THE FORMATION OF BILIRUBIN FROM HEMOGLOBIN IN VIVO*

Abstract

About 80 to 85 per cent of the fecal bile pig-mients are believed to be derived from the hemo-globin of senescent erythrocytes that are destroyed in the reticuloendothelial system (1). It is not known, however, whether the hemoglobin of se-questered red cells is converted quantitatively to bilirubin and eventually to urobilinogen, or is in part metabolized to other products (2, 3). Earlier studies of this problem in man have re-vealed that the rate of fecal urobilinogen excretion falls short of the expected output as calculated from total red cell volume and mean erythrocyte life span (4-6). This has been attributed to incomplete intestinal conversion of bilirubin to urobilinogen (3, 4, 6, 7), destruction of urobili-nogen in the large bowel (3, 4, 6), and loss of pig-ment through intestinal absorption (3, 4, 6, 8). At-tempts to circumvent these difficulties by estimat-ing bilirubin excretion through a T-tube in the common bile duct have been unsatisfactory (9, 10) because this technique does not permit com-plete bile collection. In animals with an external biliary fistula, this obstacle has been overcome, but the rate of endogenous bilirubin excretion was found to exhibit marked fluctuations (11, 12), which rendered difficult comparison of the ob-served values with the endogenous production of bilirubin calculated from hemoglobin turnover, or with excess bilirubin formation after intravenous injection of a hemoglobin load. In animals with chronic bile fistulae, these acute fluctuations in pig-ment output tend to balance out, but the necessity of giving oral bile supplements to replace drainage losses (11, 13) results in falsely high pigment ex-cretion due to intestinal absorption and entero-