Unconjugated Bilirubin

Bilirubin is a catabolic product derived from the heme metabolism. Although it is potentially toxic, the body has elaborate physiologic mechanisms, which can detoxify and disposition this substance in the body. This substance is formed when there is breakdown of heme, a substance that forms part of the hemoglobin. The metabolism of bilirubin by liver consist of four interrelated but distinct stages which are, uptake from the circulation, intracellular storage, conjugation with glucuronic acid, and biliary excretion. When abnormalities occur in one or more of these stages, they can result to hyperbilirubinemia condition where there are elevated levels of unconjugated bilirubin alone or there are elevated levels of both conjugated and unconjugated bilirubin. 

How unconjugated bilirubin is processed by the liver

Almost, 96 percent of the plasma bilirubin is termed as unconjugated. Bilirubin has a yellow pigment and it is this substance, which is responsible for the yellow color you find in bruises and the yellowish discoloration in persons with jaundice condition. As old red cells pass through spleen, they are eaten up and broken down by macrophages. In this process, the heme, which is the part of hemoglobin molecule present in red blood cells, is broken down into unconjugated bilirubin. 

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This unconjugated or free bilirubin is not soluble in water but it is lipid soluble. In order for the unconjugated bilirubin to be converted to water-soluble molecules, it has to pass through the liver. The liver conjugates the substance using the glucuronic acid and makes it water-soluble. From the liver, the water-soluble bilirubin goes into the bile and then to the small intestines. Some of the conjugated bilirubin does not get to the liver to be conjugated, it remains in the large intestine where it is metabolized into urobilinogen, and then sterobilinogen, which makes the feces have the brown color. 

Causes of elevated unconjugated bilirubin in blood

Unconjugated bilirubin is increased when there is overproduction of bilirubin as may happen with hemolysis without necessarily a liver disease. The level is also increased if there is an inherited or acquired disorder, which affects the uptake or glucuronidation of bilirubin. Transient elevated levels of unconjugated bilirubin may also occur in the process of absorption of large hematomas. 

The common causes of unconjugated hyperbilirubinemia are overproduction of bilirubin, neonatal jaundice, and Gilbert’s syndrome. When bilirubin test is done and it is found out that you have a lot of bilirubin, which is mostly unconjugated, this means that the substance has not yet been to the liver. What this may imply is that you may have a situation where too much heme is being broken down in a way that it exceeds the pace at which the liver conjugates the bilirubin. 

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If the level of heme breakdown is high, then the liver may have too much unconjugated bilirubin to convert into water-soluble substance. This will mean that there is more of unconjugated bilirubin in plasma waiting to be conjugated. This unconjugated bilirubin continues to circulate in bloodstream until it is converted to conjugated form. 

Moreover, if there is something wrong with the ability of the liver to conjugate bilirubin such as a congenital or gene disorder where a person does not have the enzyme necessary for conjugating bilirubin like the case of Gilbert’s syndrome, it may also cause the unconjugated levels of the substance to increase in plasma. 

On the other hand, if you have elevated levels of conjugated bilirubin, it means that it has already passed the liver and changed to water-soluble form. However, this may indicate that there is something that is preventing the secretion of conjugated bilirubin into the bile such as a liver disease including hepatitis. A biliary obstruction may also cause the bilirubin to back up or remain in the blood. 

Effects of elevated levels of unconjugated bilirubin in newborns

Excessive unconjugated bilirubin causes damages in developing brain cells in infants. This substance may cause mental retardation, developmental disabilities, learning disabilities, hearing loss, and eye movement problems. Therefore, elevated levels in newborns should be identified and treated fast. In newborns, only unconjugated bilirubin is increased in physiologic jaundice and hemolytic disease of the infant. 

Physiologic jaundice in newborn is caused by immature liver, which lacks enough enzymes to conjugate bilirubin. If the baby’s liver cannot conjugate the bilirubin, this substance (unconjugated bilirubin) is retained in blood, and the levels keep on increasing. If it is not treated, it can pass the blood-brain barrier thus causing damages to the brain. The baby needs to be monitored closely to determine the levels of the unconjugated form of bilirubin. The levels can be reduced by exposing the infant to ultraviolet rays. 

Considering that the liver processes bilirubin, it means that the bilirubin going into the liver and the one being released out are in different forms. Once the bilirubin passes in the liver, it is conjugated and made water-soluble. Tests for unconjugated bilirubin may be done to establish the cause such as Gilbert’s syndrome, hemolysis, mild chronic hepatitis, Crigler-Naijar syndrome, and post viral hepatitis. Bilirubin is either measured as total levels or conjugated levels. The unconjugated level is obtained by subtracting the conjugated amount from the total bilirubin.

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