Liver Function Tests PDF

Liver Function Tests Dr Karan Rana Learning Outcomes  Basic structure and functions of the liver.  Conditions that can involve liver malfunction especially jaundice. Liver Disease  Fifth biggest killer in the UK and the only major cause of death that is increasing.  Around 1 in 25 peop...

Liver Function Tests Dr Karan Rana Learning Outcomes  Basic structure and functions of the liver.  Conditions that can involve liver malfunction especially jaundice. Liver Disease  Fifth biggest killer in the UK and the only major cause of death that is increasing.  Around 1 in 25 people in the UK have tested positive for abnormal liver function. Liver Ultrastructure  Liver gets 70% of blood from the portal vein and 30% from the hepatic artery. Sinusoidal space Kupffer cell Nucleus Parenchymal cell (hepatocyte) Sinusoidal space Biliary canaliculus 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. Jaundice  Abnormally high plasma concentration of bilirubin.  >21 mmol/l.  Prehepatic.  Hepatocellular.  Cholestatic. Metabolism and transport of bilirubin Spleen Haemoglobin Liver haem globin Bilirubin diglucuronide iron bilirubin albumin (conjugated) Active transport of conjugate across Bilirubin-albumin the canaliculus bilirubin (unconjugated) Bile duct urobilinogen b a Kidney bilirubin c t Portal vein urobilinogen e Urobilinogen r (entero-hepatic urobilinogen i in urine circulation) urobilin a Large Intestine Prehepatic jaundice  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 Hepatocellular damage  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. 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. 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. Biochemical serum tests for hepatocellular damage  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. Biochemical serum tests for hepatocellular damage  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.  Summary  Conditions dysregulating liver function present with critical implications. Most notably Jaundice.  These include, pre-hepatic, hepatocellular and Cirrhosis.  AST, ALT and GGT are all biomarkers which can help diagnose liver dysfunction but have various pros and cons.