the role of clinical biochemistry in liver disease Flashcards
what are in a liver disease blood test? 7
- Serum bilirubin
- Serum alanine amino-transferase- ALT
- serum aspartate amino-transferase- AST
- Serum alkaline phosphatase- ALP
- serum gamma glutamyl transpeptidase- GGT
- Serum albumin
- Plasma prothrombin
what factors influence serum transaminase findings? 7
- Serum activates of ALT and AST are based on three factors:
- The extent of the damage to the tissues releasing transaminases
- The amount of transaminase in that tissue
- The rate of clearance of the enzyme from the circulation
- The half-life for ALT= 47 hours and AST= 17 hours
- Complicating factor= hepatocytes have two forms of AST- cytosol and mitochondrial
- BMI can increase ALT over guideline range
what are the considerations for interpretations for transaminases? 3
- Biological variables (diurnal variation, dietary factors, race, weight)
- Reference range selection (population exclusion criteria, skewed distribution curve)
- Drugs (prescribed and over the counter)
describe ALP? 4
- Alkaline phosphatase:
catalyses the hydrolysis of the phosphate monoesters - Membrane bound and mainly found in the liver and bone
- In the liver it is found in cells which are next to the canaliculi
- Upregulated (rather than released due to damage) in response to bile duct obstruction and infiltrative or space occupying lesions within the liver
describe GGT? 3
- Mainly found in the hepatobiliary system
- Increase in blood concentration due to induction/ increase
- Synthesis by drug or alcohol, biliary obstruction, liver tumours (smaller increase seen in hepatitis)
what are the routine protein tests? 2
- Serum albumin concentration
- Prothrombin time (INR)
describe the production of bilirubin from haem? 4
- 80% of bilirubin is from the red cells taken up by the reticuloendothelial system for degradation
- Haem oxygenase releases the iron from the haem molecule to form biliverdin
- Biliverdin is then converted to bilirubin by biliverdin reductase
- Bilirubin released is tightly bound to albumin
describe the two different types of bilirubin in the blood stream?
- Conjugated=
- 40% of total
- Water soluble
- Excreted in bile
- If elevated, it appears in the urine giving it a dark colour
- .
- Unconjugated=
- Not water soluble
- Bound to albumin and therefore does not appear in the urine
describe the presenting features of liver disease? 4
- Jaundice (with or without itching)
- Pain
- Non-specific
- Incidental laboratory finding
describe the diagnosis of liver disease? 3
- Clinical presentation
- Pattern of routine liver testes
- How these point to more specific tests including diagnostic radiology
what are the causes of obstructive jaundice? 7
- Extrahepatic:
- Gallstones
- Malignancy
- Pancreatitis
- .
- Intrahepatic
- Hepatocellular disease
- Drug induced cholestasis
- Cholangitis
- Cirrhosis
what are the markers of liver fibrosis? 3
- The FIB-4 score
- NFS
- The enhanced liver function test- combines 3 serum markers measures by immunoassay
what are come causes of hepatocellular disease? 11
- Infections:
- Viral- hepatitis
- Parasitic- malaria
- Bacterial
- .
- Metabolic:
- Alcohol
- Drugs- paracetamol poisoning
- NAFLD
- .
- Autoimmune:
- Primary biliary cholangitis
- Primary sclerosing cholangitis
- .
- Genetic:
- A1AT deficiency
- Hemochromatosis
- Wilson’s disease
describe the investigation into persistent elevated serum ALT? 10
- LFTs including GGT and AST
- Total protein, albumin, immunoglobulins
- Glucose
- Full blood count
- Autoimmune profile
- Iron, transferrin saturation, ferritin
- Copper
- Viral studies
- Carbohydrate deficient transferrin
- Drug history
what are the NAFLD risk factors? 8
- Present when >5% of hepatocytes are steatotic in patients who do not consume excessive alcohol
- Age
- Males
- Metabolic syndrome
- High in Hispanic people
- Diet- saturated fat, high fructose
- Sleep apnoea
- Genetic