ChemPath: LFTs and cases
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List some functions of the liver.
• Intermediary metabolism • Protein synthesis • Xenobiotic metabolism • Bile synthesis • Reticulo-endothelial system
Define intermediary metabolism.
Enzyme-catalysed processes within cells that extract energy from nutrient moleculaes and use that energy to construct cellular components.
List some examples of processes that count as intermediary metabolism.
• Glycolysis • Glycogen storage • Gluconeogenesis • Amino acid synthesis • Fatty acid synthesis
List some metabolic consequences of liver failure.
• Reduction in blood sugar due to a lack of glycogen • Lactic acidosis (reduced ability to metabolise lactic acid) • Increased ammonia (no longer able to process amino acids)
What are the main stages of xenobiotic metabolism in the liver?
• Chemical modification (e.g. redox, acetylation by CYP450 enzymes) • Conjugation (glucuronidation or sulphation) • Excretion
Outlie the roles of the liver regarding hormone metabolism.
• Vitamin D hydroxylation • Steroid hormones (conjugation and excretion) • Peptide hormones (catabolism)
What are the constituents of bile?
• Water • Bile acids/salts • Bilirubin • Phospholipids • Cholesterol • Proteins • Drugs and metabolites
What are the functions of bile?
• Excretion • Micelle formation • Digestion
Describe the metabolism and excretion of bilirubin.
• Red cells are broken down to produce haem, iron and globin • Heme breaks down to form bilirubin • Bilirubin is bound to albumin in plasma • This unconjugated bilirubin travels to the liver where it becomes glucuronidated • The conjugated bilirubin is released into the bile
What are the main cells of the reticuloendothelial system found in the liver?
Kupffer cells
What are the roles of Kupffer cells?
• Clearance of infection and lipopolysaccharides (LPS) • Antigen presentation • Immune modulation (e.g. cytokine production)
What are the main markers of liver synthetic function?
Albumin Prothrombin Time
Where are ALT and AST found?
Within the cytoplasm of hepatocytes
What is the function of ALT and AST?
Catalyse the transfer of alanine and aspartate to the alpha-keto group of alpha-ketoglutarate, thereby producing pyruvate and oxaloacetate.
Other than the liver, where else is ALT and AST found?
Muscle, kidney, bone, pancreas
Describe the rise in ALT and AST seen in alcoholic liver disease.
AST: ALT > 2:1 in alcoholic liver disease
Describe typical ALT and AST levels in cirrhosis.
• May be raised • May be normal in long-standing chronic liver disease
What is the role of gamma-glutamyl transferase?
Catalyses the transfer of gamma-glutamyl groups between peptides
Where is GGT found?
Hepatocytes and epithelium of small bile ducts NOTE: also found in kidney, pancreas, spleen, heart, brain and seminal vesicles
List some causes of raised GGT.
• Alcohol abuse • Bile duct disease (e.g. gallstones) • Hepatic metastases
What is the likely function of ALP?
Catalyse the hydrolysis of a large number of organic phosphate esters at an alkaline pH.
Where is ALP found?
Liver isoenzyme is found in the sinusoidal and canalicular membranes (bile ducts) Other sources: bone, small intestine, kidneys, placenta, white blood cells
List some hepatobiliary causes of raised ALP.
• Obstructive jaundice • Bile duct damage (e.g. PSC, PBC) • Elevated to a lesser degree in viral and alcoholic hepatitis
List some non-hepatobiliary causes of raised ALP.
Bone disease (e.g. Paget’s) Pregnancy