UREMIA 531 



(3) Uremia may not depend on intoxication of tlie nerve cells, but 

 upon the nieclianical effects of edema involving these cells. 



One of the striking features of autopsies of uremics is often the ."wet brain" 

 and the excessive amount of cerebrospinal iluid wiiicii, during life, may be found 

 lo be under a heightened pressure. We l<nu\v that not only general but localized 

 edemas occur in nephritis, and tliat localized edema in the brain may be associ- 

 ated Willi and apparently responsible for paralyses, convulsions, hyperirritability 

 and mania. The wet brain of nephritis is similar to the wet brain of acute 

 alcoholism and delirium tremens. Oftentimes the nervous symptoms of uremia 

 are distinctly focal, and a complete hemiplegia from hemorrhage may be exactly 

 simulated; convulsive seizures identical with those of brain tumor may be seen. 

 It is extremely dillicult to explain these localizations by the action of a soluble 

 poison, and simple if we assume a local edema. It is, of course, as dilhcult to 

 explain the localization of the edema, but we know that in nephritis lucalized 

 edemas do occur, so we have a basis for the assumption of localized cerebral 

 edemas. A general acidosis is usual in nephritis and marked in uremia as'i 

 but we have no means of knowing whether local acidosis occurs in the nervous 

 system that may be responsible for local edemas according to Fischer's hypothe- 

 sis. Or, osmotic ell'ects may be responsible, in view of the demonstrated high 

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

 niized rabbits is prolonged by giving them water.sse In any event, the existing 

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

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

 sideration. 



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 endothelial 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 kidneys 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 0.7% 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 



35d Henderson, Bull. Johns Hopkins Hosp., 1914 (25), 141; Peabody, Arch. Int. 

 Med., 1915 (16), 955. 



35eCouvee. Zeit. klin. Med.. 1904 (54), 311. 

 35f Jour. Med. Res., 1907 (17), 291. 



