Jaundice

Jaundice

1. 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).

2. 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.

3. 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.

4. 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.

5. 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).

6. 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

7. History

   • Ask about: blood transfusions, IV drug use, body piercings, tattoos, sexual activity, travel abroad, jaundiced contacts, family history, alcohol, medications

8. 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