The actual amount of uric acid excreted on a purin free diet varies from .25 gram to .6 gram, and on a mixed diet from .5 gram to 1 gram in the twenty-four hours, and it rises rapidly with the increase of flesh foods or glandular organs in the dietary.

Even after its formation in the body its quantity by no means remains constant, as it is in part further decomposed and much changed before excretion. The various steps in the process of the formation of uric acid from nuclein are of great interest, chiefly on account of the important part played therein by ferments. The first stage is effected by nuclease, which liberates the two purin bases adenin and guanin from the nucleic acid, and these are again attacked by the adenase and guanase forming respectively hypoxanthin and xanthin by the substitution of an oxygen atom for the amino group. These two deamidising enzymes are succeeded by oxidising ferments or oxidases, which convert hypoxanthin into xanthin and xanthin further into uric acid.

The active agent in the disintegration of uric acid is the uricolytic enzyme, which is capable of decomposing quite half of it into urea (and perhaps lactic acid), carbonic acid, and water. It has been estimated that about one half of the hypoxanthin nitrogen, and one quarter of the nuclein purin nitrogen appears in the urine as uric acid, while one third of the caffein nitrogen is excreted as basic purin nitrogen, The liver and spleen contain considerable proportions of these enzymes, and it is more than probable that alcohol destroys or inhibits the action of the uricolytic ferment in the liver. It is indeed possible that inhibition of this ferment may be achieved by other agencies, viz., the sea air and the east wind, both of which have a tendency to cause an increase in the output of uric acid, and undoubtedly exert some malign influence on the liver. Toxins such as tea, coffee, tobacco, etc, may also have the same action.

Three or four years ago Wiechowski declared that no satisfactory proof had been adduced that urea was the end-product of purin metabolism in mammals, but that in man uric acid, and in dogs allantoin, were the excretory products of purin bases. Ackroyd has now in the main confirmed this view so far as dogs are concerned, because by perfusing normal saline through the excised liver, as being the least likely to upset the normal ferment action, he found that a small quantity of allantoin was produced, and that the uric acid was destroyed and partly converted into allantoin, with no indication of urea.

Variable quantities of uric acid are oxidised in different people at various times, and in every case the uric acid discharged in the urine is only the balance left over from the original amount formed after deduction of the amount destroyed.

Increase of the excretion of uric acid may be due to -

(1) An increase in the consumption of exogenous purins.

(2) Increased destruction of the cells in the body.

(3) Diminished oxidation of uric acid in the body.

(4) Increased washing out of stores retained in the body. There is, however, no proof of the retention of uric acid in the body excepting temporarily in gout, although exogenous purins may remain for days in the body.

(5) The possibility of a synthetic formation of uric acid in the body from substances other than nuclein or purins.

As has been already mentioned, uric acid is the terminal product of protein katabolism in birds and reptiles, where it is formed in the liver unquestionably in a synthetic manner, urea, strange to say, being its immediate precursor. When the liver in these animals is extirpated or artificially excluded from the circulation, lactate of ammonia is excreted instead. Now we know that during exercise lactic acid is developed in the muscles as a fatigue product, and that many other acids in small amounts, such as carnic acid, inositic acid, with small quantities of urea and at least three purin bodies - hypoxanthin, xanthin, and uric acid - are to be found. Lactic acid is likewise to be found in the stomach in the early part of digestion, and in large quantities in the alimentary canal in indigestion. We have also seen that protein is broken down into ammonia, and in this way carried to the liver, and so all the elements for the synthetic formation of uric acid would appear to exist. But at any rate in normal circumstances there is not a sufficiency of lactic acid to reach the circulation, and although in abnormal circumstances it may do so, no definite proof exists of this method of formation of uric acid in mammals.

Uric acid, however, is certainly formed in most of the organs of mammals, and some observers declare that the muscles by the oxidation of hypoxanthin are prominent in this action. Spriggs, on the other hand, declares that the source of by far the greater part of the endogenous uric acid is to be looked for in the non-muscular tissues. It is important to remember that the organs which form it are also capable of destroying it. The ingestion of water has no influence on the formation of uric acid, and but little on its excretion.

It may be established as a principle that purin excretion is fairly constant for any person living under the same physiological conditions. In any individual, however, continued administration of salicylates will cause an increase in the excretion of uric acid, the quantity gradually diminishing day by day for about five days until the effect is lost. As this occurs alike in mixed feeders and purin-free feeders, it may be taken for granted that it is the endogenous uric acid which is thus affected. The increase in the excretion of uric acid may be re-established either by daily increasing the dose of salicylates or ceasing their administration for a couple of days and then resuming the original dose. On the cessation of the salicylates the excretion of uric acid is diminished to a point below the normal. Various explanations have been offered for this action. Some hold that it is due to an actual solution and loss of the uric acid in the tissues; others that it is caused by increased metabolism of the nucleins; while others again declare that it is due to diminished destruction of the endogenous uric acid by inhibition of the uricolytic ferment. Another hypothesis is that the salicylates act as bactericides, preventing, or at least lessening, putrefaction in the colon, and this is interesting in view of the suggested influence of the bacillus coli in uric acid formation.

A more recent explanation is that, like all antiseptics, the salicylates produce much irritation of the intestinal mucous membrane, in addition to killing the bacteria, both of which factors militate against the complete breakdown of the proteins to a stage in which they may be absorbed, and hence proteins are excreted with the faeces. This would certainly account for the decidedly laxative properties of salicylates, especially in the form aspirin and novaspirin.

Purin bases chiefly in the form of methyl-xanthins are found in the urine to the extent of about 8 per cent. of the uric acid excreted, and it should be noted that the one cannot be substituted for the other. A large quantity of xanthin bases occur in the faeces from (1) unabsorbed nuclein substance in the food, (2) the nuclein substance of the epithelium separated from the mucous membrane of the bowel wall in a fashion analogous to the shedding of the epidermis.