296 DISTURBANCES OF CIRCULATION 



cause prompt clotting, but in the pleura and other serous cavities the 

 blood may remain fluid for some time, possibly because of lack of 

 cellular injury that might cause liberation of fibrin ferment. ^° If the 

 blood does not become infected, the rapidity of subsequent changes 

 depends chiefly upon the location and amount of blood. Small ex- 

 travasations of blood into the tissues are subjected to the action of the 

 tissue cells and of leucocytes emigrating freely from the capillaries; 

 large masses of blood are but little affected by these agencies, the 

 leucocytes within the mass soon die, and secondary changes go on very 

 slowly. In small subcutaneous hemorrhages (e. g., a bruise) enzymes 

 from the invading leucocj^tes and tissue-cells soon dissolve the small 

 quantities of fibrin present; even earlier the stroma of the red cor- 

 puscles is so altered that hemolysis occurs and the hemoglobin escapes 

 and diffuses into the tissues. This hemolysis may be brought about 

 by the action of proteolytic enzymes on the corpuscles, or bj^ the hemo- 

 lytic action of the products of protein splitting. Soon the hemoglo- 

 bin disintegrates, forming the masses of pigment so characteristic 

 of old hemorrhagic areas, and also giving rise to the discoloration 

 observed beneath the skin in the later stages of resorption of hemor- 

 rhagic extravasations. The first products of the splitting of hemo- 

 globin are: (1) The protein, glohin, which constitutes 94 per cent, 

 of the hemoglobin; and (2) the iron-containing coloring-matter, hem- 

 atin (in the absence of oxygen the pigment is reduced hematin or 

 hemochromogen) . As hematin may be experimentally obtained by 

 the action of proteases upon hemoglobin, the decomposition of the 

 hemoglobin in the tissues is probably accomplished in a similar way 

 by the proteases of the leucocj'^tes, tissue-cells and blood plasma; the 

 globin is thus digested away and the soluble products carried off, 

 while the insoluble hematin remains. ^^ The hematin gradually un- 

 dergoes further changes, forming an iron-free pigment (hematoidw) 

 and an iron-containing pigment [hemosiderin) . 



Hematoidin is nearly or quite identical with the bile-pigment, hili- 

 rubin, and is absorbed from the hemorrhagic extravasation and elimi- 

 nated as bilirubin in the bile. Possibly some of the hematoidin 

 undergoes transformation into urobilin, and is then eliminated in the 

 urine. Hemosiderin seems to be relatively insoluble and, therefore, 

 is more slowly removed, so that it may be found at the site of a hem- 

 orrhage after the other evidences of blood extravasation have been 

 removed. It may be easily demonstrated by staining with potassium 

 ferrocyanide, the Prussian blue that is formed being readily dis- 

 tinguished. Unstained hemosiderin generally appears in the form 



3" Denny and Minot (Anier. Jour. Physiol., 1916 (30), 455) believe that the 

 blood really does clot, and that it remains lluid wiuMi withdrawn because the 

 fibrinogen has l)een removed by clotting. Zahn and Walker (Biochem. Zeit., 1913 

 (58)^ 130), however, consider that the fibrinogen is altered by the pleural endo- 

 thelium, so that it cannot clot. 



^' More fully discussed in the consideration of "Pigmentation," (^hap. xviii. 



