Jaundice

Question 1

Jaundice

Answer 1

• Yellowish pigmentation of skin, mucous membranes and sclera due to increased levels of bilirubin.
• Clinically detected when serum bilirubin is above 2.0-2.5mg/dL.
• Severe 30-40mg/dL.

Question 2

Normal serum bilirubin.

Answer 2

0. 3-1.2 mg/dL
   - A balance between rate of bilirubin production and rate of biliary excretion.
   - During first 2 weeks of life the process of conjugation and excretion of bilirubin is not fully mature.

Question 3

Types of hyperbilirubinemia.

Classify jaundice based on underlying cause.

Answer 3

1. Unconjugated hyperbilirubinemia.

2. Predominantly conjugated hyperbilirubinemia.

Question 4

Mechanism of unconjugated hyperbilirubinemia.

Answer 4

1. Excessive extrahepatic production of bilirubin.
2. Reduced hepatocyte uptake.
3. Impaired conjugation.

Question 5

Mechanism of Predominantly conjugated hyperbilirubinemia.

Answer 5

1. Decreased hepatocellular excretion.

2. Impaired bile flow.

Question 6

Where do conjugated and unconjugated bilirubin accumulate?

Answer 6

Systemic circulation.

Question 7

Unconjugated bilirubin

Answer 7

• Insoluble in water at physiologic pH
• Present in circulation in tight complexes with serum albumin.
• Cannot be excreted in urine even when its levels are high in blood.

Question 8

Kernicterus.

Answer 8

Neurological damage produced in infants due to crossing of unconjugated bilirubin through immature blood brain barrier.

Question 9

Conjugated bilirubin.

Answer 9

• Water-soluble
• Nontoxic
• Loosely bound to albumin in plasma
• Excess ca be secreted in urine.

Question 10

Classify jaundice based on pathologic mechanism.

Answer 10

1. Hemolytic jaundice.
2. Hepatocellular jaundice.
3. Obstructive jaundice.

Question 11

Crigler-Najjar Syndrome Type I

Answer 11

• The abnormality is impaired conjugation of bilirubin.
• Autosomal recessive disorder.
• Complete absence of UGT1A1.

Question 12

Crigler-Najjar Syndrome Type II

Answer 12

• Less sever and non-fatal.
• Partial deficiency of UGT1A1 enzyme.
• Autosomal dominant with variable penetrance.
• Phenobarbital treatment can improve (unlike Type 1)

Question 13

Gilbert syndrome

Answer 13

• Relatively common, harmless, asymptomatic.
• Autosomal recessive.
• Mild, chronic unconjugated fluctuating hyperbilirubinemia.
• Mutations in the UGT1 > inadequate synthesis of UGT1A1 [30 percent activity]

Question 14

Dubin-Johnson Syndrome

Answer 14

• Benign autosomal recessive.
• Darkly pigmented liver due to melanin like granules of epinephrine metabolites.
• Due to complete absence of multidrug resistance protein 2 [MRP 2]

Question 15

Rotor Syndrome

Answer 15

• Rare form of asymptomatic conjugated hyperbilirubinemia.
• Due to many defects, such as hepatocellular uptake, intracellular binding and excretion of bilirubin pigments.
• Autosomal recessive trait.
• Liver is morphologically normal.