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. 
Xencki, 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. physiol. 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; 
Kaufmann, Arch, de physiol. norm, etpath., Paris, 1894, p. 531. 
3 Eck, Trav. Soc. d. natur. de St. Pitcrsbourcj, 1879, tome x. 
4 Arch, de sc. biol., St. Petersbourg, 1892, tome i. p. 401 ; Arch. f. exper. Path. 
u. Pharmakol., Leipzig, 1893, Bd. xxx'ii. 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./, exper. Path. u. Pharmakol., Leipzig, 1896, Bd. xxxvii. S. 26. 
