Bilirubin is the main bile pigment that is formed from the breakdown of heme in red blood cells. The broken down heme travels to the liver, where it is secreted into the bile by the liver. Normally, a small amount of bilirubin circulates in the blood. Serum bilirubin is considered a true test of liver function, as it reflects the liver's ability to take up, process, and secrete bilirubin into the bile.
Bilirubin production and excretion follows a specific pathway. When the reticuloendothelial system breaks down old red blood cells, bilirubin is one of the waste products. This "free bilirubin", is in a lipid-soluble form that must be made water-soluble to be excreted. The free, or unconjugated, bilirubin is carried by albumin to the liver, where it is converted or conjugated and made water soluble. Once it is conjugated into a water-soluble form, bilirubin can be excreted in the urine. An enzyme, glucuronyl transferase, is necessary for the conjugation of bilirubin. Either a lack of this enzyme, or the presence of drugs that interfere with glucuronyl transferase, impairs the liver's ability to conjugate bilirubin. Because the bilirubin is chemically different after it goes through the conjugation process in the liver, lab tests can differentiate between the unconjugated or indirect bilirubin and conjugated or direct bilirubin. The terms "direct" and "indirect" reflect the way the two types of bilirubin react to certain dyes. Conjugated bilirubin is water-soluble and reacts directly when dyes are added to the blood specimen. The non-water soluble, free bilirubin does not react to the reagents until alcohol is added to the solution. Therefore, the measurement of this type of bilirubin is indirect. Test results may be listed as "BU" for unconjugated bilirubin and "BC" for conjugated bilirubin. Total bilirubin measures both BU and BC.
Bilirubin concentrations are elevated in the blood either by increased production, decreased conjugation, decreased secretion by the liver, or blockage of the bile ducts. In cases of increased production, or decreased conjugation, the unconjugated or indirect form of bilirubin will be elevated. Unconjugated hyperbilirubinemia is caused by accelerated erythrocyte hemolysis in the newborn (erythroblastosis fetalis), absence of glucuronyl transferase, or hepatocellular disease. Conjugated hyperbilirubinemia is caused by obstruction of the biliary ducts, as with gallstones or hepatocellular diseases such as cirrhosis or hepatitis. Elevated serum bilirubin test results may also be caused by the effects of many different drugs, including antibiotics, barbiturates, steroids, or oral contraceptives. In chronic acquired liver diseases, the serum bilirubin concentration is usually normal until a significant amount of liver damage has occurred and cirrhosis is present. In acute liver disease, the bilirubin is usually increased in relation to the severity of the acute process.
Almost all of the bilirubin produced is excreted as one of the components of bile salts. Bilirubin is the pigment that gives bile its characteristic bright greenish yellow color. When the bile salts reach the intestine via the common bile duct, the bilirubin is acted on by bacteria to form chemical compounds called urobilinogens. Most of the urobilinogen is excreted in the feces; some is reabsorbed and goes through the liver again and a small amount is excreted in the urine. Urobilinogen gives feces their dark color. An absence of bilirubin in the intestine, such as may occur with bile duct obstruction, blocks the conversion of bilirubin to urobilinogen, resulting in clay-colored stools.
The following is a review of the normal pathway for bilirubin production and excretion and its relationship to laboratory assessment of liver function:
Jaundice is the discoloration of body tissues caused by abnormally high levels of bilirubin. Bilirubin levels greater than 3mg/dl usually produce jaundice. Once the jaundice is recognized clinically, it is important to determine whether the increased bilirubin level is prehepatic or posthepatic jaundice. A rise in unconjugated bilirubin indicates prehepatic or hepatic jaundice and is treated medically, whereas a rise in conjugated bilirubin indicates posthepatic jaundice a condition that may require bile duct surgery or therapeutic endoscopy.
Physiologic jaundice of the newborn is a result of the immature liver's lacking sufficient conjugating enzymes. The newborn's inability to conjugate bilirubin results in high circulating blood levels of unconjugated bilirubin, which, if untreated, passes through the blood-brain barrier. The bilirubin level must be monitored closely to prevent brain damage. Bilirubin levels can be decreased by exposing newborns to ultraviolet light.