Physiological Conditions
It is now recognised that the purin bases of the body exist not only in the bound form (nucleic acid), but also free, especially in muscular tissue. Also, that from such free purin bases uric acid can be readily formed as from those liberated by the disruption of nucleic acid. Thus, inosinic acid, a nucleotid first isolated from meat extract, yields phosphoric acid and the purin base, hypoxanthine. In possession of these facts, we shall be better able to appreciate the significance of the researches of Burian and others.
(a) Muscular Exercise.—According to Burian a large increase in the excretion of uric acid was found to follow muscular exercise. The same observer also noted the presence of hypoxanthine in defibrinated blood after its perfusion through the hind legs of a dog whose muscles had been thrown into tetanus. Moreover, subsequent to contraction, the muscles themselves contained an increased amount of oxypurine. From these findings Burian concluded that hypoxanthine was a product of muscular action, and that this substance or its precursor, inosinic acid, was an important source of endogenous uric acid. The uric acid thus formed by oxidation was then partly destroyed in the liver and partly excreted by the kidneys. But Burian noted also during activity of the muscles that a certain amount of the purin bases failed of oxidation, and consequently a larger amount of the same, as compared with uric acid, passed into the circulation.
Kennaway, discussing the effect of muscular exercise on the excretion of endogenous purins, noted that during unaccustomed exercise the uric acid output of the kidneys diminished, but that of the purin bases is relatively augmented, but, on the whole, he found that the total purin output (bases plus uric acid) was not very much increased.
Leathes and others, investigating the effects on uric acid excretion of strenuous exercise, established the occurrence of a distinct increase. Given that the same kind of exercise is practised on the day following, the said increase is much less marked. If, however, some different form of muscular activity is undertaken, another increase in uric acid follows. It would appear, therefore, that, despite conflicting evidence, the balance of opinion favours the view that muscular activity does lead to increase in endogenous uric acid excretion.
(b) Periodic Variations.—Leathes noted diurnal and nocturnal variations in the excretion of endogenous uric acid, the maximum occurring within the early waking hours, and sinking to a minimum towards the evening. His experiments, he held, indicated a variation in the actual formation of endogenous uric acid at different periods of the day. Rockwood also found that an increase occurred during the daytime, and Pfeil, that there was a morning rise in the amount of uric acid passed. The fact that doubt still obtains as to whether muscular exercise has any effect on endogenous uric acid excretion, renders explanation of this diurnal variation difficult. This especially as there are no fluctuations in the urinary functions that could in any way account for it.