Pathology of Jaundice

Question 1

Two functions Bile

Answer 1

1. Emulsify Fat

2. Eliminate bilirubin + excess cholesterol

Question 2

Formation + Transport of unconjugated Bilirubin

Answer 2

RBCs uptaken by splenic M0 -> Degradation to Globin + Heme -> Degradaion of heme to Fe + Biliverdin -> Conversion to Unconjugated Bilirubin -> Trtanport across cell membrane to blood (transported by albumin to Liver)

Question 3

Processing of unconjugated Bilirubin

Answer 3

Unconjugated Bilirubin-Albumin separated + transported into hepatocyte -> GSTs + UGT it convert to Conjugated Bilirubin -> transport into bile canaliculi via MRP2 to drain to Gall bladder

Question 4

Main Causes of Jaundice

Answer 4

• INC Production of Bilirubin (unconjugated)
• Reduced hepatic uptake (Inconjugated)
• Impaired Conjugation (Unconjugated)
• Impaired transport into cancaliculi (Conjugated)

Question 5

Pathologies of INC production

Answer 5

• Extravascular hemolytic Anemia

- Ineffective erythropoiesis

Question 6

Pathologies of reduced hepatic uptake

Answer 6

• Generalized Lover Cell injury

- Interference of net uptake by hepatocytes

Question 7

Pathologies of impaired conjugation

Answer 7

• Physiologic Jaundice of Newborn (Low UGT levels)
• Gilbert Syndrome (Lower/Absent UGT Levels)
• Crigler-Najjar syndrome

Question 8

Pathologies of impaired transport of conjugated bilirubin

Answer 8

• Dubin-Johnson syndrome

- Rotor syndrome

Question 9

Intrahepatic Cholestasis Causes

Answer 9

• Drugs (steroids, OICs)
• Neonatal Cholestasis
• Pregnancy (estrogen)
• Familial

Question 10

Extrahepatic Cholestasis

Answer 10

• Gallstone of CBD
• Benign stricture (PSC or Post-op[ scar)
• Congenital Biliary Atresia
• Malignancy of Bile Ducts or a/s LNs

Question 11

Neonatal Cholestasis Morph

Answer 11

• Morph: Lobular dissaray; Multinucleated Giant hepatocytes;

Question 12

Pregnancy-induced Cholestasis

• Genetics
• S/S

Answer 12

• G: ABCB4 + MDR3 Mutation

- S/S: Cholestasis w/ marked pruritis in last trimester; High bile acid levels

Question 13

Pathological Features of Cholestasis

Answer 13

• enlarged hepatocytes w/ intracytoplasmic bile pigments
• Bile plugs in dilated bile canaliculi
• Apoptotic hepatocytes

Question 14

Morph/Hist of Large Bile Duct Obstruction

Answer 14

• stromal edema w/ infiltrative Lymphocytes
• Ascending Cholangitis -> Periductal N/0 into bile duct epithelium + Lumen
• Periportal fibrosis w/ hepatic scarring + irregular nodules
• Parenchymal Feathery degeneration of periportal hepatocytes w/ *Mallory-Denk bodies + Bile infarcts