vii KATABOLIC CONSTITUENTS OF UKINE 411 



flow of gastric (and intestinal) secretion containing ammonium 

 salts persisted so long as the animal; retained its normal vivacity, 

 and diminished progressively during the aggravation of the 

 phenomena of auto-intoxication, during which only was there 

 increase of urea in the blood. In short, toxic phenomena were 

 not developed so long as the gastro-intestinal surface functioned 

 as the vicarious excretory system in place of the kidneys, and 

 when this vicarious function ceased, auto-intoxication set in, and 

 soon led to the death of the animal. 



In the advanced stages of Bright's disease also, when the 

 impermeability of the urinary passages has become marked, a 

 very complex syndrome of auto-intoxication phenomena makes its 

 appearance, which is known to pathologists as uraemia a most 

 inappropriate term, since this state depends less on the retention 

 of urea than on the sum of the other mineral and organic sub- 

 stances normally present in the urine, which exert a far greater 

 toxic action on the tissues. This was first demonstrated by Gallois 

 in Bernard's laboratory (1859), who found that the injection of 

 strong doses of urea into the blood did not produce permanent 

 disorders, such as are observed in the diseases caused by the 

 so-called " uraemia." 



That urea in and per se is not toxic to vertebrates can also be 

 deduced from the striking fact, first pointed out by von Schroder 

 (1890), that the blood of certain fishes (Selachia) normally contains 

 urea in a concentration of 2 - 6 per cent, which approximately 

 corresponds with that at which it is normally present in human 

 urine. According to Baglioni (1905, see Vol. I. p. 297), the high 

 content of urea in the blood of these fishes is not only innocuous, 

 but even essential, in order that the myocardium shall function 

 properly. 



Another method of demonstrating that the urine, as a whole, 

 normally contains toxic substances, consists in its intravenous 

 injection into animals, on which (when the quantity injected 

 reaches a certain maximum that increases with the body- weight) 

 toxic phenomena set in that are rapidly fatal. Feltz and Hitter 

 (1881) first performed this experiment successfully on rabbits, and 

 Bocci, at Moleschott's suggestion, shortly afterwards on frogs. 

 But the credit of establishing the importance of this method of 

 determining the toxicity of natural urine and its principal com- 

 ponents, is undoubtedly due to Bouchard (1887). He always 

 employed rabbits, by injecting the fresh urine either of a healthy or 

 of a sick man into the auricular vein, and then observed the toxic 

 phenomena, which varied with the varying dose of urine injected. 

 He gave the name urotoxia to the amount of toxic constituents 

 necessary for the lethal dose per kilo, of the animals experimented 

 on, and urotoxic coefficient to the amount of urotoxias eliminated 

 with the urine in 24 hours per kilo, body-weight. 



