Give an account of the production and excretion of bilirubin.

Outline:

·        Formation of bilirubin in reticuloendothelial system

·        Conjugation of bilirubin

·        Secretion of bilirubin into bile

·        Excretion of bile pigments

Essay:

            Most of the bilirubin in the body is formed in the tissues by the breakdown of hemoglobin. After about 120 days in the circulation, red blood cells are taken up and degraded by the reticuloendothelial system, particularly in the liver, spleen and bone marrow. When hemoglobin is destroyed, the protein portion, globin, may be reutilized either as such or in the form of its constituent amino acids. The iron of heme enters the iron pool and is stored as ferritin. The iron-free porphyrin portion of heme is degraded mainly in the reticuloendothelial cells of the liver, spleen and bone marrow to form bilirubin.

            The formation of bilirubin takes place in the microsomal fractions of the reticuloendothelial cells by a complex enzyme system called heme oxygenase. The porphyrin part of heme is converted to biliverdin and finally to bilirubin. Bilirubin is only sparingly soluble in plasma and is transported to the liver by binding to albumin. Free bilirubin enters the liver cells, where it is next bound to cytoplasmic proteins. It is next conjugated to glucuronic acid in a reaction catalyzed by the enzyme glucuronyl transferase in the smooth endoplasmic reticulum. Each bilirubin molecule reacats with 2 uridine diphosphoglucuronic acid (UDPGA) molecules to form bilirubin diglucuronide which is then transported against a concentration gradient via an active process into the bile canaliculi.

            The conjugated bilirubin is stored in the gallbladder and is released into the duodenum via the cystic and bile ducts. As the conjugated bilirubin reaches the terminal ileum and the large intestine, the glucuronides are removed by bacterial enzymes and the pigment is subsequently reduced by fecal flora to urobilinogens. In the terminal ileum and large intestine, a small fraction of the urobilinogens is reabsorbed and reexcreted through the liver or kidney where it is converted to the yellow urobilin and excreted in the urine. Most of the urobilinogens of the feces are oxidized by intestinal bacteria to sterocobilin, which gives stools their characteristic brown color.