Hyperbilirubinemia

Ans. is ‘a’ i.e., Physiological jaundice; ‘b’ i.e., Breast milk jaundice; ‘c’ i.e., Gilbert syndrome

Ans. is ‘d’ i.e., Crigler-Najjar syndrome

Predominantly Unconjugated fliperbilirubinenrict

Excess production of bilirubin Hemolytic anemias

Resorption of blood from internal hemorrhage (e.g. alimentary

tract bleeding, hematomas)

Ineffective erythropoiesis syndromes (e.g. pernicious anemia, thalassemia)

Reduced hepatic uptake

Drug interference with membrance carrier systems

Some cases of Gilbert syndrome Impaired bilirubin conjugation

Physiologic jaundice of the newborn (decreased UGT I A I activity,

decreased excretion)

Breast milk jaundice (b-glucrurondases in milk)

Genetic deficiency of UGT 1 AI activity (Crigler-Najjar syndrome types I and II)

Gilbert syndrome (mixed etiologies)

Diffuse hepatocellular disease (e_.g. viral or drug-induced hepatitis, cirrhosis)

Predominantly conjugated hyperbilirubinemia

Deficiency of canalicular membrane transporters (Dubin-Johnson syndrome, Rotor syndrome) Impaired bile flow.

Ans. is ‘a’ i.e., Rotor syndrome

Conjugated hyperbilirubinemia is seen when ‑

Impaired secretion of conjugated bilirubin into bile→ Dubin Johnson syndrome, Rotor syndrome.

Impaired bile flow → Obstructive jaundice, primary biliary cirrhosis, Neonatal cholestasis, e.g. Extrahepatic biliary atresia/neonate idiopathic hepatitis, Choledocal cyst, Sclerosing cholangitis, Caroli disease, Metabolic (Tyrosinemia, Wolman disease, Nieman pick disease, Galactosemia, Fructosemia).

Ans is ‘c’ i.e., Gilbert syndrome

Ans. is ‘b’ i.e., Dubin Johnson Syndrome

Ans. is ‘b’ i.e., Dubin-Johnson syndrome

Dubin-Johnson syndrome is an autosomal recessive disorder.

o Note sure about option d.

Ans. is ‘a’ i.e., Breast milk jaundice

The answer is C (Rotor syndrome)

Rotor’s syndrome is an autosomal recessive inherited disorder characterized by a deject in biliary excretion leading to conjugated hyperbilirubinemia:

Answer is D (Dubin Johnson Syndrome)

Dubin Johnson syndrome is associated with conjugated hyperbilirubinemia & not unconjugated hjperbilirubinemia. Dubin Johnson Syndrome results from a hereditary defect in excretion of conjugated bilirubin across the canalicular membrane and leads to conjugated hyperbilirubinemia.

Dubin Johnson syndrome is an inherited disorder charachterized by defective excretion of conjugated bilirubin from hepatocytes into biliary canaliculi. It thus presents with a clinical picture similar to obstructive jaundice with conjugated hyperbilirubinemia and absence of urobilinogen in urine.

Hemolytic Anemia typically presents with unconjugated hyperbilirubinemia and elevated urinary urobilinogens. Gilberts syndrome and Cri2ler Najjar syndrome also present with unconjugated hyperbilirubinemia. Urinary Urobilinogens are however not elevated in these conditions. Urobilinogen may never the less be present in urine (N or in these conditions

Ans. C i.e. Gilbert syndrome

Gilbert syndrome presents with unconjugated hyperbilirubinemia

Ans. C: Dubin-Johnson Syndrome

This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile.

The conjugated hyperbilirubinemia is a result of the defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into the bile.

Pigment deposition in lysosomes causes the liver to turn black.

Other causes of conjugated/direct hyperbilirubinemia:

• Hepatocellular diseases:

– Hepatitis:

• Neonatal idiopathic hepatitis
• Viral (Hepatitis B, C, TORCH infections)
• Bacterial (E. colt, urinary tract infections)

–        Total parenteral nutrition

–        Hepatic ischemia (post-ischemic damage)

–        Erythroblastosis fetalis (late, “Inspissated Bile Syndrome”)

Metabolic disorders:

• Alpha-1 antitrypsin deficiency
• Galactosemia, tyrosinemia, fructosemia
• Glycogen storage disorders
• Cystic fibrosis

Biliary tree abnormalities:

–         Extrahepatic biliary atresia: In first 2 weeks, unconjugated bilirubin predominates; elevated conjugated bilirubin is late.

–        Paucity of bile ducts

–        Choledochal cyst

–        Bile plug syndrome

Causes of unconjugated/indirect hyperbilirubinemia:

• Increased lysis of RBCs (i.e., increased hemoglobin release)

–        Isoimmunization (blood group incompatibility: Rh, ABO and minor blood groups)

–        RBC enzyme defects (e.g., G6PD deficiency, pyruvate kinase deficiency)

–        RBC structural abnormalities (hereditary spherocytosis, elliptocytosis)

–        Infection (sepsis, urinary tract infections)

–        Sequestered blood (e.g., cephalohematoma, bruising, intracranial hemorrhage)

–        Neonatal Jaundice

–        Polycythemia

–        Shortened life span of fetal RBCs

Decreased hepatic uptake and conjugation of bilirubin

–        Immature glucuronyl transferase activity in all newborns: term infants have 1% of adult activity, preterm infants have 0.1%.

–        Gilbert Syndrome

–        Crigler Najjar Syndrome (Non-hemolytic Unconjugated Hyperbilirubinemia): inherited conjugation defect (very rare)

–        Breastmilk Jaundice (pregnanediol inhibits glucuronyl transferase activity)

Increased enterohepatic reabsorption

–        Breastfeeding jaundice (due to dehydration from inadequate milk supply)

Ans. is ‘a’ i.e., Dubin johnson syndrome

Breast milk jaundice –

• Decrease bilirubin uptake across hepatocyte membrane.
• Entero-hepatic recirculation.
• Leads to indirect hyperbilirubinemia.

Crigler najjar & Gilbert syndrome (deficiency of glucuronyl transferase)

• Decrease conjugation leads to Indirect hyperbilirubinemia.
• Defect in hepatocyte secretion of conjugated bilirubin.
• Leads to direct hyperbilirubinemia