Dr. Haig depends for his estimation of uric acid in the urine on the Haycraft process, which he considers rapid and very constant in its results. Even although it may be all he claims for it from a clinical point of view, it is evidently not accurate enough to satisfy the requirements of scientific research, and it is significant that every physiological chemist of repute has discarded it long ago as unreliable. If I may speak from my own experience in a fairly long research on the subject, I should say that it over-estimates the quantity of uric acid. In any case, I submitted samples of the same urine from which I had been working to the most competent observers - one using Haycraft's process, the other the Ludwig-Salkowski method - whose names I am not at liberty to publish, with the most discordant and absolutely irreconcilable results.

The most exhaustive and trustworthy research on the urine has been made by Professor Folin, of Harvard, and he has formulated a series of laws governing its chemical composition, which are of such general applicability that they are now accepted by physiological chemists in the light of principles. The three leading points in Dr. Haig's theory are: -

(1) That the relation of uric acid to urea is constant, viz., 1 to 35 or thereabouts.

(2) That the quantity of water in the urine varies from hour to hour and from day to day inversely as the uric acid excreted along with it.

(3) That the acidity of the urine varies inversely with the excretion of the uric acid, and directly with the excretion of urea, being low when the uric acid is high, and high when the urea is low.

Folin And The Chemistry Of The Urine

In each of these conclusions he is at variance with Professor Folin, who finds that: -

1. "When the total amount of protein metabolism is greatly reduced the absolute quantity of uric acid is diminished, but not nearly in proportion to the diminution in the total nitrogen, and the percentage of the uric acid nitrogen in terms of the total nitrogen is therefore much increased."

As regards the urea, he finds that it is "the only nitrogenous substance which suffers a relative as well as an absolute diminution in the total protein metabolism." The evident amount of uric acid will therefore increase out of proportion to urea when the quantity of protein food is diminished, and diminish when the quantity of protein food is increased. The relation, therefore, cannot be constant. It is a mistake to think that in the absence of food the hourly excretion of endogenous uric acid will be constant, for evidence is accumulating to show that under exceptional circumstances, such as starvation or a low nitrogenous diet, the absolute quantity of endogenous uric acid eliminated may be diminished, although in Chittenden's long experiment the output of uric acid was very little affected. It is also notable that the ingestion of a purin-free meal increases the uric acid output during the hours immediately following the ingestion of the food above the quantity obtained during abstinence. When in similar circumstances purin-free egg-proteins are administered a still greater quantity of uric acid is eliminated.

Haig's accurate observation that uric acid is excreted chiefly in the morning hours, when the output of urea is moderately low, and is diminished in the evening hours, when urea appears in greater quantity, is in practical agreement with the results of an investigation made into the subject by Leathes and Cathcart, who are, however, unable to give assent to the assumption that the excretion is controlled by the acidity of the urine. According to Leathes, the total nitrogen-content of the urine is greater during the night than during the day, confirming the belief that the renal activity is at its maximum during the night. The uric acid excretion, on the other hand, is greatest in the morning, between 10 a.m. and 1 p.m., steadily declining until it reaches its minimum in the earlier part of the night, an augmentation being observed at the usual waking hour of 7 a.m., and gradually increasing thereafter. He is chary of offering any explanation of these facts, but insists that they are occasioned by diminished functional activity of some organ other than the kidney.

It is fair to add that Leathes' observations were made on subjects who were fed every three hours during the day on purin-free meals, at each of which the same volume of fluid was consumed, with the express object of eliminating irregularity in excretion. This variation from ordinary conditions doubtless accounts for some otherwise unexplained differences, and with some diffidence I advance the following suggestion, which renders it unnecessary to appeal to the reaction of the urine. During the activities of the day, when the muscular metabolism is at its height, the skin and lungs are called upon to make greater excretory efforts than the kidneys, and hence a greater volume of blood passes through the former, whereas during the muscular repose of the night the kidneys are in a better position for obtaining a larger share of blood, and thus exercising their function as the chief excretory organs of nitrogenous waste. Few people eat much after 7 p.m. or between that hour and 8 a.m., and as a rule what they do eat, even in the morning, contains a minimum of protein. Hence most of the urea is expelled before the time for getting up, and as the excretion of uric acid is now at its height, its proportion in relation to urea is therefore markedly increased in the morning hours. Urea is manufactured in the body independently of muscular action, the quantity being controlled entirely by the supply of protein food, whereas uric acid and creatinin are in some way associated with muscular contraction, and their excretion begins to increase the moment the organism wakes to active movement. Burian and Schur consider that endogenous purins formed in the tissues are there oxidised to uric acid, some of which is destroyed by the liver, and some of which is excreted as such by the kidneys. They believe this is proved by the effects of diuretics, which increase the elimination of uric acid by increasing the flow of blood to the kidney, and do this without affecting the other nitrogenous constituents of the urine. They further believe that half the total quantity of the blood passes through the kidneys.