Alcohol Related Liver Disease

Question 1

Alcohol metabolism

Answer 1

1. Ethanol –> acetaldehyde (ADH)
2. Acetaldehyde –> acetate (ALDH)
3. Acetate –> CO2 + H2O

Question 2

kinetics of alcohol metabolism

Answer 2

zero order kinetics - fixed rate that cannot be exceeded (easy to overload pathway)

Question 3

Rate limiting step of alcohol metabolism

Answer 3

ability for liver to re-oxidise NADH to NAD

Question 4

Disulphiram

Answer 4

Antabuse - inhibits breakdown of acetaldehyde –> bad hangover

Question 5

Alcohol metabolism in heavy drinkers

Answer 5

Normal pathway filled up - use overflow pathway - uses CYP2E1 to convert ethanol to acetaldehyde (this generates reactive oxgen species that damage hepatocytes). The alternate pathway has increased reoxidation of mitochondrial NADH (increased O2 and ATP consumption –> hypermetabolic state

Question 6

Metabolic disturbances in alcoholics

Answer 6

1. lack of pyruvate for gluconeogenesis –> hypoglycaemia
2. NADH reducing agent used for lipogenesis –> steatosis
3. Pyruvate converted to lactate –> lactic acidosis
4. Oxidative + toxic metabolites –> inflammation

Question 7

Comorbidities that increase risk of harm in ALD

Answer 7

age
diabetes
diets high in fat (promote inflammation in liver)