434 METABOLIC ABNORMALITIES, AUTOINTOXICATION 



of technique and interpretation that they are now largely dis- 

 regarded.) 



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, 1 but rather 

 to more toxic antecedents of the nitrogenous constituents of the 

 urine. Urea represents but the final product of a long series 

 of reactions by which the huge proteid molecule is broken up 

 into its " building-stones," the various amino-acids, and these in 

 turn are decomposed in such a way that their NH 2 groups are 

 combined with carbonic acid 2 and eliminated as the diamido- 



/NH 2 

 compound of carbonic acid, namely urea, O = O^ . We 



know that the liver is able to accomplish the conversion of 

 amino-acids to urea, for it has been experimentally shown that 

 if leucin and glycocoll are passed through the vessels of the 

 isolated liver they disappear in part, while an increased amount 

 of urea escapes from the hepatic veins. It is probable that the 

 liver is the chief site of urea formation, but it is also probable 

 that urea can be formed in other organs. We do not know, 

 however, the intermediate steps by which the amino-acids of 

 the proteid molecule are converted into urea. It has been 

 repeatedly shown that urea can be formed from ammonium salts 

 of organic acids (including ammonium carbonate), and ammonia 

 is a constant product of autolysis, being characteristically more 

 abundant as a product of autolytic proteolysis than as a prod- 

 uct of tryptic proteolysis ; therefore, one of the antecedents 

 of urea is probably ammonia, which is somewhat toxic and 

 especially hemolytic. 3 Another antecedent of urea is ammonium 

 carbamate, which stands in structure intermediate between urea 

 and ammonium carbonate, as shown by the following graphic 

 formula : 



/OH /O NH 4 /NH 2 /NH 2 



= C< 0:=C< = C< 0=C< 



X)H \0 NH 4 X O NH 4 \NH 2 . 



(carbonic acid) (ammonium carbonate) (ammonium carbamate) (urea) 



That ammonium carbamate is probably an important precursor 

 of urea has been shown particularly through the results of 

 studies of dogs with Eck's fistula, 4 which consists of a fistula 



1 See Bradford, Practitioner, 1901 (67), 507. 



2 Arginin alone of all the amino-acids is known to split ofi urea directly 

 from its molecule. 



3 Concerning the toxicity of ammonium salts see Rachford and Crane, 

 Medical News, 1902 (81), 778. 



4 See Hahn, Massen, Nencki, and Pawlow, Arch. f. exp. Path. u. Pharm., 

 1893 (32), 161. 



