What markers are measured to assess liver function?
- - Serum albumin & bilirubin
- - Prothrombin Time (PT)
- - Serum ALT and AST
- - Serum ALP and GGT
- - Urinary bilirubin & urobilinogen
What is the half-life of albumin and why is this clinically important?
- ~ 20 days.
- Important because albumin levels can be normal in acute liver disease.
Why is PT a useful marker of liver disease?
- Short half life so is sensitive indicator of both acute and chronic liver damage.
- NB - must check Vit K levels are normal because they affect PT and deficiency is common in biliary obstruction.
Is the majority of serum bilirubin conjugated or unconjugated?
In short, what is the physiological function of ALT and AST?
What do elevated levels of these markers potentially indicate?
- - To catalyse reaction between amino acid and alpha-keto acid (e.g. pyruvate)
- - Elevated ALT and AST can indicate hepatocellular damage.
What is the landmark dividing the left and right liver lobes?
- Falciform ligament
What is the significance of bilirubinuria?
- - Due to conjugated (soluble) bilirubin in urine.
- - Found in patients with jaundice due to hepatobiliary disease, but absent if unconjugated bilirubin is major cause of jaundice
What other tissues is AST expressed in?
- - Heart
- - Muscle
- - Kidney
- - Brain
How do ALP & GGT change in cholestasis?
- Rise in parallel due to similar excretion pathway.
If ALP is normal but GGT is elevated, what can this be used as a marker for?
- - Useful guide to alcohol intake
- NB - Raised GGT in isolation does not necessarily indicate liver disease
Where is the ligamentum teres? How is it formed?
- - Inferior aspect of the falciform ligament.
- - Formed as a remnant of the umbilical vein.
Main arterial blood supply to the liver? Where does this arise in relation to aortic branches?
- - Hepatic artery
- - Stems from celiac trunk
Name the 3 pathways of ethanol to acetaldehyde metabolism. State the location in the cell of each pathway.
- - Alcohol dehydrogenase pathway (cytosol)
- - Cytochrome P450 2E1 (microsomes)
- - Catalase (peroxisomes)
The major pathway of alcohol metabolism involves alcohol dehydrogenase (ADH), producing acetaldehyde. Why can this lead to tissue damage?
- - A byproduct of this reaction is the reduction of NAD by 2 electrons to form NADH+.
- - This creates a highly reduced cytosolic environment in hepatocytes, leaving them prone to damage from byproducts of alcohol metabolism, such as free radicals & acetaldehyde.
What are the stages of liver disease caused by alcoholism? Briefly describe each stage.
- 1. Alcoholic Fatty Liver Disease
- - No cell damage
- - Reversible upon cessation of alcohol intake
- 2. Alcoholic Hepatitis
- - Invasion by polymorphonuclear leukocytes & hepatocyte necrosis.
- 3. Alcoholic Cirrhosis
- - Micronodular formations (<3mm) but can include macronodules
- - Not reversible
Byproducts of ehthanol metabolism, such as acetaldehyde and ROS interact with amino acids to form adducts. Why do these adducts contribute to liver damage?
- - The body recognises acetaldehyde adducts are foreign; generated immunoglobulins against them.
- - The immunoglobulins (antibodies) bind to the adducts and induce an immune response against the hepatocytes containing them.
- - This is known as immune-mediated hepatotoxicity.
Acetaldehyde forms adducts with serotonin and dopamine. What are the implications of this?
Serotonin and dopamine are neurotransmitters. Alteration of their normal pharmacological function may have neurological implications and could contribute to the cognitive changes seen with alcoholism.