40 A MANUAL OF PHYSIOLOGY 



living cells does hasten the destruction of leucocytes and blood- 

 plates or that alteration in them on which the liberation of the 

 precursors of the ferment depends, it is evident that it is just this 

 ' restraining ' influence of the vessels, if it is due to anything 

 more than the mere smoothness of their endothelial lining, which 

 has to be explained. The best answer which can be given to the 

 question is : First, that the quantity of thrombokinase free in 

 the plasma at any given time must be small, since no evidence 

 of its presence in fluoride plasma can be obtained. If thrombo- 

 kinase is liberated in the circulating blood, we may assume that 

 it is changed into some inactive substance or quickly eliminated. 

 And it appears that, unlike the true ferments, thrombokinase 

 acts quantitatively i.e., in proportion to its amount upon 

 thrombogen. Second, an antithrombin exists in the circulating 

 plasma, and even if fully formed fibrin-ferment were present, it 

 could not cause coagulation until the antithrombin had been 

 neutralized. This antithrombin is probably not manufactured 

 in the blood, or at least not exclusively in the blood, but in the 

 tissues, and there is no reason to deny the vessels themselves a 

 share in its production, even if its presence has not hitherto been 

 demonstrated in the internal coat (L. Loeb). So that living 

 blood within the living vessels may be said to be acted upon by 

 two sets of influences, one tending to favour coagulation, the 

 other to oppose it. Under normal conditions, the processes that 

 make for coagulation never obtain the upper hand. But anything 

 which interrupts the circulation, and consequently the free inter- 

 change between blood and tissues, interferes with the elimination 

 or neutralization of the precursors of fibrin-ferment, and with 

 the entrance of the substances that render the fully-formed 

 ferment inactive. In the clotting of extravascular plasma, free 

 from corpuscles, we may indeed see the continuation, under 

 modified conditions, of a normal process always going on within 

 the bloodvessels. In the lungs it would seem that the forces 

 which favour coagulation are feeble, or the forces that resist it 

 strong, for blood, after passing many times through the pul- 

 monary circulation without being allowed to enter the systemic 

 vessels, loses its power of clotting. 



The liver is another organ whose relations to the coagulation 

 of the blood are peculiar. We have already mentioned that the 

 injection of commercial peptone, which consists chiefly of pro- 

 teoses, into the blood of dogs causes it to lose its coagulability. 

 The effect gradually passes away, till after some hours. the original 

 power of coagulation is restored (p. 55). The liver is known 

 to be intimately concerned in the production of this remarkable 

 result, for if the circulation through it be interrupted, the injec- 

 tion of proteose is ineffective. Further, if a solution of proteose 



