908 METABOLISM. 



It must not, however, be assumed that the whole of this ultimate 

 metabolism occurs in the liver, for, as a matter of fact, after complete 

 destruction of the liver by disease, or after its complete removal or 

 destruction by operation, the urea of the urine does not wholly dis- 

 appear, although in large measure replaced by ammonium salts (and 

 under some circumstances by leucine and tyrosine). It is not certainly 

 known in what other organs urea may be formed. The occurrence of a 

 large amount of urea in the muscles of Elasmobranchs might seem to 

 point to the muscles as the possible source of such urea. 1 But, on the 

 other hand, as we have seen, v. Schroder was unable to obtain any 

 evidence of the appearance of urea in blood perfused through muscles 

 of dogs. It is, on the whole, more probable that other glandular organs 

 may have some share in its production. 2 



The total removal or destruction of the liver in mammals has been 

 rendered possible, by the discovery that it is feasible to establish a permanent 

 communication between the portal vein and the inferior vena cava (Eck's 

 fistula), 3 and thus, after tying the hepatic artery as well as the portal vein, to 

 shunt the liver altogether out of the circulation ; in fact, after such a fistula 

 is established, the organ may be altogether removed. A large number of 

 such operations have been made upon dogs by Halm, Massen, Nencki, 

 and J. Pawlow, and the results upon general, and especially nitrogenous 

 metabolism, carefully recorded. 4 About one-third of the number in which 

 the fistula was established recovered from the effects of the operation, but 

 those in which the organ was completely removed only lived a few hours. 

 Many of those with the Eck fistula refused food. These soon showed 

 symptoms of convulsions, and eventually died. Those which fed well 

 recovered weight, and showed no very obvious symptoms, unless given an 

 excess of proteid food; this invariably brought on convulsions. The same 

 result was produced by giving carbamic salts with the food (although these 

 produce no such symptom in normal dogs). The urea was only slightly 

 diminished in those with the Eck fistula only (but greatly so when the liver 

 was completely removed) ; the uric acid excreted was at first greatly increased 

 (four times), but afterwards became normal ; the ammonium salts in the urine 

 were increased, and were partly in the form of carbamate. Merely tying the 

 hepatic artery in rabbits may also cause the appearance of ammonium lactate in 

 the urine, 5 a result probably due to interference with its oxidation to car- 

 bonate of ammonia, and the synthesis of this to urea. The amount gradually 

 diminishes, under these circumstances, as a collateral arterial circulation 

 becomes established in the liver. 



Nencki, Pawlow, and Zaleski 6 found that the portal blood of flesh-fed dogs 

 contains three and a half times as much ammonia as the hepatic blood. 

 Nevertheless the amount in the portal vein (which they calculated to have 

 been 4 '73 grms. in ten hours in a dog weighing 9 '5 kilos.) was too small to 



1 The muscles of Elasmobranchs were found by v. Schroder (Ztschr. f. pliysiol. Chem,, 

 Strassburg, 1890, Bd. xiv. S. 576) to contain 2 per cent, of urea ; the blood, 2' 6 per cent. ; the 

 liver, 1 '36 per cent. The amount found in the muscles remained the same after removal 

 of the liver. It is therefore evident that the conditions of nitrogenous metabolism are 

 quite different in these animals from those met with in mammals. 



2 Cf. Miinzer, Arch. f. exper. Path. u. PharmakoL, Leipzig, 1894, Bd. xxxiii. S. 164; 

 Kaufmami, Arch, de physiol. norm, etpath., Paris, 1894, p. 531. 



3 Eck, Trav. Soc. d. natur. de St. P&ersbmirg, 1879, tome x. 



4 Arch, de sc. biol., St. Petersbourg, 1892, tome i. p. 401 ; Arch. f. exper. Path, 

 u. Pharmakol., Leipzig, 1893, Bd. xxxii. S. 161. See also Stern, ibid., Bd, xix. S. 45 ; 

 and v. Schroder, ibid., S. 373. 



5 Zillessen, Ztschr. f. physiol. Chem., Strassburg, 1891, Bd. xv. S. 387. 



6 Arch. f. exper. Path. u. Pharmakol., Leipzig, 1896, Bd. xxxvii. S. 26. 



