Biliary Excretion of Waste Products: Elimination of Bilirubin
The liver is well known to metabolize and excrete into bile many compounds and toxins, thus eliminating them (usually) from the body. Examples can be found among both endogenous molecules (steroid hormones, calcium) and exogenous compounds (many antibiotics and metabolities of drugs). A substantial number of these compounds are reabsorbed in the small intestine and ultimately eliminated by the kidney.
One of the most important and clinically relevant examples of waste elimination via bile is that of bilirubin. Additionally, the mechanisms involved in elimination of bilirubin are similar to those used for elimination of many drugs and toxins.
Bilirubin is a useless and toxic breakdown product of hemoglobin, which also means that it is generated in large quantities. In the time it takes you to read this sentence aloud, roughly 20 million of your red blood cells have died and roughly 5 quintillion (5 x 1015) molecules of hemoglobin are in need of disposal.
Dead, damaged and senescent red blood cells are picked up by phagocytic cells throughout the body (including Kuppfer cells in the liver) and digested. The iron is precious and is efficiently recycled. The globin chains are protein and are catabolized and their components reused. However, hemoglobin also contains a porphyrin called heme that cannot be recycled and must be eliminated. Elimination of heme is accomplished in a series of steps:
- Within the phagocytic cells, heme is converted through a series of steps into free bilirubin, which is released into plasma where it is carried around bound to albumin, itself a secretory product of the liver.
- Free bilirubin is stripped off albumin and absorbed by - you guessed it - hepatocytes. Within hepatocytes, free bilirubin is conjugated to either glucuronic acid or sulfate - it is then called conjugated bilirubin.
- Conjugated bilirubin is secreted into the bile canaliculus as part of bile and thus delivered to the small intestine. Bacteria in the intestinal lumen metabolize bilirubin to a series of other compounds which are ultimately eliminated either in feces or, after reabsortion, in urine. The major metabolite of bilirubin in feces is sterobilin, which gives feces their characteristic brown color.
If excessive quantities of either free or conjugated bilirubin accumulate in extracellular fluid, a yellow discoloration of the skin, sclera and mucous membranes is observed - this condition is called icterus or jaundice. Determining whether the excessive bilirubin is free or conjugated can aid in diagnosing the cause of the problem.
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