The Cause of the Inflammatory Phenomena
Garrod’s discovery that uric acid was present in the blood in gout not unnaturally led to the assumption that herein lay the origin of its symptomatology, and what else than confirmatory could be the deposition of uratic deposits here and there in the body. The corollary seemed obvious that, given the presence of a certain proportion of uric acid in the blood, then gout must result. But, unfortunately, it was not so; for, lo! and behold, an excess of uric acid in the blood is in no sense pathognomonic of gout.
Thus, the blood in leukæmia contains a high percentage of uric acid, in some cases exceeding that found in gout, and enduring, moreover, for a longer period. Yet no symptoms distinctive of gout appear, nothing that can be referred to uric acid. But it was contended the reason why gout does not ensue is because simultaneously with increased formation there is increased elimination of uric acid. But, unfortunately, despite augmented excretion, the percentage of uric acid in the blood is still maintained at a high level, and still no gout occurs.
Moreover, it is met with also in nephritis, simple and pernicious anæmia, intestinal inflammation, certain fevers, notably in malaria between attacks, and in typhus after the febrile stage, pneumonia, plumbism, etc. Indeed, the ubiquitousness with which uric acid is found in the blood, and this in conditions wholly distinct from gout, would of itself seem sufficient to dissipate any lingering doubts as to its being anything more than a symptom of gout and not its proximate cause.
Obviously, with these revelations the uric acid theory was within measurable distance of being uprooted. Deposed from its high estate as a causal agent, and accredited with only a symptomatic value, the question arose whether indeed this bogey, “uric acid,” was even capable of fulfilling a minor rôle, of originating any symptoms, much less gout, in its entirety. In other words, is uric acid toxic or non-toxic?
Non-Toxicity of Uric Acid
The adherents of the uric acid theory did not hesitate to attribute to its toxic action, not only the severe phenomena of acute attacks, but even all the functional disorders of so-called irregular or visceral gout. By the more ardent advocates, such as Haig, we were treated to a word picture of how solid crystals of uric acid erupted out of the blood-stream, and anchoring themselves in nerve sheathes, the renal substance and the mucous membrane, gave birth to chronic neuralgias, nephritis, rhinitis, and so forth. But, alas, there is very serious doubt as to whether uric acid or the urates are capable of acting even as mechanical, much less as true toxic irritants.
Perhaps the most cogent evidence of the slight toxic effects of uric acid or urates is that derived from a study of the uric acid infarcts so frequently noted in infants dying within the first two weeks of birth. According to Gideon Wells, “little or no change occurs in the renal tubule as a result of these depositions, except such as can be attributed to their mechanical effect.” This same observer, discussing this question of the toxicity of uric acid, observes, “It may be safely stated that at the present time there exists no good evidence which makes it probable that uric acid is responsible for any pathological conditions whatever, except uric acid calculi, uric acid infarcts in the kidneys, and certain manifestations of gout.” His further conclusion is that uric acid possesses but a very slight degree of toxicity, and that an actual intoxication of the organism with this substance probably never occurs.
Again, we have the fact that in instances of malnutrition in children excess of uric acid may occasionally be found in the blood. Yet no symptoms comparable to gout occur, even though uric acid calculi form. Also, as has been pointed out, showers of uric acid may be present in their urine, and yet no symptoms arise, save those referable to mechanical irritation of the renal or vesical tissues.
Turning to experimental researches, the evidence is cumulative as to the non-toxicity of uric acid. Rabbits and dogs seem quite irresponsive, either to its ingestion in large quantities in their food, or to repeated intravenous injections of 1 or 2 grammes thereof, save only that the urine showed a large increase in uric acid.