Jaundice

Question 1

Define jaundice.

Answer 1

Yellow discolouration of skin, sclerae and mucosae due to increased plasma bilirubin.

Question 2

Normal and abnormal values of bilirubin.

Answer 2

Normal plasma bilirubin levels are below 21 micromol/L.

Clinical jaundice may not become apparent until serum bilirubin is greater than 51 micromol/L.

Question 3

Normal bilirubin metabolism.

Answer 3

Its metabolism occurs in 3 phases — pre-hepatic, intra-hepatic, and post-hepatic.

Pre-hepatic:
1. Haemoglobin is broken down into globin and haem.
2. Haem is broken down into porphyrin and iron.
3. Porphyrin is converted to unconjugated bilirubin.
4. Bilirubin binds to plasma albumin and transported to the liver.
5. This is taken up by the liver.

Intra-hepatic:
5. In the liver, the bilirubin is conjugated with glucuronic acid by hepatocytes, making it water soluble, and can be excreted in bile.

Post-hepatic:
6. Conjugated soluble bilirubin is secreted in bile and transported through the liver + cystic ducts.

7. It is either stored in the gallbladder or passes into the duodenum.
8. Some is taken up again by liver – enterohepatic circulation.
9. The rest is either: (1) excreted in the stool or (2) converted to urobilinogen by gut bacteria.
10. This is either reabsorbed or excreted by kidneys, or converted to stercobilin, which colours faeces brown.

Question 4

Give 4 causes of pre-hepatic jaundice.

Answer 4

1. Haemolytic anaemias - sickle cell anaemia
2. Malaria
3. Drugs.
4. Gilbert’s syndrome (deficiency in UDP Glucuronyl Transferase).
5. Crigler-Najjar syndrome.

Question 5

What is Gilbert’s syndrome?

Answer 5

Deficiency in UDP Glucuronyl Transferase.

Resulting in raised unconjugated bilirubin.

Question 6

Give 4 causes of hepatic jaundice.

Answer 6

1. Viral hepatitis.
2. Alcoholic hepatitis.
3. Drugs.
4. Cirrhosis.
5. Non-alcoholic fatty liver disease (NAFLD).
6. Autoimmune liver disorders.
7. Metabolic causes of intra-hepatic jaundice.
8. Malignancy of the biliary system.

Question 7

Give 5 causes of post-hepatic jaundice.

Answer 7

1. Gallstones.
2. Surgical strictures.
3. Extra-hepatic malignancy.
4. Pancreatitis.
5. Parasitic infection.
6. Blocked stent.

Question 8

What can cause raised unconjugated bilirubin?

Answer 8

A pre-hepatic problem e.g. haemolysis due to sickle cell disease, spherocytosis, hypersplenism, Gilbert’s syndrome etc.

Question 9

What can cause raised conjugated bilirubin?

Answer 9

Raised conjugated bilirubin indicates a cholestatic problem e.g. liver disease (hepatic) or bile-duct obstruction (post-hepatic).

Question 10

Describe the urine and stools in someone with pre-hepatic jaundice.

Answer 10

Urine and stools are normal. There is no itching and the LFT’s are normal.

Question 11

Describe the urine and stools in someone with cholestatic jaundice.

Answer 11

Dark urine and pale stools. There may be itching and LFT’s are abnormal.

Question 12

Give 3 symptoms of jaundice.

Answer 12

1. Biliary pain.
2. Rigors - indicate an obstructive cause.
3. Abdomen swelling.
4. Weight loss.

Question 13

Tests to investigate jaundice.

Answer 13

Tests:
* Liver enzymes:
- Very high AST/ALT suggests liver disease, but there are some exceptions.
- E.G. AST can be high in muscle injury

• Biliary obstruction:
• 90% have dilated intrahepatic bile ducts on ultrasound.

Question 14

Give 3 causes of unconjugated hyperbilirubinaemia (pre-hepatic jaundice).

Answer 14

haemolysis - malaria, DIC. ineffective erythropoiesis. impaired hepatic uptake - drugs (contrast agents, rifampicin), RHF. impaired conjugation - Gilbert’s syndrome, Crigler-Najjar.

Question 15

What will the urine and faeces look like in conjugated hyperbilirubinaemia (hepatic/post-hepatic jaundice)?

Why?

Answer 15

Urine = dark - conjugated bilirubin is soluble, so excreted in urine.

Faeces = pale - less conjugated bilirubin enters gut.

Question 16

Give 3 causes of conjugated hyperbilirubinaemia due to hepatocellular dysfunction.

Answer 16

Viruses - hep, CMV, EBC. drugs - paracetamol od, isoniazid, rifampicin, pyrazinamide, statins, sodium valproate. alcohol. cirrhosis. liver metastases/abscesses. haemachromatosis. autoimmune hepatitis. septicaemia. syphilis. alpha1-antitrypsin deficiency. Budd-Chiari. Wilson’s disease. Right heart failure.

Question 17

Give 3 causes of conjugated hyperbilirubinaemia due to impaired hepatic excretion (cholestatic / obstructive jaundice).

Answer 17

Primary biliary cirrhosis, primary sclerosing cholangitis, drugs, common bile duct gallstones, pancreatic cancer, compression of the bile duct, choledochal cyst.