460 TEXT-BOOK OF PHYSIOLOGY 



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 diminish 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 

 other 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, 

 been shown to be the salts of ammonia the carbonate, carbamate, and 

 lactate. The increase in the ammonia of the urine simultaneously with 

 the decrease in the urea renders it extremely probable that these salts are 

 antecedents of urea and that the transformation takes place in the liver 

 cells. The chemic change that takes place is simply the abstraction of two 

 molecules of water as shown in the following formula: 



(NH 4 ) 2 C0 3 - 2 H 2 = 



The source of the ammonia is probably in part the intestine, as this 

 compound is one of the products of the hydrolysis and cleavage of the proteins 

 during digestion. That this is the case is apparent from the fact that the 

 blood of the portal vein always contains more ammonia that the blood of 

 any other region of the vascular apparatus. The advantage to the body 

 that results from the conversion of ammonia to urea is that it prevents an 

 ammonia intoxication with its attendant evils that would otherwise arise. 



It will be remembered that the ammo-acids, as tyrosin, leucin, glutamic, 

 and aspartic acids, diamino-acids and bases, as lysin, arginin, histidin which 

 are also products of the hydrolysis of proteins during digestion are capable 

 of being absorbed as such by the epithelial cells of the villi and mucous mem- 

 brane. After absorption they are transmitted by the blood to the tissues of 

 the body generally by which they are directly utilized in the formation of 

 tissue protein or perhaps stored for future use, for there is evidence for the 

 belief that tissues have a capacity for the storage of amino-acids, which in 

 the case of muscles amounts to from 70 to 80 milligrams per 100 grams. 

 After saturation of the tissues, so to speak, with amino-acids, there yet re- 

 mains a certain percentage in the blood which undergoes a cleavage into an 

 NH 2 portion and an organic portion; the former is then converted to am- 

 monia and subsequently to urea by the liver cells, the latter, the organic 

 portion, contributes to the production of fat or sugar, which in due time is 

 oxidized and thus contributes to the store of body-heat. 



From the foregoing facts it is evident that given the presence of ammonia 

 salts in the blood of the portal vein the appearance of urea in the urine" is 

 readily accounted for. There is also evidence for the belief that in the 

 muscles and perhaps other tissues as well, amino-acids, those resulting from 



