The analyses of different urine samples have shown that the amount of water present in urine seems to influence indirectly its constitution. It could thus be seen that while very diluted urine, corresponding to a large amount of water excreted, is usually alkaline, concentrated urine, corresponding to small amounts of water excreted, is generally acid. Furthermore, it could be seen that these changes are related to more profound metabolic differences. When related to the nitrogen metabolism, it could be seen that diluted urines are rich in free ammonia while concentrated urines in uric acid. We have thus investigated the relationship between these two factors, the amount of water excreted and the form under which the nitrogen is eliminated.

The comparative physiology shows us that the manner under which nitrogen is excreted varies for different animals according to the amount of water available in the surrounding environment. In fish, with water almost unlimited, nitrogen is excreted in the form of ammonia. The high toxicity in this form of nitrogen excretion is counter balanced by the amount of water in which the excreta are diluted. Fish are ammonioselic. In terrestrial mammals, where the amount of water available is more limited, the excretion of nitrogen is made in the form of urea which is much less toxic than ammonia. The danger of poisoning the drinking water through excreta is thus reduced. Mammals are ureoselic animals. For birds, for whom water is scarce, the form of nitrogen excretion is of uric acid, which through its low solubility in water, has little chance to contaminate the drinking water. Birds are uricoselic. Based on this relationship between water availability and the type of nitrogen excretion, we looked for a similar relationship in humans between the excretable amount of water and the type of nitrogen metabolized under normal and abnormal conditions. An immediate confirmation was obtained in those abnormal conditions where the amount of water excreted is abnormal. As already seen above, in subjects having a high diuresis, which in general would correspond to a high amount of water available to be excreted from the body, the urine is usually alkaline, the alkalinity due to ammonia. On the opposite side of the normal, there are subjects with a very reduced urinary excretion. In patients eliminating only two to three hundred cc. in 24 hours, the amount of uric acid in the urine is manifestly increased. Upon standing, these urines always show a reddish deposit formed mostly by uric acid. Relating this to comparative physiology, while the normal subjects would appear ureoselic, those with polyuria can be considered as ammonioselic and those with oliguria, uricoselic.

We tried to see if a change in the form under which the nitrogen is eliminated can be induced by changing the amount of water available to be excreted. Normal subjects whose urines were tested for certain periods of time for their content of ammonia, urea and uric acid, were given 1 to 2 liters of water to drink. The highly diluted urine which was subsequently excreted, became alkaline. The total amount of ammonia increased while urea and uric acid were slightly reduced. The same subjects were later given a dry diet for 12 hours or more. The specific gravity of the urine in most of these cases was above 1.026, indicating a kidney with normal concentration capacity. Although the content in ammonia decreased manifestly in these urines, the increase in uric acid excreted was minimal. We submitted the same subjects to a diet with fluids reduced to a minimum, for 3 to 4 days. Under these conditions, the excretion of uric acid started to increase. Great intake of water would thus transform a normal ureoselic individual into an ammonioselic in only a few minutes. A similar passage into uricoselic was seen to need days, and even then it showed only minimal changes. This can be explained by the fact that while ammonia in urine appears largely through changes taking place in the kidney cells themselves, uric acid results from more profound metabolic changes, which concern especially the nitrogenous bases, particularly the purines.