Bilirubin
From Wikipedia, the free encyclopedia
Bilirubin is a yellow breakdown product of normal heme catabolism. Its levels are elevated in certain diseases and it is responsible for the yellow color of bruises and the brown color of feces. Bilirubin reduction in the gut leads to a product called urobilinogen, which is excreted in urine.
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[edit] Bilirubin blood tests
Bilirubin is either in the insoluble form, unconjugated bilirubin (also indirect bilirubin), or bound to glucuronic acid to form the so called conjugated bilirubin (also direct bilirubin). The indirect form is insoluble and it is transformed into a soluble or direct form, in the liver. Total and direct bilirubin levels can be measured from the blood, but indirect bilirubin is calculated from the total and 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. To further elucidate the causes of jaundice or increased bilirubin, it is usually simpler to look at other liver function tests (especially the enzymes ALT, AST, GGT, Alk Phos), blood film examination (hemolysis, etc.) or evidence of infective hepatitis (e.g., Hepatitis A, B, C, delta E, etc).
Bilirubin is an excretion product, and the body does not control levels. Bilirubin levels reflect the balance between production and excretion. Thus, there is no "normal" level of bilirubin.
Bilirubin is broken down by light, and blood collection tubes (especially serum tubes) should therefore be protected from such exposure.
[edit] Interpretation
The reference range for total bilirubin is 2 - 14 μmol/L or 0.3 - 1.9 mg/dL. For direct bilirubin, it is 0 - 4 μmol/L or 0 - 0.3 mg/dL.
Mild rises in bilirubin may be caused by
- Hemolysis or increased breakdown of red blood cells.
- Gilbert's syndrome - a genetic disorder of bilirubin metabolism which can result in mild jaundice, found in about 5% of the population.
Moderate rise in bilirubin may be caused by
- Drugs (especially anti-psychotic, some sex hormones, and a wide range of other drugs).
- Hepatitis (levels may be moderate or high).
Very high levels of bilirubin may be caused by
- Neonatal hyperbilirubinaemia, where the newborn's liver is not able to properly conjugate the bilirubin (see jaundice).
- Unusually large bile duct obstruction, eg stone in common bile duct, tumour obstructing common bile duct etc.
- Severe liver failure with cirrhosis.
- Severe hepatitis.
- Crigler-Najjar syndrome
- Dubin-Johnson syndrome
Cirrhosis may cause normal, moderately high or high levels of bilirubin, depending on exact features of the cirrhosis
[edit] Jaundice
Jaundice may be noticeable in the sclera (white) of the eyes at levels above about 30-50 μmol/l, and in the skin at higher levels. Jaundice is classified depending upon whether the bilirubin is free or conjugated to glucuronic acid into:
- Conjugated jaundice
- Unconjugated jaundice
Neonatal hyperbilirubinemia - other cause is increased destruction of blood cells (Fetal hemoglobin resorption) over liver's capacity to conjugate
[edit] Bilirubin toxicity
Unconjugated hyperbilirubinaemia in the neonate can lead to accumulation of bilirubin in certain brain regions, a phenomenon known as kernicterus, with consequent irreversible damage to these areas manifesting as various neurological deficits, seizures, abnormal reflexes and eye movements. Aside from specific chronic medical conditions that may lead to hyperbilirubinaemia, neonates in general are at increased risk since they lack the intestinal bacteria that facilitate the breakdown and excretion of conjugated bilirubin in the feces (this is largely why the feces of a neonate are paler than those of an adult). Instead the conjugated bilirubin is converted back into the unconjugated form by the enzyme b-glucoronidase and a large proportion is reabsorbed through the enterohepatic circulation.
[edit] Bilirubin benefits
Reasonable levels of bilirubin can be beneficial to the organism. Evidence is accumulating that suggests bilirubin can protect tissues against oxidative damage caused by free radicals and other reactive oxygen species. Statistical analysis of people with high normal or slightly elevated bilirubin levels in blood shows that they have a lower risk of developing cardiovascular diseases.
[edit] Chemistry
Bilirubin consists of an open chain of four pyrroles (tetrapyrrole); by contrast, the heme molecule is a ring of four pyrroles, called porphyrin.
Bilirubin is very similar to the pigment phycobilin used by certain algae to capture light energy, and to the pigment phytochrome used by plants to sense light. All of these contain an open chain of four pyrroles.
Like these other pigments, bilirubin changes its conformation when exposed to light. This is used in the phototherapy of jaundiced newborns: the illuminated version of bilirubin is more soluble than the unilluminated version.
Several textbooks and research articles show incorrect chemical structures for the two isoforms of bilirubin. [1]
[edit] Trivia
Bilirubin was used as a wordplay in The Silence of the Lambs (novel), Lecter gives the name of the killer as Billy Rubin; after he escaped a sheet of paper with the formula for bilirubin is found in his cell, annotated to resemble the name of Lecter's nemesis Chilton.
In Juan Luis Guerra's song, 'Me sube la bilirrubina', the protagonists' Bilirubin levels increase as a result of unrequited love.
[edit] See also
- Primary sclerosing cholangitis
- Primary biliary cirrhosis
- Gilbert's syndrome, a genetic disorder of bilirubin metabolism which can result in mild jaundice, found in about 5% of the population.
- Crigler-Najjar syndrome
- Biliary atresia
