NECROSIS 369 



process, whicli is perhaps due to intracellular proteases that act spe- 

 cifically on nucleoproteins, and which may be designated as nucleases.^ 

 Nuclear staining by the usual methods depends upon an affinity of tlie 

 acid nucleoproteins (in which the nucleic acid is not completely 

 saturated by j)r()teins) for basic dyes. Presumably in karyolysis the 

 first step consists in a splitting of the nucleoprotein of the chromatin 

 into nucleic acid and protein; this can be accomplished, according 

 to Sachs, by the ordinary trj'psin, and presumably, therefore, by the 

 trypsin-like enzymes of the cell. Corresponding with this cliange 

 we should expect the free nucleic acid to give an intense staining 

 with basic stains, and this has frequently been described by those 

 who have studied the cytological changes in anemic necrosis,* and 

 called pijoiosis. As supporting this view still further may be quoted 

 Arnheim 's "' observation that in alkaline solutions the nucleus soon 

 stains diffusely and weakly, and not at all after twelve to eighteen 

 hours; this is to be explained by the fact that nucleic acid is both 

 dissolved and neutralized by alkaline solutions. Acids developed in 

 injured cells may, by combining with the basic elements of the n\\- 

 cleoproteins, render them still more acid and highly basophilic ; thus, 

 in muscles showing waxy degeneration from accumulation of lactic 

 acid the muscle nuclei will be found pycnotic (see waxy degenera- 

 tion). After the nucleic acid has been freed from the protein by 

 the autolytic enzymes, it is still further decomposed by the "nu- 

 clease" or similar intracellular enzymes that have the property of 

 splitting nucleic acid into the purine bases that compose it — cor- 

 responding with this change the hyperchromatic nucleus loses its 

 affinity for stains, and karyolysis is complete. "When extensive ne- 

 crosis occurs there will result, therefore, an increased elimination 

 of purines, as was found by Jackson and Pearce ^ in animals with 

 severe hepatic necrosis from hemotoxic serum. 



A careful analytical study of the chanses taking place in the autolyzinor spleen, 

 for the purpose of correlatino^ the chemical and microscopical chancres, has been 

 made by Corper," whicli corroborates tlie interpretation of necrosis advaiu-e<l 

 above. Pie found tliat during the stage when pycnosis is tlie cliief feature tliere 

 is no appreciable change in the nucleus; tliat is. the nucleic acid has not been 

 split into free purines and the rest of its components: at this stage but I'ttle 

 change has occurred in the lecithin, and a very slight amount of proteolysis is 

 demonstrable. During the stage of karvorrhexis and karyolysis the most active 

 disintegration is taking place, about one-fourth of the nucleic acid becoming dis- 

 integrated by the time all nuclear structures have disappeared : in tlie same 

 period nearly lialf the lecithin (phosphatids) is hydrolyzed. while about one- 

 fourtli the coagulable protein has l)een hydrolyzed into non-coagulable compcninds. 

 After this stage tlie changes are very slow. It is somewhat surprising to find 

 that wlien no vestige of nuclear substance remains in stainable form, tliere 



3 See Purine Metabolism, Chap. xxi. 



4 Schmaus and Albrecht, Virchow's Arch., 1895 (138). supp., p. 1; Ergeb. a\W. 

 Pathol.. 1806 (3). 486 Hiterature). 



■"'Virchow's Arch.. ISnO (120), 367. • 

 ••Jour. Exper. Med., 1007 (0), 560. 

 TJour. Exper. Med., 1912 (15), 429. 

 24 



