UREMIA 533 



glycine are passed through the vessels of the isolated liver they di-siq)- 

 pear in part, while an increased amount of urea escapes from the he- 

 patic veins. It is probable tiiat t lie liver is the chief site of urea formation, 

 but it is also probable that urea can b(^ formed in other organs. We 

 do not know, however, the intermediate steps by which the amino- 

 acids of the protein molecule are converted into urea. It has been 

 repeatedly shown that urea can be formed from ammonium salts of 

 organic acids (including anunonium carbonate), and ammonia is a 

 constant protluct of autolysis, being characteristically more abundant 

 as a product of autolytic proteolysis than as a product of tryptic pro- 

 teolysis; therefore, one of the antecedents of urea is probably ammo- 

 nia, which is somewhat toxic and especially hemolytic.^ Another 

 antecedent of urea is ammonium carbamate, which stands in structure 

 intermediate between urea and ammonium carbonate, as shown by the 

 following graphic formulse: 



/OH /O-NH4 /NH2 /NH2 



O = C< O = C< O = C< = C< 



\0H \O-NH4 \O-NH4 \NH2 



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



That ammonium carbamate is possibly an important precursor of 

 urea has been shown particularly through the results of studies of 

 dogs with Eck's fistula,^ which consists of a fistula between the portal 

 vein and the inferior vena cava, the blood from the portal system 

 then passing directly into the general circulation without first passing 

 through the liver. In such animals the urine becomes poor in urea 

 and relatively rich in ammonium carbamate. At the same time, the 

 dogs show severe symptoms of intoxication from which they die, and 

 which are similar to the symptoms that follow intravenous injection 

 of ammonium carbamate. Ammonium carbamate, being a substance 

 of considerable toxicity^ when free in the blood, it has, therefore, 

 been quite widely considered that it may be an important factor in 

 the production of uremic symptoms. On the other hand, it seems 

 most probable that the condition of uremia does not depend upon 

 one but upon many various and varying substances, especially as 

 Hawk^ found that sodium carbamate did not produce uremic symp- 

 toms in his Eck fistula dogs, while Liebig's extract did.^ Clinicallj^, 

 the symptoms of uremia in different cases are widely different; thus 

 if uremia is due to complete suppression of urine through mechanical 



^ Concerning the toxicity of ammonium salts see Rachford and Crane, Medical 

 News, 1902 (81), 778. 



« See Hahn, Massen, Nencki, and Pawlow, Arch. f. exp. Path. u. Pharm., 1893 

 (32), 161. 



' See Bickel, "Exp. Untersuch. liber Cholaemie," Wiesbaden, 1900. 



8 Amer. Jour. Physiol., 1908 (21), 260. 



^ Fischler believes the intoxication which occurs after feeding meat to Kck 

 fistula dogs to be an alkalosis, probably from NH3 salts (Deut. Arch. khn. ?.Icd., 

 1911 (104), 300). 



