Gout, with a section on ocular disease in the gouty

by Llewellyn J. Llewellyn

Gouty tophi, like all pathological concretions, are laid down in accordance with a definite law. In the first instance, a central nucleus is essential. To this must be added a “binding substance” or structural framework of different nature from the main mass of the concretion.

Garrod, discussing the intimate structure of “chalk-stones,” observes that, “the large amount of phosphate of lime occasionally met with is probably derived not only from the tissue in which the chalk-stones have been developed, but likewise from secondary deposition, the result of ordinary inflammation around the original nucleus (urate of soda) which acts as a foreign body.”

It is, however, quite possible that some substance other than urate of soda constitutes the primary nucleus, for, as we now know, concretions most frequently gather around masses of mucin, clumped bacteria, desquamated cells, precipitated proteins, etc. Thus, the renal uric acid infarcts, supposed to result from disruption of the nucleo-proteins of the fœtal nucleated red corpuscles, take origin around injured epithelial cells, which latter form the nucleus.

As to gouty tophi, too, it has been suggested that they form in response to any toxin, resistance to which may involve death of the tissue cells with consequent disruption of their nucleins and formation of urates. Such was the view held by Woods. Hutchinson, who also thought that the calcareous accretions might be regarded as “protective,” analogous to the formation of shells in the invertebrates, the process here consisting in the deposition of lime salts in cells already saturated with uric acid and urates.

In any case, whatever be the exact nature of the nucleus, the urate of soda collects thereupon, the acicular crystals tending to assume the form of radiating needles. But the successive depositions not being of regular incidence, the surface of the crystals, in the intervals of quiescence, becomes covered by mucin, animal or earthy matter. Hence, the concretions display not only a radiating, but a concentric or laminated structure.

The mucin acts as the “binding substance,” the crystals lying in its meshes, and, moreover, remaining as the framework of the concretion even after the crystals are dissolved out; in other words, the gouty tophus is made up of a blend of crystalloids and colloids, evolved from solutions of the same character.

The importance of recognising the true nature of this binding substance, i.e., mucin, merits a brief digression, in light of Ebstein’s view that local tissue necrosis is a necessary antecedent to uratic deposition. Now, exhaustive studies of the histology of uratic deposits, both those experimentally induced and of spontaneous gouty origin, have been conducted by Freudweiler, His, Krause, and Rosenbach.

All their results, according to Gideon Wells, “indicate that uric acid and urates excite some slight inflammatory reaction, cause a slight local necrosis, and seem to act as a weak tissue poison.” According to Rosenbach, however, this sequence is not invariable, inasmuch as he noted that such deposits may occur without inducing necrosis. More pertinently to our contention, however, is it that Krause’s experience seems to indicate that errors of interpretation were possible. Thus, he suggests that part of the material in the areas of uratic deposits merely constituted the framework of a crystalline deposit, though such were currently regarded as strands of necrotic tissue.

But, to resume, tophi being blends of crystalloids and colloids, we must recollect that the suspension capacity of colloidal solutions for crystalloids is much superior to that of simple solutions, by reason of the fact that at the surface of each colloidal particle there exists a zone in which the crystalloids are much more closely aggregated than elsewhere, thus permitting more crystalloids to be dissolved in the solvent between the colloidal particles. But, be it noted, this same tendency to concentration of the crystalloids at the surface of the colloidal elements leads to the colloids acting as determinants of precipitation when crystalloids are in excess. Accordingly, when the crystalloids pass out of solution, they form crystals or precipitates intimately blended with the colloids. Thus, for example, when uric acid crystallises out of urine it carries with it the colloidal pigments. On the other hand, if the colloids are precipitated, the solvent capacity of the solution being consequently depreciated, the crystalloids are deposited in intimate relation with the colloids.

Again, Schade has pointed out that colloids may precipitate in reversible form or not. If in irreversible (e.g., fibrin) form, the concretion will remain permanent. But if the colloidal precipitate is reversible, it may be redissolved, as happens with the uric acid infarcts of the infant’s kidney. In conclusion, we see, therefore, re crystalloids and colloids in animal juices, that the conditions of their solubility are most complex, and though they do not explain the nature of gout, the variations doubtless stand in intimate relation to the formation of tophi.