to the air: this is a familiar instance of a widespread occurrence in the vegetable world, the formation of a humous substance. These humous substances are allied to carbohydrates, and also to aromatic bodies, as on fusing with potash they yield pyrocatechin, protocatechuic acid, as well as volatile fatty acids. Some appear to be nitrogenous, and such a one is formed, according to Udranszky,' from urea and the normal carbohydrates of the urine on heating with a mineral acid. The dark colour of herbivorous urine, and also that in carboluria, is stated by Udranszky to be due to similar humous pigments, and according to him the pyrocatechin obtainable from such urines is due to the decomposition of the humous substances they contain. The experiments, however, do not appear to me to fully bear out these statements, and until fuller light is thrown on the subject, Udranszky's conclusions must be accepted with caution.

1 Zeit. physiol. Chem. ii. 537; xii. 33.

CHAPTER XLII

OTHER ORGANIC CONSTITUENTS OF THE URINE

A NUMBER of organic constituents, in addition to those already described, may occur in small quantities in the urine. We may divide these into the following groups :

(1) Non-nitrogenous acids: oxalic, succinic, and lactic acids. (2) Fatty acids.

(3) Glycero-phosphoric acid.

(4) Carbohydrates: dextrose, animal gum.

(5) Ferments: especially pepsin.

(6) Mucin.

(7) Cynurenic and urocanic acids.

Oxalic acid (C,H,O4).-The free acid never occurs in the urine, but it is united with calcium to form an oxalate, which, under ordinary circumstances, is held in solution in the urine by the acid phosphate of sodium. Schultzen found that 0.1 gramme (15 grain) was excreted daily by men. Neubauer in some cases found it wholly absent. It is much more abundant in the urine of horses and pigs.

It occurs in excess in the urine after the ingestion of rhubarb and cabbage, the former of which contains an especially large amount of the acid.

It is increased in a condition called 'oxaluria,' in which the most prominent subjective symptom is nervous depression. Oxaluria occurs in a variety of ailments; an increased secretion of uric acid is generally accompanied with an increase of oxalic acid. It also occurs in excess in certain cases of catarrh of the urinary passages.

When present in excess it is in the form of a precipitate of crystals of calcium oxalate. Such crystals are frequently found in the 'lateritious deposit' of febrile urine. Such crystals form, as a rule, after the urine has stood a few hours, especially if it contains excess of mucus, or spermatozoa, as in spermatorrhoea. This deposition of

crystals is probably the result of an acid fermentation.

Crystals of calcium oxalate (C,CaO, +2H2O) are distinguished by their form, quadratic octahedra with a short principal axis; these are

1 Arch. f. Anat. u. Physiol. 1868, p. 719.

often termed 'envelope crystals' (fig. 98). Occasionally dumb-bell forms are seen. The crystals are further characterised by their extreme insolubility; they are insoluble in ammonia, in acetic acid, and soluble with difficulty in dilute hydrochloric acid.

On account of the insolubility of calcium oxalate, oxalic acid is generally estimated as the calcium salt. The origin of oxalic acid in the body is uncertain. Frerichs and Wohler found that dogs fed on uric acid had an increase of calcium oxalate in their urine. The close relationship between uric acid and oxalic acid appears to be undoubted, as may be seen by consulting the account already given of uric acid (p. 729).

FIG. 98.-Crystals of
Calcium Oxalate.

Calculi consisting of calcium oxalate (mulberry calculi) are exceedingly hard and insoluble. Stones consisting of a mixture of uric acid and calcium oxalate are fairly common.

Succinic acid (C,HO1), the third term of the series of acids of which oxalic acid is the first, has been occasionally found in the urine (Meissner '), especially after the ingestion of asparagus (Hilger 2). Salkowski,3 v. Longo* (after ingestion both of asparagus and asparagine), and Baumann3 (after ingestion of sodium succinate) failed to find it in the urine.

Lactic acid (C,H,O,).-This probably does not occur in normal urine. It has been found in the urine combined with bases after great muscular activity;" according to Colasanti and Moscatelli the form of lactic acid which then occurs is sarcolactic acid. It has also been found in cases of trichinosis, acute yellow atrophy of the liver, liver cirrhosis," diabetes," phosphorus poisoning," rickets,13 leucocythæmia," osteomalacia,15 and in animals after extirpation of the liver 16 (see p. 735).

16

Fatty acids. These occur in normal urine in mere traces (0·008 gramme daily). They consist of formic, acetic, butyric, and propionic acids, and the amount in the day's urine can be increased by treating the urine with oxidising agents to 0.9 to 1.5 gramme (v. Jaksch 17).

1 Meissner and Shepard, Untersuchungen ü. d. Entstehen der Hippursäure, Hanover, 1866.

2 Liebig's Ann. clxxi. 208.

4 Zeit. physiol. Chem. i. 213.

5 Ibid. p. 215.

3 Pflüger's Archiv, iv. 95. 6 Spiro, Ibid. p. 117.

7 Gazz. Ital. xvii. 548. The occurrence of lactic acid in the urine (except in frogs) after muscular work is denied by Marcuse, Bied. Centralbl. 1887, p. 92.

8 Simon and Wibel, Ber. d. deutsch. chem. Ges. 1871, p. 139.

9 Schultzen and Riess, Ann. des Charité Krank. xv. 1.

10 Bunge, Physiol. Chem. trans. by Wooldridge, p. 345.

11 Bouchardat, Maly's Jahresb. 1876, p. 155.

12 Schultzen and Riess, loc. cit.

13 Gorup-Besanez, Lehrbuch, 1878, p. 606.

14 Körner and Jacubasch, Arch. f. path. Anat. xliii. 196.

15 Moers and Myk, Zeit. anal. Chem. 1869, p. 520; Arch. f. klin. Med. v. 486.

16 Minkowski (in geese), Arch. exp. Path. und Pharmak. xxi. 41; Marcuse (in frogs), Pflüger's Archiv, xxxix. 425; Nebelthau (in frogs), Zeit. Biol. xxv. 123. The acid appears to be sarcolactic (Nebelthau). 17 Zeit. physiol. Chem. x. 536.

The amount of fatty acids also increases during the occurrence of the ammo niacal fermentation of urea (Salkowski).'

The amount of fatty acids in the urine is increased in certain febrile conditions to 0.06 gramme, and in certain liver diseases to 0 6 to 1 gramme per diem. This condition is called lipaciduria by v. Jaksch. The acids are apparently free in the urine.

Glycero-phosphoric acid (C,H,PO,) occurs in normal urine to the extent of 15 milligrammes per litre. It is increased in nervous diseases (Lepine) and after chloroform narcosis (Zuelzer).

Carbohydrates. Dextrose. The occurrence of abundant quantities of grape sugar in the urine is one of the most prominent symptoms of the disease called diabetes. The question, however, we have now to consider is, Does sugar occur in normal urine? The answer has been sought by many observers, a large number of whom state that sugar is, and a nearly equally large number of whom state that it is not present.3 The conclusion one would draw from a list of references such as is given below is, that if sugar is present at all, it occurs in very small quantities. The difficulty of the investigation is increased by the fact that urine contains several substances that reduce alkaline solutions of cupric hydrate; these are uric acid, hippuric acid, pyrocatechin, glycuronic acid, and creatinine. None of these, however, undergo the alcoholic fermentation on the addition of yeast, and this does take place with the reducing substance of normal urine (Abeles). Some of the older opponents of the view that urine contains sugar said that, even if sugar is formed, it is the result of the decomposition of indican; this, of course, was when physiologists held the idea that the indican of urine, like that of plants, was a glucoside. We have already seen (pp. 79 and 743) that the so-called indican of urine is not a glucoside. The balance of evidence appears to me to be clearly in favour of the existence of a small quantity of dextrose in normal urine. The most recent work at the subject is that of Wedenski. He shook up a large quantity of normal urine with benzoic chloride; by this treatment insoluble benzoyl compounds of carbohydrates, if present, separate out.

1 Zeit. Physiol. Chem. xiii. 264. Salkowski considers that during the fermentation they originate from the carbohydrates of the urine. See also Tanigati, ibid. xiv. 471. * Klüipfel and Fehling, Sotnichewski, Zeit. physiol. Chem. iv. 214.

5 For most of the following references I am indebted to Hoppe-Seyler's Physiol. Chem. p. 828. Those who state sugar is present are: Brücke (Wien. Akad. Sitzungsber. xxix. 346), Bence Jones (Chem. Soc. Quart. Journ. xiv. 22), Tuchen (Virchow's Archiv, xxvii. 26), Ivanoff (Diss. Dorpat, 1861), Meissner and Babo (Zeit. rat. Med. (3), ii.), Pavy, (Guy's Hosp. Rep. xxi. 413), Abeles (Centralbl. med. Wiss. 1879, Nos. 3, 12, and 22), Udranszky (Zeit. physiol. Chem. ii. 537; xii. 33), Wedenski (Ibid. xiii. 122), Salkowski (Ibid. xiii. 264), Hagemann (Pflüger's Archiv, xliii. 501). Those who state that sugar is absent are: Friedländer (Arch. d. Heilk. vi. 97), Maly (Wien. Akad. Sitzungsb. lxiii. 2), Seegen (Ibid. Ixiv. 2), Külz (Pflüger's Archiv, xiii. 269).

Such a precipitation does occur.

Elementary analysis showed the probable presence of two carbohydrates; these were separated by treatment with soda; part remains undissolved, and gives the reactions of dextrose; the part that dissolves gives the characters of

animal gum.

Animal gum.-This carbohydrate radicle of mucin (see p. 480) was originally found in the urine by Landwehr.'

Milk sugar. This often occurs, but in small and variable quantities, in the urine of nursing mothers (Blot, de Sinetz, Hofmeister, Kaltenbach 3). Hofmeister precipitated urine with lead acetate and ammonia, filtered, decomposed the filtrate with sulphuretted hydrogen to get rid of lead, filtered, shook the filtrate with silver oxide, filtered, decomposed the filtrate with sulphuretted hydrogen to get rid of silver, filtered; to the final filtrate barium carbonate was added, and the mixture evaporated to dryness. Alcohol removed milk sugar from the residue, and characteristic crystals of it were obtained by evaporating off the alcohol. Kaltenbach further showed that this substance was milk sugar, as he obtained galactose and mucic acid from it.

6

8

Inosite.-Small quantities of inosite have been found in normal urine by Cloetta, Gallois,' Strauss, Külz'; in the urine of cases of Bright's disease by Cloetta, and in diabetic urine by Mosler and Schwanert.10 Dahnhardt" obtained 01 gramme of inosite from 8 kilos. of oxen's urine. Feeding with inosite does not increase the amount in the urine (Külz).

It may be detected in the urine as follows 12:-Several litres of urine feebly acidified are completely precipitated with lead acetate and filtered. The filtrate is warmed and completely precipitated with basic lead acetate. After standing forty-eight hours the precipitate is collected, washed, suspended in water, and treated with a stream of sulphuretted hydrogen; the lead sulphide is filtered off. Uric acid separates from the filtrate after some hours; this also is filtered off. The solution is then evaporated to a syrup on the water-bath, and absolute alcohol added. The precipitate is dissolved in hot water, and three or four times the volume of 90 per cent. alcohol added. Ether is cautiously added till a permanent cloud appears; the inosite crystallises out, and may be collected; it will then give its characteristic tests (p. 101).

Ferments. Pepsin.-Several observers (Brücke, Sahli,13 &c.) have found pepsin in the urine. The following is an abstract of Leo's 14 work on the subject. Small pieces of fibrin soaked in the urine absorb the pepsin therefrom; on removing them to 0.1 per cent. hydrochloric acid they are rapidly digested. Control experiments with fibrin not previously soaked in urine gave negative results. Morning urine is richest in pepsin.