

THE METABOLISM OF PROTEIN 651 



Influence of Liver on Ammonia-Urea Ratio. Experimental Observa- 

 tions: (1) REMOVAL OF LIVER. There are several facts which indicate that 

 other causes than acid-production may interfere with the conversion of am- 

 monia into urea. What are these causes? Since, as we have seen, 

 the liver is the organ which most actively converts amino acids 

 into urea, it would be natural to expect that, when the functions of 

 this organ were interfered with, relatively more of the nitrogen excre- 

 tion would occur as ammonia and relatively less as urea. In order to 

 determine the exact significance of the liver as a urea-forming organ, 

 two types of investigation have been used; namely, (1) observation of 

 the changes produced in the ammonia-urea ratio in the urine by partial 

 or total removal of the liver; and (2) observation of the urea-forming 

 power of a liver perfused outside the body. 



To remove the liver from the circulation the portal vein is brought 

 in apposition with the vena cava, the two are sewed together, and a 

 passage opened between them, after which the portal vein is ligated above 

 the anastomosis (forming the so-called Eck fistula). The portal blood 

 then passes directly into the vena cava, and the liver is now supplied 

 only by the hepatic artery. The animals live for a considerable time 

 after the operation, and the urine frequently contains relatively less 

 urea and more ammonia than normal. The results are, however, not 

 nearly so striking as would be expected if the liver were the main seat 

 of urea formation. The experiments have nevertheless brought to light 

 a fact of considerable clinical interest namely, although the animals 

 may thrive if kept on a diet not containing an excess of flesh, they im- 

 mediately begin to develop peculiar symptoms, not unlike those of ec- 

 lampsia or uremia, when they are fed with large amounts of flesh food. 

 Most of the symptoms can be referred to abnormal stimulation of the 

 central nervous system, and examination of the urine has shown a large 

 increase in the excretion of ammonia and a change from the normal 

 acid reaction to an alkaline one. 



At one time it was assumed that the toxic symptoms were caused by 

 the presence in the blood of ammonium carbamate, since large quantities 

 of the calcium salt of this substance could be separated from the urine. 

 It is now known, however, that the ammonium carbamate is present only 

 because of the excess of ammonium carbonate, the two salts existing to- 

 gether in solution according to the laws of mass action. That the intox- 

 ication is not due to ammonium carbamate does not exclude the pos- 

 sibility that it may be due to ammonia itself, although it is more likely 

 that other nitrogenous metabolites, produced when excess of flesh food 

 is taken, are the responsible agents. 



If the liver is entirely removed by ligating the hepatic arteries in an 



