SITE OF BILE PIGMENT FORMATION 539 



cells are the endothelial and reticulum cells of the spleen, the capillary 

 endothelial cells of the liver (Kupffer or stellate cells), and of the 

 adrenals and bone marrow, the macrophages of the connective tissue 

 and migratory cells derived from them. Thus, attempts were made 

 to block bile pigment formation by filling the reticuloendothelial 

 cells with colloids. These were at first without conspicuous success, 

 but thorium dioxide was found to be effective {1024.,2834). Hence 

 the causation of severe jaundice by arsine or phenylhydrazine can 

 be prevented by injections of thorium dioxide as well as by extirpa- 

 tion of liver or spleen {85-88,1393,231^0,2591,2850). The observations 

 of Minkowski and Naunyn are now explained by the fact that in 

 birds the reticuloendothelial cells are more concentrated in the liver 

 than in mammals; in fact, Minkowski noted biliverdin in the cells 

 of the spleen and bone marrow of the geese. The evidence for and 

 against the importance of the reticuloendothelial system has been 

 summarized by Aschoff and his pupils, by Rosenthal, who adhered 

 to Minkowski's theory, and by other workers (85-88,303,1717,1718, 

 18Jf2,18U,22Jf0,2338,2989). 



Extrahepatic bilirubin formation, e.g., in hematomata, cysts, and 

 transudates, has long been known and can occasionally reach large 

 proportions (c/. below). More important was the demonstration that 

 bile pigment is formed in hepatectomized animals. Dog's blood 

 usually does not contain bilirubin, but after liver extirpation the bile 

 pigment formed extrahepatically accumulates since it is no longer 

 excreted by the liver (Mann and co-workers, 1857,1858,1861 ; Makino, 

 181^7; Rich, 2239,22If0; Taniguchi, 2737; Royer, 2388). The increase 

 of bilirubin in the plasma after hepatectomy is not striking, particu- 

 larly in view of the fact that part of the yellow pigment was found 

 to be different from bilirubin ("xanthorubin," "hemorubin," 687, 

 1897,2337; cf. Chapter IV, Section 8.1.). 



The formation of bile pigments in the cells of the reticuloendothelial 

 system is now no longer in question, but it has not yet been proved 

 that they are not also formed in other cells and there is no certainty 

 about the relative role which various organs — liver, spleen, and 

 bone marrow — play in it. Lepehne (1718) supported a dualistic 

 theory, assuming both types of cells to form bilirubin. Rosin and 

 Doljanski observed that the epithelial liver cells of rats treated with 

 allyl formate or urethane take up red cells (234-2) ; see also the observa- 

 tions of Stein on tissue cultures under Section 7.3. Aschoff, while 

 denying that the epithelial liver cells played any other role than that 



