686 THE SEAT OF FORMATION OF UREA 



normal, and yet convulsions occurred just the same. Other 

 points of contrast between the two sets of experiments are 

 as follows : in their experiments practically no bile could have 

 been produced, the urine was not alkaline but extremely acid 

 and contained lactic acid. There can be little doubt that they 

 were right in ascribing the symptoms in their dogs to an acid 

 intoxication by intermediate metabolic products. 



The numerous observations on men the subjects of liver 

 destruction have equally failed to bring forward any con- 

 clusive evidence that the liver is not the only organ which can 

 form urea. The changes in the urine observed in cases of 

 advanced destruction of the liver by acute yellow atrophy 

 or cirrhosis are similar to those in Salaskin and Nencki's dogs. 

 But the actual degree of liver destruction is in those cases even 

 more uncertain, and a condition of acid intoxication almost 

 certainly exists in them. We are bound to conclude that there 

 is at present no proof that tissues other than the liver can 

 manufacture urea from anything but arginin. There is another 

 difficulty in the interpretation of observations on destruction 

 of the liver which is important. The various steps in the 

 breaking down of tissue proteid, which we now ascribe to the 

 activity of numerous tissue ferments, cannot be looked upon 

 as a number of isolated phenomena which can take place in 

 the body quite independently of each other. They are to be 

 looked upon rather as a series of events in a continuous cycle 

 of changes, and, if one is prevented, the whole cycle may be 

 interfered with. We know that in the liver many of the 

 terminal changes in proteid katabolism take place. When that 

 organ is largely destroyed we cannot assume either that any 

 alterations in metabolism which ensue represent nothing but 

 the series of changes which would be normally carried out in 

 the liver, or that proteid katabolism goes on in all other tissues 

 in an undisturbed and normal manner. This assumption be- 

 comes all the more impossible when we know that many of 

 the intermediate products of proteid metabolism are poisonous 

 to the tissues. 



Acid intoxication or acidosis, one of the auto -intoxications 

 by intermediate metabolic products, may be briefly considered 

 here, because it throws a side-light on the relation of ammonia 

 to urea in the body. The acids of which we know most in this 



