UREMIA 525 



UREMIA - 



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 j^et 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 rea- 

 sons 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 nor- 

 mal 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 very slight toxicity, and their effects do not explain 

 uremia. Injections of urine into animals may cause more or less 

 disturbance, but it is different, on the whole, from the manifestations 

 of uremia. (The experiments of Bouchard and his school present 

 such serious errors of technique and interpretation that they are now 

 largely disregarded.) 



For these and other reasons, it is 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 NHo groups are combined with carbonic acid * and 

 eliminated as the diamido-compound of carbonic acid, namely urea, 



2 General r^snin^ with literature bv: Honigmann. Ergeb. der Pathol., 1894 

 (Bd. 1, Abt. 2), 639; 1902 (S), .'549 • Ascoli, Vorlesimgen iibcr Uriimie. Jena, 

 1903. 



3 See Dresbach. Jour. Exp. Mod., 1900 (."i). 31;"). 



4 Arginine alone of all the amino-acids splits off urea directly from its molecule. 



