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.
Biochemical tests following hepatitis B infection
- HBs Ag – surface antigen (immunoassay)
- Anti HBc – antibody to core.
- Anti HBs – antibody to surface.
Biochemical tests following hepatitis B infection
- HBs Ag – surface antigen (immunoassay)
- Anti HBc – antibody to core.
- Anti HBs – antibody to surface.
Non-biochemical tests
- Biopsy to confirm cirrhosis.
- Ultrasound to confirm fatty liver
What is Cholestatic liver disease?
- The failure of normal amounts of bile to reach the duodenum.
- Obstruction: gallstones (cholesterol/bilirubin/calcium salts); pancreatic carcinoma.
- Drug-induced: many agents e.g. several antibiotics.
- Primary biliary cirrhosis: chronic autoimmune condition, typically affects women in mid-life.
- Progressive obstruction of bile ducts within the liver, often develop a severe pruritus (itchy skin).
- Primary sclerosing cholangitis: chronic autoimmune condition common in patients with ulcerative colitis.The ducts carrying bile within and outside the liver become inflamed, thickened, scarred (sclerotic) and obstructed.
Biochemical tests for cholestatic liver disease: Alkaline phosphatase is elevated in cholestatic liver disease
p-nitrophenyl phosphate + H2O⇢ phosphate + p-nitrophenol (absorbs at 405 nm)
Specific liver isoform, but this is not detectable on a auto-analyser.
- Also found in bone (osteoblasts), placenta and intestinal epithelium.
- Elevated in bone disease, cholestatic and to a lesser extent hepatocellular disease.
Alkaline phosphatase is elevated in cholestatic liver disease: Mainly conjugated bilirubin is elevated in cholestatic liver disease.
- Conjugation mechanism is functioning normally but conjugated bilirubin refluxes back into plasma.
- Bilirubin detectable in urine.
- Conjugated bilirubin is water soluble so it is filtered into the urine at the kidney.
- If biliary obstruction substantial: no urobilinogen in urine and light coloured faeces with high fat content.
- Bilirubin has to get into the gut before urobilinogen is formed.
Defined by blockage of the bile duct so bilirubin is not being sent to the large intestine. Bilirubin goes back and damage the liver.
Metabolism and transport of bilirubin in CLD
Putting it all together
- Combinations of tests can be much more powerful than a single test.
- E.g. 21yo student returns from Asia with flu-like symptoms.
- Appeared jaundiced, bilirubin in urine.
- Subsequently shown to be infected with hepatitis virus type A.
True or false: Bilirubin is hydrophobic
How is it excreted?
True
Bilirubin binds to albumin and is transported to the liver to be conjugated then transported through the bile duct into the large intestine to be broken down (to urobilogen) and excreted in the urine (can be detected by a dipstick). Brown urine indicative of prehepatic jaundice
Difference between prehepatic and cholestatic liver disease
Prehepatic = large amounts of urobilogen
Cholestatic= large amounts of conjugated bilirubin in the blood, large amounts of bilirubin in the urine and stools become pale in colour and contains large amounts of fat
