The recorded increases in endogenous urinary purin are, they consider, far too great to be the outcome of the stimulation of so small a proportion of the cells of the body as those of the digestive tract. On the other hand, they do not deem it necessary to assume that the whole of the endogenous uric acid is the outcome of nuclear disruption, concurring with Burian’s view, that a moiety thereof may be derived from the hypoxanthine of muscular tissue.
Endogenous Uric Acid Excretion
The researches of Leathes and his collaborators permit the deduction that endogenous uric acid excretion bears a definite relation to the activity of cellular processes. Given unchanged physiological conditions, e.g., muscular exercise, the amount of the endogenous uric acid excreted is, for the same individual, fairly constant, and this irrespective of diet; but it is not the same for different individuals, even those of identical body weight.
According to MacLeod, the endogenous excretion in an adult man fluctuates between 0·12 and 0·20 per cent. purin nitrogen. The average daily endogenous uric acid output of a normal adult, as stated by Walker Hall, is about 0·5 gram, while that of a gouty individual is 0·45 gram.
Now Burian and Schur’s original contention was that, in a given individual on a purin-free diet, the endogenous purin output was constant, and this despite marked variations in the amount of the purin-free food digested.
Recent researches, however, of Folin and of Hopkins and Hope, indicate that this dictum must be modified to this extent, viz., that although it is true that the endogenous excretion continues remarkably constant, with moderate variations in the amount of purin-free food, it is not so in the presence of marked variations.
The subject (Hopkins and Hope), after a fast of six hours, was given a meal of bread and potatoes, and at every subsequent hour estimates were made of the amount of urea and uric acid excreted in the urine.
| Time. | Urea. Grams. | Uric acid. Milligrams. | Amount of urine. C.C. |
|---|---|---|---|
| 10-11 | 1·07 | 26 | 175 |
| 11-12 | 1·13 | 27 | 118 |
| 12-1 p.m. | 1·07 | 24 | 164 |
| 1-2 (meal). | 0·64 | 21 | 60 |
| 2-3 | 1·12 | 22 | 43 |
| 3-4 | 1·16 | 38 | 41 |
| 4-5 | 0·84 | 40 | 53 |
| 5-6 | 1·16 | 56 | 59 |
| 6-7 | 1·20 | 39 | 56 |
| 7-8 | 1·37 | 30 | 95 |
| 8-9 | 1·47 | 33 | 183 |
| 9-10 | 1·33 | 24 | 155 |
| 10-11 | 1·33 | 23 | 180 |
It is clear from the results obtained that a very definite increase of endogenous purin excretion ensued, and that the said increase occurred sooner as regards uric acid than urea. This bears out what Mares demonstrated many years ago, viz., that the greatest increase in uric acid excretion occurs in a few hours after a meal, whereas the increase in the case of urea comes more tardily, not reaching its maximum until some hours after.
Horbaczewski referred such increase in uric acid excretion to a digestive leucocytosis; in other words, that the uric acid was the outcome of destruction of the leucocytes, and consequent formation of purin from the released nucleic acid. Unfortunately for this theory, the period of most marked augmentation in uric acid excretion ensues when the leucocytes are most in evidence in the blood-stream, not after they have disappeared, as would be the case if uric acid was derived from the purin product of the nucleic acid liberated by leucocytic destruction. We have a parallel instance in the case of pneumonia, in which it has been shown that the elimination of uric acid and other purins is at its acme when the leucocytes are most abundant; in other words, the highest uric acid output coincides with the period of most marked leucocytosis, whereas during the post-critical stage, viz., when leucocytes are being destroyed in great numbers, the output of uric acid is very markedly lowered. Discussing Horbaczewski’s theory in light of the above criticisms, MacLeod suggests, “that the facts appear to indicate that the purin substance is a metabolic product of the living leucocytes,” and not, so to speak, the chemical outcast of their disruption and death.