546 XI. HEMOGLOBIN CATABOLISM, I 



of the liver in animals and man which normally excrete bilirubin 

 {53It.,9 Jt.J4.,l 1^62 ,1650) . The biliverdin icterus in regurgitation jaundice 

 {2990) must be explained as due to liver damage. 



It is possible that in the animal body biliverdin still combined with 

 globin is reduced to bilirubin globin (c/. below). 



8.3. Bilirubin in Blood Plasma 

 8.3.1. Normal Concentrations of Plasma Bilirubin. The 



presence of bilirubin in human blood serum was first noted by Gilbert 

 and co-workers {999) in 1903 and was proven by van den Bergh and 

 his co-workers {;22 1,225, 233, 237) by the reaction with diazotized 

 sulfanilic acid (Ehrlich's diazo reaction, c/. Chapter IV, Section 4.3.) 

 and other diazonium compounds, as well as by isolation of bilirubin. 

 Bilirubin has not been found in the sera of some animals (such as 

 dog, rabbit, guinea pig, hare, and rat) {cf. 1226,1232); it would be 

 of interest to search for biliverdin in these sera. 



While earlier estimations gave a bilirubin content of below 0.5 mg. 

 per 100 ml. of normal human serum, estimation with modern methods 

 indicates a somewhat higher median value of about 0.75 mg. per 

 100 ml. {3109) and values up to 1.5 mg. per 100 ml. have been found 

 in healthy persons {2160). While the earlier methods gave too low 

 values, the modern methods tend perhaps to give somewhat too high 

 values {cf. Chapter IV, Section 6.1.). Horse serum contains 1.9 to 

 3.1 milligram per cent {1039). 



The discussion between Heilmeyer {cf. 1213, p. 185) and Muller {1997) 

 as to whether bilirubin or hemoglobin contributes more to the yellow color 

 of the normal serum is rather pointless. The bilirubin content varies physi- 

 ologically and the hemoglobin content depends on the method of isolation 

 which usually causes a slight hemolysis. With {311-1) has recently claimed 

 that the yellow color of normal and pathological sera is partly due to bili- 

 fuscins {cf. Section 9.3.3.). 



The bilirubin content of blood depends on the degree of hemo- 

 globin breakdown and on the excretory power of the liver; of the two 

 factors the second is of more decisive influence. Blood bilirubin is 

 therefore increased in diseases in which a very rapid hemoglobin 

 breakdown occurs, as well as in those in which the liver is damaged or 

 the excretion of the bile blocked by a stone or tumor. 



8.3.2. "Direct" and "Indirect" Bilirubin. Van den Bergh dis- 

 covered that the bilirubin in normal sera, in sera of patients suffering 

 from hemolytic anemia, and in hemorrhagic fluids behaved to diazo- 



