The important researches of Sir William Roberts on the chemistry of uric acid in gout have thrown some light upon the nature of the changes that occur during the process of uratic infiltration of the tissues ("Uric Acid, Gravel, and Gout," 1892). Having shown that the urates in gouty joints consist chiefly of an almost insoluble sodium bi-urate, while in the serum of the blood, and in other similar alka line fluids, uric acid enters into combination as a soluble quadri urate, he concludes "that in the normal state uric acid is primarily taken up in the system as quadri-urate, and that it is finally voided with the urine as a quadri-urate. In perfect health the elimination of the quadri-urate proceeds with sufficient speed and completeness to prevent any undue detention of it in the blood. But ih the gouty state this tranquil process is interrupted, either from deficient action of the kidneys or from excessive introduction of urates into the cir culation or from some other cause, and the quadri-urato lingers unduly in the blood and accumulates therein. The detained quadri rtrate, circulating iu a medium which is rich in sodium carbonate, gradually takes up an additional atom of base and is thereby trans formed into bi-urate. This transformation alters the physiological problem. The uric acid, or rather a portion of it, circulates no longer as the more soluble and presumably easily secreted quadri-urate, but as bi-urate, which is less soluble, and probably also—either for that reason or because it is a compound foreign to the normal econ omy—less easy of removal by the kidneys. The bi-urate thus pro duced exists at first in the gelatinous (soluble) modification, but with the lapse of time and increasing accumulation it passes on into the almost insoluble crystalline condition, iced then precipitation becomes imminent, or actually takes place." Sir William Roberts then shows that these changes are accelerated by the increase of uric acid in the solvent medium, and goes on to say : " Assuming that the inflammatory arthritic attacks in gout are directly due to copious and sudden precipitation of crystalline stars and needles of sodic bi-urate in the cartilages and fibrous structures of the joints, the evidence before me indicates that such copious sudden precipitation can only take place when the fluids bathing these structures are impregnated with uric acid in at least the proportion of 1 part in 2,500. Below this point the precipitation occurs slowly and scantily and only in the form of short scattered needles. . . . It is quite conceivable that this Blighter precipitation in the tissues of short scattered needles might account for certain irritations in the various organs, such as characterize irregular or larval gout; but it could scarcely engender downright inflammatory attacks. It is fur ther conceivable that the presence in the blood of such scattered needles might constitute foci around which clotting might take place, and that the thrombosis not infrequently observed in gouty cases might thus be accounted for. The impregnation of the blood in gouty persons with uric acid to the extent of these lesser degrees is within the range of observed actualities." Sir William further shows that the precipitation of urates is facil itated by the addition of sodium salts to the solution, and by reduc tion of the temperature. In this way he explains the more frequent deposit of urates in the joints of the feet rather than in the deeper and warmer regions of the body, since it appears, from analysis, that the synovia and articular cartilages contain a larger percentage of sodium salts than exists in any other tissue (toe. cit., p. 103). In this result of laboratory experiments Roberts and Haig are at variance, for Haig claims that uric acid is more soluble in alkaline fluids con taining di-sodic phosphate than in those which contain the acid sodium phosphate. Probably, however, the presence of sodium salts that furnish the base for sodium urates is the important fact in the case.
The author then proceeds to show that it is possible in the joints of dead animals to produce a uratic infiltration of the cartilage that shall exactly counterfeit the deposits in a gouty articulation (ioc.
p. 105.) " Tarsal bones of a pig were suspended in wide-mouthed phials charged with a saturated solution of bi-urate made in hot water and then cooled. The phials were chloroformed, corked, and placed in the warm chamber or at the temperature of the room. Re-precipita tion of the bi-urates takes place in two or three days. If the bones are now examined, the articulating ends are found to be encrusted with a chalky matter which cannot be wiped off with a towel or removed with a nail-brush. If vertical sections of such cartilages are exam ined with the microscope, the deposit is seen to be situated in the substance of the tissue, close beneath the synovial surface of the cartilage, and to be composed of a dense felt of fine needles of bi urate." This deposit is supposed to occur as an infiltration from the synovial fluid rather than as a result of any primary morbid changes in the cartilages. In this particular Roberts and Ebsteiu, therefore, are not agreed.
Roberts also proceeds to explain the superior tendency of synovia, to thus deposit urates by stating that the fluid is especially rich in sodium salts which favor the precipitation of uric acid, and that the isolation and stagnation of the articular contents may be supposed to aid the process. In this connection he quotes an observation made by Frerichs, who found that " stall-fed horses and oxen, lead ing an idle existence, had twice as much synovia in their joints as similar animals roaming in the meadows or doing work. . . . In the idle animals the synovia was more watery and contained less albumi noid matters, but, and this is significant, a larger proportion of min eral salts, which consist almost entirely of sodium salts. We might conjecture from this fact that if horses and oxen were liable to uratic precipitations, the idle stall-fed animals would be more subject to such deposits than the same animals leading a more active life. Perhaps we may discern herein one reason why men who lead a sedentary life are more subject to gouty deposits than men who take active exercise." As for the uratic deposits in the joints, Sir William Roberts con siders them as not necessarily permanent. He agrees with those who teach that they may sometimes exist in the articulations without exciting the manifestations of gout; and, conversely, attacks of acute articular gout may occur without any uratic deposits discoverable after death. When urates are slowly and moderately precipitated, the first of these conditions obtains; when long intervals of her lth succeed the articular crises, the second condition may result from the gradual solution and removal of the deposit. He is also of the opin ion that the phenomena of articular inflammation are for the most part the consequences of mechanical injury caused by the presence of the infiltrated salts. He cannot admit any poisonous effects from uric acid or its salts, and is therefore inclined to suppose that in the irregular forms of gout there is really an overlooked precipitation of urates in different parts of the body, where they excite disorder by mechanical interference with the function of the affected structure.
That this is not an improbable hypothesis is shown by the fact that the blood-serum in gouty subjects is often supersaturated with sodium bi-urate, so that precipitation into the tissues may be very easily occasioned.
In this learned exposition of the chemistry of the author has made an invaluable contribution to science; but with the excep tion of the demonstration of the different states of combination into which uric acid may enter, he adds very little to our knowledge of the pathogeny of gout. With the witty German professor we may say, after reading these interesting lectures, that gout seems to consist in the excessive facility with which quadri-urates are transformed into bi-urates. But whence this morbid facility? The question remains unanswered.