Pathological Chemistry of Uric Acid

In so far as the chemistry of gout is considered, the main part of the discussion must be concerned with two conditions: - 1. The existence of a crystalline separation of acid sodium urate in portions of necrotic tissue. 2. The existence of an increased uric acid content of the blood. Von Wollaston had noted, as early as the end of the eighteenth century, the occurrence of a crystalline separation of acid sodium urate (sodium biurate, Roberts; mononatrium urate, Tollens). This condition is so closely associated with gout that it and the so-called "gout necrosis," which has been found characteristic in all histological investigations of gouty changes, must be considered together. And this state remains peculiar to gout, in spite of the fact that even without any clinical history of gout, there is at times demonstrable at autopsy a precipitate of urates in the enlarged joints of sufferers from atrophic kidney, especially of those who have also had chronic lead poisoning. And further, it is peculiar in spite of the fact, to which we can testify, that at times it has been impossible to find the chalky deposit on which the essential existence of gout depends at autopsy of persons who, during life, have suffered constantly from gout. The urate deposits* are by no means limited to typically enlarged joints, but appear also in other joints, in the tendon sheaths, in the ear (as in the well-known tophi), and Ebstein has even mentioned the bone marrow as an occasional location. The question of the source of the urate deposits has given rise to many theories, which we may examine to better advantage after we have made ourselves more familiar with the causes of the supersaturation of the blood of gouty patients with uric acid. This state of saturation was asserted by Garrod, and has since been demonstrated by the quantitative determination of the uric acid, as well as by the "thread" experiment. While the blood serum of a healthy person or of a fever patient contains only minute traces of uric acid, - according to our investigations from 1.5 mg. to 2.0 mg. at the most in 200 cc. of blood serum - in the blood of a gouty individual we meet with a marked increase (as much as 17.5 mg., Weintraud). Besides, Weintraud, Klemperer and Magnus-Levy, especially, have shown an increase of uric acid in the blood of those suffering from gout; and we have observed in many cases of gout an increase of the total nitrogen retention which, as shown by us in another article (H. Strauss: Die chronischen Nierenentzundungen in ihren Einwirkungen auf die Blutflussigkeit. Berlin, Hirschwald, 1902), is coincident with an increase of uric acid in the blood serum. In the ascitic fluid of a gouty patient, who was also suffering from atrophic kidney and cirrhosis of the liver, twelve days before a typical attack of gout we found 2.6 mg. of uric acid nitrogen, which is equivalent to 7.8 mg. of uric acid per 100 cc. of fluid. The total nitrogen, excluding the nitrogen of the albumen, amounted to 45. mg. and the ammonia nitrogen to 4.0 mg. These values for the uric acid and the ammonia are significantly higher than for the normal. At another time we found in the ascitic fluid of this case 5.2 mg. of uric acid nitrogen, equivalent to 15.6 mg. of uric acid. Although there is, so frequently, an increase of uric acid in the blood serum in gout, yet this condition does not offer an exclusive diagnostic peculiarity; for, as it has been shown, there is also an increase of uric acid in the blood in pneumonia (Salomon, von Jaksch, Petren), in nephritis (von Jaksch, Klemperer, Magnus-Levy, and numerous other observers,) and also in leukemia (Klemperer, Magnus-Levy and others) and, further, the body fluids show an increase of uric acid under the influence of X-ray treatment. In contracted kidney with uraemia, values for uric acid as high as 16.05 100 cc. of blood have been ob tained, and in leukemia as high as 22.6 mg. in 100 cc. of blood. In thirty-seven cases of chronic nephritis we have found a minimum value of 1.1 mg. and a maximum value of 10.5 mg. uric acid in 100 cc. of blood serum. The increase of uric acid in the blood may therefore be due to various causes, and is of interest for our purpose only in so far as the actual effects are concerned, and not as the consequence, of one cause more than another.

* Deposits of urates have been detected in almost all the structures of the body, even in the meninges. In a suspected case of gout, I once found a tophus in the external auditory canal - the only deposit to be found. [Editor.]