472 TEXT-BOOK OF PHYSIOLOGY. 



fasting condition that for a period of 10 days, there is a daily excretion 

 of about 21 grams of urea equivalent to about 63 grams of protein metabo- 

 lized. If it be accepted that approximately 63 grams of tissue protein are 

 metabolized each day then of the 34 grams of urea excreted, 13 grams must 

 come from about 40 grams of metabolized food protein. That the urea that 

 comes from the tissue protein is a rather constant factor and that the urea 

 that comes from the food protein is a variable factor is shown by the fact that 

 the amount of urea excreted rises and falls proportionately to the protein con- 

 sumed. As to the particular tissues that are undergoing protein metabolism 

 there is much obscurity. Contrary to what might be expected there is ap- 

 parently but little protein metabolism in muscle tissue for there is no parallel- 

 ism between urea production and muscle work. Even after severe labor 

 extending over a period of some hours there is no noticeable increase in the 

 urea excreted. 



Seat of Formation and Antecedents of Urea. It has been stated in a 

 foregoing paragraph that the excretory organs are engaged in the process of 

 eliminating from the blood, rather than in elaborating, the end products of 

 metabolism. Therefore the supposition is that the kidneys are not the seat 

 of urea formation but only the means by which it is eliminated from the 

 blood. This supposition is rendered highly probable from the following 

 facts: the blood of the renal artery contains from one-third to one-half 

 more urea than the blood of the renal vein; ligation of the renal arteries 

 or removal of the kidneys leads to an accumulation of urea in the blood to an 

 extent four times the normal amount in 24 hours; perfusion of the excised 

 kidney, which still retains its physiologic activity, with blood containing 

 known antecedents of urea is unattended with urea formation. These and 

 other facts of a similar character confirm the view that the kidney does not 

 manufacture but simply excretes urea brought to it by the blood. Since 

 urea is always present in the blood to an extent of from 0.04 per cent, to 

 0.06 per cent., i.e., from 4 to 6 grams per 10,000 grams, and that it is being ex- 

 creted at the rate of about 1.5 grams per hour, it is evident that it is being as 

 constantly formed in some one or more organs, and discharged into the 

 blood. 



The experimental evidence now at hand indicates the liver as the chief 

 organ engaged in this process. The following facts support this view, viz. : 

 destructive diseases of the liver, e.g., acute yellow atrophy, interstitial hepa- 

 titis, and suppuration, largely dimmish the production of urea but increase the 

 amount of the ammonium salts in the urine; the establishment of an Eck 

 fistula (the union of the portal vein with the ascending vena cava whereby 

 the liver is almost entirely excluded from receiving compounds absorbed 

 from the intestine) is followed by a decrease in the production of urea and 

 an increase in the ammonium content of the urine; the perfusion of the 

 liver of a recently killed animal with a given amount of blood containing 

 ammonium salts will be followed after the lapse of several hours by an amount 

 of urea in the blood two or three times the normal quantity. These and 

 oiher facts indicate that the chief seat of urea formation is to be found in 

 the liver cells. 



The antecedents of urea, out of which the hepatic cells construct urea 

 have, for chemic reasons as well as from the foregoing experimental results, 



