But if the cause of uric acid retention lies neither in the kidneys nor in the blood, there must exist something abnormal in the gouty individual which renders impossible what may be termed a compensatory uric acid excretion. Now, as disclosed in the previous chapter, experimental research, in diseases other than gout, has shown that the bodily tissues have an appreciable capacity for retention of uric acid (Fine). This, moreover, gains probability from the fact that Wiechowski, in his prolonged studies as to the possibility of uric acid decomposition in the human body, was never able to detect any evidence of uricolysis. Furthermore, on the clinical side, the fact that intravenous injection of uric acid does not produce a corresponding degree of uricæmia seems, as Bass and Herzberg suggest, to indicate that in gout the retention capacity of the tissues for uric acid is augmented. Lastly, in the precipitation and anchoring of urates in the tissues in gout, we have objective proof, i.e., tophi, that the uric acid is actually held in the tissues.
Does not this seem to indicate that there are peculiarities of tissue in the gouty? What, then, the subtle change that determines the retention and deposition of urates in the tissues in gout?
May we not, with Walker Hall, hazard the reflection that there may be differences between the nucleotides of normal and gouty tissues? For, doubtless, if there be peculiarities of tissue in the gouty, these will be reflected in abnormalities of tissue function and metamorphosis.
Gowlland Hopkins, discussing the metabolism of purins, holds that in gout there is some disturbance or defect in the fermentative functions of the tissues. Of a verity the range of intranuclear activities offers scope enough when we recollect that the cells of all tissues contain not only nucleinase, but also nucleotidase and nucleosidase. Even so, the resultant nucleins, the nucleotides, and nucleosides, have still further changes of deaminisation and oxidation to undergo, these carried out in the liver and elsewhere!
We may talk of defects in the enzymatic functions of the tissues, but, viewing gout clinically, and more particularly the hypersensitiveness of its victims to the most varied stimuli, dietetic and other, one inclines rather to predicate in their instance an inherent instability of nuclein metabolism. For in the gouty, as Walker Hall observes, “a slight injury or indiscretion of diet, an overloaded intestine, or increased toxicity of the intestinal flora, may be followed by a disturbance of the general nuclein metabolism, and a local reaction in certain tissues.”
With this pronouncement all clinicians will be in accord, and herein, too, we may, I think, discern how the latent tissue idiosyncrasies of the gouty are evoked, i.e., by infection; in other words, that, under the influence of these morbific agents, the innate morbid potentialities of the gouty become overt and manifest.
The exact modus operandi whereby the assumed organisms or their toxins determine the efflorescence of gout is uncertain. We know that, following the intake even of non-purin-containing foodstuffs, an increase in uric acid excretion ensues, and that the same is the outcome of the stimulation of general nuclein metabolism. Is it not conceivable that the responsible toxin acts in like fashion, and haply by disturbing the orderly sequence of those exquisitely delicate enzymatic reactions which culminate in the formation of uric acid, and with which potentialities every living cell in the organism is dowered? Further than this we, pending future researches by the bio-chemists, may not go, for “the positive material is much too insufficient, and much too ambiguous.”
In conclusion, I would postulate that in gouty subjects:—
(1) There is an inherent abnormality or instability of nuclein metabolism, and conjoined therewith an enhanced tissue affinity or augmented retention capacity for uric acid.
(2) These latent tissue peculiarities, through the agency of infections or sub-infections, become manifest as gout.