Liver function tests Flashcards
True or false: Liver disease is he fifth biggest killer in the UK and the only major cause of death that is increasing
True
True or false: Around 1 in 20 people in the UK have tested positive for abnormal liver function.
False
Around 1 in 25 people in the UK have tested positive for abnormal liver function.
Liver gets what percentage of blood from the portal vein?
70%
Liver gets what percentage of blood from the hepatic artery.
30%
What are the main Liver Functions?
- Excretion of nitrogen: makes urea.
- Protein biosynthesis: albumin, clotting factors.
- Metabolism of many drugs.
- Metabolism: main site of gluconeogenesis, makes very low density lipoprotein.
- Formation of Bile:
Phospholipids, Bile salts, Cholesterol, Bilirubin- a breakdown product of haem
What is jaundice?
- Abnormally high plasma concentration of bilirubin.
- >21 mmol/l
- Prehepatic.
- Hepatocellular.
- Cholestatic.
Metabolism and transport of bilirubin
What is Prehepatic jaundice characterised by?
- Markedly increased unconjugated bilirubin in blood due for example to haemolytic anaemia.
- No bilirubin in urine.
- Bound to albumin so not filtered by kidney.
- Detected with dipsticks impregnated with diazo reagent.
- Urobilinogen in urine.
- Urobilinogen is water soluble so it can be excreted in urine.
- Doesn’t recycle via liver because uptake system is saturated.
- Orange urine due to conversion of urobilinogen to urobilin.
- Detectable with Erlich’s reagent (p-dimethylaminobenzaldehyde).
- Large amounts of stercobilinogen in the stools
Prehepatic jaundice
What are some causes of Hepatocellular damage?
Direct damage to the liver
- Viruses: Hepatitis A, B and C most common.
- Latter two can become chronic infections.
- Poisons and drugs: carbon tetrachloride (dry cleaning solvent), paracetamol overdose, death cap fungi.
- Alcohol can cause cirrhosis.
- Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).
- NAFLD - fatty liver without inflammation and fibrosis consequent on obesity but can develop to…
- NASH - fatty liver with inflammation and fibrosis which can lead to cirrhosis.
A cirrhotic liver has a nodular surface and scarring (fibrosis) is present
What is cirrhosis?
- Normal liver has smooth surface and dark purple colour.
- Cirrhotic liver has a nodular surface and yellow/ green colour.
- Sequence of events:
- Injury (e.g. alcohol) > inflammation > cell death > fibrosis (stellate cells produce collagen) > regeneration.
- Nodules of regenerating cells are surrounded by fibrous tissue.
A biopsy and staining in the histopathology lab can detect cirrhosis.
Name the biochemical serum tests for hepatocellular damage
- The indicator which comes up first is usually alanine aminotransferase (ALT).
- 2-oxoglutarate + L-alanine L-glutamate + pyruvate
- Widely distributed (present in cardiac and skeletal muscle) but highest activity is in liver.
- Not by itself specific of liver disease e.g. increased in myocardial infarction.
Aspartate aminotransferase (AST) is often measured with alanine aminotransferase.
- Aspartate (Asp) + α-ketoglutarate ↔ oxaloacetate + glutamate (Glu)
- Widely distributed present in cardiac and skeletal muscle, liver and kidney.
- In liver disease will increase but to usually a smaller extent than ALT. Not specific.
Gamma glutamyl transferase
Assayed by:
L-g-glutamyl-p-nitroanilide + glycylglycine
L-g-glutamylglycylglycine + p-nitroanilide (absorbs at 405 nm)
- Origin primarily the hepatobiliary system so serum activity largely derived from liver.
- No longer thought of as of being of any use to discriminate between hepatocellular and cholestatic liver disease.
- Sensitivity for indication of increased alcohol intake 52-94% (activity induced).
- Enzyme synthesis is also induced by phenytoin and carbamazepine.
A history of alcohol abuse should prompt a GGT test
Biochemical tests for hepatocellular damage: Plasma albumin
- Biological half life of albumin is 20 days so not reduced in acute liver disease.
- In chronic liver disease concentration of albumin in plasma is reduced due to reduced synthesis and loss of albumin into the extravascular compartment.