General pathology · Environmental pathology
Alcohol: how it injures the liver, brain, heart and fetus !
- Mechanism
Breaking down alcohol creates acetaldehyde and an excess of NADH; these injure the liver, pancreas, brain, heart and developing fetus.
Updated 2026-11-01
What it is
Ethanol is metabolised mostly in the liver by alcohol dehydrogenase and, with heavy use, by CYP2E1. Acetaldehyde, oxygen free radicals and the shift in the NADH/NAD+ ratio injure the hepatocyte, and the same toxins act on other organs. Alcohol is also a carcinogen and a teratogen, and in Latin America it is one of the leading risk factors for disease and injury.
Structure
- Steatosis: large fat droplets push the nucleus aside (macrovesicular), at first around the central vein.
- Alcoholic hepatitis: swollen (ballooned) hepatocytes, Mallory-Denk bodies of tangled keratin and neutrophils around them.
- Pericellular «chicken-wire» fibrosis around the central vein, then small regular nodules of cirrhosis.
- Grossly the fatty liver is large, yellow and greasy; the end-stage cirrhotic liver is small and finely nodular.
Step by step
- Alcohol dehydrogenase turns ethanol into acetaldehyde; aldehyde dehydrogenase turns it into acetate.
- Both steps produce NADH: gluconeogenesis and fatty acid oxidation slow, and fat synthesis rises.
- Triglycerides build up in hepatocytes: steatosis, reversible if drinking stops.
- With heavy use CYP2E1 is induced and releases free radicals; acetaldehyde binds proteins and harms mitochondria.
- Kupffer cells, activated by gut endotoxin, release TNF and attract neutrophils: alcoholic hepatitis.
- Hepatic stellate cells turn into myofibroblasts and lay down collagen: fibrosis and micronodular cirrhosis.
- Outside the liver: pancreatitis, thiamine deficiency in the brain, cardiomyopathy and injury to the fetus.
Alcohol beyond the liver
| Organ | Lesion | Key point |
|---|---|---|
| Brain | Wernicke encephalopathy, Korsakoff syndrome, cerebellar atrophy | Thiamine deficiency; mamillary bodies and anterior vermis |
| Heart | Dilated cardiomyopathy, atrial fibrillation after a binge | Direct toxicity to cardiac myocytes |
| Pancreas | Acute and chronic pancreatitis | Thick secretions, early enzyme activation, calcifications |
| Oesophagus and stomach | Mallory-Weiss tear, gastritis, varices from cirrhosis | Vomiting and portal hypertension |
| Blood | Macrocytosis, folate deficiency | Poor diet and direct marrow toxicity |
| Fetus | Fetal alcohol spectrum disorder | No safe amount in pregnancy is known |
In the lab
- AST typically rises more than ALT (ratio above two), with raised GGT and macrocytosis.
- Hypoglycaemia, lactic acidosis and high uric acid reflect the excess of NADH.
Test yourself
Think of the answer, then tap the question to see it.
What are Mallory-Denk bodies and where are they classically seen?
Eosinophilic clumps of damaged keratin intermediate filaments in hepatocytes; classic in alcoholic hepatitis (also seen in MASLD and Wilson disease).
Why does a person who drinks heavily without eating become hypoglycaemic?
The excess of NADH from ethanol metabolism blocks gluconeogenesis, and glycogen stores are already used up.
Which vitamin deficiency causes Wernicke encephalopathy in alcohol use disorder?
Thiamine (vitamin B1) deficiency; it damages the mamillary bodies and the area around the third ventricle.
Which enzyme is induced by chronic drinking and makes acetaminophen more toxic?
CYP2E1, which forms more of the toxic metabolite NAPQI while glutathione is often low.
Related
- Fatty change (steatosis)
- Intracellular accumulations: cholesterol, proteins, hyaline, glycogen
- Fibrosis in organs: TGF-β and the myofibroblast
- Chemical (toxic) cell injury: direct and after metabolism
- Oxidative stress and free-radical injury
- Liver regeneration
Related conditions
- Alcoholic liver disease (biochemistry)
- Alcohol use disorder
- Fetal alcohol spectrum disorder
- Acute pancreatitis
- Chronic pancreatitis
- Cirrhosis
- Wernicke encephalopathy (thiamine deficiency)
- Dilated cardiomyopathy
- Atrial fibrillation
- Acute alcohol (ethanol) intoxication
- Alcohol withdrawal and delirium tremens
- Mallory-Weiss syndrome
- Hepatocellular carcinoma
- Oesophageal cancer
- Megaloblastic anaemia (B12 or folate deficiency)
- Disulfiram–ethanol reaction
Elsewhere in DurgiPedia
- Ethanol metabolism
- Alcohol dehydrogenase (ADH)
- Aldehyde dehydrogenase 2 (ALDH2)
- Cytochrome P450 2E1 (CYP2E1, MEOS)
- Acetaldehyde
- Thiamine (vitamin B1)
- Liver: lobule, acinus, hepatocytes, sinusoids, Kupffer cells
- Alcohol: fetal alcohol spectrum disorder
In Pharmacology
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Alcohol (World Health Organization, 2026); Alcoholic liver disease: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Alcohol use disorder: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.