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Liver function and liver function tests - Coggle Diagram
Liver function and liver function tests
Non-alcoholic liver disease
Alcoholic liver disease
Liver
Located under the ribcage above the gall bladder and pancreas
Supplied by the hepatic artery and portal vein
The central vein takes blood away from the liver
Liver lobule
Hexagonal structure
Contains the interlobular artery, vein and bile duct. Hepatocytes, the central vein and the hepatic sinusoid
Between hepatocyes and endothelial cells in the liver lobule there is the disse space
the disse space contains stellate cells
Stellate cells secrete bits of matrix
Kupfer cells sit below endothelial cells the lobules
Kupfer cells fight infection and cause inflammation
Hepatocytes form 80% of the liver mass
They do most of the work in the liver
Functions of the liver
Metabolism
Metabolises carbohydrates, lipids and amino acids
liver releases glycogen to maintain normal blood glucose when levels are low
It can also cause proteins to be broken down into amino acids to be transformed into glucose
Its also involved in ketogenesis
Storage
Glycogen, vitamins and minerals
Synthetic function
Produces albumin, clotting factors, transport proteins, VLDL, transferrin
Also produces bile acids
Detoxification and excretion
The liver makes things water soluble by tagging them with polar residues
This means we can excrete them in bile and urine
Commonly glucuronic acid is used but it can be glycine, taurine or SO4
There are two phases in the process
Phase 1 - An oxidation or hydrolysis reaction where a reactive group is attached (e.g., OH)
Phase 2 - A conjugation reaction where the water-soluble group is attached to the reactive one
Metabolism of paracetamol
3 main pathways
Arylsupho-transferase
Sulphate conjugate
NON TOXIC
Cytochrome P450
N-acetylbenzoquinoneimine
Glutathione
Glutathione conjugate
Paracetamol 3-mercapturic acid
NON TOXIC
Binding with cell constituents, causing hepatotoxicity and nephrotoxicity
Produces TOXIC metabolite
about 5% metabolised via this pathways forming an incredibly toxic metabolite
UDP-glucuronyl transferase
Glucuronide conjugate
NON TOXIC
Liver function tests
Routine LFTs determine the presence of liver disease
Bilirubin
Anion transport
Aminotransferases
Hepatocyte damage
Gamma glutamyl transferase
Cholestasis
Alkaline phosphatase
Cholestasis
Liver disease that occurs when the flow of bile is blocked or obstructed
Albumin
Protein synthesis
Pro-thrombin time
Protein synthesis
Clotting cascade
Intrinsic pathways
Extrinsic pathway - equates pro-thrombin time
If this time is increased it indicates an issue with pro-thrombin synthesis
tests to determine the causes of liver disease
Observing biochemical markers / metabolites
Paracetamol, tumour markers, specific proteins
virology investigations
Hepatitis A, B and C etc.
Immunology investigations
Imaging studies
Genetic studies
Biopsies
Bilirubin
Comes from the metabolism of haem
Excess bilirubin in blood and tissues gives jaundice
First metabolised in 2 phases
First to biliverdin
Then to bilirubin
In this process the 02 is introduced, the Fe3+ is removed and the CO is removed
How does the liver get rid of bilirubin
Liver opens the chain of the bilirubin and attached glucuronic acid residues
the enzyme UDP-Glucuronyl transferase is key to this
its then excreted via bile
Types of jaundice
Pre-hepatic
Increase bilirubin production
Doesnt ususally signal liver disease
Caused by haemolysis, GI bleeding and bruising
Important to determine if its caused by inherited disorders where the liver cant conjugate bilirubin well
Gilberts disease
Congenital hyperbilirubinaemia
Can be a problem in neonates due to Kernicterus
Premature babies aren't able to conjugate bilirubin until UDP-Glucuronyl transferase are expressed
Can get sever unconjugated hyperbilitrubinaemia
Very high bilirubin is toxic to the brain of a neonate
Treated with phototherapy
Hepatocellular
Damaged hepatocytes
Diminished bilirubin uptake ability in the liver
Diminished excretion too
Diminished excretion means some conjugated bilirubin can escape back into the blood and eventually find its way to the urine
Cholestatic
Obstruction of the bile flow
Causes large amounts of conjugated bilirubin to show up in urine as liver can uptake and conjugate it but not excrete it
ALT and AST
When theres a problem with cholestasis their production is induced
ALT = Alanine transferase
AST = Aspartate aminotransferase
Both released after hepatocyte damage
Usually tests just show for ALT as its more specific to the liver
Measuring their ratios can be helpful
AST:ALT over 1 can indicate advances in cirrhosis and fibrosis
Elevated ratio can also be associated with alcoholism
Significant liver injury may be present without elevated ALT/AST as after a certain amount of damage you have few hepatocytes left to damage and release
Can take around 12-24 hours for these enzymes to be present in blood
Alkaline phosphatase and gamma glutamyl transferase
GGT induced by
Cholestatin
Certain drugs
Alcohol
Alk phos induced by
Cholestasis
Alk phos can arise from other sources
Bone
PLacenta
Intestine
Markers of fibrosis
Liver biopsy is the gold standard for diagnosing fibrosis
Some biomarker scoring systems are in use
Fibrosis-4 score
Hyaluronic acid
ELF testing (Enhanced liver fibrosis test)