432 HANDBOOK OF PHYSIOLOGY. 



the other hand, if the blood be from a fasting animal, there is no in- 

 crease of urea. Evidently, then, the blood from a well-fed animal con- 

 tains something which the liver cells are capable of transforming to 

 urea. And, finally, if the liver be removed and the animal kept alive, 

 as has been done (Pawlow), there is a marked diminution in the quan- 

 tity of urea in the urine. The power of the liver to form urea is thus 

 demonstrated, and, moreover, the fact that the liver forms from some 

 antecedent substance the greater part of the urea eliminated. 



The question which now presents itself is, What is this antecedent 

 substance or substances? 



Urea is the end-product of the oxidation of proteids. It was formerly 

 thought that urea was formed directly from some .antecedent among the 

 closely related products of proteid metabolism, such ascreatin, creatinin, 

 leucin, tyrosin, xanthin, hypoxanthin, etc. Creatinin at one time 

 seemed the most probable source, because in laboratory experiments it 

 decomposes into urea and sarcosin. Attention was also directed to 

 leucin and tyrosin, which are found in practically all the glandular 

 organs of the body. It was found that when leucin was fed to a dog, 

 the amount of urea in the urine was considerably increased, but that 

 leucin itself did not appear; the same phenomena were noticed with 

 glycin, sarcosin, and the amido acids. It was also known that in 

 acute yellow atrophy of the liver, a disease characterized by degeneration 

 of the liver cells with consequent loss of functional power, the urea of 

 the urine was replaced by leucin and tyrosin. Experimental investiga- 

 tion, however, did not justify any of these theories. 



Finally it was found that when ammonia was fed to animals, the 

 nitrogen appeared in the urine in the form of urea. Due investigation 

 of this fact led to the belief that proteids were first broken down to an 

 ammonia stage and then again built up into urea by the liver. For a 

 long time it was thought that this stage was represented by ammonium 

 carbonate, but in view of recent experiments this idea has been given 

 up, and it is now believed that ammonium carbamate is the true ante- 

 cedent. 



In these experiments the liver was first shut out of the general cir- 

 culation by (Eck's fistula) connecting the portal vein with the hepatic 

 artery; the results of this operation are, for all practical purposes, 

 equivalent to actual removal of the liver. When animals survived this 

 operation it was found that they could live if fed very carefully on a 

 mixed diet from which proteids were almost entirely eliminated, but 

 that if the food contained an excess of proteids, convulsions ensued and 

 proved fatal. Further investigation of the composition of the urine 

 and blood showed that proteid metabolism was represented in them by 

 ammonium carbamate and not by urea. Ammonium carbamate was then 



