creation date: 2026-08-04 15:56
tags: Workups
Jaundice
Background
Jaundice, also known as hyperbilirubinemia, refers to a yellow discolouration of body tissue due to the accumulation of excess bilirubin.
Normal serum total bilirubin levels are <17 mcmol/L
- Conjugated (direct) bilirubin 2–9 mcmol/L
Pathophysiology
The breakdown of bilirubin involves several steps and dysfunction of any of the steps may lead to jaundice.
Pre-hepatic:
- Senescent or defective RBCs break down into heme and iron
- Heme undergoes reactions which become biliverdin and then bilirubin
Hepatic:
- Bilirubin (unconjugated) in circulation gets transported to hepatocytes via albumin (provides solubility in blood)
- Bilirubin is taken into the hepatocyte alone and bound in the cytosol
- Bilirubin is then conjugated with glucuronic acid
Post-hepatic:
- Bilirubin (conjugated) is released into bile to be secreted into the small bowel
- Conjugated bilirubin is not reabsorbed through the intestine mucosa
- Colonic bacteria deconjugates and metabolizes bilirubin into urobilinogen, of which 20% is reabsorbed (80% excreted via feces)
- Reabsorbed urobilinogen undergoes enterohepatic circulation and excreted via the kidney and urine
Differential Diagnosis
Conjugated hyperbilirubinemia
Decreased intrahepatic excretion of bilirubin:
- Hepatocellular disease
- Viral hepatitis A, B, D
- Alcoholic hepatitis
- Cirrhosis
- Metabolic dysfunction-associated steatohepatitis
- EBV, MV, HSV
- Wilson’s disease
- Autoimmune disease
- Cholestatic liver disease
- Primary biliary cholangitis
- Primary sclerosing cholangitis
- Infiltrative disease
- Amyloidosis
- Lymphoma
- Sarcoidosis
- Tuberculosis
- Sepsis or hypoperfusion states
- Total parenteral nutrition
- Drugs
- OCPs
- Rifampin
- Probenecid
- Steroids
- Chlorpromazine
- Arsenic
- Herbal medications (eg. Jamaican bush tea, kava kava)
- Hepatic crisis in sickle cell disease
- Pregnancy
Extrahepatic cholestasis (biliary obstruction):
- Choledocholithiasis
- Tumours
- Extrahepatic biliary atresia
- Acute pancreatitis or chronic pancreatitis
- Strictures
- Parasitic infections
Others:
- Dubin-Johnson syndrome (defect of canalicular organic anion transport)
- Rotor syndrome (defect of sinusoidal reuptake of conjugated bilirubin)
Unconjugated hyperbilirubinemia
Excess production of bilirubin:
- Hemolytic anemia
- Extravasation of blood in tissues
- Dyserythropoiesis
Reduced hepatic uptake of bilirubin:
- Gilbert syndrome
Impaired conjugation:
- Crigler-Najjar syndrome
- Hyperthyroidism
- Estrogen
Initial Evaluation
History
History should include the duration of jaundice and elucidate associated symptoms which may distinguish etiology.
- Joint ache
- Rash
- Myalgia
- Changes in urine/stool
- Fever/chills
- Right upper quadrant pain
History should include:
- Drug and alcohol use
- Other toxic substances
- Risk factors for hepatitis (travel, unsafe sex, alcohol use)
- HIV status
- Personal or family history of any inherited disorders or hemolytic disorders
Physical Exam
Examination should include:
- Skin and and ocular sclera for severity of jaundice
- Abdominal exam
- Muscle wasting
- Signs of chronic liver disease
- Palpable lymph nodes
- Volume status
Investigations
Laboratory studies include:
- Liver function tests
- Serum bilirubin
- Hepatocellular workup (viral serologies, autoimmune antibodies, serum ceruloplasmin, ferritin)
- Cholestatic workup (abdominal ultrasound, CT, MRCP etc.)