URINE 147 



discharged. This is strikingly different from what occurs in the case 

 of carbonic acid ; the more the muscles work, the more carbonic acid 

 do they send into venous blood, which is rapidly discharged by the 

 expired air. Muscular energy is derived normally from the combus- 

 tion of non-nitrogenous material ; this is very largely carbohydrate. 

 If the muscles, however, are not supplied with the proper amount of 

 carbohydrate and fat, or if the work done is very excessive, then they 

 consume some of their more precious protein material. 



Where is Urea formed? The older authors considered that it 

 was formed in the kidneys, just as they also erroneously thought that 

 carbonic acid was formed in the lungs. Prevost and Dumas were the 

 first to show that after complete extirpation of the kidney the forma- 

 tion of urea and other waste products goes on, and these accumulate 

 in the blood and tissues. Similarly, in those cases of disease in 

 which the kidneys cease work, urea is still formed and accumulates. 

 This condition is called urcsmia (or urea in the blood), and unless the 

 waste substances are discharged from the body the patient dies. 



Urcemia. This term was originally applied on the erroneous supposition 

 that it is urea or some antecedent of urea which acts as the poison. There 

 is no doubt that the poison is not any constituent of normal urine ; if the 

 kidneys of an animal are extirpated the animal dies in a few days, but there 

 are no uraemic convulsions. In man also, if the kidneys are healthy or 

 approximately so, and suppression of urine occurs from the simultaneous 

 blocking of both renal arteries by clot, or of both ureters by stones, again 

 uraemia does not follow. On the other hand, uraemia may occur even while 

 a patient with diseased kidneys is passing a considerable amount of urine. 

 What the poison is that is responsible for the convulsions and coma is 

 unknown. It is doubtless some abnormal katabolic product, but whether 

 this is produced by the diseased kidney cells, or in some other part of the 

 body, is also unknown. 



Where, then, is the seat of urea formation ? The facts of experi- 

 ment 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. In these circumstances the liver receives blood only 

 by the hepatic artery. The amount 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 yelloio atrophy, urea is almost absent from the 



L 2 



