Unconjugated bilirubin (indirect bilirubin) is a product of heme breakdown. Unconjugated bilirubin is insoluble and travels in the blood attached to albumin. Conditions that result in increased heme breakdown (e.g., hemolysis, infections) can lead to increased levels of unconjugated bilirubin.
Unconjugated bilirubin is insoluble (hydrophobic). It is carried through the circulation bound to albumin through a non-covalent bond. Unbound unconjugated bilirubin is neurotoxic.
Heme is a component of hemoglobin. It is a metal complex containing iron that can bind and release oxygen. Degradation of heme by heme oxygenase results in the formation of biliverdin, which is then reduced to unconjugated bilirubin by biliverdin reductase.
Red blood cells contain a protein called hemoglobin, which gives them a red color and plays a crucial role in the exchange of oxygen and carbon dioxide, primarily acting as a carrier of these molecules. Degradation of hemoglobin results in the formation of bilirubin.
Damaged red blood cells are recognized and degraded by macrophages of liver and spleen, which degrade heme into unconjugated bilirubin.
Conjugation of unconjugated bilirubin with glucuronate results in the formation of conjugated bilirubin, which is water-soluble and can be excreted in the bile. Conjugated bilirubin is then metabolized by the gut bacteria into urobilinogen, which is excreted in the feces as stercobilin and gives the stool brown color. Conditions that result in obstruction of bile flow (e.g., stones, tumors, or strictures in the biliary system) result in increased levels of conjugated bilirubin.
After bilirubin is conjugated, the conjugated form is actively secreted into the bile canaliculi and reaches the small intestine. A minority of the conjugated bilirubin also enters interstitial space and bloodstream. When there is an obstruction of bile flow, conjugated bilirubin backs up in the blood, and the levels rise above the normal values (<0.3 mg/dL).
Urobilinogen is synthesized by the bacteria in the intestines. A minor portion of urobilinogen is reabsorbed into the blood and reaches the liver and kidneys. The reduction of urobilinogen results in the formation of urobilin, which gives the urine its yellowish color. The proportion of urobilinogen that doesn't get reabsorbed is directly reduced to stercobilin, a brown pigment that gives the fecal matter its brown color.
A portion of urobilinogen is fecally eliminated and reduced to a brown pigment known as stercobilin. This process takes place in the intestine by the action of intestinal bacteria.
The proportion of urobilinogen that is reabsorbed in the blood also ends up in the urine, where the reduction of urobilinogen results in the formation of urobilin, a yellow pigment that gives the urine its yellowish color.
Circulation of bilirubin, biliary acids, and other substances (eg, drugs) between the liver and intestines is known as enterohepatic circulation. This process involves the transport of substances from the liver to the small intestine through bile, absorption of these substances into the blood through enterocytes, and retrograde transport to the liver.
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