UREMIA 539 



osmotic pressure of the blood in uremia, and the fact that the life of nephrecto- 

 niizcd rabbits is prolonged by giving them water.*" In any evcnt^ the existing 

 evidence on the pathogenesis of uremia does not exjjlain it on a toxicologic basis, 

 and hence the alternative explanation of cerebral edema must be taken into con- 

 sideration. Ervin" proposes the hypothesis that convulsions occur when the 

 blood pressure becomes lower than the intracranial pressure so that the blood sup- 

 ply of the brain is reduced; the convulsion raises the blood pressure. He comments 

 on the ditHculty in explaining the transient character of uremic convulsions if 

 caused by concentration of chemical poisons. 



On the other hand the pathologist recognizes evidence of systemic 

 intoxication in uremia. The uremic pericarditis and endocarditis, 

 which have often failed by ordinary methods to yield bacteria, are 

 apparently toxic processes. The diphtheritic colitis indicates vicari- 

 ous excretion of poisonous substances. Structural changes are found 

 in cells that suggest poisoning; chromatolysis of the cortical ganglion 

 cells has been repeatedly observed in uremia, and in nephrectomized 

 rabbits Lewis*''" found acute parenchymatous and fatty degeneration 

 of the myocardium and endothehal cells of the liver. The localized 

 edemas of nephritis often show a fluid of the character of an exudate 

 rather than a transudate. 



It would seem, despite the prevailing opinion to the contrary, that 

 it is entirely possible that the manifestations of uremia may be caused 

 by the known nitrogenous substances that the Iddneys have failed to 

 excrete, and that the only difficult thing to explain is the failure of 

 investigators to consider the time element in experimental intoxica- 

 tions. The presence of 200 mg., and upwards, of nonprotein nitrogen 

 per 100 c.c. of blood, which is often found in uremia, indicates that 

 the blood plasma that is bathing the tissue cells contains somewhere 

 between 0.5 and 1.0% of soluble organic substances, a strength of 

 solution that certainly does not require any very high degree of 

 toxicity when continuously maintained at this concentration, as it is in 

 nephritis. The reported experimentally determined toxicities with 

 these substances have only represented transitory conditions which are 

 entirely dissimilar to the actual conditions in the body. They corre- 

 spond to the cases of high nonprotein nitrogen in the blood in in- 

 testinal obstruction, bichloride poisoning, etc., in which absence of the 

 uremic symptom complex has been noted and remarked upon. To 

 study the relation of uremia to retained metabohtes we need observa- 

 tions on their effects when maintained in the organism for long periods 

 at the concentrations occurring in uremics and this can be done readily 

 by such methods as have been devised by Woodyatt.^^ A start in this 

 direction is furnished by Hewlett, Gilbert and Wickett,^- who found 

 that when large doses (100 to 125 gm.) of urea were given to normal 

 men there occurred symptoms comparable to those of asthenic uremia. 



« Couvee, Zeit. klin. Med., 1901 (54), 311. 

 " Jour. Amer. Med. Assoc, 1918 (70), 1208. 

 4"" Jour. Med. Res., 1907 (17), 291. 



"Jour. Amer. Med. Assoc, 1915 (65); 2067; Jour. Biol. Chem., 1917 (29), 

 355. 



