The Formation of Bilirubin from Hemoglobin

About 80 to 85 per cent of the fecal bile pigmients are believed to be derived from the hemoglobin of senescent erythrocytes that are destroyed in the reticuloendothelial system (1). It is not known, however, whether the hemoglobin of sequestered 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 revealed 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 urobilinogen in the large bowel (3, 4, 6), and loss of pigment through intestinal absorption (3, 4, 6, 8). Attempts to circumvent these difficulties by estimating bilirubin excretion through a T-tube in the common bile duct have been unsatisfactory (9, 10) because this technique does not permit complete 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 observed 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 pigment output tend to balance out, but the necessity of giving oral bile supplements to replace drainage losses (11, 13) results in falsely high pigment excretion due to intestinal absorption and entero-