768 PHYSIOLOGY 



was held till recently, however, on the ground of experiments by Voit, that 

 creatine administered in the food appeared in its entirety as creatinine in the 

 urine, so that if creatine were liberated from the muscles in their normal 

 processes of metabolism it would pass to the kidneys and be excreted as 

 creatinine without undergoing further decomposition. On this account too 

 the creatinine in the urine was regarded as derived almost exclusively from 

 the creatine taken in with the food. The analyses given in Folin's Tables 

 show that in one respect at any rate this view was incorrect. Creatinine is 

 excreted in considerable quantities even when the man is on a creatine- free 

 diet, or even when his food is almost free from protein. It has been found 

 moreover by Folin that creatine administered by the mouth may disappear 

 in the body. This is especially the case if the animal or man is on an in- 

 sufficient protein diet, but there is no evidence of a corresponding increase 

 in urea formation. If a larger amount be given creatine appears as such in 

 the urine. In most cases a certain minute proportion escapes and causes an 

 increase in the quantity of creatinine. Under abnormal circumstances, e.g. 

 during illness, when the physiological activities of the body are lowered, a 

 portion of the creatine may be found in the urine in an unchanged con- 

 dition. If creatinine is to be regarded in any way as the index of tissue 

 metabolism its amount ought to vary with the extent of this metabolism. 

 Thus it should be increased when there is an exaggeration of the disintegrative 

 processes in the tissues, and should be diminished when the nutritive changes 

 in these tissues, especially in the muscles, are reduced to a minimum. The 

 end-products of tissue metabolism therefore should be increased under the 

 following conditions : 



(1) Increased motor activity involving increased wear and tear of the 

 muscular tissues. 



(2) In fevers, especially in those where there is severe toxaemia and rapid 

 wasting of the muscles of the body. 



On the other hand, it should be diminished where the activity of the 

 muscular tissue is reduced to a minimum, as under the influence of sleep or 

 soporifics, or where the bulk of the muscular tissue is reduced as well as its 

 activity, as in cases of widespread muscular atrophy and paralysis. 



The excretion of creatinine has been investigated under these various 

 conditions by Van Hoogenhuyze and Verploegh, and their results fully bear 

 out the view expressed above as to the intimate relation of creatinine with 

 the tissue metabolism of protein. 



During protein starvation the uric acid output, though diminished, does 

 not show a change which is at all proportional to that shown by the urea. 

 This substance also might therefore represent an end-product of tissue 

 metabolism. Since, however, uric acid is an outcome of the metabolism of 

 a special group of bodies, the nucleins and purine bases, we shall have to 

 devote a complete section to its consideration. 



Although the urea is diminished in protein starvation, it still remains the 

 most abundant nitrogenous constituent of the urine. We are therefore not 

 justified in excluding this substance from the products of tissue metabolism. 



