Aetiology

1. Prehepatic Causes:
a) Haemolytic anaemia:
– Blood tests: increased reticulocytes, decreased haptoglobins, increased heme and globin
– Aetiologies:
– Intravascular: transfusion reactions, DIC, TTP, HUS
– Extravascular:

• Intracapsular: haemoglobinopathies (e.g., sickle cell anaemia, thalassaemia), cell
  membrane defects (e.g., hereditary spherocytosis), enzyme deficiencies (glucose-6
  phosphate deficiency, pyruvate kinase deficiency)
• Extracapsular: hypersplenism or infections (Malaria, Bartonellosis)

b) Drug-induced:
– Mainly Anti-epileptics and antibiotics
– Specific reactions:

• Haemolysis of RBCs: methyldopa & sulfasalazine
• Hepatitis: paracetamol overdose, Rifampicin
• Cholestasis: co-amoxiclav, flucloxacillin, HRT, combined oral contraceptives,
  corticosteroids
• Hepatic idiosyncratic reactions: NSAIDs, aspirin, amiodarone, sodium valproate

c) Gilbert syndrome:
– Autosomal recessive
– Isolated increased bilirubin
– Genetic or associated with stress situations

d) Crigler-Najjar syndrome:
– Type 1: in neonates, it can lead to kernicterus and death if untreated
– Type 2: not associated with kernicterus or death

2. Hepatic Causes:
a) Viral infections: Viral hepatitis, EBV & HIV
b) Alcohol-related:
– Alcoholic hepatitis
– Alcoholic fatty liver (steatosis)
– with cirrhosis and jaundice from chronic alcohol use

c) Non-alcoholic fatty liver disease
d) Autoimmune liver diseases:

• Primary biliary cirrhosis (associated with antimitochondrial antibodies, linked to
  middle-aged women, sx’s of fatigue/itch & jaundice)
• Primary sclerosing cholangitis (associated with ANCA, linked to IBD and
  cholangiocarcinoma, involves strictures and fibrosis of the bile ducts and is more
  common in men)
• Autoimmune hepatitis (isolated ALT/AST elevation [norm ALP], associated with
  anti-smooth muscle and antinuclear antibodies)

e) Metabolic:
– Haemochromatosis
– Wilson’s disease

f) Biliary tumours:
– Hepatocellular carcinoma (most common primary liver tumour, linked with hepatitis B & C.
Risk factors: men, advanced age, cirrhosis)
– Cholangiocarcinoma (strong link with PSC)
– Gallbladder cancer (linked to hepato-splenomegaly, mass in RUQ [Courvoisier’s sign])

3. Post-hepatic Causes:
a) Gallstones:
– Risk factors: Female, Fertile, Forty, Fat
– Complications: biliary colic, nausea, vomiting, jaundice, acute cholecystitis, cholangitis
(Charcot’s triad), gallstone-associated pancreatitis

b) Surgical strictures (post-cholecystectomy/liver transplant = Post-op Jaundice)

• Complications: chronic cholestasis, recurrent cholangitis, secondary biliary cirrhosis

c) Extrahepatic malignancy:
– Pancreatic cancer (obstruction of the lower common bile duct)
d) Pancreatitis (acute swelling or chronic fibrotic changes = jaundice)
e) Parasitic infections (malaria = haemolysis)