is usually present, but in very 
 small amount ; occasionally, it is absent. The sediment is 
 liable to contain a very few formed renal elements (casts 
 and renal cells), although they, too, may be absent. It 
 is, however, the rule to find, at least, evidences of a renal 
 congestion (active hyperemia), and sometimes coexisting 
 primary kidney disease. 
 
 TYPHOID FEVER. 
 
 The quantity of urine is diminished — 500 c.c, to 800 
 c.c; the color is very high (absolute increase of the pig- 
 ments) ; the reaction is strongly acid ; the specific gravity 
 is usually very high — 1030 to 1040 ; the normal solids are 
 relatively increased. During the first week of the disease 
 the solids, except the chlorides and phosphates, are abso- 
 lutely increased, the former being only slightly diminished 
 while the latter are usually much diminished. The quantity 
 of urea may go as high as 60 to 70 grams. The uric acid 
 is also much increased, and the urine not infrequently con- 
 tains a heavy deposit of amorphous urates. Albumin is 
 almost always present ; the quantity varies from the slightest 
 possible trace to j^ of i per cent., the amount being 
 dependent on the height of the fever, the toxemia, and the 
 nature of the resulting renal affection. Peptone is said to 
 be present in the urine in typhoid fever, especially in the 
 more severe types of the disease. The sediment is almost 
 certain to contain renal casts, an excess of renal epithelial 
 cells, and a variable quantity of blood — usually a small 
 amount. 
 
 An active hyperemia that is more or less severe is the 
 rule in typhoid fever. Sometimes a genuine acute nephritis 
 develops at the onset or during the height of the disease, 
 masking in many instances the true nature of the primary 
 malady ; in such cases the prognosis is always to be con- 
 sidered grave. An acute nephritis developing during con- 
 valescence from typhoid fever is quite common, but, as a 
 rule, not so serious as when it dev^elops early in the dis- 
 ease ; it usually makes its appearance after the fall of the 
 fever. Convalescence from an acute nephritis, which has
 
 YELLOW FEVER. 381 
 
 developed late in typhoid, is usually slow, but complete 
 recovery is the rule. 
 
 Pyuria is a common complication of the disease. The 
 pus is the evidence of a cystitis or a pyelitis, and in the 
 experience of the author the latter is the more common. 
 Under these circumstances the urine invariably has the 
 characteristics of a chronic cystitis or chronic pyelitis, and it 
 usually contains a large number of typhoid bacilli. Orchitis 
 is occasionally met with during convalescence ; it is usu- 
 ally associated with a catarrhal urethritis. In pyelitis, cys- 
 titis, or urethritis from this cause treatment with the formal- 
 dehyde compound known as nrotropin is usually highly 
 satisfactory. 
 
 In the urine of typhoid fever the diazo reaction of Ehrlich 
 is often obtained. (See p. 182.) The clinical value of the 
 reaction is doubtful ; it is certain that its value is lessened 
 by its occurrence in acute miliaiy tuberculosis and various 
 other diseases associated with high fever. 
 
 YELLOW FEVER. 
 
 The quantity of urine is much diminished from the first. 
 The color is high or dark, depending upon the amount of 
 blood present ; rarely, it is bloody. The specific gravity is 
 usually below the normal, but it may be high. The urea is 
 often relatively diminished, but it may be normal ; abso- 
 lutely, it is much diminished ; sometimes it is totally absent 
 (Purdy). Although there is, without doubt, an increased 
 production of urea during the stage of fever, yet, according 
 to> Cunnisset, the elimination of urea is always less than 
 normal, the degree of diminution being in direct proportion 
 to the danger of the disease, and affording an important 
 element in prognosis. The chlorides are usually both rela- 
 tively and absolutely diminished. Albuminuria is regarded 
 by Guiteras as the third characteristic symptom of the 
 disease. In the mild cases the amount of albumin is 
 usually small, but in the severe cases the quantity of 
 albumin is large and there may be numerous tube casts of 
 varioug kinds, renal epithelium, an abundance of blood, and 
 all the evidences of a severe acute nephritis. Or perhaps 
 complete suppression of the urine may supervene, and 
 death may occur in uremic convulsions or coma within 
 twenty-four or thirty hours. When albumin is present in
 
 382 DISEASES OUTSIDE OF THE URINARY TRACT. 
 
 the urine on the first day of the disease and continues on 
 the second day, Guiteras states that it indicates a severe 
 case. The urine frequently contains bile. 
 
 TYPHUS FEVER. 
 
 In this disease the urine is scanty in amount and highly 
 febrile. It is highly colored and strongly acid. Occasion- 
 ally, it is alkaline, and has a veiy offensive odor. Relatively, 
 the urea is increased ; absolutely, much diminished ; leucin 
 and tyrosin may take the place of the urea, as in acute 
 yellow atrophy of the liver. The uric acid is relatively in- 
 creased, and it may be absolutely increased, especially 
 during the early stages of the disease. The chlorides are 
 both relatively and absolutely greatly diminished, and may 
 be absent. Albumin is invariably present, but usually in 
 small amount, except in the severe cases attended with acute 
 nephritis. Under such circumstances the urine is bloody 
 and bears the other characteristics of an acute nephritis. 
 (See p. 294.) The proportion of cases in which an acute 
 nephritis occurs varies much in different epidemics ; its ex- 
 istence, howev'er, adds decidedly to the gravity of the case. 
 A true hemoglobinuria may be seen in the severe cases. In 
 the mild cases the characteristics of the urine are those of 
 a severe active hyperemia or renal congestion. The sedi- 
 ment contains numerous hyaline and granular casts and 
 renal cells ; also a varying amount of blood. At the time 
 of the crisis copious amounts of urine of low specific gravity 
 and pale color are passed. Retention of urine is of fre- 
 quent occurrence ; the region of the bladder should be 
 frequently examined, and the catheter used if required. 
 
 RELAPSING FEVER. 
 
 In relapsing fever the urinary system is the seat of varj'ing 
 morbid conditions, some of which are of great importance in 
 determining the prognosis. Albuminuria is present in a very 
 large number of the cases, and is not necessarily a cause of 
 very serious alarm. When, however, an abundant excretion 
 of albumin is accompanied by the presence of large numbers 
 of renal casts, renal cells, and much blood, the prognosis is 
 grave. The affection of the kidneys may vaiy from a 
 simple congestion to an actual acute nephritis, the latter
 
 PNEUMONIA. 383 
 
 being sometimes hemorrhagic in character. Complete sup- 
 pression of urine is sometimes present. Hematuria may be 
 profuse and exhausting ; it is a grave comphcation and is 
 often followed by a fatal issue. Glycosuria has been 
 observed during the course of some cases. 
 
 PNEUMONIA. 
 
 Early in the disease the urine presents the usual charac- 
 teristics found in acute febrile conditions attended with 
 exudation. The quantity of urine is very small — often less 
 than 500 c.c. ; the specific gravity is high — 1030 to 1040; 
 the color is very high, the amount of pigment being both 
 relatively and absolutely increased. The quantity of urea 
 is increased. In some instances the urea is diminished 
 after the first few days of the disease ; such cases are 
 usually characterized by delayed convalescence, diarrheal 
 attacks, tuberculosis, pleurisy with effusion, empyema, etc. 
 The uric acid is usually very much increased, especially 
 just after the crisis, and very often the urine contains a 
 very heavy deposit of amorphous urates, and is colored a 
 carmine, deep red, or brown. 
 
 The chlorides are very much diminished and may be 
 entirely absent, especially between the third and fifth days 
 of the disease. The reappearance of the chlorine is evi- 
 dence of beginning convalescence — the beginning of the 
 absorption of the serous exudation from the diseased lung. 
 The chlorine always reappears or commences to increase in 
 quantity before evidences of beginning convalescence can be 
 made out by auscultation and percussion or by a fall in the 
 temperature. 
 
 Albumin is invariably present in pneumonia — often only 
 the slightest possible traee in mild cases, and a large trace to 
 y% of I per cent, in the severe cases. Sometimes a large 
 amount of albumin and a bloody or smoky urine indicate 
 the presence of an acute nephritis. In a large proportion 
 of all cases the albumin is evidence of a more or less severe 
 toxic condition. According to v. Jaksch, the appearance of 
 peptone in the urine is indicative of the beginning of resolu- 
 tion. 
 
 The sediment usually contains a few (or numerous) hya- 
 line, fine, and brown granular casts, numerous renal cells, 
 and abnormal blood globules. Blood may be present in
 
 384 DISEASES OUTSIDE OF THE URINARY TRACT. 
 
 abundance, when the sediment usually has the other char- 
 acteristics of an acute diffuse nephritis. (Compare p. 294.) 
 
 The urine may contain bile pigment. 
 
 During convalescence from pneumonia the quantity of 
 urine increases and may exceed the normal ; the quantity 
 of urea and uric acid return to, and sometimes fall below, 
 the average normal, while the chlorides gradually become 
 increased, finally returning to normal. 
 
 PULMONARY TUBERCULOSIS. 
 
 In the average uncomplicated case of pulmonary tuber- 
 culosis the urine does not present any special peculiarities. 
 The quantity is usually diminished, especially if there is 
 fever ; if no fever, the quantity may be increased, even in 
 uncomplicated cases. If amyloid infiltration be present as 
 a complication, the quantity of urine is usually increased. 
 In the average case of pulmonary phthisis with fever the 
 color of the urine is higher than normal, the specific gravity 
 is moderately increased, and the reaction is strongly acid. 
 The normal solids are relatively increased ; absohitely, dimin- 
 ished. The urea is usually diminished, but the extent of 
 the diminution is dependent on the appetite, the general 
 metabolism, and the fever. The uric acid is generally 
 increased, while the sulphates are only moderately dimin- 
 ished. The chlorides are usually somewhat diminished, 
 but the quantity of chlorine is largely dependent on the 
 character of the food taken. If there is marked diarrhea, 
 the chlorides will be found absolutely very much dimin- 
 ished. In some cases of pulmonary tuberculosis the phos- 
 phates are absolutely increased, especially when the lung 
 tissue is breaking down rapidly. 
 
 Albumin is probably present in the urine of every case 
 of advanced phthisis. As has been stated, subacute glomer- 
 ■ ular nephritis and amyloid infiltration are frequent compli- 
 cations of pulmonary tuberculosis. (See pp. 301, 318.) 
 Under such circumstances the quantity of albumin is large. 
 If such complications are not present, the quantity of albu- 
 min is usually small — slightest possible trace to a trace. 
 
 The sediment usually contains an occasional (or a few) 
 renal cast, renal cell, and a very small amount of blood ; 
 in other words, evidence of a more or less marked renal 
 congestion.
 
 MALARIAL FEVER. 385 
 
 Besides the liability of an amyloid infiltration, or a sub- 
 acute glomerular nephritis as a complication, tubercular 
 ulcerations in the kidney, pelvis of the kidney, or the 
 bladder are very likely to occur. Pyuria is then the most 
 prominent feature of the urine. In all such cases the 
 urinary sediment should be very carefully examined for 
 tubercle bacilli. 
 
 MALARIAL FEVER. 
 
 During the pyrexia the urine has the usual characteris- 
 tics of a fever urine. The quantity is small, the color is 
 high, and the specific gravity is increased. After the chill 
 and the fever the urine is often increased in amount and of 
 low specific gravity. There is always an increase in the 
 elimination of urea during a paroxysm, and Jaccoud has 
 noted that this increase commences even before the chill, so 
 that careful quantitative estimations of urea will often fore- 
 tell the approach of a paroxysm. This increase of the 
 urea excretion he observed two hours before the chill in 
 quotidian, and six or eight hours before in tertian, fever. 
 He regards the increased urea as a reliable indication for 
 the proper time for administering quinine in order to antici- 
 pate the chill. During the paroxysm the chlorine is elimi- 
 nated in normal amount. On the days between paroxysms 
 both the urea and chlorine are usually diminished. 
 
 -The urine usually contains albumin, but generally in 
 small amount — slightest possible trace. If an acute neph- 
 ritis develops, the quantity of albumin is large — ^ to i^ 
 of I per cent. The sediment generally contains renal casts, 
 renal cells, and a few blood globules. The renal disturb- 
 ance is usually of the nature of a renal congestion or active 
 hyperemia. 
 
 An acute nephritis in malaria is not very common in 
 New England. Thayer, ^ who has recently made a study 
 of the urine in malaria at the Johns Hopkins Hospital, 
 draws the following conclusions : 
 
 (i) Albuminuria is of frequent occurrence in the malarial 
 fevers of Baltimore, occurring in 46.6 per cent, of the cases 
 studied. (2) It is considerably more frequent in estivo- 
 autumnal infections than in the other forms, occurring in 
 58.3 per cent, of these instances against 38.6 per cent, in 
 
 ' " Amer. Journ. Med. Sciences," Dec, 1898, p. 646. 
 . 25
 
 386 DISEASES OUTSIDE OF THE URINARY TRACT. 
 
 the regular intermittent forms. (3) Acute nephritis is not 
 an unusual complication of malarial fever, having occurred 
 in 2.7 per cent, of the cases treated in the wards and 
 between i and 2 per cent, of all cases seen at the hospital. 
 (4) The frequency of acute nephritis in estivo-autumnal 
 fever is much greater than in the regular intermittent forms, 
 having been observed in 4.7 per cent, of the cases treated in 
 the wards and in 2.5 percent, of all cases seen. (5) The 
 frequency of albuminuria and nephritis in malarial fever, 
 while somewhat below that observed in the more severe 
 acute infections, such as typhoid fever, scarlet fever, and 
 diphtheria, is yet considerable. (6) There is reason to believe 
 that malarial infection, especially in the more tropical coun- 
 tries, may play an appreciable part in the etiology of chronic 
 renal disease. 
 
 Paroxysmal hemoglobinuria is sometimes a complication 
 of malaria. Like an acute nephritis, this complication is 
 perhaps more common in the Southern States and tropical 
 countries than in New England. Out of several hundred 
 cases of malarial fever at the Boston City Hospital, the 
 author has only once met with hemoglobinuria. The rela- 
 tion of this condition to malaria is not so close as has been 
 thought by many writers. Bastianelli asserts that it is 
 practically proved that malarial hemoglobinuria occurs only 
 in infections with the estivo-autumnal parasite. No doubt 
 it has frequently been confounded with malarial hematuria. 
 
 Malarial hematuria of renal origin is sometimes encoun- 
 tered, especially in the estivo-autumnal form of the disease. 
 In such cases the evidences of tubular disturbance of the 
 kidney (casts, renal cells, etc.) is usually very slight. 
 
 ERYSIPELAS. 
 
 In this disease the urine is scanty in amount, highly 
 colored, and of high specific gravity. Relatively, the solids 
 are all increased ; absolutely, diminished, especially after the 
 first two or three days of the disease. Albuminuria is 
 almost constant ; usually, the quantity of albumin is small, 
 varying between a very slight trace and a large trace. A 
 true acute nephritis is quite common ; the quantity of albu- 
 min may then reach, or even exceed, i per cent. The 
 sediment always contains renal casts, usually an excess of 
 renal epithelium, and a few (or numerous) blood globules,
 
 CHOLERA. 387 
 
 both free and adherent to casts. The number of casts and 
 cellular elements, and the quantity of blood, may be very 
 large, indicative of an acute nephritis. In the experience 
 of the author an acute pyelonephritis in erysipelas is not 
 uncommon. Chronic pyelitis is sometimes the result of 
 the acute pyelitis ; convalescence from this complication is 
 usually slow. In case the erysipelas is complicated by 
 pneumonia, ulcerative endocarditis, or septicemia, a severe 
 acute pyelonephritis is quite sure to follow, and the prog- 
 nosis is thereby rendered grave. 
 
 CHOLERA. 
 
 In the first two or three days of this disease — algid or 
 collapse stage — the quantity of urine is very small, or 
 there may be complete suppression ; the color is normal or 
 pale, sometimes smoky ; the specific gravity is either normal 
 or diminished ; and the reaction is faintly acid. The urea 
 is very much diminished ; this marked diminution is un- 
 usual in most acute diseases, and in cholera it is prob- 
 ably due to the fact that a large proportion of the urea is 
 eliminated with the intestinal discharges. In case of sup- 
 pression of urine a considerable amount of urea may be 
 eliminated by the sweat glands ; indeed, it is sometimes 
 eliminated in sufficient quantity to cause a coating of urea 
 on the skin, especially in the axillae and groins. The uric 
 acid is also much diminished. The chlorides are very much 
 diminished, or they may be absent. The phosphates are, 
 like the urea, very much reduced. 
 
 The indoxyl — indoxyl-potassium sulphate — is much in- 
 creased, and in rare instances the urine has a blue color 
 and contains a deposit of indigo. In early times, before 
 the recognition of the cholera bacillus, the high indoxyl 
 was considered an important element in the diagnosis 
 of cholera. It should be borne in mind, however, that a 
 large increase in the indoxyl is frequently found in other 
 conditions than cholera, such as peritonitis, intestinal ob- 
 struction, etc., so that too much reliance can not be placed 
 on a high indoxyl in the diagnosis of cholera. 
 
 During the algid stage the urine invariably contains albu- 
 min. The quantity varies, but it may be large and frequently 
 indicates the presence of an acute nephritis. Often the albu- 
 minuria disappears with the subsidence of the algid stage.
 
 388 DISEASES OUTSIDE OF THE URINARY TRACT. 
 
 The sediment contains renal casts, often in large num- 
 bers, many renal cells, and a few (or numerous) blood 
 globules. If an acute nephritis, the quantity of blood will 
 be large, and there will be a large number of brown granu- 
 lar, blood, epithelial, and fibrinous casts. 
 
 After the third day, in a favorable case, the quantity of 
 urine rapidly increases, the color is pale, and the specific 
 gravity is very low. Coincident with this increase of the- 
 urine there is a rise in the urea, chlorides, phosphates, and 
 other solids. The urine may temporarily exceed the normal 
 — for example, it may rise to 60 to 80 grams and then 
 gradually return to the normal. The chlorides and phos- 
 phates, however, do not, as a rule, exceed the normal. In 
 case of an acute nephritis during the algid stage a typical 
 convalescent stage of acute nephritis is seen when the patient 
 begins to improve. 
 
 But the complication of an acute nephritis during the col- 
 lapse period may be the direct cause of death by uremic 
 coma. In cholera, after the third day, if the quantity of 
 urine does not increase, the albumin does not diminish, and 
 the urea and chlorine do not begin to rise in quantity, the 
 prognosis can be considered very grave. 
 
 SCARLET FEVER. 
 
 The urine in this disease is subject to much variation. It 
 is very common, and, indeed, the rule to find evidences in 
 the urine of a severe renal congestion or an acute nephritis 
 (sometimes the acute interstitial form). But in many in- 
 stances the kidneys escape without greater damage than 
 occurs in other acute febrile affections. An acute nephritis is 
 most common in the second or third week of the disease, and 
 may develop after a very mild attack of scarlet fever. Not 
 infrequently, an acute nephritis makes its first appearance 
 late in the period of desquamation, when it usually exists 
 in a mild form. As a rule, the earlier it develops, the more 
 severe it is. 
 
 The renal disturbance varies greatly in intensity, but in 
 all instances during the height of the fever the urine is 
 diminished in quantity and of high specific gravity. It has 
 a high or smoky color, an intensely acid reaction, and the 
 normal solids are relatively increased, especially the urea 
 and uric acid ; they are absolutely diminished except during
 
 SCARLET FEVER. 389 
 
 the first da}' or two of the disease. If there be dropsy, the 
 chlorides and urea are very much reduced, especially the 
 former. Three distinct grades of cases may be recognized. 
 
 Mild Cases. — The urine has a high color, and invariably 
 contains albumin — usually the slightest possible trace to a 
 trace. The sediment contains an occasional (or few) hyaline, 
 granular, and brown granular casts, renal cells, and a few 
 blood globules, Iree and attached to casts ; in other words, 
 there is evidence of a mild renal congestion or active hyper- 
 emia. Edema is absent, and the convalescence from the 
 fever is scarcely interrupted. 
 
 Severe Cases. — The urine has a smoky color and con- 
 tains considerable albumin — usually varying in amount be- 
 tween a large trace and y^ of i per cent. The sediment 
 contains many hyaline, granular, and brown granular, a few 
 epithelial, blood, and fibrinous casts ; also many renal cells 
 and frequently small caudate cells from the superficial layer 
 of the pelvis of the kidney ; considerable altered blood, and 
 a few pus-corpuscles — the evidences of an acute pyelo- 
 nephritis. Edema, especially about the eyelids, is a con- 
 stant symptom ; there may be edema of the feet. The 
 renal symptoms then dominate the entire case. The con- 
 dition may continue and finally become chronic, but fortu- 
 nately, in a majority of the cases, the disease yields to judi- 
 cious treatment, and complete recovery takes place. 
 
 Very Severe Cases. — In this class of cases there is 
 usually either complete suppression of urine or the passage 
 of a small quantity of very dark (almost black) urine, 
 which contains a high quantity of albumin — from ^ to 
 I y^ per cent. The sediment contains the same elements 
 that are found in the severe cases, but in much larger num- 
 bers — a very severe acute pyelonephritis. There is marked 
 dropsy, vomiting, and convulsions, and the child dies with 
 the symptoms of acute uremia. 
 
 In the favorable cases of acute pyelonephritis the third or 
 convalescent stage soon makes its appearance, when the 
 quantity of urine increases, the color is very slightly smoky 
 or pale, and fat appears in the renal cells and is found 
 attached to the casts. As previously stated, with judicious 
 treatment complete recovery usually takes place. Occa- 
 sionally, convalescence becomes prolonged and a chronic 
 nephritis results. Sometimes a marked chronic pyelitis is 
 the result of the acute pyelitis.
 
 390 DISEASES OUTSIDE OF THE URINARY TRACT. 
 
 The urine in scarlet fever should in all cases be carefully 
 watched, owing to the fact that renal complications are 
 among the most common. 
 
 DIPHTHERIA. 
 
 In diphtheria, as in other acute infectious diseases, renal 
 complications are common ; they are, however, less common 
 than in scarlet fever. The quantity of urine is diminished ; 
 the color is high, or, if an acute nephritis, smoky ; the spe- 
 cific gravity is high — 1025 to 1035. Relatively, the normal 
 solids are increased, but absolutely, diminished. Albu- 
 minuria is a constant symptom in all severe cases, and, in 
 fact, albumin is present in nearly all of the milder cases. 
 It varies in amount from the slightest possible trace to a large 
 trace. If an acute nephritis develops, it may exceed y^ of 
 I per cent. The sediment contains renal casts, renal cells, 
 and a small amount of blood both free and on casts — evi- 
 dences of an active hyperemia. 
 
 An acute nephritis is, however, not uncommon. It may 
 appear quite early in the disease. Occasionally, it begins 
 with complete suppression of urine. In comparison with 
 scarlet fever the renal changes lead less frequently to gen- 
 eral dropsy. The sediment usually contains, besides brown 
 granular, blood, epithelial, and fibrinous casts, many renal 
 cells, much blood, and numerous small caudate cells from 
 the pelvis of the kidney — evidences of an acute pyelo- 
 nephritis. The course of the nephritis is usually favorable. 
 Occasionally, there are convulsions, and the patient dies from 
 acute uremia. Sometimes a chronic nephritis follows an 
 acute nephritis. Acute nephritis is a less frequent compli- 
 cation of diphtheria since the advent of the antitoxine treat- 
 ment of this disease. 
 
 Hibbard and Morrissey ^ have found that a glycosuria is 
 not uncommon in diphtheria. 
 
 SMALLPOX. 
 
 In this disease the urine has the usual typical character- 
 istics of fever. The quantity of urine is small, the coloring- 
 matters are increased, and the specific gravity is high. 
 Relatively and absolutely, the urea is generally increased, 
 but it may, rarely, be absolutely much diminished ; under 
 
 ' " Journ. of the Society of Med. Sciences," Feb., 1898.
 
 ACUTE GENERAL PERITONITIS. 391 
 
 such circumstances, leucin and tyrosin may appear in the 
 urine instead of urea. The chlorides, sulphates, and phos- 
 phates are absolutely somewhat diminished. The uric acid 
 is increased, and the urine, on cooling, frequently deposits 
 amorphous urates. 
 
 Albumin is invariably present in the urine in all cases of 
 smallpox, and it generally makes its appearance with the 
 onset of the disease. The sediment contains renal casts, 
 renal cells, and a moderate amount of blood both free and 
 adherent to casts. An active hyperemia, which is usually 
 quite severe, is the rule. Occasionally, a true acute 
 nephritis develops, especially in the malignant forms. The 
 urine frequently contains bile pigment. In the hemorrhagic 
 form of the disease hemoglobinuria may be a prominent 
 feature of the urine. Care should be taken not to confound 
 a hemoglobinuria with a hematuria accompanying an acute 
 nephritis. 
 
 ACUTE GENERAL PERITONITIS. 
 
 In this disease the quantity of urine is very small, the 
 color is high, and the specific gravity is above the normal. 
 A prominent feature of the urine is the very large excess of 
 indoxyl. Relatively, the normal solids are increased, except 
 the chlorides, which are very much diminished or absent ; 
 absolutely, the solids are diminished. Albumin is generally 
 present, and in the sediment will be found renal casts, renal 
 .cells, and a variable amount of blood — in other words, 
 evidences of a more or less severe active hyperemia of the 
 kidneys. 
 
 In localized peritonitis the chlorides are not, as a rule, 
 much diminished, if at all ; the degree of diminution is, 
 however, dependent on the extent of the pathologic process 
 and the amount of serous exudation. 
 
 INTESTINAL OBSTRUCTION. 
 
 In this condition the urine is small in amount, and there 
 may be almost complete suppression, particularly when the 
 obstruction is high up in the bowel. This is probably due 
 to the excessive vomiting and the small amount of liquid 
 taken. The urine has a high color, and the specific gravity 
 is above the normal — 1025 to 1035. Relatively, the solids 
 are increased ; absolutely, diminished. When the obstruc-
 
 392 DISEASES OUTSIDE OF THE URINARY TRACT. 
 
 tion occurs in the small intestine, the indoxyl is usually very- 
 high ; in one case the amount of indoxyl reported was as 
 high as 98 milligrams. Albumin is usually present, but in 
 small amount ; and the sediment contains renal casts, renal 
 epithelial cells, and a little blood. In the majority of cases 
 of intestinal obstruction the renal disturbance is of the 
 nature of a renal congestion or toxic irritation. 
 
 ACUTE YELLOW ATROPHY OF THE LIVER. 
 
 The twenty-four-hour quantity of urine is small, the re- 
 action is strongly acid, and the specific gravity is low. The 
 urine contains both bile pigments and the bile acids. Rela- 
 tively and absolutely, the normal solids are much diminished. 
 The urea is present in very small amount or it may be 
 absent. Instead of the urea, leucin and tyrosin, one or 
 both, are usually, although not constantly, present in the 
 urine ; of 23 recent cases collected by Hunter, in 9 neither 
 was found; in 10, both were present; in 3, tyrosin only; 
 in I, leucin only. Both leucin and tyrosin have character- 
 istic crystalline shapes (see pp. 225, 226), and are found in 
 the urinary sediment. In the search for these crystals it is 
 advisable to previously render the urine acid with acetic acid 
 and concentrate by evaporation. The phosphates and uric 
 acid are very much reduced. The urine always contains 
 albumin, which may be present in considerable quantity — 
 ^ to ^ of I per cent. The sediment contains numerous 
 hyaline, granular, and fatty casts, fatty renal cells, and 
 compound granule cells ; in other words, the urine indicates 
 a more or less marked fatty degeneration of the kidneys. 
 The casts and renal cells are usually stained yellow by the 
 bile pigment. 
 
 Acute yellow atrophy is of rare occurrence and is rapidly 
 fatal. It is characterized by jaundice and marked cerebral 
 symptoms, and anatomically, by extensive necrosis of the 
 liver-cells with reduction in the volume of the organ. The 
 symptoms produced by phosphorus-poisoning closely 
 simulate those of acute yellow atrophy, but it should be 
 borne in mind that the two conditions are not identical.
 
 HYSTERIA. 393 
 
 HYSTERIA. 
 
 During and immediately following an attack of hysteria 
 the twenty-four-hour quantity of urine is much increased, 
 not infrequently going as high as 5000 c.c. The color is 
 very pale and watery ; and the specific gravity is low — 1002 
 to 1012 ; the reaction is faintly acid. Relatively, the solids 
 are much diminished ; absolutely, normal or only slightly 
 diminished, and sometimes they are increased. The urine 
 is frequently free from albumin ; on the other hand, it may 
 be present in very small amount — slightest possible traee. 
 The sediment usually contains only a moderate excess of 
 squamous epithelial cells. If the urine contains albumin, 
 after centrifugalizing the sediment will be found to contain 
 an occasional hyaline and finely granular cast, renal cell, 
 and blood globule — in other words, evidences of a very 
 slight active hyperemia, perhaps the result of increased 
 activity of the kidneys. Since hysteria is more common in 
 the female than in the male, the presence in the urine of a 
 profuse vaginal secretion will in many instances account for 
 a very slight albuminuria, without necessarily having any 
 evidence of a renal disturbance. 
 
 Charcot has called attention to the fact that in hysteria 
 the quantity of urine may be very small. He records a 
 case in which the patient suffered from v^omiting and diar- 
 rhea, and in which there w^as complete suppression of urine 
 for eleven days. Deception was not possible, as the 
 patient was closely watched. 
 
 CEREBROSPINAL MENINGITIS. 
 
 In this disease the urine has the characteristics of a fever 
 urine accompanied by exudation. The quantity of urine is 
 small ; the color is normal or pale, and sometimes it is 
 high ; the specific gravity is usually somewhat above the 
 normal ; and the reaction is only faintly acid or it may be 
 alkaline. The total quantity of urea is high, the increase 
 usually amounting to 25 per cent, or more (Purdy). The 
 phosphates are much increased in the early part of the dis- 
 ease, so that upon performing the heat test for albumin 
 without the customary addition of acetic acid, an abundant 
 precipitate is thrown down by the test ; later in the disease 
 the phosphates become diminished. The chlorides are
 
 394 DISEASES OUTSIDE OF THE URINARY TRACT. 
 
 greatly diminished from the first and may, in rare instances, 
 be absent. Albumin, which is invariably present, varies in 
 quantity from the slightest possible trace to ^ or ^^ of i 
 per cent., but is dependent on the amount of renal involve- 
 ment and the quantity of blood present. Glycosuria has 
 been noted in some instances. The sediment contains hya- 
 line, granular, and brown granular casts, renal epithelial 
 cells, and more or less blood. 
 
 The renal disturbance is usually an active hyperemia, 
 which may be quite severe. Rarely, an acute nephritis 
 with marked hematuria develops, especially in the malig- 
 nant types. 
 
 In certain cases there is sometimes doubt as to the 
 diagnosis between typhoid fever and an acute cerebrospinal 
 meningitis. Aside from a bacteriologic investigation, an 
 examination of the urine is sometimes of assistance in arriv- 
 ing at a conclusion. The principal differences in the urine 
 in the two diseases are as follows : 
 
 Meningitis. Typhoid Fever. 
 
 Fever Urine with Exudation. Fever Ut'ine without Exudation. 
 
 Color. — Normal or pale. Color. — Very high. 
 Reaction.— Y2\xi'i\^ acid, neutral, or Feactiojt. — Strongly acid. 
 
 alkaline. 
 Chlorine. — Much diminished or ab- Chlorine. — Slightly diminished. 
 
 sent. 
 
 Phosphates. — Much increased. Phosphates. — Diminished. 
 
 MELANCHOLIA. 
 
 In this disease the total quantity of urine is usually much 
 diminished, no doubt in part due to the ingestion of very 
 little liquid. The specific gravity is high, and the coloring- 
 matters and normal solids are relatively increased. The 
 urine is frequently heavily loaded with urates and oxalates. 
 The indoxyl is generally increased. The irritating action 
 of the concentrated urine, and in some instances the 
 mechanic irritation by the crystals of uric acid or calcium 
 oxalate, may be the cause of slight albuminuria and a renal 
 congestion (active hyperemia). 
 
 ACUTE MYELITIS. 
 
 Owing to an involvement of the sphincters in this dis- 
 ease retention or incontinence of urine is an early symptom. 
 An acute or chronic cystitis may rapidly develop, when the
 
 EPILEPSY. 395 
 
 urine becomes faintly acid or alkaline, bloody, and purulent. 
 In such cases the danger of a pyelonephritis by extension 
 is very great ; not infrequently, death occurs during uremic 
 coma. One very prominent feature of the urine in acute 
 myelitis is a marked increase in the indoxyl. 
 
 EPILEPSY. 
 
 Temporary albuminuria accompanied by more or less 
 renal disturbance is of frequent occurrence, especially in 
 those cases of epilepsy in which the convulsive seizures 
 succeed each other very rapidly. Immediately following 
 the attacks the quantity of urine is often much increased, 
 the color pale, the specific gravity low, and the reaction 
 faintly acid. At this time the urea, phosphates, and uric 
 acid are said to be increased. 
 
 As suggested by Taylor, ^ the question of auto-intoxica- 
 tion is to be considered as a possible cause of albuminuria 
 and the renal disturbances in cases of severe nervous 
 affection. It is quite probable that the nervous disease 
 itself may give rise to certain products that are later ex- 
 creted by the kidneys. This is, however, contrary to the 
 view, as generally held, that the effete products normally 
 excreted by the urine are sometimes retained in the body, 
 and that they are the direct cause of various nervous dis- 
 turbances. 
 
 ACUTE ARTICULAR RHEUMATISM. 
 
 In acute rheumatism the urine has the characteristics of 
 that of an acute disease. It is small in quantity, has a high 
 color, and a high specific gravity — 1025 to 1030. Rela- 
 tively, the quantity of urea is increased, absohitely, usually 
 diminished. The uric acid is often both relatively and abso- 
 lutely increased, sometimes to a much larger extent than in 
 most of the other acute diseases. The urine, upon cooling, 
 may contain an abundant deposit of amorphous urates. 
 The chlorides and phosphates are only moderately dimin- 
 ished in an uncomplicated case ; the sulphates are often in- 
 creased. If a pericarditis develops, the chlorides and phos- 
 phates become very much diminished, and may temporarily 
 entirely disappear from the urine. A sudden fall in the 
 
 1 "Boston Med. and Surg. Journ.," Sept. 22, 1898.
 
 396 DISEASES OUTSIDE OF THE URINARY TRACT. 
 
 amounts of these two constituents of the urine is, therefore, 
 indicative of a serious complication. 
 
 Albumin is usually present, but in very small amount — 
 slightest possible trace. Rarel)', it occurs in large quantity 
 attended by an acute nephritis, of which the urinary sedi- 
 ment bears abundant evidence. In the average case of 
 acute rheumatism the sediment contains only a very few 
 renal casts, renal cells, and an occasional blood globule, free 
 and adherent to casts ; in other words, the sediment is char- 
 acteristic of an active hyperemia. 
 
 GOUT. 
 
 During an attack of gout the volume of urine is gener- 
 ally diminished, the color is high, and the specific gravity 
 is above the normal. The uric acid is diminished during 
 the paroxysm ; although it is probably formed in unusual 
 quantities in this disease, the deposit of urates in the joints 
 and tissues accounts for the deficient elimination by the 
 kidneys. Usually, the quantity of urea is not materially 
 altered during the paroxysm of gout. The phosphates are 
 generally much diminished. Albumin is nearly always 
 present, but usually in very small amount. The sediment 
 contains hyaline, granular, and brown granular casts, renal 
 cells, and altered blood free and adherent to casts — the evi- 
 dences of a secondary active hyperemia of the kidne}-. 
 
 Between the attacks or paroxysms, the quantity of urine 
 is normal or even increased. The normal solids are usually 
 about normal, except the uric acid, which is now eliminated 
 in increased amount ; this is especially marked immediately 
 following the paroxysm. Evidence of a more or less marked 
 renal irritation persists between the attacks. 
 
 It should be borne in mind that in chronic gout a chronic 
 interstitial nephritis is not uncommon. Under such circum- 
 stances the quantity of urine is increased ; absolutely, the 
 urea is much diminished, albumin is present, but usually in 
 minute quantity, and the casts in the sediment are generally 
 of the small, narrow, hyaline, and finely granular order. 
 
 Sugar may be found intermittently in the urine of gouty 
 person.s — gouty glycosuria. The condition may pass into 
 true diabetes, but it is usually veiy amenable to treatment. 
 Oxaluria may also be present. Calculi are not uncom- 
 mon in gouty subjects.
 
 ANEMIA. 397 
 
 ANEMIA. 
 
 In the various forms of anemia the urine presents certain 
 characteristics that are common to all. The twenty-four- 
 hour quantity is generally diminished — looo c.c. to 1200 
 c.c. ; the color is pale ; the specific gravity is below the 
 normal — about 1015 ; and the reaction is acid. Relatively 
 and absolutely the normal solids are diminished, but the 
 degree of diminution is dependent largely on the appetite 
 and general metabolism. 
 
 In simple anemia and chlorosis the urine occasionally 
 contains the slightest possible trace of albumin and formed 
 renal elements in the sediment ; on the other hand, albu- 
 min and renal casts may be absent. 
 
 In leukemia the presence of a minute trace of albumin 
 and renal casts is perhaps more common than in simple 
 anemia. Fatty cells and fat adherent to the casts are not 
 uncommon. The indoxyl is frequently increased. Abso- 
 lutely, the urea is diminished. The uric acid excreted is 
 always in excess, and, perhaps, as suggested by Salkowski, 
 stands in direct relation to the splenic tumor or to the 
 abundant leucocytes. The proportion of uric acid to urea 
 may be as high as i to 15. 
 
 In pernicious anemia the urine, although usually pale, 
 may be highly colored from the excess of so-called patho- 
 logic urobilin (Hunter and Mott). The uric acid is in- 
 creased. Albumin, var}dng in quantit)- from the slightest 
 possible trace to a trace, is usually present in the late stages 
 of the disease, and the sediment usually contains renal casts, 
 granular renal cells, and a small quantity of blood. Von 
 Jaksch has noted the presence of peptonuria in this disease, 
 but so far as known it has little or no significance. 
 
 SCURVY. 
 
 In this disease the quantity of urine is reduced, the 
 coloring-matters are increased, and the urine may contain 
 a large amount of blood pigment — hemoglobinuria. Abso- 
 lutely, the normal solids are diminished, especially the 
 chlorine. The urine is generally albuminous, and some- 
 times albumin is present in large amount, especially if there 
 be hemoglobinuria or an acute nephritis. The sediment 
 usually contains renal casts, renal cells, and in case of
 
 398 DISEASES OUTSIDE OF THE URINARY TRACT. 
 
 hemoglobinuria an abundance of brown granular matter. 
 Hematuria is sometimes present, and under all circum- 
 stances should be distinguished from a hemoglobinuria. 
 The author has occasionally met with a genuine acute 
 nephritis in this disease. A more or less marked renal 
 congestion is not uncommon. 
 
 CARBOLIC AQD POISONING. 
 
 In this condition the urine is diminished in quantity ; 
 the color is variable, being usually pale or normal when 
 freshly voided, but upon standing exposed to the air 
 becomes smoky and finally very dark ; occasionally, the 
 urine is dark when it is passed. This characteristic change 
 of color, following the external or internal use of carbolic 
 acid and other phenol compounds, is due to an oxidation 
 of the decomposition products of the phenol or phenol 
 compounds. (See Color of the Urine, p. 25.) The 
 specific gravity is usually normal or diminished ; it may be 
 above the normal. The reaction is acid. Relatively, the 
 normal solids are normal or diminished, depending upon 
 the severity, and occasionally they are relatively increased ; 
 absolutely, diminished, especially the ordinary sulphates, 
 while the conjugate sulphates are much increased. (See 
 Phenol-potassium Sulphate, p. 88.) 
 
 The urine contains albumin ; usually a very slight trace, 
 but in the severe cases it may be as high as ^^ of i per 
 cent. The sediment contains hyaline, granular, and brown 
 granular, and sometimes epithelial casts, renal cells, and 
 abnormal blood free and adherent to the casts. A more 
 or less marked renal congestion is the rule, but occasion- 
 ally a true acute nephritis is present. 
 
 Care should be taken not to confound a dark urine fol- 
 lowing the use of phenol compounds with a urine contain- 
 ing melanin, in which case the urine is often pale when 
 passed, but upon exposure to the air becomes dark. (See 
 Melanin, p. 190.) 
 
 POISONING BY PHOSPHORUS AND ARSENIURETED 
 HYDROGEN. 
 
 The characteristics of the urine in cases of poisoning by 
 arseniureted hydrogen and phosphorus are, for the most 
 part, identical. Hemoglobinuria is the principal symptom.
 
 POISONING BY PHOSPHORUS. 399 
 
 The quantity of urine is diminished. The normal sohds are 
 greatly diminished, especially the urea. In severe cases 
 leucin and tyrosin may appear in the urine. Albuminuria is 
 inv^ariably present ; usually, the amount of albumin is large, 
 although the quantity will depend on the severity of the 
 case. The sediment will contain numerous brown granular 
 and fatty casts, fatty and brown granular renal and com- 
 pound granule cells, a variable but usually small amount of 
 blood, and sometimes crystals of leucin and tyrosin — evi- 
 dences of extensive fatty degenerative changes in the 
 kidney plus a hemoglobinuria.
 
 APPENDIX A. 
 
 METHOD OF RECORDING URINARY EXAMINA- 
 TIONS. 
 
 The advisability of making and preserving urinary records 
 is obvious, since it is only by this means that the progress 
 of disturbances or diseases of the kidney (favorable or un- 
 favorable) can be followed from week to week, or month to 
 month, or year to year. Such records should be made on 
 separate sheets of paper provided for the purpose and in- 
 corporated with the clinical history and physical examina- 
 tion of the patient, or be kept in a book by themselves with 
 cross-references to the volume containing the clinical his- 
 tory, etc. For ordinary use printed urine blanks (see p. 
 401) can be obtained, and as each test is made the result, 
 indicated by abbreviations, should be affixed to the spaces 
 left for the purpose. 
 
 The abbreviations used upon the blank forms have the 
 following meanings : UpJi. = urophaeine ; hid. = indoxyl ; 
 
 67. = chlorine ; &. = urea ; W. =^ uric acid ; Sf. = sul- 
 phates ; E. P. ^^ earthy phosphates ; A. P. =^ alkaline 
 phosphates ; S/'. Gr. = specific gravity ; Sed. = sediment ; 
 A/d. = albumin, etc. 
 
 The common abbreviations used in recording the results 
 of analysis are : -f = increased ; — = diminished ; n = 
 normal. For much increased or much diminished : m + 
 and m — , respectively ; similarly, si. -f and si. — for a 
 slight increase and slight decrease. Other abbreviations, 
 according to the habit and convenience of the recorder, 
 may equally well be adopted. 
 
 The plan of incorporating the urinary records into book 
 form is to be encouraged, especially for those who make a 
 large number of analyses. Such a book properly indexed 
 can be prepared by any competent printer at a moderate 
 cost. A record of this kind is far more serviceable and 
 convenient than the separate sheets. 
 
 400
 
 RECORD OF URINARY EXAMINATIONS. 401 
 
 ANALYSIS OF URINE. 
 
 Date 
 
 Name j 
 
 Amt. in t7oenty-four hours ^=^ Sp. Gr. 
 
 Color =. Sed. = 
 
 Odor = 
 Reaction = 
 
 uph. = cr. (fc)= a. = E. p. 
 
 Ind. = C/.= Sf.= A. F. 
 
 Albumin = 
 Bile Pigments = 
 Sugar = 
 Sediment = 
 
 C C/. := grams. P^0^= grams. 
 
 Quant. - 
 
 ( CI. = " Sugar = " 
 
 Diagnosis = 
 26
 
 402 URINARY EXAMINATIONS. 
 
 Tabular Arrangement of Heller's Tests (modified). 
 
 Physical Properties. 
 
 Color. — Pale, normal, high, or dark. 
 
 Odor. — 
 
 Reaction. — Acid, neutral, or alkaline. 
 
 Sp. Gr. — By urinometer. 
 
 Sediment. — Slight, considerable, or much. 
 
 Normal Constituents. 
 
 IjROPHiEiNE (Uph.). — 7 c.c. HjjSO^ -\- double quantity of Ur. 
 = immediate garnet-red color. 
 
 INDOXYL (Ind.). — 15 c.c. HCl (-\- 2 gtt. HNO3) + 30 gtt. 
 Ur. =: amethyst color, developing in from five to twenty 
 minutes. 
 
 Urea (U.).— With NaOBr. (Squibb's apparatus.) 
 Uric Acid (\J.).—}4 tt. Ur. + HCl = U cryst. in 24°. 
 
 Chlorine (CI.).— Ur. + HNO, + AgNO, (1:8) = soHd 
 ball of AgCl, if normal. 
 
 Sulphates (Sf.).— i^ tt. Ur. + BaCl^ sol. (1:4 sol. + HCl) 
 = ppt. j/2 concav. of tt. in from eighteen to twenty- 
 four hours, if normal. 
 
 Earthy Phosphates (E. P.). — }4 tt. Ur. + NHpH = ppt. 
 j( to yz in. in tt., in from eighteen to twenty-four hours, 
 if normal. 
 
 Alkaline Phosphates (A. P.). — Filtrate from E. P. -\- MgSO^ 
 sol. (MgSO, + NH^Cl + NH^H) = ppt. }4 to }{ in. 
 in tt., in from eighteen to twenty-four hours, if normal. 
 
 Abnormal Constituents. 
 
 Albumin (Alb.). — Heat or HNO3 = coagulum or zone. 
 
 Bile Pigments. — Marechalt's test (iodine). 
 
 Sugar. — Fehling's solution. Phenylhydrazin test. Fermenta- 
 tion test. 
 
 Sediment. — Let settle or centrifugalize, and examine by micro- 
 scope.
 
 ORDER OF APPLYING TESTS. 403 
 
 ORDER OF APPLYING TESTS. 
 
 In the routine analysis of a urine it is advisable first to 
 note the twenty-four-hour quantity, the color, the odor if 
 at all peculiar, the reaction, and the specific gravity. The 
 next in order should be the tests for urophaeine and indoxyl, 
 and then the test for albumin. If more than a trace of 
 albumin be present, it must be removed before testing for 
 chlorides, sulphates, or sugar. Having removed the albu- 
 min by heat from one-third or one-half of a test-tube of the 
 urine after the addition of one drop of acetic acid (see p. 
 129) the test for chlorides, sulphates, and sugar should 
 then be performed. If in the test for albumin a zone of 
 acid urates appears, it should be noted. Such a zone 
 indicates a relative excess of uric acid and urates. The 
 tests for earthy and alkaline phosphates are next in order, 
 and then the test for bile pigments. 
 
 The quantitative test for urea should be performed in 
 every instance, and this is most conveniently done by 
 means of the Squibb or the Doremus apparatus. The per- 
 centage should be noted, and the total number of grams of 
 urea calculated. If sugar be present, it should also always 
 be quantitated, and the total quantity reported in grams. 
 
 The amount of sediment that a urine contains can only 
 be determined after the urine has completely settled. The 
 degree of opacity of the urine can not always be considered 
 acriterion of the amount of sediment present. A urine may 
 be very turbid, for example, by bacteria, and yet contain 
 very little sediment. As soon as the sediment has com- 
 pletely settled, it should be carefully examined by means 
 of the microscope for casts, renal cells, fatty cells, fat adher- 
 rent to the casts, blood, pus, crystalline elements, etc. 
 
 METHOD OF MAKING DIAGNOSES OF DISEASES OF THE 
 KIDNEYS FROM THE URINE. 
 
 The diagnoses of the different diseases of the kidneys 
 are made chiefly by exclusion. 
 
 It has been shown that, even in a single affection of the 
 kidneys, the characteristics of the urine vary with the severity 
 of the process and the extent of the diseased condition : 
 furthermore, that diseases of the kidneys are very liable to 
 become complicated by other pathologic conditions of these
 
 404 APPENDIX A. 
 
 organs. Thus, the urine becomes modified to a greater or 
 less extent from what one would find if the original disease 
 were uncompHcated. For example, a subacute or chronic 
 disease of the kidneys is very liable to be complicated by a 
 more or less severe acute process ; under such circum- 
 stances, the underlying subacute or chronic process may be 
 partially or entirely obscured by the acute complication. 
 Obviously^ an absolute standard of disease, to which an un- 
 k)ioiun specimen of urine should conform, is entirely out of the 
 question. In other words, a urinary disease is not invariably 
 accompanied by a urine of specific character, but by charac- 
 teristics subject to more or less variation. 
 
 In the foregoing pages of this work the author has 
 endeavored to outline a fairly typical urine of each disease. 
 Having made an accurate examination of an unknown speci- 
 men of urine, it will be found that the characteristics of such 
 a urine harmonize in a general way with those known to be 
 associated with this or that disease. 
 
 In the consideration of a given urine that shows evidence 
 of a renal disturbance or disease (presence of renal casts) 
 the first and most important feature from the standpoint of 
 diagnosis is the total quantity of urine. 
 
 A diminished quantity (less than 1500 c.c.) is, as a rule, 
 indicative of any of the following conditions : 
 
 1. Active hyperemia. 
 
 2. Passive hyperemia. 
 
 3. Acute nephritis (first and second stages). 
 
 4. Subacute glomerular nephritis (all stages). 
 
 5. Chronic renal diseases toward death. 
 
 An increased quantity (more than 1500 c.c.) is strongly 
 suggestive of any of the following conditions : 
 
 {a) Convalescence from severe active hyperemia. 
 
 {p) Convalescence from acute nephritis. 
 
 ic) Chronic interstitial nephritis. 
 
 {d^ Chronic diffuse nephritis. 
 
 (r) Amyloid infiltration. 
 
 Having limited the probable renal disturbance or disease 
 to the class characterized by a small or a large quantity of 
 urine, the next step is to distinguish between the different 
 renal conditions of that class by means of the quantities of 
 normal solids, the amount of albumin, and the peculiarities 
 of the sediment — /. e., the presence or absence of blood on 
 casts, the presence or absence of fat from the kidney, the
 
 METHOD OF MAKING DIAGNOSES. 405 
 
 size and character of the renal casts, etc. In this way the 
 most probable disturbance or disease of the kidneys can 
 usually be narrowed down to one or, perhaps, two of the 
 conditions under consideration. 
 
 Having arrived at the most probable renal affection, the 
 next step is to determine the location and nature of any 
 complications that may be present, whether in the kidneys 
 or in some other portion of the urinary tract. 
 
 In the application of this plan of urinary diagnosis it is 
 obvious that the student must thoroughly familiarize him- 
 self with the characteristics of the urine of each disease of 
 the kidneys, as well as of those of other portions of the 
 urinary tract.
 
 APPENDIX B. 
 
 REAGENTS AND APPARATUS FOR QUALI= 
 
 TATIVE AND QUANTITATIVE 
 
 ANALYSIS OF URINE. 
 
 The reagent bottles should be made of pure, clear glass, 
 free from lead and other impurities. Those for liquid 
 reagents should have a capacity of about 250 c.c, while 
 those for solid reagents need not have a capacity over 
 120 c.c. All bottles should be fitted with ground-glass 
 stoppers, and should have labels upon them in raised glass 
 letters, or a ground-glass label with black letters, and the 
 chemic symbol of the reagent below and separate from the 
 lettering. 
 
 Many of the reagents given below are not really neces- 
 sary for the ordinary routine analysis of urine, but for 
 efficient laboratory work all of those given will be found 
 necessary. 
 
 LIQUID REAGENTS. 
 
 Sulphuric acid, C. P. (H^- Tinct. iodine, U. S. P. 
 
 SOJ. 
 Hydrochloric acid, C. P. 
 
 (HCl). 
 Nitric acid, C. P. (HNO3). 
 Acetic acid (HQHgO,). 
 Amnionic hydrate (NH^- 
 
 OH). 
 Sodic hydrate (NaOH), U. 
 
 S. P. 
 Magnesia mixture. (See p. 
 
 108.) 
 Sol. potassium ferrocyanide 
 
 (I : 10). 
 
 Sol. lead acetate (i : 5). 
 Sol. basic lead acetate (i : 5). 
 Alcohol, 95 per cent. 
 Sodic hydrate for urea. (See 
 
 P- 52.) 
 Bromine (modified) for urea. 
 
 (See p. 53.) _ 
 Fehling's solution. (Seep. 
 
 H7-) 
 
 A. Cupric sulphate so- 
 lution. 
 
 B. Alkaline tartrate so- 
 lution. 
 
 406
 
 REAGENTS. 
 
 407 
 
 Sol. barium chloride. (See 
 
 p. 112.) 
 Sol. ferric chloride — aqueous 
 
 (I : lo). 
 Millon's reagent. (See p. 
 
 i68.) 
 Esbach's reagent, (See p. 
 
 131-) 
 Sol. silver nitrate (i : 8). 
 
 Phenylhydrazin (pure). 
 
 Chloroform. 
 
 Formaline. 
 
 Sol. boric acid (saturated). 
 
 Standard sol. silver nitrate. 
 (See p. 102.) 
 
 Standard sol. uranium ni- 
 trate. (See p. 109.) 
 
 Distilled water. 
 
 SOLID REAGENTS. 
 
 [AH reagents should be chemically pure. 
 
 Cupric sulphate. 
 Caustic soda. 
 Sodium chloride. 
 Potassium iodide. 
 Potassium chromate. 
 Ammonium sulphate. 
 Magnesium sulphate. 
 Ammonium chloride. 
 Sodium acetate. 
 Potassium ferrocyanide. 
 
 Potassium chlorate. 
 Picric acid. 
 Citric acid. 
 Lead acetate. 
 Sulphanilic acid. 
 Sodium nitrite. 
 Sodium carbonate. 
 Mercuric chloride. 
 Potassium bromide. 
 Sodium nitroprusside. 
 
 APPARATUS. 
 
 Test-tubes. 
 
 Test-tube brush. 
 
 Test-tube rack. 
 
 Bunsen burner with two feet rubber tubing, or a spirit lamp. 
 
 Urinometer (Squibb or other of reliable make). 
 
 Urinometer glass with foot and parallel sides. (See Fig. 2.) 
 
 Wine-glasses. (See Fig. 13.) 
 
 Urea apparatus (preferably Squibb' s). 
 
 Urine glasses. (See Fig, 24.) 
 
 Funnels, large and small. 
 
 Filter papers (cut) 4, 6, and 8 inches in diameter. 
 
 Glass tubing for pipettes. 
 
 Glass rods (assorted sizes). 
 
 Litmus paper (red and blue). 
 
 Graduates (100, 500, and looo c.c). 
 
 Evaporating dishes (assorted sizes up to one liter). 
 
 Crucibles. 
 
 Porcelain spatula.
 
 408 APPENDIX B. 
 
 Platinum wire inserted in glass rod. 
 
 Platinum foil. 
 
 Burettes (50 c.c, graduated in tenths of a cubic centimeter). 
 
 Retort stand with burette clamp attached. 
 
 Tripod with copper-wire gauze to cover. 
 
 Triangles. 
 
 Water-bath (preferably copper with rings). 
 
 Crucible tongs. 
 
 Beakers (nests of six). 
 
 Wash bottle (500 c.c). 
 
 Flask (250 c.c). 
 
 Liter flask (graduated on neck). 
 
 Graduated pipettes (5, 10, and 50 c.c). 
 
 Dropping bottle, bulb stopper. 
 
 Esbach's albuminometer. 
 
 Accurate thermometer. 
 
 Accurate balances, turning at i milligram. 
 
 Microscope — Zeiss, Leitz, or Bausch and Lomb, with nose- 
 piece ; objectives corresponding to 3, 5, and 7 of Leitz 
 make, and i and 3 eye-pieces, Leitz make ; Abbey con- 
 denser ; and -^ oil immersion lens. 
 
 Glass slides, cover-glasses, cedar oil, and Canada balsam 
 (in solution). 
 
 Centrifuge capable of 2000 revolutions per minute.
 
 Plate io 
 
 10 20 30 iO 50 CO 70 SO 90 
 
 r 
 
 100 no 120 ISO 11,0 Vto leo 170 
 
 MnhiiilnPM
 
 Spectra (after Neubauer and Vogel). 
 
 1. (!, Oxyhemoglobin ; 3, hemoglobin, free from oxygen. 
 
 2. Methemoglobin : a, in neutral solution ; l>, in alkaline solution. 
 
 3. a, Hematin in acid alcoholic solution ; 5, in ammoniacal solution ; c, 
 reduced hematin. 
 
 4. a, Urobilin in acid solution ; /', zinc salt in ammoniacal solution.
 
 Spectra, Continued (after Neurauer and Vogel). 
 
 5. Hematoporphyrin : a, acid ; l>, alkaline ; r, neutral ; d, metallic 
 spectra. 
 
 6. Bilicyanin : a, in acid solution ; b, in alkaline solution. 
 
 7. Uroerythrin.
 
 Plate i i 
 
 30 iO 50 RO 
 
 110 no 
 
 F 
 
 130 
 
 no 
 
 GC0.50 iO 30 -i'O 10 600 5S9 80 TO 60 50 Ifi 30 20 
 
 C J^ ^ '^ 
 
 656.3 S89.3 527 oU.S 
 
 493 SO 
 
 F 
 
 i86
 
 NDEX 
 
 Abnormal blood, 231 
 
 constituents of the urine, 1 17 
 Abscess of the kidney, 326 
 
 of the prostate, 353 
 Absolute solids, 37 
 Acetone in the urine, 171 
 
 clinical significance of, 171 
 detection of, 172 
 Legal' s test for, 172 
 quantitative estimation of, 172 
 Acetonuria, 17 1 
 Acid, carbonic, 1 1 5 
 
 conjugate sulphuric, 1 14 
 
 damaluric, 30 
 
 damolic, 30 
 
 fatty, 97 
 
 fermentation, 32 
 
 hippuric, 80 
 
 lactic, 97 
 
 nucleic, 75 
 
 oxalic, 96 
 
 phenylic, 30 
 
 phosphoric, determination of, 109 
 
 sarcolactic, 97 
 
 succinic, 97 
 
 sulphuric, ill 
 
 taurylic, 30 
 Acidity, causes of diminished, ^^^ 
 
 of increased, 34 
 Acids, biliary, 178 
 Active hyperemia, 282 
 
 severe, 286 
 Acute articular rheumatism, urine in, 
 
 .395 
 diffuse nephritis, 292 
 general peritonitis, urine in, 391 
 myelitis, urine in, 394 
 yellow atrophy of the liver, urine 
 in, 392 
 Albumin in the urine, 1 18 
 
 approximate estimation of, 123 
 
 detection of, 122 
 
 quantitative estimation of, 130, 
 
 132 
 removal of, 129 
 testing for, method of, 122 
 Albuminometer, Esbach's, 131 
 
 Albuminuria, causes of, 119 
 
 clinical importance of, 1 19 
 
 false, 121 
 
 functional or physiologic, 1 20 
 
 of adolescence, 121 
 Albumoses, 134 
 
 clinical significance of, 135 
 
 detection of, 136 
 Albumosuria, 135 
 Alcapton, 28 
 
 as a reducing agent, 150 
 Alkaline carbonates, 29, 32 
 
 phosphates, 107 
 detection of, 108 
 
 tide, 32 
 Alkalinity of the urine, 32 
 Allantoin, 76 
 
 detection of, 77 
 Almen's tannin solution, 142 
 Ammoniacal decomposition of the 
 
 urine, S3 
 Ammonio-magnesium phosphate, 215 
 Ammonium urate, 211 
 Amorphous urates, 212 
 
 treatment of sediment contain- 
 ing, 212 
 Amphoteric reaction, ^3 
 Amyloid concretions, 260 
 
 infiltration, 317 
 Analysis of calculi, 280 
 Anemia, urine in, 397 
 Antialbumose, 134 
 Antipeptone, 137 
 Anuria, 25 
 
 Apparatus for analysis of urine, 406 
 Appendix, 400 
 Aromatic oxyacids, 82 
 
 substances in the urine, 80 
 Arsenic in the urine, 184 
 
 test for, 185 
 Ascarides in the urine, 269 
 
 Bacteria in the urine, 263 
 
 cause of turbidity, 30 
 Bacterial casts, 256 
 Barfoed's reagent, 165 
 
 409
 
 410 
 
 INDEX. 
 
 Barium chloride, standard solution of, 
 
 "3 
 
 solution for sulphates, 1 1 2 
 Bausch & Lomb hand centrifuge, 203 
 Bile in the urine, 175 
 Biliary acids, 178 
 
 clinical significance of, 179 
 detection of, 180 
 isolation of, 179 
 quantitative estimation of, 181 
 pigments, 175 
 
 clinical significance of, 176 
 detection of, 177 
 Bilirubin-calcium, 176 
 Bilirubin in the urine, 224 
 Biuret reaction, 139 
 Black urine, 28 
 Bladder, cancer of, 348 
 epithelium from, 245 
 inflammation of, 342 
 tuberculosis of, 346 
 tumors of, 348 
 Blood, abnormal, 231 
 in the urine, 230 
 
 treatment of sediment containing, 
 231 
 normal, 230 
 Blood-casts, 254 
 Blood-pigment, Teichmann's test for, 
 
 235 
 Bloody color of the urine, 28 
 Blue color of the urine, 28 
 Boric acid as a preservative, 23 
 Bowman, theory of, 17 
 Bromides in the urine, 187 
 
 Cadaverin, 222 
 Calcium carbonate calculi, 278 
 oxalate, 96, 217 
 calculi, 277 
 
 clinical significance of, 220 
 crystals of, 218 
 phosphate, 215 
 urate, 212 
 Calculi, urinary, 270 
 
 chemic examination of, 280 
 constituents of, 272 
 Calculous pyelitis, 335 
 Calculus, vesical, 344 
 Cancer of the bladder, 348 
 of the kidney, 328 
 of the prostate, 357 
 Cane-sugar in the urine, 170 
 Carbohydrates in the urine, 145 
 Carbolic-acid poisoning, urine in, ^c 
 Carbonates in the urine, 115 
 
 alkaline, 29 
 Casts, bacterial, 256 
 
 Casts, bacterial, classification of, 248 
 crystalline, 256 
 epithelial, 253 
 false, 257 
 fatty, 255 
 fibrinous, 250 
 granular, 252 
 hyaline, 248 
 renal, 247 
 waxy, 251 
 Cells, compound granule, 246 
 
 seminal, 245 
 Centrifugal method of estimating al- 
 bumin, 132 
 chlorides, 105 
 phosphates, iii 
 uric acid, 70 
 of obtaining sediment, 200 
 Centrifuges, 202, 203 
 Cerebrospinal meningitis, urine in, 
 
 393 
 Chloral in the urine, 186 
 Chlorides, 99 
 
 clinical significance of, lOO 
 
 detection of, loi 
 
 quantitative estimation of, loi 
 Chlorinated lime, solution of, 52 
 Cholera, urine in, 387 
 Cholesterin in the urine, 22S 
 
 detection of, 229 
 Chronic diffuse nephritis, 314 
 
 interstitial nephritis, 305 
 Chyle in the urine, 30, 360 
 Chyluria, 360 
 
 Collection of urine for analysis, 22 
 Coloring-matters, 90 
 Color of the urine, 25 
 
 under normal conditions, 25 
 under pathologic conditions, 26 
 Compound granule cells, 246 
 Concretions, 270 
 
 amyloid, 260 
 
 calcium carbonate, 278 
 oxalate, 277 
 
 cystin, 278 
 
 fibrin and blood, 280 
 
 indigo, 279 
 
 phosphatic, 277 
 
 prostatic, 280 
 
 uric acid and urates, 276 
 
 urostealith, 279 
 
 xanthin, 278 
 Constituents of normal urine, 21 
 
 of lu'inary calculi, 272 
 Convalescence from acute nephritis, 
 296 
 
 from severe active hyperemia, 287 
 Corpora amylacere, 259 
 Cover-glasses, 206
 
 INDEX. 
 
 411 
 
 Crystalline casts, 256 
 Cyclic albuminuria, 121 
 Cystic disease of the kidney, 329 
 Cystin, 31, 221 
 
 calculi, 278 
 
 detection of, 223 
 Cystinuria, causes of, 222 
 
 clinical significance of, 223 
 Cystitis, acute, 342 
 
 chronic, 344 
 
 Dark color of the urine, 27 
 Day- and night-urine, 23 
 
 collection of, 23 
 Deutero-albumose, 135 
 Dextrose in urine, 145. See Glucose. 
 Diabetes mellitus, 368 
 
 insipidus, 375 
 
 phosphatic, 108 
 Diabetic coma, 373 
 Diacetic acid in the urine, 1 74 
 
 clinical significance of, 174 
 detection of, 175 
 Diaceturia, 174 
 Diagnosis of kidney disease from the 
 
 urine, 403 
 Diamines in the urine, 222 
 Diazo reaction, Ehrlich's, 182 
 Diffuse nephritis, acute, 292 
 
 chronic, 314 
 Diminished acidity, causes of, T^'i, 
 
 quantity of urine, causes of, 24 
 Diphtheria, urine in, 390 
 Distoma hematobium, 267 
 Donne's test for pus, 239 
 Dysalbumose, 135 
 
 Earthy phosphates, 106 
 
 cause of turbid urine, 29 
 
 detection of, 108 
 
 quantitative estimation of, IIO 
 
 Echinococci, 268 
 
 Ehrlich's diazo reaction, 182 
 
 Einhom's saccharimeter, 160 
 
 Electric centrifuge, 202 
 
 Epilepsy, urine in, 395 
 
 Epithelial casts, 253 
 
 Epithelium in urine, 241 
 
 Erysipelas, urine in, 386 
 
 Esbach's albuminometer, 131 
 
 method of quantitating albumin, 
 
 131 
 
 Ethereal sulphates. 83, 114 
 
 formation of, 83 
 Eustrongylus gigas, 269 
 Extraneous substances in urine, 261 
 
 False albuminuria, 121 
 
 casts, 257 
 Fatty acids in urine, 97 
 
 casts, 255 
 Febrile acetonuria, 171 
 Fehling's solution, 147 
 
 test for sugar, 147, 155 
 Fermentation, acid, 32 
 
 -test for sugar, 152, 159 
 Ferments in the urine, 97 
 Fever urine, 378 
 Fibrin in the urine, 143 
 
 clinical significance of, 143 
 detection of, 143 
 Fibrinous casts, 250 
 Filaria sanguinis hominis, 267, 360 
 Florence reaction for seminal fluid, 
 
 259 
 Fokker-Salkowski method for estimat- 
 ing uric acid, 58 
 Folin's method for estimating uric 
 
 acid, 70 
 Formalin as a preservative, 23 
 Fowler's hypochlorite method for 
 
 urea, 58 
 Frohn's reagent, 153 
 Functional albuminuria, 120 
 Functions of the kidneys, 17 
 Furfurol reaction for bile acids, 181 
 for tyrosin, 227 
 
 Gases in the urine, 364 
 
 General diseases, urine in, 379 
 
 Globulin in the urine, 132 
 
 clinical significance of, 133 
 quantitative estimation of, 133 
 
 Globuloses, 1 34 
 
 Glomerular nephritis, subacute, 300 
 
 Glucose in the urine, 145 
 bismuth test for, 153 
 detection of, 146 
 Fehling's test for, 147 
 fermentation test for, 152 
 isolation of, 146 
 methylene-blue test for, 154 
 Nylander's test for, 154 
 phenylhydrazin test for, 150 
 quantitative detennination of, 155 
 Trommer's test for, 147 
 
 Glycosuria, 368 
 
 permanent, 368. See Diabetes 
 
 Mellitus. 
 temporary, 368 
 traumatic, 369 
 
 Glycuronic acid in the urine, 169 
 
 isolation and detection of, 170 
 
 Gmelin's test for bile pigment, 177 
 
 Gonococci, 266
 
 412 
 
 INDEX. 
 
 Gonorrhea, 358 
 
 Gout, urine in, 396 
 
 Gram' s method of staining gonococci, 
 
 266 
 Granular casts, 252 
 Grape-sugar in the urine, 145. See 
 
 Glucose. 
 Greenish tint to the urine, 28 
 Guanin in the urine, 71 
 
 Halliburton's table of colors, 28 
 Hand centrifuge, 203 
 Heat-test for albumin, 125 
 Heidenhain, experiments of, 18 
 Heintze's method of estimating uric 
 
 acid, 66 
 Hematogenous icterus, 178 
 Hematoidin in the urine, 224 
 Hematoporphyrin in the urine, 187 
 clinical significance of, 189 
 detection of, 190 
 separation of, 189 
 spectra of, 188 
 Hematuria, 232 
 
 clinical significance of, 232 
 Hemialbumose, 134 
 Hemin crystals, 236 
 Hemipeptone, 137 
 Hemoglobin in the urine, 142 
 oxy-, 142 
 reduced, 142 
 Hemoglobinuria, 362 
 Hepatogenous icterus, 1 78 
 Heteroalbumose, 134 
 Heteroxanthin, 73 
 
 detection of, 74 
 High color of the urine, 25, 26 
 Hippuric acid, 80 
 detection of, 81 
 quantitative estimation of, 82 
 Hoffman's test for tyrosin, 226 
 Hopkin's method of estimating uric 
 
 acid, 67 
 Hoppe-Seyler, classification of, 21 
 Hyaline casts, 248 
 Hydatid cysts of the kidney, 268 
 Hydrochinone in the urine, 27 
 Hydrogen peroxide in the urine, 1 16 
 Hydronephrosis, 337 
 
 symptoms of, 338 
 
 urine in, 338 
 Hydrooaracumaric acid in the urine, 
 
 82 
 Hydruria, 25 
 Hyperemia, active, 282 
 
 passive, 289 
 
 severe active, 286 
 
 Hypobromite method of quantitating 
 
 urea, 50 
 Hypochlorite method of quantitating 
 
 urea, 50 
 Hypoxanthin, 74 
 
 detection of, 75 
 Hysteria, urine in, 393 
 
 Icterus, hematogenous, 176, 178 
 
 hepatogenous, 176, 178 
 Increased acidity of urine, causes of, 34 
 
 quantity of urine, causes of, 24 
 Indigo-blue, 84 
 Indigo calculi, 279 
 Indigo-red, 84 
 Indoxyl -potassium sulphate, 84 
 
 clinical significance of, 85 
 
 detection of, 86 
 Infiltration, amyloid, 317 
 Inorganic constituents of the urine, 99 
 Inosite in urine, 167 
 
 detection of, 168 
 
 isolation of, 168 
 Interstitial nephritis, chronic, 305 
 
 senile, 313 
 Intestinal obstruction, urine in, 391 
 Iodides in the urine, 187 
 Iodoform test for acetone, 172. See 
 
 Licbeu^ s Test. 
 Iron in the urine, 116 
 
 detection of, 116 
 
 Jaffe's urobilin, 90 
 
 Jaundice, 176, 178. See Icterus. 
 
 Kidney, abscess of, 326 
 
 cystic disease of, 329 
 
 disturbances and diseases of, 282 
 
 tuberculosis of, 321 
 
 tumors of, 328 
 Kidneys, functions of, 17 
 Kreatin, 77 
 Kreatinin, 77 
 
 detection of, 79 
 Kreatinin-zinc chloride, 78 
 
 Lactic acid in the urine, 97 
 Lactose in the urine, 164 
 
 detection of, 165 
 
 isolation of, 164 
 Laiose in the urine, 166 
 
 detection of, 167 
 Lead in the urine, 184 
 
 test for, 185 
 Legal' s test for acetone, 172
 
 INDEX. 
 
 413 
 
 Leo's sugar, i66. See Laiose. 
 Leucin, 224 
 
 detection of, 225 
 Sherer's test for, 225 
 Leucocytes in the urine, 236 
 Leucomaines in the urine, 196 
 Levulose in the urine, 165 
 
 detection of, 166 
 Lieben's test for acetone, 172 
 Liebig' s method of estimating urea, 47 
 Lipaciduria, 97 
 Liver, acute yellow atrophy of, urine 
 
 in, 392 
 Local caseating tuberculosis, 321 
 Loetfler's methylene-blue solution, 
 
 266 
 Ludwig, theory of, 18 
 
 Magnesia mixture, 108 
 Malarial fever, urine in, 385 
 Marechalt's test for bile pigments, 177 
 Melancholia, urine in, 394 
 Melanin in the urine, 26, 190 
 
 clinical significance of, 191 
 
 detection of, 191 
 Melanogen, 190 
 Meningitis, cerebrospinal, urine in, 
 
 Mercuric nitrate, standard solution of, 
 
 48 
 Mercury in the urine, 186 
 
 test for, 186 
 Methemoglobin, 27 
 Method of taking specific gravity, 37 
 
 of testing for albumin, 122 
 Micrococcus ureee, 264 
 Micro-organisms in the urine, 263 
 Microscopes, 206 
 Microscopic examination of urinary 
 
 sediments, 206 
 Miliary tuberculosis, acute, 321 
 Milk sugar in the urine, 164 
 Millon's reaction for proteids, 117 
 
 reagent, 168 
 Mohr's method of estimating chlorine, 
 
 lOI 
 
 Mounting of urinary sediments, 202 
 Mucin in the urine, 98, 140 
 Murexide test for uric acid, 66 
 Myelitis, acute, urine in, 394 
 
 Neisser, gonococcus of, 266, 358 
 Nephritis, acute diffuse, 292 
 chronic diffuse, 314 
 
 interstitial, 305 
 interstitial, 305 
 senile, 300 
 
 Nephritis, subacute glomerular, 300 
 Neubauer-Salkowski method of esti- 
 mating chlorine, 103 
 Nitric acid test for albumin, 122 
 Nomenclature, 19 
 Nonorganized sediments, 208 
 Nonpathogenic bacteria in the urine, 
 
 263 
 Normal blood, 230 
 
 urine, constituents of, 2 1 
 
 quantitative composition of, 21 
 urobilin, 90 
 Nucleic acid, 75 
 
 detection of, 76 
 Nucleo-albumin, I40 
 
 clinical significance of, 141 
 detection of, 141 
 Nylander's test for sugar, 154 
 
 Obstruction, intestinal, urine in, 
 
 391 
 Obstructive suppression, 25 
 
 Odor of the urine, 30 
 
 Oliguria, 25 . , . , 
 
 Order of application of chemical 
 
 tests, 403 
 Organic constituents of normal urine, 
 
 41 
 Organized sediments, 230 
 Origin of urobilin, 90 
 Oxalate of calcium, 96, 217 
 
 crystals of, 218 
 Oxalic acid in the urine, 96 
 Oxyacids, aromatic, 82 
 Oxybutyric acid, A-, in the urine, 160 
 Oxyhemoglobin, 142 
 
 Paraoxyphenyl-acetic acid in the 
 
 urine, 82 
 Parasites, 267 
 Paraxanthin, 75 
 
 detection of, 75 
 Parkes' table of urinary constituents, 
 
 21 
 Passive hyperemia, 289 
 of pregnancy, 290 
 Pathogenic bacteria in the urine, 265 
 Pathologic urobilin, 90 
 Peculiar odor of the urine, 31 
 Pelvic epithelium, 243 
 Penicillium glaucum, 265 
 Pepsin in the urine, 97 
 Peptone, 136 
 
 clinical significance of, 137 
 
 detection of, 138 
 
 separation of, 1 38 
 Peritonitis, urine in, 391
 
 414 
 
 INDEX. 
 
 Permanent glycosuria, 368. See Dia- 
 betes Mellitus. 
 Pettenkofer's test for bile acids, 180 
 Phenol -potassium sulphate, 88 
 clinical significance of, 88 
 detection of, 89 
 determination of, 89 
 Phenylglucosazone, 151 
 Phenylhydrazine test for sugar, 1 50 
 Phosphates, 106, 214 
 
 alkaline, 107 
 
 clinical significance of, 107, 216 
 
 earthy, 106 
 
 quantitative determination of, 109 
 
 separate estimation of earthy and 
 alkaline, no 
 Phosphatic diabetes, 108 
 Phosphaturia, 107 
 Phosphorus-poisoning, urine in, 398 
 Physical properties of the urine, 24 
 Physiologic albuminuria, 120 
 Pigments, biliary, 175 
 Piotrowski's reaction for proteids, 1 17 
 Pipette for sediments, 205 
 Piria's test for tyrosin, 227 
 Pneumaturia, 364 
 Pneumonia, urine in, 383 
 Polariscope, estimation of sugar by, 
 
 160 
 Polyuria, 25 
 
 Potassium ferrocyanide test for albu- 
 min, 126 
 
 permanganate, standard solution of, 
 68 
 
 urate, 212 
 Preservation of urinary sediments, 261 
 Preservatives for urine, 23 
 Prostate, abscess of, 353 
 
 cancer of, 357 
 Prostatic epithelium, 245 
 
 plugs, 257 
 Prostatitis, acute, 351 
 
 chronic, 353 
 
 tubercular, 356 
 Protalbumose, 134 
 Proteids in the urine, 117 
 color-reactions of, II7 
 general precipitants of, I18 
 
 reactions of, 1 17 
 separation and identification of, 
 
 139 
 Proteoses, 134 
 Ptomaines in the urine, 191 
 Pulmonary tuberculosis, urine in, 384 
 Purdy's electric centrifuge, 202 
 
 method of quantitating sugar, 158 
 Pus in the urine, 236 
 
 clinical significance of, 239 
 Donne's test for, 239 
 
 Pus-casts, 255 
 Putrescin, 222 
 Pyelitis, acute, 331 
 
 calculous, 335 
 
 chronic, 333 
 Pyonephrosis, 339 
 
 symptoms of, 340 
 
 urine in, 340 
 Pyuria, 236 
 
 Quantitative composition of the 
 
 urine, 21 
 determination of albumin, 130 
 
 of bile acids, 181 
 
 of chlorides, loi 
 
 of globulin, 133 
 
 of hippuric acid, 82 
 
 of phosphates, 109 
 
 of sugar, 155 
 
 of sulphates, I12 
 
 of urea, 47 
 
 of uric acid, 66 
 Quantity of urine in twenty-four 
 hours, 24 
 
 Reaction of the urine, 31 
 Reagents for analysis of urine, 406 
 Receptacles for urine. 22 
 Records of urinary examinations, 
 
 400 
 Red blood-corpuscles, 230 
 Relapsing fever, urine in, 382 
 Relative solids of the urine, 37 
 Removal of albumin by heat, 129 
 Renal calculus, 324 
 
 casts, 247 
 
 embolism, 327 
 
 epithelium, 242 
 Retention of urine, 25 
 Rheumatism, acute articular, urine in, 
 
 395 
 
 Saccharimeter, Einhorn's, 160 
 Santonin in the urine, 29 
 Sarcina urinse, 265 
 Sarcolactic acid in the urine, 97 
 Scarlet fever, urine in, 388 
 Scurvy, urine in, 397 
 Sediment-glass, 204 
 Sediments, ammonio-magnesium phos- 
 phate in, 215 
 
 ammonium-urate in, 211 
 
 amorphous urates in, 212 
 
 bilirubin in, 224 
 
 blood in, 230
 
 INDEX. 
 
 415 
 
 Sediments, calcium oxalate in, 217 
 phosphate in, 216 
 classitication of, 207 
 cystin in, 221 
 epithelimn in, 241 
 extraneous substances in, 261 
 fragments of tumors in, 349 
 hematoidin in, 224 
 hippuric acid in, 80 
 leucin in, 224 
 leucocytes in, 236 
 mounting of, 262 
 nonorganized, 208 
 organized, 230 
 preparation of, for microscopic 
 
 examination, 206 
 pus in, 236 
 renal casts in, 247 
 spermatozoa in, 258 
 tyrosin in, 226 
 urates in, 210 
 uric acid in, 208 
 Seminal cells, 245 
 Senile interstitial nephritis, 300 
 Serum-albumin, 1 18 
 Serum-globulin, 132 
 Sherer's test for leucin, 225 
 Silver nitrate, standard solution of, 
 
 102 
 Skatoxyl-potassium sulphate, 87 
 
 clinical significance of, 88 
 Smallpox, urine in, 390 
 Smegma bacilli in the urine, 324 
 Smoky color of the urine, 27 
 Soda, chlorinated, solution of, 51 
 Sodium chloride, 99 
 
 hypobromite, solution of, 52 
 nitrite, 182. See Ehrlich' s Reac- 
 tion. 
 urate, 210 
 Solids of the urine, 37 
 
 by specific gravity, 40 
 determination of, 39 
 relative and absolute, 37 
 Specific gravity, 34 
 
 causes of variation, 34 
 method of taking, 37 
 Spermatozoa in the urine, 258 
 
 detection of, 259 
 Squibb' s apparatus for urea, 50 
 Staining of tubercle bacilli, 323 
 
 of gonococci, 266 
 Standard solution of barium chloride, 
 
 113 
 
 of nitrate of silver, 1 02 
 of uranium nitrate, 109 
 Subacute glomerular nephritis, 300 
 Succinic acid in the urine, 97 
 Sugar in the urine, 145 
 
 Sugar in the urine, detection of, 146 
 
 quantitative determination of, 155 
 Sulphanilic acid, 182. See EhrlicIC s 
 
 Reaction. 
 Sulphates in the urine. III 
 
 clinical significance of, 112 
 
 detection of, 112 
 
 ethereal, 83 
 
 quantitative detemiination of, 
 112, 114 
 Sulphuretted hydrogen in the urine, 
 
 31 
 
 Tabular arrangement of Heller's 
 
 tests, 402 
 Tsenia echinococcus, 269 
 Teichmann's test for blood pigment, 
 
 235 
 
 crystals, 236 
 Temporary glycosuria, 368, 37 : 
 Tests, chemical, order of application 
 of, 403 
 
 for albumin, 122. 125 
 Total solids, 38 
 Toxicity of the urine, 196 
 Transparency of the urine, 29 
 Traumatic glycosuria, 369 
 Tribromphenol, 89 
 Triple phosphate, crystals of, 215 
 Trommer's test for sugar, 147 
 Trypsin in the urine, 98 
 Tubercle bacilli in the urine, detec- 
 tion of, 323 
 Tuberculosis, local caseating, 321 
 
 of the bladder, 346 
 
 of the kidneys, 321 
 
 of the prostate, 356 
 
 pulmonary, urine in, 384 
 Tumors of the bladder, 348 
 
 of the kidney, 328 
 Turbidity due to amorphous urates, 30 
 
 due to bacteria, 30 
 
 due to earthy phosphates, 29 
 Typhoid fever, urine in, 380 
 Typhus fever, urine in, 382 
 Tyrosin, 226 
 
 clinical significance of, 228 
 
 detection of, 226 
 
 Uhle, table of, 44 
 
 Uranium nitrate, standard solution of, 
 
 109 
 Urates, 210 
 Urea, detection of, 47 
 
 ferment, t^t, 
 
 oxalate, 41 
 
 phosphate, 41
 
 416 
 
 INDEX. 
 
 Urea, properties of, 41 
 
 quantitative determination of, 47 
 
 theory of formation of, 43 
 Uremia, 365 
 Ureometer, Doremus', 56 
 
 Hinds', 57 
 Ureteral epithelium, 244 
 Ureteritis, 341 
 Urethral epithelium, 245 
 Urethritis, 357 
 Uric acid, 59 
 
 clinical significance of, 65, 213 
 crystals of, 208 
 decomposition products of, 61 
 detection of, 66 
 
 quantitative determination of, 66 
 properties of, 61 
 Urinary coloring-matters, 90 
 
 concretions, 270 
 
 chemic examination of, 280 
 composition of, 272 
 
 constituents, Parkes' table of, 21 
 
 sediments, 199 
 
 method of obtaining, 200 
 Urine, abnormal constituents of, 117 
 
 alkalinity of, 32 
 
 ammoniacal decomposition of, ^3 
 
 analysis of, apparatus for, 406 
 
 black, 28 
 
 color of, 25 
 
 glass, 204 
 
 increased acidity of, 34 
 quantity of, 24 
 
 inorganic constituents of, 99 
 
 normal, 21 
 
 odor of, 30 
 
 of chronic disease, 379 
 
 organic constituents of, 41 
 
 preservatives for, 23 
 
 reaction of, 31 
 
 reagents for analysis of, 406 
 
 receptacles for, 22 
 
 relative solids of, 37 
 
 retention of, 25 
 
 solids of, 37 
 
 specific gravity of, 34 
 
 toxicity of, 196 
 
 transparency of, 29 
 
 turbidity of, 29 
 Urinometer, 35 
 
 glass, 35 
 
 Urinous odor, 30 
 
 Urobilin, clinical significance of, 92 
 
 detection of, 92 
 
 normal, 90 
 • origin of, 90 
 
 pathologic, 90 
 Urochrome, 92 
 
 detection of, 93 
 Uroerythrin, 94 
 
 detection of, 95 
 
 significance of, 94 
 Urophxin test, 92 
 Urorosein, 95 
 
 detection of, 95 
 Urostealith calculi, 279 
 
 Vaginal discharge in the urine, 241, 
 246 
 epithelium, 246 
 
 Vegetable substances in the urine, 28 
 
 Vesical calculus, 344 
 
 Villous tumor of the bladder, 348 
 
 Vogel's scale of colors, 26 
 
 Volatile acids, 30 
 
 Volhard and Falck's method of esti- 
 mating chlorine, 104 
 
 Waxy casts, 251 
 
 Weidel's reaction for heteroxanthin, 
 
 75 
 for paraxanthin, 75 
 Weyl's test for kreatinin, 79 
 
 Xanthin, 72 
 
 bases, 71 
 
 isolation of, 75 
 
 concretions, 278 
 
 detection of, 73 
 Xanthoproteic reaction, 117 
 
 Yeast fungus in the urine, 264 
 Yellow atrophy of the liver, acute, 
 
 392 
 fever, urine in, 381 
 Yvon and Berlioz, comparative table 
 of, 22
 
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 NOTHNAGEL'S ENCYCLOPEDIA 
 
 OF 
 
 PRACTICAL MEDICINE 
 
 Edited by ALFRED STENGEL. M.D. 
 
 Professor of Clinical Medicine in the University of Pennsylvania ; Visiting 
 Physician to the Pennsylvania Hospital 
 
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 . in the original German. In view of these facts, Messrs. W. B. Saunders & Com- 
 pany have arranged with the publishers to issue at once an authorized edition 
 of this great encyclopedia of medicine in English. 
 
 For the present a set of some ten or twelve volumes, representing the most 
 practical part of this encyclopedia, and selected with especial thought of the needs 
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 and will choose the editors of the different volumes. 
 
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 who do not care to subscribe for the entire work at one time. 
 
 This American edition of Nothnagel's Encyclopedia will, without question, 
 form the greatest System of Medicine ever produced, and the publishers feel con- 
 fident that it will meet with general favor in the medical profession.
 
 NOTHNAGEL^S ENCYCLOPEDIA 
 
 VOLUMES JUST ISSUED AND IN PRESS 
 
 VOLUME I 
 Editor, William Osier, M.D., F.R.C.P. 
 
 Professor of Medicine in Johns Hopkins 
 University 
 
 CONTENTS 
 Typhoid Fever. By Dr. H. Curschmann, 
 of Leipsic. Typhus Fever. By Dr. H. 
 CfRSCHMANX, of Leipsic. 
 
 Handsome octavo volume of about 600 pages. 
 Just Issued 
 
 VOLUME II 
 
 Editor, Sir J. W. Moore, B. A., M.D., 
 F.R.CP.I., of Dublin 
 
 Professor of Practice cf Medicine, Royal College 
 of Surgeons in Ireland 
 
 CONTENTS 
 
 Erysipelas and Erysipeloid. By Dr. H. Lex- 
 )iAKTZ, of Hamburg. Cholera Asiatica and 
 Chokra Nostras. By Dr. K. xon Lieber- 
 MEISTER, of Tiibingen. Whoooing Cough 
 and Hay Fever. By Dr. G. Sticker, of 
 Giessen. Varicella. By Dr. Tii. von JUR- 
 i^ENSEN, of Tiibingen. Variola (including 
 Vaccination). Ey Dr. H. Immermann, of 
 Basle. 
 
 Handsome octavo volume of over 700 pages. 
 Jtist Issued 
 
 VOLUME VII 
 Editor, John H. Musser, M. D. 
 
 Professor of Clinical Medicine, University of 
 Pennsylvania 
 
 CONTENTS 
 
 Diseases of the Bronchi. By Dr. F. A. Hi .ff- 
 MAN.N, of LeipMC. Diseases of the Pleura. 
 By Dr. Rosenbach, of Berlin. Pneumonia. 
 Bv Dr. E. Aufrecht, of Magdeburc 
 
 VOLUME VIII 
 Editor, Charles G. Stockton, M. D. 
 
 Professor of Medicine, University of Buffalo 
 CONTENTS 
 
 Diseases of the Stomach. By Dr. F. Riegel, 
 of Giessen. 
 
 VOLUME IX 
 Editor, Frederick A. Packard, M. D. 
 
 Physician to the Pennsylvania Hospital and to the 
 Children's Hospital, Philadelphia 
 
 CONTENTS 
 
 Diseases of the Liver. By Drs. H. Quincke 
 and G. Hoppe-Seyler, of Kiel. 
 
 VOLUME m 
 Editor, "WiUiam P. Northrup, M. D. 
 
 ProfessoV of Pediatrics , University and Bellevue 
 Medical College 
 
 CONTENTS 
 
 Measles. By Dr. Tit. von Jurgensen, of 
 lubingen. Scarlet Fever. By the same 
 author. Rotheln. By the same author. 
 
 VOLUME X 
 Editor, Reginald H. Fitz, A.M., M. D. 
 
 Hersey Professor of the Theory and Practice 
 of Physic, Harvard University 
 
 CONTENTS 
 
 Diseases of the Pancreas. B>y Dr. L. Oser. 
 ot Vienna. Diseases of the Suprarenals. 
 
 By Dr. E. Neusser, of Vienna. 
 
 VOLUME VI 
 Editor, Alfred Stengel, M. D. 
 
 Professor of Clinical Medicine, University of 
 Fennsyliuima 
 
 CONTENTS 
 
 Anemia. By Dr. P. Ehrlich, of Frankfort- 
 on-the-Main, and Dr. A. Lazakus, of Char- 
 lottenburg. Chlorosis. By Dr. K. von 
 NooRDEN, of Frankfort-on-the-Main. Dis- 
 eases of the Spleen and Hemorrhagic 
 Diathesis. By Ijr. .M. Littkn, of ikrlin. 
 
 VOLUMES IV, V, and XI 
 Editors announced later 
 
 Vol. IV. — Influenza and Dengue. By Dr. O. 
 
 LeichtensteRn, of Cologne. MalarialDis- 
 
 eases. By Dr. J- Mannaberg, of Vienna. 
 \ol. \. — Tuberculosis and Acute General 
 
 Miliary Tuberculosis. By Dr. G. C' irnet, 
 
 of Berlin. 
 
 Vol. XI. — Diseases of the Intestines and 
 Peritoneum. By Dr. H. Nothnagel, 
 
 of Vienna. 
 
 19
 
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 Haynes — A Manual of Anatomy, . . 
 
 Heisler — A Text-Book of Embryology 
 
 Leroy — Essentials of Histology, . . . 
 
 Nancrede — Essentials of Anatomy, . . 
 
 Nancrede — Essentials of Anatomy 
 Manual of Practical Dissection, . . 
 
 nd 
 
 BACTERIOLOGY. 
 
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 Frothingliani — Laljoratory Guide 
 
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 ology 
 
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 Thomas— Diet-Lists 
 
 13 
 
 CHEMISTRY AND PHYSICS. 
 
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 Wolff — Essentials of Medical Chemistry, . 
 
 CHILDREN. 
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 Children, 
 
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 Meigs — -Feeding in Early Infancy, .... 
 Powell — Essentials of Diseases of Children, 
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 nosis 
 
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 gology and Otology 6 
 
 Gleason — Essentials of Diseases of the Ear, 15 
 
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 Gradle — Ear, Nose, and Throat, 22 
 
 Griinwald and Grayson— Atlas of Dis- 
 eases of the Larynx 16 
 
 Haah and De Schweinitz — Atlas of Exter- 
 nal Disea-.es of the Eye 16 
 
 Haah and De Schweinitz^ Atlas of Oph- 
 thalmoscopy, 17 
 
 Jackson — .Manual of Diseases of the Eye, 8 
 
 Jackson — Essentials of Diseases of Eye, 15 
 
 Kyle — Diseases of the Nose and Throat, . 9 
 
 GENITO-URINARY. 
 
 An American Text-Book of Genito-^Jri- 
 
 nary and Skin Diseases, 2 
 
 Hyde and Montgomery — Syphilis and the 
 
 Venereal Diseases 8 
 
 Martin — Essentials of Minor Surgery, 
 
 Bandaging, and Venereal Diseases, ... 15 
 Mracek and Bangs — Atlas of Syphilis and 
 
 the Venereal Diseases 16 
 
 Saundby — Renal and Urinary Diseases, . . 11 
 Senn — Genito-Urinary Tuberculosis, ... 12 
 ■yecki — Sexual Impotence, 14 
 
 GYNECOLOGY. 
 
 American Text-Book of Gynecology, 
 
 Cragin — Essentials of Gynecology 15 
 
 Garrigues — Diseases of Women, .... 6 
 Long — Syllabus of Gynecology, . .. 
 Penrose — Diseasesof Women, . . . 
 Pryor — Pelvic Inflammations, . . . 
 Sihaeffer & Norris — Atlas of Gynecology, 17 
 
 HYGIENE. 
 
 Abbott — Hygiene of Transmissible Diseases 3 
 
 Bergey — Principles of Hygiene 22 
 
 Pyle — Personal Hygiene 11 
 
 MATERIA MEDICA, PHARMACOL- 
 OGY, AND THERAPEUTICS. 
 
 American Text-Book of Therapeutics, . . i 
 Butler — Text-Book of Materia Medica, 
 
 Therapeutics, and Pharmacology, ... 4 
 
 Morris — Ess. of M. M. and Therapeutics, 15 
 
 Saunders' Pocket Medical Formulary, . . 11 
 
 Sayre — Essentials of Pharmacy 15 
 
 Sollmann — Pext- Book of Pharmacology, . 22 
 
 Stevens — Manual of Therapeutics, ... 13 
 
 Stoney — Materia Medica for Nurses, . . 13 
 
 Thornton — Prescription-Writing 13
 
 MEDICAL PUBLICATIONS OF \V. B. SAUNDERS 6- 
 
 CO. 
 
 MEDICAL JUPySPRUDENCE AND 
 TOXICOLOGY. 
 
 Chapman— M e d i c u 1 J urispi udence and 
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 Golebiewski and Bailey— Atlas of Dis- 
 eases Caused by Accidents 17 
 
 Hofmann and Peterson— Atlas of Legal 
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 NERVOUS AND MENTAL 
 DISEASES, ETC. 
 
 Brower — Manual of Insanity 22 
 
 Chapin — Compendium of Insanity, ... 5 
 Cliurcll andPeterson — Nervous and Men- 
 tal Diseases c 
 
 Jakob & Fisher— Atlas of Nervous System, 17 
 Shaw— Essentials of Nervous Diseases and 
 
 Insanity ic 
 
 NURSING. 
 Davis — Obstetric and Gvnecologic Nursing, 6 
 Griffith— The Care of the Baby, . . . 
 Hart — Diet in Sickness and in Health, 
 Meigs — Feeding in Early Infancy, . . 
 Morten — Nurses' Dictionary, .... 
 Stoney— Materia Medica for Nurses, 
 Stoney — Practical Points in Nursing, . 
 Stoney — Surgical Technic for Nurses, 
 Watson — Handbook for Nurses, . . 
 
 OBSTETRICS. 
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 Norris— Syllabus of Obstetrics, . 
 Schaeffer'and Edgar- Atlas of Obstetri- 
 cal Diagnosis and Treatment 17 
 
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 Histology 16 
 
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 nique o 
 
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 peutics, 14 
 
 PHYSIOLOGY. 
 
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 Stewart— Manual of Physiology, .... 13 
 
 PRACTICE OF MEDICINE. 
 
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 LockWOOd — Manual of the Practice of 
 
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 Morris — Ess. of Practice of Medicine, . . 15 
 Salinger and Kalteyer— Modern Medi- 
 cine u 
 
 Stevens — Manual of Practice of Medicine, i ^ 
 
 SKIN AND VENEREAL. 
 
 An American Text-Book of Genito- 
 urinary and Skin Diseases 2 
 
 Hyde and Montgomery— Syphilis and tlie 
 Venereal Diseases, . . . ' g 
 
 Martin— Essentials of Minor Surgery, 
 Bandaging, and Venereal Diseases. . .' 15 
 
 Mracek and Stelwagon— Atlas of Diseases 
 of tho Skm j5 
 
 Stelwagon— Essenti, lis of Diseases of the 
 Skin jr 
 
 SURGERY. 
 
 An American Text-Book of Surgery, . . 2 
 An American Year-Book of Medicine and 
 
 Surgery ^ 
 
 Beck — Fractures 4 
 
 Beck — Manual of Surgical Asepsis, ... 4 
 
 Da Costa — Manual of Surgery, 5 
 
 International Text-Book of Surgery, . . 8 
 
 Keen — Operation Blank, 8 
 
 Keen — The Surgical Complications and 
 
 Sequels of Typhoid Fever 8 
 
 Macdonald— Surgical Diagnosis and Treat- 
 ment g 
 
 Martin— Essentials of Minor Surgery, 
 
 Bandaging, and Venereal Diseases, . . 15 
 
 Martin— Essentials of Surgery 15 
 
 Moore — Orthopedic Surgery 10 
 
 Nancrede — Principles of Surgery, .... 10 
 
 Pye — Bandaging and Surgical Dressing, . 11 
 
 Scudder — Treatment of Fractures, ... 12 
 
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 Senn — Practical Surgery 12 
 
 Senn — Syllabus of Surgery, 12 
 
 Senn — Pathology and Surgical Treatment 
 
 of Tumors 12 
 
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 peutics 14 
 
 Zuckerkandl and Da Costa — Atlas of 
 
 Operative Surgery 16 
 
 URINE AND URINARY DISEASES. 
 
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 Wolflf — Handbook of Urine-Examina- 
 tion, 22 
 
 Wolflf — Essentials of Examination of 
 Urine 15 
 
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 Bastin — Laboratory Exercises in Botany, . 4 
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 Gould and Pyle— Anomalies and Curiosi- 
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 Grafstrom— Massage 7 
 
 Keating — How to Examine for Life Insur- 
 ance, s 
 
 Saunders' Medical Hand-Atlases, ' '. '. 16,17 
 Saunders' Pocket Medical Formulary, . . 'n 
 Saunders' Question-Compends, . . . 14,15 
 Stewart and Lawrence— Essentials of 
 
 Medical Electricitv le 
 
 Thornton— Dose-Book and Manual of 
 
 Prescription-Writing 13 
 
 Van Valzah and Nisbet— Diseases of the 
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