Jaundice
Jaundice (icterus) refers to yellow pigmentation of skin, sclerae and mucosae due to
increased plasma bilirubin
 visible at >35micromol/L
Classified by site of problem (pre-hepatic, hepatocellular, post-hepatic) or by the type
of circulating bilirubin (conjugated or unconjugated)
Kernicterus is seen in infants with unconjuated hyperbilirubinaemia and involves
deposition of jaundice in the basal ganglia, which can cause opisthotonus (state of a
severe hyperextension and spasticity in which an individual's head, neck and spinal
column enter into a complete "bridging" or "arching" position)
Bilirubin metabolism
Bilirubin is formed from the breakdown of haemoglobin. It is conjugated with
glucuronic acid by hepatocytes, making it water soluble. Conjugated bilirubin is
secreted into bile and passes out into the gut. Some is taken up by the liver again and
the rest to converted to uribilinogen by gut bacteria. Urobilinogen is either
reabsorbed and excreted by the kidneys, or converted to stercobilin which colours
faeces brown.
Pre-hepatic jaundice
Increased bilirubin production – haemolysis, decreased liver uptale or decreased
conjugation  unconjugated bilirubin enters the blood
As it is water insoluble, it does not enter urine resulting in unconjugated
hyperbilirubinaemia
Causes: physiological (neonatal), haemolysis, dyserythropoeisis (disorder in the
production of red blood cells), Gilberts and Crigler-Najjar Syndromes
Hepatocellular Jaundice
Hepatocyte damage, usually with some cholestasis
Causes: viral hepatitis (A,B,C, CMV, EBV), drugs (see table), alcoholic hepatitis,
cirrhosis, liver mets/abscess, haemochromatosis, autoimmune hepatitis, septicaemia,
leptospirosis, alpha-1-antitrypsin deficiency, Budd chiari, Wilson’s disease, Dubin
Johnson and Rotor syndromes (failure to excrete conjugated bilirubin)
Cholestatic (Obstructive) Jaundice
If the common bile duct is blocked, conjugated bilirubin overspills into the blood
causing conjugated hyperbilirubinaemia. Being water soluble, it is excreted in urine,
making it dark. Less conjugated bilirubin enters the bowel, and the faeces become
pale. When severe it can be associated with an intractable pruritus which is best
treated by relief of the obstruction.
Causes: common bile duct gallstones, pancreatic cancer (head of pancreas), lynph
nodes at the porta hepatis, drugs (see Table), cholangiocarcinoma, PSC, PBC, biliary
atresia, Mirrizi’s syndrome (obstruction secondary to compression of common hepatic
duct by gallstone impacted in cystic duct)
Clinical Features:
Ask about – blood transfusions, IVDU, piercings/tattoos, sexual activity, travel,
contacts, FH, alcohol, all medications
Examine for: signs of chronic liver disease, hepatic encephalopathy,
lymphadenopathy, hepatomegaly, splenomegaly, ascites, and palpable gall bladder
(which in conjunction with painless jaundice suggests cause other than gallstones)
Pale stools with dark urine = obstructive jaundice
Tests:
screening tests in suspected liver disease see below
Urine – nilirubin is absent in pre-hepatic causes, urobilinogen is absent in posthepatic causes
Haematology – FBC, Clotting, blood film, reticulocyte count, Coomb’s test
Biochemistry – U+E, LFT (bili, ALT, AST, alk phos, GGT, total protein, albumin)
USS – Are the bile ducts dilated >6mm (obstruction)?
Are there gallstones, hepatic mets or a pancreatic mass?
ERCP – if bile ducts are dilated and LFT not improving
Perform a liver biopsy if bile ducts are normal
Consider CT/MRI if abdominal malignancy suspected clinically
NB Causes of Jaundice in a previously stable patient with Cirrhosis:
Sepsis – especially from UTI, pneumonia
Alcohol
Drugs
GI bleed
Drug-Induced jaundice
Haemolysis
Hepatitis
Cholestasis
Antimalarials
Dapsone
Paracetamol overdose
Anti-TB (r, I, p)
Statins
Sodium valproate
MAOIs
Halothane
Antibiotics – fluclox, fusidic acid
Anabolic steroids
OCP
Prochlorperazine
Chlorpromazine
Sulphonyureas
Gold
What is a Liver Screen?
Tests for suspected liver diseases:
VirusesEBV, CMV, Hep B and C serology
Iron studies
for haemochromatosis – raised ferritin and iron, low TIBC
Alpha-1-antitrypsin deficiency
Wilson’s disease –
serum copper and caeruloplasmin reduced
PBC –
raised anti-mitochondrial antibodies
PSC –
raised ANA, AMA and ANCA may be +ve
AIH –
raised ANA and anti-smooth-muscle antibodies
All immunoglobulins: raised IgA in alcoholic liver disease, IgG in AIH and IgM in
PBC
Hepactocellular carcinoma – raised alpha-feto-protein
Conjugated and unconjugated bilirubin