The metabolism of the body is not normally derived from the oxidation of nitrogenous foods. Failing a sufficient supply of other kinds of food, they may be used as sources of energy; but we must picture them as splitting into carbonaceous and nitrogenous portions. If, after the reserve of glycogen in the liver has been brought low by abstention from carbohydrates and fats, nitrogenous food is consumed, and the muscles are then called upon to do severe work, the amount of carbonic acid and water given off rises at once. The excess of urea derived from the nitrogenous food which was destroyed for the purpose of liberating the energy which the muscles expended makes its appearance some time later. If the diet contains a sufficiency of carbohydrates, muscular work does not increase urea. The output of urea is exceedingly steady. It is not increased by muscular work, nor diminished, beyond a certain limit, by absence of food. The tissues are constantly throwing off nitrogen-containing molecules, which, if the body is not to waste, must be as constantly renewed.

Uric Acid.—When nitrogenous metabolism has reached the bottom, when albuminous substances have been shaken into the simplest and most stable compound or compounds which the muscles are capable of making (we know not whether the end-products be one or many), they are carried to the liver by the blood. The mammalian liver converts them into urea; the liver of birds and reptiles changes them into uric acid. Uric acid is not, however, completely absent from the urine of carnivorous animals. In Man the amount excreted is about 0·8 gramme per diem, but subject, even in perfect health, to considerable variations (0·2 gramme to 1·4 gramme). There is no reason for thinking that uric acid is made in the liver of mammals. On the contrary, it seems to be either an end-product of the disintegration and oxidation of leucocytes ([cf. p. 53]), or, like certain other more complex nitrogenous compounds which appear in very small quantities in the urine, the relic of albuminous food which has missed the broad down-path, via muscles and liver, to the kidney. It is a troublesome burden for lymph and blood, and, unfortunately, the kidney finds difficulty in throwing it out. Uric acid has a pernicious way of accumulating in tissue-spaces, producing all the malevolent symptoms of gout. During an acute attack of gout the quantity of uric acid in the system may be largely increased. It may be so abundant in the blood that, when a sample is allowed to cool, uric acid begins almost immediately to crystallize out. Speaking generally, it is right to ascribe gout to an over-production of uric acid; but it must be remembered that the balance between elimination and production is very delicately adjusted. During an attack of gout the amount excreted in the urine is not increased; frequently it is less than usual. The clearing up of the attack is accompanied by abundant excretion of urates, or lithates (λίθο, stone), as they used to be called, because the “stones” which are found in the bladder consist largely of uric acid. From this it appears that faulty distribution and inadequate excretion have more to do with the development of the symptoms of gout than over-production. In a previous chapter ([p. 140]) we gave as the predominant cause of gout acid fermentations in the stomach. It does not, by any means, follow, however, that we were right in correlating imperfect digestion with an excessive formation of uric acid. It may well be that the gouty symptoms to which hampered peptic digestion gives rise are due in larger measure to a disturbance of the composition of the body-fluids which renders them unfit to carry uric acid to the kidneys in such a form, or in such relation to the fluid in which it is dissolved, as will insure its escape into the urinary tubules. The interference with the efficient working of the system caused by accumulation in it of uric acid gives a particular interest to all that is known regarding the nature and origin of this substance.

Uric acid has the formula C₅H₄N₄O₃. It is a more complicated and a more stable body than urea. The deposits of guano in Peru contain uric acid (the excrement of birds) which has remained practically unchanged for years—for centuries, perhaps. Its chemical nature is not completely understood. It can be readily made to yield urea; and it can be formed by conjugating urea with a nucleus derived from lactic acid ([cf. p. 13]). Its formula is therefore commonly represented as that of a diureide—a substance containing two urea radicles:

CO HN—CO
|
C—NH
| CO
HN—C—NH

But notwithstanding this inclusion in its molecule of two radicles of urea, it is safe, when one thinks of the contrast between urea and uric acid, to lay stress, in the case of the former, on the binding of nitrogen to hydrogen; in the case of the latter, on the binding of nitrogen to carbon.

Uric acid is soluble with difficulty; it crystallizes in rhombs. It forms salts, normal and acid. Those which appear in the urine are always acid salts. As a treatment for “stone,” lithia water has long had a reputation which it probably deserves, the acid urate of lithium being the most soluble salt of uric acid which the kidney can secrete. When uric acid is in excess in urine, brown crystals of uric acid are deposited as “gravel” soon after it is passed. Even when not in excess, uric acid crystals appear after a sufficient time. In other cases uric acid, when in excess, is thrown down in the form of a cloud of acid urates of sodium and other bases, which renders the urine turbid. These urates are redissolved when the water is warmed.

The more fortunate of human beings need never concern themselves with the chemical history of uric acid. It is always present in their body-fluids. It is excreted by the kidney. Its formation is of no greater interest than that of creatinin and other nitrogenous compounds which escape the almost universal reduction to urea. Persons who have a uric acid diathesis are in a very different plight. Every scrap of evidence bearing upon its origin is of supreme importance. Unfortunately, the evidence collected as yet is scanty, and its application for remedial purposes impracticable.

The only disease in which uric acid is invariably in excess is leucocythæmia. This is a condition or habit marked by the presence in the blood of a very great number of white blood-corpuscles and a paucity of red ones. The connection between this disease and the production of uric acid is made plain by certain experiments in diet. If flesh which contains relatively a large proportion of cell-nuclei is eaten, the uric acid excreted is markedly increased. Sweetbread, especially “neck sweetbread”—i.e., thymus gland—is a mass of comparatively small cells with large nuclei. If thymus gland be substituted for all other meaty foods, the quantity of uric acid appearing in the urine is doubled. A large increase in the quantity of ordinary meat or fish consumed also increases uric acid, because all meat-fibres contain nuclei. If egg-albumin be taken instead of meat, uric acid is not increased. A sudden excess of muscular work leads to an increase in uric acid, owing presumably to the unusual activity of the tissues. This used to be very noticeable in the case of young men during the first few days of “training” under the old system; but it may have been due to the generous consumption of chops and steaks, rather than to the increase in physical work, and consequent destruction of tissue. Nuclei contain nucleo-proteins, which split into proteins and nuclein. Chemically, it is reasonable to attribute to nuclein the parentage of uric acid; a plausible line of descent can be traced. The association of leucocythæmia with the production of uric acid is probably due to the destruction of leucocytes which are present in abnormal numbers ([cf. p. 53]).

Such is the evidence at present in the hands of physiologists. Naturally, physicians have endeavoured to turn it to account. Patients have been recommended to avoid animal foods which contain nucleo-proteins—to take, instead of meat and fish, eggs, milk, cheese, vegetable-albumins. Certain physicians contend that such a diet is followed by the happiest results; others, equally competent, and perhaps less biassed by “medical theory”—the most dangerous of handicaps for anyone who practises an art which must ever remain empirical—are satisfied that equally good results are obtained by excluding from the diet eggs, milk, and cheese. Physiological discoveries suggest treatment. Modern medicine is in the fullest sense applied physiology. But treatment based upon theory must be controlled by unprejudiced observation. It is possible that the gouty diathesis may be held in check in certain cases by the exclusion from the diet of certain kinds of nitrogenous food. The experience of generations has taught us that the injudicious use of such articles of diet as fruit, pastry, sugar, which do not contain nitrogen, is the main factor in inducing an attack of gout; that imperfect digestion, sluggish circulation, insufficient activity on the part of the kidneys, lead to the accumulation in tissue-spaces of the fons et origo malorum. Even sweetbread, which with the precision of a chemical experiment increases the production of uric acid by a healthy person, is not necessarily found unwholesome by those who are inclined to gout. It is amongst the most digestible of all meat foods, and easy digestion covers a multitude of metabolic sins.