74 THE SIMPLER NATURAL BASES 



creatinine is diminished when the tissue metabolism is decreased. 

 New-born infants excrete per kilo, of body weight one-third of the 

 creatinine excreted by adults [Amberg and Morrill, 1907 ; Funaro, 

 1908]. Old people excrete less than young adults, and women less 

 than men [Benedict and Myers, 1907, I]. In muscular dystrophy 

 [Spriggs, 1907], in Basedow's disease [Forschbach, 1908], in hepatic 

 disease [Mellanby, 1908], in diabetes [Krause, 1910], and in other patho- 

 logical conditions [Shaffer, 1908] the creatinine output is diminished. 

 On the other hand the more rapid metabolism of fevers causes an in- 

 creased creatinine output [Leathes, 1907] and this applies also to artificial 

 hyperthermia [Myers and Volovic, 1913]. The latter authors record 

 an increase up to 36 per cent. As will be seen, however, the decrease 

 in creatinine output is also in accordance with the theory which 

 regards creatine as the precursor of creatinine ; when the output of the 

 latter substance falls off, the former may take its place in the urine, 

 as in diabetes and in hepatic disease. 



Folin's denial of a genetic relationship between creatine and crea- 

 tinine has not met with general acceptance. It was endorsed by af 

 Klercker [1907] and by Lefmann [1908], but, as has been pointed out 

 by van Hoogenhuyze and Verploegh [1909], Lefmann's results hardly 

 support his conclusion and rather indicate a partial conversion of 

 injected creatine to creatinine. Most authors do not agree with Folin's 

 sharp differentiation between muscular creatine and urinary creatinine ; 

 there is a good deal of evidence in support of the view that one of these 

 substances is derived from the other. Mostly creatine has been re- 

 garded as the precursor of creatinine, but Mellanby [1908] takes the 

 converse view. According to him creatinine is formed in the liver 

 from substances brought there by the blood stream, and is subsequently 

 rendered innocuous by hydration to creatine. In the young chick 

 creatine is at first absent from the muscles and gradually increases 

 until the saturation point is reached, and then the excess of creatinine 

 is excreted as such in the urine. Other investigators agree with 

 Mellanby in regarding the liver as the seat of transformation, but 

 consider the change to be in the opposite direction, viz. a dehydration 

 of muscular creatine to creatinine which is then excreted. When the 

 activity of the liver is impaired, as in phosphorus poisoning and in 

 hepatic disease, some creatine escapes dehydration and appears in the 

 urine as such (see above). 



A further argument for the view that creatine is converted into 

 creatinine and then excreted, has recently been supplied by Myers 

 and Fine [1913, I], who find that the creatine content of muscle 



