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# Carbon monoxide, methemoglobin and cyanide

- Mechanism
- Exam priority: medium

Three poisons starve tissues of oxygen even when the lungs work: two spoil hemoglobin and one stops cells from using oxygen.

Updated 2026-11-01

Also called: Carboxyhemoglobin, Methemoglobinemia, Histotoxic hypoxia

## Key points

- CO: normal PaO₂, falsely normal SpO₂ (a two-wavelength oximeter reads carboxyhemoglobin as oxyhemoglobin). Measure by co-oximetry.
- CO and methemoglobin shift the dissociation curve left: less O₂ carried and harder to unload.
- Methemoglobinemia: chocolate-brown blood, cyanosis that does not improve with O₂, SpO₂ stuck near 85 %. Causes: topical local anesthetics, dapsone, nitrites; cytochrome b5 reductase deficiency.
- Cyanide: high SvO₂ ("arterialized" venous blood), severe lactic acidosis, normal PaO₂. Sources: fire smoke, nitroprusside, poorly processed bitter cassava.
- Closed-space fire: think of CO and cyanide together.
- None of the three responds to raising FiO₂ the way lung-related hypoxemia does.

## What it is

Carbon monoxide takes the O₂ site on hemoglobin with roughly 200–250 times greater affinity and also stops the remaining O₂ from being released. Methemoglobin is hemoglobin with ferric iron (Fe³⁺), which carries no O₂ and also shifts the curve left. Cyanide leaves hemoglobin alone: it blocks cytochrome c oxidase, so cells cannot use the O₂ that reaches them. In all three, PaO₂ can be normal.

## How it works, step by step

- CO binds heme with an affinity hundreds of times that of O₂ and occupies transport sites.
- The remaining hemes on that molecule hold O₂ more tightly and do not release it in the tissues (left shift).
- In methemoglobin the iron is oxidized to Fe³⁺, which cannot bind O₂; the other hemes hold their O₂ more tightly.
- Normally cytochrome b5 reductase reduces methemoglobin back; oxidants overwhelm this defense.
- Cyanide binds the iron of cytochrome c oxidase (complex IV) and halts the respiratory chain.
- Without oxidative phosphorylation cells switch to anaerobic glycolysis: ATP falls and lactate rises, especially in brain and heart.

### Oxygen–hemoglobin dissociation curve

**P50** 17.2 mmHg **Arterial blood** 59 % **Mixed venous blood** 54 % **O₂ given up to the tissues** 5 %

With 40% HbCO those sites no longer carry O₂ (the plateau falls) and the rest release it less well (left shift): that is why the harm is greater than in an anaemia of the same size. A standard pulse oximeter may still read normal.

Left shift (P50 17.2 mmHg): Hb holds O₂ more tightly and gives up less in the tissues.

- Current curve
- Normal curve (pH 7.40 · 37 °C)
- Arterial blood (PO₂ 100)
- Mixed venous blood (PO₂ 40)
- O₂ given up to the tissues

See how CO lowers the plateau and shifts the curve left; compare with anemia, which lowers the plateau without shifting it.

## Telling them apart

| Feature | Carbon monoxide | Methemoglobin | Cyanide |
| --- | --- | --- | --- |
| What fails | Transport (site occupied) | Transport (oxidized iron) | Cellular use of O₂ |
| PaO₂ | Normal | Normal | Normal |
| SpO₂ (standard oximeter) | Falsely normal | ≈85 %, does not rise with O₂ | Normal |
| Clinical clue | Headache, several people affected, cherry-red skin (rare) | Chocolate blood, cyanosis | Very high lactate, high SvO₂ |
| Dissociation curve | Left shift | Left shift | Unchanged |

## Clinical notes

- Gas heaters and braziers in closed rooms cause CO poisoning in cold areas such as the Cundinamarca–Boyacá highlands.
- Methemoglobinemia after topical local anesthetics for endoscopy: cyanosis with normal PaO₂.
- Bitter cassava contains cyanogenic glycosides; traditional processing (grating, soaking, cooking) removes them.

## Memory aid

CO steals the seat, methemoglobin breaks the seat, cyanide leaves the passenger nowhere to get off.

## Test yourself

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

## Why can a standard pulse oximeter read 98 % in severe CO poisoning?

It uses two wavelengths and carboxyhemoglobin absorbs much like oxyhemoglobin, so it is read as saturated. Co-oximetry is needed.

## Why is anemia with half the hemoglobin better tolerated than 50 % carboxyhemoglobin?

In anemia the curve does not shift and the remaining hemoglobin unloads O₂ normally; CO also shifts the curve left and keeps O₂ in the blood.

## Why does the cyanosis of methemoglobinemia not improve with oxygen?

The problem is not PaO₂ but oxidized iron that cannot bind O₂; more inspired O₂ does not change that hemoglobin.

## Why does cyanide poisoning cause lactic acidosis with well-oxygenated venous blood?

It blocks complex IV: cells do not consume O₂, blood returns nearly saturated and ATP comes from anaerobic glycolysis, which produces lactate.

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## Related topics

- [Oxygen transport and the dissociation curve](https://durgical.com/en/physiology/oxygen-transport-and-the-dissociation-curve/)
- [Oxygenation: SpO₂, PaO₂, cyanosis and oxygen therapy](https://durgical.com/en/physiology/oxygenation-spo-pao-cyanosis-and-oxygen-therapy/)
- [Oxygen content, delivery and extraction](https://durgical.com/en/physiology/oxygen-content-delivery-and-extraction/)
- [The causes of hypoxemia](https://durgical.com/en/physiology/the-causes-of-hypoxemia/)

## Related conditions

- [Carbon monoxide poisoning](https://durgical.com/en/conditions/carbon-monoxide-poisoning/)
- [Methemoglobinemia](https://durgical.com/en/conditions/methemoglobinemia/)
- [Cyanide poisoning](https://durgical.com/en/conditions/cyanide-poisoning/)
- [Glucose-6-phosphate dehydrogenase (G6PD) deficiency](https://durgical.com/en/conditions/glucose-6-phosphate-dehydrogenase-deficiency/)

## In Biochemistry

- [Hemoglobin variants (HbA, HbA2, HbF, HbS, HbC)](https://durgical.com/en/biochemistry/topics/hemoglobin-variants/)
- [Cytochrome c oxidase (complex IV)](https://durgical.com/en/biochemistry/enzymes/cytochrome-c-oxidase/)
- [Hemoglobin and 2,3-BPG](https://durgical.com/en/biochemistry/enzymes/hemoglobin-and-2-3-bpg/)
- [Electron transport chain and oxidative phosphorylation](https://durgical.com/en/biochemistry/pathways/electron-transport-chain-and-oxidative-phosphorylation/)
- [Lactate](https://durgical.com/en/biochemistry/molecules/lactate/)

## In Pharmacology

- [Local anesthetics](https://durgical.com/en/pharmacology/classes/local-anesthetics/)

[← All of physiology](https://durgical.com/en/physiology/)

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: [22.5 Transport of Gases](https://openstax.org/books/anatomy-and-physiology-2e/pages/22-5-transport-of-gases) (OpenStax (Rice University), 2022); [Carbon monoxide poisoning: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/002804.htm) (MedlinePlus, US National Library of Medicine, 2026); [Methemoglobinemia: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000562.htm) (MedlinePlus, US National Library of Medicine, 2026); [Hydrogen Cyanide](https://pubchem.ncbi.nlm.nih.gov/compound/768) (PubChem, NCBI, 2026); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 41). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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Representative model, for educational purposes only.

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