Jaundice

Question 1

What is the definition of jaundice

Answer 1

Jaundice refers to yellowish discolouration of skin, sclera and mucus membranes due to raised bilirubin.

Question 2

Explain the metabolism of bilirubin

Answer 2

Bilirubin uptake in the liver is mediated by carrier proteins

On the smooth ER bilirubin is conjugated with glucoronic acid, xylose or ribose

Conjugated bilirubin is water soluble and is secreted by the hepatocytes into the biliary canaliculi

Converted to stercobilinogen (urobilinogen) (colorless) by bacteria in the gut

Oxidized to stercobilin which is colored and excreted in the feaces

Question 3

What are the intrahepatic and extrahepatic disorders that lead to conjugated hyperbilirubinemia

Answer 3

Intrahepatic disorder:
- Hepatocellular disease of any cause (eg, viral hepatitis)
- Biliary disorders (eg, PBC,PSC)
- Dubin-Johnson syndrome
- Rotor syndrome
- Cholestasis of pregnancy
- Benign recurrent intrahepatic cholestasis

Extrahepatic disorder (obstruction)
- Biliary tract pathology (e.g. stone, tumor or stricture)
- Pancreatic pathology (e.g.carcinoma)

Question 4

What are the conditions leading to unconjugated hyperbilirubinaemia

Answer 4

Increased bilirubin production
- Hemolysis
- Ineffective erythropoiesis

Reduced uptake or conjugation
- Neonatal hyperbilirubinemia
- Fasting
- Gilbert’s syndrome
- Crigler-Najjar syndromes

Question 5

How does prehepatic (hemolytic) jaundice develop

Answer 5

Results from excess production of bilirubin following hemolysis such as in autoimmune diseases: Heamolytic disease of the newborn, structural RBC abnormalities: Sickle cell, or breakdown of extravasated blood

Question 6

How does intrahepatic jaundice develop

Answer 6

It is due to impaired uptake, conjugation or secretion of bilirubin and is usually indicative of a generalized hepatocyte dysfunction.

Hyperbilirubinaemia usually accompanied by other abnormalities in biochemical markers of liver functions

Question 7

How does post hepatic jaundice develop

Answer 7

It is caused by an obstruction of the biliary tree.

Plasma bilirubin is conjugated and other biliary metabolites accumulate in th eplasma leading to pale colored stools and dark urine

In a complete obstruction urobilin is absent from the urine

Question 8

What are the biochemical patterns for liver damage for the following:
- Hepatocellular
- Cholestasis

Answer 8

Hepatocellular:
- Transaminase: 8-200 x ULN
- Alk phosphatase: 1-3 x ULN

Cholestasis
- Transaminase: 1-8 x ULN
- Alk phosphatase: 3-8 x ULN

Question 9

Define Gilbert’s syndrome

Answer 9

Caused by decreased ability of the liver to conjugate bilirubin – often correlated with fasting or illness

Can be treated with small doses of phenobarbital to stimulate UDP glucuronyl transferase activity

Question 10

Define Crigler-Najjar Syndrome

Answer 10

Characterized by a complete absence or marked reduction in bilirubin conjugation

Present with a severe unconjugated hyperbilirubinemia that usually presents at
birth

Condition is fatal when the enzyme is completely absent

Treated by phototherapy (10-12 hrs/day) and liver transplant by age 5

Question 11

Define Dubin-Johnson and Rotor’s syndromes

Answer 11

Characterized by impaired biliary secretion of conjugated bilirubin

Present with a conjugated hyperbilirubinemia that is usually mild