EXCRETION OF BILIRUBIN 549 



Most biochemists who have had experience with the cHnical appH- 

 cation of the distinction between "direct" and "indirect" bihrubin 

 agree that it is of some value for the distinction between hemolytic 

 and obstructive jaundice, although very high bilirubin values in 

 hemolytic jaundice may make the reaction also appear to be "direct." 

 A rough observation of whether the reaction is predominantly direct 

 or indirect is probably all that is required, and little more is likely to 

 be learned by quantitative measurements, or ill-defined and arbitrary 

 distinctions such as between delayed, biphasic, and indirect reactions 

 {cf. Chapter IV, Section 7.2.). 



8.4. Excretion of Bilirubin 



8.4.1. Excretion by Liver into Bile. Injected bilirubin is rapidly 

 removed from the blood stream by the liver {78,m7,2174M60). 

 Bilirubinemia with a normally functioning liver is therefore rather 

 low, even if much blood pigment is destroyed, e.g., in paroxysmal 

 hemoglobinuria (3115), after administration of phenylhydrazine 

 {1393), or in hemolytic anemia, as long as the excretory function of 

 the liver has not been damaged {2071). The human gall bladder 

 contains 12-40 mg. bilirubin. The capacity of the liver to remove 

 injected bilirubin from the blood stream provides a more sensitive 

 measurement of liver function than the level of serum bilirubin. A 

 bilirubin clearance test has been worked out on this basis by von 

 Bergmann and his co-workers {2U,6o6,1138,U57,2592,2683,2686, 

 2691,3009). 



8.4.2. Enterohepatic Circulation. Bilirubin passes with the bile into the 

 intestine and is found in tlie duodenum. In the intestine and occasionally in 

 infected bile passages, bilirubin is transformed into urobilin and urobilinogen 

 {cf. the next section). In the first days of life the newborn excretes bilirubin 

 {2741) while the meconium contains biHverdin. Reabsorption of bilirubin 

 from the intestine and re-excretion from the blood stream through the liver 

 (enterohepatic circulation) were first assumed by Wertheimer on the basis 

 of experiments with phylloerythrin of sheep bile, which is however a por- 

 phyrin, not a bile pigment. While enterohepatic circulation of bilirubin was 

 supported by the experiments of ]\Ic]\Iaster and other workers (340,1828, 

 1925,2231,2385), most of the later workers have been unal)ic to confirm these 

 results and to find any evidence for reabsorption of bilirubin from the intes- 

 tine (287.311,1533,18l7,2412,24(!0,25i8,2737,30U-3052). Against tlic experi- 

 ments of Scholderer (2460) and Sackey and co-workers (2412), who found no 



Cohn {W)a) reporteci that the Harvard workers have isolated tlie protein which "alone 

 of adequately purified plasma proteins" combines with bilirubin to give "indirect 

 bilirubin." (/. also Martin (1877a). 



