Bilirubin and Jaundice

Bilirubin and Jaundice

Unconjugated hyperbilirubinaemia

• Pre-hepatic (acholuric)
• Hepatocellular

Conjugated hyperbilirubinaemia

• Hepatocellular
• Intrahepatic obstruction
• Extrahepatic obstruction

Note:

• <20% of bilirubin conjugated = Unconjugated hyperbilirubinaemia
• >50% of bilirubin conjugated = Conjugated hyperbilirubinaemia

Unconjugated hyperbilirubinaemia

Classification:

• Pre-hepatic (acholuric) (vast majority. Secondary to increased bilirubin production
• Hepatocellular. Secondary to reduced hepatocyte uptake of bilirubin.

Cause:

• Haemolysis (must be 2 x normal to be significant) – Rarely causes rise over 70 micromol/L
  • haemolytic anaemia
  • erythroblastosis foetalis
  • pernicious of prematurity
• Congenital
  • Gilbert disease (GD)
  • Crigler-Najjar syndrome (CS)
• Iatrogenic
  • Drugs: chloramphenicol, gentamicin, pregnanediol
• Physiological
  • Neonatal jaundice and Breast-milk jaundice

Conjugated hyperbilirubinaemia

• Hepatocellular – Diminished hepatocyte function. If severe can be associated with unconjugated hyperbilirubinemia due to total inability to conjugate bilirubin
  • hepatitis – Viral, toxic, alcoholic, autoimmune
  • cirrhosis
  • leptospirosis
  • Drugs
    • liver parenchymal injury (toxic hepatitis)
    • halothane, paracetamol, methyldopa, phenytoin, barbiturates, MAOI, sulphonamides
• Intrahepatic obstruction (hepatic canalicular disorders)
  • Hepatitis (viral)
  • Cirrhosis (Primary biliary cirrhosis)
  • Intrahepatic cholestasis
  • Drugs
    • indomethacin, erythromycin
    • chlorpromazine, isoniazid, flucloxacillin, OCP
  • Congenital
    • Dubin–Johnson syndrome
    • Rotor syndrome
• Extrahepatic obstruction
  • Calculi, tumour, scar tissue in common bile duct or hepatic excretory duct
  • Gallstones, carcinoma of head of pancreas and lymphoma with extrinsic nodal compression of the porta hepatis are commonest

Serum Bilirubin

Measures unconjugated and conjugated (Normal range: 6-24 micromol/L). Initial result details TOTAL bilirubin measured

• Clinically detectable jaundice
  • Conjugated hyperbilirubinaemia – 35 micromol/L
  • Unconjugated hyperbilirubinaemia – 45 micromol/L
• Ratio of unconjugated and conjugated helps to determine cause of hyperbilirubinaemia
  • Predominantly unconjugated (<20% bilirubin conjugated)
  • Predominantly conjugated (>50% bilirubin conjugated)

Urine Bilirubin

Ward Test Urine (WTU) or laboratory for may assess urine for Urine bilirubin and Urine urobilinogen

Urine bilirubin:

• Conjugated bilirubin excreted into GIT is reabsorbed in very small amounts
• Kidneys filter soluble form and it appears in urine
• Bilirubin is NOT normally present in urine
• Urine -dark in colour, usually brown with yellow foam
• Presence of bilirubin implies Conjugated hyperbilirubinemia

Urine urobilinogen:

• Normal: 1-4mg/day (compared to 250mg in stool)
• Absence of urobilinogen
  • Conjugated – Complete extrahepatic obstruction or Broad spectrum antibiotics destroying intestinal flora
• Low levels of urobilinogen
  • Unconjugated – Congenital (Crigler-Najjar syndrome, Gilbert syndrome)
  • Conjugated – Complete extrahepatic obstruction
• Increased levels
  • Unconjugated – haemolysis, highly alkaline urine or eating bananas up to 48 hours before test

CCC Differential Diagnosis Series
NEURO	Anosmia, Ataxia, Blepharospasm, Bulbar and Pseudobulbar palsy, Central Pontine Myelinosis, Cerebellar Disease, Chorea, Cranial nerve lesions, Dementia, Dystonia, Exophthalmos, Eye trauma, Facial twitches, Fixed dilated pupil, Horner syndrome, Loss of vision, Meningism, Movement disorders, Optic disc abnormality, Parkinsonism, Peripheral neuropathy, Radiculopathy, Red eye, Retinal Haemorrhage, Seizures, Sudden severe headache, Tremor, Tunnel vision
RESP	Bronchial breath sounds, Bronchiectasis, High airway pressures, Massive haemoptysis, Sore throat, Tracheal displacement
CVS	Atrial Fibrillation, Bradycardia, Cardiac Failure, Chest Pain, Murmurs, Post-resuscitation syndrome, Pulseless Electrical Activity (PEA), Pulsus Paradoxus, Shock, Supraventricular tachycardia (SVT), Tachycardia, VT and VF, SVC Obstruction
GIT	Abdominal distension, Abdominal mass, Abdominal pain, Asterixis, Dysphagia, Hepatomegaly, Hepatosplenomegaly, Large bowel obstruction, Liver palpation abnormalities, Lower GI haemorrhage, Malabsorption, Medical causes of abdominal pain, Rectal mass, Small bowel obstruction, Upper GI Haemorrhage
GUT	Genital ulcers, Groin lump, Scrotal mass, Urine colour, Urine Odour, Urine transparency,
MSK	Arthritis, Shoulder pain, Wasting of the small muscles of the hand
DERM	Palmar erythema, Serious skin signs in sick patients, Thickened Tethered Skin, Leg ulcers, Skin Tumour, Acanthosis Nigricans
ENDO	Diabetes Insipidus, Diffuse Goitre, Gynaecomastia, Hirsutism, Hypoglycaemia, SIADH, Weight Loss
HAEM	Splenomegaly
PAEDS	Floppy infant
MISC	Anaphylaxis, Autoimmune associated diseases, Clubbing, Parotid Swelling, Splinter haemorrhages, Toxic agents and abnormal vitals, Toxicological causes of cardiac arrest
IMAGING	CHEST: Atelectasis, Hilar adenopathy, Hilar enlargement on CXR, Honeycomb lung, Increased interstitial markings, Mediastinal widening on mobile CXR, Pulmonary fibrosis, Pseudoinfiltrates on CXR, Pulmonary opacities on CXR, ABDO: Gas on abdominal X-ray, Kidney mass, BRAIN: Intracranial calcification, Intracranial structures with contrast, Ventriculomegaly, OTHER: Pseudofracture on X-Ray,
LABS	LOW: Anaemia, Hypocalcaemia, hypochloraemia, Hypomagnesaemia,  HIGH: Bilirubin and Jaundice, Hyperammonaemia, Hypercalcaemia, Hyperchloraemia, Hyperkalaemia, Hypermagnesaemia,  ACID BASE: Acid base disorders, Resp. acidosis, Resp. alkalosis, Creatinine, CRP, Dipstick Urinalysis, Laboratory Urinalysis, Liver function tests (LFTs), Pleural fluid analysis, Urea, Urea Creatinine Ratio, Uric acid, Urinalysis, Urine Electrolytes

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