532 ABNORMALITIES IN METABOLISM 



UREMIA2 



The cause or causes of the severe, often fatal, intoxication that 

 may occur when the outflow of urine is completely checked, or when 

 it is qualitatively and quantitatively altered for long periods of time, 

 have not yet been definitely determined. As the kidney seems to be 

 the chief organ for the removal of the products of nitrogenous metab- 

 olism, it is naturally assumed that uremia is the result of a retention 

 of these products, but as yet it has not been ascertained which of the 

 many products is responsible, and, indeed, there are very good reasons 

 for questioning if the substances present in normal urine do or can 

 cause uremia when their elimination by the kidney is defective. 

 There is no question but that the urine contains toxic substances. 

 Among them are the salts of potassium, which, however, cannot alone 

 explain all the urinary toxicity, for the symptoms produced by the 

 injection of urine are different from those produced by potassium salts, 

 and it has been found that the inorganic constituents (ash) of urine are 

 less poisonous than the entire urine. Furthermore, toxic mixtures of 

 organic, ash-free substances have been obtained from normal urine. ^ 

 Of the known normal constituents of the urine there are few, however, 

 that are toxic to any considerable degree, and these occur in but very 

 small quantities. Urea is generally considered as almost absolutely 

 non-toxic, the animal body withstanding injection of large quantities 

 without appreciable injury. Uric acid, the purine bases, hippuric 

 acid, creatinine, and the urinary pigments are all possessed of ver}^ 

 slight toxicity, and their effects do not explain uremia. Injections of 

 urine into animals may cause more or less disturbance, but it is differ- 

 ent, on the whole, from the manifestations of uremia. (The experi- 

 ments of Bouchard and his school present such serious errors of tech- 

 nique and interpretation that they are now largely disregarded.) 



For these and other reasons, it has been generally considered that 

 the intoxication of uremia is not due solely or chiefly to the substances 

 that are normally eliminated in the urine, but rather to more toxic 

 antecedents of the nitrogenous constituents of the urine. Urea repre- 

 sents but the final product of a long series of reactions by which the 

 huge protein molecule is broken up into its "building-stones," the 

 various amino-acids, and these in turn are decomposed in such a way 

 that their NH2 groups are combined with carbonic acid"* and eliminated 



.NHo 



as the diamido-compound of carbonic acid, namely urea, = C\ 



We know that the liver is able to accomi)lish the conversion of amino- 

 acids to urea, for it has been experimentally shown that if leucine and 



^General r6sum6 with earlier literature by: Honigmann, Ergeb. der Pathol., 

 1894 (Bd. 1, Abt. 2), 639; 1902 (8), 549; Ascoli, Vorlesungen iibcr Uriimie, Jena, 

 1903. 



' See Drcsbach, Jour. Exp. Med., 1900 (5), 315. 



* Arginine alone of all the amino-acids splits off urea diroctlj' from its molecule. 



