THE URINE 323 



the tubules pick it out from the blood in spite of its high 

 dilution in that fluid, and reject sugar, which is sixteen times as 

 much: p * 



It is evident that the disintegration of protein material which 

 leads to the formation of urea may be occurring in the actual 

 protein of the tissues {endogenous production), or it may be taking 

 place in the protein substances absorbed from the intestinal 

 canal which are not part of the tissues. This is known as ex- 

 ogenous production. It is not possible to say exactly how 

 much is contributed from each source, but it would seem that 

 the major portion is furnished from the protein food substances 

 not built into the protein of the tissues. 



The historyof urea is still very incomplete, but it is nowgenerally 

 accepted that it is formed, though perhaps not exclusively, in the 

 liver, and that the kidneys are only its path of excretion. The form 

 in which the antecedents of urea arrive at the liver is not definitely 

 known, nor, indeed, are the various stages existing between 

 protein and urea agreed upon. We have seen (pp. 189, 255) 

 that the protein molecule, under the influence of pepsin, trypsin, 

 and erepsin. is gradually reduced from complexity to simplicity, 

 and in so doing its nitrogen appears as ammonia, monamino- 

 acids, and diamino-acids. There is no reason to doubt that what 

 occurs in the intestinal area in the breaking up of the protein 

 molecule may also occur in the tissues. Muscles, for instance, 

 contain ammonia in large quantities. Ammonia is formed in 

 the body tissues by intracellular ferments, and is carried by the 

 blood to the liver. The form in which it is carried is not agreed 

 upon, but as the ammonia in the tissues unites with carbon 

 dioxide, it is probably carried either as ammonium carbamate 

 or carbonate. In the liver the conversion of this into urea by 

 the loss of a molecule of water is easy to understand. If the 

 blood of the portal vein be experimentally compelled to pass into 

 the posterior vena cava without circulating through the liver, 

 the output of urea is decreased, while the ammonia compounds 

 increase in the blood and cause poisoning. The blood of the 

 portal vein is found to contain three or four times more ammonia 

 compounds than arterial blood, and there can be no doubt that 

 these highly poisonous compounds are converted in the liver 

 into the less poisonous urea. It is well known that monamino- 

 acids, resulting from protein disintegration, such as leucine, 

 glycine, and aspartic acids, may be converted into urea, and it is 

 most likely that this change is effected during their passage 

 through the liver. The diamino-acids, represented in the body 

 by histidine, lysine, and arginine, are also capable of conversion 

 into urea. Arginine, for example, is acted upon by the ferment 

 arginase, which is found in the liver, kidneys, and other organs, 



