688 BURRILL B. CROHN 



The incidence of hemorrhage with the inflammatory reaction in the pan- 

 creas was attributed to injury and necrosis of the adjacent blood vessels, 

 even before the inflammatory reaction in the gland tissue itself was well 

 marked. Where a large vessel is involved, the hemorrhagic aspect of the 

 clinical case predominates, thus giving the case the appearance of pan- 

 creatic hemorrhage, so called "pancreatic apoplexy." These cases are now 

 all regarded as mere phases of pancreatic inflammation and necrosis 

 (Pratt (6)). To the activation of the proenzyme trypsinogen and the 

 potency of steapsin increased by the entrance of bile (as well as by other 

 substances) was attributed, the necrosis and self-digestion of the pan- 

 creas; the liberation of its activated ferment (steapsin) caused the 

 fat necrosis. A further injurious influence was attributed to the saponi- 

 fication of fats due to the simultaneous activation of the pancreatic lipase 

 with damage to the pancreatic tissue by the fatty acids and more particu- 

 larly the soaps so formed (Hess(a)). 



These important experiments were a few years later confirmed and 

 added to by Polya. By the injection into the pancreatic ducts of activated 

 trypsin, or commercial trypsin, as well as of enterokinase and succus 

 entericus, experimental pancreatitis was successfully reproduced. If the 

 trypsin were heated the effect was lost. Activated pancreatic secretion 

 acted in the same way as activated trypsin and similarly lost this power 

 when heated. The injection of activated substances during the digesting 

 state of the gland, while not essential, gave the most striking results 

 (Hess(a)). That autodigestion of the pancreas spontaneously took place 

 post mortem had been amply pointed out by Chiari(6). 



The Toxic Element in Pancreatic Necrosis. The above mentioned 

 experiments and observations did much toward clarifying our con- 

 ceptions of the mechanism of production, and the chemical nature of 

 pancreatic necrosis. The actual toxic agent producing the fulminat- 

 ing symptoms and death in pancreatitis remained however in doubt. 

 The experiments of Hess, Gulecke, Polya and others had demonstrated 

 that the insertion of pieces of pancreatic tissue, or the creation of an 

 intraperitoneal pancreatic fistula led to a severe toxic reaction and often 

 to death. The toxic reaction was generally attributed to the absorption 

 of pancreatic secretion containing activated ferments. Both the trypsin 

 and steapsin were independently held responsible for the fatal outcome 

 of the experiments. Many authors had shown that the intravenous in- 

 jection of pancreatic juice activated with intestinal secretion produced 

 toxic death. 



Von Bergmann and Gulecke doubted that trypsin was the sole toxic 

 agent and attributed to another chemical toxin derived from the necrotic 

 pancreas the severe phenomena induced. They showed that autolyzed pan- 

 creatic tissue was much more toxic than fresh tissue, and that pancreatic 

 broth was still more poisonous in its effects when injected intraperitoneally. 



