Gout, with a section on ocular disease in the gouty

by Llewellyn J. Llewellyn

Pathological States

Endogenous uric acid is increased under certain pathological conditions. Leathes’ recent work confirmed the view that there is an increased production of nitrogenous waste in fevers. After taking a large dose of anti-typhoid serum his temperature rose to 103° F. Experimenting on himself, he found his output of urea, uric acid, and creatinine all increased, but of all three uric acid showed the most marked alteration. The question now arises as to whether such is due to increased production or diminished destruction. Some further experiments conducted by Leathes on himself may serve to elucidate this point. Subjecting himself for a prolonged period to cold baths, a similar increase in his uric acid output ensued. This would appear to indicate that, through increased loss of heat, the bodily processes of combustion were augmented to maintain the body temperature, with, as a consequence, increased uric acid excretion.

In leukæmia protein-destroying forces are at work, and the urine contains large quantities of uric acid. The same is attributed to the formation and destruction of enormous numbers of leucocytes, but the urinary findings in this respect have been extremely variable. While increased uric acid elimination has been vouched for by many authors, some have noted increase in the purin bases, sometimes with, and sometimes without increase in the uric acid; while others again have even noted a decrease in uric acid and phosphoric acid excretion.

Apart from these contradictory findings, it would appear, according to Magnus-Levy, that in acute leukæmias the relation between the number of leucocytes and the uric acid output is most variable. Lastly, the different types of leukæmia present differences in regard of their uric acid output, the increase in the myelogenous variety being much more marked than in the lymphatic form.

Wells, discussing these conflicting data, considers that they are but the reflex of the “known fluctuations in the course of the pathological processes of leukæmia; the number of leucocytes, the size of the lymphatic organs, and the general condition of the patient all vary greatly from time to time, often with remarkable rapidity and the excretion of products of metabolic activity must vary likewise.” Continuing, he observes that the enormous increase in the amount of lymphoid tissue in the body and blood must give rise to a greatly augmented nuclein katabolism, with sequential appearance of uric acid, purin bases, and phosphoric acid in the urine. This he holds to be well demonstrated by the increased elimination of uric acid and purin bases, together with a general increase in the nitrogen output such as has been frequently noted in sequence to the therapeutic use of X-rays in leukæmia, this attributable to the increased autolysis known to be induced by X-rays.

As to this question of the relationship of leucocytosis to uric acid excretion, it must be borne in mind that the number of leucocytes and the excretion of uric acid do not always vary directly. Parallel studies of the blood and urine have shown that leucocytosis does not invariably accompany increased uric acid excretion. Indeed, Hutchison and MacLeod have recorded cases of leucopenia without any reduction in the amount of uric acid eliminated.

Also, we have to recall that on a purin-free diet the amount of endogenous uric acid is more than can come from nuclein destruction in the body. As suggested by Burian, some may be derived from the hypoxanthine in muscular tissue. In short, while nuclein disintegration is the outstanding source of endogenous purin, yet, for the reason cited, it cannot be regarded as the sole source, for the exact origin of all the endogenous purin is not as yet established.

In conclusion, it would appear that some drugs influence more or less markedly the excretion of endogenous uric acid, notably, atophan; but discussion of these will, we think, be best postponed to the section dealing with the medicinal treatment of gout. Meanwhile we shall proceed to consider the vexed question of the formation within the organism of uric acid by synthesis.