bilirubin metabolism & jaundice
DESCRIPTION
Bilirubin Metabolism & Jaundice. Formation of Bilirubin from Heme. Heme is degraded in RE system (esp. liver & spleen) 85% from RBCs 15% from turnover of immature RBCs & cytochromes Heme heme oxygenase biliverdin (green) - PowerPoint PPT PresentationTRANSCRIPT
Bilirubin Metabolism &
Jaundice
Formation of Bilirubin from Heme
Heme is degraded in RE system (esp. liver & spleen)85% from RBCs 15% from turnover of immature RBCs & cytochromes
Heme
heme oxygenase
biliverdin (green)
bilirubin (red-orange) bile pigments
In Blood with albumin
UNCONJUGATED BILIRUBIN(or INDIRECT BILITUBIN)
Salicylates & sulfonamides can displace bilirubin from albumin & so bilirubin enters CNS causing neural damage
Bilirubin Metabolism in the Liver
• Uptake of Bilirubin by hepatocytes: Bilirubin dissociates from its carrier albumin & enters hepatocytes
• Conjugation of Bilirubin: In hepatocytes, bilirubin is conjugated with two molecules of glucuronic acid by the enzyme glucuronyl transferase
• Excretion of bilirubin into bile: Conjugated bilirubin (bilirubin diglucuronide) is transported into bile canalculi & then into bile. Process is energy dependent & is impaired in liver diseases
Bilirubin Metabolism in the Intestine
Conjugated bilirubin bacteria in the intestine Urobilinogen
Stercobilin Reabsorbed in stool (brown) Kidney Urine Urobilin (yellow)
OVERVIEW OF BILIRUBIN METABOLISM
Jaundice
Yellow color of skin, nail beds & sclera caused by deposition of bilirubin secondary to increased bilirubin levels in blood
(hyperbilirubinemia)
JAUNDICE IS NOT A DISEASEHOWEVER,
IT IS A SIGN OF AN UNDERLYING DISEASE
Types of Jaundice
1- Hemolytic Jaundice2- Obstructive Jaundice3- Hepatocellular Jaundice
Hemolytic Jaundice
Massive lysis of RBCs in hemolytic anemiae.g. sickle cell anemia
Bilirubin is produced in a rate faster than rate of conjugation by the liver
Blood:Increased blood unconjugated (indirect) bilirubin
Urine: Urobilinogen is increasedNo bilirubin in urine (Color of urine is normal)as it is bound to albumin
StoolDark colorIncreased stercobilin (produced from increased urobilinogen)
Obstructive Jaundice
In bile duct obstruction:Conjugated bilirubin is prevented from passing to the intestine.Thus, it is regurged to blood increasing conjugated (direct) bilirubin in bloodExcessive conjugated bilirubin is excreted in urine giving the yellowish brown color of urine
Blood:Increased conjugated (direct) bilirubinGGT & ALP are markedly elevated (ALT is normal or mildly elevated)
Urine:Bilirubin appears in urineThus, color is yellowish brownUrobilinogen is reduced
StoolPale (low stercobilin)
Hepatocellular Jaundice
FirstLiver damage (by hepatitis or hepatitis) causes low conjugation efficiency leading to increased unconjugated (indirect) bilirubin in blood
Second Conjugated bilirubin is not efficiently secreted into bile. Instead, diffuses to blood increasing conjugated (direct) bilirubin in blood
BloodIncreased BOTH unconjugated (indirect) & conjugated (direct) bilirubinALT & AST levels are markedly elevated
Urine:Bilirubin is present in urineSo, urine color is yellowish brown
StoolPale (low stercobilin)
BLOOD URINE
GGT & ALP ALT & AST CONJUGATEDBILIRUBIN
UNCONJUGATEDBILIRUBIN BILIRUBIN UROBILINOGEN
NORMAL NORMAL N:0 - 0.2 mg/dl N: 0.2 – 1 mg/dl NIL TRACE NORMAL
NORMAL NORMAL N:0 - 0.2 mg/dl INCREASED NIL INCREASD HEMOLYTICJAUNDICE
MARKED INCREASE
Normal or
mild increaseINCREASED N:0 - 0.2 mg/dl PRESENT Decreased or absent OBSTRUCT.
JAUNDICE
Normalor
mild increase
MARKEDINCREASED INCREASED INCREASED PRESENT Decreased or absent HEPATOCEL.
JAUNDICE
LABORATORY INVESTIGATIONS IN TYPES OF JAUNDICE
Jaundice in Newborns
• In newborns (especially premature), Bilirubin accumulates as the liver enzyme bilirubin glucuronyl transferase (responsible for conjugation of bilirubin) is low at birth. (The enzymes reaches adult levels in about 4 weeks)
• Accordingly, unconjugated bilirubin is increased in blood. Elevated bilirubin in excess of the binding capacity of albumin can diffuse into basal ganglia & cause toxic encephalopathy (kernicterus)
• Treatment Exposure of the newborn skin to blue fluorescent light which converts bilirubin to more polar & hence water-soluble isomers These isomers can be excreted into bile without conjugation to glucuronic acid.
Congenital hyperbilirubinemia
Bilirubin is elevated in blood due to inherited defects in the bilirubin metabolic pathway
Crigler-Najjar syndromeLow activity of glucoronyltransferase (conjugating enzyme)Rare Inherited l disease Severe hyperbilirubinemia in neonates (unconjugated bilirubin)Complicated by kernicterus & early death
Gilbert`s syndromeDecreased production (expression) of glucoronyltransferaseRare autosomal dominant traitMore common menOccurs in 2-3 % of menUsually asymptomatic hyperbilirubinemia Liver function tests are normal
Dubin-Johnson syndromeDefect in transfer of conjugated bilirubin into the biliary canalculiConjugated hyperbilirubinemia.