538 LECTURE XXIII. 



hand, that calcium chloride exerts a particularly favorable action upon 

 the rapidity of the coagulation. The necessity for the presence of lime- 

 salts was proved clearly by Arthus, and Arthus and Pages. 1 They showed 

 that blood collected, as it flows from the animal's* body, in a solution 

 of alkali oxalate does not clot. If, however* a slight excess of lime- 

 salts is added to this oxalate plasma, a clotting at once takes place. 

 It is tempting to compare the clotting of blood with the coagulation of 

 casein by rennin. The latter would correspond to the fibrin ferment. 

 This ferment changes fibrinogen into fibrin, which may form an insoluble 

 calcium salt, and is precipitated. This simple explanation of the clotting 

 of blood has, however, been shown to be incorrect. The lime-salts must 

 act in some other way. 



In order to understand the clotting of blood, and the processes which 

 take place in this connection, it is necessary to bear in mind the following 

 points. In discussing the digestive ferments we were constantly confronted 

 by the fact that the ferments as such are not given up by the cells, but in 

 the form of their antecedents, to which in general we gave the name of 

 zymogens. The transformation of these inactive substances into active 

 ferments is brought about by various agents. How was it with trypsino- 

 gen? We remember that this was changed into trypsin by the so-called 

 enterokinase which is given up by the epithelial cells of the intestinal 

 membrane, and is contained in the intestinal juices. Again we remember 

 that a substance called secretin has been obtained from the blood, which 

 incites the gland-cells of the pancreas into greater activity. The secretin 

 is likewise found in the intestinal membrane in a preliminary stage, which 

 is activated by acid. We do not know how secretin influences the action 

 of the pancreas, whether it acts directly upon the gland-cells or indirectly 

 by increasing the blood-supply. At all events it is evident that the forma- 

 tion of ferments is a very complicated process, and even when the zymogen 

 has been formed it does not at all signify that the fermentation will take 

 place. 



In accordance with this aspect, we must next find out whether the fibrin- 

 ferment, sometimes called thrombin, possesses a zymogen stage in its 

 development, and if so, how it is brought into activity. Further investi- 

 gation has in fact shown that the fibrin-ferment does exist originally in an 

 inactive form. We will call this simply the zymogen of the fibrin-ferment. 

 This zymogen may be obtained in large amounts from the oxalate plasma 

 and becomes active only after being treated with calcium chloride solution. 

 In this way the fibrin-ferment is obtained. This ferment is capable of 

 causing coagulation in the oxalate plasma, from which the calcium salts 



1 Arthus: Doctor's Thesis, Paris, 1890. Arthus and Pages: Arch. Physiol. 22, 739 

 (1890); Arthus: Compt. rend. soc. biol. 45, 435 (1893); Arch. Physiol. 1896, 47, and 

 Compt. rend. soc. biol. 64, 526 (1902). 



