Jaundice

Question 0

Indicators of hyperbilirubinemia

Answer 0

jaundice

dark pigmentation of the urine (inc. conj. bilirubin excretion)

Question 1

DDX for yellowing of the skin

Answer 1

a. jaundice (+ scleral icterus, distributed pigmentation)
b. carotenoderma (palms, soles, forehead, nasolabial fold, - sclera)
c. quinacrine (+ sclera)

Question 2

Causes of

a. hyperbilirubinemia
b. direct
c. indirect

Answer 2

Hyperbilirubinemia

(1) overproduction of bilirubin;
(2) impaired uptake, conjugation, or excretion of bilirubin; or
(3) regurgitation of unconjugated or conjugated bilirubin from damaged hepatocytes or bile ducts

Direct Bilirubinemia (Conjugated)

• decreased excretion into the bile ductules
• backward leakage of the pigment

Indirect (Unconjugated)

• overproduction
• impairment of uptake
• impaired conjugation of bilirubin

Question 3

Causes of Isolated Conjugated Hyperbilirubinemia

Causes of Isolated Unconjugated Hyperbilirubinemia

Answer 3

Causes of Isolated Conjugated Hyperbilirubinemia
A. Inherited conditions
1. Dubin-Johnson syndrome
2. Rotor’s syndrome

Causes of Isolated Unconjugated Hyperbilirubinemia
A. Hemolytic disorders
1. Inherited
a. Spherocytosis, elliptocytosis Glucose-6-phosphate dehydrogenase and pyruvate kinase deficiencies
b. Sickle cell anemia
2. Acquired
a. Microangiopathic hemolytic anemias
b. Paroxysmal nocturnal hemoglobinuria
c. Spur cell anemia
d. Immune hemolysis
e. Parasitic infections
1. Malaria 2. Babesiosis

B. Ineffective erythropoiesis
1. Cobalamin, folate, thalassemia, and severe iron deficiencies

C. Drugs
1. Rifampicin, probenecid, ribavirin

D. Inherited conditions

1. Crigler-Najjar types I and II
2. Gilbert’s syndrome

Question 4

Crigler-Najjar Type I
Crigler-Najjar Type II
Gilbert’s Syndrome

Answer 4

Crigler-Najjar type I

• neonates
• severe jaundice [bilirubin > 342 μmol/L (>20 mg/dL)]
• neurologic impairment due to kernicterus, frequently leading to death in infancy or childhood.
• complete absence of bilirubin UDPGT activity due to UDPGT gene muntation
• totally unable to conjugate, hence cannot excrete, bilirubin

Crigler-Najjar Type II

• serum bilirubin levels 103–428 μmol/L (6–25 mg/dL)
• reduced mutation in UDPGT gene
• enzyme activity can be induced by phenobarbitals
• survive into adulthood

Gilbert’s Syndrome

• reduced bilirubin UDPGT activity to approximately 1/3 of normal
• mild unconjugated hyperbilirubinemia <103 μmol/L (6 mg/dL)

Question 5

Dubin-Johnson Syndrome vs Rotor Syndrome

Answer 5

Dubin-Johnson syndrome

• mutations in the gene for multiple drug resistance protein 2
• altered excretion of bilirubin into the bile ducts

Rotor’s syndrome
- hepatic storage of bilirubin