ON eck's fistula 7 



a cataleptic state was noted. With 0'6 grm. per kilogram tonic and 

 clonic convulsions were produced (simulating epilepsy), the saliva flowed 

 from the mouth, the pupils were dilated. Anaesthesia and blindness 

 were present Usually, the dogs recovered. With larger doses tetanus 

 with opisthotonus and cessation of respiratory movements, followed by 

 death, were observed. 



Exactly the same symptoms were produced in Eck's fistula dogs by 

 placing carbamate of sodium in the stomach, the contents of which had 

 previously been neutralized by giving sodium carbonate. On the other 

 hand, no symptoms, except occasional vomiting, followed a gastric 

 administration of carbamates to normal dogs. 



From these interesting observations it seemed justifiable to conclude 

 that the symptoms seen in Eck's fistula dogs are due to poisoning by 

 carbamic acid. The liver is the (chief) site of urea formation, the 

 immediate precursor of urea is carbamic acid, and large amounts of this 

 substance are contained in the portal blood (being formed in the intestine, 

 especially when flesh is being digested). Therefore, when the portal 

 blood does not traverse the liver before entering the systemic circulation, 

 the carbamic acid which it contains is retained somewhere in the 

 organism until present in sufficient amount to induce poisoning. 



Accepting these observations as correct, there would appear to be 

 little doubt that carbamic intoxication is the cause of the symptoms, but 

 if we consider the chemical nature of carbamic acid, and especially the 

 extreme rapidity with which, in the presence of water, it becomes 

 converted into ammonium carbonate, then it would appear that 

 poisoning by ammonium is more probably the true explanation. When 

 carbamate of ammonium comes in contact with water the following 

 reaction ensues : — 



ONH4 ONH4 



co< + H20 rt C0< 



NH2 ONH4 



The two arrows in this equation indicate that complete conversion of 

 carbamate into ammonium carbonate does not occur, but, on account of 

 reversible action, only until a certain equilibrium between carbamate and 

 carbonate is established.* 



* Haskins and I have recently shown that this decomposition of carbamate is extremely 

 rapid, and that the relative amount of carbamate which remains undecomposed is relatively high. 



(271) 



