8-bilirubin

8/3/2019 8-Bilirubin

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Bilirubin


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Bilirubin is a yellow

breakdown product of normalheme catabolism.

Its levels are elevated in certain

diseases and it is responsiblefor the yellow colour of bruisesand the brown colour of feces.

Bilirubin reduction in the gutleads to a product calledurobilinogen, which is excretedin urine.


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It is thought to be a toxin because it is associatedwith neonataljaundice, possibly leading to

irreversible brain damage due to neurotoxicity. Like these other pigments, bilirubin changes its

conformation when exposed to light. This is usedin the phototherapy of jaundiced newborns: the

illuminated version of bilirubin is more soluble thanthe unilluminated version.


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Metabolism

Formation

of Bilirubin:Overview

Hemoglobin Heme

Globin

Biliverdin Bilirubin(insoluble)

Bilirubin-albuminconjugate

Bilirubin diclucorinide

Bilirubin

Excreted

Spleen

Blood

Liver

O2,

NADPH

Fe2+

, CO

H2O,NADP

+

HO

The BilirubinPathway:Overview

Bilirubin diglucuronide (soluble)


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Erythrocytes (red blood cells) generatedin the bone marrow are destroyed in thespleen when they get old or damaged.This releases hemoglobin, which isbroken down to heme, as the globin parts

are turned into amino acids.

The heme is then turned intounconjugated bilirubin in the

macrophages of the spleen. Bilirubin is bound to albumin and

transported in plasma from the

reticuloendothelial system to the liver, as


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In the liver, bilirubin is made watersoluble by hepatocytes which conjugate

bilirubin with glucuronic acid to formconjugated bilirubin (BC).

BC is secreted from hepatocytes to the

bile canaliculi of the liver and istransported from the liver via the gallbladder and common bile duct to the

gastrointestinal tract.


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In the ileum and colon, bacteria

converts bilirubin intostercobilinogen.

Stercobilinogen is oxidized to

stercobilin, which is excreted in the

feces.

While most bilirubin is excreted asstercobilin, a small amount ofstercobilinogen is reabsorbed into

the blood, modified by the kidneys,


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Function

Bilirubin is created by the activity ofbiliverdin reductase on biliverdin.Bilirubin, when oxidized, reverts to

become biliverdin once again. Thiscycle, in addition to thedemonstration of the potent

antioxidant activity of bilirubin, hasled to the hypothesis that bilirubin'smain physiologic role is as a
http://g/wiki/Biliverdinhttp://g/wiki/Biliverdin


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1-Toxicity

Unconjugated hyperbilirubinaemia in the

neonate can lead to accumulation ofbilirubin in certain brain regions, a

phenomenon known as kernicterus, withconsequent irreversible damage to theseareas manifesting as various neurological

deficits, seizures, abnormal reflexes andeye movements.
http://g/wiki/Reflexeshttp://g/wiki/Reflexes


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2-Toxicity

Aside from specific chronic medicalconditions that may lead tohyperbilirubinaemia, neonates in general are

at increased risk since they lack the intestinalbacteria that facilitate the breakdown andexcretion of conjugated bilirubin in the feces(this is largely why the feces of a neonate

are paler than those of an adult). Instead theconjugated bilirubin is converted back intothe unconjugated form and a large proportion

is reabsorbed through the enterohepatic
http://g/wiki/Enterohepatic_circulationhttp://g/wiki/Enterohepatic_circulationhttp://g/wiki/Enterohepatic_circulationhttp://g/wiki/Enterohepatic_circulation


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Benefits

Reasonable levels of bilirubin can bebeneficial to the organism. Evidence isaccumulating that suggests bilirubin

can protect tissues against oxidativedamage caused by free radicals andother reactive oxygen species.Statistical analysis of people with highnormal or slightlyelevated bilirubinlevels in blood shows that they have alower risk of developing

cardiovascular diseases.
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Blood tests
http://g/wiki/Enterohepatic_circulation


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Bilirubin is in one of twoforms:

Abb. Name Soluble? Reaction

"BC" conjugatedor direct

Yes (bound to

glucuronic

acid)

Reacts directly when dyes are added

to the blood specimen.

"BU" unconjugated orindirect

No

Free bilirubin does not react to the

reagents until alcohol (methanol) or

caffeine is added to the solution.

Therefore, the measurement of this

type of bilirubin is indirect. (It is

transformed into a soluble or direct

form, in the liver. )
http://g/wiki/Enterohepatic_circulationhttp://g/wiki/Enterohepatic_circulationhttp://g/wiki/Enterohepatic_circulationhttp://g/wiki/Enterohepatic_circulationhttp://g/wiki/Enterohepatic_circulationhttp://g/wiki/Enterohepatic_circulationhttp://g/wiki/Enterohepatic_circulationhttp://g/wiki/Enterohepatic_circulationhttp://g/wiki/Enterohepatic_circulationhttp://g/wiki/Glucuronic_acidhttp://g/wiki/Glucuronic_acidhttp://g/wiki/Caffeinehttp://g/wiki/Caffeinehttp://g/wiki/Glucuronic_acidhttp://g/wiki/Glucuronic_acid


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Total bilirubin measures both BU and

BC.

Total and direct bilirubin levels can be

measured from the blood, but indirect

bilirubin is calculated from the total and

direct bilirubin.

Bilirubin is broken down by light, and

therefore blood collection tubes(especially serum tubes) should be

protected from such exposure.


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Interpretation

Different sources provide referenceranges which are similar but not identical.Some examples for adults are providedbelow (different reference ranges are

often used for newborns):

mol/L mg/dL

total bilirubin 5.117.0 0.31.0

direct bilirubin 1.05.1 0.10.3


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Mild rises in bilirubin may be

caused by

Hemolysis or increased breakdown ofred blood cells.

Gilbert's syndrome
http://g/wiki/Hemolysishttp://g/wiki/Gilbert's_syndromehttp://g/wiki/Gilbert's_syndromehttp://g/wiki/Hemolysis


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Moderate rise in bilirubin may be caused

by

Drugs (especially anti-psychotic, somesex hormones, and a wide range of

other drugs). Hepatitis (levels may be moderate or

high).

Biliary stricture (benign or malignant)
http://g/wiki/Recreational_drug_usehttp://g/wiki/Anti-psychotichttp://g/wiki/Sex_hormonehttp://g/wiki/Hepatitishttp://g/wiki/Hepatitishttp://g/wiki/Sex_hormonehttp://g/wiki/Anti-psychotichttp://g/wiki/Anti-psychotichttp://g/wiki/Anti-psychotichttp://g/wiki/Recreational_drug_use


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Very high levels of bilirubin may be caused

by

Neonatalhyperbilirubinaemia, wherethe newborn's liver is notable to properly conjugate

the bilirubin. Unusually large bile duct

obstruction, eg stone incommon bile duct, tumourobstructing common bileduct etc.

Severe liver failure with

cirrhosis.


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Jaundice

Jaundice may be noticeable in thesclera (white) of the eyes at levels ofabout 30-50 mol/l, and in the skin at

higher levels. Jaundice is classifieddepending upon whether the bilirubinis free or conjugated to glucuronic acidinto:

1. Conjugated jaundice

2. Unconjugated jaundice


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also can be classified intoJaundicethree categories, depending on which

part of the physiological mechanismand the pathology affects. The threecategories are:

1. Pre-hepatic: The pathology isoccurringpriorthe liver

2. Hepatic: The pathology is located

withinthe liver3. Post-Hepatic: The pathology is

locatedafterthe conjugation ofbilirubin in the liver


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Pre-hepatic

Pre-hepatic jaundice is caused byanything which causes an increased rate

of hemolysis (breakdown of red bloodcells). As seen in:

Malaria

Certain geneticdiseases, such as sicklecell anemia, spherocytosis and glucose6-phosphate dehydrogenase deficiency

Commonly, diseases of the kidney.


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2- Hepatic

Hepatic jaundice causes include:

o Acute Hepatitis

o alcoholic liver disease.

o Neonatal jaundice, is common, occurring inalmost every newborn as hepatic machinery forthe conjugation and excretion of bilirubin doesnot fully mature until approximately two weeks

of age.


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Post-hepatic

Post-hepatic jaundice, also calledobstructive jaundice, is caused by aninterruption to the drainage of bile in thebiliary system.

The most common causes are gallstones in

the common bile duct, and pancreaticcancer in the head of the pancreas. Also, agroup of parasites known as "liver flukes"live in the common bile duct, causing

obstructive jaundice. The presence of pale stools and dark urine

suggests an obstructive or post-hepaticcause as normal feces get their color from

bile pigments.

L b R l
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Laboratory Results

Blood Tests

Pre-hepaticJaundice

Hepatic

Jaundice

Post-hepatic

Jaundice

Totalbilirubin

Normal

IncreasedIncreased Increased

Conjugated

bilirubin Normal Increased Increased

Unconjugate

d bilirubinIncreased Increased Normal


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Urine Tests

Healthy

Individual

Pre-

hepatic

Jaundice

Hepatic

Jaundice

Post-

hepatic

Jaundice

Urineurobilinoge

n

Present Increased Increased -

Urinebilirubin

- - Increased Increased

8-bilirubin

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