FAT NECROSIS 323 



necrosis could be produced. It therefore seems certain that 

 trypsin alone cannot produce fat necrosis, and that the decrease 

 in strength of lipase in a pancreatic extract is associated with a 

 corresponding decrease in power to produce fat necrosis. But, 

 on the other hand, lipase of liver or blood-serum alone, or 

 when mixed with trypsin, will not produce fat necrosis. The 

 possibility remains that pancreatic lipase is different from liver 

 or serum lipase, and can by itself cause fat necrosis ; more prob- 

 ably, however, the production of fat necrosis depends upon a 

 double action, trypsin causing the death of the cells, and lipase 

 splitting the fats. 1 The fatty acids alone will not cause necro- 

 sis of fat-cells, and it was shown that the first steps in the pro- 

 cess consist of a necrosis of the surface endothelium extending 

 into the connective and fat tissue ; this may occur in a few 

 minutes, while evidence of fat-splitting can be obtained only 

 after about three hours, and the splitting occurs only in cells 

 that have already become necrotic ; hence the fat-splitting is 

 not the cause of the necrosis, but occurs subsequent to the necro- 

 sis. After about four hours a substance appears in the decom- 

 posed fat that stains with hematoxylin, which is probably 

 calcium. 



Fat necrosis may be produced by any means that will cause 

 the escape of pancreatic juice from the natural channels within 

 the gland. In human pathology it has followed trauma and 

 acute infection of the gland, but the most common cause is prob- 

 ably the blocking of the ampulla of Yater by gall-stones, which 

 permits the bile to back up into the pancreatic duct, where it 

 produces an acute inflammation of the pancreas (Opie 2 ). Flex- 

 ner 3 has shown that it is the bile salts that cause the inflam- 

 mation, and also that this effect is decreased or prevented by 

 the presence of large amounts of colloids. As a result of injury 

 by bile salts, or any other agent that produces cell death, the 

 dead and injured cells are digested by the pancreatic juice which 

 then makes its escape into the surrounding fat tissue. Wells' 

 experiments showed that the lesions of fat necrosis may be pro- 



1 When fat tissue dies in the body from other causes, the lipase normally con- 

 tained within the fat tissue does not cause the changes seen in fat necrosis. It is 

 possible, therefore, that the combining of newly split fatty acids by the alkali of 

 the pancreatic juice is responsible for the formation of the large amount of 

 soaps found in fat necrosis. Otherwise we might expect the lipase to produce 

 only an equilibrium, and that, in the case of fat, seems to exist when most of 

 the substance is neutral fat. In support of this idea I found that strong alka- 

 lies injected into fat tissue sometimes caused changes very closely resembling 

 areas of fat necrosis in the early stages. 



2 Bull. Johns Hopkins Hosp., 1901 (12), 182. 



3 Jour. Exp. Med., 1906 (8), 167. 



