Transcript HYPERBILIRUBINEMI301.5 KB

HYPERBILIRUBINEMI
Prof.Dr.Arzu SEVEN
HYPERBILIRUBINEMI
(Bilirubin>1mg/dl in blood)
• Types of bilirubin:
• İndirect bilirubin=free
bilirubin=unconjugated bilirubin
• Free bilirubin en route to liver from RES,
where it is produced from the breakdown
of heme porphyrins.
.
• As it is water _insoluble, it requires
methanol to be coupled with diazo reagent
• Direct bilirubin=conjugated
bilirubin=bilirubin glucuronide:
• Bilirubin that is ready to be excreted into
the bile
• As it is water soluble, it can react directly
with diazo reagent.
Only conjugated bilirubin can occur in the
urine .
• DELTA bilirubin:
• Conjugated bilirubin that is covalently
bound to albumin, has a longer half life in
plasma than conventional conjugated
bilirubin
.
• It remains high during the recovery phase
of obstructive jaundice after the remainder
of conjugated bilirubin has decreased to
normal level.
• Hyperbilirubinemi may be due to:
• a)production of more bilirubin than normal
liver can excrete:PREHEPATİC
• b)failure of damaged liver to excrete
normal amounts of bilirubin, impaired
hepatic uptake, conjugation or secretion of
hepatic bilirubin:INTRAHEPATIC
• C)obstruction of the excretory ducts of
liver:POST HEPATIC
• Depending on the type of bilirubin present
in plasma, hyperbilirubinemia may ve
classified as:
• 1)retention hyperbilirubinemia due to
overproduction.
• 2)regurgitation hyperbilirubinemia due to
reflux into the bloodstream because of
biliary obstruction.
• Because of its hydrophobicity only
unconjugated bilirubin>20-25mg/dl can
cross the blood_brain barrier into the
central nervous system.
• Toxic encephalopathy due to
hyperbilirubinemi (KERNİCTERUS) can
occur in retention hyperbilrubinemia.
• Choluric jaundice occurs in regurgitation
hyperbilirubinemia.
• Acholuric jaundice occurs only in the presence
of excess unconjugated bilirubin.
.
• Obstruction of the biliary tree is the
commonest cause of conjugated
hyperbilirubinemia .
Blockage of the hepatic or common bile
ducts,most often due to a gallstone or
pancreas head cancer
• Conjugated bilirubin can not be excreted
due to obstruction
it regurgitates into hepatic veins γ
lymphatics
it appears in blood γ urine
(choluric jaundice)
• Cholestatic jaundice: all cases of
extrahepatic obstructive jaundice
Dubin Johnson Syndrome
• Benign autosomal recessive disorders
• Conjugated hyperbilirubinemia in
childhood or during adult life
• Mutations in the gene encoding MRP-2,
the protein involved in the secretion of
conjugated bilirubin into bile
• Centrilobuler hepatocytes contain
abnormal black pigment derived from
epinephrine .
Rotor Syndrome
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Rare benign condition
Chronic conjugated hyperbilirubinemia
Normal liver histology
Abnormality in hepatic storage
Neonatal physiologic jaundice
• Accelerated hemolysis around the time of
birth
• Immature hepatic system for the
uptake,conjugated and secretion of
bilirubin
• enzyme activity
UDP_glucuronic acid
• Therapy: Phenobarbital
Phototherapy (blue light)
Crigler –Najjar Syndrome Type I
(congenital nonhemolytic jaundice)
• Rare
• Autosomal recessive
• Severe congenital jaundice
(bilirubin>20mg/dl)
• Fatal within 15 months of life
• Phototherapy
Crigler –Najjar Syndrome Type II
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Rare
Inherited
More benign than type I
bilirubin<20mg/dl
Phenobarbital
Gilbert Syndrome
• 30% of enzyme activity is preserved
• Harmless
Toxic Hyperbilirubinemia
• Toxin- induced liver dysfunction due to
choloroform, arsphenamines,
acetaminophen, carbon tetrachloride,
hepatitis virus, cirrhosis
Amanita mushroom poisoning