368 RETROGRESSIVE CHANGES 



cells of its body do not die for some time, as shown by the following 

 examples: (1) We can cause the heart to beat for a considerable 

 period after its removal from the body; (2) if we perfuse a mixture 

 of g'lycocoll and benzoic acid throug-h the kidney of a recently killed 

 animal, synthesis of these substances into hippuric acid will occur; 

 and (3) the epithelium of the skin can be removed from the body of 

 an animal lono: after death and transplanted successfully on another 

 animal. So, too, in ordinary cell death (necrobiosis) not all the 

 enzymes are destroyed together. When all are destroyed at once, 

 as by strong chemicals or by heat, the customary disintegrative 

 changes do not take place. If, however, not all the enzymes are 

 thrown out of function, then the others may be able to act, producing 

 the disintegrative changes by which histologists ordinarily recognize 

 cell death. These tlisintegrative changes are, for the most part, ap- 

 parently brought about by the intracellular proteases, that is, through 

 autolysis. This may be shown as follows:^ If we take two pieces 

 of fresh normal tissues from an animal, and in one kill the enzymes 

 by heating to 100° C, then implant both aseptically into the abdom- 

 inal cavity of an animal of the same species, it will be found that 

 the changes that follow in the two will be very unlike. In the un- 

 heated tissue nuclear changes soon occur, so that they lose their ca- 

 pacity for taking up basic stains, the cytoplasm becomes granular 

 and fragmented, the tissue becomes friable so that it is difficult to 

 secure good sections, and the changes are in general similar to those 

 seen in areas of necrosis. The boiled tissue, on the other hand, 

 retains its capacity for nuclear staining for months, except at the 

 periphery, where it is slowly attacked by leucocytes and the enzymes 

 of the blood plasma. Therefore it would seem that the characteristic 

 changes of necrosis depend ehietly upon the intracellular enzymes, 

 rather than upon the infiltrating plasma as Weigert - and other early 

 writers imagined. In areas of anemic necrosis (see "Infarcts") 

 we have another case, in which the oxidizing enzymes are thrown 

 out of function through lack of oxygen, while the otlier enzymes are, 

 presumably, at first luuiffected. From studies of infarcts it would 

 seem that the intracellular proteases bring about the subsequent 

 nuclear and cytoplasmic alterations, but that the eventual digestion 

 of the area is accomplished by the invading leucocytes working slowly 

 inward from the periphery. Apparently when the sui^i)]y of materials 

 from outside ceases, and when the oxidation ]>ro('esses of the cells no 

 longer accomplish necessary steps of synthetic reai-tions or destroy 

 products of protein catabolism, the proteases continue to split proteins 

 without the balancing by the above-mentioned factors, with a resulting 

 disintegration of the cells. 



Karyoljjsis and Ldri/orrhf.rls are, Ihcu, Ihe i-esult of an autolytic 



1 Wells, .Tour. Med. Kcsoarcli, liMXI (15 1. lift. 



2 Cent. f. Path., 1801 (2), 78,5. 



