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Bilirubin
Bilirubin is a yellow breakdown product of heme. Heme is a special ring shaped molecule that is found in
hemoglobin. The heme ring holds the iron atoms of
heme and is
essential to the oxygen carrying capacity of blood.
Bilirubin is essentially a waste product, formed when
hemoglobin is
broken down. It is not soluble in water and is carried to the liver
bound onto albumin. Bilirubin is made water soluble in the liver by
conjugation with glucuronic acid. As part of bile, the soluble
bilirubin then passes through the common bile duct and is either
temporarily stored in the gallbladder or passes right away into the
gut. Some of the excreted bilirubin may be reabsorbed (entero-hepatic
circulation). Bacteria in the intestines modify bilirubin, causing the
brown color of feces. The yellow colour of urine is a result of
products derived from bilirubin.
In diseases where too much hemoglobin is broken down or the removal
of bilirubin does not function properly, the accumulating bilirubin in
the body causes jaundice.
Bilirubin blood tests
Bilirubin is found in blood either bound to albumin ("indirect") or in
the soluble form ("direct"). The terms "direct" and "indirect" refer
to the fact that soluble bilirubin can be measured directly, whereas
insoluble, or indirect, bilirubin must be solubilised before
measurement. Bilirubin is broken down by light, so blood tubes
(especially serum tubes) should be protected from such exposure.
Although both direct and indirect bilirubin can be measured
separately, it is more common to just measure total bilirubin. When we
try 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 basically an excretion product and the body does not
control levels. Bilirubin levels reflect the balance between
production and excretion. Thus strictly speaking there is not a normal
level of bilirubin.
The reference range for total bilirubin is 2 - 14 μmol/L. For direct
bilirubin, it is 0 - 4 μmol/L.
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Mild rises in bilirubin
- hemolysis or increased breakdown of blood.
- Gilbert's syndrome - slightly increased bilirubin due to an inherited
enzyme deficiency. This has no clinical significance.
Moderate rise in bilirubin
- Drugs (especially anti-psychotic, some sex hormones, and a wide range
of other drugs).
- Hepatitis (levels may be moderate or high).
- Cirrhosis (may be normal, moderate or high, depending on exact
features of the
cirrhosis).
Very High levels
- Neonatal hyperbilirubinaemia (see jaundice).
- Usually large bile duct obstruction, eg stone in common bile duct,
tumor obstructing common bile duct etc.
- Severe liver failure with
cirrhosis.
- Severe hepatitis.
Bilirubin toxicity
Hyperbilirubinaemia in the neonate can lead to kernicterus in which
there is damage to certain brain regions. The newborn has abnormal
reflexes and unusual eye movements.
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.
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