15.1 Biochemistry: Alcohol and the liver Flashcards
What progression happens in the liver with alcohol damage?
Fatty infiltration, alcoholic hepatitis then cirrhosis (irreversible fibrous degradation)
What is the most significant pathway for alcohol conversion?
Alcohol dehydrogenase (conversion to acetaldehyde)
What is neurotoxicity as a result of alcohol consumption? (and how does it occur?, symptoms?)
Wernicke Korsakoff Syndrome (thiamin deficiency- injection can reverse)
-Symptoms: uncoordinated eyes, confabulation etc.
What proportion of functioning hepatocytes do you need for adequate performance?
40% ([serum albumin] usually normal in chronic liver diseases until cirrhosis is present)
How is alcohol first metabolised?
First pass metabolism by alcohol dehydrogenase from the gastric mucosa (fats slow)
What is the process of alcohol oxidation in the liver?
Ethanol to acetaldeyde (with ADH) to acetate to Acetyle-CoA
oxidised for energy -TCA cycle or converted to fat
Is alcohol dehydrogenase inducible?
No, MEOS (microsomal ethanol oxidising system) is utilised instead- CYP 2E1 induced
What happens with Warfarin and alcohol consumption?
Warfarin destruction by CYP 2E1 occurs, need to increase dose for effect
Why are cells damaged with chronic alcohol consumption? (3)
Alcohol depletes glutathione from mitochondria, free radicals produced
Also, MEOS pathway (CYP2E1) loads cell with free radicals
Alcohol in gut promotes iron absorption (catalyst for free radical production)
How are sex hormones affected by chronic alcohol consumption?
Low testosterone in men, stimulating microsomal modification/destruction of steroids
What is a pharmalogical management strategy for alcohol?
Disulfiram (inhibits aldeyhyde dehydrogenase, nausea etc. w/ consumption)
What rate is alcohol cleared at?
10g alcohol/hr (decrease of 0.015% blood alcohol/hr)
What is foetal alcohol syndrome (FAS)?
Esp. in first trimester, alcohol consumption can affect development (brain much smaller)
