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 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 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