640 URIC-ACID METABOLISM AND GOVT 



tion of the deposits, a fact in harmony with the known increased ehmination of 

 uric acid during the attack. 



That urates may cause necrosis of the tissues has been definitely estabUshed, 

 and this may lead to connective-tissue formation and contraction.^^ But the 

 actual increase of uric acid in the blood and tissues in gout is so slight that we are 

 not warranted in saying that the usual tendency to sclerosis in all the organs in 

 gout is due to the action of uric acid, rather than to some other unknown agent 

 or agents. Excess of uric acid in the blood is by no means pathognomonic of 

 gout, for we may have relatively great excesses of uric acid in the blood in leuke- 

 mia, in some cases of nephritis, and after eating large amounts of nucleoproteins, 

 without a symptom of gout. Furthermore, it is quite possible that the precursors 

 of uric acid, the purine bases, are responsible for more harm than the uric acid it- 

 self. Thus, administration of adenine to dogs and rabbits will produce degenera- 

 tive changes in the kidneys, associated with the deposition of substances resembling 

 uric acid and urates in the renal tissue; and MandeP^ states that purine bases 

 may cause fever, independent of inlection. 



Many have looked upon renal alterations, leading to failure of 

 excretion of uric acid, as the primary cause of gout; but the evidence 

 in favor of this is faulty, because frequently renal changes are slight 

 or entirely absent in gout, whereas marked nephritis of all forms may 

 exist without the coexistence of gout, and, as mentioned above, the 

 kidney in gout may show no lack of ability to excrete uric acid injected 

 into the tissues. Magnus-Levy, however, seems to believe that a 

 renal retention of uric acid is of importance, and that it may occur with- 

 out morphological changes in the kidneys. The newer methods of 

 blood analysis (Folin) have given support to this view, and, as pointed 

 out in preceding pages, Fine^^ and numerous others have called attention 

 to the fact that in early interstitial nephritis the blood shows a greater 

 increase in uric acid than in urea or <?reatinine, as if the diseased kidney 

 found more difficulty in excreting uric acid than the other substances. ^^ 

 As a result the blood in early nephritis may show quite the same fig- 

 ures for uric acid, urea and creatinine as are found characteristically 

 in gout. Although in some cases one finds normal amounts of uric 

 acid in the blood in gout, this seems to be exceptional. Hence we 

 are still confronted with the question whether gout is anything more 

 than a form of nephritis in which chiefly uric acid excretion is impaired 

 or whether there does exist a special disease, gout, which causes 

 uric-acidemia more or less independently of renal abnormalities.*^ 



URIC-ACID INFARCTS^" 



Uric-acid infarcts, as the deposits of urates and uric acid observed in the 

 kidneys of at least half of all children dying within the first two weeks of life are 

 called, give evidence of the slightness of the toxic effects of these substances upon 

 the tissues. Usually little or no change occuri- in the renal tubules as a result of 



^^ Because the gouty tophi do not suppurate, even when ulcerated through the 

 skin, it has been suggested that the urates have antiseptic properties. Bcudix 

 (Zeit. klin. Med., 1902 (44), 165), however, could not demonstrate such antiseptic 

 properties experimentally. Not always do the tophi consist solely or even largely 

 of urates, but these may be replaced by calcium salts (Kahn, Arch. Int. Med., 

 1913 (11), 92). 



<*« Amcr. Jour. Physiol., 1904 (10), 452; 1907 (20), 439. 



" Jour. Amer. Med. Assoc, 1916 (66), 2051. 



" See also Denis, Jour. Biol. Chem., 1915 (23), 147. 



'"' See McClure, Arch. Int. Med., 1917 (20), 641. 



60 See discussion by Wells and Corper, Jour. Biol. Chem., 1909 (6), 321. 



