The subject of gout is one of the most baffling in the literature of metabolism. Despite the brilliant work upon the purins during the last ten years, work which has been illuminated by the discovery of the formula of nucleic acid by Levene, the nature of gout remains as much of a mystery as ever.

Just as the whole trouble in diabetes turns upon the inability of the organism to destroy sugar, so the symptoms manifested in gout are dependent upon the deposit of acid urate of sodium in certain localities. One of the earliest descriptions of gout comes from Sydenham, who suffered for forty years from the disease and published an extended account of it in 1683. It was Garrod1 who first established the fact that uric acid was present in the blood of gouty persons. He believed that this excess of urate was the cause of gout, the excess being deposited from the blood in the joints in the form of crystals. The problem of metabolism in gout is a problem of the factors entering into the cause of this deposit of urate. The general metabolism, exclusive of the purin factor, is exactly the same as in health. Magnus-Levy2 proved that the oxygen absorption and carbon dioxid elimination is the same in gout as in health. The cause of the trouble must be sought elsewhere than in a reduced general oxidation power of the tissues.

Clinical experience teaches that the predisposing causes are excessive eating, little muscular exercise, the abuse of alcoholic beverages, and lead-poisoning.

Beebe3 has administered alcohol in various forms to a normal individual. He finds that even large doses have no effect on the hourly excretion of uric acid in a fasting man. The endogenous purin metabolism is therefore unchanged by the ingestion of alcohol. It is important to know that alcohol is apparently without effect upon such part of the purins as may be directly derived from cell metabolism. Further investigation of this subject by Landau1 has revealed the fact that the influence of alcohol is different in different individuals, and that usually there is a slight increase in the output of endogenous purins after taking alcohol. Mendel and Hilditch2 report the same results. Administration of alcohol equal to 500 calories, together with a purin-free diet, to a man previously unaccustomed to alcohol caused a slight decrease in the elimination of nitrogen and a slight increase in that of uric acid. Otherwise the urinary analysis showed little or no change, even when alcohol was administered for weeks.

1 Garrod: "The Nature and Treatment of Gout," 1859.

2 Magnus-Levy: "Berliner klinische Wochenschrift," 1896, xxxiii, 416.

3 Beebe: "American Journal of Physiology," 1904, xii, 13.

Pollak3 has shown that in chronic alcoholics the retention of ingested purins is favored.

Minkowski,4 with a master hand, summarized modern knowledge concerning gout as follows:

1. The deposit of urate in the tissues is the first change which takes place in the formation of the specific gouty nodules. These tissues are not necrotic, as taught by Ebstein.

2. The tissue changes in the vicinity of the gouty nodules are in part due to mechanical, in part to chemical or osmotic, action, caused by the precipitated urates.

3. The acute inflammation in gout, as observed during the attack, is produced in the vicinity of the urate deposits through some unknown cause. Traumatic, toxic, or infectious elements appear to be collectively active in this regard. The attack probably constitutes the reaction of the organism to rid itself of uric acid, an effect which is only partly realized.

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1 Landau: "Deutsches Archiv fur klinische Medizin," 1909, xcv, 280.

2 Mendel and Hilditch: "American Journal of Physiology," 1910-11, xxvii, 1.

3 Pollak: "Deutsches Archiv fur klin. Med.," 1906, lxxxviii, 224.

4 Minkowski: von Leyden's "Handbuch der Ernahrungstherapie," 1904, ii, p. 277.

4. An accumulation of uric acid in the blood is a constant accompaniment of gout.

5. The increased quantity of uric acid in the blood must not be considered as the cause of the precipitation of urates in the gouty nodules. There must be certain local influences which favor the deposit of urates; for Klemperer has shown that the blood of gouty patients may dissolve much more uric acid than is actually present in it; and again, the blood in leukemia may contain as much uric acid as in gout, without there being any indication of a deposit of urate.

6. The uric acid elimination is the same in the gouty as in the normal person, except at the time of the attack. Before the attack there is retention, but during and after the attack an increased excretion of uric acid in the urine.

7. The accumulation of uric acid in the blood is not due to a diminished oxidation of uric acid, but rather to a diminution in the quantity excreted in the urine.

8. It is not certain that the lessened excretion of uric acid is due to a disturbance of renal function. Very likely it depends upon the presence of uric acid in some abnormal chemical union. This abnormal substance may be with difficulty eliminated in the urine, but may lend itself readily to the formation of tophi (p. 532).

9. The ultimate cause of the unusual behavior of uric acid in gout is probably an abnormal metabolism within the nuclei of the cells, where the nucleic acid content is the means of solution and conveyance not only of the purin bases but also of uric acid.

The opinions of other modern workers vary somewhat from those of Minkowski, as appears in the following:

Almagia,1 in Hofmeister's laboratory, has performed some interesting experiments and concludes that the older view of Garrod is correct - that is, that an excess of urates in the blood is the cause of gout. Almagia finds that thin strips of cartilage suspended in dilute neutral solutions of sodium urate absorb the salt, do not destroy it, but cause it to be deposited in fine crystals within the cartilage. He furthermore injected 5 to 7 grams of uric acid into the peritoneal cavity of rabbits, a dose which usually killed them. On testing the liver, spleen, muscles, and lungs with the murexid test for uric acid, negative results were obtained, whereas cartilage gave a positive reaction indicating the presence of urates. Almagia concludes that the deposit of urates in the cartilage of a gouty patient is but the result of a temporary or permanent increase in the uric acid content of the blood. The liability of cartilage to contain deposits of urates has received no satisfactory explanation. Exposure to cold, stagnation of the blood flow, and the richness of cartilage in sodium salts have been suggested as possible reasons for the precipitation of the urates.

1 Almagia: "Hofmeister's Beitrage," 1906, vii, 466.