BOUGHT WITH THE INCOME FROM THE SAGE ENDOWMENT FUND THE GIFT OF Mttnvu 13- Sage 1891 ^.H:a-f:l:.3j& s:)/:t|g3^ Cornell University Library RB 53.N47 1863 A guide to the qualitative and quantitat 012 373 811 Cornell University Library The original of tiiis book is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924012373811 A GUIDE TO THE QFAUTATIVE A5D QUAOTITAIIVE MALYSIS OF THE TJEINE, DESIGNED ESPECIALLY POB THE USE OP MEDICAL MEN. DK. C. NEUBAUER and DE. J. VOGEL. FOURTH EDITION, CONSIDERABLY ALTERED AND BNLABOliD. ( With i Plates and 28 Woodcuts.) TRANSLATED BY "WILLIAM 0. MAKKHAM, F.K.P.L., FH1SIC1AN 10 ST. HART'S HOSPITAL. THE NEW SYDENHAM SOCIETY, LONDON. MDCCCLXm. LONDON ! Frinted ty 1. >v. Koobi, 9, Xirby Street. Hatton Oardoa. 6fH NOTICE. The translation of the third edition of this work was completed two years ago, and some sheets of it had already passed through the press, when a fourth edition of it was announced as forthcoming ia Germany. As this;, the fourth edition, had undergone complete revi- sion, and contained many important additions, it was thought advisable to await its appearance before publishing the translation. Through the kindness of Dr. Neubauer and Dr. Vogel in furnishing the Society with proofs of the new edition as it was passing through the press in Germany, the Translator has been enabled to produce the English version very soon after its appearance in Germany. London, July, 18fi3. PREFACE TO THE FOURTH EDITION. The first edition of this work on the Analysis of the Urine was presented to the Medical Profession in 1854, subsequent to a course of Lectures on the subject dehvered by me to Medical Men and Pharmaceutists at Wiesbaden. The chief object which I had in view in its production was, that it should be of service to the physician engaged in practice. The favourable reception which it met with convinced me that it had not altogether failed in this respect; and induced me when, in 1856, the book was a second time called for, once again to work out thoroughly the whole subject- matter of it. Besides this, in order to meet a desideratum. Prof. J. Vogel undertook what now forms the Second Division of the work, the Semiology of the Human Urine. In this new form the book appeared in 1856; and again a third time in 1858. Another edition, the fourth, has now been called for. In this fourth edition I have still endeavoured above all to keep the practical in view, so as to render the book a safe guide for the Physician and the Pharmaceutist in their investigations into the state of the urine. The medical student it is hoped will also find in it a clear description of the chemical characters of the normal and abnormal constituents of the urine. The first part treats of the chemical character of the different normal and abnormal consti- tuents of the urine, and contains many new methods for their pre- paration and tests ; several of the processes formerly given have been worked out anew, and the whole subject brought up to a level with the science of the day. Moreover, the large number of investigations into the urine, which have been made in the laboratory here by viii PREFACE TO THE FOURTH EDITION. myself, and by Medical Men and Pharmaceutists, has enabled me to alter and improve the method of Quantitative Analysis described in the second part. The method given in this part for estimating the whole of the fixed constituents of the urine, the volumetrical analysis of phosphorus by means of uranic oxide, the estimation of creatinine, and the volumetrical analysis of albumen are entirely new. The volumetrical analysis of chlorine by means of the silver- solution after Mohr, the sulphuric acid-, and sugar-volumetrical analysis, and the estimation of albumen and alkalies, have all undergone con- siderable alterations. I have to thank the Publishers of Fnnke's Atlas of Physiological Chemistry, for the permission given me to use their plates. C. NEUBAUEE. Wiesbaden, November, 1862. CONTENTS OF THE FIRST DIVISION OF THE BOOK, BY DR. C. NEUBAUER. Introduction Page . 1 FIRST PART. 1. The physical and chemical characters of healthy urine . The organic normal constituents of the urine. 2. Urea 3. Creatine 4. Creatinine 5. Xanthine 6. Uric acid 7. Hippuric acid 8. Phenylic acid Taurylic acid Damaluric acid Damolic acid 9. Urine-pigments Uroheematine Uroxan thine Urrhodine Page . 8 . 15 . 18 . 22 . 25 . 33 . 38 . 40 . 40 . 40 . 42 . 42 . 44 . 45 Uroglaucine . . 45 Uroerythrine . . 49 1 0. Inorganic constituents of the urine . .49 11. Chloride of sodium . 50 12. Chloride of potassium . 53 13. Sulphates . . 54 14. Acid phosphate of soda . 55 15. Phosphate of lime and mag- nesia . .58 16. Iron . . .60 17. Ammoniacal salts . 61 18. Silicic acid . . 63 Abnormal constituents of the urine. . 64 . 69 Grape sugar 70 . 80 19. Albumen 20. Appendix 21. Diabetic sugar- 22. Alkapton 23. Inosite . • -83 24. Bile . . -84 Bile-pigments . • 85 Cholepyrrhine . 85 Biliverdine . • 86 25. Bile-acids . .88 Taiirocholic acid . 88 Glycochollo acid . 89 26. Lactic acid . ■ 91 27. Acetic acid . • 95 28. Butyric acid . . 96 29. Benzoic acid . . 98 30. Fat . . • 100 31. Sulphuretted hydrogen . 101 32. AUantoine . . 102 33. Leucine . -105 34. Tyrosine . .107 35. Sediments of the urine- General remarks . 110 CONTENTS OF THE FIRST DIVISION. Inorganic sediments. Bee. 36. Uric acid 37. Urates . 38. Oxalate of lime Page 113 114 , 116 39. Earthy phosphates 40. Cystine 41. Tyrosine Page 118 120 123 Organic sediments. 42. Mucus and epithelium 43. Blood . 44. Pus . 123 125 128 45. Urinary casts 46. Spermatozoa 47. Fungi— Infusoria 130 131 132 Accidental constituents of the urine. 48. General remarks . 134 — 1. Inorganic compounds 136 -2. Organic compounds . 140 SECOND PART. 49. Quantitative analysis of the urine 50. Determination of the quan- tity of urine passed in a given time 51. The specific gravity of the urine 52. Determination of the quan- tity of water and of soluble matters in the urine 53. The quantity of incombus- tible salts in the urine . 54. The quantity of colouring- matter in the urine 55. The volumetrical method . 56. Apparatus required 67. Mode of procedure 58. The quantity. of chlorine in the urine 59. Estimation of the mercury (after Liebig) . 60. Estimation of the urea 61. Estimation of the phos- phoric acid, with salts of uranic oxide 143 145 147 150 156 159 161 162 168 169 177 179 190 62, 196 199 201 205 210 214 Estimation of the phospho- ric acid with per-chloride of iron Estimation of the free acid in the urine . Estimation of the sulphuric acid Estimation of the sugar . Estimation of the iodine . Estimation of the iron Estimation of the uric acid 217 Estimationof thecreatinine 220 Estimation of the albumen 222 71. Estimation of the lime and magnesia . . 227 72. Estimation of the ammonia 233 73. Estimationof the ammonia and potash by means of bi-chloride of platinum . 74. Estimation of the potash and soda 75. Estimation of the carbonic acid 76. Estimation of the whole of nitrogen 77. Estimation of the fat 236 237 239 240 243 CONTENTS OF THE SECOND DIVISION. THIRD PART. Method to he followed in the qualitative and quantitative analysis of the urine. Sec. 78. Qualitative method 79. Process for testing the pre- sence of soluble bodies in the urine . 80. Microscopical characters of urinary sediments 81. Mode of preserving urinary sediments Page 244 245 250 255 Sec. 82. 83. Quantitative analysis of the urine . .258 Directions for the approxi- mative estimation of the different constituents of the urine . . 265 Analytical examples . 268 CONTENTS OF THE SECOND DIVISION OF THE WORK, BY DB. JULIUS VOGEL. Introduction . 281 FIRST PART. Quantitative changes in the urine. 84. Colour of the urine . 286 99. Hippuric acid in the urine 327 85. Odour of the urine . 290 100. Earthy phosphates in the 86. Clearness and turbidity of . urine . . 329 the urine . . 291 101. Oxalate of lime in the 87. Chemical reaction of the urine . . 331 urine . . 292 102. Cystine in the urine . 336 88. Albumen in the urine . 299 103. Xanthine — Hypoxanthine 89. Fibrine in the urine . 306 — Guanine — Guanoxau- 90. Blood in the urine . 307 thine — Tyrosine in the 91. Blooddissolvedintheurine 310 urine . . 337 92. Fat in the urine .312 104. Mucus and epithelium in 93. Bile-pigments in the urine 314 the urine . . 338 94. Biliary acids in the urine 315 105. Pus in the urine . 339 95. Sugar in the urine . 316 106. Cancerous and tubercular 96. Accidental abnormal con- matters in the urine . 342 stituents . . 321 107. Urinary casts in the urine 345 97. Urinary sediments . 323 108. Fun gi — Infusoria — Kies- 98. Sediments of uric acid in the urine . . 348 and of urates . 324 109. Spermatozoa in the urine 350 CONTENTS OF THE SECOND DIVISION. SECOND PART. Sec. Pago 110. Qnantitative changes in the urine . .351 111. Quantity of the urine . 362 112. Solid residue and specific gravity of the urine . 360 113. Quantity of pigment mat- ter in the urine . 368 114. Complicated quantitative analyses . .372 1 15. General rules of quantita- tive analysis . .374 116. Quantity of urea in the urine . . 378 in health . 384 in disease . 385 117. Quantity of uric acid in urine . . 386 Bee. rage 118. Quantity of free acids in the urine . . 389 119. — ammonia in the urine. 391 120. — chlorine and chloride of sodium in the urine . 393 121. — sulphuric acid in the urine . . 402 122. — phosphoric acid in the urine . , 409 123. — earthy phosphates in the urine . .415 124. — creatinine, allantoine, leucine, and tyrosine in the urine . .418 125. Concluding observations . 419 126. Urinary calculi and urinary concretions in the urine 431 CONTENTS. ALPHABETICAL INDEX. Page Accidental constituents of the Bile-acids . Page 88, 315 urine 134, 321 Blood in the urine . . 307 Acetic acid . 95 — indication Of 125, 307 Acidity of the urine, estimation — dissolved . 310 of . 199 Butyric acid . 96 Acrolein . . 101 Cancer in the urine . . 342 Albumen, characters 64, 299 Carbolic acid . 38 — quantitative estimation of, Carbonic acid, estimation of in 222, 304 the urine . 239 — indication of . 301 Casfeine . 70 Albuminose . 70 Chemical reaction of the urine 292 Alkaline urine 237, 294, 322 Chlorine, estimation of . 169 Alkapton . . 80 — quantity and indication of . 393 AUantoine . 102, 28 Cholepyrrhine . 85 Alloxan . 29 — indication of . 314 AUoxantine . 30 Cholesterine 91, 100 Amide of acetic acid . 36 Cholic acid . 88 Ammonia, test . 61 Choloidic acid . 88 — quantitative estimation of. Cobalt in the urine . . 322 233, 391 Copper in the urine . . 322 Ammonia, acid urate of, . 115 Copper solution . 205 Ammonio-phosphate of mag- Creatine . 15 nesia 119, 329 Creatinine, characters, tests . 18 — indication of . 330 — quantitative estimation of . 220 — as a sediment . 119 Creatinine chloride of zinc . 20 — quantity of . 417 Cystine . 120 Ammoniacal salts . 61 — indication of . 336 Analytical examples . . 268 Damaluric acid . 40 Antimony in the urine . 322 Damolic acid . 40 Apparatus, analytical . 162 Diabetes . . 353 Arsenic in the urine , . 322 Diabetic sugar 70, 316 Ash of the urine . 156 — quantitative estimation of Barium, volumetrical solution 205, 317 of . 202 — indication of . 319 Baryta, acetate of . . 96 Epithelium 123, 338 Baryta, butyrate of . . 97 Exsiccator . . 152 Benzoic acid . 98 Fat, characters, tests 100, 312 Benzo-glycholic acid . . 36 — quantitative estimation of Biliverdine . 86, 314 243, 313 Bile . 84 — indication . 313 Bile-pigments 85, 314 Fibrine 69, 306 — indication of . 314 — indication . 307 ALPHABETICAL INDEX. Foreign bodies in the urine 134, 321 Free acids in the urine, estima- tion of . , . 199 — indication of . . 390 Fungi . . 132, 348 Glycine . . 36, 89 Glycocoll . . 36, 89 Glycocholic acid . . 89 Guanine and guanoxanthine . 337 Hippuric acid, properties, tests 33, 327 — indications of — preparation of Haemato-crystalline . Hsematoglobuline . Haematuria Hypoxanthine Incineration Incombustible salts, estimation of, in the urine Indican Indigo Infusoria . .132, Inorganic constituents of the urine Inosite Iodine, estimation of 210, Iron, tests . — quantitative estimation of — solution of perchloride of Kieatein Lactic acid Lactide Lead in the urine Leucine . . 66, 105, 419 Lime, quantitative estimation of 227 — lactate of . .92 — oxalate of . 116,331 — phosphate of . 119,329 — urate of . . 115 Lime and magnesia, phosphate of . . . — quantitative estimation of . Lime, phosphate of . — quantity of in urine Magnesia, phosphate of — quantitative estimation of . Mercury in the urine — estimation of — volumetrical solution of, for the determination of chlorine in the urine — volumetrical solution for the determination of urea in the urine . . .181 Mucus . . 123, 338 328 34 126 310 308 337 156 156 44 44 348 49 83 322 60 214 197 349 91 92 822 58 231 58 417 58 231 136, 322 177 170 Mucus-corpuscles Murexide . Nickel in the urine . Nitrobenzine Nitrogen, estimation of Omichmyloxide Oxalic acid Oxaluric acid Oxaluria . Parabanic acid Phenylic acid Page . 124 . 30 . 322 . 36 . 240 . 49 . 116 . 29 . 334 . 29 . 38 Phosphoric acid, estimation of 190 — indication . .411 Picrinic acid . . 39 Pipettes . . .163 Potash-glucose . . 72 Potash, quantitative estimation of . . . 237 Proteine-compounds . . 61 Pus . . 128,339 — indication of . . 340 Quantitative analysis of the urine . . 145, 351 Quinine . , . 142 Sand in the urine . . 323 SarcinsB in the urine 133, 349 Sarcosine . . .17 Silver, volumetrical solution of 175 Silicic acid . . 63 Soda, acid phosphate of . 55 — estimation of . . 237 — urate of . .114 Sodium, chloride of, charac- ters and tests . . 50 — quantitative estimationof 169, 393 — indication . . 401 Solid residue of the urine 156, 360 Specificgravity of the urine 147,360 Spermatozoa . 131, 350 Sulphates, indication of . 54 Sulphuretted hydrogen . 101 Sulphuric acid, estimation of . . 201,402 Sugarin the urine, characters 70, 316 — quantitative estimation of . . 206,317 — indication of . .319 Taurine . . .89 Taurocholic acid . . 88 Taurylic acid . . 4o Trimethylamine . . 6 Tubercular matter in the urine 342 Turbidity, &c. of the tirine . 291 Tyrosine . . 107, 123,337 Uranic oxide solution . 190 Urates . . .114 EXPLANATION OF PLATES. PLATES I. TO III., FIGS. 1 to 4, ARE TAKEN FROM DR. O. FUNKE'S PHYSIOLOGICAL ATLAS. Pl« Prf 6 ilKii 'H-.:l , ■' unp. PLA.TE I. Fig. 1. Hippurio acid, obtained from healthy human urine, and t e-cryatallised out of water. Besides the ordinary prisms, crystals perfectly similar to those of the triple-phosphate are often formed, especially when the hippurio acid is slowly deposited. Crystals of this sort may he seen in the lower third of the figure to the left. Fig. 2. Urio acid in different forma, partly prepared from solution and crystallisa- tion of chemically-pure Uric acid, partly from urinary sediments by the action of acids on urates, and partly from spontaneous deposition out of urine. The various forms of urio acid, from the most ordinary kind, viz,, the simple rhombic tables with obtuse rounded angles, up to the more rare modifications, may be readily recognised in the figure. The dumb-bell shaped forms, shown in the upper part of the figure to the left, which also sometimes appear spontaneously, are well represented. Funke always obtained them by dissolving ohemictilly-pure uric acid in concentrated caustic potash, and then decomposing the solution under the microscope by means of concentrated hydrochloric acid. Fig. 3. Urinary sediment, consisting of uric acid, urate of soda, and oxalate of lime from the urine of a person convalescent from typhus. ; A formation of uric acid crystals, not unfrequently met with in sediments, con- sists of large, dense bundles, two of which are joined together at their base; these bimdles are composed of an infinite number of long, fine, whetstone - shaped crystals, which are for the most part colourless. The brilliant, letter-cover shaped crystals are oxalate of lime. The little roundish and angular dark-coloured gran- ules, lying singly, or massed together in irregular groups, consist of urate of soda, which always appears in the urine in this molecular form. (Compare Plate II., Figs. 1 and 2.) Fig. 4. Urinary sediment, consisting of epithelial cylinders, and numerous epithe- lial cells, taken after death from the bladder of a patient who had died of typhus. The cylindrical tubes consist of the epithelial lining of the renal tubuli, whose round nucleated cells are distinctly visible, through a fine granular mass of mole- cules. The club-, caudate-, and spindle-shaped nucleated epithelial cells are de- rived from the ureters, the pelves, and cahces of the kidneys. Fig. 5. Urinary sediment, consisting of cylindrical hyaline bodies, epithelial cells of the bladder, and mucus-corpuscles, from a patient suffering under acute miliary tuberculosis. These urinary cylinders are more rarely met with than the last-mentioned kind ; they are hyaline and homogeneous, and require care to distinguish them from the surrounding fiuid. In this case they here and there appear unusually distinct, in consequence of being covered with small granules of urate of soda. Their extre- mities are somewhat globular and distended. Moreover, there are seen roundish, long, or polygonal, and for the most part distinctly granular pavement-epithelium of the bladder, and very granular mucus-corpuscles. Fig. 6. Urinary sediment, consisting of cylinders of fibrine, blood-, and pus-cor- puscles, and epithelial cells from the albuminous urine of a typhus-patient, in whom post-mortem examination showed well-marked inflammatory infiltration of the cortical substance of the kidneys. The granular cylindrical bodies formed of a well-marked molecular mass, are fibrinous coagula (croupous exudation) from the renal tubuli, whose shape they in fact represent. Some of them contain blood- and pus-corpuscles, a considerable number of which are also seen free, the blood-corpuscles being most of them swollen, and some few of them with the central depression still distinctly visible. The bipolar epithelial cells have been already described under Fig. 4. PLATE II. Fig. 1. Urinary sediment, consisting of urate of soda from the morning urine of a tuberculotis patient. The ordinary whitish, yellowish, or tile-red deposit, which is separated from concentrated acid urine as it cools in the air (especially in febrile states of the body), almost invariably consists of tirate of soda, in the form of molecules and grannies. When rapliy separated, these granules are very fine, and generally deposited together in groups, as here shown. "When the urine has stood some little time (Fig. 4), a few fermentation-fimgi may also be seen, and occasionally epithelial cells of the bladder, which are mostly very granular and round (see the right lower border). Fig. 2. Urinary sediment, consisting of urate of soda, phosphates, and muous- coagulum, from urine which has stood three days. Here the urate of soda is seen separated in the form of much larger and darker granules, and in larger masses than in the former case. The regularly granular and membranous-like forms seen in the centre of the figure, are fragments of the pellicle of amorphous phosphatio earths, which often forms on the surface of urine undergoing decomposition in the air. The smaller and broader twisted bands, which consist of extremely fine points and granules, ranged together in rows, are muous-ooagula, which are not unfrequently met with in acid urine ; and may be easily mistaken for the urinary casts above spoken of. Here also we find fermentation-fungi in rows and masses (as at the under border), and a few very granular mucus-corpuscles. Fig. 3, Urinary sediment, consisting of triple-phosphates, and of numerous mucus- corpuscles, found in the recently passed turbid alkaline urine of a patient suffer- ing under vesical catarrh. The crystals of ammonio-phoaphate of magnesia are of different forms ; but may be readily recognised, without crystallographic or chemical analysis. The mucus- corpuscles are rather small, very contracted, and granular, and for the most part united by their borders into large groups. Fig. 4. Urituiry sediment, consisting ofwrate of soda, uric acid, and fermentation- fungi, from urine which has undergone the acid-fermentation. Normal urine, and almost every kind of acid, abnormal urine, after long standing, undergo the acid-fermentation. Small nucleated fermentation-fungi form as the fermentation advances, and increase by gemmation, and in this way form simple and branched rows, as shown in the figure. At the same time, the yellow- coloured uric acid crystals are gradually separated from the ordinary form of urate of soda, and changed into the simple forms here shown. Moreover, small octohedra of oxalate of lime (as seen at the upper right border) often appear. Fig. 5. Urinary sediment, consisting of crystals of triple-phosphate and urateof am- monia, from urine which has passed into the stage ofalkaline-fermen tation, taken from apatient suffering from paraplegia consequent on disease of the spinal cord. The crystals of triple-phosphate shown are those most commonly met with in decomposed urine. The urate of ammonia is first of aU separated in the form of fine molecules, out of which are gradually formed little globular bodies, which are dark, strongly refractive of light, and become at last studded with fine needle- points of different lengths, like the thorn-apple. Fig. 6. Nitrate ofwea, separated hy means of nitric acid from highly-concentrated human wine. Pip 4' Rg,6 TufTeii Wepi sc ngA. FiA 5 TuCfeo Wc?I ac WW«Bt,-imp PLATE III. Fig. 1. Urinary sediment, consisting of crystals of uric acid from the urine of a girl suffering from acute rheumatism during the menstrual period. Numerous well-marked yellow, vesiole-liie, distended blood-corpuscles of different sizes are seen, as well as brownish-yellow rhombic tables, and other forms of uric acid, which are for the most part disposed in groups and glands, representing the ordinary forms of urinary sediment, which so often appear as a yellow-shining granular sand. Figi 2. Human blood-corpuscles, treated with water. The gradual changes which the blood-corpuscles pass through, under the action of water, are seen in the figure (proceeding from the left border of it to the right). The cells in the first place swell out, take a somewhat lens-like form, and at length become spherical, the point of central depression being gradually elevated, and at last bulging oilt. At the same time, the diameter of the disc is necessarily diminished. They consequently appear smaller, the central shade becomes indis- tinct and at length disappears, whilst at the borders a circular shadow appears ; in a few cells lying at the border the lens-shaped form is distinctly seen. By further action of the water, the cells become paler and more indistinct, so as to be with difficulty distinguished from the surrounding fluid, the contents of the cells— in consequence of the imbibition of water — having the same light-refracting power as the water around them. They appear as extremely fine hyaline vesicles, and at last become wholly invisible. By adding a concentrated solution of neutral salt to the water, the corpuscles again appear as angular, misshapen, indented forms (as seen to the right of the figure). Fig. 3. Pus-corpuscles. In the lower half of the figure, normal pus-corpuscles are seen in the form of round, pale, indistinctly-granular vesicles of different sizes ; some of them having a single round, excentrically-placed nucleus, and some again a compound nucleus. Some of the cytoid corpuscles, as the figure shows, have a well-defined contour, whilst ia others the contour appears indistinctly marked. In the upper half of the figure are seen the results of the action of acetic acid on pus-corpuscles. The cor- puscles swell out, their surface becomes smooth, and so hyaline that their contour is hardly distinguishable ; the nuclei consequently appear in various numbers and forms, sometimes single, round, oval, of a biscuit- or horse-shoe shape, sometimes two, three, and four in number, and of different forms and differently grouped, re- sulting from the division of the single nucleus. Fig. 4. Cystine taken from a vesical calculus, and re-cry,stdlliied out of ammonia. Figs. 5 and 6 represent the most im.portant and frequently mit with organic forms which a/re found in urinary sediment in cases of cancer of the bladder. For the special explanation of the single figures and their signification, see - Section ovi. PLATE IV. (Table of Colours after Vogel.) Fig. 1. Pale-yellow. Fig. 6. Bed. „ 2. Bright-yellow. „ 7. Brownisli-red. „ 3. Yellow. „ 8. Eeddisli-lffowii. „ 4. ReddiBh-yellow. „ 9. Brownisli-blaok. 5. Yellowish-red. PI V[. IPale-re-lJ^H Z.Briijht-Yelluw. S.Tdlow tReddish-VeUew 5. yellowish - red,. 6 Red IBrownuh-red. SJUddish-browrv. 9BrowTdsh-hladc. Tuffea We;t,sc Vf West, imp Table of Colours of the Urine. (VOGEL) INTRODUCTION. The rapid development which Chemistry has undergone during the last decennial period has caused its influence to be generally felt, both in the arts and sciences. Manufacturers and agriculturists have at length become convinced of its importance, and, consequently, study it with zeal. Chemistry has also been of great service to the healing art, and, doubtless, will render it stiQ further services. To this science, in fact, must be attributed, in great part, the advances made by physiology and pathology in modern times. The functions of respiration and nutrition have become more comprehensible since chemistry, with its balance and weights, has determined the character of the metamorphic processes. Physiolo- gists and physicians have long understood the importance of a careful study of these processes ; and have referred to them when giving an account of the greater or less rapidity of the changes going on in the body. Zoo-chemical analysis has also necessarily advanced under the active zeal of so many observers, and has undergone a rapid development. It has taught us that the urine is a collection of the products of the decomposition of the animal structures, and that from the study of the urine we may hope to obtain positive conclusions concerning the nature of the organic processes going on in the diseased, as well as in the healthy, body. The urine has, indeed, been at all times an especial object of study with zoo-chemical analysits. Several substances have been discovered, and many phenomena observed in it, from which we are enabled to draw conclusions concerning the functions of the animal economy. Heretofore, and up to a late date, the analysis of the urine has been a long and difficult process ; indeed, almost impracticable in the hands of the physician. But it is not so now. The physician, armed with the simplest and newest methods of analysis, is now able b 2 INTRODUCTION. in a short time, and at the bedside of the patient, to test the urine, and thereby to discover in it the presence of abnormal consti- tuents, or to determine the quantity of any of its normal consti- tuents. This method of analysis of the urine, combined with a scientific application of the microscope, enables us to arrive at positive conclusions concerning changes going on in the body. It is intended, in the following pages, to give, in the first place, a sketch of the urine in its healthy state ; and also to point out the peculiar changes which it undergoes, as consequences of its acid and alkaline fermentations. In the first portion of the work the chemi- cal characters of all the normal, as well as abnormal, organic and inorganic, constituents of the urine will be detailed. Their appear- ance, also, under the microscope, will be especially considered. In the second portion of the work, the different methods to be used in determining the quantity of the constituents of the urine will be described, as well as the necessary precautions, manipula- tions, and modifications required in carrying them out. The third part will contain a practical guide to the qualitative and quantitative analyses of the urine and its sediments, — such as the chemistry of the present day affords. A clear idea of the contents of the work may be obtained from the following summary : — I^EST Paet: 1. Physical and Chemical Characters of the Healthy Urine. 2. Normal Constituents. a. Organic. b. Inorganic. 3. Abnormal Constituents. 4. Sediments. 5. Accidental Constituents. Second Paet: Determination of the Weight of the Organic and Inorganic Constituents of the Urine. Thied Past: 1. Practical Guide to its Qualitative Analysis. 8. Characters of the Sediments under the Microscope. 3. Practical Gxiide to the Quantitative Analysis of the Urine. 4. Practical Guide to the Approximative Valuation of the Quantity of its Constituents. FIRST PART. SECTION I. The physical and chemical characters of healthy urine. The urine, pbysiologically consideredj is a peculiar organic secretion, which is separated from the body by special organs, the kidneys. It contains, in solution, various nitrogenous and saline compounds, the products of the transformations of the tissues, which are no longer serviceable for the purposes of nutrition. The constituents of the healthy urine are, in the main, to be re- garded as products of the metamorphoses of the tissues of the body. The most important of them are the following organic nitrogenous compounds : — Urea, uric acid, hippuric acid, xanthine, and crea- tinine ; and colouring and extractive matters. Urea is the most important constituent of human urine. It is the chief product of the retrograde metamorphoses of the nitro- genous tissues, and undoubtedly results from their oxidation, although we are quite ignorant of the way, in which the oxidation is effected. Notwithstanding the many attempts which have been made, urea has unfortunately not yet been artificially produced by the action of powerful oxidising agents on proteine-compounds.* In addition to the compounds above-named, the mineral consti- tuents of the blood, rendered useless for the purposes of life, — and other matters, which, having been introduced into the body, either interfere with, or do not assist in its nutrition, — are also discharged with the urine, either unchanged or decomposed. The kidneys, moreover, through the urinary secretion, regulate the amount of water in the blood, and maintain it at a pretty equable quantity. • The statement made by Bechamp, that urea may be produced by the action of permanganate of potash on proteine has not been confirmed by Stadeler and myself 4 GENERAL CHARACTERS OF HEALTHY URINE. The healtliy urine, then, is a very complex fluid ;'and its composition differs in different classes of animals. The difference between the urine of carnivorous and the urine of herbivorous animals shows that food exercises a manifest influence over its composition. The urine of carnivorous mammaKa does not differ essentially from that of man. In its fresh state it is clear, and of a light-yellow colour, has an unpleasant odour, a bitter taste, and an acid reaction. The quantity of urea in it is considerable ; but that of uric acid is some- times exceedingly small. The uric acid may, indeed, entirely disappear for a time ; but in such case, it soon reappears, and then in increased quantity, as happens, for example, in the case of animals which are allowed freedom of movement after having been shut up in a cage. The urine of herbivorous, differs considerably from that of carnivorous animals. It is readily recognised by its constant muddy condition and alkaline reaction, as well as by the presence in it of a considerable amount of carbonates of the alkalis and alkaline earths. It often contains a largish quantity of urea, and, generally, an abundance of hippuric acid. Uric acid is not found in it ; and phosphatic salts exist in it only in very small quantities. Oxalate of lime, with crystals of carbonate of lime, are always pre- sent in the sediment of this urine. The influence of food on the composition of the urine is also clearly shown, when an herbivorous animal is fed on animal diet, or when it has been kept for a long time fasting, and its life sustained solely at the cost of its own tissues. Under such circumstances, the urine very soon loses its natural alkaline character, and becomes acid ; urea appears in it in considerable quantity j carbonate of lime is no longer found in the sediment ; and an appreciable quantity of uric acid is generated in it. It thus assumes completely the characters of the urine of a carnivorous animal — a fact of which anyone may readily convince himself by experiments on rabbits. The reverse of this happens when a carnivorous animal is fed on vegetable food. The urine of birds, and of amphibious animals, &c., differs alto- gether from that of the mammalia, showing that the organisation of the animal exercises a distinct influence over the composition of its urine. Healthy human urine, as a rule, resembles that of carnivorous animals. When recent, it is clear, and of a bright amber colour, has a distinct acid reaction, a saltish bitter taste, and a peculiar GENERAL CHARACTERS OF HEALTHY URINE. 6 aromatic odour. Stadeler has, after much labour, thrown some light upon the nature of the odorous matter of the urine; but his experiments refer to the urine of cows rather than to that of man. He succeeded, by the distillation of a large quantity of cows' urine, in recognising as the source of the odour a series of peculiar vola- tile acids, viz., phenylic add, and taurylic, damaluric, and damolic acids. Human urine contains much smaller quantities of these acids ; and it was only when a considerable amount of it was operated upon, that the presence of phenylic acid could be distinctly recognised by its characteristic reactions. The specific gravity of healthy human urine varies between 1*005 and 1"030 — according to the age, the sex, the constitution of the body, and the food. The cause of the constantly acid reaction of healthy human urine has been much disputed. Liebig thinks, that it depends chiefly upon the presence of an acid phosphate. According to the researches of Lehmann, however, there can be no doubt, that in many cases, free hippuric and lactic acids exist in the urine, and consequently assist in giving it its acid reaction. The urine may be preserved for a long time, protected from the contact of air in a closed glass vessel, without suffering any particular decomposition. But when exposed to the air, peculiar and important changes take place in it, and these we shall next more particularly consider. When fresh urine is left to itself in an open vessel, slight clouds of mucus, which gradually sink to the bottom of the vessel, usually soon begin to form in it. In this mucus we find, under the microscope, some pavement epithelium of the bladder and urethra, as well as mucus-corpuscles, united together by fine granular shreds of mucus. A deposit of urate of soda, also, may be often readily recognised in it. When the urine has been left at rest a still longer period, and especially under the influence of a moderate degree of hea.t, its acid reaction becomes stronger; and distinct crystals of impure uric acid are at the same time deposited on the sides and bottom of the glass. This increase of its acidity usually goes on for some days, and may even continue for two or three weeks. The acidity, however, at last begins suddenly to diminish, and gradually disappears. The urine now changes its colour, and becomes lighter; a whitish, iridescent pellicle forms on its surface; and the presence of an unpleasant ammoniacal odour indicates that it has become alkaline. The crystals 6 GENERAL CHARACTERS OF HEALTHY URINE. of uric acid disappear, and whitish granules, and colourless, highly- refractive prismatic crystals are formed. These two phenomena may be distinguished by the names of acid and alkaline fermentations of the urine. Scherer has arrived at some interesting conclusions in reference to the decompositions which attend these fermentations. The most important are the following : — He considers that the vesical mucus of the urine is the original promoter of the acid fermentation. He, in fact, regards it as a ferment, whose presence occasions a decompo- sition of the extractive colouring-matter of the urine, this matter being thereby converted into lactic and acetic acids. In this way the increase of free acid in the urine is produced. A consider- able' quantity of fungi, at the same time, may be seen in the urine, under the microscope. These may be regarded both as the proof, and probably, also, as the promoter of the fermentation ; they closely resemble the cellules of the yeast-plant in their external characters, but are somewhat smaller ; their mode of growth is similar, and so also their linear arrangement. In consequence of the formation of the above-mentioned powerful acids, the bases of the readily decom- posed urates are separated from the uric acid, which is then thrown down in the shape of well-formed crystals. Crystals of oxalate of lime may also almost always be detected in this uric-acid sediment. Of their manner of origin I shall speak more fully under the head of the sediments. {Plate II. Fig. 4.) The free acid of the urine, after a longer or a shorter period, at length begins to diminish, and then commences the second stage of the urine fermentation, the alkaline. The urea is now decomposed, and converted into carbonate of ammonia;* the crystals of uric acid, which had been gradually separated, disappear, and whitish granules of urate of ammonia, as well as prismatic crystals of urate of soda, which often stud the dissolving crystals of uric acid, in a radiated form, take their place. [Plate II. Fig. 5.) As the de- composition proceeds, and as the alkaline reaction commences, a * Beside the carbonate of ammonia, small quantities of other volatile bases, — so-oaUed substitution ammonias,— appear to be formed. Of these , Dessaignes has already noticed one called (Cj H, Trimethylamine N | C^ Hg (C, H, which is characterized by its odour of sea-fish. It was observed by him during the distillation of a large quantity of human urine. GENERAL CHARACTERS OF HEALTHY URINE. 7 part of the ammonia unites with the phosphate of magnesia of the urine, and large quantities of beautiful crystals of phosphate of mag- nesia and ammonia are thrown down. {Plate II. Figs. 3, 5.) This particular decomposition is closely related to the formation of sedi- ments, and I shall, therefore, have occasion to refer to it again. The urea is by far the most important of the constituents of the urme. We have already seen that it is, essentially, the final product of the retrograde metamorphoses of the tissues. It is the medium through which the nitrogen, which has become useless to the body, is again restored to the inorganic world. Separated from the body, and brought into contact with decomposing and putrefying matters, urea is readily converted into ammonia and carbonic acid, and under these forms becomes food for plants, and so again commences its circuit of changes. Uric acid stands next in importance to tirea, and is likewise the product of the decay of the nitrogenous constituents of the body. As a chemical compound, it must be placed above urea, being, by oxidation, finally converted into urea and carbonic acid. The quantity of it in the urine is considerably less than that of urea ; and, unlike urea, it is not found free in the urine, but combined with bases, particidarly with soda. Besides uric acid, we also meet with small quantities of hippuric acid in urine. The source of the hippuric acid has not yet been determined ; but it is very probable that it is formed, Like urea and uric acid, from the retrogressive metamorphoses of the tissues. In addition to these compounds, urine always contains a small quantity of xanthine and creatinine — substances which are also found in the juice of fiesh — and colouring and extractive matters, of whose chemical nature, origin, &c., we unfortunately at present know very little. Of the mineral constituents, the phosphates, and especially the acid phosphate of soda, hold a conspicuous place in healthy urine. Small quantities of the earthy phosphates, phosphates of Hme and phosphates of magnesia, and a considerable quantity of chlorides, viz. chlorides of sodium and potassium, with traces of chloride of anmionium, are also present in it. Lastly, we invariably find, as a constituent of urine, sulphuric acid, which, together with the phosphorus of the phosphatic salts, are derived chiefly from the sulphur and phosphorus of the used-up proteine- compounds of the body. A certain and, altogether, not an incon- siderable quantity of carbonic acid, derived from the blood which is 8 UREA. continually passing through the kidneys, highly charged with that gas, is evacuated with the urine. Traces of oxide of iron and of silicic acid are also fotind in the ashes of unTie. Besides these normal — organic and inorganic — constituents, the urine may contain pathological and accidental constituents. Of the numerous pathological constituents of urine, albumen, sugar, bile, and fat may be particularly mentioned j tliey appear in the urine as consequences of special diseased conditions of the body. The accidental vary much in kind, and are introduced into the body either accidentally or designedly. They are discharged from the urine either unchanged or after having undergone chemical decom- positions. They will be specially treated of in the Pourth Part. We shall now proceed to the more particular consideration of the different normal, organic and inorganic, as well as of the pathological and accidental, constituents of the urine. THE NORMAL ORGANIC CONSTITUENTS OF THE URINE. SECTION II. UUBA. Composition : — In 100 parts: Carbon . . . 20-000 Hydrogen . . . 6-666 Nitrogen . . . 46-667 Oxygen . •. . 26-667 100-000 • „. n tr AT2r> d™*: ie i_ tv T I XT A. Oeomrence. — Urea exists in the urine of mammalia, of birds, and of reptiles, but is most abundant in the urine of carnivorous animals. It is also constantly present in the blood, and often in considerable quantities after extirpation of the kidneys, and in Bright's disease. The fact of the quantity of urea increasing in the blood after extirpation of the kidneys, tends to show that this substance is UREA. 9 formed in the blood and not in the kidneys — ^that it is, in fact, the product of the oxidation of unserviceable nitrogenous materials — the results of the wear and tear of the tissues, and also of the superfluous nitrogenous matters, which have been introduced into the blood. Urea does not exist in the juice of muscles, but it may be artificially obtained out of certain bodies — creatinine, xanthine, hypoxanthine, &c. — which are present in this juice. Consequently, we may assume, that this class of bodies (to which also the uric acid found in the blood belongs) is converted into urea and other compounds by the action of oxygen and the free alkalis, and then discharged from the body by the kidneys. Thus, uric acid, creatine, glycine, allantoine, guanine, theine, gelatine, and superfluous nitrogenous nutritive materials, when intro- duced into the blood, are converted into urea and other compounds, and so cause a rapid increase in the quantity of urea in the urine.* Urea is also found in healthy blood, in the amniotic fluid, and in the vitreous and aqueous humours of the eye. Funke and others have found it to be a normal constituent of the sweat. Wurtz likewise found it in the lymph and chyle of different animals. It does not appear to be normally present in the muscles of man, and of the vertebrata generally ; at least no one has yet succeeded in finding it there. It probably, however, exists in the muscles and organs of many of the lower animals. Notable quantities of it were found by Stadeler and Frerichs in the muscles, and in almost all the organs of many cartilaginous fishes, whilst in the corresponding parts of bony fishes it was sought for in vain. Urea is found in nearly all the fluids of the body, when its excretion through the kidneys is interfered with or suppressed. In such case, an in- crease of it is first observed in the blood, and after that it soon appears in the serous exudations ; it has also been found in the bile and the ssQiva, in vomited matters, and even in pus and milk. Undei*suoh circumstances, the sweat also contains much urea, so that even a slight crust of urea may sometimes remain after the evaporation of the sweat (Schottin). When urea is introduced into the body it is not decomposed under normal, conditions, but is rapidly removed, so that in the course of a few minutes a distinct increase of the urea may be often observed in the urine. Gallois saw a rabbit weighing two kilogrammes killed by 20 grammes of urea ; first * I must here call attention to an interesting investigation into the physiological action of the spleen and the sources of the urea, by Fiihrer and G-. Ludwig, in the Archiv fiir Physiolog. Heilkunde, 1855. Heft 3 and 4. The authors offer, as the result of their researches, the following conclu- sion : The urea, during normal nutrition, is essentially derived from the solution of the morphotic elements of the blood, and all superfluous food taken into the body occasions an excessive formation and destruction of these elements. 10 UREA. of all, its respiration was retarded, then came on weakness of the limb, tremblings, twitchings, general convulsions, rigidity, and death. The urine of a healthy man, under mixed diet, contains on an average from 2-5 to 3-2 p. c. of urea; hence, from 22 to 35 grammes of it are discharged in the twenty-four hours. The quantity of the urea excreted, however, varies much, and is greatly influenced by the weight of the body and the food taken. Lehmann found the quan- tity of urea to amount to 58 grammes in the twenty-four hours under a purely animal diet, and to diminish to 15 grammes under a non- nitrogenous diet. The urea does not, however, wholly disappear from the urine, even when no food is taken. There are several methods by which urea may be artificially pro- duced. For example, cyanate of ammonia, which has an elementary composition similar to that of urea, is, when heated in solution, readily changed into urea. Urea may be also produced from creatine, allantoine, aloxan, oxamide, and many other bodies. Uric acid, when subjected to the action of powerful oxidising agents, yields, as its ultimate products, urea, carbonic acid, and water. Nathansen has lately discovered two other modes of forming urea, which seem to indicate that urea is probably an amide of carbonic acid. He obtained urea by heating carbonic ether with an excess of ammonia; and also by the action of chloro-carbonic acid on dry ammoniacal gas. I can corroborate both these facts. B. Preparation: — 1. Vrom, the urine. — Two volumes of urine are mixed with one volume of the solution of baryta, as used in the quantitative ..analysis of urea. The mixture is filtered, in order to remove from it the precipitate of phosphate and sul- phate of baryta, which is formed, and is then evaporated to dryness in a water-bath. The residue is treated with alcohol, and, after filtration, evaporated to dryness. The saline products thus obtained are treated with pure alcohol. The solution now contains pure urea, which, on evaporation, crystaUises in colour- less needles. Should the urea not be perfectly colourless, it may be made so by subsequent treatment with pure animal char- coal. 2. From cyanate of ammonia. — Eighty grammes of anhydrous ferro-cyanide of potassium are heated over a gentle fire, with thirty grammes of carbonate of potass, until a portion of the mass, on trial, hardens into a colourless glass. The crucible containing UREA. U the mixture is then removed from the fire, and 150 grammes of red- lead are added to it very gradually, and in smaU quantities at a time ; the mass is again heated about ten minutes, and kept con- stantly stirred, and then poured upon an iron plate. When it has cooled, the crude cyanate of potass is moistened with a solution of 80 grammes of sulphate of ammonia in 400 to 500 grammes of water, and when all of it is dissolved, the solution is filtered and evaporated to dryness. The dried saline mass is then treated, and several times digested, with small portions of alcohol (100 to 200 grammes, SOJ) ; the solution is filtered, the alcohol separated by dis- tillation, and the residue then left to crystaUise. 0. Microscopical characters. — When pure urea is rapidly depo- sited from a concentrated solution, it appears, under the microscope, in the form of white, shining, sUky needles. But when the crystal- lisation takes place slowly in a weak solution, beautiful silky, white, nearly transparent, shining, striated, four-sided prisms, terminated by one or two obhque facets, are formed. (Funke, Tlate II. Fig. 4.) D. Chemical cha/racters. — Urea has a bitterish, cool taste, resem- bling that of saltpetre. Its crystals contain no water, are permanent in the air, and readily dissolve in water and in alcohol. Its solu- tions are neutral. In ether it is almost whoUy insoluble. 1. When urea is moderately heated on platina, it melts and gives off ammonia ; but when the heat is increased it becomes solid again, takes a brown colour, and is at last completely consumed, leaving no trace of carbon behind. When the heat is carefully appKed, much ammonia is given off at 150" to 160° C. (SOa" to 320° Fahr.) ; and the remains of the pre- viously melted urea harden into a mass of cyanuric acid 3 (C^ H^ ISr^.OJ = (C, H3 ^3 O, -H 3 N H3), with which are mixed small quantities of other products of the decomposition (ammeHde C^ H^ N, O, and biuret G, H, N, OJ. 2. Urea is decomposed when heated with strong mineral acids, with sulphuric acid, for instance, or with caustic potass or soda, two equivalents of water being added to its elements, and carbonic acid and ammonia formed. (Quantitative analysis by Eagsky and Heintz.) It also undergoes a similar decomposition, first, when we add to its solution putrescible organic nitrogenous matters — ^the cause of the alkaline fermentation of the urine — and, secondly, when it has been exposed for a long time in a closed tube, to a 12 UREA. temperature above 100" C. (Fahr, 212°). (Quantitative analysis by Bunsen) C, H, N, 0, + 2 H = 2 C O, + 2 N H,. 3. When nitrous acid, or a solution of nitrite of suboxide of mercury in nitric acid is added to a solution of urea, the urea is converted into water, carbonic acid, nitrogen, and ammonia. (Liebig, Wohler, Ludwig, and Krohmever.) C, H, N, O, + N O, + N 0„ HO = 2CO^ + 2]Sr + NH, O, NO, + HO. Consequently 1 gramme of urea causes 1'2 gramme of gas to be given off. 4. A solution of urea heated with nitrate of silver yields an in- soluble deposit of cyanate of silver, and the solution contains nitrate of ammonia. By this method we reconvert it into the same com- binations (cyanic acid and ammonia), from which we obtain it artificially. 5. Oxide of mercury forms several definite combinations with urea, in which, according to circumstances, two, three, or four equivalents of the oxide of mercury are combined with one equivalent of urea. Oxide of silver forms a similar combination with urea, three equivalents of the oxide uniting with one of urea. 6. A solution of nitrate of mercury, added to a solution of urea, yields a white flocculent precipitate, the composition of which varies with the degree of concentration of the fluid. The precipitate may have a composition answering to either of the following formulae : — NO„Ur + 2HgO or NO„Ur-|-3HgO or NO^Ur + 4iHgO Corrosive sublimate, on the other hand, occasions no precipitate in weak acid solutions of urea ; but in an alkaline solution it does so readily. Liebig's quantitative determination of the urea and of the chlorine is founded on this fact. 7. Urea mixed with a solution of hypochlorite of soda is con- verted into nitrogen, carbonic acid, and water. The carbonic acid is rapidly absorbed by the ley, so that the quantity of the urea may be determined directly by measurement of the nitrogen. (Davy.) 8. Urea, in an alkaline solution, energetically resists the oxidising agency of hypermanganate of potash; on the other hand, in hydro- chloric acid solutions it readily decomposes, especially when heated, and is converted into carbonic acid and ammonia. This property of urea tends to indicate that it is the final product of the retro- UREA. 13 gressive metamorphoses of the tissues ; for in an alkaline solution, and so, therefore, in normal blood, it is not oxidised by oxidising agents. Hereby, also, it is essentially distinguished from uric acid, creatine, guanine, &c,, which are, in a manner, one step higher in composition. Urea also remains unaffected when in contact with ozone, under whose influence uric acid is rapidly decomposed and urea produced. 9. Just as urea arises from the union of cyanic acid and ammonia, so likewise are compound ureas — combinations perfectly analogous to ordinary urea-compounds — formed when cyanic acid is com- bined with the homologous bases of alcohol radicles instead of ammonia, for example, with ethylamine : (^^^^. . . (^ Thus, N < H instead of with ammonia N < H (h (h These combinations exactly correspond to urea, excepting only that a part of the hydrogen is replaced by the alcohol-radicles — ^for example, by ethyl C^ H^, by methyl C^ Hj, &c. Thus, we have : Urea . . . C J g N, O, 'h Ethyl-urea C, j g^jj = j^^ 0^ Dimethyl-urea C, C, H, N, O, (ZH Ethylmethyl-urea C, C, H, N, 0, (2H &c. AU these compounds resemble urea ; they yield, with nitric acid, salts difficult of solution ; and by the action of potash two equiva- lents are decomposed into carbonic acid and two equivalents of base. For example : Ethyl-urea C, H, N, O,.— (H (O.H, C,H,N,0, + aH0 = 3C0,-i-NH-[-NH (h (h (Ethylamine). 14 UREA. The isomeric dimethyl-urea again yields : — 0. h, n, o, + 2 h o = 2 c 0, + 2 n- h (h (Methylamine). 10. Urea forms crystallisable compounds with many salts — with corrosive sublimate, chloride of sodium, nitrate of lime, chloride of calcium, &c. It likewise produces, with many acids — such as suc- cinic, tartaric, citric, and gallic acids — as well as with inorganic acids, crystallisable salts, two of which, the nitrate and oxalate, are of especial interest. a. Nitrate of urea. — C^ H^ N, O^ N 0„ HO. A concentrated solution of uiea, mixed with pure moderately concentrated nitric acid, free from nitrous acid, throws down, on cooling, white, shining plates or scales. These are for the most part single, but some of them are massed together, overlying one another. When the quantity of urea is small, the formation of the salt may be observed under the miorosoope, and in the following way : — one end of a little bit of thread is laid in the drop which is to be tested for urea ; the drop itself and one-half of the thread is then covered with the glass, and the other end of the thread moistened with a drop of pure nitric acid. In this way, two fluids being gradually mixed together, the formation of crystals goes on very regularly on both sides of the thread which is under the glass ; so that we can examine the crystals during formation. First of all, we observe rhombic plates or short prisms, whose acute angles measure 82°, as well as numerous complicated forms. The forms by removal of their obtuse angles and by flattening are converted into hexagonal plates or six-sided prisms. The development of these crystals, however, only goes on regularly when the processs is slow. "When the crystallisation is rapidly conducted numerous six-sided tile-shaped plates, superimposed the one on the other, are formed. Obtuse octahedra with a rhombic base, of slight durability, and having an acute angle of 82°, are also frequently formed at the moment when the two fluids come in contact; other crystals are also rapidly deposited on these, and hence the primitive octahedra pass into the rhombic or hexa- gonal plates before-mentioned. Lastly, we notice very characteristic twin- crystals, which, from a peculiar arrangement, difficult of description, result in crystalline formations, which very closely resemble the well-known forms of gypsum. {Plate II. Fig. 6.) This salt remains unchanged in the air, dissolves freely in water, but not readily in water mixed with nitric acid, and scarcely at aU in alcohol containing nitric acid. Rapidly heated on platina-foil it detpnates, and at 140'' C. (Falir. 284'') is decomposed into carbonic acid, nitrous oxide, urea, and nitrate of ammonia. CREAT4NE. 15 On mixing a concentrated solution of nitrate of urea with oxalic acid, the second compound, oxalate of urea, is precipitated. b. Oxalateofurea.—% (C, H, N, OJ, C, Oj + 4 H 0. This com- pound, also formed by the mixture of oxalic acid with a concentrated solution of urea, is deposited in the shape of long thin plates or prisms. "When the formation of the crystals is observed under the microscope, they usually appear in the form of hexagonal plates, like those of nitrate of urea, and, more rarely, as four-sided prisms. (Fnnke, Flate II. Fig. 6.) Oxalate of urea dissolves readily in water, but is precipitated from its solution on the addition of an excess of oxalic acid. It is decomposed by heat into carbonate of ammonia and cyanuric acid. E. Tests. — To demonstrate the presence of urea in urine, it is sufficient, in most cases, to evaporate a small quantity (15 to 20 grammes) of urine to the consistence of syrup, in a water-bath ; this residue is then repeatedly washed with alcohol, so long, in fact, as a drop of the. solution, evaporated on a watch-glass, leaves any trace behind it. The urea is now contained in the alcoholic solution, and when the spirit has been driven off in a water-bath, is left as a more or less impure residue. Dissolved in a little water, and treated partly with pure nitric acid and partly with a concentrated solution of oxalic acid, it forms the two above-mentioned compounds. "When very minute quantities are used, the crystallisation of nitrate of urea may be observed under the microscope — the crystalline forms, described above under the head of Nitrate of Urea, being produced. Any albumen contained in the urine must be first of all separated by the addition of a drop of acetic acid and boiling; the solution is then filtered and treated as already described. This process must always be followed when urea is sought for in the blood. SECTION III. Composition :- _ Ckbatine. In 100 parts : Carbon . . . Hydrogen . . Nitrogen . . Oxygen . . (Anhydrous) . . 36-64 . 6-87 . 32-06 . 24-43 100-000 Formula : C,H,N3 0/+ 2 HO. 16 CREATINE. A. Occurrence. — Creatine is found in the juice of muscles both striped and unstripedj in quantities varying from 0*07 to 0-33 p. c. Scherer found only 0'0388 p. c. in horse-flesh. According to Verdeit and Marcet traces of it exist in the blood. W. Miiller and Larch also found it in the brain ; but it has not yet been discovered in the glandular organs. With regard to its presence in the urine, the reader is referred to what is said under the head of Creatinine. Little positive is known concerning the physiological import of creatine. Its presence in the juice of muscle, and its highly nitrogenous composition would lead us to regard it as an important agent of nutrition j but its ready conversion into urea, creatinine, and sarcosine (all of which are undoubtedly to be considered as excretions), gives to it rather the character of an excretion, holding a position, in the stages of retrogressive tissue-metamorphoses some- what midway between the most complex proteine-bodies, and the simpler forms (urea, &c.). Creatine, therefore, is more nearly related to urea than to proteine-bodies. B. Freparation. — ^Flesh finely chopped, or rubbed down with rough glass-powder is mixed with an equal, or one and a-half times its volume of spirits of wine, gently heated in a water-bath, and its fluid then expressed. The spirits of wine is first of all distilled off from this fluid, and the remainder carefully precipitated by acetate of lead. The filtrate is then freed from lead by sulphuretted hydrogen, and, when separated from sulphide of lead, is evaporated to the consistence of syrup in a water-bath. The crystals which separate are collected after an interval of a few days, freed from their mother- ley by being laid on blotting-paper, and then crystallised out of hot water. 0. Microscopic chwracters. — Pure creatine forms colourless, per- fectly transparent, glistening crystals, which belong to the mono- clinic- system. (Punke, Plate III. Fig. 1.) They are usually disposed in groups, somewhat similar to those assumed by sugar of lead. ' When a dilute solution of creatine is placed in a concave object-glass, and allowed to evaporate spontaneously, we first observe at the border of the fluid a formation of long prismatic crystals, which are thickest at their free extremities, and gradually become thinner towards their other ends. Towards the centre of the fluid very regular crystals are gradually formed," and in particular prisms, which are often united together at their acute angles in a fan-like shape. A few crystals here and there in the middle CREATINE. 17 present a oharaoteristic bulging-out, similar to that of lactate of zinc : these become thinner towards their extremities, and are bounded by.two plain surfaces. There also often appear thick, apparently rectangular plates, some- times singly, and sometimes in larger numbers. D. Chemical characters. — Oreaiirie has a bitter, pungent taste. It dissolves in 75 parts of cold 'water. Boiling water takes up a much larger quantity of it, but as it cools, the creatine separates in the form of shining crystalline needles. Alcohol takes up only 1 in 9410 parts ; and in ether it is completely insoluble. Its aqueous solution has no action on vegetable ^colours, has a bitter taste, and very readily undergoes decomposition. Dessaignes has recently succeeded in forming crystalHsable 'compounds of creatine with sulphuric, hydrochloric, and nitric acids. 2. When creatine is boiled for a long time in a solution of baryta, it is converted into urea and sarcosine : C, H„ N3 0, = C, H, N, 0, -^ C, H, N O, (creatine) (urea) (sarcosine) ; and if the boiling be continued still longer, the urea is changed into carbonic acid and ammonia, the ammonia escaping, and the carbonic acid uniting with the baryta. The sarcosine may be obtained, though with difficulty, in the form of colourless crystals. 3. Creatine dissolves without change in dilute mineral acids; but when boiled in concentrated acids, it gives off water, and is converted into creatinine : C3 H„N, 0,-4 H = 0, H,N,0, (creatine) (creatinine). 4. Chloride of zinc produces no precipitate with perfectly pure creatine. (Schlossberger). 5. Creatine is not affected by the action of peroxide of lead; but it is decomposed by permanganate of potass; the products, how- ever, of this decomposition are, with the exception of carbonic acid, unknown. It is possible that urea may be one of the products formed. 6. When a solution of creatine is boiled with an excess of oxide of mercury, carbonic acid is evolved with separation of metallic mercury, and the solution contains the oxalate of a powerful base of methyluramine (C^ H, N,), which, according to Dessaignes, is to be considered as a conjugate of urea and methylamine, effected with separation of water. 18 CREATININE. C, H, N3 + 2 H O = a H, N, 0, + N [ ^ ^ (Urea) E. Tests. — (See Creatinine.) 2H. O.H3 (Methylamine). section iv. Cejbatinine. Composition : — In 100 parts : Carbon .... 42-48 Hydrogen . . . 6'19 Nitrogen . . . 37-17 Oxygen . . . 14-16 100-000 Formula : C. H, N, O,. A. Occv/rrence. — Creatinine is the most powerful organic base met with in the body ; it was first discovered by Liebig in the crystal- line precipitate, which Heintz, and after him, Pettenkofer, obtained by the action of a solution of chloride of zinc on concentrated urine. Liebig found cireatine, as well as creatinine, in this chloride of zinc compound, and was consequently led to the conclusion that both these bodies exist originally in the urine. Heintz, however, after- wards showed, by carefully-conducted experiments, that fresh urine does not contain creatine. He found that the creatine is formed through the decomposition of the chloride of zinc compound, the creatinine of which takes up water and is converted into creatine. This view has been since confirmed by Liebig and Dessaignes. Again, creatine is readily converted into creatinine by abstraction of its water, and therefore the creatine which is always found in the juice of flesh, may be converted into creatinine by the loss of water either ill the flesh itself or more probably in the blood, and thus be eventually discharged with the urine in the fol-m of creatinine. Lehmann considers, rightly enough, that further investigation is required to show whether the creatine of muscle is invariably con- verted into creatinine, and thus evacuated^ or whether it tnay not also assist in the formation of urea; the lattier view is in some degree favoured by its ready conversion into sarcosine and urea when boiled with baryta-water. Dessaignes, on the othdr hand, is of opinion that the juice of muscle originally contains creatinine only, like the CREATININE. 19 urine ; and that it is only after its separation, and under the long- continued action of heat, that the greater part of it is converted into creatine in the neutral fluid. But this view I cannot accept. By Stadele/s new method, creatine is obtained from muscle so readily and in such a pure state, that it is difficult to conceive how, in so short a time, the greater part of the. creatinine can be converted into creatine by the taking up of water. According to my own observations, Q'6 to 1"3 gramme of crea- tinine is passed by a healthy man, living on a good mixed diet, in an average quantity of from 1500 to 1600 C. C. of urine, during the twenty-four hours. Verdeil and Marcet found creatinine in the blood as well as in the urine of man and the juice of muscle ; Socoloff found it in the urine of horses and of sucking-calves ; Dessaignes, in the urine of the cow ; Liebig, in that of the dog. According to Soberer, it is also present in the amnio,tic fluid. B. Microscopic c^arac/e^-^.^-Creatinine crystallises in the form of very glistening, colourless prisms, which belong to the monocHno- metric system. (Panke, Plate III. Fig. 2. 2nd Edit. IV. 5.) c. Chemical characters. — Creatinine forms the strongest organic base met with in the animal kingdom. Its taste is almost as pun- gent as that of ammonia. It is soluble in eleven parts of waiter, at 12«' to 20° C. (Eahr. 54° to 68°), and in a much less quantity of boHiag water. 100 parts of cold alcohol dissolve about one part of creatinine. Boiling alcohol takes up a larger quantity, which is separated again in crystalline masses, as the alcoiiol cools. Ether dissolves only a very small quantity of it. . Its solutions have a strongly alkaline reaction, and a caustic taste, like that of dilute ammonia. Creatinine behaves like ^ nitijle base ; it unites directly with 1 eg^. of iodide, of ethyle, and so parses j^9,to,io.dide,of ethyle-or^atinine, frOjip wMc^, by treatment with oxide of silver theethyle-cre^atinineis separatedas aBowerful base, and may be obtained in a crystalline form. 1. A concentrated solution of chloride of zine, added to a solu- tion of creatinine, immediately throws down a crystalline precipitaite. When vwy slowly formed, the crystals are distinctly prismatic .; but when quidkly produced, and as seen under the microscope, &ie needles are observed concentrically grouped together, forming either perfect rosettes, or tufts which cross each other, or of which each two c 2 20 CREATININE. are connected by their short stalks, so as to resemble brushes pass- ing one into the other. When creatinine is separated by chloride of zinc from the watery extract of urine, the compound is obtained for the most part in the form of dark warty masses, which show very little of a crystalline structure even under the microscope. Sometimes, however, distinct crystalline glands, fine needles, united together in brush-like and stellate masses may be recognised. From the alcoholic extract of urine, precipitated with an alcoholic solution of chloride of zinc, the creatinine-chloride of zinc compound is always obtained in the form of a pale, yellowish powder, which, under the micro- scope, is found to consist almost wholly of yellowish, transparent, well- defined globules or balls of different sizes. Vpon these globules, under high magnifying powers (400 diameter), distinctly-marked striae are observed. On dissolving a little of the powder in boiling water, the production of regular crystalline forms may be observed under the microscope. A drop of the solution, when nearly Cold, is placed upon the object-glass, and a little solu- tion of chloride of zinc added to it by means of a thread, and in the manner above-described under the head of Nitrate of Urea, p. 14. The formation of crystalline glands, already described as characteristic of creatinine-chloride of zinc, often of considerable size, is soon observed on both sides of the thread. 2. A moderately concentrated solution of creatinine, mixed with an equally concentrated solution of nitrate of silver, coagulates into a network of acicular crystals, which are soluble in boiling water, but separate from it as it cools. 3. Corrosive sublimate throws down a curd - like precipitate, which in the course of a few minutes is converted into a confused mass of fine colourless crystals. 4. A solution of protonitrate of mercury does not at once produce a precipitate in a dilute solution of creatinine ; but if a solution of carbonate of soda is added guttatim until it becomes permanently cloudy, the compound (Cj H, N^ 0^, N O, -I- 2 Hg 0) soon ap- pears in the form of beautiful microscopic crystals. The precipitate is readily formed in concentrated solutions; and, if no free nitric acid is present, without the addition of soda. 5. Ammonia is evolved when creatinine is heated with an ammo- niacal salt. 6. Creatinine forms with hydrochloric, nitric, and sulphuric acids, compounds which are soluble in water, and crystallise readily : — a. Hydrochlorate of creatinine crystallises in the form of transpa- rent prisms and broad plates. With bichloride of platinum it yields a CREATININE. 21 compound similar to that with potash and ammonia ; but this com- pound is very soluble and crystallises in crimson prisms. h. Sulphate of creatinine yields concentrically grouped, trans- parent, square tables. It is especially to be noted that creatinine-chloride of zinc — ^the most important compound of creatinine — ^is not precipitated from hydrochlorate of creatinine, &c., on the addition of a solution of chloride of zinc. The separation, however, at once takes place, if, before the addition of the chloride of zinc solution, a sufficiency of acetate of soda is mixed with the creatinine-salt. 7. Under the action of protoxide of mercury, peroxide of lead and sulphuric acid or permanganate of potash, creatinine, as well as creatine, is converted into oxalic acid and oxalate of methyluramine (C3H,N3 0, + 4 = C,H,N3 + C, dj. 8. Creatinine is produced from creatine by the action of mineral acids, the creatinine losing 4 equivalents of water. But when a solu- tion of creatinine, in which an alkali is present, is allowed to stand for some time, the creatinine takes up water, and again passes into the form of creatine. Heat favours this transformation. (Liebig, Dessaignes.) D. Tests. — hs urine contains only a small quantity of creatinine, a large amount of the fluid is required for its successful demonstration. In most cases, however, from 200 to 300 C. C. suffice for its quali- tative analysis. Fresh urine is neutralised with a little milk of lime, and the phosphoric acid then thrown down by a solution of chloride of calcium. The precipitate is separated by filtration, and the ffitered fluid quickly evaporated to dryness in a water-bath. The residue thus obtained is extracted with strong, or, best of all, with absolute alcohol, allowed to stand for some hours, and filtered; the clear fluid is then treated with a few drops of a concentrated solution of chloride of zinc free from acid. The mixture, after being weU shaken, soon becomes turbid, and the separation of the creatinine-chloride of zinc is completely effected in forty-eight hours. The compound is washed on a filter with spirits of wine, dried, and microscopically examined. (See C. 1.) To obtain the creatinine in a pure state, the compound is dissolved in a small quantity of boiling water, and the oxide of zinc and hydro- chloric acid separated by boiling the fluid for at least a quarter of an hour with freshly-precipitated and well-washed hydrated oxide of lead. The filtered liquid is rendered colourless by boiling with animal charcoal, and evaporated to dryness. The residue, which 22 XANTHINE. always consists of a mixture of creatinine and creatine, is then treated with cold strong spirits of wine, whereby the creatinine is dissolved and the creatine left. On evaporation of this spirituous solution we obtain pure crystals of creatinine; the creatine may also be readily obtained in a pure form from the part of the residue which was in- soluble in alcohol, by re-crystaUisation, out of a little boiling water. It should be obsetved, however, that when a very dilute solution of creatinine-chloride of zinc is treated with oxide of lead, creatine alohe, and no creatinine whatever is found in the residue. The creatinine, in a dilute solution and under long exposure to heat, passes again into the state of creatine by takiilg up 4 equivalents of water. Should the urine operated upon contain albumen, the albumen must be previously separated from it by coagulation. Creatinine is distinctly characterised by its strong basic properties, by its readiness to form double compounds with metallic salts, and salts with acids. It is, moreover, distinguished from creatine by its inuch greater solubility in alcohol, and by the form of its crystals. The characters of creatine are not so well marked ; we have, in fact, tio other more certain test of it, than what we obtain through a com- parison of it with pnte creatine, its crystalline form, &c. SECTIbN V. Xanthine. Compositioii : — In 100 parts: Carbon . . . , . 39-5 Hydrogen . . . a-6 Nitrogen . . . , . 36-8 Oxygen . . . . 21-1 100 -0 Formula: C,„H,N,0,. A. Occwrenee. — Xanthine, until recently, was only known as a very rare constituent of certain urinary calculi. Scherer and Stadeler have, however, now shown that it is widely distributed throughout the animal economy^ Scherer found xanthine in the human urine, in the spleen, the pancreas, and the brain ; in ox's liver, the thymus- gland of the calf, and the muscles of the horse, of the ox, and of fishes J he also found it in an enlarged spleen and in the liver, in a case of yellow atrophy of the liver. The xanthine was generally XANTHINE. 23 found associated with hypoxanthine, and in the spleen, the liver, and the brain, with uric acid also. B. Microscopic cAaracters. — Xanthine is amorphous, and presents no crystaRine form under the microscope. It is usually deposited, from its boiling watery solution, in the form of colourless flaies, sometimes also as a fine powder, presenting the appearance of minute roundish granules under the microscope; these granules, in the flocculent precipitate, are grouped together, and in the powdery pre- cipitate remain separate, 0. Chemical characters. — Xanthine forms hard white masses, which assume a shining, waxy appearance when rubbed with the nail. It is almost insoluble in cold, but slightly soluble in boiling water. It has been artificially prepared from guanine. 1. Xanthine is soluble in ammonia, potash-ley, and in hydro- chloric, nitric, and sulphuric acids, From the alkaline solutions it is precipitated on the addition of an acid j and yrith the acids it forms crystalline compounds. 2. A cold, saturated aqueous solution of xanthine, treated with cor- rosive subhmate, yields a white precipitate. When boiled with acetate of copper, yellowish-green fiakes are thrown down. Its ammoniacal solution is precipitated by chloride of cadmium and chloride of zinc, as well as by acetate of lead. This last precipitate, on standing, often takes the form of shining scales. 3. Nitrate of silver, added to the nitric acid solution of xanthine, occasions a flocculent precipitate, which is dissolved by boiling, and again precipitated as the solution cools. The silver-compound, when quickly cooled, shows, under the microscope, a confused mass of fine crystalline needles ; when slowly cooled, however, it yields wavellite- like aggregations of fine crystals. Nitrate of alver, added to an ammoniacal solution of xanthine, produces a gelatinous precipitate, which is insoluble in ammonia. QoH^N^O. + ZAgO. 4. Xanthinej when heated with nitric acid, is dissolved without evolution of gas. The solution on evaporation yields a yellow residue, which is not rendered purple by ammonia ; caustic potash gives to the residue a reddish-yellow colour, which becomes a beautiful violet-red when heated. 5. Xanthine dissolved in hot, strong hydrochloric acid, yields, if allowed to cool slowly, beautiful microscopic crystals of hydrochlorate of xanthine, which form six-sided plates, lying together in groups 24 XANTHINE. and glandular masses. Very frequently, however, only round and egg-shaped forms are met with. The nitrate has a similar, though not so characteristic a form of crystallisation ; and here, again, we observe glands of rhombic plates and prisms. D. Tests. — ^Fresh, healthy urine, in quantity not less than from 100 to 200 pounds, is evaporated in a water-bath to from one-sixth to one-eighth of its original volume, and its phosphoric acid re- moved by precipitation with baryta-water. The filtrate is again eva- porated until the salts are crystallised out of it ; the mother-liquor thus obtained is then well diluted with water, a solution of acetate of copper added, and boiled for some time. A dirty-brownish precipi- tate is thus obtained, which is first decanted and then washed on the filter with cold water until aU chlorine-reaction has disappeared. By treating this precipitate with hot nitric acid, we obtain a brownish solution, from which the impure xanthine-silver compound is preci- pitated by nitrate of silver. The crystalline compound, after being washed, is dissolved in boiling dilute nitric acidj any remaining flocculi of chloride of silver removed by filtration, and the filtrate set aside and allowed to crystallise slowly. The collected crystalline silver-compound is freed from nitric acid by digestion with an am- moniacal solution of silver ; the washed precipitate diffused through water,boiled, and the compound decomposed by sulphuretted hydrogen. The boiling filtered solution deposits, when concentrated, coloured flocculi of xanthine, and the remainder is obtained by farther evapo- ration. The preparation thus obtained is, however, always much discoloured; but by solation in strong hydrochloric acid and treat- ment with animal charcoal, the purification is readily effected. The filtrate, thus freed from colour, yields, when evaporated, hydro- chlorate of xanthine, from which pure xanthine, with all its peculiar characters, may be obtained by repeated treatment with ammonia, and by subsequent removal of the chloride of ammonium by washing with cold water. The quantity obtained is, after all, very small ; from 600 pounds of urine I collected, after previous removal of the creatinine, very little more than one gramme of pure xanthine. URIC ACID. 25 Composition : In 100 parts : SECTION VI. Ueic Acid. Carbon Hydrogen Nitrogen Oxygen Water . 35-714 1-191 33-333 19-048 10-714 100-000 Formula : Ci„ H, N, 0, + 2 H 0. A. Occurrence. — Uric acid is present in the urine of entire classes of animals, and in some animals of a vpry low class. The excrements of birds (guano), of snakes, of reptiles, and of insects, contain much uric acid. It has also been found in the blood, especially after extirpation of the kidneys, by Strahl and Lieberkiihn,* and more recently by Garrod.f According to Garrod, the quantity of it in the blood is always increased in cases of gout. Moreover, it has been found in the spleen, the parenchyma of the lungs and the liver of the ox, as well as in gouty deposits. The quantity of uric acid in human urine depends less upon the nature of the food than upon special conditions of the internal organs of the body; in this respect, it differs from urea. The quantity of uric acid excreted in twenty-four hours by a healthy man, under normal circumstances is, according to Becquerd, between 0-495 and 0-557 gramme. In some experiments which I lately made on a vigorous young man, twenty-three years of age, 0-827 gramme of uric acid was passed in twenty-four hours, with 36-4 grammes of urea in 3,000 C. C. of urine. Purther observations have shown me, that the quantity of uric acid differs much at different times, and may vary as much as from 0-2 gramme to 1 gramme in the twenty-four hours. According to Ranke, the relative quantity of the uric acid to the urea varies from as 1:50 to 1 : 80 in the twenty-four hours. An increase of uric acid in the urine is caused especially by derangement of the digestion, and also by defective nutrition. It is, likewise, increased in all febrile conditions of * Strahl und Lieberktihn. Harnsaure im Blute, etc. Berlin, 1848. t Dr. Garrod on Gout, &c. 26 URIC ACID. the body, and in affections of the lungs. The readj decomposition of uric acid by oxidising agents seems clearly to indicate, that its origin in the body has a close connexion with the respiratory process. Many facts favour this idea. Liebig, when he discovered cyanuric acid in the urine of a dog, observed, that no uric acid whatever was present in it ; but Lehmann, on the other hand, has distinctly de- monstrated its presence in the blood of a dog. Such a condition, how- ever, undoubtedly occurs in other animals : in the urine of the pig and of the monkey, for instance, neither Bossingault nor Bibra could find uric acid. Much smaller quantities of uric acid, exist in the urine of car- nivorous animals than in human urine ; Yauquelin,* indeed, found the urine of a lion, entirely free from uric acid. According to Lehmann, however, when this animal is deprived of its freedom, and shut up for a long time in a cage, uric acid appears in considerable quantity in its urine, — as happens to man under like conditions, — and is separated from the urine as an acid urate of soda. Stadeler, moreover, has succeeded in demonstrating the presence of aUantoine in dog's urine, when the respiration of the animal was impeded. Uric acid, when introduced into the healthy body, is converted into carbonic acid and ureaj but should the oxidising processes of the body be in any way retarded, as happens during sleep, it wiU also produce oxalic acid. Uric acid may be considered as a twin excretion with urea ; but its more intimate constitution has not yet been ascertained, notwithstanding that very great labour has been bestowed upon the subject. A series of highly interesting products of its decomposition have, however, been discovered. This much we may conclude, from the chemical characters of uric acid, viz., that it is, like creatine, one of the representatives of the retrogres- sive metamorphoses of the nitrogenous constituents of the body ; and that it stands higher in the scale than urea, being itself, by oxidation, converted into carbonic acid and urea. That it under- goes, at least in part, similar changes in the animal organism, ap- pears almost certain from the demonstrated fact of the presence of uric acid in the liver and spleen of herbivorous animals, in whose urine it is entirely absent. B. Tr&peuration, 1. From human urine. — Urine freshly voided in the morning, is filtered and mixed with hydrochloric acid (20 0. C. to 1 litre of urine), and allowed to stand for forty-eight hours. * Sohweiger's Journ. V., p. 175. URIC ACID. 27 The uric acid is, in this manneij separated in crystals, more or less coloured, and fitted for microscopie study. U. From tlie excrements of serpents. — 'The faeces of a serpent are boiled with a solution, containing one part of caustic potash in twenty parts of water, until they have lost their ammoniacal smell. Carbonic acid is then passed through the filtered solution, until it has almost entirely lost its alkaline reaction j acid urate of potash is thus separated, and is collected and washed with water. After washing, the potash-salt is dissolved in a solution of potash, and then filtered into dilute hydrochloric acid, care being taken, that there be an excess of the acid ; the precipitate formed is pure uric acid, which, after washing and drying, appears as a fine, light powder. c. Microsccpical akaracters. ^-JJnG acid appears under the microscope in several forms, but usually a,s smooth, rhomboidal tables, which are sometimes coloured, always remarkably trans- parent and of different, sometimes of considerable size. These tables often undergo modification in form; thus, spindle-shaped figures result from the rounding off of their obtuse angles, and, with these, short, cask-shaped cylinders are frequently mingled. Hexagonal plates, rectangular tables, or right rectangular four- sided prisms, with horizontal terminal planes, are also often met with; the last are frequently peculiarly disposed, being grouped together in glandular-shaped rosettes. Besides these> there are other forms, saw-like, fan-shaped, and dentated crystals, &c. {Plate I. Figs. ^ Mid B ; Plate II. Fig. 4 ; Plate III. Fig. 1.) I have obtained many different forms of uric acid crystals, by mixing normal urine with varying quantities of hydrochloric acid ; the nature of these crystals is readily ascertained, by comparing them -with the crystaUine forms given by Funke. Any doubt existing as to the nature of particular crystals, may be readily re- moved, by converting them into some more ordinary form of uric acid. The crystals are dissolved on the object-glass of the micro- scope, in a little caustic potash ; and, on the addition of a drop of hydrochloric acid, crystals of the more ordinary form, table-, or spindle-shaped, soon appfear. D. Chemical characters. — ^Pure uric acid, obtained from the ex- crement of serpents, consists of white, softish, and excessively light, crystalline scales, which present, under the microscope, the forms above described. It has neither taste nor smell ; is very slightly soluble in water, one part of uric acid requiring 14,000 to 15,000 28 URIC ACID. parts of cold, and 1,800 to 1,900 parts of boiling water for its solution. The solution does not redden litmus. It is very little soluble in dilute hydrochloric acid, and quite insoluble in alcohol and ether. It is readily dissolved, without decomposition, in concentrated sulphuric acid, but is thrown down from the solution on the addition of water. 1. Uric acid is readily dissolved in a solution of phosphate of soda, and also in several other salts of the alkalies. It takes from these salts, and combines with, a part of their base, and so occasions the formation of acid salts. It is in this way that acid phosphate of soda, which is the chief cause of the acid reaction of the urine, is formed. By dissolving uric acid in a warm solution of phosphate of soda, it is easy to obtain a fluid, having a similar acid reaction to that of the urine, from which, on concentration, urate of soda is deposited in crystals. (For the separation of this last salt from the urine, see Sediments.) 2. Uric acid, heated in a glass tube, is decomj)osed without under- going previous fusion. It is converted into urea and cyanuric acid (which are sublimed in the form of a ring), hydrocyanic acid, and a little carbonate of ammonia, whose presence is easily recognised by its smell. Besides these, peculiar oily products appear, and a porous coal containing nitrogen remains as a residue. 3. Uric acid made into a thickish paste with water, and boiled with peroxide of lead, is decomposed into four bodies : carbonic acid, allantoine, urea, and oxalic acid. The allantoine (which exists naturally in calves' urine) and the urea may be readily recognised by their mode of crystallisation ; the oxalic acid remains in combination with the oxide of lead, and the carbonic acid escapes with effervescence. According to Pelouze, a small quantity of allanturic acid is formed at the same time. It is not improbable that the urea resulting from this decomposition is a product of a further oxidation of the allantoine, and the carbonic acid of the oxalic acid, so that the simple decomposition of uric acid by peroxide of lead yields only allantoine (Cg Hj N^ 0^) and oxalic acid. a„ H,N,Oe + O + 2 H = 0, H^N, 0, + 0,0^ (Uric acid.) (Allantoine.) 4. When one part of uric acid is gradually mixed with four parts of concentrated nitric acid (1-42 sp. gr.), the uric acid is dissolved with effervescence, and the whole solution at last con- URIC ACID. 29 verted into a crystalline mass. The niic acid is decomposed into alloxan and urea. The uric acid is separated in crystals, but the alloxan, in consequence of the simultaneous formation of nitrous acid, is immediately decomposed into carbonic acid and nitrogen, which escape with effervescence. In the formation of alloxan and urea from uric acid, two equivalents of water and two of oxygen are added to the uric acid : — C,„H,N,0, + 20 + 2H0 = C,H,N,03 + C,H,N,0, (Uric acid.) (Alloxan.) (Urea.) Alloxan, when further treated with nitric acid, takes up two equivalents of oxygen, and is converted into two equivalents of carbonic acid, and one equivalent of parabanic acid :— ^ Ca H, N, O, + 2 = 0, H, N, O, + 200, (Alloxan.) (Parabanic Acid.) Parabanic acid passes into oxaluric acid through the addition of two equivalents of water : — 1 eq. parabanic acid 0, H, N, O, + 2 H O = 1 eq. oxaluric acid Cg H^ K^ O3 ; the oxaluric acid, again, when boiled in water, is finally decomposed into oxalic acid and urea : — 1 eq. oxaluric acid 0^ H^ N, 0^ 1 eq. urea 0, H^ N, 0, 2 eq. oxalic acid C^ O, CeH.N.O, On comparing these various formulae together, we find -that one equivalent of uric acid by the addition of four equivalents of water, and four equivalents of oxygen, are at last decomposed into two equivalents of urea, two equivalents of carbonic acid, and two equivalents of oxalic acid, passing through the intermediate forms of alloxan, parabanic acid, and oxaluric acid : 1 eq. uric acid C,„ H^ N^ O, 2 eq. urea 0^ H, N, O^ 4 eq. water . H. 0^ 2 eq. oxalic acid C, 0, 4 eq. oxygen O^ 2 eq. carbonic acid C, O^ If the oxalic acid be further oxidised by the addition of two equivalents of oxygen, there will remain as the final products of the decomposition of the uric acid: carbonic acid, and urea. The complete oxidation of the uric acid may be thus exemplified : — 30 URIC ACID. 1 eq. uric acid 0,„ H, N, O, 2 eq. urea . . 0, H, N, 0^ 4 eq. water H 0, 6 eq. carbonic acid Cg 0,j 6 eq. oxygen 0^ C.^H.N.O,, It is evident from this, that the uric acid must, in the normal condition of things, undergo decomposition in the body ; and we find that, by an excess of permanganate of potash, it is directly converted into carbonic acid and urea j and that when the oxidation is less complete, it passes into the form of allantoine, carbonic acid, oxalic acid, urea, and other products.* 5. By the action of reducing agents, such as sulphuretted hydro- gen, hydrogen, &c., upon a solution of alloxan, crystals of a new compound, alioxantine, axe precipitated (CgHsN^O,,). AUoxantine is much less soluble than alloxan; it crystallises in oblique four- sided prisms, and becomes red under the action of ammoniacal vapour. Alloxan and alloxantine are the source from whence mu- rexide proceeds — the most important of the uric acid reactions. Thus, when a solution of alloxan and alloxantine are mixed with ammonia, it becomes of a purple-red colour, and after a time deposits crystals of murexide (C„ H, N^ 0,, -F N H, purpurate of ammonia). Murexide crystallises in four-sided prisms, having a greenish cantha- rides-Kke jeflexion ; when pulverized it forms a brown powder, and dissolves in water with a deep purple colour. It serves on all occa- sions as a test for uric acid. 6. Uric acid, when treated with moderately dilute nitric acid, is dis- solvedj and alloxantine is then found in the solution. By carefully evaporating the solution almost to dryne^, and by the further addi- tion of nitric acid, alloxan will be formed out of the alloxantine. If the mixture be now acted upon by ammonia, the beautiful colour of murexide, which passes into a purple-blue on the addition of caustic potash, is obtained. By the aid of this test, the presence of the smallest quantity of uric acid may be recognised. If the residue is treated with potash or soda, insteafi of with ammonia, we obtain a beautiful purplish-violet solution, ,the colour of which becomes gradually paler when heated. Before the fluid is wholj^r evaporated, its beautiful colour is completely lost. (Distinction from Xs;Qthine, p. Z4>.) * Annal. d. Chem. und Pharm. Bd. 99, p. 206. URIC ACID. 31 7. Uric acid forms salts with different bases, all of which are more or less readily soluble in water^ the most soluble being that of hthia. From these solutions the uric acid is precipitated in a crystalline form, on the addition of hydrochloric, acetic, and other acids. The precipitation takes place immediately in concentrated solutions ; but in dilute solutions, as in the urine, it requires from twenty-four to thirty'Six hours for its completion. The crystals are readily re- cognised under the microscope. A description of its different salts will be found under the head of Sediments. 8. An alkahne solution of uric acid immediately reduces nitrate of silver, even without heat. When paper, upon which a drop of nitrate of silver-solution has been let fall, is moistened with a solution of soda, in which only a trace of uric acid is dissolved, a dark-brown spot is immediately produced, though not more than IM5 part of uric acid be present. A much less quantity, otIsto of a gramme, produces in the course of a few seconds a visible yellow reaction, and this, too, without the assistance of heat. (Scbiff.) 9. A white precipitate of urate of the suboxide of copper is pro- duced, when a solution of uric acid in potash is added to an alkahne solution of copper. On heating this precipitate to boiling with an excess of the copper-solution, the uric acid is oxidised, red suboxide of copper is separated, whilst the products of oxidation of the uric — viz., allantoine, urea, and oxaUc acid remain in solution. E. Tests. — I shall only treat here of the method of finding uric acid in the urine. There are two methods, either of which may be depended upon, by which uric acid may be separated from the unne and tested. 1. A small quantity of urine, say ten to fifteen grammes, is eva- porated in a porcelain basin over a water-bath to a syrupy consistence — any albumen accidentally present in it having been previously removed by boiling, with the addition of a drop of acetic acid, and subsequent filtration. Prom the residue, the urea, together with the extractive matters and the salts soluble in alcohol, are removed by frequent washings with alcohol ; the uric acid with the insoluble salts, and a httle mucus being left. The salts are next extracted by the addition of a small quantity of dilute hydrochloric acid, so that at last the uric acid alone remains, mixed with a little mucus. Por the more certain detection of uric acid, the following tests may be resorted to : — a. A small portion of the uric acid is placed on a watch-glass with 32 URIC ACID. a few drops of nitric acid, and more or less perfectly dissolved by a gentle heat. The solution on being evaporated in a water- bath leaves a reddish residue. This residue when moistened with dUute ammonia (one in ten parts of water), instantly produces the purple-red colour of murexide, which passes into a beautiful violet, on the addition of a drop of caustic potash solution. When the quantity of uric acid is very small, the test will fail, should too much ammonia be employed; consequently, it is better to blow the vapour of ammonia off a glass rod dipped in a solution of am- monia on to the residue. By this means the test wiU show, with certainty, the presence of even mere traces of uric acid. b. The residue is dissolved in a few drops of potash solution, which leaves the mucus undissolved; and from this solution of urate of potash the uric acid is separated in a crystalline form on the addition of hydrochloric acid, and may be recognised by its microscopic characters. 2. A larger quantity of urine (100 to 150 grammes), is mixed in a glass vessel, with 6 to 8 grammes of hydrochloric acid, and allowed to stand for twenty-four to forty-eight hours ; at the end of this time the uric acid is separated ia the form of coloured crystals, which partly float on the surface of the fluid, and are partly deposit- ed on the sides and bottom of the glass. These crystals are readily recognised as uric acid, both by the aid of the microscope, and also by testing them, when removed by filtration, with nitric acid and ammonia. 3. If the quantity of the fluid to be tested for uric acid is small, 4 to 8 grammes of it are poured into a flat watch-glass, 6 to 12 drops of strong acetic acid added, and a few liaen threads laid in it. The fluid is allowed to stand eighteen to twenty- four hours, in a temperature not exceeding 16° to 20° C. (61° to 68° Fahr.). At the end of this time, the uric acid is deposited on the threads in the form of crystals, which may be then examined microscopically. This process is of especial service in testing the serum of the blood of gouty subjects for uric acid. {Dr. Garrod.) Composition : — In 100 parts : Carbon Hydrogen Nitrogen . Oxygen . Water HIPPURIC ACID. 33 SECTION YII. HippuEic Acid 60-335 4-469 7-821 22-347 5-028 100-000 Eormula : C„ H, N 0,, H 0. A. Occurrence. — Hippuric acid is met with cHefly in the urine of herbivorous animals. It is present both in healthy and in un- healthy human urine, and Liebig states, that he has found it under the same conditions as uric acid; it rarely, however, appears as a sediment. The later experiments of Hallwachs, however, show that the normal quantity of hippuric acid passed during the twenty-four hours is greater than has hitherto been supposed. Hallwachs ob- tained, from the twenty-four hours' urine of different persons, about 1 gramme of hippuric acid, and this, too, when animal food was taken in excess. Its quantity is increased under the influence of a purely vegetable diet, and in some diseased conditions particularly in the acid urine of fever, and in diabetes. The hippuric acid, in urine of this kind when somewhat stale, is readily converted into benzoic acid. Benzoic acid passes off with the watery vapour on evaporation of the urine, — a fact which may explain why its presence in urine has been so long overlooked. Conversely, benzoic acid passes readily into hippuric acid. Hippuric acid, for example, is easily obtained from the morning urine of a person who has taken benzoic acid on the preceding evening. I have in this way obtained from 6 to 8 grammes of hippuric acid. The benzoic acid, even when taken in large quantity (2 to 3 grammes), exercises no disturbing influence during its passage through the body. The urine often appears cloudy, although there is no increase of its free acid, as Lehmann supposed, and yields, after slight evaporation, and upon the addition of hydrochloric acid, crystals of hippuric acid. Several other bodies, such as Peruvian balsam, also produce hippuric acid in their passage through the body. Succinic acid, however, according to Hallwachs, does not produce any increase of d 34 HIPPURIC ACID. the hippuric acid, when taken internally, as was asserted by Kiihne ; it could not, in fact, be discovered either in the urine or in the faeces, and consequently appears to have undergone complete decomposition in the body. Yerdeil and DoUfus found hippuric acid in the blood of oxen, as well as in their urine, and Hervier has also found it in diseased human blood. Schlossberger has demonstrated the presence of hippuric acid in the scales of the skin in ichthyosis. Hippuric acid is probably the product of the decomposition of the nitrogenous constituents of the body ; for, as indeed may be gathered from its constitution [Chemical Cka/racters 3 and 8), there are always indications of the presence of a benzoyl-compound in it ; and Guckelberger has artificially prepared benzoic acid and benzo- nitrile, by the action of nitric acid on proteine-bodies. Why then may not the nitrogenous compounds undergo Hke decompositions within the body, and the products be afterwards separated with the mine, in the form of hippuric acid ? Such an idea receives strong support from the well-conducted researches of Hallwachs. He did not, in fact, discover benzoic acid, or any benzoyl-com- pound in the ordinary food of the- cow ; so that the benzoyl-radical of hippuric acid could not possibly be derived directly from the food ingested. Hippuric acid is undoubtedly an excretion j but of its origin, we cannot speak with certainty. B. Micrascqpic characters.' — ^A boiling saturated solution of hip- puric add allowed to cool rapidly, when observed under the micro- scope, throws down a precipitate of fine needles and scales. But regular, well-formed i crystals, are separated from a cold saturated solution on evaporation ; these 'crystals are milk-white, semitrans- parent four-sided prisms and cdlumns, terminating in two or four planes; their ©lememtaiy foim is invariablya right rhombic prism. (Plate I. Fig. 1.) A few of the crystails are occasionally seen to re- semble the crystals of ammonioiphosphate of magnesia, from which, however, hippuric acid is readily distinguished by its chemical characters. c. Preparation. — ^The fresh urine of the horse or cow (6 to 6 litres) is boiled for a few minutes with an excess of milk of lime, and filtered ; the clear sdlution of hippurate of lime ,is then 'rapidly evaporated to one-eighth or one-tenth 'of its original volinne, and treated with hydrochloric acid. In the course df twenty-four hours the hippuric acid is crystallised. It is then purified by a second HIPPURIC ACID. 35 adjHiixture with milk of lime, and the filtered solution, after the addition of hydrochbac Bcid, left to crystallise. M the crystals are stiU impure, they may be once again dissolved m wEfter, and mixed with well-burnt animal charcoal ; and on the cooling of 'the solutioiB, will be separated in long, coloudess, eemitransparent crystals. A second deposition gf crystals may be. obtained by eva- poration of jthp mother-liquid. lioewe treats , fresh lurine with sulphate of zinc, lajid evaporate? it together with the resulting piEecipitate to one-sixth of its volume, filters it quicldy, and separates the hippuric ^cid from the filtrate by means of hydroohloric ,acid. Tiie hippuric acid .must be purified by a second crystallisation. This method yields a very pure pre- paration. Gossman gjives us a good method for purifying colouired hippurjo acid. The crystals are dissolved in a sufficiency of dilute sodar-ley, and a solution of permanganate of potash then dropped into the solution, when heated to boiling, until, on testing a little of the filtered fluid, a pure white precipitate is obtained on the addition of hydrodhlorie acid. The whole filtrate is then treated while hot with a slight excess pf hydrqcflilorie acid, ^nd allowed to crystallise. " D. Chemical c^arac^er*. —:- Hippuric acid has a weak, bitterish taste, but no smell; ^'00 pasts of coljl ;water aire required for its solutipn j bat it is much more .soluble in boiling w^ex- AloohQl readily dissolves it J ether also di§solv-esrit,.bwt wt so jeadfly,- Its solutions redden litmus, strongly. 2. Hippuricacid .heated ima tjest-tube,- after the manner men- tioned in speakjug of urea, Iw8^ iatp m- ojly liquid, which, on cwling, hardens intp a milk-whitte cry^taUine ma§§. When strongly heated it decomposics, a ■subJim.^'te of bjen?.oie .9pid jwd pf benzoatp of ammonia being formed ; at the same time a im red, oily drops appear, which have a peculiar smell like that of ^e^ hay, become soHd m Pftojing, and aje soluble ip alcphpl and ^tmmpnia, but not in water. JSubjected ,to a stronger \ii»\ it ^ivfis pff an intense odour, like that of hydBocyaWP acid, leawga pprous, coaly mass, which is perfectiy pombustible.. By these peeuliw chwapters, hippu- ricacid niay be readily recognised. ajlji distinguished from uric aqid and benzoic aci^ with which Ja^t apid especially it.has wany points of resemblance. In the dry distjJfetioj), if thp heat is not allowed to exceed ,850° C. (48?° I'ahr.), .fee hippuric aqid gives off benzpic d 2 36 HIPPURIC ACID. acidj slightly reddened by the presence of some foreign body^ traces of hydrocyanic acid, and of a liquid compound, benzo-nitrile (C,^ Hj N), having an odour very similar to that of bitter almonds. 3. Hippuric acid is unaltered by dilute mineral acids; but it is decomposed when heated with concentrated hydrochloric, sulphu- ric, or nitric acid. Crystals of benzoic acid are separated from the mixture as it cools; and a peculiar compound, glycocoll C^ Hj N 0, (glycine or glycocine), having in its fre» state a slightly acid reaction, remains in solution, in union with the mineral acid : — (hippuric acid) (benzoic acid) (glycocine). Glyooooll may be artificially prepared by the action of ammonia on ohio-racetio acid, bo that it may be considered as an amide of acetic acid. Cj j 5'ti 0,. Through the action of glycocol-oxide of zinc (amide of acetate of zinc) on chloro-benzoyl, Dessaignes, in fact, reproduced hippuric acid, this last being recognised in the form of benzoic acid, to which one atom of hydrogen is added, through the radicle of the amide of acetic acid, in 0* f H O * * I n'h,! Similar relations are presented to us by gallic acid. 4. Hippuric acid mixed with putrescent or fermenting matters is mostly converted into benzoic acid. This is the reason why ex- perimenters often fail to find it in stale urine j the benzoic acid, thus formed, readily passing off with the watery vapour, whenever the urine is evaporated after the addition of a little hydrochloric acid. 5. When hippuric acid is dissolved in nitrous acid, or when nitric oxide is passed through a solution of it in nitric acid, a non- nitrogenous acid, benzo-glycollic acid (C„ H, OJ is formed, and nitrogen given off: — (C„ H,NO. + N03 = C,. H. 0, + 2N + HO). A similar decomposition occurs, when hippuric acid is dissolved in an excess of dilute potash-ley, and chlorine passed through the cold solution as long as any nitrogen is given off. 6. Hippuric acid forms crystallisable salts with bases; and may be separated from their solutions (when concentrated) in the form of long needles, by the addition of hydrochloric acid. 7. The intensely bitter almond-like smell of nitro-benzine is pro- duced when hippuric acid, subjected to the action of strong boiling nitric acid, is evaporated to dryness, and the residue heated in a glass- HIPPURIC ACID. 37 tube. Benzoic acid gives a similar result. Cinuamic acid is dis- tinguished by the characteristic odour of cinnamon. As mere traces of nitro-benzine yield a strong and somewhat lasting smell, this test may be used for ascertaining the presence of even very small quan- tities of hippuric acid. (Liicke.) No reaction of this kind is given by albumen, gelatine, uric acid, sugar of urine, salioine, Balioyluric acid, oholoidinio acid, anisic acid, pyrogallio acid, picric acid, naphthaline, phthalic acid, indigo, and isatine. B. Tests. — Hippuric acid can only be recognised in its pure form ; for it is only then that it exhibits characteristic marks. Benzoic acid is the only body with which it can be confounded, and from this acid it may be readily distinguished by the following tests : • — 1. Hippuric acid crystallises under the microscope in the forms above mentioned; benzoic acid, on the other hand, crystallises in scales, small columns, or six-sided needles, whose primary form is a right rhombic prism. (Ihinke, Plate I. Mg. 6.) 2. Dry hippuric acid, when heated, undergoes characteristic decom- positions (see 2) ; but benzoic acid passes off undecomposed, in the form of a thick, white, pungent vapour. 3. Hippuric acid contains nitrogen ; benzoic acid does not. In order to distinguish it, a small quantity of hippuric acid is heated with soda-lime— a mixture of caustic soda and caustic lime — in a narrow glass tube ; thereupon, ammonia is soon given off, and may be recognised either by its smell, or by its property of blackening paper, moistened with a solution of subnitrate of mercury. Uric acid is readily distinguished from hippuric acid by the form of its crystals, by its reactions with nitric acid and ammonia, as well as by its insolubility in alcohol and ether, in which hippuric acid is soluble. Hippuric acid may be obtained from the urine by the two fol- lowing methods ; but the urine must, in both cases, be perfectly fresh. (See D. 4.) 1. From 800 to 1000 C. C. of urine are evaporated nearly to dryness in a water-bath, the residue triturated with powdered sulphate of baryta, acidulated with hydrochloric acid, and completely extracted with alcohoh After neutralising this alcohohc extract with soda-ley, the greater part of the alcohol is distilled off, and the remaining syrupy fluid, after the addition of oxalic acid, being kept stirred, is dried in a water-bath. The dried mass is next exhausted by a large quantity of ether, to which a Kttle alcohol has been added, and the 38 PHENYLIC ACfD. ethereal solution evaporated by distillation almost to dryness. The crystalline residue is then heated with miUt of limej in order to remove the oxalic acid, filtered, the filtrate evaporated to a very small volume, and slightly acidulated with hydrochloric acid. Crystals of hippltric wiU now form in it in the course of a short time ; and may then be tested chemically and microscopically. Exceedingly small quantities of hippuric acid may be distinguished by the nitrobenzine reaction. (See Chemical oAa/racters, 7.) If the urine contains much hippuric acid, as it does after a dose of benzoic acid has been' taken, crystals of hippuric acid may usually be obtained, by- the simple addition of a little hydrochloric acid to the urine evaporated to the cotisistence of syrup. These crystais may be readily separated by alcohol from the uxicacidj which is also thrown down. 2. The second method is Liebig's {Annalen der Chemie u: Pha/rm. 18M). The urine with a few drops of hydroehlorie acid added to it, is evaporated to a syrup, and shaken with an equal volume of ether. If, as often happens, the ether, on separating, is not clear, one-twentieth of its volume of alcohd is added to the mixture, after it has stood for an hour. The layer of ether, containing the hippuric acid and some traces of urea, is re- moved with a pipette, and shaken up with 'small quantities of water; in this way the alcohol and urea are removed, the hip- puric acid remaining in solution in the ether, from which it may be obtained by evaporation in a crystalline form. The crystalsj if necessary, may be obtained perfectly colourless, by boiling with animal charcoal. In this operation, however, a considerable quantity »f the hippuric acid is lost. Of th«se two methods of testing uric acid, I give a decided preference to the first. SECTION VIII. PheNylic Acid {carbolic acid, or phenyl-alcohol). Composition : — In 100 paxts : Carbon .... 76'93 Hydrogen . . . 6"4j0 Oxygen .... 16-67 lorHQula s C,, H, 0, H 0. 100-00 PMENYLIC ACID. 39 A. Oemvrrenoe. — ^Phenylic acid was discoyrared by Wohler in casto- reum, and afterwards by Stadeler (togethei with tanrylic, damolii^ apd damalnric acids)> as a constant constituenlrO'fthe urine of cows, horses, and man. This acid has poisonous qualities, and is obtained fconi human urine ia very small quantities' omly, so that it is. at present doubtful whether it really exists ready-formei iii the urijift,.or whether it is formed during the process required for its- preparation. These acids, or the matters at least out of which they are formed, appear to be the cause of the odour of the urine. Stadeler considers that they all pre-exist in the urine, and that they aiie, therefore, products of the metamorphic processes. Phenylic acid i» also found in coal-tar; it is formed during the dry distillation of salicine with lime, as weU as in the decomposition of many organic bodies at a red heat, &c. Schlieper obtained traces of it from thei products Q& the oxidation of gelatine. c. Chemica/l chartieters. — Anhydrous phenylic acid crystallises in long colourless needles, which melt at 35° 0. (95" Pahr;), and boil at IBS'* C. (370? Fahr.). It has a smoky smell, is corrosive;. and poisonous. It is scarcely soluble in water, but readily dissolves in alcohol artd ether. Its solution coagulates albHm©n>, and ia strongly antiseptic. 1. The following compounds are formed by the action of nitric acid on phenylic acid : first of all nitro-, then dinitro-phenylic acid, and lastly, trinitro-phenylic acid (G,^ H^ [3 N OJ O + H 0), usually known by the name of 'picyric acid,' or 'Welter's bitter,' and which may be also formed by the action of nitric acid on inddgp, salicine, &c. 2. Phenylic add, acted on by chlorine, produces di- and trichloro- phenylic acids, two and three equivalents of the hydrogen of ihe phenylic acid being replaced by the chlorine. (C^ H, CI Q + H 0, and C,, H, CI3 O + H O.) 3. Per-salts of iron produce a violet-colour in a solution of phenylic Wd, which takes a bluish shade, and, after a time, turns to a dirty-white cloudiness. 4. Nitrates of silver and mercury are reduced by phenylic acid. 5. A chip of deal, soaked in a watery solution of phenylic acid, and dipped in dilute hydrochloric acid, becomes of a deep-blue colour when exposed for a few moments to the sun's raysv The colour firmly resists the action of chlorine ; under its influence the blue takes a lighter shade, but soon regains its depth, when the slip of wood is re-dipped in dilute hydrochloric acid. 40 TAURYLIC AND DAMALURIC ACID. 6. Phenylic acid forms, with sulphuric acid, sulpho-phenic acid, whiph will remain fluid during months. 7. With caustic potash solution it hardens into ' a crystalline mass. 8. Benzonitrile, 0,^ H N (see Hippuric Acid, which is one of the products of the decomposition of hippuric acid, may be regarded V IT as a phenylcyanide p" -^'> the phenyl group is, indeed, in all respects, very closely related to the benzoyl and salicyl compounds. Phenylic acid is also formed during the dry distillation of most of the salicylic salts, as well as of benzoate of copper — a fact worthy of note in reference to its formation in the urine. Stadeler has also discovered a series of other acids closely resem- bling phenylic acid. They are : — 1. Taurylic acid, C,^ Hj 0^ (?), which is isomeric with anisole. It is distinguished from phenylic acid by its higher boiling-point, and also by its forming a fixed compound with concentrated sulphuric acid, which separates at first as a fine white detritus, and then gradually accumulates into roundish masses. 2. Bamaluric add. — Composition .• — In 100 parts : Carbon . . . 65-62 Hydrogen . . 9-38 Oxygen . . . 25-00 100-00 Formula : C„ H„ O, 4- H 0. Damaluric acid is an oily fluid, having an odour of valerianic acid : it is heavier than, and slightly soluble in, water, and gives it a strongly acid reaction. It forms very characteristic salts with bases. The baryta-salt crystallises in united tufted prisms, which are soluble in water, and form an alkaline solution. The salt is infusible, but after exposure to a red heat, yields carbonate of baryta in the form of the original salt J it contains 39-18 per cent, of baryta. With silver it forms a white powder, which is not affected by the action of light j this salt contains 49-36 per cent, of oxide of silver. Acetate of lead yields, with a solution of damaluric acid, a white precipitate, which appears under the microscope as fine prisms clustered together in roundish masses. 3. Damolic acid is the least known of these compounds. It is DAMOLIC ACID. 41 oily, and heavier than water, and only shghtly soluble in it. It forms with baryta a crystallisable and fusible salt, containing 27*50 per cent, of baryta. The damolic acid-salt crystallises the first out of a solution of damalurate and damolate of baryta. Mode of obtaining and separatmg these four acids : — 1. The separation of them all together from the urine. Presh cow's urine (80 lbs.) is mixed with hydrate of lime, boiled, then decanted off from the superfluous lime, and evaporated to one- eighth of its original quantity; hydrochloric acid is added to the filtered solution, and after standing twenty-four hours, the mother- liquor is decanted from the precipitated hippuric acid and distilled. By repeated rectification of the milky fluid obtained by the first distillation, an oil-like, lightish-yellow liquid is obtained, the greatest part of which sinks to the bottom of the water which passed over with it. The presence of phenylic acid in this oil may be readily shown by its reaction with perchloride of iron, as well as by the blue colour it produces on a slip of fir-wood. The quantity of it in human urine is very small.* 2. Separation of the acids singly : — The oil, together with the water obtained by the process just described, is mixed with an excess of hydrate of potash (the quan- tity used being weighed), and then subjected to distillation. A nitrogenous, powerfolly smelling oil, whose nature has not been closely investigated, passes over with the distillate. As much sul- phuric acid is added to the residue in the retort as is sufficient to neutralize five-sixths of the potash employed. The fluid resulting is then distiEed, so long as a precipitate is formed in the distillate on the addition of acetate of lead. By repeated distillation of this pro- duct over common salt, the greater part of the acids are at last obtained in an oily form^ — a very small portion of them remaining in the watery solution, and giving it a strongly acid reaction. To separate these acid compounds, the distillate is saturated with car- bonate of soda, and frequently shaken during the following twelve hours; the oily layer is then separated from the soda-salts by ether. a. Acids, which are not retained by the carbonate of soda : — From the ethereal solution obtained, as thus described (2.), the ether is removed by distillation, and the residue again mixed with * Annul, der Chemie u. Pharm., vol., xcvii., p. 134. 42 URINE-PIGMENT. strong potash-ley, amd subjected to distiUatioa. The potash-con- pound which ];emains bekkd ia decomposed withr bicarbonate of potash, and the product of. the. distillation eatiiely deprived of its water by chloride of calcium. By fractional distiliatien the greatest part passes over at 180° to 195" C. (354° to 383* Fahr.), and consists of phenylic and taurylic acids, which again by repeated fractional distillation can be paitially separated. The acids differ chiefly in this, that taurylic acid boils a* a higher temperature than phenylic acid; and that with concentrated sulphuric acid', taurylic acid forms a soEd, and phenyKc acid, a permanently fluid compound. S. Acids which are retained by the carbonate of soda : — The solution of the salts of soda, which has been freed of its phenylic and taurylic acids by ether, is evaporated, decomposed by sulphuric acid, and distilled. The distillate, which has an odour' of butyric acid and separates into an oily and a watery layer, is boiled with an excess of carbonate of baryta, and then left to crystallise. By fractional crystallisation various salts of baryta, containing different quantities of baryta (27 to 41 per cent.), are formed. The chief con- stituent is the acid, whose salt contains rather more than 39 per cent, of baryta (third, fourth, and fifth crystallisation). This acid is- the damaluric acid C,, H„ O3 + H (see Damalurio avid). The next acid, whose salt contains 2 7 "4 per cent, of baryta (first and second crystallisation, is damolic acid. (See Bamolic acid.) The other baryta salts (in the evaporated mother-hquor) are a mixture of damaluric acid with another salt of baryta ; but whether the acid in this salt is butyric, valerianic, or some new acid|, has not yet been ascertained. Human urine contains only a very small quantity of these acids. And if the urine employed in their preparation be not perfectly fresh, a certain amount of acetic acid is invariably produced. SECTION IX. UEINE-PiGMBDTS. Composition unknown. 1. Urohamatine. — It is probable that the normal colouring- matter of the urine, like bile-pigment, is a modification or product of the decomposition of the hsematine, and is formed from it during the passage of the blood through the kidneys. Dr. G. Harley has of late carefully investigated this subject. He succeeded UROH^MATINE. 43 in the preparation of a pure substance, -which: he satisfied himself, after careful inrestigatioui was modified heematine of the bloodj — an opinion which is confirmed by the discovery, that this substance always contains iron. Dr. Harley calls this body nrohsematine. The following is the method of its preparation :—A. large quantity of urine is evaporated until the fluid has become of the colour and consistence of treacle; the pigment-matter is then extracted by alcohol,, and, duriiig its- evaporation, the salts which crystallise are to be removed; from time to time. The alcohol, dfeeply tinged, is heated to boilkg, and, while boiling, treated with milk of lime, until the colour disappears. It is then filtered^ and well washed with water and ether. The compound of lime and colouring-matter, when dry, is treated with hydrochloric acid and' alcohol, and filtered ; the alcohohc solu- tion is mixed with an e^al quantity of ether, and being frequently shaken, left to stand for several' dap, in order that the ether may take up as much as possible of the colouring-matter. On the addition of water, the ether, charged with the colouring-matter, separates and is removed. The ethereal solution has a very beautiful, wine-red Colour; but it is not yet perfectly pure, and must be washed with water to free it from any remaning trace of adds, and from salts and resinous matter. If this washing, however, is carried too far, a small quantity of the colouring-matter will be thrown down. The ethereal solution, thus purified, is then evaporated, and the pure colouring-matter Mt on the saucer as a dark-red, amorphous, resinous,, substance, which becomes of a splendid red-colour when dissolved in alcohol and ether ; and in many respects, especially in relation to acids and alkahes, closely resembles haematine. When this colouring-matter is burnt, a Httle residue remains, which con- sists solely of oxide of iron. The pigment-matter thus obtained is insoluble in nitric, hydro- chloric, and sulphuric aeids, even in the strongest, and also in tartaric and oxalic acids. It is soluble in ammonia, hydrate of soda, and potash ; insoluble in a solution of chloride of sodium, in chloride of barium and in water; but soluble in alcohol, ether, and chloroform, as is also blood-hsematine in its pure state. Scherer, in his experiments, prepared the colouring-matter of the urine by precipitating it with neutral and basic acetate of lead, and then treating the compound of pigment and lead-oxide with alcohol, mixed with hydrochloric acid. Dr. Harley succeeded in resolving 44 UROXANTHINE. the product thus obtained into four separate bodies, by treating ii with ether, alcohol, and alcohol mixed with hydrochloric acid. The beautiful red ethereal extract, when evaporated nearly to dryness, leaves a shining residue, in which a fatty sort of substance is found. This substance was recognised by Dr. Harley as an animal resin. The alcoholic solution behaves in a similar way. By evaporating these solutions, and washing the residue with water and chloroform, the resin is removed, and the pigment-matter obtained pure. The mass which is insoluble in the alcohol, when treated with alcohol mixed with hydrochloric acid, is resolved into two other substances, whose nature has not been investigated by Dr. Harley. The first two kinds of pigment-matters, soluble in alcohol and ether, exhibit results so similar, when acted upon by tests, that they must, in the present state of science, be considered as one and the same. Hence, according to Dr. Harley's investigations, there are three kinds of pigment-matters. {Wwzburger Verhdl. Bd. 5. 1854. Jour.f. Pract. Chemie. Bd. 64, p. 264.) 2. Uroxcmthme (Heller), Indican (Schunck). — HeUer gives the name of uroxanthine to a substance, of which only a small quantity is present in healthy urine ; but which, on the other hand, is often found in large quantities in diseased states of the urine. It gives the urine an intensely light-yellow colour, and has the peculiar character, when acted upon by acids, &c., of producing two new pigments, viz., uroglaucine and urrhodine, a saccharine substance being at the same time separated. According to the late investiga- tions of Schunck, this body, which is found both in healthy and in abnormal urine, appears to have a similar constitution to indican obtained by him from the indigo-plant. Indican is obtained from the indigo-plant iu the form of a light brownish syriip, which is soluble in water, alcohol, and ether. This, the mother- substance of indigo-pigment, is readily decomposed when acted upon by sulphuric and hydrochloric acids, &c. ; the colouring-matters, indigo-blae, indigo-red, &c., being separated, and a saccharine sort of substance, redu- cible by oxide of copper, indigo-gluoine (Cu Hjo Ou), leucine, and volatile fatty acids (acetic acid, formic acid, &c.) remaining in solution. Indican is separated from its solution by an ammoniacal solution of acetate of lead. The substance obtained from the urine appears perfectly similar to this indican ; and under the action of acids it likewise yields blue and red pig- ments, a sweetish body capable of reduction by oxide of copper being at the same time produced. URRHODINE. 45 3. Uroglaucine and Urrhodine. — These substances are occasionally found in the sediment of abnormal urine. As before said, they are, according to Heller, products of the oxidation of uroxanthine. According to Schunck, they are very probably derivatives of indican. a. Urrhodine — Indigo-red. — When the ethereal solution is eva- porated, the colouring-matter is left in a solid form, and presents no appearance of crystallisation. It may, however, be obtained in an indistinctly crystalline form by the very slow evaporation of an alcoholic solution. The crystals of urrhodine are nearly black, and only present a carmine-red when in very thin layers. In an amor- phous state, urrhodine forms rosy-red granules. It is insoluble in water, but soluble in cold alcohol and ether, to which it imparts a beautiful red colour. (Heller's Archiv, 1846. p. 21.) b. Uroglaucine.- — ^Uroglaucine presents itseE in the form of a blue powder, which, under the microscope, is found to consist of fine- pointed needles ; these needles are rarely single, but usually joined together in sets of two, three, or more. For the most part, they are grouped together in star- and sun-like shapes, which again unite together into larger masses, having a radiated form. Uroglaucine may be sublimed, and is reducible with sulphate of iron, &c. It is often found in the urine in degeneration of the kidneys, and, according to Virchow, sometimes in a crystalline form. The cyanurine of earlier observers is a mixture of the blue and red colouring-matter of the urine. A. Preparation (after Schunck). — ^Urine is treated with acetate of lead as long as any precipitate is formed, and filtered ; the filtrate is then precipitated with an excess of ammonia, whereby the indican (uroxanthine) is thrown down in combination with oxide of lead. The precipitate, collected and washed, is completely decomposed with cold dilute hydrochloric or sulphuric acid, and the solution filtered. If much of the indigo-forming substance is present, the filter and the precipitate will have already become of a bluish shade, and so also wiU the surface of the brown filtrate; but if only a small quantity is present, the blue pellicle will appear on the filter in the course of 34 to 48 hours, but never later. The brown filtrate deposits a dark brown powder, after the indigo-blue, which gradually separates by boiling, is removed. This powder has the same appearance as that which is obtained directly from the extrac- tive-matter of the urine by boiling it with acids, a,nd is partly 46 UROGLAUCINE. soluble in soda-ley with a brown colour, and partly insoluble. The undissolved part is separated by boiling alcohol into two bodies, one of which is dissolved with a purple-blue colour, and appears to be identical with indigo-red, and the other has the properties of indigo- blue. [Jour, fur Frae. Chem. Vol. 75, p. 378.) B. Prepa/ration (after Kletzinsky and Heller). — Urine, which has been turned to an indigo-blue colour by admixture with fuming hydrochloric acid, is thoroughly precipitated rwith acetate of lead, and the filtrate, freed froja, any excess of oside of lead by sulphuretted hydrogen, is evaporated to Tonenthird. The fluid, while warm, is poured into double or treble its volume of fuming hydrochloric acid, and allowed to stand for some days; during which time a thin, copper-red, variegated peUacle is formed on its suifaep, and .the fluid gradually becomes turbild. It is next filtered, and the bluish-black mass which is separated thoroughly washed with water, and, after drying over sulphuric acid, treated with ether, which thereupon takes a darkish-red, or purplish hue, and contains a red amorphous, Tiesinous-like mass, urrhodine (indigo-red, according to Schunci). 'JHoR residue left by the ether is boiled with alcohol, and the deep corn-flower blue solution left at rest in a closed flask. In the course of a month a deep black vdvety sediment is deposited, which frequently contains rudimentary crystals. (The elementary analysis of this precipitate agrees completely with that of indigo^blue, according to Kletzinsky.) According to my own experience, urine rich in uroxanthinedoes not require this complicated process ; ,for when iinixed with an equal volume of hydrochloric acid, it very soon throws down the pigment. The quantity obtained is always vM:y small, and not less than ten to twenty .pounds of urine should .be operated Uippn. G. Tests.^-'^hs, following vary neat itest .©f ,H§llgr may be em- ployed for ascertaining the piesenoe pf eyen small iquwRtities of iiroxanthine in the urine. Piom 3 to 4 G- 0. lOf strong fuming hydrochlomic acid are mixed m a test tube withffrom twenty ,to forty drops of the urineito betested. If uroxanthisoe is present the mixture assumes a reddish-iviolet or intense hWe cciloui;, in consequence of the decomiposition of the urpxapliiine. If the .reaction be indistinfit because of the small .quantity of uroxainthine in the urine, it may be readered much more marked jby the addition of two. or three drops of stEong nitric acid; thereupon, in the course of a few minutes, buit.not immediately, a beautiful violet-colour is produced, which at first plays TESTS OF URINE— PIGMENTS. 47 somewhat into a blue, but afterwards more into a red, and sooner or later assumes a dirty-red, and lastly, agaia beeomes yellow. The coloration generally shows itself without the addition of the nitric acid ; but with the aid of this aoid the smallest traces of uroxanljhine may be recognised. In this reaction, as in ihe others, the nroxanthine is resolved into unhodine, nroglaucine, and sugar. I have had an opportunity of observing for a lengthened period the presence of uroxanthine in the urine of a young man. He was about eighteen or twenty years of age, and apparently of sound constitution, and had -secreted &.e pigment-matter at various times and for long periods together. On the addition of an equal quantity of hydrochloric acid or nitric acid to -this urine, it quickly became of a violet hue, gradually grew darker, and at last assumed a deep dark-blue colout. On shaking the mixture, and after it had been allowed to stand a short tiine, the colouring-matter separated in the iorm either of, a deep-blue scum, or as .a thin, shining, reddish-blue, glistening pellicle. The colouring-matter, when washed, ;appeared as a deep-blue pffliwdec, with a reddish coppery grain j it was dissolved by feoiliog alcohol; but the greater part of it separated again as the alccdiol cooled, the solution remaining of a violet or reddish colour. (Urrhodine.) The product thus obtained sublimed at a moderate heat, forming a beautiful red vaipour, which was deposited as a reddish-blue sub- limate. This subUmate, under the microscope, presented the groups ■of needles above described. ' It could not be distinguished from sublimed indigo ; and its conduct, when treated with concentrated sulphuric and nitric acids, and especially with reducing agents, such as protoxide of iron, and sulphide of ammonium, corresponded entirely with that of indigo.* Evaporation of the urine entirely destroyed the pigment, so that it could not be obtained from the residue. Nitrous acid also decomposed it. I would call attention to a peculiar effect produced on this urine by 'HJcenttated sulphuric acid. When one-sixth to -one-fourth of its volume of concentrated sulphuric acid was added, without shaking, to a small quantity of the urine, there appeared, first of all, at the pointioficontact of the two fluids, a Teddish shade, which gradually became darker, and, spreading through the whole fluid, imparted to it a deep dark-red colour, passing into a purple-videt- * Annalen der Chem. und Pharm. Bd. 90, p. 120. 48 TESTS OF URINE— PIGMENTS. red. This play of colours exactly resembles that which occurs when urine containing bile is treated with sugar and sulphuric acid ; only, in the case referred to, the colours appeared without any addition of sugar. When the pigment was decomposed by evaporation the play of colours could not be obtained. Carter availed himself of this reaction of uroxanthine, when brought under the action of concentrated sulphuric acid, as a test. Por this purpose a test-tube is filled about one inch with the urine to be examined, and one-third of its volume of concentrated sulphuric acid (of J.-83 sp. gr.) carefully poured into the urine, down the side of the tube, which is then shaken. The mixture thereupon assumes more or less of a violet-blue, according to the amount of indigo- forming body which it contains. The process described must, how- ever, be accurately carried out. If the sulphuric acid be of a differ- ent degree of concentration, or if it be added guttatim, &c., the test will either fail altogether or the result will be unsatisfactory. If the urine contains much urohsematine, or bile-pigment, they must be previously separated by a little acetate of lead. If any sulphate of lead should be afterwards precipitated on the addition of sulphuric acid, the test is not interfered with, for the precipitate rapidly sinks, and does not interfere with the coloration of the fluid. On neutralis- ing the sulphuric acid with ammonia, and shaking the mixture with onie-third of its volume of ether, the fluid divides into three layers. The uppermost layer is of a ruby-red, and contains dissolved urrhodine: the middle one is blue, and contains indigo-blue (uroglaucine) in suspension ; and the lowest, containing ordinary urine-pigment, is of a transparent yeUow colour. By this process, which is, however, far from perfect. Carter has shown the presence of indican in the blood. Although indican is very frequently present in healthy urine, at least in small quantities, it is probable that in some diseases its quan- tity is so much increased as to render it a sign of disease, and conse- quently it is worthy the attention of physicians. At all .events, indican (indigo-blue, &c.) becomes of much interest when ^flkrded as a proljable product of the decomposition of proteine-bomes — a view which is strongly supported by the nature of the products of the decomposition of indican, amongst which (as already mentioned) we find leucine and volatile fatty acids, together with a saccharine substance. INORGANIC CONSTITUENTS OF THE URINE. 49 A comparatively large amount of indigo is obtained from the urine of the horse and the cow. Creosote and oil of hitter almonds, taken even iu small quantities, increase considerably the quantity of indigo-blue in the urine. {B^tmisky.) "We may readily conceive, that a vast number of different shades of colour, greenish, grass-green, blue, violet, red, may be imparted to the urine through the union of lu-ohsematine with varying quan- tities of urrhodine and uroglaucine. 4. TJro&rythrme. — ^Uroerythrine is the pigment which gives to sediments of uric acid and urate of soda their brick, or rosy-red colour, the intensity of which increases on exposure to the air. It also appears in solution in abnormal urine, and gives to it its red colour. Nothing more, however, is known of this pigment. (Heller's Archiv. 1853, p. 391.) In conclusion, I must speak of a substance which Scharling has discovered in the ethereal extract of urine. {Annal. d. Chem. u. Pharm. Bd. 42 p. 2S6.) He has not, however, yet succeeded in obtaining this substance, which he calls oxide of omichmyl, perfectly pure, nor has he closely investi- gated its nature. Oxide of omichmyl has a resinous appearance, readily melts in boiling wa- ter into a yellow liquid, is soluble in alcohol, in ether, and in alkalies. It has an acid reaction ; but it is not clear whether this peculiarity is proper to it, or depends upon the presence of some adherent acid. In its dry state it has the smell of castoreum, and in its moist a urinous odour ; moistened with oil of turpentine, it emits a violet odour. Nothing certain is known of its chemical constitution ; nor has its elementary analysis been yet made out. section x. Inoeganio Constituents of the Ueine. In addition to the organic substances already described, the healthy urine contains varying quantities of certain inorganic bodies, which remain as an ash when the urine has been evaporated, and the residue exposed to a very high temperature. We find, in fact, the whole of these bodies in the ash, with the exception of a little ammonia, which is driven off by the heat. During incineration these inorganic substances undergo new arrangements, being oxidised and reduced by the action of charcoal and the oxygen of the air. Hence they are found in the ash, in. combinations different from those which they had when dissolved in the urine. If, however, the e 50 CHLORIDE OF SODIUM. lieat applied in the incineration be too great, appreciable quanti- ties of one or other of these bodies may be completely driven off. The acid phosphate of soda of the urinej for instance, after the evaporation of the urine and the incineration of the residue, becomes intimately mixed with the ash ; but if the mass be strongly heated, a portion of the phosphorus is reduced by the action of carbon on the phosphoric acid, and driven off. This fact suffices to show the great care which is required in conducting the incineration, of which process I shall speak more particularly in the Second Part of the work. As inorganic bases, the urine contains aoda, potash, lime, and magnesia in union (especially the soda and potash) with uric and hippuric acids, and also with sulphuric, phosphoric, and hydro- chloric acids. Small quantities of iron and silicic acid are also found in the urine; so, also, is ammonia, especially when the urine is alkaline. The urine contains no free gases, with the exception of a little carbonic acid and nitrogen. Sulphuretted hydrogen some- times appears in it in its unhealthy conditions. The quantity of in- combustible salts of the urine varies in different persons, and under different pathological conditions of, the body. In men it may vary between 9 "06 and 24'50 grammes, and in women between 10 '28 and 19"63 grammes. Lehmann, when living on a mixed diet, found in his urine 15"245 grammes daily, the quantity varying between 9-652 and 17'284 grammes. We shall next describe the different salts found in the urine. section xi. Chloride of Sodium. A. Occurence. — ^Nearly the whole of the , chlorine found in the lajine is combined with sodium. The quantity of chloride of sodium which is separated with, the urine varies in different persons, and at different periods of the day. Hegar, in his inaugural thesis, has given us the results of observations respecting these variations, made on eight persons. They are, shortly, as foUows : — The average quantity of chlorine passed in twenty-four hours was 10,'4j6 grammes, which corresponds with 17"5 grammes of chloride of sodium. The quantity of chloride of sodium in the urine was most abundant after CHLORIDE OP SODIUM. 51 midday; — during the night the quantity diminished considerably, but it increased again in the morning. Bodily exercise increases, and' slight deviations from health readHy lessen its secretion. The quantity of chlorine, again, is much diminished after beer-drinking. As regards the total amount of chloiide of sodium secreted during twenty-four hours, the latest observations of Bischoff differ somewhat from those of Hegar's. (Bischoff, Ber Hamstoff.. 1853. p. 33.) Bischoff found that in hisi own. urine the quantity, varied between 8*64 and 24<'84! grammes in the twenty-four hours, the average being 14-73. The quantity of: chloiide of sodium in the urine is remarkably diminished in many diseases, and, indeed, in all diseases in which a large amount of exudation has taken place. Eedtenbacher found that the quantity of chlorides was often: reduced to • a minimum in pneumonia, so that, in. some cases, no precipitation whatever occurred: on' the addition of a salt-of; silver to the: urine. B: Mioroscopkal cMracierSi^^HonAe of sodiujto> observed under the microscope, crystallises in beautiftd, wellr formed, regular pyra- midal cubes. It undergoes, however, a distinct modification when separated from a solution containing urea; — ^in. such' case, the ordinary cubes are replaced by octohedral and tetrahedral forms. This peculiar, character' of chloride- of sodium- has been turned to account in determining ttie presence of small quantities of urea in animal fluids. It hasj however, been' founds thati even, pure chloride of' sodium, especially when sepausted. in the form of/ very small crystals, assumes varied cambitations of: its regular forms of crystftUisationj andithat.iti has a particular tbndency to do so when the solution contains any, organic matter. This method, therefore, of testing the presence of urea has been abandoned. 0., Chemical characters. — 1. Chloride of sodium readily dissolves in water, and impartsto the solution a very saline taste*. When water is added to pure, roughly-broken, .crystallised rock-saltj at; .a tempera- ture of la*' to 24^ C, (54*' to76P Fahr.), and the mixture shaken from time tO' time during '241 hours, it' is found that; it invariably takes up the same quantity of salt;. In 10 C. G. of this solution, when filtered: and clear, Liebig: and. others found;, as an average of several closelyiagreeifng observationsj 3*1 84 grammes of chloride of sodiumo* Of this fact we make constant use in quantitative analysis'. 2. Mtrate of silver occasions a white curdy precipitate in' all fluids which contain, ckloride of sodium, the precipitate being e2 52 CHLORIDE OF SODIUM. insoluble in nitric and hydrochloric acids. When, however, a solution of nitrate of silver is added to urine which has been acidulated with nitric acid, the pigments of the urine are also thrown down by the nitrate of silver, and, consequently, the precipitate is not pure chloride of silver. This fact is worthy of note in reference to the quantitative analysis of the chlorine of the urine by the aid of nitrate of silver. 3. Sub-nitrate of mercury, added to chloride of sodium, imme- diately throws down a precipitate of subchloride of mercury, which is almost whoUy insoluble in acids. 4. "When a concentrated solution of chloride of sodium is mixed with an equally concentrated solution of protonitrate of mercury, both salts are decomposed; nitrate of soda is formed, and the fluid solidifies into a thickish crystalline mass of corrosive subKmate. The same decomposition also takes place in weak solutions of these salts ; but in such cases the corrosive sublimate remains in solution. We found, under the head of Urea, that when nitrate of mercury is added to a solution of urea a precipitate of oxide of mercury and urea is thrown down. Protochloride of mercury, on the other hand, throws down no precipitate, either in neutral or acid solutions of urea. The following method, adopted by Liebig in carrying out the quantitative analysis of chloride of sodium in the urine, will now be easily understood : — The phosphoric and sulphuric acids are in the first place separated from the urine by the addition of nitrate and of caustic baryta; the alkaline filtrate is then rendered neutral or slightly acid by nitric acid ; so that the fluid consists of a weak acid solution of chloride of sodium and urea. A solution of dilute protonitrate of mercury is now dropped into it, and where the fluids come into contact a white precipitate is observed, which disappears when shaken. This precipitate is a combination of urea and prot- oxide of mercury. As,- however, chloride of sodium is present in the solution, the nitrate of mercury is immediately converted into corrosive subhmate, which does not throw down urea in a weak acid solution. The precipitate consequently disappears, and leaves the solution as clear as it was originally. This proceeding is again and again repeated, nitrate of mercury being gradually dropped into the solution, until the whole of the chloride of sodium in it is exhausted by the union of its chlorine with the mercuty. At this point, on the further addition of the protonitrate of mercury, as there is no longer any chloride of sodium to change the nitrate into a CHLORIDE OP POTASSIUM. 53 chloride, we obtain a permanent precipitate of urea and oxide of mercury. If, therefore, we know the exact quantity of nitrate of mercury which has been used, we can readily calculate the quantity of chloride of sodium in the urine, one equivalent of oxide of mercury corresponding with exactly one equivalent of chloride of sodium. 5. When a few drops of a solution of neutral chromate of potash are added to a neutral solution of chloride of sodium, containing phosphate of soda, and a solution of nitrate of silver then dropped through a pipette into the mixture, the whole of the chlorine is, in the first instance, thrown down in the form of chloride of silver. But, if more of the solution of silver be now dropped into the mixture, chromate of silver is formed, and imparts to it a permanent red colour. Up to this stage of the process, the phosphoric acid remains completely dissolved, the salt of silver precipitating these three acids in the following order: — Chlorine, chromic acid, and phosphoric acid. (Mohr's volumetrical method.) D. Tests. — The reaction described with nitrate of silver, always serves as a test for the presence of chloride of sodium in the urine. The phosphoric acid in the urine, it is true, also throws down a precipitate with nitrate of silver; but this precipitate — phosphate of silver — is soluble in nitric acid, which the chloride of silver is not. Consequently in testing the urine for chlorine we must, either before or after the nitrate of silver is dropped into it, render the mixture strongly acid by the addition of nitric acid. In the first case, the phosphate of silver will not be thrown down; and in the second, it will be immediately dissolved, the chloride of silver alone remaining, in the form of a cheesy flocculent precipitate. In urine which has been evaporated to a syrupy consistence, chloride of sodium crystallises, after a short time, in cubes or octo- hedra, which are readily recognised. The presence of the soda may be shown by the peculiar character of salts of soda, viz., that when heated to redness on platinum wire in the inner blowpipe-flame, they produce an intensely yellow colour. section xii. Chloride op Potassium. Urine contains chloride of potassium as well as chloride of 54 SULPHATES IN THE URINE. sodium j and the two salts have exactly similar crystaHiae forms. The presence of potash in the urine is tested in the following way : — A little hydrochloric acid is first, added to it, and then an equal volume of a mixture of alcoihol and ether, and, lastly, a solution of chloride of platinum. In the course of a few hours, beautiful octo- hedra of the double chloride of potassium and platinum, mingled with ammonio-chloride of platimiuM, are deposited from the mixture, and may be readily recognised under the miBiPoaoope. section xiii. Sulphates. A. Occurrence. — Numerous researches concerning the quantity of sulphates in the urine have been recently made under Vogel's directions. Prom these it appears that the average quantity of sulphuric acid passed with the urine, by an adult, is 2'094i grammes in twenty-four hours. The quantity increases during digestion, is somewhat less during the night, and falls to its minimum in the forenoon. The amount of sulphates is increased for a time by large drau^ts of water, but is afterwards proportionally diminished. (Grnner.) Sulphates taken by the mouth are wholly discharged with the urine in the course of the following eighteen to twenty-four hours. The ingestion of pure sulphur increases the sulphur-con- stituents of the urine. There is no doubt that the sulphur, which is introduced into the body with the proteinesubstances of the food, is gra- dually oxidised and converted into sulphuric acid, which, again, united with alkalies, is afterwards discharged with the urine. Consequently, a rich animal diet increases the sulphuric acid as well as the urea in the urine. Diseases have a marked influence over the excretion of sulphates, sometimes increasing and sometimes diminishing the quantity of them in the urine. B. Chemical cha/racters. — Some of the sulphates are soluble, and some of them insoluble, in water. The insoluble salts are mostly white, and the soluble colourless in their crystalline state. The sulphates of the alkalies and alkaline earths are not decomposed at a high temperature; but if heated with charcoal, or with organic matters which yield charcoal, they are reduced to the state of sulphurets, and their presence may be then recognised by the odour ACID PHOSPHATE OF SODA. 55 of sulphuretted hydrogen, which they give off wheu the heated mass is moistened with a httle acid. When this test is tried on clean silver, a black spot is left on it. 1. Chloride of barium, added to solutions of the sulphates, occa- sions a white, pulverulent precipitate of sulphate of baryta, which is insoluble in hydrochloric and nitric acids. 2. Acetate of lead throws down sulphate of lead. 3. Sulphuretted hydrogen may be produced when organic matters, mixed with sulphates, are exposed in a moist si^ate to a moderately warm temperature. It is possible, therefore, that the sulphurettqij hydrogen which is occasionally met with ia the urine may be formed- in a similar way. c. Tests. — The sulphates yield, with salts of baryta, a predpitalie which is insoluble in acids, and recognisable even when the solution is exceedingly diluted. Consequently, in testing the urine for its sulphates, we first of all render it strongly acid by the addition of nitric acid or hydrochloric acid, for the same reasons as given in the case of chloride of sodium, and then add to it a solution of chloride of barium or nitrate of baryta. The precipitate which results — sulphate of baryta — is a sure indication of the presence of sulphuric acid. If, therefore, we take a certain volume of urine, say IOC. C, and add to it an equal or sufficient quantity of chloride of barium and hydrochloric acid, we obtain, from the greater or less quantity of precipitate which is thereby thrown down, an approximative estimate of the amount of sulphates present in it. section xiv. Acid Phosphate of Soda. A. Occurrence. — According to Liebig, this salt is undoubtedly present in the urine, and is, moreover, in most cases, the chief cause of its acid reaction. With regard to the amount of phosphoric acid in the urine, numerous calculations have been made, especially by Breed. {Annal. der Chem. u. Pharm. Bd. 78, p. 150.) From 8-765 grammes to 5*180 grammes was the average quantity of phos- phoric acid passed during twenty-four hours by several persons. It appears to me, however, from numerous experiments, which have been lately made, that this quantity of phosphoric acid is some- 56 ACID PHOSPHATE OF SODA. what too high for the 24 hours — a fact which may be readily explained by the defective method of analysis (with perchloride of iron) hitherto employed. I have not found more than 2 grammes of phosphoric acid in healthy urine during the twenty-four hours, since I have employed the volumetrical method with a solution of a sesqui- salt of uranium for determining the quantity of phosphoric acid. A new series of experiments, made under normal conditions with this very sensitive method of analysis, is much needed. Phosphoric acid was found to be somewhat augmented by increase of drink ; but, according to Winter, this happened only during the first two or three hours after drinking. Winter also found that the quantity of phosphoric acid in the urine was considerably greater during the night than in the morning, and that it was greatest in the afternoon ; for as Winter and Breed both observed, the taking of food increased very greatly the quantity of phosphoric acid. In diseased states of the body the variations are considerable, as we may readily imagine ; according to Heller, they vary in much the same way as the sulphates do. B. Chemical characters. — 1. The acid phosphate of soda dissolves readily in water, and imparts to it an acid reaction. It is not altered when exposed to a red heat ; but if previously well-mixed with charcoal or any organic matters, and then heated, part of its phosphoric acid is decomposed, and phosphorus, which immediately passes off in vapour, is formed. 2. Chloride of barium and nitrate of baryta, added to the solution of phosphate of soda, throw down a precipitate of phosphate of baryta, which is readily dissolved in acids. , 3. Phosphoric acid forms, with lime and magnesia, compounds insoluble in water, but which dissolve, even in acetic acid, without decomposition. The phosphate of lime and the phosphate of magnesia, which we meet with in the urine, are held in solution by the free acid, or the acid salts of the urine. When the urine is neutralised by ammonia, the phosphate of lime is thrown down unchanged, but the phosphate of magnesia unites with ammonia, and forms a precipitate of ammonio-phosphate of magnesia. It is in this way that the ammonio-phosphate which appears as a sediment in alkahne urine is formed. The alkaline reaction of urine usually depends upon the presence of carbonate of ammonia, which is produced by the decomposition of the urea ; but whenever this decomposition takes place, the free acid of the urine disappears. ACID PHOSPHATE OF SODA. 57 and the earthy phosphates no longer remain in solution. The phosphate of lime, under such circumstanceSj separates , in an amorphous form, and the phosphate of magnesia in beautiful crystals of the ammonio-phosphate of magnesia. 4. Perchloride of iron, added to a solution of the phosphates, which has been rendered acid by free acetic acid, throws down a yel- lowish-white gelatinous precipitate of perphosphate of iron. This compound is soluble in all acids, except acetic acid j consequently, when we desire to precipitate the phosphoric acid out of any solution by perchloride of iron, we must take care that it does not contain any free acid except acetic acid. Should any other free acid be present, acetate of soda and free acetic acid must be added to the solution before the precipitation by perchloride of iron is effected ; by this means the solution is converted into an acetic acid solution, in which the phosphate of iron is insoluble. This reaction is made use of, after Liebig's method, in the volumetrical analysis of phosphoric acid. 5. A solution of phosphate of soda, mixed with a solution of protonitrate of mercury, immediately produces a copious white pre- cipitate of phosphate of mercury, which soon crystallises when it is left at rest. Corrosive sublimate, on the other hand, when mixed with phosphate of soda, does' not occasion any cloudiness in the solution. Consequently, if a solution of chloride of sodium is added to a mixture of phosphate of soda and nitrate of mercury before the precipitate crystallises, an interchange takes place between the phosphate of mercury and the chloride of sodium, — corrosive sublimate and phosphate of soda being formed. Corrosive sublimate, however, does not decompose phosphate of soda, and the fluid therefore remains bright and clear, in consequence of the disappear- ance of the precipitate which was at first formed. Liebig has grounded upon this fact a plan for ascertaining with tolerable accuracy the quantiiy of oxide of mercury in a solution of nitric acid. One equivalent of phosphate of mercury requires for its decomposition exactly one equivalent of chloride of sodium ; if, therefore, we know the quantity of chloride of sodium which is employed, we also know the quantity of mercury in the solution tested. We make use of this method in the preparation of standard solutions of mercury for the determination of chloride of sodium and urea, after Liebig's method. 6. When a hot solution of a phosphatic salt, which is soluble in 58 PHOSPHATES OF LIME AND MAGNESIA. water or acetic acid, is treated • witli sesquiacetate or nitrate of uranium, a yellow precipitate of phosphate of uianium is imme- diately produced. And if an ammoniacal salt, in sufBcient quantity, be present, the precipitate will also contain amtaonia (2 (Ur^ Og) N H4 O, P Oj + X H 0) ; but it yields, like the former, when heated to redness^ pyrophosphate of the sesquiosdde of uranium, 2 (Ur^ O3) P Oj. The precipitate is not soluble either in water or acetic acid, but dissolves readily in mineral acids ; when, however, an excess of an acetate is add^d to the latter the whole of the precipitate is again thrown down. We now make use of this test in the volumetrical analysis of phosphoric acid. D. Tests. — (See Section xv.) SECTION XV. Phosphates oi' Limb Airb Magnesia. Both of these earthy phosphates, as already stated, are present in a state of solution in acid urine; they are, however, precipitated whenever the urine is rendered alkaline. We obtain a tolerably accurate idea of the quantity of earthy phosphates in the urine by invariably employing the same volume of urine, 10 C. C, for example, and observing the quantity of pre- cipitate which is thrown down on the addition of an alkali; I shall, in the Third Section, call attention to the experience of Beneke on this subject. The quantity of earthy phosphates varies considerably both in the urine of health and disease ; on this point Beneke has made a great number of observations. (See Beneke, Der PAospAorsawe und oxalsm/re Kali;. Gottingen, 1850.) Lehmann found that under a mixed diet the average quantity of earthy phosphates discharged with the urine in twenty-four hours was 1'093 gramme ; Lecanu, on the other hand, makes the quantity vary, during the twenty-four hours, from 0-029 to 1'960 gramme. The amount of phosphates in the uiine seems to bear a very close relation to the nature and quantity of the food which is taken ; it is, for instance, much greater under a purely animal than under a vegetable diet. Lehmann, in the twelve days during which he lived solely upon animal food, passed an average of 3'562 per cent, of phosphates in twenty-four PHOSPHATES OF LIME AND MAGNESIA. 59 hours. Tlie quantity of the phosphate of hme is often considerably diminished in the xirine of young children and of women in the puerperal 'state. In the latter, indeed^ and particularly in' the sixth to eighth month of pregnancy, it often happens, that the urine con- tains no lime. Am extended series of observations, whidh I made in the case of four healthy young men, coraceming the separation of the earthy phos- phates, gave the following results : — 1. From 0"9441 to J'Oia gramme was the average amount (in fifty^two obsH-vations) of earthy phosphates passed during twenty- four hoiu^s by adult men of twenty to twenty-five years of age, under normal conditions. The maximum reached an average of 1'138 to 1"263 ; once only was 1"554 gramme passed in the tw^ity-four hours. The average minimum was 0*8 ; on one occasion the minimum was only 0"328 gramme. 2. The average quantity of phosphateof lime found> in fifty-two observations, was O'Sl to 0"37 gramme. The maximum (mean) quantity was between 0'39 to 0*52 ; it once reached to 0"616 gramme. The minimum was tolerably constant 0'25; once only was it 0"15 gramme. 3. The average amount of phosphate of magnesia in fifty-two observations was 0-64 gramme. The average maximum quantity was 0*77 j once only it reached to 0-938. The mean of the minimum quailtity was 0*5 ; the minimum in one case was as low as 0-178 gramme. 4. Under normal conditions of the body, an average of about 3 eq. of 2 Mg 0, P Oj was passed with the urine for each equivalent of 3 Ga 0, P O . 100 parts of the phosphates contained an average of about 67 per cent, of phosphate of magnesia, and 33 per cent, of phosphate d! lime. 5. Salts of lime, taken by the mouth, either do not pass away at aU with the urine, or only in very small quantities ; the amount therefore, of the normally secreted phosphates is not appreciably in- creased by their ingestion. 6. In diseases, the absolute quantity of earthy phosphates differs considerably from the normal standard, and so also does the relative proportion between the phosphates of lime and magnesia. 2'ggig, There is no difficulty in ascertaining the presence of phosphoric acid in acid urine. The precipitate of earthy phosphates, which is immediately thrown down on the addition of ammonia, is a 60 IRON IN THE URINE. sure test of its presence. We can also readily discover whether or not the urine contains other phosphates, besides the precipitated phosphates of lime and magnesia, by filtering the precipitate which is thrown down by the ammonia, and testing the filtrate, after it has been made acid by acetic acid, with a small quantity of perchloride of iron ; if a whitish-yeUow precipitate be thereby thrown down, the presence of some other phosphate in the urine is indicated. The earthy phosphates are found in the form of 'sediment in alkaline urine, and will be therefore spoken of under the head of Sediments. In order to separate the lime from the magnesia in the precipitate which is thrown down by ammonia, and which consists of phosphate of lime and ammonio-phosphate of magnesia and the precipitate is dissolved in acetic acid, a little chloride of ammonium added, and then a solution of oxalate of ammonia, which precipitates the lime in the form of an oxalate j the magnesia remains in solution, and may be afterwards precipitated from the filtrate by ammonia in the form of ammonio-phosphate of magnesia. section xvi. Ieon. A, Occurrence. — Iron is rarely found, except in the ash of urine, and then only in exceedingly small quantity. According to Dr. Harley, it is a constant constituent of urohsematine, which leaves an ash of nearly pure oxide of iron when strongly heated. Iron may be readily obtained from the ash of urine which contains blood ; and this fact was been made use of as being demonstrative of the exist- ence of blood in the urine, when its presence could no.t be shown microscopically — there being no corpuscles visible in it. This test is, however, a very unsafe one in several respects, for, when prepara- tions of iron have been taken by the mouth, the urine often contains a quantity sufficient to make its presence immediately recognisable by ordinary reagents ; and then, again, in other cases, iron is found only in very small quantity in the ash. B. Chemical characters. — Sulphide of ammonium, added to solutions of protoxide and peroxide of iron, throws down a black precipitate of sulphuret of iron, which is readily soluble in hydro- chloric and nitric acids. AMMONIACAL SALTS. 61 2. Perrocyanide of potassium, added to a solution of peroxide of iron, occasions a deep-blue precipitate of ferrocyanide of iron (Prussian blue) Cfy 3 + 4 Pe. The precipitate whicb it forms in solutions of protoxide of iron is of a bluish-white colour, and, consists of ferrocyanide of potassium and iron (K, Fe 3, Cfy 2). 3. Sulphocyanide of potassium does not affect solutions of the protoxide of iron, but it produces an intensely red colour of sulpho- cyanide of iron in solutions of the per-salts. 4. If a solution of permanganate of potash is added to an acid solution of a salt of the protoxide of iron, the protoxide passes wholly into a state of peroxide ; and when this stage of the process is attained, a few drops more of the solution of permanganate of potash, added to the mixture, impart to it a beautiful red colour, 10(PeO,SO3) + 8SO3 + KO,Mn,O, = 5(i'e,O3,SSO3)+KO, SO, + 2(MnO,SO,). c. Tests. — Yoi testing and ascertaining the presence of iron in the urine, the ash obtained from the urine is always employed. The ash is dissolved in a little hydrochloric acid, and the solution divided into two portions. One portion is boiled with a drop of nitric acid, and sul- phocyanide of potassium then added to it ; thereupon, if only the smallest quantity of iron be present, the fluid wiU assume a reddish colour, and if a considerable quantity of it, a deep dark-red colour. When mere traces of iron are present, the change of colour is best observed by placing the tube over a white ground and inspecting it from above. If, instead of sulphocyanide of potassium, we add to the second portion of the fluid — after boiling it with nitric acid and diluting it — ^ferrocyanide of potassium, we shall find that in a short time blue flocculi of Prussian blue separate in it; and if the quantity iron be considerable, the Prussian blue wiM be immediately thrown down of a beautiful colour. section xvii. Ammoniacal Salts. The determination of the presence of ammoniacal salts in normal urine is attended with much difBculty. We well know how readily the colouring and extractive matters of the urine undergo decomposition, and how easily the urea passes into carbonate of ammonia, especially 62 AMMONIACAL SALTS. when the other matters (mentioned above) are also present in it. This is doubtless the reason why opinions differ so much concerning the origin and the quantity of ammonia present in healthy urine. Ammonia is always found in the products of the distillation of healthy urine, which has an acid reaction, however low the tempera- ture at which the distillation is effected; and yet the remaining concentrated urine is often found to redden litmus, even more strongly than it did at first. This apparently contradictory pheno- menon may be thug explained: — ^The acid phosphate of soda of the urine, when heated, causes decomposition of the urea, in consequence of which ammonio-pbosphate of soda is formed. Now this salt has the property, even, at 100° C. (312° Fahr.), of giving off ammonia, and returning again to the state of acid phosphate, of soda. Consequently, so long as the distillation, continues,, the acid phos- phate of soda acts upon the urea; and the urine therefore always retains its acid reaction, whUfet: a conadersble quantity of ammonia is found, in the distillate. Withi a little oaie, however, the presence of, small quantities of aiinmoniacal salts in healthy urine may be ascertained withi certainty ; the inFestigatiojis of Heintzj of Bbussingault, and of myself, leave no doubt on this point, TcS. show the presence of ammoniacal salts in acid urine, freshly passed healthy urine is, precipitated by. a solution of sugar of lead, mixed with acetate of lead, filtered, and the filtrate treated; cold in a flask with; milk of lime. The flask is- then closed with a stopper, to which a piece lOf moistened, turmario-paper is attached. This testi- paper quickly, becomes brown. Whence oomes the ammonia thus eliminated in the cold, by milk of- lime?' Urea is not decomposed in the cold by. milk of lime ; nor are the jagment and extractive mat- ters separated by oxide of lead. Consequently^, we must consider it as demonstrated, that freshly-passed healthy urine contains ammoniacal salts, at least until some body is discovered in normal urine {precipi- tated with sugar of lead and acetate of lead), which is capable of leing decomposed in the course of a few seconds by milk of lime, in the cold, with evolution of ammonia. I made use, in my experi- ments, of Schlossing's method. This process is founded on the fact, that an aqueous_ solfetion of ammonia allows the ammonia to pass off in vapour, at an ordinary temperature, and in a comparatively short space of titne, when exposed in thin layers to the action of the air in a shallow vessel. The ammonia which thus passes off i may SILICIC ACID. 63 be fixed -by a standard solution of sulphuric acid, and its quantity determined. Having satisfied myself of the practicability and correctness of this method, I proceeded to ascertain the quantity of ammonia passed by healthy men in 24 hours. My experiments show that an average of 0"724!3 gramme of ammonia, corresponding with 3'2783 grammes of sal-ammoniac, was secreted by men of from twenty to thirty-six years of age during 24 hours. The quantity varied in 24 experiments betweeii 0'3125 and 1"3096 gramme of ammonia, corresponding. with 1'4272 and 3"8038 grammes, of sal-ammoniac. I made my experiments on two healthy men of twenty and thirty- six years of a.ge, and found that the latter passed on an average the largest quantity of ammonia in the 24 hours. The following Table will show the difference : — Maii,20 years old. Man 36 years old. Difference. A __^ /<.. , A__ ' NH, NH^Cl. NH3 NH^Cl, NB3 NH^Cl. In 24 hours . 0-6137, 1-9305 0-8351, 2-6361 0-2214, 0-7056 In 1000 CO. I 0-3939, 1-2390 0-5245, 1-65601 0-1306, 0-4170 of urme . . ) " ' The greatest part of the sal-amnloniac taken by the mouth passes away unchanged with the urine. SECTION XVIII. Siijcio Acid. Urine coi^tains only a very sjnall quantity of, silicic acid. The following is the process for obtaining it,: — :A largish quantity of urine is evaporated in a platinum or silver basin, ai^d, the re^due reduced to an asli. The ash i§ mixed with an excess of, purp car- bonate of spda and pptash, a.nd fuse^d for some time in a platinum crucible. The mass is then .^ disspl,Vied in vifater, the mixture acidified with hydrochloijc acid, and evaporated tq dryness in, a platinum. dish in a water-bath,, The reside is washed with watefr,, ani^, the silicic acid remaipiS behind in ajpure, state. The silicic acid thus obtained is a white powder, without tpte or smeU, and, feels. gritty between the teeth. It, is,inspj«blei.in.vi[ater and in acids, but is completely dissolved, leayi^g np residue, when boiled in a solution of carbonate of soda. (Signs of purity.) , 64 ALBUMEN. ABNORMAL CONSTITUENTS OF THE IJEINE. SECTION XTTf. Albumen. Composition : — Scherer. Mulder. In 100 parts Carbon . . 54-§83 53-5 Hydrogen . . 7-035 7-0 Nitrogen . . 15-675 15-5 Oxygen . \ Snlphur . 5 22-365 22-0 1-6 Phosphorus ) 0-4 100-0 Its rational formula is not known. A. Occurrence. — ^Albumen is the most important of the different materials required for the maintenance of the body ; its serves for its nourishment, as weU as for the restoration of the used-up tissues. It is therefore present in large quantities in all parts of the body, and forms the chief constituent of the blood, the lymph, and the chyle, of all serous fluids, and of the liquid of cellular tissues. Patholo- gically, albumen is found in the urine, under very various conditions — ^in slight, as well as in the most serious disorders of the body. In a perfectly healthy state of the body no albumen passes away with the urine. Observation teaches us, that its presence in the urine is not invariably a consequence of kidney-disease, for there are periods in the course of many chronic and acute diseases, during which albumen appears in the urine. Its occurrence is most constant in those affections of the kidneys to which the name of " Bright's disease " has been given. It is not the object of this book, nor is it my intention to give an account of the different diseases in connexion with which albumen is found in the urine. This much, however, is certain, that it is necessary to test for albumen every specimen of pathological urine, the condition of which we wish to investigate ; for, as we have seen, the presence of albumen in the urine is not associated with any one particular form of disease. The presence of albumen in the urine is not indicated by any special microscopic characters. B. Chemical chp/racters. — Albumen belongs to the class of nitro- ALBUMEN. 65 genous principles of animal and vegetable bodies, which Mulder has associated under the head of "proteine-bodies." All these com- pounds — albumen, caseine, fibrine, syntonine, &c. — are closely allied in their percentage composition, and have a great resemblance in their chemical characters, but differ in their actual constitution. The chief representative of this class is albumen, whose importance in the animal economy is great. Albumen presents itself to us under various modified forms. Two of its conditions, the soluble and the insoluble, require especial notice. We find it in a soluble state in all parts of the body. Its solution does not depend solely upon the presence of water, but IS m part attributable to the presence of saline matters, and more especially of a free alkali. "When a solution of pure albumen is evaporated in vacuo, or at a temperature of 50° C. (122" Pahr.), the dissolved albumen is left as a pale-yellow, translucent mass, which may be easily reduced to a white powder. It swells in water to a gelatinous mass, and is only partially soluble in it; when, however, a small quantity of any alkaKne salt is added, its complete solution rapidly takes place. The plane of polarisation is turned to the left by a solution of albumen. The influence of numerous bodies, and sometimes, indeed, the action of the air alone, converts the soluble into the insoluble form of albumen. Eecently-formed insoluble albumen has a whitish flocculent appearance, is without taste or smell, and, under the microscope, shows as an amorphous granular coagulum. When dry, it forms a yellow, horny, translucent mass, which is easily pulverised, and is insoluble in water, alcohol, ether, and dilute acids. Soluble albumen is coagulated and converted into the insoluble form by most of the acids, when they are added to the solution of albumen in slight excess. Organic acids, however, with the exception of tannic acid, do not precipitate albumen from its solutions. Albumen exhibits, with most tests, the same characters as other proteine-bodies. The following phenomena presented by it are worthy of note : — 1. Albumen is completely dissolved when exposed to the action of a solution of caustic potash or soda ; the solution has a yellowish colour, and contains the albumen in an altered state. On neutral- ising the alkali with an acid, the dissolved albumen is thrown down, and sulphuretted hydrogen, proceeding from the sulphur contained in the modified albumen, is evolved. 66 ALBUMEN. 2. Concentrated acetic acid, assisted by heat, also dissolves albu- men ; and in this solution ferrocyanide and ferricyanide of potassium throw down peculiar precipitates. 3. A violet-red coloured fluid is produced when albumen is heated with concentrated hydrochloric acid, and, better stOl, wij;h the addition of a Little sulphuric acid. 4. Concentrated nitric acid colours it yellow when heated. (Xan- thoproteic acid.) 5. A solution of one part of mercury in two parts of nitric acid containing four and a-half equivalents of water (sp. gr. I'^l), is the most delicate test for albumen, as well as for all proteine-bodies, whether dissolved or undissolved. An albuminous fluid, heated with this solution of mercury to from 60° to lOO* C. (140° to 213" Pahr.), becomes of an intensely red colour, which does not disappear on exposure to the air, or after long boiling. 6. Albumen becomes of a brownish-yellow when a solution of iodine in acid hydriodio acid is added to it. This reaction is espe- cially well observed under the microscope. 7. Heated on platinum foil, albumen rapidly becomes browu' — swells up and gives off an odour like that of burnt horn. The bulty carbonaceous mass remaining is burnt with difiiculty, and leaves a greyish ash, consisting chiefly of lime and phosphoric acid. 8. Albuminous bodies subjected to dry distillation, as well as under the influence of oxidising agents, and when imdergoing putre- faction, are decomposed into a number of new compounds — amongst others, into formic acid and acetic acid, into fatty acids, butyric and valerianic, benzoic acid, oil of bitter almonds, and into two crystal- line compounds, leucine and tyrosine. 9. A solution of albumen, heated in a test-tube over a spirit lamp, becomes turbid at a temperature of about 75° to 80° C. (167° to 176° Fahr.). The coagulation commences at the surface of the fluid, and then extends gradually downwards through the tube. A white flocculent coagulum, which, under certain circumstances, is more or less coloured, is thus formed, the albumen passing into an insoluble form. Several points are worthy of notice in reference to this simple test: — When the solution of albumen is very much diluted, the turbidity will often appear only at a boiling heat ; and to obtain a distinct coagulum, it may be necessary to boil it for a long time, and then allow it to stand. When the fluid has a slightly acid reaction, and provided there be no excess of acid present. ALBUMEN. 67 complete coagulation usually occurs. But if the solution be neutral or slightly alkaline, heat often occasions merely a slight turbidity, even though a considerable quantity of albumen is present. In such case, the albumen remains in solution with the alkali. If, howeve*, before heating the solution, acetic acid is added to neutralise the alkali, the albumen is completely coagulated and thrown down in large flocculi. Care should be taken not to add an excess of the acid, because albumen is more or less dissolved by free acetic acid during the boiling. The coagulum thus obtained is the insoluble form of albumen, and comports itself, in relation to solvents, acids, and alkalies, as above described. When heated, and particularly when boiled, it is dissolved by acetic and hydrochloric acids, — ^the latter acid giving it a reddish-blue colour. 10. Dilute nitric acid added to albuminous solutions throws down a white precipitate of nitrate of albumen, which is soluble in a large quantity of water — an important fact. Other mineral acids produce a Hke effect. 11. Strong alcohol produces complete coagulation of albumen in solution. Dilute alcohol occasions a precipitate, but does not convert the albumen into its insoluble form. 12. Most of the metallic salts, and Hkewise alum, occasion dif- ferently constituted precipitatesa The precipitate caused by subli- mate of mercury is of especial interest. 13. Sugar and concentrated sulphuric acid become of a beautiful red colour with all proteine-bodies, just as happens in the case of gallic acid. (See Qallio Acid.) Schultaei 14. An albuminous solution tlirns the plane of polarisation to the lefti Hoppe availed himself of this property of albtimen for its quan- titative determination. The divergence, which is proportional to the degree of concentration, is as marked as in the case of a solution of grape-sugar of similar percentage. 15. Albuminous bodies, treated with a solution of sulphate of copper, and heated, after the addition of caustic soda or potash, imparts to the solution a beautiful violet colouri The reaction does not take place, or at all events is imperfecti if the alkali is added before the salt of copper. c. Tests. — The presence of albumen in the urine is ascertained by a very simple process, which, if carefully performed, leads to positive results. The reaction of clear or previously filtered urine is first f2 68 ALBUMEN. tried, and a test-tube, half full of it, is then heated over a spirit lamp. E it contains albumen and has an acid reaction, the surface of the urine becomes turbid when the heat exceeds 70° C. (158° Pahr.), and coagulation of the albumen quickly follows. If the urine be either neutral or alkaline, the coagulation will not take place, for reasons above given, or there wiU be at most only a milky tnrbidness. But if before heating we add to the urine a Kttle acetic acid, carefully avoiding an excess, a flaky coagulation will take place in the urine when boiled. If, again, the urine be very acid, and contains, for instance, free hydrochloric or nitric acid, which may readily happen when these acids have been taken internally, boiUng may fail to produce coagulation of the albumen. To obtain the albumen in such case the urine must be, first of aU, sufficiently neutralized with very dilute ammonia. When all these precautions have been taken, if we obtain, on boiling the mine, a turbidity or precipitate, which on cooling is not dissolved by nitric acid, we may consider the absence of albumen in it demonstrated. Cases, however, are occasionally met with, in which a precipitate is formed on boihng the urine (particularly if the urine is only slightly acid or neutral), but in which, nevertheless, no trace of albumen is present. Such precipitate consists of phosphatic eaiths, which in slightly acid urine are generally held in solution by the free carbonic acid. On the expulsion of the gas by boiling, the phosphates are precipitated in a flocculent form, and can then scarcely be distinguished by the eye from coagulated albumen. All doubt as to its nature is immediately removed by the addition of a few drops of dilute hydrochloric acid to the urine (when cooled), in which the precipitate is suspended. If the precipitate consists of phosphates it wiU immediately disappear, and leave the fl.uid clear, but if of albumen, it will remain unchanged. This state of the urine very frequently occurs, and therefore the subsequent testing with nitric acid should never be omitted, whenever any slight tur- bidity results from boiling. A second specimen of the clear or previously filtered urine is treated with one-fourth its volume of pure, moderately-concentrated, nitric acid. A distinct turbidity of the fluid thereupon results, if only a very small quantity of albumen be present, and a dense white precipitate if the quantity be considerable. The test with nitrio acid may, according to Heller, be also applied in the following very neat way : — A little pure concentrated nitrio acid is poured ■APPENDIX. 69 into a champagne-glass, and the urine to be tested then allowed, by means of a pipette, to run down the side of the glass and spread over the surface of the acid. When this is carefully done, the urine floats on the surface of the acid, and their admixture takes place slowly and gradually. In most cases, an intensely red, violet, or blue ring — the reaction of uroxanthine — presents itself at the point of contact of the two fluids. The observer must uot consider this play of colours as a bile-pigment reaction, unless a green colour is distinctly visible under the blue. If the urine contains mere traces of albumen, this test exhibits at the part where the fluids come in contact a circular turbidity well defined above and below. This reaction lasts for some length of time ; but the coagulated albumen at last sinks to the bottom of the glass. A turbidity, which at the first glance seems of a similar nature, may occur, when the urine is rich in urates. In this case, also, a ring-shaped turbidity is formed ; but the ring is placed higher than the position of the albuminous ring. The lower and also weU-defined border lies higher than the point of contact of the two fluids, and generally also higher than the upper border of the albumen turbidity; moreover, it is not weE-defined above, but vanishes gradually towards the surface of the urine. If the urine contains albumen, and at the same time a large quantity of urates, two rings may be formed — a lower albuminous ring, which is gene- rally separated by a clear layer from the upper stratum of turbidity formed by the urates. In such case, it is better, previously to testing, to dilute the urine with two or three parts of water, in order to prevent the reaction with the urates, or at least to reduce it to a minimum. Turbidity caused by urates also disappears when the urine is gently heated, and all doubts as to its nature are thereby at once removed. In very concentrated urine a precipitate of nitrate of urea may also take place ; but it is of a crystalline form, and immediately disappears on the addition of water. APPENDIX. SECTION XX. Fibrine — another of the proteine-bodies — is sometimes met with in the urine, appearing in the form of large coagula, particularly in acute inflammations of the kidneys and urinary passages. Urine of this nature always contains blood, and is consequently albuminous also. The peculiar tubular cylinders, which Frerichs regards as com- pressed fibrinous coagula, will be treated of under the head of Sedi- ments. Cases are also occasionally met with in which fibrine is separated from the arine, partly in gelatinous masses, and partly as granular or thread particles. 70 DIABETIC SUGAR. The presence of easeine in the urine has not yet been distinctly shown. Proteine bodies also, differing in their characters from ordinary proteine, are sometimes found in the urine. Thus Dr, Bence Jones (Annal. d. Chem. u.FJwm. Bd. 67, pp. 97-105) relates the case of a man suffering from moUities ossium, in whose urine he found, together with urinaiy casts, a peculiar albuminous substance, which was soluble in boiling water, precipitated by nitric acid, and then re- dissolved when heated, separating, however, from the fluid as it cooled. Its behaviour, when subjected to the other testa for albumen above-mentioned— such as acetic acid, ferrooyanide of potassium, and concentrated hydrochloric acid, — proved it to be a proteine- compound ; but its peculiar action with water and nitric acid forbid us classing it either under the head of albumen or easeine — at least so Ipng as we are unaible artificially to induce albumen or easeine to undergo this peculiar modification. Bayloa describes, uncler the name of ' albuminose,' an albuminous sub- stance wbich, aocQxdiiag to him, is also present in healthy urine. This sub- stance, Mialhe tells us, conducts itself in reference to albumen as does glucose to amylum (?). Albuminose is precipitated by tannin and several metallic salts, but not by heat, or acids, or alkalies. It is> as asserted, always present in healthy urine, and also in its abnormal states. In a cq,se of Bright's disease, however, in which the urine contained much albumen, no albuminose was found. Baylon pointed out tartrate of copper as being a very sensitive test of albuminose. The urine, after the addition of a few drops of potash-ley, is boiled, filtered, and a solution of tartrate of copper added, until the mixture assumes a lightish blue colour. In the course of an hour or two the tartrate of albuminose (?) is precipitated j it may be re-dissolved by heat, but again separates as the fluid cools. (CanstaWs Jahresberieht. 1S60, p. 270.) section xxi. Diabetic Sugak. — Gbape Sugak. Composition. — In 100 parts :— Anhydrous— Carbon , . 40-00 Crystallised — 36"36 Hydrogen . 6-66 7'07 Oxygen . . 53-31 56-57 100-00 100-00 Formula : C„ H^, 0,, C„ H,j Oj,-t- ii H DIABETIC SUGAR. 71 A. Oeourrmce. — Grape-sugar^ wluch is perfectly identical with sugar of urine, is found extensively distributed throughout the vege- table kingdom. It is also found normally in animals, and in some of the fluids of the body in its diseased comditions. It is, for instance, always present in the contents of the small intestines and in the chyle, after saccharine or amylaceous food has been taken ; in the hen's egg, whether hatched or unhatched, and in the yolk as well as in the white 5 and also in the amniotic and allantoic fluids of cattle, sheep, and pigs, and in the liver. Sugar, again, has been frequently found in the blood, and particularly in the blood of the hepatic veins. According to Lehmann's latest observations, the blood of the vena portse contains no sugar; consequently, the formation of the sugar must take place in the parenchyma of the liver. As, then, there is no doubt that sugar is normally formed in the body, and that its appearance in any of the excretions is abnormal, except, perhaps, in the merest traces, we are necessarily led to the conclusion that it gradually undergoes further changes in the body, passing through several intermediate forms with which we are not yet acquaiiited, and that it is at last completely oxidised, and passes away from the body in the form of water and carbonic acid. The numerous researches of Briicke seem clearly to show that healthy urine frequently contains traces of sugar. The sugar, how- ever, only appears in large quantities in cases of diabetes melHtus, and in such cases is found to be increased also in the blood, the matters vomited, the saliva, the sweat, &c. In other diseases sugar is also occasionally found, as for example, in cases of disturbance of the abdominal circulation. Injury of certain parts of the medulla oblongata in animals again will produce a temporary attack of diabetes. According to Lehmann, saccharine urine is observed in women twenty-four to forty-eight hours after weaning. B. Microseopkal characters. — ^Diabetic sugar usually crystallises in confused masses, which have the appearance of wart-Uke conglo- merations, and consist of small plates grouped in a cauMower form. These plates have a rhombic character. But if the separation of crystals takes place rapidly from a solution, the crystals appear, under the microscope, not in the form of plates, but of irregular, striped, and roundish masses. c. Chemical characters. — Pure grape-sugar is white, and without smell ; its taste is not nearly so sweet as that of cane-sugar, neither is it so soluble in water. Its solution has no action on vegetable 72 DIABETIC SUGAR. colours ; it turns the plane of polarisation to the right. It is com- pletely insoluble in ether, but moderately soluble in alcohol. Crystallised grape-sugar, exposed for some time to a heat of 100° C. (212° Eahr.) parts with its water of crystallisation (2 eqs.). Cane- sugar exhibits the same action with polarised hght ; its aqueous solu- tion causes a divergence of the rays to the right, and herein it agrees with crystalline grape-sugar, even to the degree of the divergence. When, however, the watery solution of cane-sugar is digested for some time with dilute sulphuric acid, the sugar takes a modified form of grape-sugar, whose solution causes a divergence of the po- larised ray to the left. This peculiar property of sugar is referred to, because it has been made of use in the quantitative analysis of sugar ; the greater or less degree of the divergence in equal volumes of the saccharine solution indicating the amount of sugar present in it. It is hardly necessary to say, that the degree of divergence must be previously determined in solutions, the amount of whose saccharine contents is accurately known. 2. Grape-sugar, when heated to 140° C. (284° P.), is converted into caramel. At a higher temperature it yields acid products of distillation, and leaves a voluminous shining ash, which is burnt with difficulty. 3. In contact with nitrogenous bodies, and especially with caseine, grape-sugar undergoes the lactic acid-, and afterwards the butyric acid- fermentation. In diabetic urine, even at a moderate tempera- ture, though more rapidly at 25° to 40° C. (77° to 104° Fahr.), the sugar turns to an acid, which, according to circumstances, is acetic, butyric, or lactic acid. 4. Digested with nitric acid, grape-sugar is converted into oxalic and saccharic acids. 6. With many bases it forms pecuKar compounds, — so-called saccharates : a. Potash-gluGOse. — 2 K O -h C,, H,, 0,^. This compound is readily obtained by the admixture of an alcoholic solution of sugar with a solution of caustic potash in alcohol. It is immediately thrown down in the form of white flocculi, which, when exposed to the air, become tenacious, adhere together, and take up carbonic acid. h. Lime-glucose. — ^This compound is obtained as a white mass when an excess of caustic lime is added to a solution of the sugar, the mixture filtered, and the filtrate treated with alcohol. c. ■ Chloride of sodium-glucose.— % (C„ H.^ 0, J Na CI -f 2 H 0. DIABETIC SUGAR. 73 A solution of grape-sugar, mixed -with a solution of cHoride of so- dium, and allowed to undergo spontaneous evaporation in the air, crystallises in large colourless, four-sided double pyramids. These crystals are hard, and easily pulverised ; they dissolve readily in water, but with difficulty in alcohol. They contain 13'3 per cent, of chlo- ride of sodium. 6. A. solution of the sugar, digested with caustic potash or soda, becomes of a beautiful reddish-brown colour, and if nitric acid be then added to it, it emits a pungent, sweetish odour, somewhat re- sembling that of caramel and formic acid. 7. A solution of indigo-carmine rendered alkaUne by carbonate of soda, and boiled with a little grape-sugar, becomes coloured, if only a small quantity of sugar be present ; the solution is first of all green, then purple-red, and if more sugar be added, of a red, and lastly, of a yeUow colour. If the hot yellow solution be now shaten up, so as to bring it under the action of the oxygen of the air, the play of colours goes on in an inverse course. The mixture takes a purple-red, then a green, and lastly, once again a blue colour ; if, however, it be allowed to stand for a short time the yellow colour wlU reappear (Mulder). This reaction is a very brilliant test, and is capable of determining the presence of a very small quantity of sugar. If only traces of sugar are present, of course only a very weak blue-indigo solution must be employed. 8. When a Kttle caustic potash and a few drops of a solution of sulphate of copper are added to a solution of the sugar, either no precipitate is formed, or that which is formed is again re-dissolved, and imparts a beautiful blue colour to the liquid. This fluid, when heated, takes, first of all, an orange-red colour, it then soon becomes muddy, and finally throws down a dirty red precipitate of sub- oxide of copper. The oxide of copper is, in this process, reduced by the alkaline solution of sugar, and the oxygen which is separated acts as an oxidising agent upon the sugar. This reaction will take place, after long standing, without the application of heat and even in the cold. Uric acid, hypoxanthine, mucus, &c., also, under heat, effect the reduction of oxide of copper with separation of red suboxide of copper. It should, however, be remarked, that many bodies, when present, prevent the separation of the suboxide of copper, as, for example, albuminous matters, such as peptone, creatine, creatinine, pepsine, trimethylamine, and ammonia, or compounds which when heated with potash give off ammonia. 74 DIABETIC SUGAR. Fm. 1. 9. Fermentation is soon observed to commence in a solution of sugar, to which a little yeast has been added, particularly if the fluid he kept at a moderate degree of heat, 12° to 25" C. (53° to 77" Eahr.). The process may be readily observed in the following way:— A is a small flask, into which the sugar is introduced with the yeast. The flask is made to communicate, through the tube c, with the flask B, which is half-fiUed with lime- or baryta-water. The tube a is closed above by a bit of wax at b. When the mixture in a is warmed to the temperature mentioned, the solution of sugar soon becomes tuibid; a distinct scum forms on its surface, and gas is given off. This gas is carbonic acid, which is separated in the form of carbonate of baryta or of lime, on being passed through the solution of lime or baryta. When the evolution of gas ceases, the fluid in a becomes clear, loses its sweet, and assumes a vinous, taste. The sugar is decomposed into alcohol and carbonic acid. When the quantity of sugar is very small, the fermentation-test may be employed in the way described by Lehmann. A long and widish test-tube is fiUed to one-fourth with quicksilver, and the fluid to be tested slightly acidulated with tartaric acid, and mixed with a little weU- washed yeast, poured on it to overflowing. The tube is closed with a caoutchouc cork, through which a narrow glass tube is passed down into the mercujy at the bottom of the tube, its ex- ternal upper extremity being bent to an acute angle. This apparatus is then warmed to a temperature of from 80° to 40° C. (86° to 104° Fahr.). If the solution contains sugar capable of undergoing fermentation, carbonic acid will very soon be evolved, and collecting under the stopper, will force the mercury up through the narrow tube. The nature of the gas may be at once ascertained by the action of lime-water. 10. A solution of grape-sugar treated with a weak ammoniacal solution of nitrate of silver, and boiled for a short time, throws down DIABETIC SUGAR. 75 metallic silver in tbe form of a bright metallic mirror. The reduc- tion is not prevented by the presence of ammoniaj and may therefore be of service under certain circumstances. It must not, however, be forgotten, tljat many other bodies, such as tartaric acid, &c., reduce the silver in a similar way. 11. A solution of bi-chromate of potash, containing a Httle free sulphuric acid, mixed with diabetic urine, imparts to the mixture, when heated, a characteristic bluish-green colour. (Krause). 12. To test the urine for sugar, aceordiog to Bottcher's method, the urine is poured into a test-glass, and mixed with an equal volume of a solution of carbonate of soda (three parts water, one part crystalUsed Na 0, C Oj) ; to this is added a Uttle basic nitrate of bismuth, and the whole then heated to boiling. If the snow- white salt of bismuth now assumes the slightest shade of dark or grey, the presence of diabetic sugar in the solution is positively indicated} for, according to Bottcher, there is no other constituent of the urine ■which acts as a reducing agent on this salt of bismuth. The urine, however, must be absolutely free from albumen ; for if it is present, black sulphuret of bismuth readily forms and may create confusion. This test also serves to distinguish cane- from grape- sugar, as cane-sugar does not occasion a similar reduction. D. Tesis. — Different methods are employed for testing the pre- sence of sugar in the urine, according as the quantity of sugar which it is supposed to contain is greater or less. If the quantity of urine passed iu the twenty-four hours is large,, for example four or five litres — ^if the colour is greenish-yellow, and the specific gravity high, above 1'020, the urine to be tested! is most probably diabetic. In such a case the presence of the sugar is easily shown, for diabetic urine comports itself with almost all tests, as a pure solution of sugar. When, therefore, the urine is free from albumen, which must be previously determined (Sect. 19), the different tests for grape- sugar may be directly employed. If albumen be present, it must be separated according to the directions given (Sect. 19). In testing for sugar we proceed as follows : — ' 1. Fifteen to twenty drops of the urine are diluted with 4 to 6 C. 0. of water, ^ C. C. of caustic soda or potash added, and a very dilute solution of sulphate of copper dropped into it. If sugar is present, the precipitate which at first forms is re-dissolved on shaking, and the fluid becomes of a clear blue colour. This blue solution is then heated nearly to boiling, whereupon a yellow cloud 76 DIABETIC SUGAR. forms, which soon, and without further heat, is followed by a separa- tion of yellow or red suboxide of copper. Care must be taken not to heat the mixture of urine and potash-ley before the addition of the copper-solution, as thereby the sugar, and especially if the quan- tity of it is small, may be so altered as to be rendered incapable of reduction by the copper salt, A second mixture, similarly prepared, is left at rest for six to twenty-four hours, without being heated, and, if sugar is present in it, a separation of suboxide of copper will also take place. This counter-test is of importance, and should never be omitted ; for most of the bodies, which (like sugar) reduce the solution of copper, require heat or long boiling for the reduction. Diabetic sugar, on the other hand, reduces the copper without heat. 2. A second specimen of the urine is diluted with an equal quantity of carbonate of soda solution, a small quantity of tris- nitrate of bismuth added to it, and the mixture boiled for a long time. A complete or partial reduction of the oxide of bismuth wiU follow, according to the amount of sugar present, and consequently a grey or black colouring be produced. When the quantity of sugar is small, only a very little bismuth should be employed ; otherwise, the reduction being slight, it may be concealed by the excess of the white salt. If the tested urine is now left at rest, the undecom- posed oxide of bismuth first sinks to the bottom, and the reduced bismuth is then distinctly seen deposited upon it in the form of a beautiful black-velvety ring. 3. Another portion of urine is poured into along but narrow test- tube, a little caustic potash solution added, and the fluid in the upper part of the tube heated to boiling. If sugar be present in the urine the boiled portion of the fluid becomes of a brownish-red colour, whilst the lower part of it retains its original appearance. The slightest change of colour may be distinctly observed in this manner. This reaction is highly serviceable as a confirmatory test. Further proofs may be obtained by the tests 7 and 10, and especially by the fermentation-test, which may be applied by the aid of the apparatus shown in Kg. 1. The sugar may be readily obtained from diabetio urine in a pure crystal- line form : for this purpose the following processes are employed : — I. The urine is evaporated to the consistence of syrup in a water bath, and the residue left at rest until the sugar has become crystallised in the form of yellowish, warty masses. From this crystalline mass the urea and DIABETIC SUGAR. 77 extractive matters are separated by the aid of absolute alcohol ; and the sugar is thea extracted from the residue by boiling it with spirits of wine and evaporating the solution. The sugar thus obtained is in a tolerably pure state, and may be freed from all trace of alcohol by repeated crystalli- sation in water. II. Lehmann's Method. — A spirituous solution of the sugar is first obtained by evaporation of the urine, and by extraction with alcohol. The solution is evaporated to dryness, the residue dissolved in water, and the watery solution saturated with chloride of sodium. The compound of chloride of sodium with sugar crystallises on evaporation, and may be obtained, after repeated crystallisation, in the form of clear translucent crystals. These crystals are dissolved in water, and carefully precipitated with sulphate of silver. The choride of silver is separated by filtration, and the filtrate evaporated to dryness. The sugar may now be obtained chemically pure by extraction with alcohol. It must be observed, however, that these processes only succeed when there is a tolerably large quantity of sugar present in the urine. Cases also occasionally occur in which the sugar of the urine cannot be crystal- lised, and in which it manifestly differs from glucose, as shown by the fact of its turning the plane of polarised light to the left. In such cases the evaporated urine always retains its syrupy consistence, and exhibits no trace of crystallisation. II. If the urine, when tested, does not offer the characteristics here given, but if on being heated it reduces the copper solution without producing any separation of suboxide of copper, and with at most only a slight yellowish coloration of the mixture, it is necessary, in order to satisfy ourselves of the presence of sugar, to separate it in as pure a form as possible, before applying the tests given above. Thus, for example, a slight reduction of the copper- solution may be produced by uric acid, when no sugar whatever exists in the urine. And even when the urine contains sugar the test cannot be depended on, because traces of suboxide of copper may be produced through the ammonia which is evolved from urea when the urine is heated with potash. In this case, however, there is at most only a yellow coloration of the mixture, without any characteristic separation of suboxide of copper ; and when the solution is allowed to stand exposed to the air it becomes blue again on the surface through oxidation. To avoid these different sources of error, a large quantity of urine, 500 to 800 C. C, is taken; any albumen present removed (Sect. 19), and the filtrate evaporated, or if the urine contains no albumen it is filtered and evaporated in a water-bath to a thick extract, which is set aside four or six hours to cool. The residue is 78 DIABETIC SUGAR. then divided as finely as may be with, poxinded pumice-stone, ex- tracted with alcohol (90 p. c), which must be freely employed, frequently shaken with, and allowed to act upon the extract for some hours. An alcoholic solution of pure caustic potash is then added to the clear filtered fluid, so long as any separation follows, an excess of it, however, being avoided. If any sugar is present> the sugar-potash is precipitated as an adhesive, resinoiis-like mass, but always in combination with other crystalline or flocculent potash- compounds. After standing twelve hours the spirit of wine is de- canted off, the precipitate, whether flocculent, crystalline, or resinous, repeatedly washed with absolute alcohol, and then dissolved in water, which, under all circumstances, is readily effected. In most cases the solution will at once give the required reaction ; but as, under certain circumstances, substances are present in this potash- precipitate which are capable of reducing the oxide of copper, we cannot even yet be perfectly sure of the existence of sugar in the urine. We therefore (as recommended by Lehmann) throw down the watery solution of the potash-precipitate, accurately neutralised with acetic acid, by a slight excess of acetate of lead, filter, remove any excess of oxide of lead with sulphuretted hydrogeuj again filter, and evaporate the fluid, which is now in most cases as clear as water, to dryness in a water-bath. In this way all the sulphuretted hydrogen is removed. The residue is dissolved in water, and the test (No. 1) applied. If it gives distinct results, we may be sure that sugar is present; as it is scarcely possible that any other substance can be present in the fluid thus obtained which will give the sugar-reactions. In applying the copper-test the mixture is allowed to stand, so that if sugar is present the suboxide of copper will be separated without the application of heat. Only a small quantity of copper-solution should be employed, so as to impart to the mixture merely a light blue colour. The last decisive proof of the presence of sugar is obtained by the fermentation-test, which, even when there is only a very small quantity of sugar in the urine, gives very satisfactory results, when applied by means of Lehmann's apparatus, above described (" Chemi- cal Character," No. 9). If sugar is present the fermentation quickly takes place. In order to be sure that tte gas evolved does not depend upon decomposition of the yeast, it is advisable to try a counter-test with yeast and pure water. DIABETIC SUGAR. 79 Leconte treats the potash-precipitate in the following way : a slight excess of tartaric acid is added to the precipitate, pre- viously dissolved in the smallest possible quantity of water, the mixture shaken, the bi-tartrate of potash separated by filtra- tion, and the filtrate, when cold, treated with chalk until it is per- fectly neutral. The filtrate is then evaporated in a water-bath, and the residue exhausted with absolute alcohol. If sugar is present, this solution, on spontaneous evaporation, will leave a syrup, which after a long time, sometimes only after months, deposits crystals, which, indeed, often make up the whole mass. But if we are contented with the fermentation-test, instead of the extraction of the sugar, Leconte advises that the watery solution of the potash-precipitate should be simply treated to saturation with dilute sulphuric acid; the sulphate of potash which separates on standing, removed by filtration, a little water added with the yeast, and the fluid introduced into the apparatus, Briicke makes use of the following methods for the finding of sugar in healthy urine : — a. The urine, 1000 to 5000 C. C, is first of all precipitated with a concentrated solution of sugar of lead, filtered, acetate of lead added to the filtrate so long as any precipitate is formed, again filtered, and finally precipitated with ammonia. This last precipi- tate is collected on a filter, washed with water, and dried between thick layers of bibulous paper, which are changed from time to time. The broken-down cakymass is now first of all roughly rubbed down in a mortar with the aid of distilled water, and a concentrated solution of oxalic acid then added, the rubbing in the mortar being continually kept up until a filtered specimen of the mixture produces no turbidity. The filtrate is then saturated with finely divided carbonate of lime, the mixture again filtered, the filtrate slightly acidulated with acetic acid, evaporated to dryness, and the residue dissolved in a small quantity of water. To this solution Briicke applies the ordinary tests, as well as the fermentation-test. Dr. Bence Jones does not decompose the lead -precipitate as Briicke does, with oxalic acid, but in a more simple manner, viz., by passing sulphuretted hydrogen through the precipitate suspended in water. By this method Dr. Bence Jones found in many samples of normal urine — 1000 to 5000 C. C. — notable quantities of sugar (2 to 3 grains in 1000 C. C. of urine). b. The urine is treated with strong alcohol, so that the mixture 80 ALKAPTON. may consist of about ^ths of absolute alcohol. For this purpose 800 C. C. of urine are mixed with 800 to 1000 C. C. of alcohol of 94 p. c. The mixture is allowed to stand until the precipitate which results is deposited, and then filtered into a beaker-glass. An alcoholic solution of potash is next added guttatim to the filtrate (the mixture being continually stirred), until litmus-paper shows a weak or distinctly alkaline reaction. The beaker-glass, well covered, is then allowed to stand twenty-four hours in the cool. The next day the fluid is carefuUy decanted, the glass reversed on filtering paper, whereby the rest of the fluid is absorbed, and allowed to stand in the air, as long as it gives off any smell of alcohol. The bottom and also the sides of the glass will now be found partly coated with crystals, which are to be dissolved in a very small quantity of water, and the solution then used for the appUcation of the tests. As, however, under certain circumstances, uric acid may find its way into the crystalline mass, it is always advisable to acidulate the watery solution of crystals with hydrochloric acid, and allow it to stand for twenty-four hours, for the purpose of separating any uric acid which may be present. The neutralised filtrate is then sub- jected to the copper-, bismuth-, and potash-test, as also, when pos- sible, to the fermentation-test. In Bodeker's process the potash is first of all separated from the concentrated watery solution of the crystalline mass by means of tar- taric acid, any excess of the latter being removed from the filtrate by means of carbonate of lime, in contact with which the fiuid is. left for some length of time; the tartrate of lime and any excess of car- bonate of lime which may have been added, are then separated by filtration, and the solution obtained used for the application of the copper-, bismuth-, and potash-tests. APPENDIX. section xxii. Alkapton. Bodeker found a peculiar substance in the urine of a man, 44 years of age, who after an attack of typhus suffered from repeated ALKAPTON. 81 attacks of cough and expectoration. This substance (to which he gave the name of altapton), when an alkali is present, absorbs a large quantity of oxygen and becomes of a brown colour. The patient at the time suffered severe pains in the back, passing down to the lower dorsal vertebrae, and thence round the body as a lumbo- abdominal neuralgia. The quantity of urine was about 1500 C. C. in the twenty-four hours, its sp. gr, 1*020 to 1"035, and contained not more than 1 per cent, of sugar. On the addition of caustic- potash the reddish-yellow colour of the urine changed (from above downwards in the test tube) into a dark brown, a large quantity of oxygen being at the same time absorbed, of which fact Bodeker satisfied himself by a special experiment. The copper solution was strongly reduced by the urine. preparation. — The urine passed during ten days — 15,000 C. C. — is precipitated with sugar-of-lead solution, and the filtrate treated with basic acetate of lead as long as any precipitate falls. The filtered mixture is no longer rendered brown by caustic potash, but shows a slight reaction of the copper reduction. Sugar, however, is not precipitated by acetate of lead ; it therefore remains in solution whilst the alkapton is thrown down. The lead-precipitate is decom- posed with sulphuretted hydrogen, and the filtrate as thus obtained is evaporated to dryness in a water bath for the purpose of separating the hydrosulphuric acid, it is then triturated with powdered sulphate of baryta, and exhausted "with ether. On evaporating the ether a dark brown mass is left, in which, after several days, crystals of hippuric acid are formed. On solution in a little cold water the crystals of hippuric acid are left, together with a brown mass. The watery filtrate possesses in a high degree the power of reducing oxides of copper and silver with caustic potash, but it is still very dark. The aqueous solution is therefore once more treated with sugar-of-lead solution, the filtrate precipitated with acetate of lead, and the washed precipitate then decomposed with sulphuretted hydrogen. The filtrate, when evaporated, leaves the alkapton in the form of a golden-yellowish, resinous, transparent mass, without a trace of crystallisation. Heated with soda-lime, much ammonia is evolved. The alkapton is soluble in all proportions in water and alcohol, very slightly soluble in ether free from water, but more so in ether containing water. The golden-yellowish solution has a slightly-acid reaction, and possesses the following characters : — g S2 ALKAPTON. 1. Caustic alkalis, potash, soda, and ammonia occasion in it neither change of colour nor precipitate when the air is excluded ; but when oxygen is allowed to act on it and the solution is concen- trated, the brownish-yellow is invariably converted into a brownish- black colour. 2. Sugar-of-lead solution has no effect on it; acetate of lead produces a well-marked white precipitate, which on exposure to the air gradually assumes somewhat of a brownish-violet colour. 3. BoUed with Fehling's copper solution, changes oiceur in it which vary according to the relative amount of copper solution and the substance reduced. If only so much of the copper solution be used as to give the fluid when boiled a blue or merely a greyish-blue colour, the whole of the reduced suboxide of copper may remain in solution and render the mixture of a yellowish colour. But if the solution is boiled with an excess of copper solution, suboxide of copper will be at once separated, at first of a yellow and then of a beautiful red. 4. Mixed with yeast, the alkapton solution shows no sign of fermentation. 5. A drop of nitrate-of-bismuth solution is treated with an excess of soda and the mixture poured into two test-glasses, to the one alkapton alone is added, and to the other alkapton mixed with a trace of diabetic sugar. When the first test is boiled the fluid merely becomes of a brownish colour; the oxide of bismuth cer- tainly throws down somewhat of a brown mass, which is formed by the oxidating action of the air, but this is not to be compared with the_ perfect reduction of the bismuth in the second tube, to which the sugar has been added. The alkapton also behaves like uric acid in relation to the copper solution and oxide of bismuth when an excess of soda is present, in so far as that the uric acid is able to reduce the oxide of copper to a state of suboxide, but not the oxide of bismuth. By this character of alkapton, in addition to its behaviour under the action of oxygen in an alkaline solution, we are able to distinguish it from sugar, and to ascertain the presence of sugar as well as of alkapton. (Annal. d. Chem. u. Pharm., vol. 117, page 98. Zeitschrift f. Ration. Med. von Pfeufier u. Henle, Srd Series, vol. 7, p, 130.) INOSITE. S3 section xxiii. Inosite. 1 Composition : — In 100 parts : Carbon .... 40-00 Hydrogen . . . 6"66 Formula :C„H,,0„ Oxygen . . . 53-34 Crystallised : 0,^ H„ 0„ + 4 H 0. 100-00 A. Oocurrence. — Until lately inosite has been found only in the flesh of muscle. Cloetta has, however, recently discovered this remarkable hydrate of carbon in the lungs (together with uric acid, taurine, and leucine), in large quantities in the iidneys also (with cystine and hypoxanthine) ; in the spleen (with uric acid, hypoxan- thine, and leucine) ; and in the liver (with uric acid). Cloetta also distinctly showed the presence of inosite in the urine in a case of Bright's disease ; he could not, however, find it in healthy urine. Neukomm found inosite most abundantly in the brain; he also met with it in the kidneys, and in diabetic urine which contained a large quantity of sugar. Vohl met with a case of diabetic urine in which the sugar was gradually replaced by inosite. According to Vohl, inosite is identical with phaseomannite discovered by him in unripe beans {phaseolus). B. Microscopical characters. — Inosite usually forms cauMower-like crystals, massed together, in groups; sometimes, however, single crystals are found three to four lines in length. These crystals belong to the kKnorombic system. (Pnnke, Plate VI. Mg. 6.) 0. Chemical characters. — Inosite loses its water of crystallisation in the air, and melts at 210" C. (410*' Fahr.). It has a distinctly sweet taste, dissolves readily in water, and is insoluble in ether and alcohol. 1. Fused inosite hardens into needles when quickly cooled, but when slowly cooled, into a homy mass. 2. Inosite does not produce alcohol when yeast is added to it. With putrid cheese it yields lactic and butyric acids. 3. When a solution of inosite is evaporated with nitric acid nearly to dryness on platina, and the residue, moistened with a little ammonia and a solution of chloride of calcium, again cau^ously evaporated tw dryness, a lively rose-red colour appears, which is visible, even though only ' of a grain of inosite be present. The true sugars do not give this reaction. 4. When inosite is boiled with a solution of acetate of copper in g2 84 BILE. caustic-potash, reduction of the copper does not take place, as in the case of grape-sugax ; but a green solution results, from which, after a time, a flocculent, greenish precipitate is separated, the upper part of the fluid becoming blue. If the precipitate is separated by filtra- tion, and the filtrate again boiled, the same play of colour will be again observed. (Cloetta.) 5. Neutral acetate of lead does not throw down a precipitate with solution of inosite ; but basic acetate of lead produces in it, when a warmed, a transparent jelly, which becomes white in the course of a few minutes, and assumes the exact appearance of paste. This is an excellent method whereby to separate inosite from animal fluids. D. Tests. — Inosite, as already observed, has been found in the urine of Bright's disease and in diabetic urine. The urine to be tested for inosite is completely precipitated with sugar of lead, filtered, and the warm filtrate treated with basic acetate of lead as long as any precipitate is formed. It is better that the urine should be concentrated to one-fourth before it is precipitated. The lead-precipitate collected after twelve hours' standing is washed, suspended in water, and then decomposed by sulphuretted hydrogen. After the filtrate has been left at rest a short time, a small quantity of uric acid separates from it; this is removed by filtration, and the fluid so concentrated as to remain permanently turbid when treated with an equal volume of alcohol. It is then heated until the turbidity disappears, and allowed to stand one or two days. The crystalline mass thus obtained is purified by re-crystaUisation, and then subjected to the tests of nitric acid, ammonia, and chloride of calcium, as well as of tartrate of copper. When the materials for operating on are abundant, the other tests may be employed as confirmatory. section xxiv. Bile. The bile-pigments and, the acids of the bile are found in the urine n pathological states of the body, as, for example, in jaundice. In pneumonia again, the bUe-acids have been occasionally met with in the urine unaccompanied with the bile-pigments. Cholesterine ap- pears to be occasionally present in the urine in cases of fatty degeneration of the kidneys. CHOLEPYRRHINE. 85 1. Bile-Pigments. Composition unknown. A. Occurrence. — Bile-pigment is found in the bile under various modified forms. It is also met with mixed with the contents of the intestines and in the excrements. In pathological states of the body, and especially in severe cases of jaundice, it is found in almost all the fluids of the body, and even in the tissues themselves. Very Uttle is yet known of the chemical nature of the bile-pig- ment, although from certain reactions it is clear that it undergoes different modifications, which are probably the products of the transformations or oxidation of some one primitive substance. a. CholepyrrMne. — Brown-pigment. — This is the bile-pigment most frequently met with, and appears, indeed, to be the primary form. Cholepyrrhine consists of a reddish-brown powder, without taste or smell, dissolves with difficulty in water and ether, but more readily so in alcohol. The alcoholic solution, which is originally brown, becomes gradually green when exposed to the air. Chole- pyrrhine, moveover, is soluble in alkalies. The feebly alkaline spirituous soljition becomes of a beautiful green on the addition of hydrochloric acid; the colour becomes of a bright blue on the addition, gwttatim, of nitric acid. The colouring-matter of fresh bile always assumes the green form of pigment when exposed to the action of the oxygen of the air, as well as when treated with acids. The action of cholepyrrhine, when treated with nitric acid contain- ing nitrous acid, is particularly interesting. When red fuming nitric acid is dropped into a solution of brown pigment, without disturbing the mixture, a zone of colours is formed in the lower part of the fluid, which passes through the shades of green, blue, and violet, into red, and finally becomes of a dirty yeUow. In this process the colouring-matter is entirely altered. Cholepyrrhine appears to be chemically identical with the biliful- vine of Virchow and Valentiner. Bihfulvine was found by Virchow, partly crystallised and partly amorphous, in the bile of the dead body, the bile having been left for a long time stagnant in the gall- bladder. Valentiner, however, succeeded, by means of chloroform, in obtaining from the bile itself, and also from fluids containing bile, &c., the substance, which exhibited, under the action of nitric acid, characteristic reactions. On evaporation of the chloroform-solution, the pigment was left in the form of beautiful translucent reddish- yellow or ruby-red crystals. These crystals were, in all respects identical with the crystals of hsematoidine, found in old extravasa- 86 BILIVERDINE. tions of blood, a fact of high physiological significance. The chloroform solution, tested with nitric acid, exhibits in a beautiful man- ner the play of colours mentioned above as characteristic of bile-sub- stances. Hence, then, we possess in chloroform an excellent and certain means of discovering the presence of bile-pigment in other fluids, &c. h. Biliverdine (green-pigment) is the form of pigment into which cholepyrrhine often passes, and into which, indeed, it may be converted. It is a dark-green amorphous substance, without smell or taste : it is slightly soluble in alcohol, but insoluble in water ; in ether it dissolves with a red colour. Hydrochloric and sulphuric acids in dissolving it become of a green colour. When a solution of biliverdine is precipitated with acetate of lead, and the precipitate, after washing and drying, is extracted with alcohol containing sulphuric acid, the alcohoHc mixture is found when filtered tinged of a green colour. A precipitate of a bluish-green appears, when soluble albumen is added to a fluid containing biliverdine, and nitric acid employed in sufficient quantity to produce its coagulation. The presence of cholepyrrine in urine may be shown even after several days, by the action of nitric acid, provided the air be per- fectly excluded. If, however, the urine is heated in an open basin, the brown pigment is graduaUy converted into biliverdine, and its presence can no longer be shown by nitric acid, which, under such circumstances, fails to produce the reaction described. c. Tests. — Urine containing bile-pigment is always tinged of a deep brown, reddish-yeUow, greenish-brown, or dark or grass-green colour. Much froth is formed in it when shaken ; and it imparts a yellow Dr greenish colour to a slip of filtering paper when dipped into it, a. Test for cholepi/rrMne, — A conical-shaped test-glass is fiUed with urine, and nitric acid, containing nitrous acid, carefully added to it, each drop of the acid being allowed to trickle down from the rim of the glass, and great care taken to prevent the fluid being shaken. If cholepyrrhine is present, we find that at the top of the glass, and particularly at the point where the two fiuids come into contact, a zone of colours is formed, which passes from green into blue, violet, and red, and, lastly, into yellow. If, in consequence of there being only mere traces of the colouring-matter present, this reaction with nitric acid does not take place, it may be pro- duced by adding to the mixture equal parts of nitric and sulphuric acids, instead of nitric acid ; or, according to Briicke, to make the test still more certain, by adding, first of aU, a few drops of nitric TEST FOR CHOLEPYRRHINE. 87 acid to the urine, so as to give to it a green colour, and then allowing 20 or 30 drops of concentrated sulphuric acid to trickle down into the urine from the side of the test-glass, so as not to mix. with the urine, but to sink down to the bottom of the glass. The test, however, succeeds best, even though the quantity of bile- pigment is very small, when applied as follows ; — Concentrated nitric acid, slightly decomposed by exposure to the light, is poured to about an inch high into a conical-shaped test-glass, and a little of the urine to be tested carefully spread over its surface by means of a pipette, pouring it on the border of the glass. If cholepyrrhine is present the play of colours commences at the line where the fluids come in contact with a beautiful green ring, which gradually extends upwards, and at its under surface exhibits a blue, violet-red, and, lastly, a yeUow ring (Kiihne). It should, however, be observed, that the whole of these colours do not invariably appear ; violet and green generaUylast the longest; but the green which appears almost at the commencement of the action is alone demonstrative of the presence of bile-pigment ; the red and violet rings may be also pro- duced by uroxanthine (indican), and the products of its decom- position. (See TJroxcmthine.) The presence of albumen in no way interferes with this' test ; a portion of the pigment is generally preci- pitated with the albumen, which is coagulated by the nitric acid, but it also beautifully shows the reaction. The nitric acid must not contain too much nitrous acid, for if it does the reaction is violent, and the play of colours rapidly passes away. The slightest traces of bile-pigment may be discovered, should the above test fail, by shaking large quantities of urine successively with chloroform, and pouring off the exhausted urine. The smallest quantity of cholepyrrhine present in the urine is taken up by the chloroform, which, when left at rest, by reason of its high specific gravity, rapidly sinks to the bottom, of a yellowish colour. The supernatant urine is drawn off, and a Httle nitric acid containing nitrous acid spread over the chloroform solution. If the slightest trace of cholepyrrhine be present, the reaction will then take place (from above downwards), and in a very brilliant form. Another portion of the chloroform-solution is evaporated in the air, and the residue examined microscopically; if any brown bile-pigment is present, single reddish-yellow crystals of cholepyrrhine are readily distinguished. (Valentiner.) The reaction with nitric acid in the chloroform solution is excessively delicate and beautiful. 88 TAUROCHOLIC ACID. section xxv. 2. Bile-acids. The starting-point of all the acids contained in the bile is cholic acid — a non-nitrogenous compound — (C^jHjgOg + HO). Cholic acid, when pure, usually crystallises in shining, colourless tetra- hedra, and sometimes, though rarely, in rhombic forms. Crystallised cholic acid, at a temperature exceeding 195° C. (383° Pahr.), gives off one equivalent of water, loses its crystalline character, and is converted into a resinous body — choloidic acid (C,j H35 Og). It undergoes the same decomposition when boiled for a long time with hydrochloric acid. Choloidic acid, the product of the decomposition of cholic acid, forms a white amorphous, resinous mass, which is insoluble in water, slightly soluble in ether, and readily soluble in alcohol. Choloidic acid melts at 150° C. (302° Fahr.) ; at 295° C. (563° Fahr.) it gives off three atoms of water, and is converted into another compound, dyslysine (C,3H,,0J. These two acids are not found in an isolated form in fresh, healthy, undecomposed bile, the cholic acid being always united with nitrogenous bodies — ^with taurine and glycocoll. Taurocholic and glycocholic acids may indeed be regarded as conjugates of cholic acid with taurine and glycocoll. 1. TaurocMic acid [C^^H^^'NOt^Sa). — This acid, found in the bile in union with soda, has not yet been obtained in a crystalline state. In its partially impure state it forms a white amorphous powder, which is strongly hygroscopic, has an intensely bitter taste, dissolves readily in alcohol and water, and is insoluble in ether. Boiled for a long time with caustic potash, it is decomposed, the cholic acid uniting with the potash, and the taurine being set free. If hydrochloric acid is used instead of potash, the same separation takes place. The cholic acid, however, is not, in such case, sepa- rated as cholic acid, but by the action of the boiling hydrochloric acid, is converted into the resinous choloidic acid. The taurine (C, H, S^ N Oj which is separated, crystallises ia the form of colourless, regular hexagonal prisms, terminating in four or six planes. (Punte, Plate III. Fig. 4.) Taurine is a nitrogenous body, containing 25 per cent, of sulphur. It dissolves readily in water, but only slightly in alcohol. Its solutions do not affect the GLYCOCHOLIC ACID. 89 vegetable colours. Strecker succeeded in producing taurine artifi- cially, by simply heating to 220° C. (428° Eahr.), isethionate of ammonia (C, H, S, N 0, - 2 H = taurine C, H, 8, N 0,) . Taurine is obtained most conveniently in the following way : — Presh ox-bile, freed from mucus, is evaporated with strong hydro- chloric acid, and the choloidic acid thus separated. The chloride of sodium is crystallised out of the strongly concentrated fluid, and the mother liquid still further evaporated j from this the taurine is precipitated on the addition of double its volume of strong alcohol. The taurine may be obtained pure in the form of large beautiful crystals on re-crystallisation from water. 2. QlycochoUc add (Cjj H^N 0„ -l- HO) also exists in healthy bile, in combination with soda. It crystallises in extremely fine needles (Ihinke, Plate IV. Kg 6), differing essentially, in this respect, from taurocholic acid. It is moderately soluble in water and in alcohol, but only slightly so in ether. It does not crystallise from its alcoholic solution, but separates, on evaporation, as a resin- ous mass ; when, however, the solution is mixed with water, it is gradually deposited in a crystalKne form, on evaporation. Boiled with caustic potash, baryta water, or hydrochloric acid, glycocholic acid undergoes decompositions similar to taurocholic acid — cholic acid, or choloidic acid being formed, and glycocoU separated. GlycocoU (C^ Hj N OJ, (glycocine, sugar of gelatine) may be arti- ficially obtained from gelatine by the action of mineral acids and also from hippuric acid, which may be considered as a conjugate of benzonic acid with glycocoU, by boiling the hippuric acid with hydrochloric acid. It forms colourless rhombic prisms (Funke, Tlaie III. Fig. 5), which are hard and unchangeable in the air, and have a taste almost as sweet as that of cane-sugar. It contains nitrogen, but no sulphur. All biliary acids, the conjugate, as well as cholic and choloidinic acids, exhibit peculiar and very characteristic reactions with sulphuric acid and sugar, the reactions depending upon the presence of pig- ment-matters, as well as upon the taurine and glycocoU. When, for example, a few drops of a solution of sugar are mixed with a watery solution of any biliary acid, and concentrated sulphuric acid added, until the mixture is heated to 50° to 70° C, (122° to 158° I"ahr.) the mixture assumes a beautiful, purple-violet colour. The following is another and very sensitive test : The biliary acid or its salt is treated with a small quantity of concentrated sulphuric 90 GLYCOCHOLIC ACID. acid, slightly warmed, and then water added to it. The resinous flakes which separate are removed from the acid, and slightly washed with water, but so as not to remove the whole of the sulphuric acid, and then gently heated in a basin until the colours appear. The residue is then exhausted with a very little spirits of wine, and the green solution evaporated, and kept stirred during the process ; the inner side of the vessel, thereupon, becomes covered with a deep indigo-colouied coating, even though only a very small quantity of the acid is present. If foreign matters be mixed with the biliary acid, or if the action of the sulphuric acid be too long continued, or the process be conducted at too high a temperature, the pig- mentary coating will be of a green colour. Tests. — A quantity of urine (300 to 500 CO.) is evaporated nearly to dryness in a water-bath, and the residue extracted with ordinary alcohol; the spirituous solution is then evaporated, and the residue extracted with absolute alcohol. The solution thus obtained, containing only a small quantity of salts, is freed from spirits of wine, the residue dissolved in a little water, the solution treated with acetate of lead, the precipitate collected after twelve hours standing, and washed and dried between folds of bibulous paper. To separate, as far as possible, the other substances which are thrown down with the lead-precipitate, the bile salt of lead is extracted with boiling spirits of wine, carbonate of soda added and the solution evaporated to dryness ; the residue is then treated with absolute alcohol in order to procure the bile-salt of soda. The salt of soda, thus obtained, always contains a small quantity of a resinous constituent of the urine mixed with the bile-acids ; this resinous body becomes of a brownish-red under the action of sulphuric acid, at times also of a lightish blue or violet, and when heated with addition of a little sugar, of a reddish or yellowish- brown. This coloration is rarely powerful enough to conceal the biliary reaction ; but if it should be found on trial to do so, the bile-acid must be once more precipitated from the watery solution with acetate of lead, the precipitate collected after standing awhile and then decomposed, as above described, with carbonate of soda. Two or three drops of sugar-solution (1 part sugar to 4 parts water) are added to the watery solution of the soda-compound, which is concentrated as much as possible, and then pure concentrated sul- phuric acid, free from sulphurous acid. Care must be taken that the temperature does not exceed 70° C. (158° Fahr.) If any bile- LACTIC ACID. 91 acid be now present, the fluid will first of all become muddy, tben clear, and at the same time yellow, soon afterwards of a pale cherry, dark carmine-red, and lastly of a beautiful purple-violet colour. The reaction becomes much more sensitive, when the soda-solution is evaporated to a few drops in a porcelain cup, a few drops of pure dilute sulphuric acid (4 parts H 0-1- 1 part S Og H 0), and a trace of sugar-solution added to it, and the mixture then carefully evapo- rated at a very gentle heat over a small lamp. The reaction was beautifully marked when only tw of a milligramme of bile-acid was present, (Neukomm). This modified process is far superior to the original one of Pettenkofer. We cannot be certain that bile- acid is present unless the fluid assumes a distinct purple'violet, as well as a red colour. Cholesterine has been occasionally found in the urine, mingled with other fats in cases of fatty degeneration of the kidneys. The sediment, which consisted chiefly of fat cells, after being collected and dried in a water-bath, was digested with a mixture of alcohol and ether. The extract, when filtered and concentrated, deposited a considerable quantity of crystals of oholeaterine, which, by their mifiroscopio characters, cannot be readily mistaken for any other substance. (Funke, Plate VI. Fig. 1.) section xxvi. Lactic Acid. Composition : — In 100 parts : Carbon . . . 40-000 Hydrogen . , . . 5"555 Oxygen . . . 44*445 Water .... lO-OOO 100-000 Pormula : Cj H^ 0, + H 0. Atomic weight of anhydrous acid = 81. A. Occwrence. — Lactic acid is found in most of the animal fluids, and particularly (under normal conditions) in the juice of muscles, and in the juices of the stomach and intestines. It is also some- times found in the blood, in the saliva, in sour milk, or milk which has been altered by disease, in the fluids of flesh, &c. It does not exist normally in the urine, but always appears in it when large 92 LACTIC ACID. quantities of lactates are introduced into the blood, as happens, for example, when that kind of food has been taken which gives rise to the formation of lactic acid. Lactic acid has also been found in the urine when the oxidating process is arrested, in disturbances of the respiration, the digestion, the nutrition, and frequently also in febrile conditions. Hence it is evident that the presence of lactic acid in the urine varies much, and that it may exist in the urine one day and be absent in it the following day. Lehmann found that lactic acid is always present in the urine when much oxalate of lime is secreted with it. Lactic acid is also formed during the acid fermentation of urine, from matters — perhaps extractive matters — ^the true nature of which is unknown ; consequently fresh urine must always be employed in testing for lactic acid, B. Chemical cJMracters. — In its pure concentrated form, lactic acid is a syrup-like fluid, having a strongly acid taste, but neither colour nor smell ; it has not yet been obtained in a crystalline form. It is soluble in water, alcohol, and ether, and absorbs water from the air. It parts with its water at 140° 0. (284° Tahr.), and at a higher temperature is decomposed' into lactide, carbonic acid, and other compounds. We have no tests distinctive of lactic acid, but the microscopic characters of some of its salts are characteristic, and consequently are of importance as tests for lactic acid. 1, Lactate of lime is obtained by the solution of carbonate of Kme in lactic acid. Observed under the microscope, it is seen to crystallise in tufts of fine needles. Of these tufts the shorter styles are so disposed that they appear like overlying pencils. (Funke, Plate II. Fig. 1.) 2, Lactate of zinc is obtained by boiling pure oxide of zinc with lactic acid. The crystals, when rapidly formed under the micro- scope, appear as globe-shaped groups of needles, which may be easily obtained of exceeding beauty. In a drop of a solution of lactate of zinc, which is allowed ■ to evaporate slowly, the first crystals which appear have club-shaped extremities. These crystals then gradually enlarge, their extremities becoming thinner, and their middle portion swelling out. This peculiar bellied-, barrelled-, or club-shaped form is very characteristic of lactate of zinc. (Funke, Plate 11. Fig. 2.) c. Tests. — The presence of lactic acid in the urine cannot be LACTIC ACID. 93 satisfactorily demonstrated, unless it be obtained nearly pure ; and even tben it exhibits, as lactic acid, no distinguishing characteristic. Consequently, we must learn its nature by elementary analysis, by ascertaining its atomic weight, and by the study of its salts. As, however, in testing for lactic acid we very rarely obtain materials sufficient for the first two kinds of experiments, we make use of the zinc-salt, which crystallises readily, and in a very characteristic form. The following is the method employed for this purpose : — Presh urine is evaporated nearly to dryness in a water-bath, and the residue then treated with an alcoholic solution of oxalic acid. The oxalate which is thus formed, as well as the oxalate of urea, remain undis- solved, the lactic acid, together with phosphoric and hydrochloric acids, remaining in solution. The fluid is then digested with hydrated oxide of lead, evaporated to dryness, and the residue ex- tracted with absolute alcohol, which dissolves the lactate of lead. The filtrate is treated with sulphuretted hydrogen, and after filtra- tion evaporated in a water-bath to a syrup ; the syrup is then shaken up with ether, which, on evaporation, leaves the lactic acid more or less pure. This is then dissolved in a little water, boiled with oxide of zinc, filtered, and allowed to crystalUse slowly on the object- glass. The presence of the lactic acid is readily recognised by the barrel- and club-shaped form of the crystals, and especially by their peculiar mode of enlargement. Scherer uses the following process, which is in every respect an excellent one, in testing for lactic acid : — ^The extract containing the lactic acid is dissolved in water, the solution precipitated with baryta and filtered. Any volatile acids which may be present in the filtrate are separated by distillation with a little sulphuric acid ; and the residue Is then left to digest several days in strong alcohol. The acid fluid is evaporated to dryness with a little milk of Ume, the residue dissolved in boiling water, and filtered while warm, to separate any superfluous lime and sulphate of lime. A stream of carbonic acid is then passed through the filtrate, which is once again heated to boiling ; the precipitated carbonate of lime is separated by filtration, the fluid evaporated to dryness, and the residue treated with strong alcohol, filtered if necessary, and the neutral filtrate left for several days to deposit the lactate of lime. If the lactic acid is present in too small quantity to produce crystals, the solution must be evaporated to a syrup, mixed with strong alcohol, and allowed to stand ; a darkish deposit, consisting of extractive matter and lime, is 94 LACTIC ACID. then usually formed. The fluid part is now poured oflF into a closed vessel, and a small quantity of ether gradually added to it. Even mere traces of lactate of lime, whose presence may be easily recog- nised under the microscope, will hereby be separated from the fluid. If there is plenty of material to operate upon, the following method, proposed by Lehmann, for the preparation of several salts, may be adopted (Lehmann, Physiolog. Chemie, Vol. 1, p. 99). The lactic acid, prepared as above described, is saturated with a solu- tion of baryta, the excess of baryta removed by a stream of carbonic acid gas, the solution filtered, the filtrate evaporated to the consis- tence of syrup, treated with alcohol, again evaporated and allowed to stand. The syrup is then poured off, and separated from the foreign crystals which are formed, dissolved in water, and decomposed with a solution of gypsum. In this way lactate of lime and sulphate of baryta are formed. The sulphate of baryta is separated by filtration, and the filtrate then allowed to crystallise, when the double brush-like forms of lactate of lime are easily recognised, together with crystals of gypsum. The whole of the lactate of lime is now dissolved in strong alcohol and decomposed, without previous filtration, with sulphate of copper. Any excess of the copper-salt, as well as of the gypsum which is formed and which is also insoluble in alcohol, is separated by filtration; and a little of the solution of lactate of copper, then allowed to crystallise under the microscope. The remaining fluid is highly concentrated by boiling, and a stick of zinc introduced into it ; if lactic acid be present, the zinc in a short time is covered with white crystals of lactate of zinc, which are also to be subjected to microscopic examination. Lastly, the solution of the salt of zinc may be precipitated by protochloride of tin. The salt of tin thus obtained is found to consist of grandular masses of crystals, forming groups of thick rhombic tablets lying one over the other. As already said, we rarely have sufficient materials to enable us to follow out the whole of this complicated process ; consequently, we must be satisfied with the preparation of the lactate of lime after the manner first described. It is useful, however, to practise these processes, in order to learn the different crystalline forms of the salts of lactic acid. It should always be remembered that artificially- formed lactic acid yields crystals different from those which are ACETIC ACID. 95 obtained from animal fluids ; conseqnentlyj only the latter kind should be operated upon. SECTION xxvn. Acetic Acid. Composition : — In 100 parts; Carbon . . . 40-00 Hydrogen . . . 6-67 Oxygen . . . 53-33 100-00 Pormula:C,H3 03 + HO. A. Occwrence. — Acetic acid appears in stale urine, in which the fermentation process has already commenced. It also forms, in large quantity, during the fermentation of diabetic urine. More- over, it has been found in the fluids of muscle and of the spleen, in leucocythemic blood, in the gastric juices in cases of severe dyspepsia, and in the sweat. It is a product of the decomposition of many animal substances, and may be formed, for instance, from the action of powerful oxidising agents upon proteine bodies, gela- tine, &c. B. Chemical Characters. — ^Acetic acid, in its concentrated form, is a colourless liquid, having a durable sour odour, and a sharp pungent taste. It boils at 120° C. (248° Fahr.), crystallises at C. 5° (41° Pahr.), and above 16° C. (60° Pahr.) becomes fluid, 1. Perchloride of iron, added to a solution of a salt of acetic acid, produces the deep-red colour of per-acetate of iron. ' %. Nitrate of silver in a neutral solution of a salt of acetic acid throws down a white crystalline precipitate of acetate of silver, which dissolves in boiling water without reduction, and crystallises out of it as the liquid cools. This salt contains 69-4 per cent, of oxijle of .silver. 3, The characteristic odour of acetic ether presents itself when a salt of acetic acid is treated with alcohol and sulphuric acid. Treated with sulphuric acid alone, the salt gives off the pungent odour of acetic acid. c. Tests. — ^Two to three litres of urine are neutralised with a 06 BUTYRIC ACID. solution of soda, provided the urine is not already alkaline, and the mixture evaporated on the open fire to a fourth or a sixth of its volume. Tartaric or phosphoric acid is then added to the residue, which is subjected to distillation, and the distillation continued, until the distniate has no longer an acid reaction. The distillate is then saturated with carbonate of soda, evaporated to dryness, and again distilled with sulphuric acid. The acid fluid thus obtained is neu- tralised with carbonate of soda, and, as it crystallises, acetate of soda is separated in the form of white prisms and needles. Butyric add may be found in the mother hquor. The analysis of the salts of silver and baryta give decisive results. Crystallised acetate of soda contains 22"9 per cent, of soda, the baryta-salt 60 per cent, of baryta, the silver-salt 69'4! per cent, of oxide of silver, and 64'67 per cent, of silver. SECTION xxvin. Butyric A.cid. Composition : — In 100 parts : Carbon . . . 54-545 Hydrogen . 7-955 Oxygen . . . 27-273 Water . . . 10-227 100-000 Formula : C, H, 0, -|- H 0. Atomic weight of the anhydrous acid 79. Its saturating capacity 10-126. A. Occurrence. — ^Butyric acid exists ready formed in butter in combination with oxide of glycerine ; it is set free in rancid butter, and is in fact the source of its disagreeable odour. It is also found in several of the animal fluids and secretions, in the sweat, for example, in the secretions of the external genital organs, in the juice of muscle, and occasionally also in the gastric juice. Accord- ing to Berzelius, free butyric acid is constantly present in the urine; but the fact has not yet been satisfactorily proved. It is, however, sometimes, though rarely, found both in healthy and in unhealthy BUTYRIC ACID. 97 urine, from which we may conclude that its presence there is not connected with any special form of disease. Lehmann occasionally found butyric acid in the urine of pregnant women, but he also often met with it in the urine of men, and of women not pregnant. A considerable quantity of butyric acid is formed, when diabetic urine is treated with powdered chalk, and the mixture allowed to ferment at a temperature of 35° to 40° C. (95° to 104° Tahr.) (Scherer, Brieflch. Mitth.) ; but at a lower temperature, and without the addition of chalk, acetic acid only is not unfrequently formed. B. Chemical Characters. — Anhydrous butyric acid is a colourless and very mobile fluid ; it refracts light strongly, and has a powerful odour. As a hydrate it forms an oily and exceedingly repulsive liquid, having an odour of rancid butter, and a pungent acid taste. It is soluble, in all proportions, in water, alcohol, and ether. Most of its salts are also soluble in alcohol and water, and give off the repulsive odour of butyric acid on the addition of mineral acids. 1. Butyric acid unites with alkalies, alkaline earths, and the metallic oxides proper. The compounds which it forms with the alkalies are deliquescent and uncrystallisable. Its other salts, on the other hand, crystallise readily. a. Butyraie of baryta is prepared by saturating butyric acid with baryta-water. When the crystallisation of this solution is rapidly efPected, the compound separates in the form of gUstening fatty scales on the surface of the fluid. These scales, examined under the microscope, appear as dense groups of iU-defined crystalline scales ; but when the solution of butyrate of baryta is allowed to evaporate spontaneously, long, flattened, and perfectly transparent prisms, mostly grouped together in stellate glands, are formed. The salt readily dissolves in water, and its solution reddens litmus paper. (Funke, Plate I. Fig, 3.) Butyrate of baryta contains 49-23 per cent, of baryta. b. Butyrate of lime readily dissolves in cold water, but nearly the whole of it separates again when the solution is boiled. It crystaUises in fine needles, has an odoui- of butyric acid, and yields, on dry distillation, butyrone and butyral. c." Butyrates of the metallic oxides are formed by the precipitation of a concentrated solution of an alkaline butyrate, by means of a solution of the corresponding metallic salt. Nitrate of silver, in this way, yields a yellowish-white crystalline precipitate of butyrate of silver, which is wholly insoluble in cold water, and contains h 98 BENZOIC ACID. 55'38 per cent, of metallic silver = 59'35 per cent, of oxide of silver. Nitrate of the suboxide of mercury yields a precipitate, which resembles that of the acetate of the suboxide of mercury, and consists of glistening scales. The bluish-green precipitate of butyrate of copper is soluble in hot water, and separates as it cools in the form of octagonal bluish-green prisms. 2. All the salts of butyric acid, when heated with sulphuric acid, yield butyric acid, which is readily recognised by its peculiar and repulsive odour. c. Tests. — It is not easy to determine with certainty the existence of butyric acid in the urine. The only tests which we have of it in small quantities (and it is only in small quantities that we have to deal with it in the urine), are its smell and the mode of crystallisa- tion of its salts, Berzelius distilled urine treated with sulphuric acid ; saturated the acid distillate thus obtained with baryta-water, and after filtration evaporated it to dryness. By this process he obtained a considerable quantity of butyric acid on treatment of the saUne residue with sul- phuric acid. Lehmann could only obtain traces of butyric acid by this process, even when he used a large quantity of urine. He describes, how- ever, a case, in which he obtained from the saline residue of the urine of a lying-in woman, who was not nursing her child, an acid fat, by simple extraction with ether. This fat smelt strongly of butyric acid, and exhibited the other characteristics of the acid. The residue obtained from the ether, on distillation with sulphuric acid, yielded a further quantity of butyric acid. section xxix. Benzoic Acid. Composition : — In 100 parts : Carbon 68"85 Hydrogen .... 4'92 Oxygen 26-28 100-00 Formula : C„ H. 0, 4 H 0. A. Occurrence. — Benzoic acid is probably present in the urine of BENZOIC ACID, 99 herbivorous animals when overworked or underfed. It is constantly found in putrefying urine, both of man and herbivorous animals, being formed through the decomposition of the hippurates. Benzoic acid is the non-nitrogenous conjugate of hippuric acid, for, as we have already seen, benzoic acid within the body takes ,np the elements of glycocine, and then appears in the urine in the form of hippuric acid. And, on the other hand, hippuric acid, when placed in contact with decomposing matters, is immediately decomposed into benzoic acid and glycocine. Benzoic acid, again, appears as the product of the decomposition of various animal substances, and particularly of proteine-bodies, of gelatine, &c. B. Microscopic characters. — Benzoic acid, when sublimed, appears in the form of fine, colourless, glistening needles and scales, and, when prepared in the moist way, in the form of scales, smaU columns, or six-sided needles, whose primary form is a right rhombic prism. Crystals obtained through the cooling of its aqueous solutions always appear under the microscope as tables of exactly 90° C. (194° Pahr.), arranged in rows, or overlapping each other ; sometimes, but not often, one of the angles is truncated, but always so as to give to both the angles 135° C. (275° Pahr.). (Eunke, Flate I. Mg. 6.) C. Chemical characters. — Benzoic acid subhmes at 240° C. (464° Pahr.), without decomposition; its vapour causes an irrita- tion of the throat, and excites coughing. It is but Uttle soluble in cold, but much more soluble in hot water ; alcohol and ether dis- solve it pretty readily. Its solutions redden litmus. 1. Most of the salts of benzoic acid are soluble in water, those only which it forms with the heavy metallic oxides are difficult of solution. The alkaline benzoates are soluble in alcohol. 2. Strong acids decompose the solutions of the benzoates, the . benzoic acid being separated in the form of white shining scales. 3. Perchloride of iron throws down from solutions of alkaline ben- zoates a brownish-yellow precipitate of benzoate of iron, which is decomposed by the action of ammonia into oxide of iron and ben- zoate of ammonia. -Treated with a little hydrochloric acid, the benzoate of iron dissolves with separation of the benzoic acid. D. Tests. — Alkaline urine is evaporated to the consistence of an extract, which is then treated with alcohol. From this alcohoUc extract benzoic acid is separated in a distinctly crystalline form on the addition of a stronger acid. If the quantity is too small to yield crystals in this way, the mass must be extracted with ether, and the h2 100 FAT. solution allowed to evaporate spontaneously. From this ethereal extract the benzoic acid is separated in a crystalline form on the addition of water. The crystals may then be examined microscopi- cally and chemically. If, again, putrefying urine be treated according to the process given for the testing of acetic acid (see Sect, xxvii.), we shaU find, at the end of the second distillation, and especially when this has been pushed a little far, that white scales and plates appear ; these remain for the most part in the condenser, and are readily recognised as benzoic acid. To distinguish benzoic from hippuric acid, see Section vn. E. 1, 2, and 3. section xxx. Fat, A. Occurrence. — Fat is not often met with in the urine. The peculiar milky-looking urine {yirina chylosa) occasionally met with does not owe its turbidity and colour to fatty particles suspended in it, but, as Lehmann states, to the presence of pus-corpuscles. Dr. Beale, however, speaks of a milky urine, containing much fat, which was during some months passed in the morning by a woman of fifty years of age. On the addition of ether the urine became perfectly clear. Quantitative analysis gave 13 "9 grammes of fat in 1000 parts. l)r. Beale considers that the chylous character of the urine results from a separation of the chyle through the kidneys. He also found cholesterine in the fat-cells passed with the urine in fatty degene;ration of the kidneys; this cholesterine dissolved in other fats could only be obtained by extraction with alcohol and subsequent crystallisation. Fatty globules are, however, often found in the urine of persons suffering from diseases which are attended with a rapid wasting of the body. B. Microscopic characters. — Fat in its free state is readily recognised under the microscope. Fat-globules present the form of flattened discs ; they possess an extraordinary power of refracting light, whereby they obtain a dark and somewhat irregular contour. Single globules are often seen under the microscope to run one into the other, and by this they may be distinguished from fat vesicles, SULPHURETTED HYDROGEN. 101 whicli are completely spherical. Pat-cells have a smooth and roundish form, but when exposed to pressure occasionally assume a polyhedral shape. Their surfaces also possess a strong refractive power; with transmitted light their contour is sharp and dark, but with reflected light their borders have a shining silvery appearance, and their centre appears whitish. These cells are easily burst by pressure, their contents escaping, and their surface assuming a more or less wrinkled appearance. (Punke, Plate VII. Figs. 3 & 4.) c. Tests. — Ks fat is very rarely met with in the urine, and only in exceedingly small quantity, it is not possible to determine its particular kind by tests. We must therefore be satisfied with recognising the presence of the fat as such. The microscopic characters of fat are so peculiar and distinctive that any one who has ever seen a fat-globule will not fail to recognise it again. Conse- quently, we always, in the first instance, test its presence with the microscope. If we fail to discover it by that means, we then evapo- rate a portion of the urine to dryness in a water-bath, expose the residue for some time to a temperature of 110° C. (230° Fahr.), and then pour over it small quantities of ether so long as the ether continues to dissolve any of it. This ethereal solution will take, up aU the fat, and when evaporated' — an operation which is best per- formed in a test-glass — ^leaves the fat as a residue. This residue may then be examined under the microscope, and if there be enough of it, by chemical agents. The production, by it of grease-spots on fine paper, as well as its properties when heated (the development of acrolein), prevent fat being mistaken for any other body. SECTION XXXI, SULPHUEETTED HYDROGEN. a Sulphuretted hydrogen is sometimes, though very rarely, found in the urine. Its presence is readily ascertained by its property of blackening paper moistened with a solution of sugar of lead. The experiment is thus best performed : — a small glass is filled half-full with the urine to be tested for the sulphuretted hydrogen, and covered with a watch-glass, to the bottom of which a little bit of the lead-paper has been attached by means of a drop of water. 102 ALLANTOINE. This paper becomes brown or black (and more readily if the urine be gently heated), according to the amount of sulphuretted hydrogen which is present. Sulphuretted hydrogen, moreover, may always be easily recognised through its odour of rotten eggs. I had once an opportunity of examining for a length of time urine which contained sulphuretted hydrogen; it was periodically secreted by a man whose lower extremities were paralysed through gout. The urine, when it contained sulphuretted hydrogen was slightly acid, of a bright yellow colour, usually threw down a sediment, and immediately blackened a piece of lead-test paper when held over it. It has been already stated, under the head of sulphuric acid (Sect. xin. B. 3), that sulphates, when exposed to a moderately high temperature in contact with organic substances, soon give rise to the formation of sulphuretted hydrogen j and in this way we may perhaps account for its formation in the urine. Sulphuretted hydrogen may also be formed in the urine from the decomposition of animal substances contained in it, and quite independently of the sulphates. Urine, for example, which contains albumen, will often in a short space of time show, by its odour, the presence of sulphu- retted hydrogen; this fact I have frequently noticed. There are some other substances, such as allantoine, leucine, and tyrosine, yet to be considered. They are very rarely found in human urine, but occasionally appear in it under pathological conditions. Oxalic acid, which is frequently present in the urine, and cystine, are chiefly found in the sediment of urine ; I shall, therefore, speak of them under that head. SECTION XXXII. Allantoine. Composition : — In 100 parts : Carbon . 30-38 Hydrogen . . 3-16 Nitrogen . . 85-44 Oxygen . 25-32 Water . . . 5-70 Formula: C, H. N, 0, -|- H 0. 100-00 ALLANTOINE. 103 A. Occurrence. — AUantoine is found in the allantoic fluid of the cow, and in the urine of calves as long as they suck or are fed on milt. Stadeler found it in the urine of a dog whose respiration was impeded ; Kohler found it in the urine of rabbits after the in- jection of oil into the lungs (compare fTnc J«<^, vi. a.); and Schottin met with it in the urine of man, after the ingestion of a large quan- tity of tannic acid. AUantoine may also be obtained by treating uric acid with peroxide of lead (Sect. yi. d. 3.), ferricyanide of potassium and permanganate of potash. (Sect. vi. d. 4.) B. Preparation. — ^Uric acid is stirred with water into a thinnish paste, and heated to boiling j peroxide of lead is then added in small quantities, as long as it (the peroxide) continues to lose its brown colour. Allantoine separates from the filtrate, as it cools, in beautiful crystals, and urea is left in solution in the mother-Uquid. c. Microscopical Cha/racters. — Allantoine appears under the mi- croscope in the form of colourless prismatic crystals, clear as water and lustrous as glass; their primitive form is the rhom- bohedric. The crystals, when separated from concentrated solutions, form stellate glandular masses. (Funke, Plate V. Fig. 4.) D. Chemical Characters. — Allantoine is tasteless ; it has no action on vegetable colours, is soluble in 160 parts of cold, and in a less quantity of boiKng water. It is also dissolved by boiling alcohol, but in great part separates again as the alcohol cools. It is inso- luble in ether. 1. Concentrated alkaUes convert allantoine, by absorption of water, into oxalic acid and ammonia. 2. By the action of boiling nitric acid it is decomposed into urea and allantoic acid (C^ H^ Nj OJ . 3. Nitrate of silver and ammonia added to a saturated solution of allantoine, throw down a white flocculent precipitate of allantoine- oxide of siver, which is found under the microscope to consist of clear and perfectly spherical particles. 4. Corrosive sublimate causes no precipitate in a solution of allantoine ; but, as in the case of urea, a precipitate is thrown down in it by a solution of nitrate of mercury. 5. Mixed with yeast and exposed to a temperature of 30° C. (86° Fahr.), allantoine is decomposed into urea, and oxalate and carbonate of ammonia. At the same time there is generated a syrupy acid, probably identical with another acid, also syrupy, which I met with, together with allantoine and urea, in treating uric acid with perman- ganate of potash. 104 ALLANTOINE. E. Tests. — ^To ascertain the presence of allaiitoine in the urine, the urine is precipitated with acetate of lead, filtered, and any excess of lead removed by sulphuretted hydrogen. The filtered solution is evaporated to dryness in a water-bath, and the residue exhausted with boiling dilute spirits of wine. When the filtrate, which is, of course, concentrated by evaporation, cools, crystals are separated, if any allantoine is present ; these, when recrystallised out of boiling water, serve for testing. In addition to the microscopic forms of pure allantoine, we have also the peculiar globular forms characteristic of allantoine-oxide of silver, (d. 3.) According to Lehmann, we may also separate the allantoine by precipitation with nitrate of mercury. The urine is thoroughly precipitated with a mixture of nitrate of baryta and caustic baryta ; the filtrate, carefully neutralised with nitric acid, is concentrated in a water-bath, and then treated with a solution of nitrate of mercury in slight excess. The precipitate which is formed, consisting of urea and allantoine-oxide of mercury, is collected on a filter and washed, suspended in water, and decomposed with sulphuretted hydrogen. The solution filtered off from the sulphide of mercury is strongly concentrated in a water-bath, and left for several days to crystallise. Any urea accidentally crystallised with the allantoine may be removed by cold alcohol. The allantoine which remains should then be once more crystallised out of boiUng water, before being made use of for the microscopic test, or for the preparation of the characteristic silver-compound. The urine of young calves is evaporated to a syrupy consistence in a water-bath, and allowed to stand for several days. The crystals that separate are washed with water, and then boiled with a little water. The solution is decolorised with animal charcoal, and- filtered while hot ; a few drops of hydrochloric acid are added to prevent the separation of phosphate of magnesia, and it is left to cool ; the allantoine then separates in the form of thin crystals united together in bundles. Calf's urine is strongly acid, differing, in this respect, from the urine of the grown-up animal, which has ceased to feed upon milk. It contains as much urea and uric acid as the urine of man, but no hippurio acid. On the other hand, the urine of the cow, which is rich in hippuric acid, contains no allantoine. LEUCINE. 105 section xxxiii. Leucine. Composition : — ' In 100 parts : Carbon . . . 54-96 Hydrogen . . . 9*92 ' Nitrogen . . . 10-68 Oxygen .... 24<-44 100-00 Formula: C,,H,3N0,. A. Occurrence. — ^Leucine was originally obtained as a product of decomposition of highly nitrogenous animal substances, when under- going putrefaction or subjected to the action of strong acids and alkalies. It has, however, of late been recognised by Virchow, I'rerichs, Gorup-Besanez, Stadeler, and others, as both a normal and pathological constituent of various organs and juices of the body, both in man and beast, being usually found associated with tyrosine. Leucine has, in fact, been found in the liver, especially when the function of the organ had been deranged ; and, together with tyrosine, in the pancreas and the pancreatic juice in considerable quantity j also in the spleen, in the upper pai-t of the intestinal canal, in the thymus, the thyroid and salivary glands, in the saliva, in- the lymphatic glands, the lungs, and the brain. Leucine has also been found in the urine in the course of certain diseases — in typhus, in small-pox, and in atrophy of the liver. B. Microscopical Characters. — Impure leucine, as obtained on its first separation from animal fluids, crystallises in granular masses, consisting of roundish, and in part concentrically striped globules, mostly of a yellowish colour, some of them finely pointed, but without any distinct crystalline form, they somewhat resemble glo- bular fat-cells. When pure, it separates in gland-like masses of leaves or scales, whose contour is often difiicult of determination. Single borders are frequently seen like sharp dark lines, so that on the first glance several crystals appear as capillary needles terminating in two points. (Punke, Plate III. Fig. 6.) c. Chemical Characters. — 1. Pure leucine takes the form of white crystalline scales, has a fatty feel, and is without taste or smell. It is not readily moistened with water, but is nevertheless tolerably 106 LEUCINE. soluble in it j it is less soluble in alcohol, and quite insoluble in ether. It readily dissolves in acids and alkalies. 2. Leucine, carefully heated to 170° C. (338° Pahr.) in a glass tube open at both ends, sublimes, without previous fusion, in white flocculent masses, which, like oxide of zinc, are in part conveyed along the tube by the heated current and escape into the air around. This peculiar mode of sublimation is very characteristic of leucine. Heated to 180° C. (356° Pahr.) leucine fuses, and is decomposed into carbonic acid and amylamine : 2 Carbonic Acid = C^ 0, (C,„ H„ 1 Amylamine = N | H (h 1 Eq. Leucine = C„ H,, N 0,. 3. It is separated in beautiful glistening scales from a boiling mixture of leucine and sugar of lead, when ammonia is carefully added, as leucine-oxide of lead. 4. A solution of nitrate of mercury does not cause a precipitate in an absolutely pure solution of leucine. Any precipitate thereby formed indicates the presence of tyrosine—*, e., if the supernatant fluid has a reddish or a rosy-red colour. 5. Leucine, when mixed with putrefying animal matters, and also when fused with hydrate of potass, is converted into valerianic acid (G,|,H,„OJ — carbonic acid, ammonia, and hydrogen, being at the same time evolved. 6. Pure leucine, carefully evaporated with nitric acid on platina foil, leaves a colourless and nearly imperceptible residue. If to this residue a few drops of caustic soda are added, and heat is applied, the leucine wiU be dissolved; the solution will be perfectly clear, or more or less discoloured, according to its degree of purity. Again, if the fluid be carefully concentrated on platina foil over a lamp, it will in a short time be gradually condensed into an oily sort of drop, which roUs about on the foil, neither moistening nor adhering to it. This property is very characteristic even of leucine which is not per- fectly pure. (Scherer.) TYROSINE. 107 section xxxiv. Tyeosine. Composition : — In 100 parts : Carbon .... 59-67 Hydrogen . . . 6-08 Nitrogen . . . 7 '73 Oxygen .... 26-52 100-00 Formula : C„H„ N 0,. A. Occurrence. — Tyrosine is formed in exactly the same way as leucine^ and is produced either somewhat later, or, more generally, at the same time as the leucine, during the decomposition of highly- nitrogenous animal matters. Like leucine, it is also found normally and pathologically in the human body ; Prerichs has found it, to- gether with leucine, in large quantities in the urine of patients sulfer- ing from typhus, small-pox, and acute atrophy of the Hver. B. Micrdscqpical Characters. — Tyrosine forms a snow-white, sUky, gUstening, adhesive mass, which consists of long shining needles clustered together ; these needles again are composed of very delicate smaller needles, grouped together in a stellate form. Tyrosine often crystalhses out of an ammoniacal solution, in globular masses, which are composed of a number of iine needles congregated to- gether in a radiating form, and jagged at the periphery, in conse- quence of small spear-shaped crystals projecting from them. Com- pressed under the object-glass, these little globules of tyrosine break down into fragments, consisting of extremely fine white needles. (Scherer.) c. Chemical Characters. — Tyrosine has neither taste nor smell ; it is almost insoluble in cold water, but readily dissolves in boiling water, and stiU more readily in acids and alkalies ; it is insoluble in alcohol and ether. 1. When treated it emits the odour of burnt horn ; it does not undergo sublimation. 2. Nitric acid carefully evaporated with tyrosine produces, in addition to oxalic acid, a yellow body — nitrate of nitrotyrosine j this residue, when treated with potash or ammonia, assumes a deep reddish-brown colour. Tyrosine, evaporated on platinum foil with 108 TYROSINE. nitric acid of sp. gr. VZ, dissolves rapidly, and assumes a lively pomegranate-yellow colour, as soon as the acid becomes warm. When evaporated it leaves a shining translucent residue of a deep yellow colour ; and if to this residue a few drops of hydrochloric acid are added, the fluid assumes a deep yellow -red colour, and when evaporated leaves a deep brownish-black residue. Scherer prefers this test even to Piria's test, on account of its easy performance. (4.) 3. Nitrate of mercury throws down from a boilihg solution of tyrosine, a red flocculent precipitate, the supernatant hquid taking an intense rosy-red colour. This test is exceedingly sensitive. If the solution of tyrosine is very dilute, it must be boiled and left at rest for a time, or tlie reaction will not take place. 4. Tyrosine, poured into a porcelain basin with a few drops of con- centrated sulphuric acid, and gently heated, dissolves, and assumes a passing red colour. If, after dilution with water, the acid is saturated with a milk of carbonate of baryta, the mixture boiled to decompose the bicarbonate of baryta, and a neutral dilute solution of perchloride of iron added to the filtrate, a beautiful violet colour appears. Only a small quantity of leucine may be present with the tyrosine. This reaction is very delicate. When diluted 6000 times, the colour appears of a lively red in a common test tube. Through a layer of the fluid two inches thick, a distinct rosy-red colour is still perceptible when the dilution is carried to 25,000, and through eight inches of the fluid when the dilution reaches even to 45,000. (Piria. Stadeler.) D. Preparation. — A mixture of 5 pounds of oil of vitriol, and 13 pounds of water, are poured upon 2 pounds of horn-shavings, and the mixture boiled for twenty-four hours, the water as it evaporates being renewed. The sulphuric acid is then removed by milk of lime, filtered, washed with boiling water, and the filtrate, after the solu- tion has been reduced to about 12 pounds, freed from the dissolved Hme by the careful addition of oxaUc acid. The filtrate is now evaporated until a crystalline pellicle begins to form on its sur- face. The gland-like masses of crystals found in it are leucine, mixed with varying quantities of tyrosine; for it rarely happens that tyrosine is altogether absent. The different degree of solubility of these two bodies in water is made use of for the purpose of separating them. The crystal- line compound is dissolved in a large quantity of boiling water. TYROSINE. 109 so that only a small portion of the crystals separates when the solution cools; these crystals are white needles of the nearly in- soluble tyrosine. The leucine may now be obtained from the mother-liquor in white crystalline masses, after treatment with animal charcoal and further concentration. — (Schwanert, Ueher Leu- cm; Dissert., Gottingen, 1857.) E. Tests. — ^Leticine and tyrosine have not yet been found in the urine of healthy people. Frerichs first discovered them in the urine of patients suffering from typhus. In acute atrophy of the liver, leucine and tyrosine are present in large quantities, whilst, at the same time, only traces of the substances such as urea, &c., which normally represent the final products of the metamorphoses of the tissues, are found in the urine. Urine of this kind often deposits spontaneously a-softish greenish-yellow sediment, consisting of round grandular masses of needles of tyrosine; and when evaporated on an object-glass, leaves numerous crystals of leucine and tyrosine. In order to obtain a largfe quantity of these bodies, Prerichs drew off the urine, which also distinctly showed the pre- sence of bUc'^igment, with a catheter, freed it from colourhig and extractive matters by precipitation with basic acetate of lead, filtered, separated the superfluous lead by sulphuretted hydrogen, and then concentrated the clear filtrate. In twenty- four hours a quantity of tyrosine,* sufficient for several analyses, was deposited.f Schmeisser, by the same process, found a large quantity of tyrosine in the urine, in a case of acute yellow atrophy of the liver. The urine was free from albumen, and by none of the known tests could the presence of bile-pigment be discovered in it. The tyrosine contained in it was crystallised out of boiHng water, and then subjected to chemical and microscopical tests. To obtain the leucine, the evaporated residue is first of all treated with cold absolute alcohol as long as the alcohol dissolves anything out of it, and then extracted with boiling alcohol of ordinary strength; in this way a darkish-brown, tenacious substance is obtained, readily soluble in water, and containing the remains of the tyrosine. The alcoholic solution last obtained, after evaporation and long- * Together with the tyrosine, another erystallisable body of a similar form, but richer in nitrogen- 8-83 per cent.— was found, t Frerichs, Deutsche Klinik, 1855. N. 31,^3. 343. 110 SEDIMENTS OF THE URINE. standing of the syrupy residue^ deposits the leucine in it in the globular form described above (Sec. xxxiii. b.), which may be sub- jected to chemical and microscopical tests. It is better, however, before testing to purify still further the leucine thus obtained. For this purpose we may make use of the compound formed by it with oxide of lead. The watery solution of leucine, freed as far as possible from the mother-ley by pressure between paper, is rendered strongly alkaHue with ammonia, and then precipitated with sugar of lead solution, or basic acetate of lead as long as any precipitate forms. The precipitated leucine-oxide of lead is collected on a filter, slightly washed, then suspended in water, and decomposed with sulphuretted hydrogen. The leucine will now be separated in a pure crystalline form from the filtrate on its evapora- tion. (Lehmann.) If the urine contains albumen, the albumen must be previously separated by heat and filtration, and the filtrate then tested for' leucine and tyrosine. Care must be taken in this experiment that the urine is used fresh ; because leucine in contact with putrefying animal substances is very readily decomposed, and valerianic acid formed. The urine described by Frerichs as obtained in the case of acute atrophy of the liver, contained 4"9 per cent, of solid residue, and O'lJ) per cent, of ash. The residue was strongly acid, and no urea could be obtained from it. It contained, besides leucine and tyrosine, a tenacious, extractive-like substance, similar to that which is formed (together with tyrosine and leucine) during the artificial decomposition of proteine-bodies by acids. The ash consists mainly of chlorine-compounds and sulphates. It is re- markable that alkaline and earthy phosphates are entirely absent. (Frerichs.) SEDIMENTS OF THE URINE. SECTION XXXV. We have already considered (see Sec. i.) the pecuHar decomposi- tions which healthy urine undergoes when left at rest for some time. These changes, which we have distinguished by the names of acid and alkaline fermentations, have a very intimate connexion with the formation and separation of its sediments. SEDIMENTS OF THE URINE. HI We will, first of all, cousider the sediment which is most frequently met with in the urine — urate of soda. We often notice that urine, which is perfectly clear when passed, separates this sediment shortly afterwards. In such case we may conclude, that the urate of soda is increased to such an extent in the urine that it cannot remain in solution at ordinary temperatures. This view is confirmed by the circumstance that the sediment is usually redis- solved when a less concentrated urine is added to it, or when it is heated. It often happens, however, that the urine remains clear long after it has attained the same temperature as the surrounding air, and that the separation of sediment does not take place for twelve or twenty- four hours after the urine has been passed. Becquerel also has ob- served that urine which throws down no sediment often contains more of the urates than urine which deposits a sediment. Consequently, the cause of the separation of the sediment must be sought else- where. Lehmann considers that the cause of the deposition of the urates is~to be found in the colouring extractive matter, which also, according to Scherer's observations, occasions the separation of free uric acid as Sediment. According to Lehmann, the solubility of the urate of soda is increased by the colouring extractive matter, and the decomposition of the pigment exercises an influence over the entire constitutic:i of this salt. We have already seen how prone the colouring-matter of the urine is to undergo decomposition, especially when subjected to the influ- ence of the air, and that free acids, in small quantities, are at the same time produced. If, therefore, we expose to the air sedimert which is originally colourless, and contains no free uric acid, the beautiful red colour of urine-pigment will first appear in the moist sediment col- lected on the filter ; and if we now endeavour to dissolve it in water, we shall find that more or less uric acid, in the form of beuatiful crystals, will remain behind. The phenomenon is readily explained. In consequence of the decomposition of the pigment free acids are formed ; these withdraw a portion of its base from the urate of soda, and uric acid is thereby separated, the filtered fluid not having an alkaline but a neutral reaction. Lehmann considers, from these facts, that he is justified in drawing the following conclusion concerning the origin of uric acid sediments : — Neutral urate of soda is dissolved in the urine, but whenever any free acid is formed through the decomposition of the pigment, the U2 URIC ACID SEDIMENT. urate of soda undergoes a change ; it loses a portion of its base, and the originally neutral salt is separated as an acid urate of soda. This view is strengthened by the fact, that the sediment usually met with consists of acid urate of soda. Scherer has pointed out in the clearest manner the mode of forma- tion of uric acid sediments ; and there is no doubt that his description is correct. Hg has proved that the decomposition of the pigment- matter is to be considered as the sole cause of their production. Sediment of free uric acid is very rarely found in fresh urine ; and we know that the acidity of urine in the first instance invariably increases, that it undergoes, in fact, the acid fermentation, and then deposits crystals of free uric acid. Scherer first observed this process ; and Lehmann concludes from it that uric acid sediments are the product of the decomposition which the urine undergoes out of the body. As we have already explained (Sec. i.), the free acid, which is produced through the action of the mucus of the bladder upon the pigmeut-matter of the urine, readily decompose the lightly-combined salts of uric acid, uniting with a portion of their base, and throwing down the uric acid in a crystalline form. Moreover, it is to be noted, that oxalate of Ume may be formed, or at all events separated, during the process of fermentation, for in most cases crystals of oxalate of lime are not found in fresh urine ; when, however, the acid fermentation-process has occasioned a precipitate of uric acid crystals, single crystals of oxalate of lime are found mingled with them) Consequently, the formation of oxalic acid appears to be intimately connected with the separation of uric acid. This fermentation-process of the urine having at length reached its maximum of acidity, a change commences. In the course of a few days, or it may be weeks, the acid disappears, and the surface of the urine becomes covered with threads of fungi, confervse, and algae ; from the neutral it gradually passes into an alkaline condition, and the crystals of uric acid, which have been separated, disappear, and are replaced by other sediments. The ammonia, resulting from the decomposition of the urea, causes a separation of earthy phosphates, of phosphate of lime as such, and of beautiful crystals of ammonio- phosphate of magnesia. At the same time a portion of the ammonia unites with the uric acid, and forms a sediment of urate of ammonia. The urine in this condition effervesces with acids ; the greater part of its pigment is decomposed, and its yellow colour almost wholly lost. This alkahne fermentation, the promoting agent of which is the URIC ACID SEDIMENT. 113 decomposed mucus of the bladder, is not in all cases preceded by tbe acid fermentation. It sometimes occurs at an earlier period, and in fact, within the bladder itself, in affections of its mucous membrane — a proof that urine is sometimes originally alkaline, even when its alkalinity is not caused by the ingestion of organic alkaline salts. Scherer has also endeavoured to show that this fermentation-pro- cess, when it tates place in the bladder, is the chief cause of the formation of urinary calculi. The ordinary sediments of urine may, in accordance with what has been said, be grouped together in the following way : — 1. Sediments caused hy the acid fermentation. — The mucus of the bladder acts as a ferment upon the pigment-matter, producing free lactic and acetic acids, whereby are thrown down, — 1. Free uric acid. 2. Acid urates (soda, &c.). 3. Oxalate of lime. 2. Sediments caused hy the alkaline fermentation. — Carbonate of ammonia is formed in the urine ; the free uric acid disappears, and the foUowins salts are separated : — 1. Ammonio-phosphate of magnesia. 2. Phosphate of lime. 3. Urate of ammonia. Infusoria, fungi, and yeast-globules are formed at the same time. We will now proceed to the particular consideration of each of these bodies. I.— UNORGANISED SEDIMENTS. section xxxvi. Ueic Acid. Uric acid is not found as a sediment except in very acid urine ; it is generally accompanied with urates, especially with acid urate of soda. As a sediment it is always coloured ; sometimes it is of a very pale yeUow, but ordinarily of a deep yellow, orange-red, or brown colour. Its crystalline condition is readily recognisable even with the naked eye; and when examined with the microscope, it exhibits the various forms already described. (Sect, vi.) Pour-sided tables or six-sided prisms of a rhombic character, which by rounding of their obtuse angles form spindle- and barrel-shaped crystals, are charac- Ill SEDIMENTS OF URATES. teristic of uric acid. Should, however, any doubt exist as to the nature of the crystals, the sediment should be dissolved on the object- glass in a drop of caustic-potash, and a little hydrochloric acid added to it. By this process we obtain the ordinary forms of the crystals. Uric acid, when mixed with any of the urates, may be separated by heat and filtration ; the uric acid salts are thereby dissolved, and the free uric acid left behind on the filter. We may also employ the chemical test, the murexide-reaction, for which an extremely small quantity of uric acid is sufficient. (See Sect, vi., Plate I. Figs. 2 and 3, Plate II. Mg. 4, Plate III. Pig. 1.) Table-shaped crystals of uric acid aggregated together in a fan-like form, as delineated by Funke in his " Atlas " Plate XII. Fig. 5, are not so frequently met with in urinary deposits. section xxxvii. Ueates. Salts of uric acid, present with free uric acid in the sediment, may be separated, as already mentioned, by warming the urine ; they separate again from the filtrate as it cools. All the urates, with the exception of urate of ammonia, are met with only in acid urine. Their colour varies much, especially when they are exposed to the air, whereby they are decomposed. They are usually of a greyish-white, white, rosy-red, brownish-red, or purple-red colour ; and in this way often resemble organic substances, such as blood, pus, &c., from which they can only be distinguished by the aid of the microscope. Chemically, their presence is readily shown by their conduct with nitric acid and ammonia (the formation of murexide), as well as by their solubility in hot water. 1. Acid urate of soda generally appears in the form of amorphous, irregular granules, of very small size. Prepared artificially, by solu- tion of uric acid in a warm solution of ordinary phosphate of soda, it is obtained as microscopic prismatic crystals, which are usually grouped together in stellate masses. Similar forms are sometimes found in the urine at the termination of its acid and the commence- ment of its alkaline fermentation. Very complicated forms are often observed under the microscope at this transition-period of the fer- mentation ; the crystals of uric acid, separated during the acid fer- mentation, are now more or less in course of re-solution, and studded SEDIMENTS OF URATES. 115 with beautiful groups of prismatic crystals of urate of soda ; at the same time concentrically striped balls — probably of urate of ammonia — may be seen here and there scattered over the prismatic crystals. This urine still slightly reddens litmus. As the fermentation proceeds, and when neutral reaction sets in, we also occasionally observe pris- matic groups of acid urate of soda ; but we now find them accompanied with fine large crystals of ammonio-phosphate of magnesia. Acid urate of soda is very little soluble in water, requiring 124 parts of boiUng, and 1,150 of cold water, for its solution. It is sepa- rated from the urine, in a crystalline form, as uric acid, on the addi- tion of hydrochloric acid. Heated with potash, it does not give off ammonia, but leaves a white residue when heated to redness. This residue, when moistened with water, turns red litmus-paper blue, and effervesces with acids (carbonate of soda). Acid urate of soda is usually found in the urine in febrile states of the body, and whenever the respiration, or rather the oxidation of the blood, is impeded. Plate II. Pigs, 1, %, Urinary sediment of urate of soda. Plate II. Fig. 4, Sediment consisting of urate of soda, uric acid, and fer- mentation-globules, in urine which has been left at rest, and is passing into the stage of acid fermentation. {Plate I. Fig. 3). 2. Acid wrote of ammonia is less frequently met with than acid urate of soda. It is usually found in alkaline urine, mixed with earthy phosphates. Under the microscope it appears to consist of opaque globular masses, from which peculiar delicate spikelets project, like the spines of a hedge-hog. When a drop of hydrochloric acid is added to it, under the microscope, the well-known crystals of uric acid soon make their appearance. It is soluble in boiling water, but separates again as the water cools. Ammonia is generated when it is treated with caustic-potash. "With nitric acid and ammonia it yields, like pure uric acid or the other salts of uric acid, the well-known murexide-reaction. — Plate II. Fig. 5. 3. Acid urate of lime is rarely met with, and only in small quantities. It forms a white, amorphous powder, very soluble in water, which when exposed to a red heat leaves behind carbonate of lime. Tests. — The recognition of the urates in urinary deposits is by no means difficult. By far the most common of them is the amorphous acid urate of soda. The ammoniacal salt is less frequently met with ; *it is always readily known by its spiked globular form. "When we have satisfied ourselves (by the formation of crystals of uric acid, on ' i2 116 OXALATE OF LIME SEDIMENT. the addition of a drop of hydrochloric acid) of the presence of a salt of uric acid in the sediment, we collect the whole of the sediment on a filter. A portion of it is heated on platinum-foil until it is converted into an ash, which is then moistened with water, and tested with turmeric-paper. If the paper becomes brown, the presence of soda or potass is indicated. Another portion of it is heated with caustic-potass ; and if ammoniacal vapour, which turns reddened litmus-paper blue, is given off, the presence of an ammoniacal salt is shown. The remainder, however small the quantity of it, may serve for the murexide test. The distinction between urate of soda and urate of ammonia is readQy shown microscopically, by treating the washed sediment with hydrochloric acid, and allowing it to evaporate slowly on the object-glass. The microscope shows (in addition to the crystals of uric acid which are separated) cubes of chloride of sodium if urate of soda was present, or the efHorescence of sal ammoniac if urate of ammonia existed in the urine. section xxxviii. Oxalate of Lime. Composition of hydrated oxalic acid ; — In 100 parts : Carbon . . . 26-667 Oxygen . . . 53.333 Water .... 20-000 Formula : C^ 0, -f- H 0. lOO-OO'O A. Origin. — Although oxalic acid is widely distributed through the vegetable kingdom, it is only met with in very small quantities in animal bodies, and always in combination with lime. Oxalate of lime appears in the urine, both normally and pathologically, as a sediment in the form of well-marked crystals. It is chiefly met with in cases of impeded respiration, in emphysema of the lungs, and during convalescence from severe diseases, particularly from typhus. According to Lehmann, the oxalate of lime is held in solution in the urine as it comes fresh from the bladder; and this seems probable, inasmuch as the oxalate is tolerably soluble in a solution of biphos- phate of soda, which is the chief source of the free acid in healthy urine. We may, indeed, according to Lehmann's assertions, readily' satisfy ourselves of this. The urine is filtered and evaporated, and moderately concentrated spirits of wine added to its soUd residue ; OXALATE OF LIME SEDIMENT. 117 ether is next shaken with the spirituous extract, and after this opera- tion we find in the alcoholic extract a sediment, which is insoluble in water, and consists of beautiful crsytals of oxalate of lime. Oxalate of lime separates from filtered urine only after it has stood for some time, together with a few uric acid crystals. Oxalate of lime, again, is often separated in large quantities, as soon as the acid fermentation of the urine commences, and is then readily found in the sediment with uric acid, (Sect, xxxv.) Vegetable diet, efiervescing wines and beer, as well as the internal use of bicarbonates of the alkalies, alkaline salts of organic acids, free uric acid and salts of uric acid often increase the quantity of oxalate of lime in the urine. Beneke has made some very interesting observations respecting the origin of oxalate of lime in abnormal urine. (Beneke, der phos- phors, und oxals. Kalh. Gottingen, 1850.) B. Microscopical Characters. — Oxalate of lime, prepared artifi- cially (as by the precipitation of a salt of lime with oxalate of am- monia, &c.), appears, under the microscope in the form of perfectly amorphous masses, in which not the slightest trace of crystallisation is observable. Separated, however, from the urine in the form of a sediment, it assumes very characteristic forms. Crystals of the oxalate of lime thus obtained appear in the form of small, shining, well- defined, perfectly transparent, square octohedra, having a strongly refractive power. Some of the crystals, however, are occasionally found with very acute angles. Beneke, in the work above referred to, also describes peculiar hourglass-shaped crystals, and others, of a square columnar form, with pyramidal summits. (Beneke, Tlate I. Figs. 4 to 10.) (Funke, Plate I. Mg. 1. Plate I. Pig. 3.) Beautiful crystals of oxalate of lime separate from urine which throws down no sediment, when a dilute solution of oxalate of ammonia is carefully poured over without disturbing it. I have in this way artificially prepared a large quantity of most beautiful crystalline forms. The relation of oxalate of lime to acid phosphate of soda is interesting. When common phosphoric acid is added to a solution of ordinary phosphate of soda, until a drop of the mixture, on testing, is found to be no longer clouded by a solution of chloride of barium (a proof that the fluid contains only acid phosphate of soda), dilute solutions of chloride of calcium and oxalate of ammonia may be added in drops, without occasioning any turbidity or sepa- ration of oxalate of lime. If very dilute caustic-soda is now care- fully dropped into this solution, which remains clear even after 118 SEDIMENTS OF EARTHY PHOSPHATES. long standing, the oxalate of lime in solution is, after a short time, separated in the form of regular crystals. Even the acid solution, obtained by boOing uric acid with phosphate of soda, may also hold oxalate of lime in solution, and often yields, when diluted, beautiful octohedra of oxalate of lime, together with crystallised urate of soda. The crystals are insoluble in water, and are scarcely affected by acetic and oxalic acids ; they are, however, readily dissolved in strong mineral acids. c. Tests. — Oxalic acid is always found in the urine in combination with lime, and is therefore readily recognised by its characteristic crystalline forms. The letter-envelope shape of the crystals is very peculiar, and cannot be confounded with any other crystalline form in urinary sediments. The only crystals with which they might possibly be confounded, are those of common salt ; but salt, unlike oxalate of Ume, is very soluble in water, and could never exist as a sediment in the urine. Sometimes we meet with larger forms of oxalate of lime, which somewhat resemble the crystals of ammonio-phosphate of magnesia ; but the solubility of this double salt in acetic acid (in which oxalate of lime is insoluble), as well as its microscopic characters,, enable us readily to distinguish the one from the other. If, again, the urine is very acid, the crystals of oxalate of lime (which, as we have already said, is tolerably soluble in a solution of acid phosphate of soda) are more readily separated when the urine is left some time at rest, and the free acid nearly neutralised, for this purpose a conical-shaped glass should be used, and when the sediment has collected in the pointed bottom, the supernatant liquid is poured off, and a drop of the fluid left at the bottom is then placed under the microscope. To test urine, which throws down no sediment, for oxalic acid, we must make use of Lehmann's process, above described, in which the alcoholic extract is shaken with ether, and the previously dissolved oxalate of lime separated in a crystalline form. section xxxix. Eabthy Phosphates. Sediments of this kind consist of phosphate of lime and ammonio- SEDIMENTS OF EARTHY PHOSPHATES. 119 phosphate of magnesia, both of which compounds are in most cases met mth together. It rarely happens that one of them exists alone in the urine. They do not form in acid urine, on account of their ready solubihty, even in very weak acids. They never appear except when the urine has undergone the alkaline fermentation, either within or out of the bladder. 1. Ammonio-phos'phate of Magnesia. — This sediment is not met with in healthy urine ; but it always appears in the form of remark- ably beautiful crystals, when the urine becomes alkaUne. In some diseases — in serious affections of the bladder or spinal marrow — large quantities of sediment is often found, consisting of these crystals. In diabetic urine, Lehmann once observed a white shining sediment, which consisted solely of ammonio-phosphate of mag- nesia, without a trace of lime. The crystals of this double compound (the triple phosphate) may be always readily recognised by their characteristic forms. The forms most frequently met with are combinations of right rhombic prisms, Plate II. Fig. 3, Fi^. 5. The crystals are insoluble in hot water, but readily dissolve on the addition of acetic acid, and may be thus distinguished from those forms of oxalate of lime to which they bear a resemblance. They are not affected by alkalies. 2. PJwsphate of Lime, as a sediment, forms an amorphous, and frequently also a crystalline powder. It is insoluble in water ; but soluble in acids, even in acetic acid, and is precipitated from their solutions by alkalies in an amorphous state. Consequently, this sedi- ment only appears in sUghtly acid, neutral, or alkaHne urine. Phosphate of hme, in urine which has only a feebly acid reaction, is frequently held in solution by carbonic acid only, and is separated in white flakes, closely resembling those of albuminous coagula, when the carbonic acid is expelled by boiUng. Sediments of crystalline phosphate of lime are also not unfrequently met with, and sometimes mingled with triple phosphates. The size, form, and grouping of the crystals of this phosphate of lime vary considerably, but they always present signs sufficiently charac- teristic to admit of their being at once recognised under the micro- scope. The crystals are sometimes solitary, and sometimes aggre- gated, frequently forming coils and rosettes. At times they are thin and acicular, often forming globe-like glands of crystals, by lying upon and crossing each other at right angles. Again, they are often small and smooth, and present sharp or pointed extremities. 120 CYSTINE. Very frequently also the crystals are thick, more or less wedge-shaped, and so attached by their pointed extremities as to describe parts, of a circle. Their free and broad extremities are usually somewhat oblique, and the perfectly formed crystals present six surfaces. Urine, which deposits much phosphate of lime in a crystalline form, is generally pale in colour, abundant in quantity, and of slightly acid reaction, but is readily rendered alkaline by the mucus with which it is mixed. According to Dr. Bence Jones, this sediment may be produced by the administl-ation of lime- water or acetate of lime. His formula for crystallised phosphate of lime is 2 Ca 0, HO, P 0^, and for the amorphous phosphate 3CaO,PO,. Tests. — The tests of the earthy phosphates, and particularly of the ammonio-phosphate of magnesia, are readily applied; the presence of these salts is sufficiently characterised both by their origin, and by their microscopic and chemical characters. Should they be mixed with other deposits, the following differential tests may be made use of Salts of uric acid readily dissolve in hot water, but the phosphates are insoluble in it. Oxalate of lime, which in certain of its forms may certainly be confounded with the ammonio-phosphate of magnesia, is insoluble in acetic acid, which readily takes up the latter. Free uric acid cannot occur simultaneously with the earthy phosphates, and is readily recog- nised both by its crystalline form, as well as by its solubility in alkalies. The murexide-reaction will always remove any doubt upon this point. Composition : In 100 parts: section xl. Cystine. Carbon . Hydrogen Nitrogen Sulphur Oxygen Pormnla: CHNSsO.. 30-00 5-00 11-66 26-67 26-67 100-00 CYSTINE.. 121 A. Origin, — Cystine was originally discovered in a urinary cal- culus, but it has since been often found in the urine in a state of solution, and precipitated out of it by acetic acid. It is also found as a sediment mixed with urate of soda. The occurrence of cystine as a urinaiy calculus is very rare; of 129 specimens of calculi only two contained cystine. (Taylor.) Cloetta has recently found cystine in the juice of the kidneys, together with inosite and hypoxanthine. Scherer on one occasion found it in the liver. Julius Miiller (Archiv d. Pharmac, March, 1852, p. 228), describes a urinary calculus containing cystine, which was removed by operation from the bladder of a boy 6 J years of age. The urine of this boy, which could only be obtained in small quantities before the operation, threw down an alkaline sediment, containing numerous mucus corpuscles, but neither uric acid nor earthy phosphates. Only a small quantity of urate of soda, but much chloride of sodium was found dissolved in it. The calculus weighed 268| grains, and contained 5B'65 per cent, of cystine. Imme- diately after the operation the urine presented an acid reaction, threw down a mucous sediment, and contained less uric acid and earthy phosphates, than healthy urine. Eight weeks later the alkaline reaction again appeared in it ; it contained much chloride of sodium and urea, but only a trace of uric acid. On standing, it deposited a sediment of ammonio-phosphate of magnesia and cystine, which was readily recognised by its crystalline form under the microscope, after the removal of the magnesian-salt by acetic acid. The filtered urine also, when acetic acid was added to it, threw down a precipi- tate in the course of twenty-four hours, which when dissolved in ammonia, left on evaporation of the solution, the characteristic micro- scopic tables of cystine. From this it follows, that the production of the cystine in the urine of this lad continued after the operation. Toel {Annual, d. Chem. et Pharm. vol. 96, p. 24) has made some interesting observations at Bremen concerning the production of this remarkable substance, in the case of two young women, by whom it was constantly passed with the urine, partly in solution and partly as a sediment. These women had suffered from calculus of the kidney. The quantity of the cystine separated reached in each an average of about 1.4 gramme in 24 hours. B. Microscopic characters. — Cystine crystallises under the micro- scope in the form of transparent, colourless, six-sided plates or prisms.. As, however, uric acid occasionally crystallises in six-sided tables, the microscopic investigation of the cystine-crystals does not 122 CYSTINE. suffice for the determination of their nature. The sediment must, therefore, be examined chemically. {Plate HI. Mg. 4.) c. Chemical characters. — Cystine is a neutral body, without taste and smell, insoluble in water, but soluble in mineral acids and in oxalic acid, with which it forms saline compounds, that readily undergo decomposition. It is not soluble in acetic or tartaric acids. 2. Cystine treated with nitric acid is decomposed and dissolved, and on evaporation of the fluid a reddish-brown mass is left, which does not give the murexide-reaction with ammonia. 3. Heated on platinum-foil, cystine does not fuse, but burns with a bluish-green flame, giving off a sharp, acid, and characteristic odour, which resembles that of prussic acid. Subjected to dry distillation, it yields ammonia and a fetid oil, a porous coal remaining as residue. 4. Caustic alkalies and carbonates of the fixed alkalies, as well as caustic ammonia, readily dissolve cystine, but carbonate of ammonia does not. Consequently, we always precipitate it from its acid solutions by carbonate of ammonia, and from its alkaline solutions by acetic acid. 5. Cystine boiled with caustic-potash, in which oxide of lead has been previously dissolved, throws down a large quantity of sulphuret of lead. (Liebig.) 6. When cystine is boiled with caustic-potash, ammonia is pro- duced, and a gas which burns with a blue flame. D. Tests. — Cystine is chiefly characterised by its crystalline form, by its solubility in mineral acids and alkalies, and by its conduct when exposed to heat or mixed with nitric acid. Liebig has also proposed as a test its reaction with caustic alkali and oxide of lead, which when boiled with cystine yield a large quantity of sulphuret of lead. But in the application of this test, it must be remembered, that other bodies which contain sulphur, such as albumen, fibrine, &c., act in a similar way ; it is therefore always necessary to ascertain that none of these bodies are present, or if any should be present, to remove them before commencing operations. Cystine may be readily distinguished from any of the earthy phosphates or urates which may be mixed with it, by boiling the urine and treating it with acetic acid. The boiling and acetic acid do not afifect the cystine, but dissolve the others. Uric acid, which, as we have already stated, occasionally crystallises like cystine in six-sided tables, is easily distinguished from it by the murexide-test. Cystine, when subjected to the same test, leaves a reddish-brown mass. TYROSINE.— MUCUS, AND EPITHELIUM. 123 section xli. Tyrosine. ( Compare with Section 34.) Stadeler aud Frericlis found a greenish-yellow crystalline sediment in the urine of a woman, who was suffering from acute atrophy of the liver, after it had been allowed to stand for a short time. This sediment was considerably increased when the urine was slightly evaporated. It was extracted by the action of dilute ammonia, and the crystals first separated from the solution were then recognised as tyrosine. Another more soluble compound, probably homologous with tyrosine, remained in the mother-liquor j it contained 8"83 per cent, of nitrogen. The tyrosine contains 7'73 per cent, of nitrogen. II. ORGANIC SEDIMENTS. SECTION XLII. Mucus AND Epithelium. Animal mucus is the product of the secretion of the mucous mem- branes, and holds in suspension the different forms of the epithelial cells, which have been separated from their surface. Urine always contains mucus, secreted from the mucous membrane of the bladder. When the urine is left at rest the mucus separates in the form of cloudy, transparent flocculi ; and if, after the mucus has thus gathered together, the urine be filtered, most of the mucus remains on the filter in separate, transparent, colourless masses; it then shrivels up and forms a shining, varnish-like layer. Mucine is the essential constituent of mucus, and the offshoot of a proteine- body ; it imparts to the fluid in which it is dissolved, even though its quantity be small, a tough, thready consistence. A solution of mucine is not coagulated by boiling (and in this it differs from albumen) ; but it readily coagulates on the addition of alcohol, which throws down the mucine in dense flocculi. Acetic acid, as well as a solution of alum preci- pitate mucine ; the thread-like masses thrown down by acetic acid somewhat 124 MUCUS— EPITHELIUM. resemble coagulated fibrins (Fiinke, Plate XI., Fig. 6 ; 2nd Ed., Plate XV., Fig. 6). Mineral acids also precipitate muoine j but the precipitate ia readily re-dissolved by a slight excess. Mucine is especially distinguished from the pyine in pus, in that it is readily precipitated by basic acetate of lead, but not by solutions of corrosive sublimate or of sugar of lead. Urine always contains mucine in solution, wMcli may be pre- cipitated as a fibrinous coagulum by the free addition of alcohol. "When urine, containing mucus in solution, is evaporated to dryness in a water-bath, the mucus assumes an insoluble form, and presents itself as a pellicle on the surface of the conceiitrated fluid. On treating with alcohol the residue, obtained by evaporation, the whole of the mucus remains undissolved. We find the so-called mucus-corpuscles, together with well-marked nucleated epithelial cells of the urinary passages, in the mucous sediment of healthy urine. These corpuscles appear under the microscope in the form of round cells, containing one or more nuclei and many granules, and cannot be distinguished by any character- istic mark from the colourless cells of blood, or from lymph-, chyle-, or pus-corpuscles. {Plate I. Figs. 4, 5, 8f 6. Plate II. Figs. 1, 2, ^ 3. Plate III. Fig. 3.) The clouds of mucus, described as present in healthy urine, are often greatly increased in diseased states of the mucous membrane, and exhibit large quantities of well-formed epithelial scales and mucous flocculi. We may conclude, that the mucous sediment, deposited when the urine is left at rest, contains no pus, and is in fact formed wholly of mucus, if we find no albumen present in the filtered urine ; when pus is present, the urine always contains albu- men corresponding in quantity- to the amount of pus-serum. (Sect. XLIV. B.) The muous-corpuscles, which are discharged from the urethra in gonorrhoea, are usually distinguished from those of the bladder by their size, and their clear and slightly granular appearance. In disease of the prostate, we meet with the cytoid corpuscles of these glands, and frequently also (as well as occasionally after gonorrhosa), we observe long mucous shreds, which appear, under the microscope, to be composed of mucus-corpuscles closely aggregated together. The dissolved mucine is often precipitated as a mucous coagulum at the commencement of the acid fermentation, probably through the action of the acids which are formed. This coagulum appears in the_ BLOOD. 125 form of narrow or broad twisted bands, arranged in rows, and consisting of extremely fine points and granules; it is very fre- quently associated with the sediments of acid urate of soda. These mucous coagula {Plate II. Fig- 3) occasionally resemble somewhat the casts of granular kidney {Plate I, Fig. 6), and may therefore be a source of error. A little practice, however, readily enables the observer to distinguish the one from the other. SECnON XLIII. Blood. The presence of blood in the urine is not a rare phenomenon, and may be demonstrated without any great dif&culty. The existence of blood- corpuscles in the urine, as shown by their microscopic charac- ters, is an important test, being demonstrative of the presence of blood. A. Microscopic cha/racters. — Normal blood-corpuscles are small round cells, probably filled with fluid matters — ^hsemato-crystalline. They cannot be confounded with any other object when examined under the microscope. They appear as thick, circular, and slightly- biconcave discs, with rounded borders, a colourless membrane, and contain a reddish, or by transmitted light, yellowish, tenacious fluid. These blood-corpuscles have no distinct nucleus, and only a few of them exhibit in their concave centre an Hi-defined nucleolus. They are for the most part massed together in a num- mular form. Their size in man equals about 0'00752 MM. {Plate I. Fig. 6. Plate III. Figs. 1^2). They undergo peculiar changes and modifications of form under the influence of alkaline salts and of other bodies. These changes require consideration. 1. The action of water on blood-eorjomcles. The alterations which blood-corpuscles undergo in water vary according to the quantity of water employed, and the length of time they have been mixed with it. (These changes are shown in Plate 126 BLOOD. III. Fig. 2, proceeding from left to right.) Under the action of water the cells swell out, assume at first a somewhat lenticular form, and finally that of a sphere; their central depression is elevated, and "gradually bulges out, which necessarily occasions a diminution of the diameter of each disc. The corpuscles now appear smaller, the central shadow gradually vanishes, whilst a circular shadow comes into view at their border. The cells, if still further subjected to the influence of water, become fainter and paler, presenting the appearance of thin hyaline vesicles, which gradually become invisible. 2. Blood-corpuscles treated with saline solutions, 8fc. Blood-corpuscles treated with a concentrated solution of a neutral salt, such as sulphate of soda, become much contracted. This change is chiefly recognised, under the microscope, by the more marked charac- ter of the central depression thence resulting ; the shadow which indi- cates it approaching nearer the border of the disc than it does in the healthy blood-corpuscles. The borders of the blood-corpuscles at the same time lose their circular form ; they become more or less distorted, oblong, or angular, and, instead of being smooth, are notched and jagged. If blood-corpuscles which have been rendered invisible by the action of water are treated with a concentrated solution of sulphate of soda, they again become visible, but appear in the form just described, distorted, angular, and jagged. (Punke, Plate IX. Mg. 3.) Plate III. Wig. 2, below to the right. Caustic alkalies and many of the organic acids, such as acetic acid, distend the corpuscle, altering its shape, and destroying it more or less rapidly. The organic colouring-matter, which forms the chief contents of the red corpuscles, can be made to assume a crystalline form when the blood is subjected to certain simple external inflaences. Punke has given it the name of hsemato-crystalline. (Funke, Plate X. Figs. 1-6.) B. Tests. — In most cases the blood-corpuscles found in urine which contains blood do not present their normal form. If the urine be acid, they may retain their shape for a tolerably long time, being only a little jagged at their borders ; usually, however, they are distended and of a spherical form. Their colour is hghter than natural ; -they still present a well-defined contour, but they no longer adhere together in nummular masses. These changes are of the BLOOD. 127 same tind as those described above, and are to be attributed to the action of the watery and saline constituents of the urine. IPlate I. Fig. 6. Plate III. Fig. 1, When the quantity of blood is small the urine containing it is left at rest for some time in a conical-shaped test-glass. The blood- globules are deposited at tbe bottom of the glass (in the apex of the cone), and the presence of the blood -may be generally at once recognised with the naked eye. The clear-filtered urine, if blood be present in it, will also be found to contain albumen. (Sect, xix. c. Tests for Albiimen.) If the microscope fails to discover blood-corpuscles or their rudi- ments, chemistry must be appealed to, but it, unfortunately, cannot give us much assistance. If the blood-corpuscles are destroyed or dissolved, they usually give the urine a reddish-brown colour j and the urine is rendered albuminous by the presence of the blood. On carefully adding acetic acid to such urine and heating it, we obtain a reddish-brown coagulam, which becomes almost black when dried. This coagulum, when dried and powdered, and treated with alcohol containing sulphuric acid, imparts to the fluid a reddish or reddish- brown colour, if haematine be present in it ; and the mixture evapo- rated and heated to redness leaves an ash which contains iron. Although iron may exist in healthy urine, its presence in the dilute alcoholic solution, above mentioned, must always be considered as indicative of blood in the urine, especially if there are other co- existing signs of the presence of blood in that fluid. Iron, however, obtained directly from the ash of urine must never be considered as a proof of the presence of blood in the urine. Heller, iu testing for hsematme, boils the urine, and then adds to it con- centrated caustic-potash. Any albumen which may have been precipitated is dissolved, and if hsematime is present, the fluid becomes of a bottle- green. On further boiling, and shaking the mixture, the earthy phosphates are precipitated, carrying down with them the heematine, and sometimes assume a brownish-red, or a blood-red, and often by diohroism yield a green colour to transmitted rays of light. According to Heller, the reaction is more certain when the colouring- matter of the blood is partially decomposed and has lost its red colour (?). If the phosphatio coagulum happens to be coloured by rhubarb, senna, santonine, &o., and not by hsematine, we shall find that it becomes violet after it has stood some time in the air, and that it is not rendered dichroistic by potash like the precipitated hsematine-coagulum. 128 PUS. SECTION XLIV. Pus. The only sure proof of the presence of pus in the urine is ob- tained through the microscope. Chemistry assists us here even less than in the case of blood in the urine. A. Microscopic characters. — Normal pus- corpuscles appear under the microscope as round, pale, indistinctly granular vesicles of various sizes. A distinct nucleus is usually visible in them j it is, inmost cases, simple, and in others spHt up and imperfect. All the cor- puscles do not possess a well-marked contour; in some of them the outline is indistinct, as if it had been washed out. 1. Pus-corpuscles acted on ly water. — When fresh pus is mixed with a good deal of distilled water, the corpuscles soon become pale and swollen, and their borders thin ; their granular surface generally disappears, the nuclei come prominently into view, and a few small, dark, point-like granules become visible. These changes may be very readily and satisfactorily studied by observation of the corpuscles of the mucous membrane of the mouth ; the simple, and in most cases lenticular nucleus of these corpuscles is very distinctly seen when water is added to them. (Punke, Plate IX. Fig. 4.) 2. Pus-corpuscles acted on by acetic acid. — Under the action of dilute acetic acid or of any other organic acid, or very dilute mineral acids, the pus-corpuscles swell up, sometimes becoming twice as large as natural ; their surface loses its granular aspect, their waUs become extremely hyaline and often burst; the jagged and torn remains of them being here and there visible in the field of the microscope, with the aid of a good light. The nuclei previously observed now come prominently into notice, varying both in form and in number; in part they appear round, oval, lenticular,, or horse-shoe shape ; and in part, again, made up of two, three, or more parts in different groups, as if from the splitting up of the simple nucleus. (Funke, Plate 11. Fig. 3, Plate VIII. Fig. 6.) Plate III. Fig. 3, upper half. 3. Caustic alkalis rapidly destroy pus-corpuscles; they do not, however, wholly dissolve them. The corpuscles often remain visible for a short time, but disappear on the addition of water, leaving a TVS. 129 gelatinous kind of residue, in which a few single points may be more or less readily recognised, B. Tests. — ^We must trust almost wholly to the microscope in searching for pus in the urine ; chemistry gives us very little assist- ance in distinguishing its characters. The appearance of pus under the microscope has been described above. The corpuscles of pus are distinguished from blood-corpuscles chiefly by their behaviour when treated with acetic acid, and also by their granular surface. {Plaie I. Fig. 6. Plate II. Fig. 3.) Pus soon sinks to the bottom in acid urine, which is left at rest, and when the supernatant urine is removed by a pipette, may be collected and subjected to microscopical examination. Blood-corpuscles are not unfrequently mixed with purulent sediments, and may be recog- nised by their red colour, or stiU more surely by the microscope. In either case[the clear, filtered urine wiU contain albumen (Sect, xix., c.) . In alkaline urine pus undergoes essential changes, which are of par- ticular interest, by reason of the fact, that alkaline urine is often evacuated containing a considerable quantity of pus, in cases of catarrh of the bladder, &c. Alkalies convert pus into a muco-gelatinous mass, which adheres to the side of the vessel, exhibits no pus-corpuscles under the micro- scope, and may be readily taken for mucus. In most cases, how- ever, in addition to this tough mass, pus-cells may be found suspended in the urine, if it be examined soon after it is passed. Pus may be readily distinguished from mucus by this behaviour Tinder the action of alkalies. The sediment in question is treated with concentrated caustic-potash ; if it consist of pus, the gelatinous mass above described is formed, and if of mucus, a thin flocculent fluid. (Donn6's Test for Pus.) As the serum of pus contains albumen, albumen is always present in urine, which contains pus ; consequently, we can always form an approximate estimate of the quantity of pus from the amount of albumen in the filtered urine — ^provided, of course, there is no co- existing albuminuria. The presence of blood in the urine must also be taken into consideration, as a source of part of the albumen found in the urine. 130 URINARY CASTS. section xlv. Ueinaey Casts oe Cylindees.- In many diseases, and especially in Bright's disease of the kid- neys, peculiar tubular or cylindrical bodies are found in the sedi- ment of the urine. These bodies have long been the subject of in- vestigation. They differ somewhat in their structure, and have consequently been divided by Lehmann into three different kinds : — 1. Cylinders, which appear to be formed of the epithelial covering of the tubules of the kidney ; these are found in almost all cases of inflammatory irritation of the kidneys, and form regular cylinders around which small cells and cell-nuclei appear grouped, somewhat in the form of a honeycomb. {Plate I. Fig. 4.) 2. Cylinders which appear to have been formed from exudation effused into the tubxdes of the kidney, whose form they retain. These cylinders consist of small granular rods, which are frequently garnished with blood- and pus-corpuscles. They seem to consist of flbrine, for they readily dissolve in alkalies,^— the blood- and pus- corpuscles, which they enclose being also thereby partly destroyed, and partly left in suspension in the fluid. They are always present in Bright's disease. (Frerichs, Die BrigMsohe KranMeit. Plate I. Mg.&.) 3. Lastly, we sometimes meet with cylinders which are hollow, and possess hyaline walls of so fine a structure that it is with difficulty they can be distinguished from the surrounding fluid. These often appear collapsed, and in folds, or as if twisted around their own axis. In the chronic form of Bright's disease they only appear singly. (Lehmann.) Plate I. Fig. 5. Teds. — ^To demonstrate the presence of these bodies, the urine, which is in most cases highly charged with albumen, is allowed to stand for some hours in a conical glass. The sediment which forms is generally white and flaky, or if other substances are present, may consist of a thickish mass. In this sediment, diamined with a 180 to 200 magnifying power, the presence of the casts, &c., is readily ascertained. Sometimes, indeed, the hyaline cylinders (described at S) may escape observation, but tiey are at once rendered visible by the addition of a solution of iodine in iodide of potassium, which gives SPERMATOZOA. 131 them a yellow colour. When, as often happens, only a few cylinders are present, different specimens must be prepared and carefully examined. Fat, pus, epithelium, blood, &c., frequently co-exist with the cylinders in these sediments. Care should be taken not to mistake the coagulated mucus in acid urine (described in Section xm.), which is often found mixed up with urate of soda, for granular urinary casts. [Plate II. Fig. 3.) See Mucus, Sect. xlii. Cancer and tubercle are described elsewhere. section xlyi. Speematozoa. Spermatozoa appear under the microscope as elements of a spherical, or of nearly a spherical form, having a well-defined tail, which is generally pointed, varies in length, and is capable of spon- taneous motion. We find them in the urine after coitus, &c. ; and they have also been frequently noticed in the urine of patients suffer- ing from typhus. The form of these spermatozoa is so characteristic, that they can- not possibly be confounded with any other microscopic objects. They are also very indestructible, a fact which much assists us in the diagnosis of semen in the urine. The urine is allowed to stand at rest for some hours in a conical-shaped glass, so that the sperma- tozoa may be separated, and sink to the bottom with the flocculi of mucus. The greater part of the supernatant fluid is then carefully poured off, and a drop of the sediment from the very bottom of the glass placed under the microscope. If the little thready bodies of spermatozoa are present, they are at once recognised by their tadpole-like form, above described. A magnifying power of 300 to 400 diameters is requisite for the purpose. In pure water, as well as in urine, especially if it be very acid or alkaline, they soon lose their movements ; they also often undergo a peculiar change of form, the hinder part pf the tail being cui'ved round towards the fore part, and spirally rolled up. The observation of Lehmann is worthy of note, viz., that urine which contains semen very readily becomes k2 132 FUNGI.— INFUSORIA. alkalinCj and that in its mucous sediment, peculiar, fine, lamellar- like, and very transparent, spets are to be found, although very few spermatozoa are visible. Clemens has frequently noticed the passing away with the urine of im- perfectly-formed semen ; the spermatozoa lying in the cells and adhering by their head and tail to the envelope ; the tails seldom showed any signs of motion, which only takes place in perfectly-formed semen. Besides these spermatic cells, Clemens often observed in the urine of patients suffering from spermatorrhoea, roundish cells of 0-0033 to 0'005"' diameter, filled with fine granules, which lay for the most part on one side of the cell. These cells are in reality the mother-cells of the spermatozoa. Such elementary bodies are generally found in the last drop of urine of patients who have been much depressed by loss of semen, and also in typhus-fever patients. (Canstatt's Jahresbericht, 1860, p. 285.) section xlvii. Fungi. — Infusoeia. Pungi and Infusoria are always found, microscopically, in urine which has stood for some time. They are also sometimes present in urine which has undergone decomposition within the bladder, as for instance, in cases of catarrh of its mucous membrane. The infusoria are generally very small, and most frequently appear as point-like monads, or as a string of pearls or branched vibrios. At the commencement of the decomposition of the mine only few vibrios are observed, but as the process advances they become more numerous, collect on the surface, and mixed ^yith triple-phosphates and fungiform a pellicle, which breaks up, and finally sinks to the bottom. Dr. Hassal noticed a second kind of infusoria in the urine, the Bodo urinarius ; those which were alive and in motion were oval and round, ^' long, and ^' broad, granular and like mucus-corpuscles. They were often broader at one end, and furnished at different points with one or more, generally two or three, threads or ciliEe. They multiplied by division. Dr. Hassal considered them to bear a close resem- blance to the Bodo intestmalis of Ehrenberg. They most commonly are met with in albuminous urine associated with vibrios. The species of fungus most frequently met with is the urine-fermentation FUNGI.— INFUSORIA. 133 fungus, having the form of roundish, or oral nucleated cells, which are formed out of the decomposed mucus. These cells exist singly, or are associated together in rows and groups. {Plate II. Figs, % and 4.) They are frequently, in advanced stages of the urine-fer- mentation, mixed with the sediments of urate of soda, free uric acid and oxalate of lime. The fungoid cellules, formed during the fermentation of diabetic urine, are oval, transparent, and considerably larger than those above described, and in their form and mode of development correspond with the ordinary yeast-plant. Their usual form is oblong, occa- sionally it is round, their size is variable; aU of them have a distinct round nucleus, which often looks like a hole. Together with them, threads of confervse are formed, containing sporules which are forked and branched; and when the urine has stood for some time, they often form a dense confused mass, which occupies the whole field of the object-glass. Dr. Hassal has found, besides these, other fungus-forms in alkaline urine which con- tains albumen. Sarcinse have lately been found by Dr, P. Munk in the urine of a man 43 years old. The freshly-passed urine had constantly an alkaline reaction, was thick, and slightly albuminous. Numerous white transparent bundles of sarcinse, somewhat rounded at the corners, were seen under the microscope, together with epitheHa, a few blood-corpuscles, pus-cells, vibrios, and triple-phosphates. The urine deposited, on standing, an abundant whitish sediment con- sisting chiefly of sarcinse and the other substances above named. During May and June this sediment formed from ^ to 5', part in the whole of the urine passed during 24 hours, and collected in a glass. In autumn the sarcinse decreased consider- ably, and almost vanished in October. Dr. Munk found in the urine single sarcinse, and also bundles containing 8, 64, and 512 sarcmse. (Fig. 3.) He also observed masses which resulted from Fig. 2. M ^^^M^ ^ *^ W^ L^ « ^^^ y \ ^^^^^M •t« m Fig. 3. 134 OCCASIONAL CONSTITUENTS OF THE URINE. the breaking-up of the large bundles. Single sarcinse were in size from 0-0008 to 0-0016 MM, ; the bundles of 8 sarcinse had a breadth of 0-0016 to 0-0034 MM.; those of 64 a breadth of 0-0032 to 0-006 MM. ; those of 512 a breadth of 0-008 to 0-012 MM. The sarcinse of the urine are therefore much smaller than the sarcinse found in the stomach. The peculiar form of sarcinse, as described by Yirchow, was distinctly recognised in the bundles and especially when the objects were rolled over under the microscope. Neither tables nor plates were seen. The reaction of the urine appeared to have no influence over the development of the sarcinse; in this case it was always alkaline; in the case observed by Welka it was sometimes acid, and occasionally neutral. {ArcMv f. Path. Anatom. u. Thysiol., Vol. xxii,, p. 570.) section xlviii. Occasional Constituents op the Ueine. Under this head are to be considered the changes which substances undergo in their passage from the blood into the urine. The im- portance of the study of these changes is evident enough. It opens to us an insight into the manifold metamorphoses, to which the materials that form the body are subjected, and into the mechanism of the animal body. A very extensive series of investigations, followed out into their smallest particulars, would, however, be necessary to enable us to arrive, in this way, at any useful and general conclusions. The most satisfactory way of proceeding is, therefore, to observe the results which follow when organic sub- stances — whose chemical composition is thoroughly known, and whose products of decomposition have been closely investigated — are introduced into the body ; from a consideration of the changes which these undergo in the body, we may arrive at conclusions concern- ing the chemical forces which are in action there, and which more especially preside over the organic metamorphoses going on in the blood. Of oxidising agents permanganate of potash is the most serviceable in such investigations, for its action on the bodies in question is particularly well marked, and, moreover, the oxidation goes OCCASIONAL CONSTITUENTS OF THE URINE. 135 on in the blood just as it does in an alkaline solution. Thus by the action of permanganate of potash the same products have been obtained from uric acid as are generated in the body when the respiration is normal or more or less disturbed : viz., carbonic acid and urea, or carbonic acid, oxahc acid and urea, or, lastly, allantoine, carbonic acid, oxalic acid, and urea.* A further illustration of the fact is given by guanine. Guanine introduced into the body is in great part converted into carbonic acid and urea ; and the same bodies (together with oxalic acid and oxyguanine (?) may be obtained from guanine by the action of per- manganate of potash. Wohler, assisted by Prerichs, was the first person who worked out this subject, and the results of his investigations are given at length in the Annal. d. Chem. u. Pharm., Vol. Ixv., p. 335. Zeitschrift fir Phymlogie, Vol. Ixv., p. 305. The following facts must be premised, before we proceed to the consideration of these accidental substances. It is evident, as a rule, that only those substances can pass un- changed iT\Jio the urine which, in the first place, do not serve for nutrition, and which, secondly, are soluble in water, and have no tendency to form insoluble compounds with the organic or inorganic materials of the body. Consequently, the most soluble of the alka- line salts will readily pass into and be found unchanged in the urine. If again we take into the body a substance which is not oxidised, but which has a tendency to undergo oxidation, we shall find it again in the urine in an oxidised state. Sulphide of sodium, which always passes into the urine in the state of sulphate of soda, is an example of this. All substances, however, which form, with the organic matters of the body, compounds that are insoluble, or diffi- cult of solution, such, for example, as most of the metals form vnth proteiae-bodies, only reappear in the urine when they have been taken in large quantities — a fact pointed out by Orfila. Moreover we find that many organic substances undergo the same changes in their passage through the body, as they may be artificially made to undergo out of the body. Others, again, become so com- pletely oxidised,, that it is not possible to find either them or the products of their decomposition in the urine. There are, on the * Stadeler, as we have already mentioned, found allantoine in the urine in cases where the respiration was impeded. \_ 136 INORGANIC COMPOUNDS. other hand, some substances which give off oxygen and appear in the urine in a lower stage of oxidation. Lastly, we have to consider the length of time required by any substance to pass into the urine. We find as a rule, that substances easy of solution are quickly separated from the body with the urine. There appears, however, to be some difference in individuals in this respect. Thus, Lehmann, for instance, has observed, that not a trace of iodine could be found in the urine of several individuals, twenty- four hours after they had taken a dose of 10 grains of iodide of potassium, whilst in others it was still present after an interval of three days. "We have now to consider the conduct of different substances in the body : — 1. Inorganic Compounds. A. Salts of the heavy metals. — The salts of the heavy metals form, with many animal substances, and particularly with proteine- bodies, compounds difficult of solution, consequently they only ap- pear in the urine when large quantities of them have been introduced into the system. In this way, Orfila found antimony, arsenic, zinc, gold, silver, tin, lead, and bismuth in the urine after large doses of the metallic salts had been taken ; but they could only be found in the liver and its secretions, as well as in the solid excrement, when taken in relatively small and oft-repeated doses. Iron, when taken inter- nally may be often immediately discovered in fresh urine by the ordinary tests ; but in other cases again it can only be foimd in small quantities in the ash of the residue of urine (Lehmann). To ascertain the presence of the heavy metals in urine, the process must be followed, which is employed injudicial cases, where salts are found mixed with organic matters. On this head, therefore, I shall refer the reader to Presenius' Introditction to Qualitative Analysis, 11th edition. Mercury. — Electrolysis has of late been frequently employed for determining the presence of mercury in the urine ; and on account of the importance of the subject, the process employed by Schneider is here described. Five grammes of chlorate of potash are dissolved in each litre of the urine to be tested, hydrochloric acid is added to impart a strong acid reaction, and the mixture then heated in a water-bath. If a dark coloration should appear during the evaporation, a further quantity of the oxidising agent is added, and the heat continued, until, on testing a portion, it is found that on the addition of MERCURY IN THE URINE. 137 hydrochloric acid, no bleaching action is exercised on the colouring- matters. There is, however, no advantage in continuing the evapo- ration of the urine until the salts crystallise, for the fluid becomes of a dark colour when concentrated up to this point. Schneider satisfied himself, by repeated experiments, that highly concentrated solutions do not serve well for the purpose of electrical analysis. In most cases a large quantity of urine is required. Schneider collected the whole of the urine passed during from three to six days — 7 to 15 litres — and after the addition of potash and hydrochloric acid, concentrated it to ^ or j. For the electro- lysis of the arine thus prepared he made use of a Smee's battery of six elements — a constant battery is equally serviceable — whose anode consists of a platinum plate four centimetres broad, and whose cathode of gold wire one millimetre thick runs into a club- shaped thickened extremity two millimetres in diameter. In order to limit the separation of the mercury to the smallest possible surface, the electrolysis is conducted in a vessel of greater breadth than height. The action is kept up for eighteen to twenty-four hours. For the further proof that mercury is present on the gold wire, at the con- clusion of the experiment, the following proceeding is resorted to. The gold wire is introduced into a carefully cleaned glass tube, drawn out at one end into a fine capillary point, and then melted and closed at the other. The wide end of the tube, containing the metal, is then heated to redness ; and if in the course of about five minutes a deposit takes place on the colder part of the tube, the deposit is then driven by heat towards the capillary end of the tube ; and the metal again . heated to see if a new sublimate appears. The portion of the tube contaiaing the metal is now separated by fusion from the capiUary portion so as to leave a short piece of the wider tube connected with the capillary portion and forming a kind of bulbular expansion. When cool the bulb is opened by nipping off the drawn-out pointed extremity, so that a little iodine may be introduced into it by means of a glass thread, and is then again closed up. The iodine-vapour rises up into the capillary portion of the tube, and disappears at the part where the mercury exists ; and then accord- ing to the quantity of iodine employed, brown, red, or yellow rings appear. If the brown rings are carefully heated, iodine is driven off, and red rings of iodide of mercury remain. The red as well as the yellow rings volatilise when more strongly heated, but are imme- diately re-deposited of a red colour, on a cooler part of the tube ; 138 ELECTROLYSIS. sometimes, however, they take a yellow hue. The yellow rings con- sist of prot- and sub-iodide of mercury ; they arise when the quantity of the iodine introduced is insufficient to form prot-iodide. On the introduction of another crystal of iodine into the capillary tube and heating, the yellow rings are readily converted into red. The red crystals appear under the microscope as rhombic octahedra, with their faces often superimposed, so as to resemble the feathery forms of sal-ammoniac. No mercury was discovered by electrolysis in three trials, in which the urine contained much iodide of potassium, the urine having been concentrated to -k after the addition of chlorate of potash and hydro- chloric acid. When, however, the urine was treated with sulphuric acid containing nitrous acid, and evaporated in a water-bath until the whole of the iodine was driven off, the cathode showed distinct traces of mercurial silvering, and subsequent testing by heat gave the manifest reaction of mercury. Consequently it is advisable that the urine to be tested should be first of all freed from any iodine which it may contain. This may be readily accomplished by heating it in a warm bath after the gradual addition of sulphuric acid containing sulphurous acid. Kletzinsky evaporates the urine (previously treated with chlorate of ■ potash and hydrochloric acid) to dryness, and then operates upon the residue with ether to separate the sublimate. This process, according to Schneider, is not to be trusted, for the residue contains the sublimate in union with the alkaline chlorides in the form of a double salt. These double compounds are almost insoluble in ether, and consequently sublimate cannot be dissolved by ether out of the residue of evaporated urine, when completely dried. I will give Schneider's results : — 1. The presence of mercury was not shown by electrolysis in the urine of syphilitic patients, who had never been subjected to mercurial treatment; 2. Similar negative results were obtained on testing the urine of persons who had been previously treated with mercury. The investigations were made in cases in which the mercurial treatment had been employed 14 days, 5 months, and 6 months previously; 3. During the internal use of the mercurial preparations the urine always contained mercury; 4. The generally received opinion of the action of iodide of potassium on the metals which are retained in the body is by no means sup- ported by the experiments of Schneider. B. Salts of ike Alkalies. — 1. Alkaline carbonates always re-appear ALKALINE SALTS IN THE URINE. 139 as such in the urine, although a portion of them is douhtless neutralised hy the free acid of the gastric juice. They render the urine either neutral or alkaline. Pree carbonic acid, effervescing wines, beer, and bicarb.onates of the alkalies occasion an increased separation of oxalate of hme in the urine, the quantity of free car- bonic acid being at the same time increased in it. 2. The ammonia of ammoniacal salts passes for the most part un- changed into the urine, I performed some experiments on this point in a young man, 20 years of age; he passed in 24 hours, as an average of twelve experiments, 0'6137 gramme of ammonia, corresponding with 1"9305 grammes of sal-ammoniac. 10 C. C. of a solution, which in the 10 CO. contained exactly 2 grammes of sal-ammoniac, were taken in the evening with a glass of water, the urine carefuUy collected for 24 hours, and then subjected to analysis. The experiments were carried on for 5 days, and during this time 9'957 grammes of sal-ammoniac were secreted in place of the 10 grammes which had been taken. (See Jov/m.f. Fract. Chemie, Vol. 64, page 281.) Whether or not a portion of the ammoniacal salt is really converted into nitric acid in the body, as asserted by Dr. Benoe Jones, is, at present, undecided. The objections, however, taken by Lehmann to this opinion are not well founded, for sulphurous acid is not capable of decomposing hydriodic acid, nor consequently of forming iodide of starch. If, in the distillation, we make use of oil of vitriol for the separation of any nitric acid which may be accidentally present, we must pre- viously free the sulphuric acid most carefully from the nitrogen- compounds, which are always present in it, and might, otherwise, occasion the nitric acid reaction. 3. Perridcyanide of potassium appears again reduced to the state of ferrocyanide of potassium. 4. Ehodankalium passes rapidly into the urine, even when taken in small quantities. 5. Sihcates, chlorates, and borates of the alkalies, when taken, re- appeaX'in the urine. 6. Iodide of potassium also passes into the urine, and may in most cases be readily discovered there by the starch-test. 7. Sulphide of potassium appears in the urine partly in the form of a sulphate, and partly unchanged. c. Salts of the Alkaline Earths. — '1. Soluble salts of baryta, when taken in tolerably large doses, may be found in the urine. 140 ALKALINE SALTS IN THE URINE. 2. Salts of magnesia and lime do not pass into the urine, or, at least, only in very minute quantities. II. Organic Compounds. A. Free Organic Adds. — 1. Organic acids, such as oxalic, citric, malic, tartaric, succinic, and gallic acids, when taken into the body in a free state, pass unchanged into the urine, according to Wohler. 2. Acids of the Benzoic acid group. — The changes which the class of acids, comprised under the head of the benzoic acid group, undergoes in the body, are interesting. It has been long known, that benzoic acid, as well as cinnamic acid, when taken into the body, reappear as hippuric acid in the urine. In like manner nitro-benzoic acid passes into nitro-hippuric acid in the body, and is separated as such with the urine. Kraut and Bertagnini have also succeeded in showing similar changes in the passage of toluylic acid and salicyHc acid through the body. The decomposition is the same in the case of all these acids, two equivalents of water being separated, and the elements of glycocoll (Ci Hj N OJ taken up, as here shown : — . (1) 0uH.O4 + C,H,NO,- 2H0 = CieH,N0e (Benzoic acid.) (Glycocoll.) (Hippuric acid.) (2) C,,HeOe + C,H,N0.-2H0 = C,sH,N0, (Salicylic acid.) (Glycocoll.) (Sahcyluric acid.) (3) C,eH,04 + C,H,N0,-2H0 = C^H„ND, (ToluyHc acid.) (Glycocoll.) (Toluric acid.) W9j^H,JQ^ + C,H.Na-2H0 = ^^oll^^« (Nitrobenzoic acid.) (Glycocoll.) (Nitrohippuric acid.) In addition to these, benzoic ether also produces hippuric acid. Oil of bitter almonds again is probably in the first instance con- verted into benzoic acid, and as such passes into the condition of hippuric acid. Lastly, it may be observed that benzoic acid,- when taken internally, has been found by Lelunann unchanged in the sweat. The other acids, which belong to the benzoic acid group, anisic acid, cumaric acid, and cuminic acid, appear, from experiments which have been made with them, to pass unchanged into the urine. Tlie changes which cinnamic acid (ds Hs OJ goes through in the THE BENZOIC-ACID GROUP. 141 body, in passing into hippuric acid (C,g Hg N OJ, were for a long time not well understood, but later researches into the constitution of this acid have now explained them. Chiozza, in his study of the anhydrous acids, observed, that cinnamic acid was split up into acetic acid and benzoic acid by the action of caustic potash. C,,H,0, + 4H0 = C,H,0, + C,,H,0, + 2H (Cinnamic acid.) (Acetic acid.) (Benzoic acid.) Taking this fact as a foundation for his operations, Bertagnini attempted, and with happy results, the artificial formation of cin- namic acid, — premising that acetic acid and benzoic acid, grouped according to their atomic constitution, were present in it. The cinnamic acid was prepared by the action of chloracetic acid on oil of bitter almonds at 120° to 130° C. (248° to 266° Fahr.). There can, therefore, be no doubt that cinnamic acid is also decomposed into acetic acid and benzoic acid within the body, and that the benzoic acid subsequently appears in the urine in the form of hippuric acid. The interesting researches of Kiihne and Hallwachs prove, that the conversion of benzoic acid, &c., into hippuric acid, &c., only takes place when bile-constituents (glycocoU or glycocholate of soda) are present. I give from their work the following results : — a. Benzoic acid or benzoate of soda, injected into the jugular or the crural vein passed away in great part unchanged with the urine. b. Benzoic acid taken by the mouth passed unchanged into the urine, when the secretion of the hver was cut off. c. The simultaneous injection of benzoic acid and bile, or glyco- cholate of soda, or pure glycocoU, into the blood, caused an abun- dant separation of hippuric acid with the urine. Prom this it follows, as might have been anticipated, that benzoic acid is only converted into hippuric acid in the blood, when glycocolate of soda, or pure glycocoU, is present there. The last experiment shows the possibility of the simple union of benzoic acid with glycocoU in the blood of the living body two equivalents of water (necessary for the formation of hippuric acid) being separated. would still fall within the limits of un- avoidable errors of observation. "W. Kaupp [Archiv. f. physiohg. Heilkunde, 1856, part 4) also found Trapp^s formula correct. The recent researches of Neubauer, however (compare p. 156, and p. 268), tell rather in favour of Haser's formula. The coefficient 2, by its simplicity, and by the readiness with which it allows the calculation to be made men- tally, recommends itself to us in the estimations and calculations made at the bedside of the patient, which never can be very accurate. In cases of this kind differences in temperature of the urine, if they do not exceed two degrees, may be disregarded. 2. "What practical conclusions can the physician draw from a knowledge of the quantity of solid residue, and of the specific gravity of the urine ? First of all, from the specific gravity we are enabled to calculate the weight of a measured quantity of urine. The calculation is simple enough : 1000 C. C. of urine of sp. gr. 1-024 weigh 1'024 grammes, and so on. Then, again, the specific gravity of the urine, and the quantity of solid constituents as thereby calculated, or as ascertained by direct experiment, often give us important indications concerning the quantitative changes going on in the nutrition of the body, and particularly concerning the quantity of solid parts and of water, which have been separated through the urine under certain condi- tions and in a certain time. OF THE URINE. 363 To judge of these conditions it is absolutely necessary for us to have an exact idea of the natural state of the urine. The mean specific gravity of the normal urine is in the adult male about 1020. From this we may calculate, that an average quantity of from 55 to 60 grammes of solid constituents are daily passed with the urine, the average daily quantity of urine being from about 1400 to 1600 C. C. A man passes on an average 4*1 grammes of solid matters per 100 kilogrammes of weight; and 1"5 grammes per hour per 100 centimetres of height. By these figures we are enabled to recognise and judge of many abnormal states of the nutrition. The daily secretion of solid constituents in the urine appears in most acute diseases to be somewhat less than in health; instead of 60, it reaching only to 40 or 50 grammes. Sick persons, however, in most cases only take fluids, which contain few solid constituents, and consequently are in somewhat the same position as starving per- sons. The separation of the solid constituents of the urine takes place LQ their case at the expense of the body, they live as it were upon their own flesh, and so grow thin. The estimation of the amount of solid constituents of the urine is of especial interest in all those cases, in which the secretion is much increased in quantity — polyuria. These cases may be divided into two well-marked groups, according to the quantity of the soUd constituents contained in the urine : 1. In one group, the over-abundant urine contains an abnormally large amount of soHd constituents, much more, in fact, than is intro- duced into the body with the food. Hence arise defect in nutri- tion, and consequently weakness and wasting of the patient. The cases belonging to this group are included under the general name of diabetes. They may, however, be subdivided into two other minor groups, according as the urine either contains sugar (diabetes mellitus), or is free from sugar, but contains a large amount of other solid constituents (diabetes insipidus) ; 2. In the other group, the over-abundant urine is of low specific gravity, and contains comparatively few solid constituents. Water, which can be readily restored to it, is the chief constituent separated from the body. In this case there is neither wasting of the body nor hectic ; but on the contrary, the process is sometimes beneficial, 364 SOLID RESIDUE the separation of morbid products from the body being thereby favoured^ as happens in many cases of hydrsemia and dropsy. This form of increase of the urinary secretion (hydruria) is therefore totally different from the diabetic form. Examples. — A woman, 31 years of age, who had long suffered from symptoms of anaemia and hysteria, with giddiness, headache, spasms of the cervical muscles, hypereesthesia of several of the verte- brae, pale face, &c., passed an exceedingly large amount of urine, the daily average, as calculated from fourteen days' observation, amounting to 3,080 C. C. The specific gravity of the urine was not much less than natural, but the amount of solid constituents in it, according to calculation, reached an average of 87 grammes daily, a quantity much greater than normal. The maximum quantity passed in 24 hours was 136 grammes, which is more than double the normal quantity. In this case, which was one of true diabetes insipidus, the increased separation of solid constituents combined with deficiency of nourishment, was, manifestly, the chief cause of the symptoms. She soon improved in health under a generous diet, with steel, and other tonics. A man, 35 years old, of Herculean frame of body, suffering from rheumatism of the neck, passed a very large quantity of urine, the daily average of twenty-four observations being 2983 C. C. Its specific gravity, however, was very low, being between 1'005 and 1'012; and the average quantity of solid constituents less than normal, amounting only to 42 grammes. The man did not appear to suffer in any way through the increased secretion of urine, and his case was evidently one of simple hydruria, not of diabetes. Many other deductions concerning the quantitative relations of the nutritive materials of the body in disease may be drawn from the specific gravity of the urine, and from the amount of its solid constituents. These will naturally present themselves to the mind of the physician. Thus, for instance, the relation of the solid con- stituents, which are separated with the urine, may be compared with the quantity of matters which are separated through the skin and the lungs ; and when the quantity of solid matters taken with the food is measured at the same time, we obtain the relative quantity of materials taken into the body, and separated from it. A know- ledge of aU these facts is of great importance in reference to the nutritive changes going on in disease ; and the means for arriving at them are of a kind which are capable of being readily introduced OF THE URINE. 365 into every clinique. So little, however, has as yet been done in this field of observation, that no positive conclusions have been at pre- sent arrived at in relation to them. The specific gravity of the urine, also, gives the physician indica- tions, which though of themselves not sufiicient to lead to any dis- tinct conclusions in diagnosis, prognosis, or treatment, are never- theless of service in leading to further investigations. The following considerations may be placed under this head :— Urea is the chief solid constituent of the urine. It generally equals in quantity all the other solid constituents of the urine to- gether, and sometimes exceeds them. Consequently, the specific gravity of the urine may serve to point out approximatively the quantity of urea in it. Such a mode of determining the quantity of urea is, however, very uncertain, and will never replace the direct method of estimating it, which is readily performed. When the quantity of the urine is much less than normal, and its specific gravity is high, we may usually conclude, in the case of healthy people, that its condition has been caused by abstinence from drink,' or by increased perspiration, and in the case of the sick by acute disease. When the urine is much greater than normal and of low specific gravity, we may conclude that a large quantity of watery fluid has been taken. In the sick, who are suffering from hydrsemia or dropsy, urine of this kind is a favourable sign, and shows that the system is making an efi'ort to get rid of the super- abundant water collected in the blood or in the tissues. If urine is passed in large quantities, and has a high or even its ordinary specific gravity, we must test it for sugar : if there be no sugar in it, the case is one of diabetes insipidus. If the quantity of urine is not increased, or if it is diminished, and yet its specific gravity is low, we may suspect the existence of an impediment to the secretion of urea, and in such a case must fear the occurrences of those symptoms, which result from the retention of urea in the body (ursemia). The solid residue of the urine is diminished in most chronic diseases, excepting diabetes. An increase of the residue indicates a more active condition of nutrition, and is therefore a favourable sign. On the other hand, an increase of the solid constituents of the urine in acute diseases, when at their height, is an unfavourable sign, because the inanition which always accompanies such cases is thereby increased and favoured. 366 SOLID RESIDUE The specific gravity of the urine, as a rule, iu acute febrile diseases stands in a ratio inverse to that of its quantity. The specific gravity, in fact, increases during the acuteness of the attack, in proportion as the quantity of the urine diminishes ; it falls with the increase of the urine, and during convalescence often sinks below the normal. We must, however, be cautious in founding any differential diagnosis upon mere observation of the specific gravity of the urine in diseases which in other respects present a similar train of symptoms. Thus, in typhus, it has been stated that the specific gravity of the urine increases much less than in other acute, and especially inflam- matory diseases ; and that, in fact, in the essentially typhous period of the disease the specific gravity was only 1'017, whilst in acute affections of the brain, in meningitis, from the beginning to the end, it was as high as from 1'028 to 1"035. Hence this difference in specific gravity has been used as a means of diagnosis in those cases occasionally met with, in which it is difficult to distinguish between typhus and such affections of the brain. — (A Ziegler, TJroseopy at the Bedside of the Patient, Erlangen, 1861, p. 8.) The idea of our being able to distinguish diseases by one single phenomenon, and one which in comparison with the other symptoms appears very unimportant, we must ascribe to the now happily admitted ontological method of comprehending diseases. By this method of division and classification of diseased processes, just as in the division of animals and plants in genera and species, the external appearances alone, with their thousand accidents are seized upon, instead of the essential character of the phenomena, their causes, and connections, and dependance being kept in view. Conclusions of such a kind cannot be rightly deduced from one single symptom of disease, unless its existence in such disease has been confirmed by numerous observations, and unless the cause of the symptom and its indication have been in some degree explained, and its necessary relation with the existing disease^ demonstrated. In the case before us, there is not only wanting a satisfactory explanation of the diminution of the specific gravity of the urine in typhus, but the very fact itself may be doubted as being true in aU cases. I can only speak of it as true in some solitary instances. At least, in numerous observations which I have made of the urine in typhus, in cases where there was a high degree of fever and a certain degree of reaction present, I found at the acme of the disease, that the specific gravity of the urine was high, as the following cases show : OF THE URINE. 367 (The figures in all cases indicate the specific gravity of the ■whole quantity of the urine passed in 24 hours during the height of the disease. The frequent blanks which appear^ result from the circum- stance that it was not always possible to collect the whole of the patients' urine free from fsecesj on account of its being often passed involuntarily with the fseces, a circumstance which frequently renders an exact quantitative analysis of the urine in typhus very difBcult, and indeed almost impossible ;) Case 1.— 3rd day, 1-019— 1-029 —1-031 —1-026 —1-024 — 2 days omitted— 1-019 —1-021— 1-016. Sul sidence of the fever. Convalescence. Case 2.-4th day, 1-028—1-029 —1-027—1 day omitted -1-028 — 1-027. Death. Case 3.— 2nd week, 1-019 —1-020 —1-018— 1-020— 1-022 — 1-026. Slow convalescence. The specific gravity of the urine in typhus, as in other acute diseases, falls as the fever departs and convalescence arrives. On the other hand, I must admit, that there are cases of typhus in which the specific gravity of the urine even during the height of the disease is low, and even less than normal. The following are examples of this :— Case 1.— 1-008— 1-014-1-017 — 2 days omitted —1-017 — 1-027 — 1-015-1-014 —1-015 —1-014 —1-012, Death, Case 2.— 1st week, 1-018 to 1-020. 2nd week, 1-012 to 1-015. Then convalescence. Case 3.— 1-021 —1-020—1-015 _1-014—1-010 —1-006 — 1-010 —1-012-1 -013 —1-015 -1-011. Convalescence. In all these cases the fever, from the beginning, had a distinctly marked adynamic character, and the general condition of the patients, especially the weak and distinctly double-pulse, afibrded much more trustworthy signs whereby to distinguish the case from one of inflammatory affection of the brain, and its membranes, than the specific gravity of the urine, which, moreover, I have not always found so remarkably high in meningitis as Ziegler states it to be. Besides this, diminution of the specific gravity of the urine occurs in other forms of fever, as well as in typhus, when they assume a weU-marked adynamic type, as in pyaemia, putrid fevers, &c. 368 PIGMENT -MATTER. section cxiii. Quantity of the Pigment-Mattee oe the Ueine. J. YoGBL, ArcMv fiir gemeinscAqftl. Arbeiten, vol. i. p. 137. The colour of the urine and its pigment matters have been already spoken of on different occasions. (Sections ix. and lit.) It is very difi&cultj indeed almost impossible, to obtain an accurate estimation of the quantity of pigment-matter in the urine, such as we are ac- customed to expect at the present day from quantitative chemical analysis. I have, therefore, proposed a method, which is much more simple and easy, for estimating the colouring-matter, and which may be practised by the physician. This method, it i« true, gives only approximative results, but it affords us interesting and valuable conclusions, which may be ^applied in diagnosis, prognosis, and treatment. This method, and the mode of employing it, has already been described iu Section lit. ; by means of the gradations of colours given in the Table IV., anyone can make use of it. As objections of different kinds have been made to this method, I will here shortly answer them :-7- First of all, it has been objected, that the colour of the urine does not depend upon any one single body, but upon several different pigment-matters. This is true enough, and has been already ad- mitted. (Section lxxxiv). But the abnormal colours of the urine, whether accidental, as when caused by rhubarb, senna, &c., or whether depending upon bile-pigment, uroxanthine, uroglau- cine, urrhodine and uroerythine, are comparatively rare, and, when present, may be readily recognised. In all such cases it would, doubtless, be a mistake to make use of the table of colours for the quantitative estimation of the pigment-matter. No fair exception, however, can be taken to the method because it is not applicable in such exceptional cases ; it very rarely indeed happens, in any quan- titative chemical investigation, that a method is applicable in every possible case. In by far the greater number of cases the urine, especially when filtered, contains either none, or only a very small quantity, of such abnormal colouring-matters ; being in most cases coloured chiefly by the ordinary colouring-matter, Heller's urophaeine. Moreover, it has been objected, that the shades of colour given in IN THE URINE. 369 the table of colours do not run in a regular series, and that through dilution of brown or of very high-coloured urine, for instance, we should not obtain exactly the same shades of colour as pale urine yields ; and consequently, that the statement, that red urine contains 32 times more, and brownish-red urine 64 times more colouring-matter, than pale yellow, is not sufficiently accurate. I am quite willing to admit, that the colouring-matter of the urine is not invariably the same under all circumstances, but that it may present modifications, which exercise an influence both over its colouring power, and over the particular shade of colour produced by it ; but this is no reason why we should not use the colour of the urine for the approximative estimation of its pigment-matter, taking care not to fix the limits of possible errors too low. Hitherto, notwithstanding the praiseworthy labours of Scherer and Harley, we have not been able to obtain the colouring-matter of the urine in a pure state, and consequently the fixing of the Hmits of error in this case is completely arbitrary. I believe, however, that I am rather above than below the mark, if I assume, that the possi- ble error may exceed by J or even J the number found. Varia- tions, therefore, which exceed these, indicate with certainty a difference in the amount of colouring-matter in two kinds of urine when compared together j whilst other variations, which are less than these, may be considered as of no value. If, for example, the quantity of pigment-matter, which a healthy person passes in 24 hours, amounts to 4, and we find that a sick person passes from 16 to 20, we may be sure that there is a con- siderable increase of the pigment-matter in this case, to the extent of at least 2 or 3 times the normal amount. So, also, we may be sure that the quantity is abnormally diminished, if the calculation only gives 1. But if the quantity is found to amount to 3'5 or 4*5, we cannot conclude with any certainty either as to its increase or diminution. Por these reasons I consider I am right in maintaining, that useful information may be obtained from this method, provided it be cautiously applied ; and that, if the hypothesis here used as a ground of explanation of its signification be correct, it may yield im- portant explanations of the nutritive processes — of the destruction of the blood-corpuscles — explanations of stiU greater value, because the means which the physician possesses, of forming an opinion as to the extent of this part of the nutritive function in the sick, is very limited. bb 370 PIGMENT MATTER The indication afforded by an increase or a diminution of the pig- ment-matter of the urine may be derived from the following considerations, which are indeed in part only hypothetical, but still, very probably, correct. There are many grounds for believing, that a portion of the blood- corpuscles undergo a retrograde metamorphosis in the living body, and are dissolved j and that their colouring-matter, hsematine, is thereby changed, and at last separated from the body in the form of the pigment-matters of the urine and bile. Consequently, we may obtain from the amount of these matters taken together, a sort of measure of the degree of decomposition of the blppd-corpuscles, which is going on. Useful hints and conclusions respecting the diagnosis, prognosis, and treatment of many diseases may be gained in this way. We are not yet able to determine what amount of blood-cor- puscles, or hsematine, corresponds with a given quantity of urine- pigment ; although I have often compared the colouring power of a known quantity of urine-pigment, as pure as possible, — and for which I have to thank Dr. Harley,— with that of a known quantity of blood-corpuscles. We know too little a,t present of the changes which the haematine undergoes before it is converted into urine- pigment. For this reason I have proposed as a standard for ascer- taining the quantity of urine-pigment, to fix at 1 the quantity of urine-pigment contained in 1000 C. C. of pale-yeUow urine, instead of attempting to measure the absolute quantity of urine-pigment by weighing, or by comparing it with the colour of a known quantity of blood-corpuscles — such means of estimating the pigment being difficult. The following are the arguments upon which the above hypo- thesis : viz., that the urine-pigment and bile-pigment are modifica- tions of the colouring-matter of the blood, is founded : — Blood-colouring matter is destroyed with difficulty. Extravasa- tions of blood in the body, as well as blood that has been subjected to various influences out of the body, retain their colour with great tenacity, or only undergo slight modifications of colour. Conse- quently, it is not probable that the colouring-matter of bloodj which has been used, and become useless for the purposes of life, passes out of the body as a colourless compound j but, on the contrary, there can be no doubt that it stiU retains some of its colour when excreted. As, moreover, the only coloured excretions of the body are the urine and faeces; we must consider the urine-pig- m THE URINE. 371 ment, or the bile-pigment (as modified in the faeces), or both of them, as formed of the used-up colouring-matter of the blood. Por such reasons, many excellent observers, Scherer, Polli, Yirchow, and Harley, have concluded that the bUe-pigment, and the urine- pigment, or both of them, are, in part, educts of the hsematine. Harley, moreover, has lately shown that the very pure urine-pigment prepared by him closely resembles, in many respects, the colouring- matter of the blood. The quantity of urine-pigment normally passed by a grown-up person, amounts, in 24 hours, to from 3 to 6, or, on an average, to about 4'8 or 0'2 per hour — 1, as above mentioned, being taken as the standard.* By means of this standard we judge of the quantity of pig- ment in the urine in a case of disease, whether it be normal or in- creased, or diminished. The quantity of urine pigment is considerably increased in all acute febrile diseases, although the urine itself is diminished ; in such cases it reaches 16, 20, and even more. The increase is still greater in fevers, during whose progress the blood undergoes disso- lution (typhus!; septic fevers). We notice, indeed, as a general consequence of these diseases, a diminution of the blood-corpuscles, and a more or less well-marked anaemic (oligocythsemic) condition of the body. Examples. — The quantity of urine-pigment in a large number of cases of pneumonia varied between 16 and 24 during the height of the fever. In a case of acute rheumatism, when the disease was at its height, it reached from 30 to 32 j in a man suffering from typhus, during several days, to between 80 and 100 ; in a man, who had inhaled arseniuretted hydrogen, to between 600 and 800 ! In the last case, however, the matter which coloured the urine differed from the ordinary urine-pigment, being nearly pure hsema- tine ; and hence the quantitative analysis of the colouring-matter, as measured by the depth of colour of the urine, can only be con- sidered as approximative; — the difference, however, between the quantity found in these cases and in normal conditions is so great, that any possible error of \, or even of \, need not be taken into consideration here. * My observations show, that the quantity of colouring-matter passed with the urine varies greatly. I found, during the 24 hours, 8 to 30 parts of colouring-matter according to the ahove scale. bb2 372 QUANTITATIVE ANALYSIS On the other hand, the quantity of urine-pigment is decidedly less than normal in many cases of disease : in those cases, for in- stance, in which there is a diminished formation of blood-corpuscles, as in chlorosis and auEemia ; in convalescence from severe diseases j in hysteria and nervous diseases, &c. In cases of this kind, the condition of the urine often serves as an aid to diagnosis and treat- ment, — the use of tonics, and especially of iron, being indicated. Examples. — The daily quantity of urine-pigment in chlorotic persons was frequently found under 1 ; and in convalescence, after severe diseases, for a long time often not more than from 1 to 2, &c. SECTION CXIV. Quantitative Alteeations oi' the Ueine, EEqumiNG com- plicated Chemical Opeeations for theie Demonstration. The quantitative alterations of the urine considered in the fore- going Sections are very easily made out. Their estimation, in fact, requires but little practice, special knowledge, and apparatus; so that the physician may himself undertake the investigation in all cases of disease in which the determination of these changes is a matter of importance. The quantitative alterations in the composition of the urine now to be spoken of have, on the other hand, been hitherto much more diificult of determination. They required, as a rule, more time than the physician could give to them, besides special chemical knowledge, and a certain amount of practice in quantitative che- mical analysis ; and, moreover, some of these processes could not be carried out correctly except in a well-furnished laboratory. Conse- quently, analyses of this kind have hitherto been undertaken almost solely by chemists for the solution of physiological questions, and rarely ever employed for practical purposes by the physician. In- vestigations of this kind have not, generally speaking, been regarded as necessary, or as capable of yielding any important information concerniag the nature, &c., of diseases ; but have been looked upon rather as superfluous and useless. OF THE URINE. 373 Under these circumstances, it was useless to expect that physi- cians would undertake such investigations ; though some few, it is true, have entered on the task, partly from love of science, and partly because they thought thereby to render important services to their patients. Happily, however, this state of things now no longer exists.. In consequence of the extensive application of chemistry to the arts and manufactures, new methods have been discovered whereby quantitative chemical analyses have been much simplified. These methods, and especially volumetrical analysis, are peculiarly adapted for the purposes of the physician, and particularly for the quanti- tative investigation of the urine. This simplified method of analysis may be accepted as perfectly accurate in respect to several consti- tuents of the urine; and we may expect that it will also soon become so in all the others. Most of the quantitative analyses of the urine, which a few years ago were difficult of performance, have in this way been so sim- plified, that any properly educated physician may readily undertake them. Loss of time in their performance, moreover, forms no excuse for the physician, in cases in which the investigation is re- quired, for a chemist may always be found ready, for a moderate con- sideration, to undertake the simplified analysis ; and, if necessary, any intelHgent attendant, or servant, provided he be careful, may, as I know from experience, be taught enough for the purpose in a very short time. The chief point for the consideration of the physician .who un- dertakes such analyses is, that he shoidd always clearly understand the object which he has in view. If he is not clear upon this point, he had better not undertake the investigation, for in such case the analysis is generally useless, and very often, indeed, productive of mischief. My chief object in the following sections will be to in- struct the physician upon these points as far as it is possible to do so at the present moment. I must, however, first premise certain general rules for the special investigation of the single constituents of the urine. These rules are given in the following Section. 374 QUANTITATIVE ANALYSIS section cxt. General Etjlbs poe Quantitative Analysis op the Urine. 1. Hitherto observers have generally made use of an indefinite quantity of urine in quantitative analysis^ and were satisfied when they had ascertained how much urea, uric add, chloride of sodium, &c,, &c., was contained in 1000 parts of it. But such an analysis, in reality, only gives us the relation in quantity in which each constituent of the urine stands to its other consti- tuents. It is therefore rarely of much service to the physician. And if, indeed, this kind of analysis be employed in the case of any one single constituent of the urine, so as to point out, for instance, how much urea, or uric acid, &c., is contained in 1000 parts of urine, the information which it gives is almost wholly useless. Quantitative analysis of the urine gives us no measure of the amount of metamorphoses going on in the body, unless, together with the relative quantities of its different constituents, the time is given in which they were secreted. We must not only learn how much urea, uric acid, &c., is contained in 1000 parts of urine, but also what quantity of them is evacuated in a given time — in 24 hours, in one hour, &c. Hence the first consideration in the quantitative analysis of the urine is to determine the time in which the urine is passed. This point is easily determined in certain patients. The urine may be collected during a whole day (24 hours), and in this way an error of scarcely a quarter of an hour can occur ; or the patient may be instructed to note carefully any shorter period during which it was evacuated. If, for example, the patient passed his urine, which was not col- lected, at eight o'clock, and at ten o'clock passed another quan- tity, which was measured and subjected to analysis, we are sure that the whole of the different constituents of the urine thus obtained, were passed during those two hours ; and from this we may readily reckon how much urea, uric acid, chloride of sodium, &c., was passed in one hour, or in any part of an hour. The determination of the quantity of the urine and of the time in which it is passed, thus forms the basis of all quantitative analyses of the urine. The greatest care and attention, in fact, should be paid to these fundamental facts, for if they are incorrectly stated, the OF THE URINE. 3?5 trouble and cost of the analysis are completely thrown away. In some cases, especially in the sick, the determination of the quantity of urine passed in a given time is often diflBcult ; sometimes the time is not accurately kept ; more frequently a certain quantity of the urine is lost with the motions or passed involuntarily ; and frequently it is carelessly thrown away or mixed with the other matters hy the nurses during the absence of the physician. He must, therefore, be prepared for and guard against these different sources of error, and in those cases where he feels that he is not safe from error, he had better refrain altogether from making an analysis, than run the risk of working out erroneous conclusions by starting upon false premisses. 2. Moreover, it is very important that the physician should learn the amount of possible error attaching to the different methods which he makes use of, and always bear it in mind, when working out his conclusions. I will point out these errors, as far as it is possible to do so, in each particular case ; and will also make a few general preliminary remarks on the subject. The amount of errof attaching to any analytical method, that is to say, the difference between the result obtained and the absolute fact, depends upon two circumstances: 1. Upon the degree of correct- ness of the method itself; and 3. Upon the skiQ and care of the analyst, the goodness of his apparatus, the purity of his tests, &c. The degi'ee of incorrectness of any method, though unavoidable, may be pretty accurately determined, and the value, indeed, of any method depends _upon its degree of accuracy. The second fact is variable ; when the analysis is badly performed the error is great, and vice versa in a good analysis it is exceedingly small. We cannot expect that every physician who performs a quantitative analysis should be an expert analyser ; but it is quite necessary that he should know what degree of trust may be placed in his analysis. And this anyone may readily find out, by repeating several times the quantitative analysis of one particular constituent of the urine with the same materials, and using the same method. The greater or less concordance offered by the results of the different analyses at once enable us to judge both as to the correctness of the method and the skill of the analyst ; we learn how far we may trust the figures obtained by him, and the value of the conclusions which are deduced from them. If in this way, and by repeated experiment. 376 QUANTITATIVE ANALYSIS we have once determined the amount of error attaching to any ana- lysis, we may, in cases in which great accuracy is not required, be contented with a single analysis. But in all quantitative analyses, where great accuracy is required, and where the materials suffice for a repetition of the analysis, a second analysis to control the first is always advisable, and if the results differ much, even a third; the mean sum of the three analyses being then taken as the result. We frequently meet with cases where great accuracy is not re- quired in the determination of the constituents of the urine : where, in fact, all we wish to know is, whether the urine contains more or less than a certain amount of one particular constituent. Por example, a healthy man passes with his urine about 10 or 13 grammes of chloride of sodium in 24 hours ; but in most acute diseases, when at their height, the amount of chloride of sodium thus discharged from the body is reduced to a minimum quantity. If, therefore, by an approximative method of analysis (which wiU be presently described) we find that less than one gramme of chloride of sodium is separated with the urine of a patient in 24 hours, we may safely conclude that a great diminution of the normal amount of the chloride of sodium in the urine has taken place. In most cases this information is sufficient for the purposes of the physician. He does not require to know the exact amount of chloride, whether it is O'l, or 0'5, or 0'8 gramme. Again, if we find, by a simple experiment, that a person passes more than 0"400 gramme of sulphuric acid with the urine in one hour, we have ascertained enough to satisfy us that the amount of sulphuric acid excreted is at least four times larger than natural. Approximative calculations of this kind may be varied according to circumstances, and are of great service to the physician. They may be rapidly performed — in two or three minutes — whilst an exact estimation would require thirty or forty minutes for its com- pletion. We must not, however, deduce from them any other con- clusions than those which are warranted by the results- obtained. It appears from this that we may carry out the quantitative ana- lysis of the urine in very different ways, according to the object which we have in view. A physician, who understands well what he is about, may, in certain cases, derive conclusions by means of an approximative quantitative analysis, rapidly performed in a couple of minutes, which are of more value to him than the results obtained through a careful analysis conducted by a highly skilled chemist. OF THE URINE. 377 The chemist may, in fact, have spent many days over the operation, and yet his labours be of no service to the physician, the particular point required by the latter having been overlooked by the chemist. This shows how important it is to keep clearly in view the object aimed at. 3. The indication afforded by the increase or diminution of any particular constituent of the urine must be considered separately under the head of each constituent ; I may, however, premise a few general remarks, which refer equally to several of its constituents. The constituents of the urine may be divided into two large classes, in accordance with their origin. Those belonging to the first class are formed in the body, and are in fact products of the operations going on in the body. Urea and uric acid, compounds which are very rarely taken into the body as ingesta, are both of this class. A diminished quantity of these bodies in the urine shows, that they have either been produced in less quantity than normal, or that they have been retained and have.aocumulate'9 in the body. Perhaps, in some rare instances, they may be evacuated in an abnormal way, or may undergo partial decom- position and conversion within the body. On the other hand, their increased secretion shows that they are either produced in abnormal quantities, or that they have been accumulated in the body, and then all at once evacuated with the urine. Most of the constituents of the urine are comprised in the second class. They are either partially produced in the body or formed out of other compounds by chemical decomposition. Some of them merely pass through the body. The amount of them, which is separated with the urine, depends in part upon the activity of the metamorphoses going on in the body ; in part, also, upon the quan- tity of them which is taken into the body as food, drink, medicine, &c. Thus, for example, the oxalic acid of the urine (as described in Section oi.) may be formed within the body, or it may have been taken into the body with different kinds of food containing oxalic acid. The sulphuric acid in the urine may result from oxidation of the sulphur contained in the proteine-compounds of the body; and it may also have been derived from the drinking of water containing sulphate of lime, &c. The quantity of chloride of sodium, again, contained in the urine may depend both upon an increased or dimi- nished action of the kidneys j and also upon the amount of the salt which has been ingested with the food. 378 QUANTITATIVE ANALYSIS We must, therefore, be very cautious in drawing conclusions from the increase or diminution in the urine of any of this class of its con- stituents. "We are not justified in ascribing the increase or diminution to any alteration in the action of the organs, or to any pathological condition, unless we are satisfied that the deranged secretion does not depend upon an increase or diminution of the quantity of the compound, which has been taken into the body. This, however, we can only learn by a quantitative determination, or at least by an ap- proximative valuation of the amount of the compound which has been taken into the body with the food in a given time. Such investigations are very laborious, and have hitherto been very rarely attempted. The truth is, that we are still very much in the dark on this subject; the statements, therefore, which have been made by diffe- rent observers concerning the increase and diminution of the different constituents of the • urine in diseases, must be received with great caution. We now proceed to consider the indications presented by the increase or diminution of the different constituents of the urine. SECTION cxvi. Ueea. Th. L. W. Bischoit. — Der Harnstoff, ah Maas des Stoffwechsels. (Urea considered as a measure of the Metamorphoses going on in the Body. Giessen, 1853.) The mode of determining the quantity of urea in the urine, and the modifications of the process required in certain cases, have been already fully described in Section Lx. ; we have here, therefore, only to consider the degree of exactitude and of error attaching to this method, and the indications which may be deduced from the results obtained by^it. Liebig's method is sufficiently accurate; comparative analyses carefully made with the same urine gave very similar results, the difference being less than one per cent. There are, how- ever, two possible sources of error attaching to this method of determining tho quantity of urea in the urine, which may, under OF UREA IN THE URINE. 379 certain circumstances, give rise to erroneous or inexact conclusions ; and these errors cannot be wholly avoided unless the original process be subjected to a long and troublesome modification. The errors are as follow : — 1. The error connected with the presence of chloride of sodium in the urine. This has already been pointed out at p. 186, as well as the means of avoiding it. I have, therefore, only a few practical remarks to make on the point. In all cases ia which we wish to obtain a very accurate estimation of the amount of urea in the urine, where, in fact, an error of from 1 to 2 per cent, is in- admissible, we must, first of all, precipitate the chlorine from the urine in the manner described at p. 186. When great accuracy is not required, this tedious process may be omitted, and then we may follow two courses : Either we may take no account whatever of the presence of the chloride of sodium. And then, in this case (excepting only when the uriue contains no chloride of sodium, or only a trace of it), the urea wiU always stand at too high a figure. The error, indeed, may amount tq 10 or even 20 per cent. It will, for instance, be great, if we compare the urine, usually rich in salt, of healthy persons, or of persons suffering from chronic diseases, with the urine of those who are suffering from acute febrile diseases, which generally contains very little chloride of sodium ; Or, we may make a correction for the amount of salt in the urine according to the quantity of the urea which has been obtained (see p. 186). This correction, however, is only approximative; and, spite of it, the error may stiU amount to as much as 5 per cent., and be either positive or negative. 2. A second source of error ui Liebig's process results from the fact that other bodies may be precipitated with the urea. In such case the weight of the urea obtained wiU be too great. This is true of aUantoine, a compound, however, which is rarely met with in the urine (see p. 189). It is true also of other nitrogenous com- pounds of the urine, which are more frequently present, and espe- cially in the sick. Kletzinsky* found, in a number of carefully made experiements, that a nitrogenous compound is in most speci- * Kletzinsky, Komparative Versuche uber den Werth verschiedener Methoden der Sarmtoffhestimmung. Heller's Archiv. 185.3. p. 252. (Com- parative experiments relative to the value of the different methods of de- termining the urea in the urine.) 380 QUANTITATIVE ANALYSIS mens of urine precipitated by a solution of sugar of lead. This compound is not urea, but, in Liebig's method, it is precipitated with the urea, and is included in the calculation made of the urea. The quantity of this compound found by Kletzinsky amounted to 4, 3, 3, 2, and 2 per cent, in healthy urine. In the urine of disease it was much greater, amounting even to about 12 per cent. Hence the quantity of the urea, especially in the urine of the sick, may be set down at too high a figure ; and in some cases the error may reach even to as much as 20 per cent. The error is often, to a certain degree, compensated for in this way : The urine in acute diseases contains very little chloride of sodium, so that the quantity of urea found in it, when compared with that in healthy urine, would be too small, unless correction were made for the chloride of sodium ; such compensation, however, is only admissible in very superficial investigations, and must not be received where accuracy is re- quired. To avoid this source of error, it is necessary to add to the urine sugar of lead solution, rendered acid with a drop or two of acetic acid, until the whole of the matters capable of being thrown down are precipitated ; any excess of lead remaining is then precipitated by svdphuretted hydrogen, and the urea determined by Liebig's method. This source of error, which was first pointed out by Kletzinsky, may probably depend, in part at least, upon the fact, as late investi- gations indicate, that other bodies, some of which are constantly and some occasionally present in the urine, are, like urea, precipitated by nitrate of mercury. Thus, besides the compounds of ammonia and allantoine, which have been already described, we have creatinine, leucine, and tyrosine. The presence of these compounds interferes with the exact determination of the urea by Liebig's method. The quantity of them in the urine is, however, for the most part com- paratively small, at least in healthy urine, seldom exceeding a few grammes in the 24 hours. What indications are to be drawn from an increase or diminution of the quantity of urea in the urine ? The normal quantity of urea in the urine naturally forms the basis of our calculations on this subject. Numerous investigations, made by different observers, show, that a well-fed healthy adult man, passes on an average from 30 to 40 grammes of urea in the 24 hours, and from 1'25 to 1'66 gramme in one hour. OF UREA IN THE URINE. 381 Thus, we find, calculating according to the weight of the body, that on the average in 24 hours from 0"37 to 0"60 gramme, and in one hour from 0"015 to 0'035 gramme of urea are passed for each kilogramme of the bod/s weight. The absolute quantity of urea passed by women, and of course also by children, is somewhat less than by men. But, on the other hand, the relative quantity passed by children, in relation to the weight of the body, is greater than in acquits. According to the researches of Uhle (Wiener, Mediz. Wochenschr. 1859, 7 to 9), children pass in the 24 hours for each kilogramme of their weight, as follows: — Children from 3 to 6 years of age, about 1.0 gramme of urea. „ 13„16 „ „ 0-4 to 0-6 „ This quantity naturally varies somewhat in different persons, and in the same person at different times, according to the bodily constitution, nature of diet, and activity of the nutritive functions of the indivi- dual. Moreover, these numbers do not include the maximum and minimum quantities of urea which occur in certain cases in perfectly healthy persons. The nature of the food has a very marked influence over the quantity of urea which is excreted. More urea is passed under a parely animal than under a mixed diet j and more under a mixed than a vegetable diet. Under abstinence from food, the smallest quantity is passed. The observations of 0. v. Franque (Treatise on the excretion of Urea in Man. Inaugural Dissertation. Inaug. AhMlg. Wiirzhurg, 1855) give us a very good idea of the degree of influence thus exer- cised over the excretion of urea. The quantity of urea passed by him in 24 hours. Under a purely animal diet, was from 51 to 92 grammes „ mixed diet „ 36 to 38 „ „ vegetable diet „ 24 to 28 „ „ non-nitrogenous diet „ 16 „ The chief indications obtained from the quantitative determination of the urea in the urine, depends upon the fact : that the amount of urea is an approximative measure of the degree of metamorphoses of theproteine compounds going on in the body. Thereby we learn 382 QUANTITATIVE ANALYSIS not only the amount of the entire metamorphoses going on in the body, but also of one particular and very important division of it. Whatever increases the metamorphoses of the proteine compounds of the body, as a rule, increases the quantity of urea, and vice versa. The production of urea is, consequently, somewhat greater during the day than during the night j it is increased by a rich animal diet, and diminished under a sparing, or chiefly vegetable, diet. It in- creases and diminishes also with the degree of activity exercised by the body and the mind. Hence, the quantity of urea in the urine may be increased or diminished in perfectly healthy persons, by a variety of accidental circumstances, which it is not necessary to mention here. The quantity of urea secreted with the urine in a given time, does not depend solely upon the amount of urea produced ; for the urea formed in the body instead of being wholly separated from it, may be in part detained in the blood and in the parenchymatous fluids. Hence, the quantity of urea increases temporarily with the increase of the urinary secretion, and diminishes with it. The quantity of urea in the urine of the sick depends upon exactly similar circumstances. A long-continued increase of the urea, invariably indicates an increased conversion of the nitrogenous elements of the body. A temporary increase of the urea, may, however, depend upon an increase of the urinary secretion, and does not necessarily indicate an abnormally large production of urea. A diminution of the quantity of urea in the urine may depend : — a. Upon a diminution of the proteine metamorphoses. 6. Upon the retention of the urea in the body, as occurs in uraemia and dropsy. The secretion of the urine during the progress of acute febrile diseases, pneumonia, typhus, &c., is generally affected in the fol- lowing way : — At the commencement of the attack, and until the fever has reached its acme, the quantity of urea is generally increased, some- times to as much as 50, 60, and even 80 grammes, in the 24 hours; and this, notwithstanding the patient is under low diet, and the secretion of the urine is diminished. As the fever diminishes, and the abnormal increase of the tissue- metamorphoses ceases, and as long as derangement of the digestion OF UREA IN THE URINE. 383 requires a diminished diet, the quantity of urea becomes less than normal. During convalescence, the quantity of urea gradually again be- comes normal. This is the usual state of the urea as observed in these cases ; but of course it may be variously modified by individual circumstances. In intermittent fevers the excretion of urea is markedly in- creased during the accession of the fever. The increase occurs before the occurrence of the cold stage— an important fact in the history of fevers. The quantity of urea is usually less than normal in most chronic diseases, which are accompanied with a diminution of the tissue- changes, or of the nutrition. During intercurrent exacerbations of fever, hectic fever, fee, it is increased. The quantity is reduced to the lowest, when diminished nutri- tion is conjoined with diminished action of the kidneys ; under such circumstances, and towards the fatal conclusion of many chronic diseases, the quantity is often very smaU, not more than from 5 to 6 grammes per day. The quantity, again, is often much diminished in dropsical states of the body, a portion of the urea being dissolved in the dropsical fluid, and so retained in the body. When, however, in cases of this kind the secretion of the urine is much increased, either sponta- neously or through the action of diuretics, the urea will for a time be separated in large quantities. The amount of the urea, under such circumstances, is much greater than the normal quantity which should be passed during that time ; the excess of the excretion over the production of urea depending upon the amount of it, which has been retained in the body. If, for a length of time together, much less urea is separated with the urine, than what may be considered the normal quantity, there is reason to fear that uraemia may result from the retention of urea and its decomposition within the body. When urine contains a large amount of carbonate of ammonia, resulting from the decomposition of urea, there will naturally be comparatively less urea than normal in it ; consequently, the quan- tity of urea fouiid in urine which is very ammoniacal, is no true measure of the quantity actually produced. The proceeding, which must be followed, in such case, in order to determine the quantity of urea, is given at p, 188. 384 QUANTITATIVE ANALYSIS The following examples are given as illustrations of the statements above given : — A. In Health, A large number of calculations made according to Liebig's method — no corrections being made for the chloride of sodium— gave the following as the quantity pf urea found in the urine of strong healthy men on full diet ; — grammes. 1 In H. the mean quantity of urea passed per hour was 2"13 2 In M 1-47 3 In J , . 1st series of experiments") ,.„ in the Summer of 1852 J 4 In the same person 2nd series of experiments') , in October, 1853 . . J The numbers given under 2, 3, and 4, are the mean of a large numberj upwards of a hundrcfl, pf pbsprvations ; consequently, they represent pretty accurately the mean production of urea in the individuals above referred to. They are, however, all of them somewhat too high, probably about 10 per cent., in consequence of the chloride of sodium not havjng been precipitated from the urine. Most of the above observations also serve, singly, to indicate the amount of urea produced at different periods of the day. The hourly production of urea was as foUows : Morning. Afternoon. Night. InM. . . . 1-7 . . . 1-58 . . . 1-2 In J., 1852 . 1-68 . • . 1-71 . . . 1-61 In J., 1853 . 2-12 . . . 1-82 . . . 1-74. From these figures it would appear, that the quantity of urea produced at different periods of the day does not vary much. During the night it was invariably less than during the day : observations also, made on the same individual at different periods of the year — as in J., in the Summer of 1852, and in October, 1853, — give nearly similar results. To show the amount of variation in the quantity of urine passed in health from hour to hour, I will give the maximum and minimum of the hourly evacuation of urea in each of the above experiments: — OF UREA IN URINE. 383 Hours. Maximum. Minimum. 1 3-12 1-54 2 2-45 0-88 3 3-41 1-05 4 2-82 0-89 B. In Disease. In Typhtts.' — 'During the height of the disease the daily quantity of urea varied between 40 and 55 grammes. As the fever di- minished it gradually fell to 20 grammes; and again gradually returned to the normal standard, as the patient recovered. In a case of typhus, which terminated fatally, the urea at the height of the fever amounted to 35, 40, and 50 grammes^ falling gradually as the disease advanced to 25, 20, and 10, and during the last 24 hours before the patient died was only 5 grammes. In pneumonia, during the height of the fever, the quantity of urea reached as high as 50, 60, and even 70 grammes ; falling as the fever receded as low as 25 and 20 ; and rising again with returning health. In a case of disease of the heart, with dropsy, the daily quantity of urea was for some time 20, 25, and 28 grammes. The secretion of urea was increased by diuretics, the quantity of urea amounting to 50 and even 60 grammes daily; the quantity, however, fell again with the departure of the diuresis. This state of things occurred several times. In a patient who had emphysema of the lungs and rigidity of the arteries, and who was suffering from an attack of acute bronchitis and oedema of the lungs, the quantity of urea was generally small, less than 30 grammes. With the occurrence of ursemic symptoms the quantity fell to 12 and even as low as 10 grammes. Under the action of diuretics, it rose again to 25 grammes. Then came another relapse, with diminution of the urine and of the urea to 11 grammes, and death. Numerous observations, respecting the quantity of urea secreted in different diseases, have been published during the last few years. They confirm, in all main particulars, the above statements which had been previously published by myself. These statements were based on very numerous observations which I made in the Clinique at Giessen, in part before the publication of Liebig's method, and at the c c 386 QUANTITATIVE ANALYSIS suggestion and with the assistance of my honoured friend. A closer study of the relation of uiea-secretion with particular diseases would lead us too far, and belongs indeed to special pathology. Those who wish to pursue the subject further, will find it fully treated in the following works: — Alfr. Vogel (Henle und Pfeufer's Zeitschr., JV. f. iv., 3) — S. Moos (Do. vii. 3) — W Brattler, Mn, Beitrag zur Urologie. (A Treatise on Urology.) Miinchen, 1858. These three works treat of secretion of urea in difierent diseases. "W. Miiller, iiher Harnstoffahsonderung, ^c, nach operativen Eingriffen (On the Secre-- tion of the Urea, &c.) Wisa. Mittheil. d. JErlang. Thys. Med. Soc, 1858, Heft 1. — E. Sander, HarnstoffausscAeidimg bei parah/t. Blodsinn. (On the Secretion of Urea in Paralysis, &c.) Virchow's Arehiv., 1858, p. 160 — P. S. Wameke Harnstoffausscheidtmg im Typhoidfieber (The Secretion of Urea in Typhoid Pever, Bill, for Laeger, xii. p. 330. The Secretion of Urea in Intermittent Fever :) Traube und Jochmann, Deutsche Klinik, 1855, No. 46 — Sidney Einger, Med.-Chvr. Trans., 1859, p. 360. The Secretion of Urea in Cholera, Pr. Lehmann, Inaug. Diss. Zurich, 1857. section cxvii. Ueic Acid. H. Eanee. — Beoh. mid Yersuche Uber die Ausscheidung der Harn- sdwre bevm Menschen, &c. Munich, 1858. (Observations and Eesearches concerning the Secretion of Uric Acid in Man, &c.) B. J. Stokvis. — Bijdragen tot der physiolog. van het acid uricum. Ned. Tjidsckr., 1859. Schmidt's Jahrb. Yol. 109, p. 3. (Treatise on the Physiology of Uric Acid.) The quantitative analysis of uric acid is to be conducted after the method described in Section lxviii. In all cases in which the urine contains sediment of uric acid or of the urates — and it is in these cases that the determination of the quantity of uric acid is most important — we must employ the whole of the &4 hours' urine for the purpose ; or, if the sediment should not be wholly dissolved in it, we must filter the urine, collect the deposit left on the filter, and add it to the urates dissolved in the urine, and from both these together OF URIC ACID IN THE URINE. 387 calculate the quantity of uric acid. This proceeding is, however, tedious and troublesome, and will therefore be seldom resorted to by the physician, who is generally able to guess with sufficient accuracy the abnormal quantity of uric acid from the amount of sediment of uric acid, or of urates, which is present in the urine. It must, however, be remembered that we cannot in all cases conclude from the presence of uric acid sediment in the urine, that more uric acid than normal is passed with the urine in a given time (see Section xcviii.). When we have determined the quantity of uric acid in the urine, we have next to learn whether the quantity obtained is normal, or is greater or less than normal. For this purpose, it is necessary to know, what is the mean quantity of uric acid passed daily or hourly by healthy persons. On this subject trustworthy data have been given us by Lehmann, Neubauer, and especially by Eanke. According to these observers, the average quantity of uric acid passed in the 24 hours by adults (male as well as female) is from 0*3 to 0'8 gramme. This mean quantity, however, differs consider- ably in different persons. And even in the same persons at different times, greater or less, and sometimes very considerable, variations occur. The nature of the food appears to exercise the chief influence over the excretion of uric acid. During fasting the quantity of uric acid is greatly diminished; it rapidly increases after eating, and indeed almost as much after taking non-nitrogenous, as after animal, food. (Eanke. — Dr. Eoberts.) In comparing the quantity of uric acid with the quantity of urea, we find considerable variations, from 1 to 28 up to from 1 to 80 gramme. Lehmann passed on an average 1"18 gramme of uric acid in 24 hours ; but he remarks that this is an abnormal quantity. According to Becquerel the mean quantity is from about 0"49 to 0'56 gramme per day. Neubauer, who made a great number of observations on two healthy persons, found in the one an average of 0-28 gramme, the maximum being 0"61, and the minimum 0'02 gramme; and in the other an average of 0*49, a maximum of 0'67, and a minimum of 0-33 for the 24 hours, Eanke, who has made numerous investigations into this subject, and also many observations in his own person, finds that the average cc2 388 QUANTITATIVE ANALYSIS quantity of uric acid passed by him in 24 hours was as follows : the mean 0"64<8 ; the maximum 0'875 gramme; the minimum 0'44!5; in other persons, 0-225 — 0-654 — 0*556 — 0-78 j average 0-707. In two women, the quantity was in one 0-410 to 0-456; average 0-429 ; and in the other 0-468 to 0-565. Eanke found the excretion of uric acid increased during the access of intermittent fever. He also found that it was increased in a patient suffering from leuksemia, that it was sometimes diminished in diabetes mellitus, and always markedly so in chronic gout (as pointed out by Dr. Garrod and Nenbauer) - According to Dr. Garrod the uric acid is in such case accumulated in the blood. Eanke also found the excretion diminished by the ingestion of large doses of sulphate of quinine^ The causes oft and the indications to be derived from, an increase or diminution of the uric acid in the urine, are still obscure and hy- pothetical. Uric acid, like urea, is a product of the body, and, in fact, of the transformations of its nitrogenous constituents. And so far the increase or diminution of uric and urea in the urine have the same signification, viz., an increase or diminution of the meta- morphotic processes of the nitrogenous elements of the body. Uric acid, however, stands one step higher than urea in the series of retrograde chemical metamorphoses ; for urea can be formed out of uric acid by oxidation. Hence, indeed, uric acid is often considered as imperfectly oxidised urea; and it has been thought that the increase of the uric acid invariably takes place at the expense of the urea whenever, through imperfect supply of oxygen, the decomposed nitrogenous elements of the body are not duly oxidised, and conse- quently in all diseases in which the respiratory function is impeded. This view, however, does not square with the fact, that a certain quantity of uric acid exists in the urine of the most healthy persons. Moreover, we find in those diseases in which an increase of the nric acid is most constantly observed — in the acute stage of febrile diseases — that the urea is always increased as well as the uric acid. We may, indeed, be sure that uric acid is something more than merely imperfectly formed urea ; but we must wait for further in- vestigations to explain its actual mode of formation, and its true signification. We have already spoken of the indication afforded by the deposi- tion of uric acid as sediment within the body (Sect, xcviii.) . OF FREE ACIDS IN THE URINE. 389 section cxviii. Pree Acids. Th. Eylandt. — Be Addorum mmptor. vi in TJrvnai acorem. Diss. Inwug,, Dorpatj 1854. J. Ch. LiHMAUN. — Bill, far Lasger, vol, xiii. 'p, 18, Schmidts Jahr. vol. 108, p. 148, De. Wm. Egberts. — ^A Contribution to Urology, embracing Observa- tions on the Diurnal Variations in the Acidity of Urine, chiefly ia relation to Food, 1859. The quantitative determination of the free acids ia the urine is readUy and quickly effected by the method given in Section Lxm. In such case, however, the analysis must be made as soon as possi- ble after the evacuation of the urine ; for the quantity of its acids is readily altered, under the influence of the acid or the alkaline fer- mentations. Numerous observations, which have been made, partly by myself and partly under my superintendence, show that a man in health passes on an average between 2 and 4 grammes of acids in a day, and about O'lO to 0-20 gramme per hour, calculated as oxalic acid. The hourly quantity varies much according to the period of the day. In a series of experiments made on four different persons, the quan- tity was found to be greatest during the night, least in the forenoon, and between these e:^tremes in the afternoon. The mean hourly quantity in an individual on whom the greatest number of observations were made, was in the night, 0*19; forenoon, 0"13j afternoon, 0-15 gramme. The quantity of acids in the uriae is undoubtedly diminished by the taking of caustic alkalies, carbonates, or of organic alkaline salts ; in fact, the acids will entirely disappear if large quantities of these salts be taken, the urine becoming alkaline, just as it does in the formation of carbonate of ammonia by decomposition of urea. On the other hand, the acidity of the urine is increased by taking mineral acids. Example. — ^In a young man who had taken large quantities of sulphuric and hydrochloric acids for along time on account of severe haemoptysis, the average daily quantity of acid in the urine (as a 390 QUANTITATIVE ANALYSIS mean of six days) was 4'4, and on one occasion reached to 7 "5 grammes. The numerous and careful observations made by Dr. W. Roberts confirm the statement of Dr.Bence Jones (see Sect.Lxxxvii.), viz., that for a certain time — from one to three hours — after meals, the excre- tion of acids with the urine is diminished, both absolutely and also in relation to the solid constituents of the urine. Not unfrequently, indeed, the urine at this period becomes for a time even alkaline. In this respect animal and vegetable food has a similar action. Dr. Eoberts ascribes the effect thus produced not so much to the secre- tion of the gastric acid juices (as Dr. B. Jones does) as to the pas- sage of the alkahne salts of the food into the blood. The amount of the acids in the urine, however, depends in all pro- bability, not only on the quantity of acids taken, but also upon the tissue-metamorphoses going on in the. body, as has been stated in Section lxxxvii. j but the mode of their formation has not yet been clearly shown. Numerous calculations made concerning the quantity of acid in the urine of the sick show, that in most diseases, acute as well as chronic, the acid is diminished, and rarely ever increased, excepting in those cases in which large quantities of mineral acids have been taken. We find, however, that during the acute stages of febrile diseases, and particularly in pneumonia and acute rheumatism, &c., the per- centage of acids in the urine is frequently increased, so that in fact the urine appears to be more acid than it is in health ; but this manifestly depends upon the diminished quantity of the urine, and its consequent concentration. The diminution of the acids in the urine of the sick undoubtedly depends, for the most part, upon the diminished ingestion of food. No more special conclusions can be derived from observations hitherto made on this subject. Examples. — In Men. In a case of pneumonia, the quantity of acid gradually increased from 0' to 1'50. The mean of eight days was 0'5 gramme. In another case of pneumonia, which ended fatally, the daily quantity varied from 0'9 to 8'0. The average of four days was r9 gramme. In a case of gastric fever the quantity varied between 0'6 and 1'6. The mean of four days was 1"1 gramme. OF AMMONIA IN THE URINE. 391 In a case of acute rheumatism, the quantity during several days was 0-7 and 1 gramme. In a case of chronic bronchial catarrh the quantity varied during eleven days between 0- and 0-8, the mean being 0-5 gramme. In a girl, who had scrophnlous glandular swellings, the quantity was 1-6 to 2-4. The mean of four days 2-0 grammes. In a woman, 30 years old, suffering from spinal irritation, 0- to 0'8. Mean of five days 0'4 gramme. In a woman, 70 years old, suffering from ascites and liver disease, 0- to 3"1. Mean of eighteen days 1'4I gramme. SECTION cxix. Ammonia. C. Netjbaueb. — Journ.f. praU. Chemie, 44, p. 177 and 278. W.'Heintz u. H. Bambeeger. WUrzburg. Medic. Wochenschrift, vol. ii. parts 2 and 3. The methods for determining the quantity of ammonia in the urine have been already described in Sections lxxii. and lxxiii. It appears from the researches of Boussaingault, Heintz, and Neubauer that human urine always contains a small quantity of ammonia. Erom many experiments made by Neubauer on different individuals, the average quantity passed by healthy adult males in 24 hours was found to be about 0"7 gramme ; the quantity may, however, be as small as 0*3, and as high as 1 gramme. So few experiments have yet been made on this subject, and espe- cially on the urine of the sick, that it is impossible for us to say with any certainty what indication the increase or diminution of ammonia in the urine offers to the physician. The following con- siderations, however, may serve as hints for assisting in the further investigation of the subject. The ammonia found in the urine is evidently derived from two very different sources. 392 QUANTITATIVE ANALYSIS 1. It is derived from the food and drink and from the air, which contains more or less of it. The quantity of ammonia, however, taken into the system in this way is generally small, and consequently the quantity excreted with the urine is, as a rule, insignificant, a little more than ^ gramme in 24 hours. Under certain conditions, an abnormally large quantity of ammo- nia may be taken into the system by healthy persons, for example, when sitting in an atmosphere filled with tobacco-smoke, and by tak- ing food which contains much ammonia, as horse-raddish, &c. In the sick, the ammonia may be introduced into the body as medicine in the form of carbonate and chloride of ammonium, &c, Neubaner has shown, that the greatest part of the sal-ammoniac which is thus taken into the body is evacuated with the urine. In all cases in which it is found that the daily amount of ammonia passed with the urine exceeds 1 gramme, the physician should ascertain on which of these causes the excess depends. 3. Ammonia may, undoubtedly, be also formed within the body, as the result of pathological changes. We know, that urea may be decomposed into carbonate of ammonia; and the idea at present held of the nature of uraemia is founded on this fact ; the theory being, that the urea retained in the blood is converted within the body into carbonate of ammonia. All nitrogenous animal compounds, and particularly the blood and so-caUed extractive matters, readily give off ammonia out of the body, when only shghtly decomposed ; hence, we may conclude, that in pathological processes attended with the formation of putrid, septic, &c., matters, the development of ammonia has already taken place within the body. In such cases, the proof of an increased separation of ammonia from the body with the urine, is of much value in diagnosis. The ammonia, it is true, may be sepa- rated through the intestines and the lungs, as well as with the urine, but, with our present means of analysis, its quantitative determina- tion is most readily and safely effected in the urine. Great care, however, is required in these investigations, for under the conditions referred to, the urea in the urine readily passes into a state of decomposition (which, as Neubauer has shown, does not happen in normal urine). Consequently it becomes very dif&cult in such cases to determine how much of the ammonia found in the urine was originally present in it when secreted, and how much has been formed by subsequent decomposition, either within the bladder. OF CHLORINE, ETC., IN THE URINE. 393 or after tbe evacuation of the urine. In cases of this kind, to avoid the chance of error as far as possibl,e, I would advise : 1. That the urine should be examined as soon as possible after its secretion from the kidneys ; for which purpose the urine in the bladder should be drawn off with a catheter, and the catheter left in the bladder, and the urine then eoUeeted for investigation, as it drops from the catheter. 2. The urine thus collected should then be freed from its colour- ing- and extractive-matters, mucus, &c., by the addition of acetate and basic acetate of lead (after the manner described in Sect, lxxii.) in order to prevent any further decomposition of it. 6ECTI0N cxx. ChLOMKE AHD ChWEIBE OB' SOBIUM, Alfr. Heoar.-^ Ueber die Ausscheidmng der Chlorverbindmngen, dv/rch den Ham. Oiessen., 1852,. (On the Excretion of Chlorine-com- pounds with the Urine). r. HowiTZ. — Hospitals Meddelelser ; andere Raehhe, vol. i. p. 64, Sehmidfs Jahrh., vol. 96. p. 282. E. Ph. HiNKEiiBEiN.-^Ce3e»' den Ueberganff des CMornatriums in den Ham. Inmug. Diss. Mariurg, 1859. (On the Passage of Chloride of Sodium into the Urine). The methods to be followed for the quantitative determination of the chlorine and chloride of sodium in the urine, will be found described in Section lviii., and in the Analytical Examples, "p. 268. The method proposed by Liebig for the quantitative determination of the chloride o f sodium, by means of nitrsite of mercury (Sect. LVIII. I.) is very convenient, and may be performed in a few minutes. In cases, in which urine treated with baryta yields, after filtration, a perfectly clear fluid, very accurate results may be obtained. Not unfrequently, however, the moment, at which permanent clouding of the urine occurs on the addition of the 394 QUANTITATIVE ANALYSIS mercury solution, cannot be exactly hit ; and in cases of this kind, when the urine under investigation contains very little chloride of sodium, a considerable degree of error — as great as from 30 to 50 per cent — may attend the calculation. The physician, however, should always make use of Liebig's method, even in such cases, for the approximative calculation of, the chloride of sodium in the urine usually adopted may yield errors equal to 100 per cent. The more complicated method of determining the quantity of chloride of so- dium by means of a graduated solution of nitrate of silver (see Sect. LTiii. II.) need only be employed when very great accuracy is required. The method of calculating the amount of chlorine in the ashes of the urine, gives very unsatisfactory results, for a considerable quan- tity of the chlorine is usually dissipated during the process of incinera- tion. Consequently all the calculations formerly made by this process are untrustworthy and useless. It is quite immaterial, whether the result obtained is reckoned from the chlorine or from the chloride of sodium ; although in many cases it is certain, that the whole of the chlorine contained in the urine is not combined with sodium. Care, however, should be taken not to compare tables of figures which indicate chlorine with those which indicate chloride of sodium ; this has happened occasionally, and led to confusion ; some writers giving their calculations in chlorine and others in chloride of sodiam (Na CI). In order to judge whether there is any abnormal increase or dimi- nution in the quantity of chlorine secreted with the urine, it is necessary that we should know what is the mean daily quantity of chlorine evacuated in health. Hegar has made a series of very careful observations on the daily and hourly secretion of chlorine with the urine in seven healthy young men. The average daily quantity of chlorine was different in each one, and varied between 7 "4 and 13'9 grammes. The mean quantity of chlorine daily passed with the urine of a grown-up man, was about 10 grammes (= 16"5 grammes, Na CI), and hourly about 0-44 gramme (= 0-73, Na CI). These figures are probably somewhat too high, for the per- sons upon whom the experiments were made were most of them students, accustomed to a fuU diet and highly-salted food, and who drank freely. A somewhat lower figure would be more correct in the case of most healthy adults, about 6 to 8 grammes of chlorine ( = 10 to 13 grammes, Na CI) daily, and 0"25 to 0'33 gramme OF CHLORINE, ETC., IN THE URINE. 395 of chlorine (= 0-41 to 0-54 gramme, Na CI) hourly. In the case of women and children the quantity of chlorine is still less. BischofiP found the mean daily quantity of chlorine, secreted with the urine in a well-fed adult man, to he 8"7 ; in a woman, 43 years of age, 5"5 ; in a girl of 18, 4*5 ; in a boy of 16 years, 5'3 ; and in a boy of three years, 0'8 grammes. Becquerel found, in the ashes of a day's urine of a healthy person, only 0"66 gramme of chlorine, a result, like all results obtained by incineration, which is value- less. Great variations in the daily and hourly quantity of chlorine thus separated from the body, occur not only in different individuals, but also in the same individual when in health. These variations foUow a distinct law. In this country, the maximum quantity of chlorine is, in health, secreted during the afternoon, the minimum during the night. Hegar found the mean quantity of chlorine secreted hourly in eight persons was : in the afternoon, 0*57 ; in the night, 0'28; and in the forenoon, 0"48 gramme. He also observed that variations from 0"20 to 1"32 gramme occurred in the quantity hourly secreted by the same persons, so that, in fact, the hourly maximum exceeded the minimum as much as even six times. The following may be received as the correct answer to the question : What is the cause of the increase or diminution of the chlorine in persons in health ? 1. The chief source of the chlorine in the urine is undoubtedly the salt which is taken with the food ; consequently, the quajitity met with in the urine is chiefly regulated by the quantity of salt thus ingested. Persons, who take large quantities of salt food, secrete a large average quantity of chlorine ; and the temporary increased ingestion of chlorine- compounds is usually followed by an increased secretion of chlorine. The greatest hourly average quantity of chlorine was passed by the individuals referred to in the above experiments during the afternoon and evening; and the reason of this is no doubt to be ascribed to the fact, that they took the largest quantity of salt with their chief meal at the middle of the day, a portion of the salt being separated from the body very soon after its entrance into the blood. Direct experiments also show, that the increased ingestion of chlorine increases the secretion of chlorine with the urine, and vice versa. 396 QUANTITATIVE ANALYSIS I'alck passed daily with the urine, while taking highlj-salted food 6'0 grammes of chlorine on the first day, 7'8 on the second, and lO'S grammes on the third day ; while taking non-salted food, he passed 2"S grammes on the first, 1"6 on the second, and 0'9 on the third day. Several persons, for the sake of experiment, took salt, but not in .excessive quantity. In all, the hourly excretion of chlorine with the urine was increased; it rose from 0"40 to I'O, and even to 1'80 gramme. In some, the cMoriae-salt which had passed into the blood was rapidly separated from the body, and in large quantities j in others, in smaller quantities and more slowly. 2. The secretion of chlorine with the urine does not depend solely upon the ingestion of chlorine; it may be diminished or increased through, other circumstances and conditions obtaining within the body itself. In all the individuals, under Hegar's observation, the hourly increase of chlorine was much greater in the forenoon (0-48) than during the night (0'28) ; and this notwithstanding that one of them was accustomed to take a highly-salted meal in the evening, and nothing but a glass of water up to the middle of the following day; and that the otiiers took salted food in the evening, and food (coffee and roll) containing only a small quantity of chlorine, on the follow- ing morning. In all of them, therefore, the body must have con- tained more chlorine during the night, than in the forenoon. From this it would appear, that there are special causes in action, which lessen the seereting action of the kidneys during the night, and incr«ase it during the forenoon. These causes are, doubtless, in part, rest of mind and body during sleep, and the greater activity of the nutritive fimctions in the morning — -causes which, as we have already seen, exercise a similar influence over the quantity of the urine and of the urea. In the case of a person, observed by Hegar, who was accustomed to continued mental labour during the greater part of the night, it appeared that the average hourly quantity of chlorine passed in the night (0-47) exceeded that of the morning urine-(0'44), thus corroborating the opinion above given. I have also often observed, that the secretion of chlorine is temporarily increased by any extra exertion of mind or body. In the same way large draughts of water, whereby the action of the kidneys is excited, and the quantity of the urine and the excretion of the urea augmented, also as a rule, temporarily increase the secretion of chlorine — a dimi- nution or remission of the activity usually following. OF CHLORINE, ETC., IN THE URINE. 397 Examples. — H. drank in the evening four glasses of water. The hourly average secretion of chlorine, which in him was only 0.13 during the night, rose in the first hours to 0"60j then fell to 0-12, and, later still, to 0"10 gramme; — in the morning it again rose to 0'51, without any food or drink having been taken, under the in- fluence of increased nutritive changes caused by riding. H. V. drank four glasses of water in the afternoon. The houtly average secretion of chlorine during the evening was 1'89, and amounted during the night to 0"57 (instead of 0'38 gramme). In the morning, two more glasses of water were taken; but the quantity of chlorine remained less than normal (0"4.?) during the whole day: during the night, indeed, it fell to 0'014; — in the morning it again rose somewhat (to 0'22)> then fell again (to 0*18 gramme), notwithstanding that bread and butter had been taken with a considerable quantity of salt. These facts show clearly that the amount of chlorine secreted does not depend solely upon the quantity of chlorine ingested, but that it is influenced by other causes, and especially by those which increase or diminish the action of the kidneys, and, consequently, the quantity of urine and the amount of urea. It is, however, very difficult to calculate accurately the amount of influence thus exercised over the secretion of the chlorine, and especially in any particular case. In attempting this, we must either supply the individual experimented on with food perfectly free from chlorine— "-whereby, indeed, it must be admitted that the correctness and utility of the results must be much disturbed; or the observer must take the trouble of accu- rately measuring the amount of chlorine contained in the food taken during the time of the experiment, as was done by Barral in some of his excellent observations.* We will now consider the secretion of chlorine in disease. On this point I have myself made a considerable number of experi- ments, and have had experiments made by others. The results obtained are as follows ; — 1. In all acute febrile diseases the secretion of chlorine with the urine rapidly diminishes, the quantity sinking to a minimum, so as sometimes to form scarcely one hundredth of its normal standard. The quantity increases as the disease passes away, and during 'con- valescence is occasionally greater than normal. Its curve runs, * J. A. Barral. Statique chimique des animaux, appliqnfie specialment S. la question du sel. Paris, 1850. 398 QUANTITATIVE ANALYSIS for the most part, parallel with that of the quantity of urine, usually in an inverse sense, like the curve of the specific gravity and colouring- matter of the urine, which is generally opposed to that of the urea at first, but frequently becomes parallel during convalescence. Examples. The chlorine rapidly diminished in a man suffering from acute pleuro-pneumonia ; — it amounted to 0'6 daily three days after the commencement of the attack; the next day to 0'3 gramme, and on the next almost reached j — from this point it con- tinually increased ; and, with tolerable regularity, as the disease passed away, and the appetite returned, until it reached the normal standard (0"4 — 1*8 — 2'6 — 5'5 — 9'0). At this point the curve became irregular, and occasionally exceeded the normal (10-7 — 13"5 — 9-7— 11-9— 15-9— 10-8). In a case of typhus the chlorine rapidly fell to a minimum, and remained several days at 0. It then gradually rose, as the disease passed away, but with variations, until it reached the normal standard. In a woman suffering from acute rheumatism and pericarditis, the chlorine fell, during the height of the fever, to 1"0, and then gradually rose during convalescence, to 6'3 grammes. In a young man suffering from severe febrile bronchial catarrh, it rapidly fell to 0"8, and then, within five days, rose to 10 "6 grammes. In an old man, also suffering from febrile bronchial catarrh, it fell to I'l, and then, during convalescence, under the influence of good living, attained the enormous height of 20'5 grammes. In a man attacked with exudative pleurisy, scarcely a trace of it was to be found in the urine : it then returned, and rose, with va- riations, without, however, reaching any high number (3'0 — 3*2 — 4-8— 1-6— 4-0— 4-5— 4-9— 4-6). The cause of this great diminution of the secretion of chlorine in all acute febrile diseases depends chiefly upon the loss of the ap- petite, and the saltless nature of the diet of the patients. In ad- dition to this, there are also, occasionally, abstractions of chlorine from the blood, as in serous diarrhoea, exudations, &c. Under all these conditions, the chlorine of the blood is manifestly dimi- nished ; and, as we see happens in health, any excess of chlorine in the blood is separated by the kidneys, it becomes plain enough why the chlorine of the urine should be diminished. The excretion of chlorine is also, to a certain extent, dependent upon the quantity OF CHLORINE, ETC., IN THE URINE. 399 of urine ; and as in all acute febrile diseases the quantity of the urine is considerably lessened, we must suppose that the diminished quantity of chlorine in such cases is in some way connected with the diminished quantity of urine. Since the above conclusions, based on my own numerous obser- vations respecting the secretion of chlorine with the urine in disease, have been published, many other memoirs have appeared on the subject : for example, those abeady referred to, by A. Yogel, Moos, and Brattler, on the subject of ureS, which also speak of the excretion of chlorine. They confirm, in all main points, the coiiclusions above given j showing, in particular, that it is not in any particular disease, as in pneumonia for example, that the diminution of chlorine in the urine is observed, but in entire classes of diseases. They also show that the diminution or disappearance of chlorine-compounds in the urine cannot be employed for the purposes of differential diagnosis, as some would have it : as, for Instance, in pneumonia. My observations have also been confirmed by those of Howitz, and P. Hoppe {Beutsehe Klinik, 1858, No. 52) in reference to the fact that this digiinution of the chlorine depends especially upon dimi- nished ingestion of chlorine (the other above-mentioned causes being, of course, also taken into consideration). An exception to the law, which holds good in all other acute diseases, occurs in the case of intermittent fevers. During the paroxysms of these fevers, and sometimes for a short time after them, but more rarely before their occurrence, the secretion of the chlorine is usually increased, and in some cases to a very great degree. Examples. — W. K. was attacked with a tertian fever. A short time before the attack, the hourly quantity of chloride of sodium evacuated with the urine was 0-07 ; during the attack it rose to 0-62 gramme, then fell to 0'39, and, during the interval, to 0-17 gramme. During the subsequent attack, the quantity again rose to 0-93, and during the interval again fell to 0-04 gramme. A. S. suffered from tertian fever. The hourly quantity of chloride of sodium, before the attack, was 0-05; — during the attack it was increased to 2-5 ( ! ) ; afterwards feU to 0.-12 gramme, and gradually rose to the normal standard, when the fever ceased. A. C. had tertian fever. The hourly quantity of chloride of sodium secreted shortly before the attack was 0-42, during the attack it was 1-30, and then fell to 0'15 gramme. It again increased towards 400 QUANTITATIVE ANALYSIS the conclusion of the inverval, reached its maximum this time shortly before the commencement of the fever, and then again fell to 0'08 gramme. The same thing naturally occurs also in women. Auguste S. suffered from tertian fever. The hourly secretion of chlorine shortly before the attack was O'lB, during the attack it reached the enormous quantity of 4"1Z, and after the paroxysm again fell to 0'06 gramme. The mean daily quantity of chloride of sodium secreted with the urine in intermittent fever is somewhat less than normal, but does not show for any length of time the marked diminution observed in other acute diseases. This probably depends upon the fact, that patients suffering from intermittent fever have generally a good appetite during the interval of the attacks, and take ordinary salted food. The increase of the secretion of salt during the attack may perhaps be attributed to an increased pressure of the blood in the blood- vessels of the Malpighian bodies of the kidneys during the cold stage of the fever. A diminution of the salt in the urine would naturally foUow its increased secretion, the blood necessarily containing a diminished quantitf of salt. 2. In chronic diseases the quantity of chlorine secreted with the urine varies much. It is generally diminished, in correspondence with the enfeebled assimilating powers, and with the smaller quantity of food taken by such patients. In some rare cases, on the other hand, it is increased. Some diseases which come under this head are of especial interest in this respect, and deserve a closer consi- deration. In diabetes insipidus, together with an increase of the quantity of urine, as well as of its solid constituents, there is very frequently an increase of the chlorine, the iacrease being either temporary or last- ing for some time. In a case of this kind I found the quantity of chlorine so much increased for some time as to reach in one day the excessive sum of 29 grammes. In dropsical patients, when the urinary secretion is partially sup- pressed, a portion of the chloride of sodium is retained in the body, and is transuded into the tissues with the dropsical effasion. If diuresis foUows, the secretion of chlorine increases, and sometimes to an enormous amount. A patient in this way evacuated on three consecutive days 33 (= 55 grammes, Na CI), 28, and 21 grammes of chlorine. In another case, the secretion of chlorine increased, under the influence of a decoction of digitalis, from 4 to 27 grammes OF CHLORINE, ETC., IN THE URINE. 401 in 24 hours, without any addition whatever to the quantity of chlorine taken into the body. That which, in the first class of cases, in diabetes, tends to the injury of the body by the abstraction of its necessary constituents, acts in the last case, in dropsy, as a cure, by removing the superabundant matters. A certain quantity of chloride of sodium appears to be absolutely requisite for the production of many of the secretions, for the purposes of assimilation, the secretion of the gastric juice, of the bile, and for the formation of many of the tissues — especially of the cartilages? — and, on the other hand, an excess of chloride of sodium in the body may act hurtfully, and in particular, by interference with the blood-formation and destruction of the albumen.* The quantitative analysis of the chlorine of the urine offers, in the present state of our knowledge, the following points for con- sideration : — In all acute diseases, a constant diminution of the chlorine indicates an increment of the disease, and a gradual increase of the chlorine its dechne. When the quantity of chlorine reaches a minimum figure — ^less than 0'5 gramme daily — we may 'conclude that the disease is intense, that there is an entire absence of appetite, and under certain circumstances that the patient has suffered from copious diarrhoea, or serous exudations. The reappearance of the chlorine in the urine enables us to form tolerably sure conclusions as to the state of the appetite and of the digestive powers of the patient. In cases of this kind an approximative calculation of the chlorine usually suffices; and an error of from 50 to 60 per cent, is not of much importance in those cases in which the secretion of chlorine is very small. A knowledge of the quantity of chlorine in the urine in chronic diseases is of importance to the physician, because it affords him in most cases a tolerably sure measure of the digestive powers of the sick person. The presence of a large quantity of chlorine, 6 to 10 grammes daUy, indicates good digestion ; a small quantity, under 5 grammes, indicates weak digestion, provided that in such cases large quantities of chlorine are not separated from the body by any other means, by watery stools or exudations ; and provided also that the diet of the patient is not such that only very little chlorine is ingested. A great increase in the secretion of chlorine, above 15 to 20 * I have more fully explained this last fact in Virchow's Handbuch der spec. Pathol, und Therap. vol. i. p. 404. dd 402 QUAKTITATIVE ANALYSIS grammes, indidates diabetes insipidus, provided the quantity of chlorine ingested has not been especially increased by food or medi- cine. Its increase is a favourable sign only in cases of hydrsemia and dropsy. By observation of the other constituents of the urine, we are often able to confirm or to modify the conclusions which have been arrived at by the observation of the quantity of chlorine. SECTION cxxi. SuLPHTjEic Acid. G. GacNEE. — Bie Awsacheidmiff der Schwrfelsawre ck/rch den Ham. Giessen, 1852. (The Excretion of Sulphuric Acid with the Urine.) Wald. Clare. — Experimenta de excretione acidi Sulfurici per TIrmwm. Dorpat, 1854. (Experiments concerning the Excretion of Sulphuric Acid with the Urine.) P. Sick. — Vers, iiber die AihmgigJeeit des Sehmefelsdwregehalts des Urines von der ScAwefekdurezufukr. Inaug. Abdhl. Tubingen, 1859. (Researches concerning the dependence of the Sulphuric Acid in the Urine upon the Sulphuric Acid ingested.) The methods employed for the determination of sulphuric acid in urine have been described in Sect. ixiv. Both the methods, by weighing and by volumetrical analysis, when carefully conducted yield satisfactory results. The volumetrical process, without boiling, which is generally inconvenient to the physician, is the most rapidly performed; the result, however, is not very .accurate, for error even to 10 per cent, may occur in its use. An approximative analysis may be more rapidly carried out, and although it is far from giving an accurate estimation of the quantity of sulphuric acid in the urine, generally suffices for the physician's purposes; it shows merely whether the sulphuric acid exceeds or is less than a certain quantity. An example will show the principle and the mode of carrying it into practice. "We will suppose, that the physician wishes to know whether the quantity of sulphuric acid separated with the urine of a sick person OF SULPHURIC ACID IN THE URINE. 403 is much increased or much diminished. The average daily normal quantity of sulphuric acid in the urine is about 2 grammes. The patient, whose urine is to be examined, has passed 3000 C. C. of urine in the 24 hours. If this quantity contains the normal amount of 2 grammes, 100 C. C. would contain 0*10 gramme of sulphuric acid. To the 100 C. C, rendered acid, as much chloride of barium is added as corresponds with 0*05 gramme of the acid, and the mix- ture is filtered. If the filtrate is not made turbid by chloride of barium, we may conclude that the patient has secreted less than 1 gramme of sulphuric acid in the 24 hours, and consequently that the secretion of sulphuric acid is considerably diminished. But if the filtrate is rendered turbid by chloride of barium, then a further quantity of the chloride — corresponding with 0'5 gramme of sul- phuric acid — ^is again added to it ; and if the filtrate is still rendered turbid by chloride of barium, it is clear the quantity of sulphuric acid is greater than normal. Approximative analyses of this kind, which are often quite sufficient for the purposes of the physician, may be performed in a few minutes in the cUnical ward, at the bedside of the patient. Even in cases in which a more accurate calculation is required, this simple process may be advantageously resorted to, preparatory to a more minute investigation. The mean quantity of sulphuric acid separated with the urine in health has been pretty accurately determined by different observers. Thus Gruner found, from experiments made upon seven young men at Giessen, that the mean daily average was 2*094. Those of the seven, who passed the smallest quantity, secreted an average of 1*509 ; those who passed the largest quantity, an average of 2*485 grammes; and thus, calculated for each 100 kilogrammes of the weight of the body, a mean of 3*19, a minimum of 2*04, and a maximum of 3'73 ; and for every 100 centimetres of height of body, a mean of 1*18, a minimum of 0*85, and a maximum of 1"35. Clare found, in the case of a young man living at Dorpat, the mean daily average of 15 days' secretion of sulphuric acid was 2*288, the minimum 1*858, and the maximum 2*973 grammes. Neubauer found, in two men living in Wiesbaden, that in the one the daily average of 17 days' secretion was 2*27, the minimum 1*70, and the maximum 3*20 grammes; and, in the other, the average of 22 days was 2*27, the minimum 1*70, and the maximum 3*20. Sick found that the average in him- self was 2*46. Prom this it appears, that the mean daily average of dd2 404 QUANTITATIVE ANALYSIS sulphuric acid .secreted with the urine in healthy well-nourished men varies from 1'50 to 2'50 grammes. Gruner and I have also made experiments concerning the hourly secretion of sulphuric acid in health and its variations. Eroin these we concludej that the general mean quantity per hour is about 0"090, the mean for the afternoon O'lOS, for the night 0-070, and for the forenoon 0*063 gramme. Hence follows the general law, that the separation of sulphuric acid is greatest a few hours after the chief midday meal, and that it then constantly decreases up to the time of the chief meal on the following day, when it again begins to increase. In different individuals, however, the secretion of the sulphuric acid, which has been ingested with the food, goes on with greater or less energy, and quicker or slower ; hence the sulphuric acid curve is more or less pronounced. The difference in the hourly secretion of sulphuric acid is, however, very great in the same individual. Thus a person excreted a maximum of 0'165 gramme during one hour, and at another time during two hours, a quantity so small as to be scarcely appreciable, or at most not exceeding 2 milligrammes. In another person, the hourly maximum was 0*317, and immediately afterwards the quantity was only 0'016 gramme per hour. Numerous experiments have also been made for the purpose of showing the causes which occasion an iacrease or diminution of the excretion of sulphuric acid in health, Erom what has been already stated, it is clear that the amount of the hourly secretion of sulphuric acid depends essentially upon the quantity of the acid which has been ingested with the food, or of other compounds containing sulphur, which have been converted into sulphuric acid within the body. It has also been shown by experiment, that compounds of sulphur, which have been introduced into the body as medicines, &c., cause an in- crease of the secretion of sulphuric acid. What has been hitherto ascertained on this subject may be gathered from the following facts : — J . The secretion of sulphuric acid is increased by the introduction into the body of sulphuric acid, of sulphates, and of other sulphur- compounds, whose sulphur is capable of being oxidised in the body, and converted into sulphuric acid. Examples. — The daily quantity of sulphuric acid was increased from 1-2 to S'O, and even to 8"28 grammes, in a patient who had taken sulphuric acid for a long time on account of haemoptysis. In numerous experiments the hourly secretion of sulphuric acid OF SULPHURIC ACID IN THE URINE. 405 was considerably increased by the ingestion of sulphate of soda ; in one experiment from 0-04i9 to 0-122 — 0-176 — 0-145 — 0-220; and in another, from O-Oil to 0-138 — 0-122 — 0-164 gramme. The increase of the acid was observed at longer or shorter intervals ; or ia other words, the sulphuric acid ingested was secreted from the body in some instances more rapidly than in others. (Gruner.) According to Krause, the sulphuric acid is increased in the urine by the internal use of sulphur ; and so also, according to the experi- ments of Boecker and Clare, after the administration of large doses of sulphuret of antimony. The researches of Sick show, that small doses of sulphate of soda, taken internally, are completely taken up, and afterwards evacuated with urine, but that when large doses are taken, a part only of the salt is separated with the urine. This is what we should naturally expect from the purgative action of large doses of sulphate of soda. 2. The secretion of sulphuric acid is markedly increased by a full meat diet. This fact may be explained by the supposition, that the sulphur contained in the proteine compounds is separated during digestion, and by oxidation is gradually converted into sulphuric acid in the blood, and then secreted as such with the urine. This in- crease of the acid in the urine sometimes takes place in a few hours, after the ingestion of meat, and sometimes not until long after, 12 to 24 hours ; the difference is probably to be ascribed to the digestion, whether it is slowly or quickly performed. The secretion of sulphuric acid is diminished by a vegetable diet. Examples. — A person, who had taken in the evening a full dinner, consisting chiefly of meat, passed, between 12 o'clock at night and 9 in the morning, 0-50 of sulphuric acid per hour instead of 0-10 ; and during the following 24 hours the quantity greatly exceeded the normal, being 7-3 instead of 2-02 grammes. Several persons whose excretions I examined, constantly passed more sulphuric acid after taking meat on the previous evening than when they had taken only bread and butter, rice broth, and so forth. The experiments made by Clare upon himself are very instruc- tive. During 3 days he took only animal food, and passed on the first day 2-094, on the second 5-130, and on the third 3-868 grammes of sulphuric acid. He then took ordinary food during 2 days, and passed the first day 3-592, and on the second 2-262 grammes of it. On the 3 following days, during which he lived upon vegetables, the acid amounted, on the first day, to 2*262, on the second, to 1-394, 406 QUANTITATIVE ANALYSIS and on the tliird to 1-022 ; and on the 2 next days, on ordinary diet, to 1*979 and 2-859 grammes. Erom this it appears, that the in- crease of the sulphuric acid caused by animal food first appeared on the second day, but continued during the first day of the ordinary diet ; and just in the same way that the diminution of the acid, pro- duced by the vegetable diet, first showed itself on the second day, and also continued during the first day of the ordinary diet. Here, however, the phenomenon occurred later than in the cases observed by me, probably on account of some individual idiosyncrasy. A sub- sequent experiment made by Clare, viz. taking meat and vegetables on alternate days, was, however, without definite results. 3. Does the amount of sulphuric acid excreted with the urine in- variably and solely depend upon the amount ingested, or (as has been already shown in the case of chloride of sodium), is its increase or diminution sometimes affected by other circumstances? Does the body, for instance, sometimes part with a portion of the sulphur or sulphuric acid, normally belonging to it, so as thereby to contain less than its normal amount of these constituents ; or, on the other hand, is a portion of the sulphuric acid ingested retained in the body under certain circumstances, rendering the quantity abnor- mally large? These questions have not yet been satisfactorily answered. Gruner and Clare have endeavoured to ascertain, experimentally, whether rest or violent exercise influence the secre- tion of sulphuric acid ; but their researches have not yielded any satisfactory results. Large draughts of water, which materially increase the secretion of urea and chloride of sodium, had no marked influence over the secretion of sulphuric acid. We are not, however, justified in concluding from these experiments, that the secretion of acid is not affected by such influences ; for their power may be very slight, or, in the experiments referred to, may have been counteracted by opposing agencies. The fact above mentioned, viz., that sulphates and the sulphur contained in flesh, when ingested, are secreted more rapidly in some persons than they are in others, renders it exceedingly ' probable, that there are other conditions or forces inherent in the body itself, which regulate its secretion, and that these forces are different in different persons, and in the same person at different times. Then, again, the well-known fact, that the sulphates taken for a long time in doses which are capable of being digested, have un- doubtedly an enfeebling influence, is, in my opinion, a proof that OF SULPHURIC ACID IN THE URINE. 407 under certain conditions, a larger quantity of them than normal may be retained in the body. To obtain a satisfactory answer to these questions, it is necessary either to determine accurately the amount of sulphur or sulphuric acid in the blood and the other parts of the body under different conditions, or to determine quantitatively the amount of sulphuric acid taken into the hody as well as the quantity excreted. Both requirements are, however, so difficult of fulfilment, that it is probable the questions above proposed wiU remain long unsolved. I have made ^several experiments concerning the excretion of sul- phuric acid in the sick ; but have not as yet obtained any particular results. I found that it was much diminished in most acute febrile diseases ; the diminution no doubt depending upon the low diet and vegetable food of such patients. Examples. — A man suffering from buccal diphtheritis, with much fever, secreted in 24 hours only 0"5 gramme of sulphuric acid. A patient with febrile catarrh, 0'39 and 0'38 gramme. A patient with pleurisy, 0'63 gramme. An exception was, however, observed in three cages of severe pneumonia j in these the acid was in part shghtly diminished, and in part considerably increased. One of them, who had been treated with large doses of digitalis, passed 2'4, 3-1, 2-9, 5-7, 4-3, 1-8, 1-1, 1-6, and 27 grammes. The pneu- monia was rapidly fatal in the' other two cases ; in the one, 2'9 and 1'4, and in the other 4*4 grammes were passed on the day the patient died. A young girl with acute rheumatic fever secreted 0*8 gramme when the fever was at its height. One with erysipelas of the face, 0'48 gramme. In chronic diseases the secretion of sulphuric acid was in many cases very small, in others somewhat larger, but generally much beneath the normal. It is generally less than normal in the dropsi- cal, in whom, however, the excretion of chlorine is greatly increased during diuresis. In chronic diseases I found the acid increased only after the use of sulphuric acid or of sulphates, and in diabetic patients living on a rich animal diet. Examples. — A patient, with icterus, passed 1'4; another, with rheumatism of the neck, I'll ; a patient with emphysema of the lungs, 1"2; another with amenorrhoea, 0'5; a girl with fluor albus, 0'7 j a patient with habitual menorrhagia, 0*97 to I'l gramme of sul- phuric acid. A dropsical patient, who, when diuresis had begun. 408 QUANTITATIVE ANALYSIS passed with the urine 33 grammes of chlorine in 3-1 hours, secreted in the same time only 1"0 gramme of sulphuric acid, and on the fol- lowing day (during which he passed 28 grammes of chlorine) only 0'5 gramme of the acid. A patient, who took sulphuric acid, secreted upwards of 3 grammes in 24 hours ; and a patient suffering from diabetes insipidus as much as 5 '2 grammes; According to Dr. B. Jones, the sulphates are much increased in the urine in diseases in which the muscular system is much engaged ; in chof ea, for example j and so also in diseases of the brain, both functional and organic — ^in delirium and in inflammation. Heller asserts the same as regards inflammatory diseases ; but he states that the sulphuric acid is diminished in chlorosis, neurosis, and in chronic diseases of the kidneys and the spinal" marrow. The methods, however, followed by both these observers were not of a kind to settle this diflcult question. Some observations made by Lehmann and Gruner are not favourable to their views. Observations made by myself in those diseases are not numerous enough to yield any deflnite result. The three cases of pneumonia, above mentioned, appear to show distinctly that the sulphuric acid is increased in many inflammatory diseases. From the present state of our knowledge upon the subject of the increase or diminution of the sulphuric acid in the ui-ine, the foUow- conclusions may be drawn : — 1. A considerable diminution of the sulphuric acid indicates that the patient has taken very little food, or only vegetables without any meat. 2. An habitually large excretion of sulphuric acid, with an excess of urea, indicates a preponderance of animal food. A tem- porary increase indicates the ingestion either of sulphur or of sul- phuric acid and its salts, or of large quantities of animal food. 3. We are not justified in considering that the increased secretion of sulphuric acid depends upon an abnormal decomposition of the sulphur-compounds of the body, except in acute febrile diseases, during which little or nothing has been taken in the way of food. OF PHOSPHORIC ACID IN THE URINE. Section cxxii. Phosphoric Acid. A..^XSTER,.~^Beitrdge zur Eentniss der UrinahsonderungbeiOesunden. Giessen, 1852. (Treatise on the Secretion of Urine in Health.) F. MosLER. — Beitrage zwr Kentniss der Urinahsondemng. Giessen, 1853. (Treatise on the Secretion of Urine.) W. Beattlee.— '^m Beii/rag zur Urologie. Miinchen, 1858. (A. Treatise on Urology.) H. "Keabbe. — Ueber die Menge der Fhosphorsaure itn, Ham., &c. VircAovfs Arehw, 1857, vol. xi. p. 478. (On the Quantity of Phosphoric Acid contained in the Urine.) H. VON Haxthausen. — Acidum FAospAorimm Urma et Excremen- torimi. Diss. Inaug. Halle, 1860. (The Phosphoric Acid in the Urine and Pseces.) The voliitnetrical method for determining quantitatively the phos- phoric acid in the urine with per- chloride of iron has been already described in Sections lxi. and lxii. It unfortunately does not give satisfactory results. Notwithstanding the greatest care, an error to the extent of even 10 per cent, may occur, and especially so if the urine contains only a very small quantity of phosphoric acid. This has been pointed out in the Analytical Examples. But there are other sources of error to which the observer is liable, as for instance, that of taking a blue speck of different degrees of intensity as a sign of the saturation, or of allowing some time to elapse, after the addition of the per-chloride of iron solution, before proceeding to the test. These disturbing causes may render the error in the hands of an un- skilful investigator as great as 20 or even 30 percent. This method, therefore, is only of service for approximative calculations ; and is not adapted for cases where accurate results are required. Conclu- sions derived from observations made according to it are only to be trusted when the differences obtained exceed 30 per cent. Differences between 15 and 30 per cent, are not worthy of consideration unless after a very large series of observations. The new process with oxide of uranium (see Section lxi.) is de- cidedly preferable, and gives much more accurate results. The observations given above, and those which follow, were most *10 QUANTITATIVE ANALYSIS of them obtained by means of the old process with per-chloride of iron. The mean conclusions^ however, derived from them agree very well with observations made with oxide of uranium at my request by H. von Haxthausen. Numerous observations have been made concerning the daily and hourly secretion of phosphoric acid in health. Breed found in four persons 3'7 grammes as the mean quantity passed in 24 hours. Winter found in one person 3-7, in a second, 4-2 and in a third 5'2 grammes. Hosier found in the same individual at different times 2'4 and 3'7. Neubauer found in one 3"1, and in another only 1"6. Aubert found 2-8. Yon Haxthausen found the mean quantity in a large number of observations made with his own urine to be 3"11 to 5*58 grammes. It appears from these observations, that the average quantity of phosphoric acid secreted by an adult male in 24 hours is about 3'5 grammes; it should, however, be remembered that the mean quantity passed by different individuals varies very much from this general average. The average hourly quantity is about 0"15 gramme. Winter has also reckoned the phosphoric acid in relation to the weight and height of the body. He found that the average quan- tity passed per hour was 0*27 for every 100 kilogrammes of weight, and O'l gramme for every 100 centimetres of height. The daily and hourly variations occurring in the same individual in health are considerable. Thus Neubauer found the daily maxi- mum of phosphoric acid to be 2'16, and the daily minimum 1'21 in the same person; in another he found the maximum 4"88, and the minimum 2'44. Hosier found a maximum of 4'86, and a minimum of 2*40 grammes. StOl greater differences are found when the hourly quantities are compared. I found in a long series of observa- tioHs made on the same person that the maximum hourly secretion was 0'216, and the minimum 0'085 gramme; both extremes were obtained on the same day, the whole series of observations being spread over 10 days. It appears, from the observations of Winter, Hosier, Haxthausen, and myself, that the hourly excretion of phosphoric acid goes on very regularly and equably in all the individual cases examined by us. It begins to increase in the afternoon after dinner, reaches its maximum in the evening, sinks again during the night, and reaches its minimum in the forenoon. The following table shows these variations as observed at different OF PHOSPHORIC ACID IN THE URINE. 411 hours of the day in 4 persons. The quantity of phosphoric acid secreted in one hour was : Afternoon. Night. Forenoon. In A. . . . 0-18 . , . 0-20 . . . 0-13 B. . . . 0-28 . . . 0-21 . . . 0-11 C. . . . 0-18 . . . 0-16 . . . 0-10 D. . . . 0-11 . . . 0-14 , . . 0-11 This tahle is instructive, in that it shows how a general law is modified by the idiosyncrasy of individuals. The curve is most marked in B, the difference between the afternoon and forenoon quantity being the greatest. In this case the greater part of the phosphoric acid taken with dinner was rapidly eliminated, the highest point of the curve being reached during the afternoon. In C. the elimination was slower, and the highest point of the curve reached in the evening. In D. the elimination was still slower, the highest point being reached in the night, although dinner was taken at one o'clock in the day, as in all the other cases ; digestion was probably less rapidly performed in this case. The following are the facts hitherto ascertained concerning the causes of the increase or diminution of the secretion of phosphoric acid : — 1. The phosphoric acid of the urine is increased by the inges- tion of phosphoric acid, and of soluble phosphates. Aubert* found that the quantity of phosphoric acid excreted with the urine was raised to 4'1 after the ingestion of 31 grammes of phosphate of soda, the normal quantity being 2*8 grammes in the 24 hours. ' Von Haxthausen also found that the excretion of phosphoric acid was invariably increased after the ingestion of .phosphate of soda. 2. The excretion of phosphoric acid with the urine is increased when phosphoric acid, in a more or less perfect form, or when sub- stances which are capable of being converted into phosphoric acid in the body, have been taken with the food. It is diminished by abstinence from food j but, unlike chloride of sodium, it does not entirely disappear even after long fasting. As a rule it is greater under an animal than under a vegetable diet. Mosler found that the phosphoric acid was reduced one-half by * Henle and Pfeufer's Zeitaobrift ftir ration. Medicin. 1862. ii. 3. 412 QUANTITATIVE ANALYSIS fasting ; and that, on the other hand, it was nearly doubled under a rich nitrogenous diet. Schmidt observed, that cats fed on ordinary food, for each kilo- gramme of weight passed 0*30 gramme of phosphoric acid in 24 hours; but that after a long fast they passed only 0'107 gramme of it. 3. It was distinctly proved in the case of chlorine, and was shown to be very probable in the case of sulphuric acid, that their excretion with the urine is influenced by diflferent conditions of the system — by the nutritive changes, &c., as well as by the quantity of these bodies which have been ingested. Numerous experiments prove that the same is undoubtedly true of phosphoric acid. It has been already shown above, that phosphoric acid taken into the body with . the food is excreted more or less rapidly in different individuals. It appears, from experiments made by myself, that a marked diminution of the phosphoric acid (0'085 gramme per hour) may follow a tem- porary increase of the excretion (0"216 gramme per hour). The secretion of phosphoric acid is usually increased by large draughts of water (together with the urea and chlorine), and in a greater propor- tion than the quantity contained in the phosphatic salts of the water. It is also increased by increased activity of the nutritive functions generally, or of the kidneys, or of both together. JProm these facts it is evident, that the quantity of phosphoric acid in the body may, under certain conditions, be increased by retention of the phosphoric acid ingested, and diminished by increase of its secretion. Consequently, a knowledge of these con- ditions becomes of the highest importance both to the physiologist and the physician. Unfortunately, however, we know nothing certain concerning their nature, nothing in fact, except what is conjectural. .And here, again, in our researches, we meet with the same difficulties as those which have been already mentioned, in reference to the determination of analogous conditions in the cases of chlorine and sulphuric acid. Besides this, it must be remembered, that the whole of the phosphatic salts are not secreted with the urine, a portion of them being, as a rule, passed with the faeces.* • V. Haxthausen has, at my request, made some observations on this point. He found, that the quantity of phosphoric acid evacuated with the faeces (as obtained from them without incineration, by extraction with dilute nitric acid) was as follows in the 24 hours : — Average (of seventeen observations) 0'666— Maximum, l-OSO — Minimum, 0'270 gramme. From which it follows that four or five times more phosphoric acid is excreted with the urine than with the feeoes. OF PHOSPHORIO ACID IN THE URINE. 413 Hence, it becomes necessary : either to determine quantitatively the amount of phosphatic salts in individual parts of the body, and under different conditions — which would require a vast number of experiments ; or, to determine accurately both the quantity of phos- phoric acid passed with the urine and the faeces, and the quantity of it ingested with the food.. The difiiculty of these processes, however, will prevent the attainment of the object desired ; and we must therefore be contented, for the present, with conjectural views concerning the nature of the conditions which affect the increase or diminution of phosphoric acid in diseases. The following are the facts which I have noted concerning the excretion of phosphoric acid in the sick ; and on this point I have made upwards of one thousand observations. In the first period of acute diseases, not pf a severe nature, the excretion of phosphoric acid is frequently found to be less than usual, probably in consequence of the low diet taken ; it then gradually increases in proportion with the quantity of food ingested by the patient. During convalescence, when an unusual amount of food is taken, the quantity of phosphoric acid is sometimes greater than normal. In d.iseases of short duration, even although they are accompa- nied with much fever, the diminution of the phosphoric acid is at times scarcely perceptible. Examples. — In a young man suffering from acute angina tonsil- laris, the quantity of phosphoric acid excreted at the time of his admission into the hospital was 2'8 grammes. — ^Emetic; severe vomiting. Low diet. Next day the quantity of phosphoric acid was 1*7 gramme. The patient improved, quarter diet. On the third day, it was 2'6 grammes j on the next, 2"5. Half diet. On the following day the phosphoric acid was 3-2 grammes. Eecovery. Slight attack of pneumonia. — Recovery in eight days. The quantity of phosphoric was 2-4,— 2-5— 2*9 — 2-4!— 2-3 grammes. In severe pneumonia, at the acute period of the inflammation : it was 1-7 — 0-8 — 2-1 — 1-2 — 0-9 — 2-1 — 1-9 — 1-1 grammes. In severe pneumonia, it was 1-6 — l-4i — 2-2 — 2-3 — 1'6 grammes. In febrile bronchial catarrh: l-4i — 1'5— 1-7 — 1-5 — 2-8 grammes. In convalescence after severe pneumonia : 3'8 — 2'7 — 3'2 — 3'5 — 3-9 — 1-8 — 2-5, &c., grammes. In same : 1-9 — 5-6 — 2-8 — 1-5 — 3-2 — 2-8 grammes. In convalescence after acute febrile bronchial catarrh: 4-8 grammes of phosphoric acid. 414 QUANTITATIVE ANALYSIS Eczematous catarrh of the digestive organsj with acute fever. Rapid course j the patient convalescent in eight days = 2'3 — 2"6 — 2-7 — 2'6 — 3-4 grammes. The following cases occurred in females : — Eheumatic fever : 2"1 — 2"3 — 2'2 grammes. Catarrh of the stomach : 1*1 — 1-2 gramme. Catarrhal fever, in the acute stage : 1'6 gramme. Convalescence from typhus j 5'2 grammes. In many cases of acute diseases, or after long abstinence from food, or towards the fatal termination of disease, the phosphoric acid excretion diminishes still more remartably. Examples. -^In a girl, during the acute stage of pulmonary catarrh, the quantity of phosphoric acid was 0'7 — 0"5 — ; and during convalescence 1*3 — 2*5 grammes. In a case of pulmonary tuberculosis, on the days preceding the patient's death, it was 0-4, — 0-4 — 0-3 — 0'3 — 0-2 — 0-1 — 0-08 gramme (the day on which he died). In fatal gangrene of the lungs, it was 3*0 — 2-5 — 2-20 — 0-7 grammes. In some exceptional cases, however, the phosphoric acid may be greater than normal during the* acme of acute diseases, as shown in the following example : — In acute pneumonia in a middle-aged man, who was treated with large doses of digitalis, and recovered, it was 4'3 — 5'1 — 4*1 — 8-4 — 7-9 — 4-5 — 2-9 — 5-0 grammes. In chronic diseases the secretion of phosphoric acid follows a very irregular course, the quantity being generally less than normal; sometimes, however, it is considerably greater. I have made nu- merous observations (30 to 40) on this point ; but it would be tedious to mention them all here. I shall, therefore, give examples showing the mean, the maximum, and the minimum, quantity. Examples in Men. — ^Emphysema of the lungs. The mean quantity of 8 days was 1'3 ; the maximum 2"3 ; the minimum 0*6 grammes. Chronic broncorrhoea. — Mean of eight days 2*7 ; maximum 4*7 ; minimum 1'3 grammes. Cancer of the liver. — Mean of eleven days 2*3 ; maximum 2*6 ; minimum 1"6 grammes. Subacute articular rheumatism. — Mean of eighteen days 2'4j maximum 3"1 ; minimum 1'7 grammes. Hemiplegia, after apoplexy.— Mean of thirty-five days 2'7; maximum 5"2 ; minimum I'O grammes. OF PHOSPHATIC EARTHS, ETC. 415 Hydruria. — ^Mean of three days 5"0; maximum 5 "8; minimTun 4"4 grammes. Dropsy. — Stage of diuresis, with great increase of chlorine-secre- tion. Mean of two days 1"8 gramme. Examples in Women. — Diabetes insipidus. Mean of fourteen days 4-8; maximum 7"8; minimum 3'3 grammes. Ascites. — Mean of fifteen days S'O ; maximum 4"7 ; minimum r? grammes. Chronic rheumatism. — Mean of seven days 8"3 ; maximum 4*2 ; minimum 2'7 grammes. Spinal irritation, 2*1 — 2"8. Mean 2-4 grammes. Amenorrhoea, 2'1 — 2*3. Mean 2*2 grammes. Scrophula, 2"6 — 5'2. Mean 3"5 grammes. Pulmonary tuberculosis, 1'5 — 3*9 (10 days) grammes. Chronic erysipelas of the face, 1"5 — 3'6 (11 days) grammes. Brattler gives the following resum^ of his observations on the sick : — The excretion of phosphoric acid is dvmvrmhed, in diseases and functional disorders of the kidneys, associated with diminished urinary secretion (Bright's disease, diseases of the heart), and in dis- eases of the digestive organs, which interfere with the absorption of the food. It is increased, in acute febrile diseases, through the increased metamorphoses of the phosphorus-containing tissues (the increase of the phosphoric acid, however, is not so constant as is that of the urea) j it is also increased in diseases where, through func- tional disorders of the kidneys, the phosphoric acid has been retained and accumulated in the blood, after the cause of the retention has been removed. (Bright's disease, cholera.) Haxthausen observed a diminution of the secretion of phosphoric acid during the access of intermittent fever. section cxxiii. Eaetht Phosphates. — Lime. — Magnesia. Beneke. — Ber Phosphorsmre Kalk., &c. Gottingen, 1850. (Phos- phate of Lime, &c.) 116 QUANTITATIVE ANALYSIS Beneke. — Zur Thysiolog. u. Patholog. des Phosphors, u. oxals, Koikes. 2 Beitrag. Gottingen, 1850. (On the Physiology and Pathology of Phosphate and Oxalate of Lime.) Kletzinsky. — Eelki's ArcUv, 1852, p. 270. C. Neubatjee. — TJeher die Erdphosphate des Horns. Jownl. fur praci. CAemie., vol. Ixvii. p. 65. (On the Phosphatic Earths in the Urine). P. HuENKE. — He Phosphatum terrarum in urind quantitaie. Diss. Inaug. Berlin, 1859. (On the Quantity of Earthy Phosphates in the Urine.) Different methods are employed for determining the quantity of earthy phosphates in the urine, according to the particular object which the operator has in view. 1. The quantity may be estimated by Beneke's method (Sect. Lxxxiii. I.). This method is quickly performed, but it yields only approximative results. 2. Again, the quantity may be obtained by the method described at p. 195. The earthy phosphates are precipitated with ammo- nia, the precipitate washed, dissolved in hydrochloric. acid, and the quantity of phosphoric acid in the solution determined by the volumetrical process. This method, however, is liable to the errors, mentioned under the head of phosphoric acid, and does not yield accurate results. Moreover, it does not give the weight of the earthy phosphates themselves, but only the quantity of phosphoric acid. Or, again, the quantity of lime and of magnesia is determined separately, either, 8. According to the method given in Section lxxi. III. j or, 4. According to Section lxxi. I. and 11. The last-mentioned method (4) is preferable to every other when great accuracy is required. The following data will assist the inquirer in determining the value which may be attached to quantities . obtained by these different methods : — Beneke considered that the quantity of earthy phosphates passed with the urine by an active healthy man in 24 hours, equalled 1"2 gramme. Lehmann passed in 24 hours 1"09 gramme of phosphates under ordinary diet ; and 3 '5 6 grammes under a purely animal diet. OF PHOSPHATIC EARTHS, ETC. 417 Bijcker passed an average daily quantity of 1'48 gramme. Mosler found the quantity of phosphoric acid united with the earths (consequently not the quantity of the phosphatic earths thfemselves) which was passed by himself, first, during six days' observation in the month of April, and secondly, during four days in October, as follows : — I. II, Per Day. Per Hour. Per Day. Per Hour. Mean . . 1-153 0-048 0-390 0-015 gramme. Maximum 1-800 0-075 0-660 0-027 „ Minimum 0-370 0-015 0-170 0-007 „ In other healthy persons the hourly average was from 0-015 to 0-019 gramme. Hegar found the quantity of phosphoric acid combined with the earths, to be, in himself, as the mean of eight days' observations, 1-31 gramme. Half-a-year later, the mean of four days' observations was 0-902 gramme. Neubauer gives the following as the results of the numerous observations which he has made. They may be received as very trustworthy, both from the accuracy with which the observations were made, as well as from the number of them, 52. The average quantity of earthy phosphates passed with the urine by a healthy man in 24 hours range between 0-941 and 1-012 grammes. The mean maximum was 1-138 to 1-263 (the greatest quantity being 1-554). The mean minimum 0-8 (the smallest quan- tity 0-328) gramme. The average daily quantity of phosphate of lime was 0-31 to 0-37 gramme. The mean maximum 0-39 to 0'52 (the largest quantity 0-616). The mean minimum 0-25 (the smallest quantity 0-15) gramme. The mean quantity of phosphate of magnesia was 0-64. The average maximum 0-77 (the largest quantity 0-938). The average minimum 0-5 (the smallest quantity 0-178) gramme. On an average there was excreted 1 equiv. of phosphate of lime to 3 equivs. of phosphate of magnesia, or 33 parts of phosphate of lime to 67 parte of phosphate of magnesia. These data are strikingly opposed to those of Kletzinsky, who found the relative quantity of the phosphate of lime and phosphate of magnesia exactly the reverse. According to him, 100 parts of e e 418 CREATININE. ALLANTOINE. the earthy phosphates consist of 67 '3 phosphate of lime, and 32'^ phosphate of magnesia.* It appears, from the investigations of Neubauer, that salts of lime, when taken into the body, do not pass into the urine, or at all events only in very minute quantities. On the other hand, Dr. W. Roberts found the earthy phosphates increased to almost double the ordinary quantity after eating. The absolute quantity of earthy phosphates in the urine, as well as the relative amount of the phosphates of lime and of magnesia, vary much in disease from the normal standard above given. Thus, it is generally admitted, that the excretion of phosphatic earths, and espe- cially of phosphate of lime, is increased in certain diseases of the bones (osteomalachia, rickets, &c.). IMrther careful investigations are much to be desired for the more perfect illustration of this sub- ject, which is of great importance in pathology as well as in physio- logy. In conducting such investigations, we must remember, that if conclusions are drawn from them respecting the metamorphosis of the whole of the phosphatic earths in the body, the phosphates contained in the fseces must be calculated as well as those in the urine. SECTION cxxiv. Ceeatinine — Allantoine — Leucine — ^Tyeosine. Creatinine is constantly present in the urine. The quantity of it was once regarded as very small ; but later investigations show that such is not the case, and that it is of importance that we should be able to determine its quantity. Por this purpose, methods for its quantitative determination in the urine have been given (see Section lxix.). Schottin {AroAiv. d. HeilM. v. Wagner. 1860. vol. i., p. 417) found only traces of creatinine in the urine. Neubauer, however, showed by a series of careful investigations {Annal, d. Chem. u. Pha/rm., vol. cxix., p. 27), that the quantity is much greater than • The process employed by Kletzinsky was found, on trial, to give in- aoourate results, His ooncluBions, therefore, on this head cannot be ac- cepted. CONCLUDING OBSERVATIONS. 419 Schottin supposed. He found in his own urine 1 gramme in 24* hours; the maximum being 1'35, and the minimum 0'76 gramme. He obtained similar results in other adult persons, 0'8 to 0*9 gramme per day. In a boy he found 0"4 gramme. Creatinine appears to be essentially a product of the metamorplicses of muscular tissue, and its increase to play an important part in many diseases. Thus in ursemic diseases it appears to be increased in the blood; and is perhaps also increased in the urine. It is to be hoped that further investigations will be made in this field, which promises rich rewards. The determination of the presence and of the quantity of allan- toine, leucine, and tyrosine in the urine also promises to add to our pathological knowledge. Our information in this direction is as yet but fragmentary and of little service to the physician. I add the following literary notices on the subject for the benefit of those who may be inclined to study the subject further. Prerichs and Stadeler {Miiller, ArcMv f. Anat. ^ Fhys., 1854, p. 393) found allantoine in the urine of dogs, whose respiration was impeded; so also did Kohler {de allantoini in wind impeditd respiraiione prasenfia),'Diss. Gorlitz, 1857. Schottih also found it in man after the ingestion of large quantities of gaUie acid (Lehmann's Handhuch der Physiol, Chemie, 1859, p. 93). Schottin {Arahiv f. Physiol. Heilkde., 11. N. f., p. 353) found leucine in a specimen of albuminous urine ; Prerichs and Stadeler found leucine and tyrosine in the urine of patients suffering from typhus and small-pox, as well as in acute atrophy of the hver. Sohmeisser also found tyrosine in the urine of a patient suffering from the last-mentioned disease {Archiv d. Pharm., Oct. 1849, vol. 150. p. 11). section cxxv. Concluding Obseetations. I have endeavoured in the preceding pages to point out, for the purposes of the physician, the signification of the different changes (qualitative and quantitative) to which the urine is liable, in the same way as medical semiology points out and determines the value of the e e2 420 CONCLUDING OBSERVATIONS. different symptoms of diseases. The information, however, obtained from the iavestigation of the urine in disease, is as yet very imperfect. StiU more important conclusions concerning the diagnosis, prog- nosis, and treatment of disease, than those which are obtained from the observation of any one single alteration of the urine, wiU. be gained from a consideration of several different alterations occurring at the same time or immediately consequent the one on the other. We may even go further than this. The changes of the urine may be compared with the abnormal conditions of other secretions — of the faeces, of the perspiration, of the pulmonary exhalation, &c. ; and from such combined facts conclusions may be arrived at concerning the state of the metamorphic processes going on in the body. It is not my intention to enter further into this wide, and still obscure, field of observation, which has, in fact, only been very recently investigated. But I am desirous of pointing out by a few examples important results which may be obtained, and without any great dif&culty, by this method of investigating diseases. The fol- lowing cases were all taken under my own personal observation : 1. A young woman, 20 years old (who had been ill for a long time), suffering from various ill-defined symptoms (thought to be indications of commencing pulmonary tuberculosis), had great thirst, diminished perspiration, but no fever. She daily passed from 3000 to 6000 CO. of urine of high specific gravity— 1-025 to 1-034, containing a large quantity of sugar. The diagnosis was clear enough — diabetes mellitus. She improved for a time under the use of an animal diet with gluten bread, and the use of alkalies — mag- nesia and bicarbonate of soda, with opium. A severe attack of pneu- monia, however, rapidly destroyed her. 2. A woman, about 36 years old, of a somewhat pasty, pale, ansemic aspect, with blue circles around the eyes, suffered from nume- rous nervous symptoms — hypersesthesia and spasms — usually known under the title of hysteria. On careful investigation it was found that her urinary secretion was much increased — between 3000 and 4000 C. G. per day. The urine was between pale and bright yeUow, its colouring matter being rather diminished than increased (3 to 5) ; it was only very slightly acid, frequently, indeed, alkaline, the free acids being much less than normal (0 to 0*6) . Its specific gravity was less than normal — ]'012 to 1*015 ; but its solid constituents, nevertheless, were much increased— 80 to 120. This increase occurred in the case of almost all the constituents of the urine — urea, 40 to CONCLUDING OBSERVATIONS. 421 49; chlorine — 20 to 30; phosplioric acid — 5 to 9; sulphuric acid--- 3 to 5 grammes. Not a trace of sugar was found in it. Diagnosis : ■diabetes insipidus. The patient was manifestly suffering from ab- normal increase of the metamorphic processes. The waste of the body was unnaturally great ; and as the patient was in poor circum- stances, this increased loss was not replaced by a richer diet. In two days the weight of the body was diminished three pounds. The calorification of the body was, however, less than normal, and the formation of blood-corpuscles defective. Under an abundant and rich diet, together with the use of tonics (quinine and iron) and opium, the urinary secretion was gradually brought to its normal state ; the patient's aspect improved, the nervous symptoms disap- peared, and her strength returned. "Whenever, however, the patient returned to her previous mode of living, she had repeated relapses of the disease — intermitting diabetes insipidus. I have often observed analogous cases as the consequence of immoderate water-drinking, of hydropathy carelessly or improperly employed, or too long continued. 3. A strong man, after a chill, complained of severe rending pains in the nect and shoulders. The skin was cool and shrivelled, the perspiration diminished. His urine was increased — 3000 to 3300 C. C. The quantity of colouring-matter was about normal— 4 to 5 ; and so also that of the free acids — 1'8 to 2'3. The specific gravity low, 1'006 to 1.008; and the amount of solid constituents some- what diminished— 36 to 40 grammes; the urea, phosphoric acid, sulphuric acid, and chlorine being rather less than the normal sum. Diagnosis : hydruria. The increase of the urine evidently depended upon an increased secretion of water by the kidneys, which occurred vicariously with a diminished secretion of the skin and the lungs. Although the hydruria continued several days, the strength and the weight of the patient did not diminish. Under a diaphoretic treatment, whereby the secretion of the skin was increased, the hydruria gradually disappeared ; and so also did the rheumatism of the neck after cupping. 4. In a young man suffering from disease of the heart — insuffi- ciency of the bicuspid valves with consecutive dilatation and hyper- trophy of the right ventricle — the urine gradually diminished in quantity, from 1600 to 1200, 800, and 600 CO.; the secretion of urea was also diminished to 26, 20, and 18 ; and so also the secre- tion of chlorine to 8, 5, and 3 ; the phosphoric acid to 2 and 1'5 ; 422 CONCLUDING OBSERVATIONS. and the sulphuric acid to 1-5 and 1 grammes. Then followed dropsical effusion into the abdomen, and oedema of the extremi- ties. Under the use of large doses of digitalis — infusion of digi- talis with acetate of potass — the urine was considerably increased, to 3000, 4000, and 4500 C. C. ; and with the urine a considerable quantity of urea, 50, 55, and 60 ; and of chlorine 35, 30, and 33 grammes were evacuated ; the sulphuric acid and phosphoric acid secreted were, however, scarcely more than usual. In this case a large quantity of water, urea, and chlorine, instead of being evacuated with the urine, had been poured out and collected as dropsical effu- sions, which were gradually removed by the abundant diuresis artifi- cially produced. The same thing occurred several times in this patient; gradual diminution of the urine, dropsical effusions, and then, after the use of diuretics, increased secretion of water, urea, and chlorine with the urine. 5. An elderly man, whose arteries were remarkably rigid, was at- tacked by a somewhat acute bronchorrhcea, the disease extending over both lungs. The condition of the patient varied remarkably. Severe attacks of dyspnoea, with small and rapid pulse of 100 to 126 beats, which sometimes rendered hipi senseless, alternated with intervals of ease. Examination of the urine showed that corresponding varia- tions occurred in the nutritive functions of the body. During some days not more than from 300 to 400 ; whilst on other days from 1200 to 1500 C. C. of urine were evacuated. Its colour changed from bright yellow to red; the colouring-matter — from 2 to 18 — was usujdly increased (access of fever) ; the specific gravity was of an average number — 1*012 to 1'023; the average amount of sohd constituents considerably less than normal — 18 to 30 grammes. The urea also varied much, but, despite the fever, was on an average much less than normal — 12 to 25 grammes; the urine also frequently con- tained a sediment of urates. The chlorine showed the greatest variations ; it was invariably diminished, sometimes only a trace of it being found in the urine — O'l to 5. The phosphoric acid and sulphuric acid were also diminished. These great variations in the metamorphic processes of the patient, indicating a profound dis- turbance of the constitution, together with the lung-affection, led us to fear a speedy collapse ; which, indeed, occurred very suddenly. In the evening the patient had expressed himself as feeling better than usual ; but during the night he complained all at once of great weakness and faintness, and died in the course of a few hours, spite CONCLUDING OBSERVATIONS. 423 of all the stimulants administered. Death -was caused by the rapid progress of the pulmonary CBdema. 6. A man, 57 years old, was attacked with pneumonia on the left side, the consequence of exposure to severe cold on a journey. He was first treated with cupping and large doses of digitalis. The fever was very acute ; the urine less scanty, than in other like cases, 900, 1000, 1950, 1500, 1350, 1200 C.C, and of high colour; the pigment-matter considerably increased — 28 to 32; the specific gravity somewhat higher than normal — 1*018 to 1-024; the solid constituents for the most part above, but occasionally less, than normal. The urea increased — 40 to 60; the sulphuric acid was increased, in the first instance — 3 "5 to 4 grammes, but afterwards was less than normal — 1"8, 1"1 and 1"6 ; the phosphoric acid nearly constantly increased — 4, 5, 7, 8 grammes. Of chlorine only a trace could be found during the first two days ; but it gradually increased — 3, 4, 7 grammes, and on the eighth day was normal. The patient rapidly recovered, despite his advanced age, and of his having pre- viously suffered from an attack of pneumonia, which had probably injured his lung ; and he left the hospital cured in ten days. The case is particularly interesting as showing the favourable effects of digitalis on the nutrition. Here, as in all cases of acute fever, there was an increase of the wear and tear of the constituents of the body, an unusually large amount of urea and colouring-matter was formed, and an increased quantity of phosphoric and sulphuric acids were separated from their organic compounds. The urine, however, was in this case, and doubtless through the influence of the digitalis, much more abundant than it usually is in such cases ; and in conse- quence the products of the decomposition of the tissues, &c., were rapidly removed from the body, and convalescence hastened. I do not mean to say that this is the only action of digitalis in such cases ; but I refer to this peculiar action of the medicine on account of its being so clearly manifested in this case. 7. A man suffered from chronic affection of the liver and the sto- mach, with organic change of structure, of a nature not easily diagnosed, associated with long-continued disturbance of the digestion, as well as severe pain. His strength was much exhausted. Here the indi- cation was, in the first place, to provide for the immediate treatment, and then, for the sake of prognosis, to investigate more closely the metamorphic changes, going on in the patient. For this purpose the urine was examined on several days ; and the following were found 424 CONCLUDING OBSERVATIONS, to be the average proportion of its constituents j — the quantity was about normal — 1"500 0. C. j the colour clear yellow, the colouring- matter less than normal — 3 ; its reaction slightly acid, its free acid being much diminished — 0'4. The specific gravity was less than normal — 1"014; and so also the solid constituents — 42 grammes. The urea was somewhat diminished — 29 ; and so also the sulphuric acid — 1"4; the phosphoric acid was about normal — 8 '3; and the chlorine — 10 grammes, rather above the normal. From this it followed, that for a time digestion was favourable, the chlorine and phosphoric acid being sufficient ; but thatj on the other hand, the metamorphosis of the proteine-tissues was diminished, the urea and sulphuric acid being deficient. The small amount of colouring- matter, and the marked diminution of the free acids indicated also a defective metamorphosis of the blood-corpuscles — a fact which was also indicated by the pale anaemic appearance of the patient. Under the influence of an abundant animal diet and tonics, the patient gained strength and spirits at least for a time; but, from the nature of the organic disease, no permanent cure could be expected. 8. Cases occur, in which a febrile increase of the metamorphic processes can scarcely be discovered, except from the condition of the urine. The pulse is perfectly quiet, the temperature of the surface of the body about natural, the appetite little affected ; and yet there is an increase in the waste of the constituents of the body, and dimi- nished activity of the kidneys — a condition always dangerous, as a cause of congestion in cases of chronic disease of the lungs, Hver, &c. Congestion, under such circumstances, readily occasions material changes in the structure of parts. The following case comes under this head : A very powerful man, 48 years old, with a broad and weU-arched thorax, presented symptoms, which led to the suspicion of the existence of commencing tuberculosis. For a long time he had suffered from cough and expectoration ; slight dulness of percussion at the apex of the right lung, with indistinct and somewhat bron- chial respiration, and r&les at this point. His inspiratory capacity was less than his bodily size would indicate. During the last few months he had wasted somewhat and lost strength. His pulse, however, was perfectly quiet, 60 to 63; his appetite tolerably good ; J-diet, with different extras ; the temperature of his extremi- ties not increased. During the night he occasionally had severe sweating. The urine, on the other hand, was very abnormal. It CONCLUDING OBSERVATIONS. 425 was much diminished in quantity — 400 to 600 C. C. ; almost always clouded with an uric acid sediment ; very high-coloured, the pigment- matter being increased — 16 to 24; of very high sp. gr.-^l'022 to 1"028; the urea rather above the average^— 28 to 35; the chlorine much diminished — 3 to 5 ; the phosphoric acid^2"5 ; and sulphuric acid somewhat less than normal — 1"5 grammes. Henccj the excretory action of the kidneys was much diminished ; the wear and tear of the tissues much greater than natural, and the blood, in consequence, overcharged with deleterious constituents! It appeared, moreover, that the patient had long suffered from some chronic disease of the skin (probably psoriasis), and that this disease had disappeared about six months ago. Many circumstandes therefore combined together in causing an inordinate action of the lungs, and must have aided in promoting the disorganisation of their structure, which was suspected to be going on. On careful investigation, it was found that, despite of the slow and tranquil pulse, there was increased action of the right ventricle ; and a congested state of the lungs was indicated by a distinct increase of the second sound of the pulmonary artery. The patient, besides, complained of dyspnoea and tightness at the chesti The main indication was, by increasing the urinary secretion to free the lungs from the irritation excited in them by the excess of excretory matters which were retained in the blood. Gentle diuretics were administered — infusion of digitalis with acetate of potash ; and infusion of herba Jacese. With increase of the quantity of urine, the patient's chest became more free, and his general condition improved ; so that after a time he was able to leave the hospital materially improved in health. Out of the hospi- tal, however, he could not obtain suitable nourishment, and indulged deeply in spirits ; his disease in consequence advanced, and in about six months time he returned to the hospital with well-marked tuberculosis of the lungs, and died in the course of a few days. 9. A man, 45 years old, was suddenly seized with acute febrile symptoms, shiverings, and heat, loss of appetite, and bloody urine. In the course of 36 hours the whole of his body, with the exception of his face, became cedematous. A few days later the patient was brought into the hospital, presenting the symptoms above described, with the addition of constant vomiting. During the first three days of his residence there, the condition of the urine was as follows : — Its quantity less than normal — 900 to 1500 C. C. ; its colour a deep blood-red. Under the microscope, a largish quantity of un- 426 CONCLUDING OBSERVATIONS, changed blood-corpuscles was found ia it, as well as numerous pus-corpuscles, and a few granular urinary casts. It was highly albuminous. Its reaction alkaline j sp. gr. low — I'OIO to 1*013 j its urea much less than normal — 8 to 20 ; chlorine diminished — 1 to 3 ; and so also its phosphorus — I'S to 2'8 j sulphuric acid much diminished — 0"-5 to 1"6 grammes. After standing for some time it deposited a mucous sediment, resulting from the action of the ammonia on the pus-corpuscles suspended in it. The perspiration — cutaneous and pulmonary exhalation — was much less than normal, 460 to 780 grammes in the 24 hours. The ingesta exceeded the egesta considerably, so that the patient increased ten pounds in weight iti the course of three days, in consequence of the increase of the dropsical swelling. Diagnosis : Morbus Brightii acutus. The most powerful remedies were used to increase the urinary and intes- tinal secretions, in order to ward off the consequences of the ursemic condition of the patient ; but without effect. AU internal remedies — sulphate of soda with acetate of potash, gamboge, with car- bonate of soda, croton oil — ^were rejected by vomiting; external applications of decoction of digitalis over the whole surface of the body were without any effect. Clysters of croton oil in linseed oil irritated the rectum so much, that they could not be repeated. The excretory action of the kidneys daily diminished ; the quantity of urine fell from 800 to 700, 500, and 450 C. C. per day ; its sp. gr. from 1"015 to I'OIO. The quantity of urea still further diminished — 6 to 8 grammes daily; and in like manner the chlorine — 0-8 to 1; the sulphuric acid — 0*4 to 0"6; and the phosphoric acid — I'S to 1*7 gramme. Symptoms of uraemia, giddiness and delirium, appeared, and gradually increased into coma and sopor, destroying the patient in a little less than three weeks from the commencement of his illness. The autopsy showed the existence, of Bright' s disease in the second stage. 10. A man, 62 years old, of strong bodily constitution, was, like the last patient, attacked with acute disease of the kidneys. Con- siderable oedema of the whole body quickly followed upon the febrile symptoms ; the blood-red urine contained a large quantity of albu- men, and presented under the microscope, traces of urinary casts, together with numerous blood-, and pus-corpuscles. In this case strong diuretics — ^piUs of gamboge and carbonate of soda produced an abundant urinary secretion, and especially after decoctions of digitalis had been extensively applied over the whole of the lower half CONCLUDING OBSERVATIONS. 427 of tlie body. The urine from the 25th of October to November 1st presented the following characters ; quantity much increasedj from 4800 to 6800 C. C. : colour red (bloody) j reaction neutral or alka- hne; specific gravity low — 1"003 to l'005j urea much increased^from 45 to 97 grammes daily j and so also the chlorine — 20 to 30 ; the sulphuric acid — 4'1 to 4-7 j and especially the phosphoric acid — 11 to 18 grammes. The dropsical swelling entirely disappeared with the increase of the urinary secretion; and so Hkewise did the threatening symptoms of uraemia (somnolence and wanderings), leaving the patient to aU appearance quite weU. After a time, however, he had another attack ; violent fever with swelling of the hps and phlyctenous eruption around the mouth, with scanty and very bloody urine. As the latter symptom indicated acute irritation of the kidneys, and as there was a complete absence of dropsical symptoms, diuretics were not administered ; and I considered it of importance to lessen the irritation of the kidneys. Linseed-tea with bitter almond-water was given ; and in the course of two days the former deep bloody-looking urine became almost colourless. 11. Hsematuria, resulting from solution of the hsemato-globuHne (see Secfion xci.). A young man, 20 years old, who had always previously enjoyed good health, complained that for the last 8 days he had felt unwell. His face was remarkably pale, and in some parts livid ; reddish-blue rings were broadly marked under the eyes. The temperature of skin natural ; pulse quick — 90 to 100, small and weak. Together with a feeling of great weariness and depression, he experi- enced pain of a slightly tearing, and dragging nature over the greater part of the body, and particularly in the extremities. There was slight catarrh of the respiratory and digestive organs, want of appe- tite, a somewhat coated tongue, diarrhoea, and distinct enlarge- ment of the spleen. He was taken into the hospital j and supposed, though erroneously, to be labouring under typhus. The febrile symptoms diminished . instead of increasing ; the weak, and often double-beating pulse became slower and fuller : the heat of the body remained natural, being generally under 37° C. (99° Fahr.), and the inteUigence unaffected. The patient, however, became gradually weaker, so that he could scarcely raise himself up : and the anaemic appearance so marked as to give him the appearance of a patient in an advanced stage of cholera. The urine, natural in quantity, was of a dark brownish-red colour, between 7 and 8 of the colour-table — similar, although not quite as dark as that which I had observed after 428 CONCLUDING OBSERVATIONS. the inhalation of arseniuretted hydrogen (see p. 310). It contained at least 300 parts of colouring-matter. No blood-corpuscles could be found in it under the microscope, in fact, no kind of solid matters. On boiling it yielded a very abundant reddish-brown coagulum of haemato-globuline, which when separated by filtration was of a slight yellowish-colour. Its other constituents were normal in quantity, with the exception of the chloride of sodium, which was some- what diminished in consequence of his scanty diet. This state of the urine, which had undoubtedly existed from the beginning of the complaint (of which he could give no account), lasted for about 8 days, and then gradually disappeared. It indicated, that the dis- ease consisted essentially in a continued partial decomposition of the blood-corpuscles within the vessels — the product thereof being se- parated with the urine (and perhaps also with the bile) — causing, by the intensity and duration of the complaint, an advanced condition of oligocythsemia. The state of the urine, combined with the great depression, and the pains in the extremities, also indicated scurvy ; but here there was no characteristic change of the gums, nor ecchymoses, &c,, nor any etiological cause to account for the produc- tion of scurvy. Mineral acids were given to the patient, first of all alone, and then in combination with quinine j and during convalescence preparations of iron. He recovered slowly, but completely. No effective cause of the complaint was discovered. Some months later, and without any appreciable cause, another attack of hsematuria occurred, but of shorter duration and less in- tense than the former. During this attack, as during the former, the patient did not suffer the slightest pain in any part of the urinary system ; nor could any satisfactory cause of the affection be discovered. 12. The following case, essentially different from the former, but arising without appreciable cause, presents an example of hsematuria vesicalis. Eriedrich P., butcher, set. 22, who had never before been ill, and whose parents were healthy (his father suffering merely from hsemorrhoids), was seized with a slight gastric affection accompanied with giddiness and singing in the ears, and entered the hospital. Some years previously he had often suffered from bleeding from the nose ; but of late he had had no kind of haemorrhage. On further investigation, it was found, that his urine was of a blood-red colour, that he suffered from dysuria, and from an involuntary and con- CONCLUDING OBSERVATIONS. 429 tinned desire to pass water^ so as to be forced to urinate every quarter-of-an-hour. The last portion of urine passed invariably con- tained a large quantity of blood. On examination, the orifice of the urethra was found natural, no pain was felt on pressure over the back part of the urethra, nor was anything abnormal found about the prostate or bladder on examination per anum. The bloody- coloured urine deposited, after standing for some time, a scanty darkish-red sediment, which was readily dispersed by shaking, and consisted solely of blood-corpuscles without any admixture of pus. The urine when filtered appeared quite free from blood, and of a bright yeUow colour ; a dark red precipitate of blood-corpuscles remaining on the filter. The urine consequently contained only blood-corpu5cles, and no Lsematine in solution. The blood-corpus- cles undoubtedly came from the bladder, and their presence probably resulted from congestion of its mucous membrane, and consequent rupture of blood-vessels. The treatment consisted in the administration of linseed-tea, with bitter-almond-water ; and under it the patient improved in health. The dysuria ceased in the course of a few days, and the blood gra- dually disappeared from the urine. 13. The following case is of interest, from its close resemblance to a case of hsematuria ; and from the fact, that the absence of this affection was first demonstrated by the microscope. An old gentleman, of 72, had had for five years an affection of the bladder, which showed itself as follows : He had always been healthy, and was, for his age, very . robust. Prom time to time, after excretion, or after mucb walking, he passed a small quantity of blood with his urine, and suffered some little pain about the region of the bladder. The simultaneous passing of gravel with his urine, led to the supposition of the presence of a calculus in his bladder; and he had consequently consulted several doctors, and had been many times examined. No stone, however, was found. His affection was therefore regarded as an hsemorrhoidal state of the bladder, and the patient had, in consequence, resorted to theKissingen and Karlsbad waters, but without deriving any essential benefit from them. He had never passed blood with his motions; nor were haemorrhoids or any enlargement of the prostate discovered. His general condition was good. There was no rigidity of his arteries. His urine was very acid, and deposited large crystalline masses of 430 CONCLUDING OBSERVATIONS. uric acid. There was also observed in it an abundant dirty-red cinna- mon-coloured sedimentj which was quickly deposited, and contained large flocculi. Before this sediment was deposited, the urine pre- sented the exact appearance as when blood is present in it ; and in fact, the patient himself and his many doctors had always hitherto considered that the sediment was caused by blood. Under the microscope, however, numerous cellular forms were found, which, on the first appearance, seemed to be blood-corpuscles, but on closer investigation, were found to be essentially different. They were round, of a red colour, like that of the blood-corpuscles, but somewhat larger, m to m" diameter; contained a distinct nucleated cor- puscle, and were unaffected by acetic acid (see Plate III. Mg. 6, Ti aa). With these were found others, some greater and some smaller, irregular and partly caudate cells, for the most part con- taining nuclei {Mg. 6, D i d 5) partly single, and partly aggregrated (forming thready flocculi visible to the naked eye), and without any trace of a fibrinous basis-membrane. The sediment of the urine also contained normal pus-corpuscles, which, after treatment with acetic acid, exhibited their usual nuclei. Prom the presence of these cells, the existence of fungoid ex- crescences (epithelioma) of the bladder was diagnosed, with tendency to acid urine and separation of uric acid. The treatment ordered was: the regular use of Pachinger water, and linseed-tea, with acetate of potash, and laurel-water. Under this treatment the con- dition of the patient was much improved. Por several months the urine was not coloured with blood ; and instead of the epithelioma cells contained merely a few pus-corpuscles, and some thready coagula of mucus. The patient now suffered merely from occasional pains in the glans penis ; and straining occurred only during the evacuation of the last drops of urine. I trust that the above examples will satisfy the reader that the investigation of the state of the metamorphic processes in the sick is of service to the physician; and that the investigation itself is not so exceedingly difficult, as some persons have imagined. But I would, at the same time, earnestly entreat those who may pursue fur- ther the path of investigation here pointed out, to confine themselves to the possible, and not endeavour, by the aid of bold hypotheses or ill-founded surmises, to assume conclusions, which our knowledge does not yet enable us to compass. Such proceeding is injurious to the interests of the sick, who trust themselves to our care ; and URINARY CALCULI, ETC. 431 cannot fail to lower, both in the eyes of the profession, as well as of the public, the value of this excellent and philosophic method of investigation of disease, viz., the consideration of the chemistry of the metamorphic processes in diseases. APPENDIX. section cxxvi. Ueinaey Calculi and othee Ueinary Conceetions. By urinary concretions, we understand deposits from the urine, which have taken place in the urinary passages, within the kid- neys, ureters, bladder, or urethra. Sometimes these concretions are small, like sand, and pass away readily with the urine; in such case, they are usually very numerous, and as a rule, occur in a crystalline form, (sand, gravel). Sometimes again, they are much larger, from the size of a pea up to that of an apple. When of a size too large to admit of their being evacuated with the urine, they are retained in the calyces or pelves of the kidney or in the bladder, and by their mechanical action excite irritation, pain, hsemorrhage, and inflammation of these parts, &c. They may also become fixed in the ureters and urethra. (Calculi.) Most of these urinary concretions are formed from sediments of the urine, which have been deposited within the urinary passages, and instead of being evacuated, have, through some cause or other, been retained there and gradually formed into large masses; or, again, the calculi may be formed of sediments which have collected round a foreign body, which has found its way into the urinary passages. In the same way urinary concretions may enlarge gra- dually, and more or less rapidly, fresh layers of sedimentary matters being continually deposited upon them. No distinct line of demarcation can be made between urinary gravel and the sediments from which they are formed, for one may pass into the other ; and the same thing is true of sand and small calcuh. Hence there is no practical advantage gained by attempting any arbitrary division of them into separate forms. 432 URINARY CALCULI, ETC. A knowledge of urinary concretions is of great importance to the medical man, on account of the inconvenience, and the danger which their presence occasions in the body. It is the business of special pathology and diagnosis to point out to us their nature and treat- ment. A knowledge, however, of the chemical composition of urinary concretions is of practical use to the physician. Thereby alone can he learn how, by proper medicinal appliances, to prevent the further formation of the sand, which mechanically irritates the urinary passages, or the still more dangerous formation of a calculus, or the further increase of a calculus which has been already formed. It is evident, moreover, that an exact knowledge of the chemical composition of a urinary calculus must form the basis of any attempts to dissolve it within the bladder. The chemical investiga- tion, also, of calculi which have been removed by lithotomy or litho- trity, is often of practical utility, inasmuch as it indicates the proper treatment for the prevention of the recurrence of like urinary concre- tions in the persons operated upon. The chemical constituents of urinary cajculi are essentially the same as those which have been already considered under the head of urinary sediments, viz : — Uric acid and urates. Xanthine. Cystine. Oxalate of lime. Carbonate of lime. Phosphate of Kme. Ammonio-phosphate of magnesia. Proteine-compounds (fibrine, mucus). Urostealith. These being mixed with minute quantities of other matters — ^ silica, alumina, &c. Many urinary concretions consist solely of some one of these constituents. Others, again, are composed of several of them ; the different constituents in some cases forming separate layers of the concretion. As the properties and tests of most of these substances have been already described, it is only necessary here to point out the general processes required for the analysis of such concretions, referring for further particulars to their special history. If we have to deal with sandy deposit, it is advisable, in the first URINARY CALCULI, ETC. 433 place, to examine it microscopically, as from the form of the crystals the chemical natm-e of the matter may be often ascertained. For chemical investigation we must isolate the particles of it as far as possible from all impurities, such as blood and pus, and then wash them with distilled water. If the particles are large, they must be reduced to a fine powder. In dealing with calculi, it must be remembered that they are fre- quently formed of layers differing in chemical composition. The stones must therefore be cut, or better still, broken in pieces, and a small quantity of powder taken from every layer which pre- sents a different appearance, and subjected to analysis. In this case, also, it is well to wash tlie powder with distilled water before com- mencing operations, in order to separate any accidental constituents of the urine which may have become infiltrated into it. The best method of proceeding, especially for those who are not practised in these analyses, is, in the first place, to heat a httle of the powdered calculus to redness on platinum foil over a spirit-lamp. If the powder be wholly consumed, or leave only a very inconsiderable amount of residue, it may consist of — I/ric acid or urate of ammonia, Xanthine (Xanthie oxide). Cystine, Proteine-bodies, Ureostealith. Next, in order to ascertain which of these substances the con- cretion is formed of, we must proceed as follows :— We first test it for uric acid- If, on treating the powder with nitric acid and ammonia, after the manner described at p. 30, 6, and p. 31, a., we obtain a distinct murexide-reaction, the concretion con- sists of uric acid or of urate of ammonia. These two substances are distinguished by the fact, that uric acid is only very slightly soluble in boiling water, whilst urate of ammonia is much more readily dissolved, and in larger quantities. As the solution cools it is again precipitated, and, on the addition of a solution of potash, gives off ammonia (Section xxxvii.). Uric acid calculi are, comparatively speaking, of frequent occur- rence, and sometimes attaia a considerable size. They are rarely white, being generally of a yellowish, reddish, or reddish-brown colour ; they have usually a smooth surface, and are tolerably hard. Urate of ammonia calculi are rarely met with ; they are usually f f 434 URINARY CALCULI, ETC. small, of a lightish or loamy colour, and of a more earthy consist- ence than uric acid calculi. If the urinary concretion is combustible, and offers no murexide- reaction, it may consist of one of the following bodies : — Xanthine (Xanthic oxide). — This substance dissolves in nitric acid without evolution of gas ; the solution on evaporation leaving a bright lemon-coloured residue, which is not reddened by ammonia, but dissolves readily in caustic potash with a deep reddish-yellow colour. The newly-discovered substance, guanine, has a similar reaction ; it is, therefore, necessary to be cautious in deciding that a urinary concretion consists of xanthine. Guanine, however, has never yet been found in urinary concretions. Calculi consisting of xanthine are extremely rare ; only a few spe- cimens, indeed, have been hitherto met with. They have a hght- brown (whitish- or cinnamon-brown) colour, are of tolerably firm consistence, take a polish like wax when rubbed, and usually consist of concentric amorphous layers, which are readily sepai-ated. Cystine calculi are also rarely met with. They are of a dull- yellow colour, have a smooth surface, and present on fracture a glistening crystalline appearance. They are softish, may be readily scraped, and when powdered impart a soapy feeling to the fingers. The following are the chemical characters of cystine : — It is soluble in caustic ammonia, and on slow evaporation of the solution crystallises in very characteristic forms — regular six-sided tables. It is also soluble in mineral acids; and on slow evaporation of an hydrochloric-acid solution crystallises in groups of divergent radi- ating needles. Cystine contains a considerable quantity of sulphur. Consequently, if a calculus, containing cystine, be dissolved in a solution of potash, and after the addition of a little acetate of lead solution the solution be boiled, a black precipitate of sulphnret of lead is thrown down, and gives the mixture an inky appearance. (See Section XL.) Calculi formed oi jaroleine-substances (of fibrine or blood-coagula) are also very rare. They present no appearance of crystallisation, give off when burnt an odour of burnt horn, are insoluble in water, ether, and alcohol, but are soluble in a solution of potash, from which they are thrown down by acids ; in acetic acid they swell up, and ' are soluble in boiling nitric acid. Calculi of uroslealith are equally rare, and have only been noticed by Heller. In their fresh state they are soft and elastic, like caout- URINARY CALCULI, ETC. 435 chouc to the touch. They shrink up when dried, assume a light- brown or blackish colour^ become brittle, and hard, but soften again, when warmed. When heated they fuse, intumesce and give off a very powerful odour, somewhat like that of mixed shellac and benzoine. They soften without dissolving in boiling water. They readily dissolve in ether; and the amorphous uro- stedlith, which remains on evaporation of the ethereal solution, assumes a violet colour when further heated. They also readily dissolve in caustic potash when warmed, and become saponified. They dissolve in nitric acid, with a slight evolution of gas, and with- out change of colour, the residue, on the addition of alkalies, becoming of a dark-yellow colour. II, If the concretion is incombustible, or leaves much residue after exposure to red-heat, it may cdnsist of — Urates, with a fixed base (soda, magnesia, Ume), Oxalate of lime. Carbonate of lime. Phosphate of lime, or of Ammonio-phosphate of magnesia. Urate of soda, wrote of lime, and urate of magnesia, are rarely met with as the sole constituents of a urinary calculus; they are, how- ever, occasionally found in varying quantities in calculi, which con- sist chiefly of other substances, in uric acid and urate of ammonia, calculi, for instance. In order to ascertain whether any of these bases are contained in a uric acid calculus, we boil the pulverised calculus in distilled water, and filter the solution while hot. The urates, being more soluble in hot water than uric acid, will, if present, be contained iu the filtrate. The filtrate is then evaporated, and the residue heated to redness. The fixed bases will remain in the incinerated mass, which, if it renders moistened turmeric-paper brown, we may 6on- clude contains soda or potash. The soda is distinguished by the yellow tinge which it imparts to the fiame of the blow-pipe. If too great heat has not been applied to the residue, magnesia and lime, if present in it, will remain iu the forms of carbonates ; these are insoluble in water, but dissolve readily in dilute acids. Prom such solutions the earths- are precipitated as ammonio-phosphate of mag- nesia, and as phosphate of lime, on the addition of phosphate of soda and ammonia. Oxalate of lime, when strongly heated, blackens in consequence of f f2 436 URINARY CALCULI, ETC. the combustion of its organic matter ; but by prolonged exposure to heat it becomes 'wMte, without undergoing fusion. By still further exposure to beat it is converted into caustic, lime, which renders moistened turmeric-paper brown. By a less degree of heat car- bonate of lime is formed, which dissolves in hydrochloric acid with effervescence. No precipitate is formed when this solution is neutralised with ammonia, but when oxalic acid is also added, oxalate of lime is thrown down, whose characteristic form of crys- tals may be seen under the microscope (see Section xxxviii. b). Oxalate of lime is insoluble in boiUng water, and caustic potash solu- tion; it is soluble in hydrochloric acid without effervescence. Oxalate of lime calculi are often met with, especially in children. They are either small, of a pale colour and smooth, of the size of hempseed — or they are larger, have a rough, warty, nodular surface, and are generally of a dark, brownish, or even blackish eolour — mul- lerry calcuU. These latter calculi usually cause, by their roughness, much irritation in the urinary passages, producing great distress, inflammation, and hsemorrhage. Calculi composed chiefly or entirely of carbonate of Ume are rare ; when met with, they have generally been found in large numbers in the same individual. They have a whitish-grey — rarely a darker, yellowish, or brownish— colour, and present an earthy chalk-like ap- pearance. Carbonate of lime is most frequently met with in small quantity as a component of other calculi, mixed, for instance, with oxalate of lime or earthy phosphates. Carbonate of lime concretions become black when burnt, in conse- quence of the presence of much organic matter (mucus) in them, but are readily rendered white by further heating. They are not fusible. The residue, when exposed to a strong heat, exhibits exactly the same qualities as that of oxalate of lime calculus. It either remains in the state of carbonate of lime, or is converted into caustic lime. These calculi are easily recognised by their characteristic property of dissolving in hydrochloric acid with effervescence. Ammonia-phosphate of magnesia and basio phosphate of lime usually occur together as constituents of urinary calculi. Calculi of this kind indicate, that the urine has been for a length of time ammoniacal while in the bladder, in consequence of the decomposi- tion of its urea. These calculi often become of considerable size, and have generally a whitish colour. When the phosphate of mag- URINARY CALCULI, ETC. 437 nesia and ammonia predominates in them they are softish; porous, and chalky ; but when the phosphate of hme is in excess they be- come thicker and harder. The following are their chemical characters : — They are incombustiblcj but when exposed to a strong heat, fuse into a white enamel-like mass, and have, in consequence, been called fusible calculi. They never become alkaline, however strongly heated, and may thus be distinguished from calculi of oxalate of lime and carbonate of lime. They are soluble in hydrochloric acid without effervescence, both before and after exposure to strong heat ; and the solution of the fused pulverised mass is precipitated with ammonia. To separate these two constituents— phosphate of lime and phos- phate of magnesia and ammonia — from each other, we proceed as follows: The calcined powder is dissolved in dilute hydrochloric acid, and the solution filtered. Ammonia is then carefully added to the solution, so as to leave it very slightly acid, or the solution may be completely neutralised with ammonia, and the cloudiness which appears then removed by the addition of a few drops of acetic acid. If oxalate of ammonia now be added, the lime alone will be thrown down as an oxalate, the phosphate of magnesia and ammonia remaining in solution. After separating the precipitate by filtration, the phosphate of magnesia and ammonia may be obtained by super- saturation with ammonia. Neutral phosphate of lime calculi have been met with in some very rare instances. In their physical and chemical characters they resemble calculi of the earthy phosphates ; but as they contain no magnesia, their solution in hydrochloric acid, after precipitation of the lime with oxalate of ammonia, yields no further precipitate when treated with an excess of caustic ammonia. Urinary calcuh, however, sometimes have a more complicated composition, being formed of several different constituents. Thus, for instance, there are calculi which consist of uric acid, and of urates, and of earthy phosphates ; and others again which are formed of a mixture of oxalate of lime and of earthy phosphates. Calculi have, indeed, been met with, which were composed of uric acid, urate of ammonia, oxalate of lime, phosphate of lime, carbonate of lime, and ammonio-phosphate of magnesia, that is to say, of six different constituents. These various constituents of calculi are sometimes intimately mingled together, and sometimes deposited in 438 URINARY CALCULI, ETC. separate layers, which have manifestly been formed at different periods. This is explained by the fact, that in the same patient different urinary sediments appear in the urine at different times, and are deposited upon a pre-existing calculus, and increase its size. Alternate layers oE uric acid and urates, for example, are formed, when, in a case of uric acid diathesis, the urine is at one time very acid, so that the urates are decomposed, and the uric acid separated ; and at another less acid or neutral, so that the uudecomposed urates are precipitated on the calculus. If the uric acid diathesis alternate with the oxalic acid diathesis, the calculus will be formed of alternating layers of uric acid and oxalate of lime. The calculi frequently met with, composed of alternate layers of uric acid, or oxalate of lime and phosphatic earths, are formed through the periodical re-occurrence of the uric acid or oxalic acid diathesis, the urine being rendered ammoniacal in the iatervals through decompo- sition of the urea. The decomposition in such case results from the presence of the large quantity of mucus, which is produced by the irritation of the calculus, or from temporary obstruction to the flow of the urine. Alternate layers of uric acid and phosphate of lime in the same calculus are sometimes artificially produced by drugs, as when alkalies are administered to counteract the uric acid diathesis. The alkalies make the urine alkaline, and consequently occasion a deposition of the sediment of phosphate of lime upon the calculus. Calculi usually have a nucleus, this is in some cases formed of a foreign body, around which the urinary sediments collect and become incrusted. All foreign bodies which find their way into the urinary passages, or have been formed there, such as blood-coagula, masses of mucus, and fibrine, may become the nuclei of urinary calculi. Sandy particles retained in the bladder, may also form the nuclei of calculi. In the latter case the nucleus has sometimes a different composition from the rest of the calculus, on account of the urinary sediment having undergone a change during its formation. Sometimes the calculus has a cavity in its centre instead of a nucleus ; and in such case the nucleus which originally consisted of mucus has dried and shrivelled up. In some rare cases, the nucleus is found to rattle within the calculus ; in such case it is also formed of dried-up mucus. Occasionally, the calculus consists of sandy particles, or of several small calculi, united together by a menstruum, which may, or not, have the same chemical composition as the calculi themselvejs. URINARY CALCULI, ETC. 439 These different facts must all be taken into consideration, in inves- tigating the chemical constitution of urinary calculi, and in drawing conclusions concerning the probable conditions which attend their formation. Spurious or false urinary calculi are also met with, and their dia- gnosis is of importance in cases where, for instance, an hypochon- driacal patient has got the idea into his head, that he is sufPering from calculus or gravel. Thus it has happened that sand or little pieces of stone, which have accidentally found their way into the chamber-utensil, have been taken for urinary concretions. These usually consist of silicates, and may be in most cases readily distin- guished from urinary calculi, by their external appearance and physical properties (extreme hardness), of course also by their chemical characters. On chemically examining these false concretions the characteristic properties of the substances which form urinary calculi, &c., will not be met with, and, moreover, analysis (fusion with carbonate of potasb, soda, &c., as described in Section xviii.) will generally show the presence of a large quantity of silica, which is not met with in true urinary concretions, or only in very minute quantities. Printed by J. W. Koche, S, Kirby Street, Hatton Garden. y^> ■m ■.■v:v:.v.'«ii!-i>