CH. xxxvii.] FORMATION OF UREA. 553 



nearly so. Yet there can be no doubt that the chief place from 

 which urea ultimately comes is the muscular tissue. Some inter- 

 mediate step occurs in the muscles ; the final steps occur elsewhere. 



In muscles we find a substance called creatine in fairly large 

 quantities. If creatiae is injected into the blood it is discharged 

 as creatiniue. 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 ; the muscular creatine is discharged as urea ; 

 moreover, urea can be artificially obtained from creatine in the 

 laboratory. 



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

 secreting glands, participate in the formation of urea ; but the 

 most important appears to be the liver : 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 

 formation almost ceases, and ammonia is found in the urine 

 instead. 



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

 operation that the animals do not live. But the liver of 

 mammals can be very largely thrown out of gear by connecting 

 the portal vein directly to the inferior vena cava (Eck's fistula). 

 This experiment has been done successfully in dogs ; the amount 

 of urea in the urine 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 leucine and tyrosine 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 arti- 

 ficially producing urea from casein. More recent work has shown 

 that this is true for other proteids also. If a proteid is decom- 

 posed by hydrochloric acid, a little stannous chloride being added 

 to prevent oxidation, a number of products are obtained, such as 

 ammonium salts, leucine, tyrosine, aspartic, and glutatninic acids. 



