546 WASTE-PRODUCTS 



case we have come to attach a very fundamental significance to the 

 creatinine excretion in the urine. 



It was first pointed out by Folin that with varying nitrogenous 

 intakes the behavior of the creatinine output is fundamentally different 

 from that of the output of urea. The latter rises and falls almost in 

 direct proportionality to the quantity of protein in the food. The 

 creatinine output, on the contrary, remains almost unaltered whether 

 the protein content of the diet be high or low. The creatinine output 

 is not, therefore, derived from the diet. Thus, for example, Folin 

 compared the urea and creatinine excretipn on a high protein diet 

 and a low protein diet, with the following very striking results: 



High protein diet. Low protein diet. 



Volume of urine 1170. c.c. 385. c.c. 



Total nitrogen . ... . 16. 80 grams 3. 6 grams 



Urea-nitrogen . . . . . . . 14.70 " 2.2 



Creatinine-nitrogen .... 0.58 " 0.6 



The urea output, it will be seen, fell on the low protein diet to one- 

 sixth of that obtained on the high protein diet. The creatinine output, 

 on the contrary, remained almost unaltered. 



The statement that the creatinine which is excreted in the urine is 

 not derived directly from the foodstuffs must be qualified to this extent, 

 that if creatinine be contained preformed in the diet, the greater part 

 of it is excreted in the urine unaltered within twenty-four hours. On 

 the other hand, if creatine be administered with the food it does not 

 appear in the urine either in the form of creatine or creatinine. In 

 fact it usually appears to be excreted by some other channel or else 

 retained by the body, for Folin in many instances administered crea- 

 tine without causing any increase even in the total nitrogen of the 

 urine. It has been suggested by Mellanby that bacteria in the intestine 

 decompose the creatine and retain it in their tissues. However this 

 may be, these observations render it certain that the creatine which is 

 contained preformed in a meat-diet is not the source of the creatinine 

 in the urine. 



Since the output of creatinine is so extraordinarily independent of 

 fluctuations in the diet, Folin regards it as originating in the Endog- 

 enous Metabolism of the tissues themselves, while a great part of the 

 urea arises from the destruction by deaminization of amino-acids 

 which have never become part of the living protoplasm of the body, 

 and therefore represents a product of Exogenous Metabolism. The 

 exogenous metabolism rises and falls with the intake of foodstuffs, but 

 the endogenous metabolism persists practically unchanged under a 

 variety of nutritional conditions. It represents the "wear and tear" 

 or irreversible spontaneous decomposition of the tissues. 



It is questionable, however, whether the creatinine output represents 

 the endogenous metabolism of the whole body or whether it does not, 

 on the contrary, arise from the endogenous metabolism of the muscular 



