Alcoholic Liver Disease

Question 1

ALDs three major, distinctive but overlapping lesions.

Answer 1

1. Hepatic Steatosis (fatty liver)
2. Alcoholic hepatitis
3. Alcoholic cirrhosis

Question 2

Why are females more susceptible to ALD?

Answer 2

• Estrogen increases gut permeability to endotoxins.
• Also, estrogen increases production of pro-inflammatory cytokines and chemokines resulting in injury to liver cells.
• Females develop advanced liver disease with substantially less alcohol intake.

Question 3

HCV & HBV

Answer 3

Iron overload and chronic infections with HCV and HBV can increase the severity of ALD and hasten progression to cirrhosis in chronic alcoholics.

Question 4

ALD; can be caused by how much amount and duration?

Answer 4

1. Short term ingestion of 80g of alcohol over one to several days > mild and reversible hepatic steatosis.
2. Daily intake of 80g or more ethanol > increases risk of severe hepatic injury.
3. Daily consumption of 160g or more for 10-20 years > severe injury.

Question 5

CYP2E1

Answer 5

Metabolism of alcohol in the liver by CYP2E1 in the
microsomes produces reactive oxygen species (such as hydrogen peroxide and superoxide ions), which cause lipid peroxidation of cell membranes leading to injury to hepatocyte.

Question 6

Mechanisms of Liver Injury by Ethanol.

Answer 6

1. Oxidative stress/Reactive Oxygen Species.
2. Immune and Inflammatory Mechanisms by Forming Chemical Adducts.
3. Increased Redox (NADH: NAD+) Ratio.
4. Increased production of Proinflammatory Cytokines.
5. Direct toxicity by forming Protein Adducts.
6. Hypoxic Damage
7. Reduced levels of ADH and ALDH Isozymes.
8. Abnormal metabolism of Methionine.
9. Malnutrition and Deficiencies of Vitamins.
10. Induction of Enzymes.

Question 7

Decreased NAD+ in cytoplasm.

Answer 7

Decreased NAD+ inhibits oxidation of fatty acid and leads to accumulation of fat in the live.
Could also cause lactic acidosis.