For it is possible, as Kionka suggests, that normally uric acid, on its way to urea, may pass through a glycocoll stage. Now, in the gouty individual the glycocoll may not be entirely transformed to urea, and its excess in the tissue fluids may lead to uric acid deposits. Perhaps, as Walker Hall observes, “since hepatic deficiency is generally admitted in the gouty, diminished destruction of uric acid and glycocoll may go hand in hand.”
In healthy cartilage glycocoll is undemonstrable. But, according to Kionka, if bruised or damaged, a considerable amount thereof is formed. Now, when blood, rich in uric acid, circulates through injured cartilage, the presence of glycocoll favours precipitation of the urates, a possible explanation of the formation of tophi. Unfortunately for the valency of this theory, Aberhalden and Schittenhelm show that the methods employed by Frey, to isolate glycocoll from cartilage, were such as yield errors which would quite account for the amount obtained by this worker. They, therefore, deny the presence of glycocoll in damaged cartilages. But, in conclusion, Kionka’s plea for a primary hepatic functional disability derives colour from the fact that the drugs which have gained most approval in the treatment of gout are those which increase the quantity of bile without augmenting the amount of bile acids; and the which are excreted in combination with glycocoll, for instance, salicyclic acid combines with glycocoll, and is excreted as salicyluric acid, and benzoic acid, which combines with glycocoll to form hippuric acid. Albeit, we must not overlook the fact that the presence of glycocoll is not peculiar to gouty urine, but, as shown by Walker Hall and Embden, is met with in other disorders. The glycocoll hypothesis as to the origin of gout is, though attractive, therefore still unproven.
Urea Excretion in Gout
According to Tilden Brown, the rhythm of urea excretion constitutes a warning as to the approach of gout. A very lowered elimination thereof he holds to be an excellent and pathognomonic symptom. The excretion of urea may at times run so low as to lead to a suspicion of renal disease. He considers that this sign may find a place in the prophylaxis of gout, a signal for the initiation of treatment with the object of lessening the severity of symptoms (viz., extent of toxic action as manifested by destruction of proteid, etc.).
This point was advanced by Brown (1905) during a discussion at the Harvard Medical Society, but as far as we know it has not been confirmed. Presumably it rested upon the assumed existence of a normal ratio of uric acid elimination to that of urea with the corollary that every deviation therefrom was due to a pathological cause. Haig held this view, which was, however, disproved by Herringham, Groves and Luff. The latter authority estimated the daily eliminations of uric acid and urea in a healthy adult man on a mixed diet for a period of fifty days, and clearly showed that no constant ratio exists in a given individual between the excretion of uric acid and urea.
Also, it is obvious that, before attaching any valency to Tilden Brown’s dictum, it is essential that it be established that the cases were instances of pure gout, unaccompanied by nephritis. Moreover, modern workers tend more and more to rely not on analyses of the urine but of the blood, especially in the unravelling of so-called metabolic disorders. Also, it may be added, that their findings in this sphere indicate no harmony between the urea and the uric acid content of the blood. Thus, Otto Folin observes, “One most interesting fact which we constantly meet with in blood analysis is that there is no correspondence between uric acid and the total non-protein nitrogen in the blood. In gout or lead poisoning, or leukæmia, the blood is uniformly rich in uric acid, yet the total non-protein nitrogen or urea nitrogen may be normal.”
Creatine and Creatinine
As before pointed out, it has been suggested that these substances may be in some obscure way related to the genesis of gout. To this end a great amount of research has been expended on the metabolism of creatine and creatinine. But although, as far as I am aware, the revelations hitherto forthcoming have disclosed no link between these substances and the development of gout, still, by reason of the potentialities possibly resident therein, a brief digression is permissible.