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

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 mmHgArterial 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.

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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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 (OpenStax (Rice University), 2022); Carbon monoxide poisoning: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Methemoglobinemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Hydrogen Cyanide (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.