558 SAMUEL H. HUKWlTZ 



Hemoglobin Pigment Metabolism. The Breaking Down of Hemo- 

 globin. Regulatory Function of the Liver in Bile-Pigment Metabolism. 

 Our conception of the decomposition of hemoglobin pigment and the cycle 

 of the blood-derived pigments has been considerably changed by recent 

 studies. The generally accepted view covering bile-pigment metabolism 

 assumes that the liver has only an eliminative function in forming bile- 

 pigments (Stadelmann(&), Minkowski(c)). This view briefly sketched is 

 somewhat as follows: Degeneration of red blood-cells frees hemoglobin 

 which is brought to the liver and there changed to bile-pigments which are 

 excreted as waste products into the intestine. Here the bile-pigments are 

 reduced to urobilin or stercobilin, some of which may be absorbed and 

 returned to the liver and again thrown out in the bile or destroyed. Some 

 of the urobilin may escape the liver and appear in the urine, especially 

 when the liver is not functioning normally. Whipple and Hooper (a) (&) 

 have brought forth seemingly incontrovertible evidence, however, to prove 

 not only the existence of an extrahepatic formation of bile-pigments, but 

 also that the liver has a constructive as well as the commonly accepted 

 eliminative function in the formation of bile-pigments. 



That the conversion of hemoglobin into bile-pigment may also occur 

 outside of the liver has gained support from the fact that old extravasa- 

 tions of blood frequently contain pigments which are identical with 

 bilirubin ; but that the conversion of hemoglobin into bile-pigments may 

 occur outside of the liver in sufficient quantity and with sufficient speed 

 to give rise to icterus has been much discussed. 



As a result of the experiments of Whipple and Hooper this question 

 has been answered in a positive sense. Thus they have shown that 

 hemoglobin introduced into the circulation of dogs, first with Eck fistula, 

 second with Eck fistula and hepatic artery ligation, third with exclusion 

 of the liver, spleen and intestine, and lastly, with head and thorax circu- 

 lation, was changed to bile-pigments in much the same way and in about 

 the same time (one to two hours) as in normal animals. 



Some knowledge concerning the cells or tissues responsible for this 

 rapid change of hemoglobin into bile-pigment has come from the further 

 observation that bile-pigments were formed when hemoglobin was placed 

 in the pleural and peritoneal cavities. This evidence points to the endo- 

 thelium of the blood vessels as the active factor. So that it is not un- 

 likely that this mechanism comes into play when the liver is excluded, 

 or when there has been excessive destruction of erythrocytes with much 

 hemoglobin freed in the plasma. Although under normal conditions it 

 is quite probable that the liver acts merely as an excretory organ for 

 the bile-pigments in the same way as the kidney does for urea, it is not 

 inconceivable that, possessed of endothelial cells, the liver might itself 

 produce some of the pigments not only from hemoglobin freed from dis- 



