SITE OF BILE PIGMENT FORMATION 541 



extracts which did not contain living tissue, they found no bihrubin 

 but "xanthorubin" in tissue culture. Stein {2618) found no bile 

 pigment formation in cultures of pure mesenchymic cells, e.g., of the 

 chick embryo spleen or heart muscle fibroblasts, while biliverdin was 

 formed (?) in cultures of chick embryo liver. 



7.3. Role of Liver, Spleen, and Bone Marrow 

 in Bile Pigment Formation 



Liver. In spite of the certainty of bile pigment formation outside the 

 liver, this organ is still considered by many as the principal site of this process, 

 even in mammals and man {1340JS47,2.S36). Blood in the hepatic vein 

 was found to contain more bilirubin than in the hepatic arteries (Mann and 

 co-workers, 311). Removal of the liver decreases not only the jaundice pro- 

 duced by arsine in geese {1959), but also that caused by phenylhydrazine in 

 dogs {2340). If Ringer solutions containing 0.^2% dissolved hemoglobin are 

 perfused through the frog liver, biliverdin is excreted in the bile {2055). 



Spleen. In his 1925 review Rich {224-0) still concluded that there was 

 no satisfactory evidence for bile pigment formation in the spleen under 

 normal conditions. Since that time a large number of papers has been pub- 

 lished on this subject which have made the evidence far more convincing 

 {634,699 J01J395J567,156S, 1777 J7S7J859,2006,2541,2834,3010),huiLauda. 

 {1659) still considers it doubtful whether the spleen removes or destroys 

 normal erythrocytes. Mann and co-workers and others found much more 

 bilirubin in the splenic vein than in the splenic artery and this has been 

 confirmed repeatedly. Urobilin excretion is decreased by splenectomy {1949, 

 2566), particularly' in hemolytic anemia {697,1016,1412,2109,2988), but 

 Singer {2566) found no decrease of bilirubin formation nor an increase in 

 the average lifetime of erythrocytes after splenectomy in dogs. The inter- 

 pretation of the results of splenectomy in animals is complicated by the 

 development of Bartotjella infection, and by the possibility that other parts 

 of the reticuloendothelial system may take over the function of the spleen. 



Adrenaline causes a contraction of the spleen and the increase of bilirubin 

 in the blood after administration of adrenaline therefore indicates its forma- 

 tion in the spleen, since blood which has been stagnant in the spleen is 

 expelled into the circulation. It is of interest that Watson and Paine {2996) 

 found that the mean corpuscular hemoglobin concentration of the erythro- 

 cytes expelled from the spleen was decreased. Immediately after splenectomy 

 adrenaline no longer produced hyperbilirubinemia in rabbits, but Fernandez 

 {746) found that after several weeks hyperbilirubinemia could be produced 

 again by adrenaline; it appears doubtful whether this can be explained by 

 assuming an action of adrenaline on the compensatory blood-destroying 

 organs which take over the function of the spleen after its removal; in this 

 instance a direct chemical action of adrenaline on hemoglobin (coupled oxida- 

 tion) is the more probable explanation. 



There is no doubt that under pathological conditions the spleen con- 



