HYPERBILIRUBINEMI Prof Dr Arzu SEVEN HYPERBILIRUBINEMI Bilirubin1 mgdl

HYPERBILIRUBINEMI Prof. Dr. Arzu SEVEN

HYPERBILIRUBINEMI (Bilirubin>1 mg/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 -25 mg/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 • • 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>20 mg/dl) • Fatal within 15 months of life • Phototherapy

Crigler –Najjar Syndrome Type II • • • Rare Inherited More benign than type I bilirubin<20 mg/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