Liver Function Tests Flashcards
Liver Functions
Protein synthesis (albumin, clotting factors, transport proteins, protease inhibitors), Detoxification, Metabolism of hormones and drugs, Bile acid synthesis, Glycogen storage, Endogenous cholesterol synthesis, Ketone synthesis
Causes of hepatocellular damage
Viral infections e.g. HAV, HBV, HCV, CMV
Hypoxia, anoxia e.g. AMI, CHF, thromboembolic diseases
Toxins e.g. alcohol, paracetamol, halothane
Accumulation of metabolites e.g. glycogen, iron, copper, alpha-1 antitrypsin
Causes of biliary tree obstruction
Intrahepatic
- HCC, liver metastasis, PBC
Extrahepatic
- intraluminal e.g. gallstones, parasitic obstruction
- luminal e.g. cholangioCA, PSC
- extraluminal e.g. pancreatic head CA, duodenal CA, CA metastasis
“True” LFT
Protein synthesis
- plasma albumin
- clotting factors except factor VIII (prothrombin time; INR) – more sensitive and earlier changes in response to liver function due to short half-life
Detoxification
- indocyanine green uptake (rarely done)
Common elements of LFT
Total protein, albumin Total bilirubin ALP GGT ALT AST (excluded nowadays due to lower specificity than ALT -- secreted by muscle cells and RBC as well)
Albumin and total protein
Albumin
- synthesised exclusively by hepatocytes
- decreases with CLD
- leads to oedema
Total protein
- albumin + globulin (Ig is not synthesised in liver)
- albumin > globulin usually
- increased IgA production in liver cirrhosis (due to defective detoxification of gut antigens by liver/ bacterial overgrowth –> trigger mucosal defence) and decreased albumin production
==> reversed A:G ratio
Bilirubin Metabolism
Haem degradation –> unconjugated bilirubin (not water soluble) –> form complex with albumin and transported to liver –> conjugation in liver –> secrete to gut via biliary tree –> ferment to stercobilin and excrete in gut or enter enterohepatic circulation and back to liver/ excreted in kidneys
==> increase in conjugated bilirubin/ bilirubinuria = BILIARY TREE OBSTRUCTION (impaired removal of bilirubin due to COMPLETE obstruction)
==> increase in unconjugated = haemolysis, blood transfusion, drugs e.g. rifampicin
ALP/GGT
Present on biliary canaliculi (responsible for releasing bilirubin into bile canaliculi)
Concentration increases with BILIARY TREE OBSTRUCTION (enzymes induced on surface and then leak back into circulation)
ALT/AST
Present in high concentrations in hepatocytes
Concentration increases with acute liver cell damage as enzymes are released to the plasma
HEPATOCELLULAR DAMAGE
ALT levels: 300U/L = any liver disease; 1000U/L = acute hepatitis; 10000U/L = fulminant hepatitis
AST only used in alcoholism (AST/ALT >2) and acute pancreatitis
LFT in chronic pathologies
Abnormalities may not be present in CLD until far advanced disease
- slow onset and physiological compensation
Non-specificities of LFT: albumin, ALP, GGT, bilirubin, AST
Hypoalbuminaemia/ Hypoproteinaemia
- malnutrition, malabsorption, fluid overload
ALP
- different isoenzymes found in liver, bone (fractures), placenta, intestine and kidneys
GGT
- enzyme induction due to alcohol, anti-convulsants
Hyperbilirubinaemia
- unconjugated bilirubinaemia from haemolysis
AST
- AMI and myositis
Possible alternatives:
- assess ALP isoenzyme to confirm source; interpret ALP in conjunction with GGT
- assess conjugated bilirubin
Assessment of severity of acute hepatitis, cholestasis, CLD
Acute hepatitis
- magnitude of ALT/AST elevation
- PT
- plasma ammonia (suspected hepatic encephalopathy)
Cholestasis
- concentration of bilirubin (only elevated in complete obstruction)
CLD
- albumin concentration
- PT
- high plasma ammonia/ low plasma urea
- AST/ALT elevation less significant as liver is shrunken
Cholestasis types and lab results
Intrahepatic: HCC, liver metastasis
- obstruction of bile flow (bile remains in canaliculi in liver - bile ducts not enlarged)
- ALP/ GGT elevation
- Bilirubin normal; can be abnormal if very severe or in PBC
- urine bilirubin normal, pigmented stool
Extrahepatic:
Partial e.g. R/L hepatic duct –> bile still able to drain sufficiently
- ALP/ GGT elevated, bilirubin may be elevated and urine bilirubin elevated, pigmented stool
Complete e.g. common hepatic duct/ bile duct –> no drainage of bile
- medical emergency!! – risk of bacteria colonising bile duct opening and migrating up –> acute cholangitis
- need triple antibiotics and relief of obstruction
- ALP/ GGT elevated, elevated bilirubin and urine bilirubin with tea-coloured urine, PALE stool, steatorrhea
Ix of acute hepatitis
Viral serology
Drugs/ Toxins: plasma ethanol, paracetamol
Ix of CLD
Hepatitis B, C
Iron overload (iron profile) Wilson's disease (urine Cu, ceruloplasmin)
(autoimmune markers)
