2017A15 Outline the clinical laboratory assessment of liver function.

Name

Abbrev

Normal value

Alanine aminotransferase

ALT

7-55 U/L

Aspartate aminotransferase

AST

8-48 U/L

Alkaline phosphatase

ALP

40-129 U/L

Gamma glutamyl transferase

GGT

8-61U/L

Bilirubin (total)

BR

3-20umol/L

Albumin

ALB

40g/L

International normalized ratio

INR

1

Albumin

·  Most abundant plasma protein

·  Also negative acute phase reactant

·  Maintain plasma oncotic pressure

·  Binding site for ions (calcium), drugs, unconjugated bilirubin, lipid-soluble substance

·  Half life 3/52 hence reduced in chronic disease

Bilirubin

·  Haem breakdown product. Normal <15μmol/L. Scleral icterus >50μmol/L.

·  Unconjugated BR transported from RES to liver on albumin

·  -> BR-monoglucuronide -> BR diglucuronide by UDP-GT

·  ↓Synthetic function -> ↑unconjugated BR

·  ↓Secretion -> ↑conjugated BR

Coagulation factors

·  Liver synthesizes all coag proteins except vWF

·  ↑ PT, aPTT

·  ±↓platelet if splenomegaly

·  Earliest sign of liver damage is ↑INR, due to short half life of VII

Hepatocellular

·  ↑ AST, ALT, BR

·  AST and ALT are present in hepatocyte cytoplasm

·  AST raised more acutely than ALT in setting of injury

AST may be more indicative of alcoholic liver disease

Cholestatic

·  ↑ ALP, GGT, BR (+/- AST, ALT)

·  ALP and GGT are leaked from damaged biliary epitheliocytes

·  Note significant cholestasis can cause hepatocellular injury also

·  Note ALP also has a bone isomer

Note acute alcohol -> ↑GGT

“Glucostat”

·  Plasma glucose may fall in liver failure

·  Liver increases plasma glucose concentration in response to glucagon, catecholamines, corticosteroids

·  Synthesises enzymes important for glycogenolysis and gluconeogenesis

Ammonia

·  Increased in liver failure

Glutathione-S-transferase

·  Leaked in centrilobular damage