THE FINAL DESTRUCTION OF PROTEID 371 



This view received substantial support in the experiments of v. Schroeder, 

 in which by artificial perfusion of an excised dog's liver with ammonium 

 carbonate or formate,, the production of urea from these salts was demon- 

 strated directly. Experiments carried out in the same way on the kidneys 

 and muscles gave only negative results. Likewise by digestion of glycocoll 

 with crushed liver tissue or liver extract, urea, or, to be more exact, a closely 

 related compound is formed (Richet, Loewi et al.). 



Indirectly the importance of the liver in this connection is shown by the 

 experiments of Nencki and Pawlow on dogs with an Eck fistula between the por- 

 tal vein and the inferior vena cava (cf. page 274) in which the liver therefore 

 received its blood by the hepatic artery only. In these animals the elimination 

 of ammonia in the urine increased and the power of the organism to form urea 

 from carbamic acid introduced into the stomach was lost. After a time char- 

 acteristic abnormal symptoms made their appearance (namely, somnolence, 

 ataxia, excitation, loss of vision, epilepsy, anaesthesia, tetanus) and these could 

 be produced at will by an abundant supply of nitrogenous food, ammonium salts, 

 or glycocoll. 



In birds and reptiles the nitrogen of the decomposed proteid leaves the 

 body chiefly as uric acid. Any information we can get as to the seat of uric 

 acid production in birds ought therefore to be strongly suggestive of the seat 

 of urea production in mammals. Birds are especially well adapted to experi- 

 mental investigation of this subject because extirpation of the liver is rela- 

 tively easy on account of the peculiar relations of the circulation. The ani- 

 mals live for as much as twenty hours after the operation. Their urine, 

 however, is very poor in uric acid, since only about three to four per cent 

 of the total nitrogen is now eliminated in this form, whereas the percentage 

 of ammonium salts (lactate) is considerably increased. Amino acids, which 

 normally are transformed into uric acid in birds, when fed to geese deprived 

 of the liver, are eliminated as ammonium lactate. Urea passes out unchanged 

 (Minkowski). The quantity of uric acid eliminated also has been increased 

 by electrical stimulation of the liver (Milroy). Hence the liver must be 

 regarded as the seat of uric acid production in birds. 



We may conclude also that urea is formed from ammonia to a very large 

 extent in the liver, and that the other organs probably have at most only 

 a small share in this function. The digestive tract is indicated as the chief 

 source of the ammonia ; for, according to the investigations of Nencki, Salas- 

 kin and others, the percentage of ammonia in the intestinal and gastric 

 mucosa is considerably greater than that of the other organs; the portal blood 

 also is considerably richer in ammonia than the blood of the hepatic arteries 

 and veins. The ammonia split off in the liver from the amino acids must 

 be taken into account also. 



There is in all this however no proof that all of the urea, exclusive of that 

 split off directly from the proteid (cf. page 369), comes from ammonia and 

 is formed in the liver. Observation shows rather that in the dog large quan- 

 tities of urea are eliminated even after complete extirpation of the liver. 

 Similarly it has been found that in diseases of the human liver where the 

 entire organ, to judge from examination of sections, had become completely 

 inefficient, more than sixty per cent of the total nitrogen in the urine has 



