[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Environmental pathology](https://durgical.com/en/general-pathology/#a-environment) › Alcohol: how it injures the liver, brain, heart and fetus

[General pathology](https://durgical.com/en/general-pathology/) · [Environmental pathology](https://durgical.com/en/general-pathology/#a-environment)

# 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

## Key points

- Steatosis → alcoholic hepatitis (Mallory-Denk bodies, neutrophils) → micronodular cirrhosis; only steatosis is fully reversible.
- NADH excess explains fatty liver, hypoglycaemia, lactic acidosis and hyperuricaemia.
- Wernicke: confusion, ataxia and ophthalmoplegia from thiamine deficiency; thiamine is given before glucose.
- Fetal alcohol syndrome: smooth philtrum, thin upper lip, short palpebral fissures, microcephaly.
- Alcohol causes cancer of the mouth, pharynx, larynx, oesophagus, liver, colon and breast.

## 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.

## Memory aid

Alcohol spends the liver's NAD+: with too much NADH the liver stores fat, stops making glucose and piles up lactate.

## 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.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/alcohol-how-it-injures-the-liver-brain-heart-and-fetus/)

## Related

- [Fatty change (steatosis)](https://durgical.com/en/general-pathology/fatty-change/)
- [Intracellular accumulations: cholesterol, proteins, hyaline, glycogen](https://durgical.com/en/general-pathology/intracellular-accumulations-cholesterol-proteins-hyaline-glycogen/)
- [Fibrosis in organs: TGF-β and the myofibroblast](https://durgical.com/en/general-pathology/fibrosis-in-organs-tgf-and-the-myofibroblast/)
- [Chemical (toxic) cell injury: direct and after metabolism](https://durgical.com/en/general-pathology/chemical-cell-injury-direct-and-after-metabolism/)
- [Oxidative stress and free-radical injury](https://durgical.com/en/general-pathology/oxidative-stress-and-free-radical-injury/)
- [Liver regeneration](https://durgical.com/en/general-pathology/liver-regeneration/)

## Related conditions

- [Alcoholic liver disease (biochemistry)](https://durgical.com/en/conditions/alcoholic-liver-disease/)
- [Alcohol use disorder](https://durgical.com/en/conditions/alcohol-use-disorder/)
- [Fetal alcohol spectrum disorder](https://durgical.com/en/conditions/fetal-alcohol-spectrum-disorder/)
- [Acute pancreatitis](https://durgical.com/en/conditions/acute-pancreatitis/)
- [Chronic pancreatitis](https://durgical.com/en/conditions/chronic-pancreatitis/)
- [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/)
- [Wernicke encephalopathy (thiamine deficiency)](https://durgical.com/en/conditions/wernicke-encephalopathy/)
- [Dilated cardiomyopathy](https://durgical.com/en/conditions/dilated-cardiomyopathy/)
- [Atrial fibrillation](https://durgical.com/en/conditions/atrial-fibrillation/)
- [Acute alcohol (ethanol) intoxication](https://durgical.com/en/conditions/acute-alcohol-intoxication/)
- [Alcohol withdrawal and delirium tremens](https://durgical.com/en/conditions/alcohol-withdrawal-and-delirium-tremens/)
- [Mallory-Weiss syndrome](https://durgical.com/en/conditions/mallory-weiss-syndrome/)
- [Hepatocellular carcinoma](https://durgical.com/en/conditions/hepatocellular-carcinoma/)
- [Oesophageal cancer](https://durgical.com/en/conditions/oesophageal-cancer/)
- [Megaloblastic anaemia (B12 or folate deficiency)](https://durgical.com/en/conditions/megaloblastic-anaemia/)
- [Disulfiram–ethanol reaction](https://durgical.com/en/conditions/disulfiram-ethanol-reaction/)

## Elsewhere in DurgiPedia

- [Ethanol metabolism](https://durgical.com/en/biochemistry/pathways/ethanol-metabolism/)
- [Alcohol dehydrogenase (ADH)](https://durgical.com/en/biochemistry/enzymes/alcohol-dehydrogenase/)
- [Aldehyde dehydrogenase 2 (ALDH2)](https://durgical.com/en/biochemistry/enzymes/aldehyde-dehydrogenase-2/)
- [Cytochrome P450 2E1 (CYP2E1, MEOS)](https://durgical.com/en/biochemistry/enzymes/cytochrome-p450-2e1/)
- [Acetaldehyde](https://durgical.com/en/biochemistry/molecules/acetaldehyde/)
- [Thiamine (vitamin B1)](https://durgical.com/en/biochemistry/molecules/thiamine/)
- [Liver: lobule, acinus, hepatocytes, sinusoids, Kupffer cells](https://durgical.com/en/histology/liver-lobule-acinus-hepatocytes-sinusoids-kupffer-cells/)
- [Alcohol: fetal alcohol spectrum disorder](https://durgical.com/en/embryology/alcohol-fetal-alcohol-spectrum-disorder/)

## In Pharmacology

- [Disulfiram](https://durgical.com/en/pharmacology/disulfiram/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

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](https://www.who.int/news-room/fact-sheets/detail/alcohol) (World Health Organization, 2026); [Alcoholic liver disease: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000281.htm) (MedlinePlus, US National Library of Medicine, 2026); [Alcohol use disorder: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/alcohol-use-disorder/) (MedlinePlus, US National Library of Medicine, 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/alcohol-how-it-injures-the-liver-brain-heart-and-fetus/