Alcohol Effect on Liver - Mechanism

  1. Alcohol Absorption and Transport to the Liver

  • Ingestion and Absorption:

    After consuming alcohol, it passes through the esophagus to the stomach and small intestine. Approximately 20% of alcohol is absorbed in the stomach, while the remaining 80% is absorbed in the small intestine. Alcohol absorption is rapid, particularly on an empty stomach.

  • Transport Through Blood:

    Absorbed alcohol enters the bloodstream via the intestinal capillaries. Through the portal vein, it is transported directly to the liver, the primary site for alcohol metabolism.
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Alcohol Entry into Liver Cells
  • Once in the liver, alcohol enters hepatocytes (liver cells) where it is metabolized primarily by:
    • Alcohol Dehydrogenase (ADH): Converts alcohol to acetaldehyde, a toxic and reactive compound.
    • Cytochrome P450 2E1 (CYP2E1): Induced by chronic alcohol consumption, it produces reactive oxygen species (ROS) alongside acetaldehyde.
    • Catalase: Plays a minor role in alcohol metabolism.
Mechanisms of Alcohol-Induced Liver Damage
  1. Acetaldehyde Toxicity:
    • Acetaldehyde binds to proteins and DNA, forming adducts that impair cell functions and trigger immune responses.
    • It disrupts mitochondrial function and induces oxidative stress.
  2. Oxidative Stress:
    • Alcohol metabolism generates excessive ROS, which damage lipids, proteins, and DNA in hepatocytes.
    • Lipid peroxidation weakens cell membranes, making cells more prone to injury and death.
  3. Gut-Liver Axis Dysfunction:
    • Alcohol disrupts gut barrier integrity, allowing endotoxins (e.g., lipopolysaccharides) to enter the bloodstream and reach the liver.
    • Endotoxins activate Kupffer cells (liver macrophages), leading to inflammation and release of pro-inflammatory cytokines.
  4. Fatty Liver Formation (Steatosis):
    • Alcohol impairs lipid metabolism, increasing triglyceride synthesis and reducing lipid export from hepatocytes.
    • This leads to the accumulation of fat in liver cells, causing alcoholic fatty liver disease (AFLD).
Progression to Liver Scarring and Cirrhosis
  1. Inflammation and Hepatocyte Death:
    • Persistent alcohol consumption causes ongoing inflammation and hepatocyte apoptosis (programmed cell death) or necrosis.
  2. Fibrosis (Liver Scarring):
    • Activated hepatic stellate cells produce excessive collagen and extracellular matrix proteins in response to chronic injury and inflammation.
    • This scarring disrupts normal liver architecture and blood flow.
  3. Cirrhosis:
    • Advanced scarring leads to liver cirrhosis, characterized by:
      • Irreversible fibrosis.
      • Loss of functional liver tissue.
      • Complications like portal hypertension, ascites, and liver failure.

Conclusion

Alcohol’s journey from ingestion to liver damage is a complex process involving absorption, metabolism, and cascading cellular injuries. Early-stage damage, such as fatty liver, is often reversible with abstinence and lifestyle changes. However, continued alcohol consumption leads to progressive scarring and cirrhosis, which is irreversible and life-threatening.