[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Central nervous system](https://durgical.com/en/general-pathology/areas/cns/) › Metabolic and toxic brain injury

# Metabolic and toxic brain injury

- Lesion

Low sugar, ammonia from a failing liver and poisons such as carbon monoxide, alcohol and methanol each damage particular parts of the brain.

Updated Nov 12, 2026

## Key points

- Hypoglycemia: large cortical pyramidal neurons and hippocampal neurons (including dentate gyrus) die; Purkinje cells are relatively spared, unlike in hypoxia.
- Hepatic encephalopathy: Alzheimer type II astrocytes in cortex and basal ganglia; ammonia impairs astrocyte function; asterixis and confusion.
- Carbon monoxide: binds hemoglobin tightly; bilateral necrosis of the globus pallidus, and delayed white matter damage.
- Chronic alcohol: atrophy of the anterior superior cerebellar vermis with truncal ataxia; also Wernicke-Korsakoff, central pontine myelinolysis and Marchiafava-Bignami disease.
- Methanol: metabolised to formic acid; retinal ganglion cell death causes blindness, with putaminal necrosis.
- Radiation necrosis: delayed fibrinoid necrosis of vessels and coagulative necrosis of white matter, months to years after treatment.

## What it is

The brain depends on a constant supply of glucose and oxygen and is exposed to anything that crosses the blood-brain barrier. Severe hypoglycemia kills neurons much like hypoxia does. Liver failure lets ammonia reach the brain, where astrocytes swell and change. Toxins have favourite targets: carbon monoxide the globus pallidus, chronic ethanol the anterior cerebellar vermis, methanol the retina and putamen. Therapeutic radiation can cause delayed necrosis of white matter.

## Step by step

- A substrate is missing (glucose) or a toxin reaches the brain (ammonia, carbon monoxide, alcohols).
- Neurons or glia with the highest exposure or need are hit first.
- Astrocytes swell and fail when ammonia is detoxified into glutamine inside them.
- Energy failure, oxidative stress and excitotoxicity kill vulnerable cells.
- Lesions take the pattern of the cell type and region most affected.

## Metabolic and toxic insults and their targets

| Insult | Favourite target | Clue |
| --- | --- | --- |
| [Severe hypoglycemia](https://durgical.com/en/conditions/hypoglycaemia/) | Cerebral cortex, hippocampus | Neuronal necrosis, Purkinje cells spared |
| [Hyperammonemia (liver failure)](https://durgical.com/en/conditions/hepatic-encephalopathy/) | Astrocytes throughout grey matter | Alzheimer type II astrocytes, asterixis |
| [Carbon monoxide](https://durgical.com/en/conditions/carbon-monoxide-poisoning/) | Globus pallidus, white matter | Cherry-red skin, delayed leukoencephalopathy |
| [Chronic ethanol](https://durgical.com/en/conditions/alcohol-use-disorder/) | Anterior cerebellar vermis | Truncal ataxia, wide-based gait |
| [Methanol](https://durgical.com/en/conditions/methanol-poisoning/) | Retina, putamen | Blindness, high anion gap acidosis |
| [Lead (children)](https://durgical.com/en/conditions/lead-poisoning/) | Brain capillaries | Edema, encephalopathy, developmental loss |
| Radiation | White matter and vessels | Delayed necrosis, mimics tumour recurrence |

## Clinical notes

- Metabolic encephalopathies are often reversible if the cause is corrected early; structural damage is not.
- Methanol poisoning outbreaks from adulterated alcohol occur in Latin America and need urgent recognition.

## Memory aid

Each poison has its address: carbon monoxide to the pallidum, alcohol to the vermis, methanol to the eye, ammonia to the astrocytes.

## Test yourself

Think of the answer, then tap the question to see it.

## Which brain structure is characteristically necrotic after carbon monoxide poisoning?

The globus pallidus, on both sides.

## What astrocytic change marks hepatic encephalopathy?

Alzheimer type II astrocytes, with enlarged pale nuclei, from hyperammonemia.

## Why does methanol cause blindness?

It is metabolised to formic acid, which poisons mitochondria of retinal ganglion cells and the optic nerve.

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## Elsewhere in DurgiPedia

- [Carbon monoxide, methemoglobin and cyanide](https://durgical.com/en/physiology/carbon-monoxide-methemoglobin-and-cyanide/)

## Connections

## Related 8

- [Global hypoxic-ischemic brain injury](https://durgical.com/en/general-pathology/global-hypoxic-ischemic-brain-injury/)
- [Thiamine and B12 deficiency in the CNS](https://durgical.com/en/general-pathology/thiamine-and-b12-deficiency-in-the-cns/)
- [How brain cells react to injury](https://durgical.com/en/general-pathology/how-brain-cells-react-to-injury/)
- [Alcohol: how it injures the liver, brain, heart and fetus](https://durgical.com/en/general-pathology/alcohol-how-it-injures-the-liver-brain-heart-and-fetus/)
- [Ionizing radiation injury](https://durgical.com/en/general-pathology/ionizing-radiation-injury/)
- [Heavy metals: lead, mercury, arsenic and cadmium](https://durgical.com/en/general-pathology/heavy-metals-lead-mercury-arsenic-and-cadmium/)
- [Chemical (toxic) cell injury: direct and after metabolism](https://durgical.com/en/general-pathology/chemical-cell-injury-direct-and-after-metabolism/)
- [Liver failure: acute, chronic and acute-on-chronic](https://durgical.com/en/general-pathology/liver-failure-acute-chronic-and-acute-on-chronic/)

## Related conditions 8

- [Hypoglycaemia (including insulin-induced)](https://durgical.com/en/conditions/hypoglycaemia/)
- [Hepatic encephalopathy](https://durgical.com/en/conditions/hepatic-encephalopathy/)
- [Carbon monoxide poisoning](https://durgical.com/en/conditions/carbon-monoxide-poisoning/)
- [Methanol poisoning](https://durgical.com/en/conditions/methanol-poisoning/)
- [Alcohol use disorder](https://durgical.com/en/conditions/alcohol-use-disorder/)
- [Lead poisoning](https://durgical.com/en/conditions/lead-poisoning/)
- [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/)
- [Neonatal hypoglycaemia (including infant of a diabetic mother)](https://durgical.com/en/conditions/neonatal-hypoglycaemia/)

[← 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: [Loss of brain function - liver disease: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000302.htm) (MedlinePlus, US National Library of Medicine, 2026); [Carbon monoxide poisoning: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/002804.htm) (MedlinePlus, US National Library of Medicine, 2026); [Methanol poisoning: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/002680.htm) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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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/metabolic-and-toxic-brain-injury/