Uric Acid in the Blood
As to the form in which uric acid circulates in the blood, Sir William Roberts believed that when dissolved in blood serum it was transformed into the relatively soluble sodium quadriurate. This authority held that in gout, either through deficient excretion or over-production, the quadriurate accumulates in the blood. Circulating therein, in a medium rich in sodium carbonate, it takes up an additional atom of the base, and is transmuted into the biurate, which is less soluble and less easily excreted by the kidneys; consequently, the biurate is hoarded up in the blood, at first in gelatinous, and later in an almost crystalline form, when its precipitation is imminent or actually ensues. This, moreover, was apt to occur at sites where the circulation was poor, the temperature low, and more particularly in regions in which the plasma contained a relatively high percentage of sodium chloride, e.g., synovial sheaths.
But, unfortunately for the valency of this otherwise plausible theory, it was proved by Tunnicliffe, Rosenheim, and others, that quadriurates do not exist as definite chemical compounds; in short, it is generally conceded that their existence should no longer be accepted.
Gudzent and Schade’s Theories
Gudzent was of opinion that uric acid can only exist in the blood as the mono-sodium-urate, of which there are two isomeric varieties, the easily soluble unstable lactam, and the stable relatively insoluble lactim urate. It is the former, or lactam, variety that accumulates in the blood in gout and, according to Gudzent, it is the transmutation thereof into the lactim modification that determines the precipitation of urates in the tissues. The lactim urate is soluble only to the extent of 8·3 mg. per 100 cc. serum, whereas the lactam form is soluble up to 18 mg.
Others, like Bechhold, maintain that the urates are present in the blood in a colloidal form, impossible of excretion by the kidneys. Thus Schade contends that, in the presence of alkalies (hydrates), uric acid or its salts may pass into a state in which it is far more soluble than usual. Moreover, on its path to crystallisation from this over-saturated solution, it passes through a colloid stage in which it is relatively stable. The maintenance of this colloid stage and consequently the retardation of precipitation is promoted by certain substances, i.e., glycerine, urea, serum, albumen, nucleic acid, etc. But hitherto the therapeutic possibilities suggested have not been invoked.
Organic Combinations
It will be recalled that purin bodies cannot be detected in the blood in health, though their administration by the mouth results in an increase in the excreta. Minkowski, to account for this, suggested that the purins in the blood were circulating in a combination which prevented them from giving the usual reactions, typical of their presence therein. We have an analogy in the masking of arsenic and iron in the cacodyl compounds and the ferrocyanide ion.[8]
The explanation proffered by Minkowski was elaborated by Von Noorden. His view was that lying at the disposal of the normal organism are a certain number of organic substances. These latter can combine with uric acid and render it soluble. It is then in this form passed through the blood in the kidneys, which eliminate from it the uric acid. Now, in gout these organic substances are deficient or wanting, and the result is that the uric acid is passed into the blood in the form of urates, the elimination of which only proceeds with difficulty; in other words, the purins normally circulate in organic combination and abnormally as salts of sodium.
It is worthy of note that, from a solution containing albuminous substances, Burian and Walker Hall found that while it was easy to remove the bulk of the purins, a certain percentage always remained which it was difficult to extract.