112 ESSENTIALS OF CHEMICAL PHYSIOLOGY 



occurs in all the living tissues, and the principal final result of this 

 proteid metabolism is urea. It may not be that the formation of urea 

 is perfected in each tissue, for if we look to the most abundant tissue, 

 the muscular tissue, very little urea is to be found. Yet there can be 

 no doubt that the chief place from which urea ultimately comes is the 

 muscular tissue. Some intermediate step occurs in the muscles ; the 

 final steps occur elsewhere. 



In muscles we find a substance called creatine in fairly large quan- 

 tities. If creatine is injected into the blood it is discharged as crea- 

 tinine. But there is very little creatinine in normal urine ; what 

 little there is can be nearly all accounted for by the creatine in the 

 food ; if the muscular creatine and creatinine are discharged as urea, 

 they must undergo some further change before they leave the 

 muscle. 



Similarly, other cellular organs, spleen, lymphatic glands, secreting 

 glands, participate in the formation of urea ; but the most important 

 appears to be the liver : at any rate this is the organ where the final 

 changes take place. The urea is then carried by the blood to the 

 kidney, and is there excreted. 



The facts of experiment and of pathology point very strongly in 

 support of the theory that urea is formed in the liver. The principal 

 are the following : — 



1. After removal of the liver in such animals as frogs, urea forma- 

 tion almost ceases, and ammonia is found in the urine instead. 



2. In mammals, the extirpation of the liver is such a serious 

 operation that the animals die. But the liver of mammals can be very 

 largely thrown out of gear by the operation known as Eck's fistula, 

 which consists in connecting the portal vein directly to the inferior vena 

 cava. Under these circumstances the liver receives blood only by the 

 hepatic artery. The amownt of urea is lessened, and its place is taken 

 by ammonia. 



3. When degenerative changes occur in the liver, as in cirrhosis of 

 that organ, the urea formed is much lessened, and its place is taken 

 by ammonia. In acute yellow atrophy urea is almost absent in the 

 urine, and, again, there is considerable increase in the ammonia. In 

 this disease leucine and tyrosine are also found in the urine ; undue 

 stress should not be laid upon this latter fact, for the small amounts 

 of leucine and tyrosine found doubtless originate in the intestine, and, 

 escaping further decomposition in the degenerated liver, pass as such 

 into the urine. 



We have to consider next the intermediate stages between proteid 

 and urea. A few years ago Drechsel succeeded in artificially pro- 



