Gout, with a section on ocular disease in the gouty

by Llewellyn J. Llewellyn

Localisation of Uratic Deposits

Uratic deposits evince a decided predilection for cartilages, tendons, muscles, and skin. This localised distribution of the depositions would seem to suggest their dependence on local tissue peculiarities. Now the presence of sodium salts in a solution diminishes the solubility of urates therein. Consequently, in seeking to explain the incidence of tophi, it was suggested that cartilage and tendons, being richer in sodium ions than the blood, this might account for the fact that urates tend to be precipitated in these particular structures.

Again, Almagia, working in Hofmeister’s laboratory, noted that thin sections of cartilage, if left for some hours in a solution of sodium urate, will take up uric acid. Direct inspection readily reveals the presence of white foci and diffuse opacities due to uratic deposits. The marked affinity of normal cartilage for uric acid is again attested by the fact that, given injection thereof in quantity into the peritoneal cavity of rabbits, the uric acid may often be detected by the murexide reaction in joint cartilage, though apparently not in other tissues.

This behaviour would appear to justify the conclusion that the observed accumulation of uric acid in the cartilages in the presence of states of uricæmia, may be explicable on this same basis. In any case, this marked affinity of even normal cartilage for uric acid seems to disprove the necessity of Ebstein’s postulate, viz., that the dissolved uric acid sets up inflammation, and that an antecedent necrosis precedes the deposition of urates. Still, even if we concede the fact that normal cartilage has a marked affinity for uric acid, how is it that in leukæmics, despite their high blood content of uric acid, no uratic deposits ensue? Does not such disparity seem to indicate that in gout some other factor intrudes? in other words, that the excess of sodium ions in particular tissues, while it may favour deposition therein, is inadequate of itself to actually determine the formation of tophi.

The Causation of Tophi

Many and divers are the theories that have been propounded to account for the genesis of tophi. For some their incidence would appear to predicate something abnormal in the conditions of uric acid solution and circulation. Others have pinned their faith to some affinity on the part of the bodily tissues for uric acid—an enhanced retention capacity on their part for this substance. Some again, impressed by the objective changes that mark the clinical evolution of tophi, have been led to regard them as concomitants or sequels of gouty inflammation. But, be the true explanation what it may, we may well preface our discussion of the various theories by the obvious comment, viz., that the origin of tophi must doubtless depend in the ultimate upon constitutional or systemic, as well as local, factors.

Solubilities of Uric Acid

In the older conceptions of the pathology of gout the hypothesis that found most vogue was that the separation of uric acid from the blood into the tissues was due to diminished alkalinity of the blood and tissue juices; but, as before pointed out, it has been established that the alkalinity of the blood is not reduced, and the theory has consequently been abandoned.

But, with the advent of Gudzent’s findings, viz., that uric acid existed in two forms—one soluble and unstable, and the other insoluble and stable, and that the former is constantly changing into the latter—another conception of the origin of tophi arose. It was supposed that, by reason of the disparity in solubility of these tautomeric types of uric acid, the blood in gouty subjects must at times be in a state of super-saturation with uric acid; and, moreover, that equilibrium could only be restored through abstraction of the urates by crystallisation.

Unfortunately for this theory, it has been shown that the blood of gouty subjects is not super-saturated therewith; indeed, over and above the highest increments hitherto met with in gouty blood, a considerable margin of solubility for uric acid is still available. In truth, the problem is by no means so simple; for the conditions governing the solvency of uric acid in the blood are bewilderingly complex, subject as they are to the manifold variations in solubility exhibited by crystalloids in the presence of the many divers colloids.