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