Bilirubin

The average lifespan of a red blood cell (RBC) is about 120 days. Reticuloendothelial cells in the liver, spleen and bone marrow remove old and damaged RBCs.

• Step 1: Red blood cells undergo hemolysis by the mononuclear phagocytes of the reticuloendothelial system. Hemoglobin is released from the RBCs and monocytes break it into its heme, iron and globulin components. Mononuclear heme oxygenase cleaves heme to produce biliverdin that is quickly reduced by biliverdin reductase to unconjugated bilirubin. Unconjugated bilirubin is a toxic hydrophobic waste product that must be made water-soluble to be excreted. This is known as "pre-hepatic," "free," "unconjugated," or "indirect bilirubin" (normal value = 0.1 - 1.0 mg/dl). The serum protein albumin binds unconjugated bilirubin making it less toxic. Serum albumin bound bilirubin is a water soluble molecule and easily transported to the liver where it is selectively absorbed by hepatocytes.
• Step 2: Hepatocytes using the liver enzyme uridine diphosphate (UDP)-glucuronyl transferase biotransform or conjugate bilirubin with glucuronate which makes it water-soluble for excretion. This is known as "posthepatic", "conjugated" or "direct" bilirubin (normal value = 0.0 - 0.4 mg/dl)
• Step 3: Conjugated bilirubin is excreted via bile salts to intestine. Bacteria in the intestine break down bilirubin to urobilinogens. About half of the urobilogen is reabsorbed and reenters the circulation via the portal system for excretion through the kidneys. Urobiligen that remains in the intestine is reduced to stercobilinogen which gives feces the brown coloring.

Direct vs Indirect Bilirubin

The enzyme, glucuronyl transferase, is necessary for the conjugation of bilirubin. 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.

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Bilirubin concentrations are elevated in the blood by conditions that increase hemolysis, decreased conjugation, or blockage of the bile ducts. In cases of increased hemolysis, 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.

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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.

Jaundice

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.

Neonatal jaundice

Physiologic neonatal jaundice

In utero the fetus compensates for a lower PaO2 by producing more RBCs and hemaglobin (Hct 60). After birth the excess RBCs are not needed and they begin to breakdown releasing bilirubin a rate greater than can be transported and cleared by the immature hepatocytes. Physiologic jaundice usual appears 2-3 days after birth, peaking days 3-5. Total bilirubin increases <5 mg/dL per day. The condition resolves by two weeks in the term infant and 3-4 weeks in the preterm infant.

Pathologic neonatal jaundice

Pathologic jaundice appears within 24 hours of birth. Total bilirubin rises faster than 5 mg/dl per day. Peak concentrations is more than 12 mg/dl in the term infant and 15 mg/dL in the preterm infant.

Free bilirubin is lipophilic and is able to cross the blood brain barrier. It is highly toxic to cells in the central nervous system.

Increased risk of Pathologic Jaundice
Infection	Blood abnormality	Other
Neonatal hepatitis Torch (T)oxoplasmosis, (O)ther Agents, (R)ubella (C)ytomegalovirus, (H)erpes Simplex. Neonatal sepsis	Hemolytic disease of the newborn Rh incompatibility ABO incompatibility Race:East Asians and American Indians Familial: G6PD deficiency	Breast feeding or inadequate nutrition Maternal diabetes preterm and low birthweight
Treatment
Blue-green light in the range of 460-490 nm is most effective for phototherapy.	Exchange transfusion

 

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