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.
Lastly, Walker Hall, discussing endogenous uric acid excretion, emphasises the necessity of discriminating between the uric acid output and the total purin output. He reminds us that the actual cell nucleins belong chiefly to the group of amino-purins, i.e., guanine and adenine, and that the oxypurines, xanthine and hypoxanthine, are intermediate products on their way to excretion, another and more advanced intermediate product being uric acid. Now, only a proportion of these intermediary products appears in the urine, this commonly cited to be approximately 50 per cent.
But this, as Walker Hall states, must be taken only as a very broad estimate, for in the same individual the output varies with the number of conditions, not as yet fully determined. But the point most emphasised by him is, that though “the uric acid output varies considerably, the total purin output does not show similar variations; for when the uric acid excretion wanes that of the purin bases usually rises. As a consequence, the total purin output is more constant, less influenced by circumstances, than the output of uric acid.”
This being so, we shall now pass on to consider other conditions influencing endogenous uric acid excretion.