Hyperbilirubinemia Disorders

Question 1

hemolytic anemia

Answer 1

• form of anemia due to hemolysis
• any cause of hemolytic anemia would lead to increased production of bilirubin
• unconjugated would be increased
  (no change in conjugated)

Question 2

neonatal jaundice

Answer 2

• increased unconjugated bilirubin during first week of life (increased bilirubin production d/t breakdown of fetal erythrocytes, low UDP-glucuronyl transferase)
• infants may be tired and poorly fed
• usually corrected with phototherapy (TRANS TO CIS BILIRUBIN, cis is excretable)

Question 3

Gilbert’s syndrome

Answer 3

• often asymptomatic except for flare ups (physiological stress)
• mutation in UDP-GT gene
• recognized in ADOLESCENCE
• mild and benign
• increased UNCONJUGATED (no change conjugated)

Question 4

Crigler-Najjar Syndrome Type 1

Answer 4

• very severe, starts early in life, apparent at birth or infancy
• defect in UDP-GT gene
• increased UNCONJUGATED bilirubin
• results in kernicterus (cerebral palsy, gaze abnormalities, spasiticity)
• phototherapy, liver transplant

Question 5

Crigler-Najjar Syndrome Type 2

Answer 5

• defect in UDP-GT gene (under 20% function)
• increased UNCONJUGATED bilirubin
• less severe than type 1
• less likely to develop kernicterus
• Tx: PHENOBARBITOL

Question 6

Dubin-Johnson

Answer 6

• mild jaundice throughout life
• may not appear until puberty or adulthood
• worsened with EtOH, birth control, infection, pregnancy
• defect in ability of hepatocytes to secrete CONJUGATED bilirubin into bile (MRP2 mutation)
• liver has black pigmentation

Question 7

Rotor Syndrome

Answer 7

• Increased conjugated bilirubin (maybe unconjugated too)
• mild jaundice throughout life
• may not appear until puberty or adulthood
• defect in OATP1B1
• enterohepatic recycling of bilirubin is compromised

Question 8

ASBT

Answer 8

• apical sodium-dependent bile acid transporter

- brings bile acids into enterocyte of ileum

Question 9

OST

Answer 9

• organic solute transporter

- brings bile acids from enterocyte to circulation for recycling

Question 10

OATP

Answer 10

• organic anion transporter
• bring in bile acid from circulation to hepatocyte
• mutation with Rotor Syndrome

Question 11

MRP2

Answer 11

• multidrug resistance protein 2
• brings bile from hepatocyte to gallbladder
• mutation with Dubin-Johnson