Jaundice

Question 1

Define jaundice

Answer 1

Yellow discolouration of the skin, sclera, and mucosa due to serum bilirubinaemia

Clinically may not become apparent until bilirubin >51 micromol/L

Question 2

Describe the metabolism of bilirubin

Answer 2

• RBCs are broken down by either macrophages (spleen) or pathology into iron and unconjugated bilirubin.
• Albumin carries bilirubin to the liver to be conjugated
• Conjugated bilirubin secreted into bile canaliculi/duodenum
• Metabolised in gut to urobiliogen and stercobilinogen
  
  • Oxidised to urobilin and stercobilin

Question 3

Classify the pathophysiology of jaundice

Answer 3

• Pre-hepatic: unconjugated
• Hepatocellular: mixed
• Post-hepatic: conjugated

Question 4

List three causes of pre-hepatic jaundice

Answer 4

• Haemolytic anaemias
  
  • Sickle cell disease; thalassemia; spherocytosis; G6PD
  • Vitamin B₁₂ deficiency; SLE: ineffective EPO
• Drugs causing haemolysis ^eg. methyldopa; sulfasalazine
• Malaria: causes haemolysis and DIC
• Gilbert’s syndrome
• Crigler-Najjar syndrome

Question 5

Differentiate Gilbert’s syndrome and Crigler-Najjar syndrome

Answer 5

Both feature unconjugated hyperbilirubinaemia, due to defective conjugating enzymes in hepatocytes

• Gilbert’s syndrome:
  
  • Incidental finding
  • Jaundice during intercurrent illness; stress; fasting
  • No treatment required
• Crigler-Najjar syndrome:
  
  • Type 1 and 2
  • Neonatal jaundice; risk of kernicterus in type 1
  • Kernicterus may occur in later life during illness; stress

Question 6

List three causes of intra-hepatic jaundice

Answer 6

• Viral infection:
  
  • Hepatitis A, B, C, D and E
  • EBV
  • HIV
• Alcohol-related liver disease
• Non-alcoholic fatty liver disease
• Autoimmune hepatitis; PBC; PSC
• Wilson’s disease; haemochromatosis; alpha-1-antitrypsin
• Liver metastases; HCC; cholangiocarcinoma
• TB medication, paracetamol OD

Question 7

Give three causes of post-hepatic or obstructive jaundice

Answer 7

• Gallstones (common bile duct)
• Primary biliary cirrhosis; Primary sclerosing cholangitis
• Surgical strictures ^eg. liver transplantation; cholecystectomy
• Extra-hepatic malignancy ^eg. pancreatic cancer; lymphoma
• Pancreatitis
• Parasitic infection

Question 8

What features indicate obstructive jaundice?

Answer 8

• Pale stools
• Dark urine

Question 9

Request five investigations for a presentation of jaundice

Answer 9

• FBC: haemolysis; infection
• U+Es: hepatorenal syndrome
• LFTs; clotting; amylase
• Viral hepatitis screen: hepatits A, B, C
• Urine dipstick
• Consider:
  
  • Auto-antibody profile
  • Ferritin; caeruloplasmin; alpha-1-antitrypsin
  • Alpha-fetoprotein
  • USS; CT; MRCP

Question 10

List three red flags in jaundice

Answer 10

• Hepatic encephalopathy
  
  • Confusion; altered mental state
  • Poor coordination; ataxia; asterixis; nystagmus
• Severe hepatic dysfunction
  
  • Bruising; purpura; petechiae
• GI bleed ^eg. haematemesis; melaena
• Sepsis
• Marked abdominal tenderness; pain
• Vomiting
• Suspected paracetamol OD