Liver Function Testing - CBS

Explain bilirubin metabolism (4 key steps)

• RBCs broken down (by spleen and liver) into haem, globin (Recycled) and Fe (recycled) - Haem, biliverdin, which forms bilirubin

• unconjugated bilirubin (water insoulable) transported to liver - conjugated by hepatocytes

• conjugated bilirubin secreted into bile - transports bilirubin into small intestine

• Gut bacteria convert bilirubin into urobilinogen:

  • 80% excreted in faeces as stercobilin

  • 2% excreted in urine as urobilin

  • 18% enterohepatic circulation

Explain the causes of prehepatic, hepatic, and posthepatic jaundice. What levels of unconjugated and conjugated bilirubin are there, and is any present in urine?

• prehepatic - Excess RBC breakdown causes excess unconjugated bilirubin, no bilirubin in urine

• hepatic - hepatocyte dysfunction, impaired uptake, conjugation, or secretion - excess of both types, bilirubin in urine

• posthepatic - obstruction of bile flow into GI tract (gallstones) - inceased conjugated bilirubin, bilirubin in urine

Explain Gilbert syndrome, Crigler-Najjar syndrome, and Dubin-Johnson syndrome

• Gilbert syndrome - reduces glucuronyl transferase activity, slightly reduced bilirubin conjugation

• Crigler-Najjar syndrome - autosomal recessive (type 1) no glucuronyl transferase, auto dominant (typep 2) reduced glucoronyl transferase

• Dubin-Johnson syndrome - reduced excretion of bilirubin (into bile) from hepatocytes, so increased conjugated bilirubin

Explain neonatal jaundice

• increased bilirubin production due to higher mass of RBCs (so increased breakdown).

• often mild and transient.

Explain the clinical significance of alkaline phosphatase (ALP)

• elevated in cholestasis, bile duct obstruction (gallstones or tumours)

• may also be elevated in bone disease, so further testing confirms

Explain the clinical significance of GGT

• located in biliary epithelium

• elevated in biliary irritation and liver disease

• certain medications, alcohol, and inflammation increase GGT

• helps confirm liver (rather than bone) problems are origin of raised ALP

Explain the significance of AST (aspartate transaminase) and ALT (alanine transaminase) in liver disease, and explain how the AST:ALT ratio can be used clinically

• intracellular hepatocyte enzymes, released when damaged

• ALT higher than AST - viral hepatitis, and non-alcoholic fatty liver disease

• AST higher - Alcohol-related liver disease

Explain how albumin and PT/INR assess liver synthetic function

• albumin - synthesised by liver, reduced in chronic liver disease, causes oedema and ascites

• PT/INR - reflects clotting factor production, useful for identifying acute liver failure, short half life makes early indicator of liver dysfunction

Explain how liver disease severity can be assessed biochemically in terms of:

1) bilirubin

2) albumin

3) prothrombin

• bilirubin assesses excretory function

• albumin - protein synthesis

• PT/INR - clotting factor synthesis