532 AliXORMALITlKS 1\ METABOLltiM 



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 liigh nonprotein nitrogen in the blood in in- 

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

 uremic sj^mptom complex has been noted and remarked upon. To 

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

 tions on their ettVcts when maintained in tlie organism for long periods 

 at the concentrations occurring in uremics and tliis 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, 

 wliich appeared only when the urea concentration of the blood had 

 reached levels of 160 to 245 mg. of urea per 100 c.c, /. e., just the con- 

 centrations that are usually seen in well developed uremia. If in these 

 experiments of brief duration such marked symptoms were produced 

 by urea, what striking eifects must be expected when these same urea 

 concentrations are continued in the blood for days and weeks at a 

 time. We must find out what results not only from urea, but from 

 creatinine and uric acid kept in the blood at tlie concentration found 

 in uremia for long periods, as well as any other substance that may be 

 increased in the blood in uremia. An experiment of a few minutes' 

 or hours' duration cannot be expected to duplicate or elucidate a con- 

 dition of weeks duration. In chronic diseases our experimental in- 

 vestigations must be of some reasonably comparable duration, and this 

 principle of investigation is now made possible by Woodyatt's methods. 

 And finally, in view of the extremely varied symptomatology of renal 

 incompetence, we must recognize that it is highly probable that in 

 different cases these symptoms vary because of different conditions. 

 In one case, urea may be the chief factor, in another the action of urea 

 Tnay be complicated by the effects of acidosis or high blood pressure 

 per se, while in others cerebral edema may be the chief influence. All 

 possible shades of cooperating influences may be expected to occur 

 Avlien the kidneys fail, and to explain the confused, variable, changing 

 picture of the uremic state.^^*^ 



35gJour. Amer. Mod. Assoc, 191.5 (65), 2007; Jour. Biol. Clieni.. 1!)17 (20). 

 355. 



35h The infliionoo of a liypotlietioal internal socrotion of the kidney (Brad- 

 ford), or of tlie products of neplirolysis (Asooli), as a eause of uremia, may now 

 ho eonsidcred as of historical interest only. (See Pearce, Areli. Int. ^led., lOOS 

 (2), 77; 1010 (.5), 133.) Tlie same is true of the attempt to explain the liiirh 

 lilood pressure as the result of adrenal hvpertrophv. (Pearce, Jour. Exp. ^led., 

 1908 (10), 735; 1910 (12), 128.) 



