HYPERSUSCEPTIBILITY 215 



tissue proteins. Jobling, Petersen and Eggstein found an increase in 

 non-specific protease with a decrease of antiferment and an associated 

 decrease of serum proteoses ; this is followed by a progressive increase 

 in non-coagulable nitrogen, proteoses and serum lipase. They, there- 

 fore, conclude that " the acute intoxication is brought about by the 

 cleavage of serum proteins (and proteoses) through the peptone stage 

 by a non-specific protease." Modern opinion thus favors an increase 

 in nitrogenous metabolism in anaphylactic shock and this may well 

 be due to a liberation or mobilization of proteases ; that the action of 

 the latter is limited to the blood appears to us not to be conclusively 

 proven. In spite of the increase in metabolism there is a fall in body 

 temperature ; therefore, there must be an increase in heat radiation. 

 In lower animals the respiratory function is of great importance in heat 

 radiation, and we suggest that the marked increase of respiration in 

 anaphylactic shock has some bearing on this problem, but we by 

 no means wish to exclude other factors that may play a part in 

 the phenomenon. 



The decrease in coagulability of the blood was first observed by 

 Biedl and Kraus and since has been amply confirmed. They believed 

 the change to be due to either a decrease of thromboplastin or an 

 increase in antithrombin. The salts of the blood apparently are un- 

 changed. Achard and Aynaud, as well as Lee and Vincent, found 

 a decrease in the number of platelets, but this was not found by Biedl 

 and Kraus. Shattuck found a delay in action of prothrombin. Pepper 

 and Krumbhaar reached the same conclusion as Biedl and Kraus con- 

 cerning a decrease of thromboplastin or an increase of antithrombin. 

 Bulger concludes, in terms which summarize our knowledge at the 

 present time, that the decrease in coagulability is " due to changes in 

 that stage of the coagulation process at which thrombin is formed 

 through the interaction of prothrombin, calcium, thromboplastin 

 and antithrombin ( ?) . These changes are probably due to variations 

 in thromboplastin." 



Desensitization or Anti-anaphylaxis. If an animal recovers from 

 anaphylactic shock its earlier hypersusceptibility is replaced by a period 

 of resistance during which injections of the specific protein produce no 

 demonstrable reaction. This refractory period lasts for a varying 

 period of time up to several weeks, and although the animal subse- 

 quently becomes hypersusceptible, it rarely reaches the same degree of 

 hypersusceptibility which it primarily exhibited. These facts were 

 pointed out in the original investigations of Rosenau and Anderson 

 and of Otto. Besredka has studied the matter extensively and has 

 found that very small doses of the protein may desensitize, doses in 

 themselves too small to lead to any observable symptoms. By repeated 

 injections it is possible to produce such a degree of resistance that the 

 animal may withstand doses 1000 times as great as that which proves 

 fatal if desensitization has not occurred. The rapidity with which 

 desensitization appears depends upon the route of injection. After 

 subcutaneous injection it may not appear for twenty-four hours ; intra- 



