Gout, with a section on ocular disease in the gouty

by Llewellyn J. Llewellyn

Growing Scepticism as to Garrod’s Pathogeny of Gout

It will be recalled that as far back as 1889 Duckworth displayed disquietude as to the adequacy of the purely chemical or purely physical view of the pathogeny of gout, as sufficing for an explanation of all its varied phenomena. Thus he writes: “It is incumbent, I believe, to invoke not only a chemical and physical basis for gouty disease, but to include also, in a comprehensive view, the marked determining influence of the nervous factor in the problem.”

Whether we agree or not with Duckworth’s view of gout “as a diathetic neurosis, due to a central neurotic taint, and originating from prolonged toxæmia,” it does, I think, mark the dawn of a reaction from the uric acid theory of its causation. Still, this latter conception continued to dominate the field until seriously called in question by the results of Magnus Levy’s researches. His revelations were, in truth, almost revolutionary, and doubts now accumulated as to the propriety of the terms “uric acid diathesis,” “uric acid intoxications,” “lithæmia,” etc., so long credited as being responsible for not only nearly all the minor ailments flesh is heir to, but especially those relating to joints and muscles, all alike attributable to the presence of excess of uric acid or urates in the blood.

To hasten the process of disillusionment there came from the side of the physiologists the announcement, almost unanimous, that uric acid, though in minimal amounts, is a normal constituent of the blood, organs, and tissues. Thoroughly purged now of their obsession as to the pathological potency of uric acid, there awoke a spirit of inquiring scepticism. On all sides it was felt that the whole problem must be looked at afresh, untrammelled by previous conceptions, no matter how high the sanction. How else, indeed, could the chaff be winnowed from the grain, the illusions born of inaccurate observations be replaced by the substantial form of truth?

Still, it would be ungracious to withhold our due meed of admiration for the masterly manner in which the views of the earlier physicians as to the causation of gout were elaborated, the shrewd and often prophetic inferences, well buttressed by arguments based on clinical and pathological analogies; these the more wonderful when we recall the meagreness of the positive material at their disposal, and that little, alas! how often ambiguous!

In light of latter day views, too, we may well admire the swiftness with which the inadequacy of Garrod’s theory to explain all the protean phenomena of gout was realised. Like Duckworth, they rightly apprehended gout to be “something beyond the resultant effects of aberrant relations of uric acid; that it consists in something more than a perversion of animal chemistry; that it is not to be explained as a mere outcome of gastric or hepatic distemper; and that it is not the appanage only of the middle-aged or elderly high liver, and intemperate drinker, because, as is well known, it affects also sometimes in early life the high thinker and the laborious bread-winner.”

That the uric acid theory should more than any other have found ready acceptance, is not so much to be wondered at. The one solitary pathological fact that emerged out of the mist of hypotheses was that established by Garrod, viz., the excess of uric acid in the blood. It survived and still survives the corroding test of time. Surely such must be the fons et origo mali, and how obtrusive the uratic deposits, so ready to hand, objective affirmations of the truth of their contention.

This apparent simplicity how delusive! yet not wholly unprofitable. For if in these latter days our knowledge of the life-history of uric acid and purin bodies in the organism has evolved from “a state of chaos and guesswork to one of system and scientific accuracy,” the seeds thereof were sown by these hardy pioneers, their, to us crude, researches in the dark regions of bio-chemistry.

Here it would appear opportune to outline our plan of procedure in approaching this abstruse subject—gout. In the coming chapter we shall attempt to define and classify the various types of the disorder before passing on to discuss its etiology and morbid anatomy.

Now all will agree that the more recent revelations of chemical physiology and chemical pathology have an intimate bearing on the problem to be considered. We shall therefore, before proceeding to the more purely clinical aspects of the disease, deal with the modern conceptions of protein and purin metabolism, more especially the latter. Subsequently our scrutiny will be narrowed to consideration of the chemical structure of uric acid, its solubility, sources, mode of formation and destruction. In possession of these facts the relationship of uric acid to gout will be dealt with, in regard to respectively uric acid excretion, uricæmia, and uratosis.