METABOLISM OF PROTEINS 583 



greater part of the excreted nitrogen, it will be well to take it 

 first. 



Formation of Urea. The starting-point of all inquiries as to the 

 place of formation of urea is the fact that it occurs in the blood in 

 small amount (4 to 6 parts per 10,000 in man; 3 to 15 parts per 

 10,000 in the dog), the largest quantity being found when the food 

 contains most protein and at the height of digestion, the smallest 

 quantity in hunger (Schondorff). Evidently, then, some, at least, 

 of the urea excreted in the urine may be simply separated by the 

 kidney from the blood; and analysis shows that this is actually 

 the case, for the blood of the renal vein is poorer in urea than that 

 of the renal artery, containing only one-third to one-half as much. 

 If we knew the exact quantity of blood passing through the kidneys 

 of an animal in twenty-four hours, and the average difference in 

 the percentage of urea in the blood coming to and leaving them, 

 we should at once be able to decide whether the whole of f he urea in 

 the urine reaches the kidneys ready made, or whether a portion of 

 it is formed by the renal tissue. Although data of this kind are as 

 yet inexact and incomplete, it is not difficult to see that all, or most 

 of, the urea may be simply separated by the kidney. 



If we take the weight of the kidneys of a dog of 35 kilos at 160 grammes 

 (^ O th of the body-weight is the mean result of a great number of 

 observations in man), and the average quantity of blood in them at 

 rather less than one-fourth of their weight, or 35 grammes, and con- 

 sider that this quantity of blood passes through them in the average 

 time required to complete the circulation from renal artery to renal 

 vein, or, say, ten seconds, we get about 300 kilos of blood as the flow 

 through the kidneys in twenty-four hours. Even at 0-3 per 1,000, the 

 urea in 300 kilos of blood would amount to 90 grammes. Now, Voit 

 found that a dog of 35 kilos body-weight, on the minimum protein diet 

 (450 to 500 grammes of lean meat per day) which sufficed to maintain 

 its weight, excreted 35 to 40 grammes of urea in the twenty-four hours. 

 If, then, the renal epithelium separated somewhat less than half of the 

 90 grammes urea offered to it in the circulating blood, the whole excre- 

 tion in the urine could be accounted for, and the blood of the renal vein 

 would still contain more than half as much urea as that of the renal 

 artery. So that the whole of the urea in the urine may be simply 

 separated by the kidney from the ready-made urea of the blood. 



Another line of evidence leads to the same conclusion : that the 

 kidney is, at all events, not an important seat of urea-formation. 

 When both renal arteries are tied, or both kidneys extirpated, in a 

 dog, urea accumulates in the blood and tissues; and, upon the whole, 

 as much urea is formed during the first twenty-four hours of the 

 short period of life which remains to the animal as would under 

 normal circumstances have been excreted in the urine. 



Where, then, is urea chiefly formed ? The answer to this question 

 is that, while some urea is probably produced from amino-acids in 

 all the tissues, one organ is particularly associated with this function 

 namely, the liver. 



