GI pathology 2 - jaundice

Question 1

What is jaundice?

Answer 1

Yellowing of the skin, sclerae and mucosae from ↑plasma bilirubin

Question 2

How is jaundice classifiied?

Answer 2

• Site of the problem
  
  • prehepaatic
  • hepatocellular
  • cholestatic/obstructive
• Type of circulating bilirubin
  
  • conjugated
  • unconjugated

Question 3

Urine colour in unconjugated hyperbilirubinaemia and conjugated hyperbilirubinaemia

Answer 3

Unconjugated hyperbilirubinaemia

• as unconjugated bilirubin is water-insoluble, it does not enter urine

Conjugated hyperbilirubinaemia

• as conjugated bilirubin is water soluble, it is excreted in the urine making it dark

Question 4

Jaundice investigations

Answer 4

• Urine
  
  • bilirubin
  • uribilinogen
• Haematology
  
  • FBC, reticulocyte count, blood film
  • clotting
  • Coombs’ test
  • haptoglobins
• Chemistry
  
  • U&Es, LFTs, GGT (Gamma-glutamyl transferase)
  • total protein, albumin
• Microbiology
  
  • blood and other cultures
  • hepatitis serology
• Ultrasound
• ERCP
• MRCP
• Liver biopsy
• CT/MRI

Question 5

What does lack of urinary bilirubin suggest about the cause of jaundice?

Answer 5

Pre-hepatic jaundice

Question 6

What may be the cause of jaundice when bilirubin is absent from urine?

Answer 6

Obstructive jaundice

Question 7

Pathophysiology of prehepatic jaundice

Answer 7

In pre-hepatic jaundice, there is excessive red cell breakdown which overwhelms the liver’s ability to conjugate bilirubin. This causes an unconjugated hyperbilirubinaemia.

Question 8

Pathophysiology of intra-hepatic jaundice

Answer 8

In hepatocellular jaundice, there is dysfunction of the hepatic cells. The liver loses the ability to conjugate bilirubin, but in cases where it also may become cirrhotic, it compresses the intra-hepatic portions of the biliary tree to cause a degree of obstruction.

This leads to both unconjugated and conjugated bilirubin in the blood, termed a ‘mixed picture’.

Question 9

Pathophysiology of post-hepatic jaundice

Answer 9

Post-hepatic jaundice refers to obstruction of biliary drainage. The bilirubin that is not excreted will have been conjugated by the liver, hence the result is a conjugated hyperbilirubinaemia.

Question 10

Pre-hepatic causes of jaundice

Answer 10

• Haemolytic anaemia
• Gilbert’s syndrome
• Criggler-Najjar syndrome

Question 11

Intra-hepatic causes of jaundice

Answer 11

• Alcoholic liver disease
• Viral hepatitis
• Iatrogenic, e.g. medication
• Hereditary haemochromatosis
• Autoimmune hepatitis
• Primary biliary cirrhosis or primary sclerosing cholangitis
• Hepatocellular carcinoma

Question 12

Post-hepatic causes of jaundice

Answer 12

• Intra-luminal causes, such as gallstones
• Mural causes, such as cholangiocarcinoma, strictures, or drug-induced cholestasis
• Extra-mural causes, such as pancreatic cancer or abdominal masses (e.g. lymphomas)