Yellow pigmentation of skin, sclera and mucosae due to increased
plasma bilirubin (visible at >35umol/L). Classified by either site of
problem (pre-hepatic, hepatocellular or cholestatic/obstructive) or
by type of circulating bilirubin (conjugated or unconjugated).
Bilirubin formed frm breakdown
of haemoglobin. 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 again by
the liver (via enterohepatic
circulation), the rest is converted
to urobilinogen by gut bacteria.
Urobilinogen is either reabsorbed
and excreted by the kidneys or
converted to stercobilin which
colours faeces brown.
Pre-hepatic
Either increased bilirubin production (haemolysis),
reduced liver uptake or reduced conjugation. Causes
unconjugated bilirubin to enter blood. As it is water
insoluble it does not enter urine resulting in unconjugated
hyperbilirubinaemia. Causes: Physiological (neonatal),
haemolysis, dyserythropoiesis, glucuronyl transferase
deficiency (Gilbert’s syndrome), Crigler-Najjar syndrome.
Hepatic/Hepatocellular
Hepatocyte damage, with some cholestasis. Causes:
Viruses: hepatitis A,B,C, etc, CMV, EBV. Drugs ie
paracetamol, sodium valproate, halothane, flucloxacillin
etc. Alcoholic hepatitis. Cirrhosis. Liver mets/abscess.
Haemochromatosis. Autoimmune hepatitis. Septicaemia.
Leptospirosis. Alpha 1-antitrypsin deficiency. Budd-chiari.
Wilson’s disease. Failure to excrete conjugated bilirubin
(Dublin-Johnson syndrome). Rotor syndrome. Right heart
failure. Toxins. Fungi.
Post-hepatic/cholestatic/obstructive
Blocked common bile duct causes
conjugated bilirubin to overspill into
the blood. Causes conjugated
hyperbilirubinaemia. Water soluble
so excreted into urine making it dark.
Less conjugated bilirubin enters
bowel so faeces become pale. If
severe can cause pruritis, best
treated by relief of obstruction.
Causes: Common bile duct
gallstones, pancreatic cancer, lymph
nodes at porta hepatis, drugs ie
paracetamol, sodium valproate,
halothane, flucloxacillin etc.
Cholangiocarcinoma, primary
sclerosing cholangitis, primary biliary
cirrhosis, choledochal cyst, biliary
atresia, Mirrizi’s syndrome
(obstructive jaundice secondary to
compression of the common hepatic
duct by a gallstone impacted in the
cystic duct, often associated with
cholangitis).
Signs & Symptoms
Signs: Signs of chronic liver disease, hepatic
encephalopathy, lymphadenopathy, hepatomegaly,
splenomegaly, ascites, palpable gall bladder (Courvoisier’s
law: palpable gallbladder + painless jaundice = cause other
than gallstones), dark urine + pale stools = obstructive
jaundice
History
Ask about: blood transfusions, IV drug use, body piercings,
tattoos, sexual activity, travel abroad, jaundiced contacts, family
history, alcohol, medications
Investigations
Urine: Check bilirubin – absent in pre-hepatic causes, and urobilinogen – absent in obstructive jaundice.
Haematology: FBC, clotting, blood screen, reticulocyte count, Coomb’s test. Biochemistry: U&E, LFT (bilirubin,
ALT, AST, alk phos, gamma-gt, total protein, albumin)(Albumin & INR show hepatic synthetic function, raised
transaminases (ALT and AST) show hepatocyte damage, raised alk phos shows obstructive jaundice but also
other things). USS: bile duct dilation >6mm, gallstones, hepatic metastases, pancreatic mass. ERCP: if bile
duct dilation and LFTs not improving. MRCP/ endoscopic USS: if conventional USS shows gallstones but no
definite common bile duct stones. Liver biopsy: if bile ducts are normal. Abdo CT/MRI: if malignancy sudpected
clinically. Consider screening tests for suspected liver disease