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CO₂ transport and the Haldane effect !

  • Mechanism
  • Exam priority: high

CO₂ travels in blood mostly as bicarbonate. When hemoglobin gives up O₂, it picks up more CO₂ and acid.

Updated 2026-11-01

Also called: Chloride shift, Haldane effect, Carbonic anhydrase

See it in 3D: Pulmonary arteries

What it is

CO₂ made by the tissues travels in three forms: as bicarbonate (most), bound to hemoglobin as carbamino compounds, and dissolved. Red cell carbonic anhydrase speeds the conversion of CO₂ to bicarbonate and hydrogen ions. The Haldane effect says deoxygenated hemoglobin carries more CO₂ and buffers more H⁺; in the lung the reverse happens.

How it works, step by step

  1. In the tissue, CO₂ diffuses into plasma and into the red cell.
  2. Carbonic anhydrase rapidly turns it into carbonic acid, which splits into H⁺ and HCO₃⁻.
  3. Deoxyhemoglobin buffers the H⁺ and also forms carbamino more readily (Haldane effect).
  4. HCO₃⁻ moves out to plasma in exchange for Cl⁻ moving in (chloride shift).
  5. In the lung, hemoglobin is oxygenated, releases H⁺ and loses affinity for CO₂.
  6. The freed H⁺ combines with HCO₃⁻, which re-enters the red cell, and CO₂ is re-formed.
  7. CO₂ diffuses into the alveolus and is removed by ventilation.

Oxygen–hemoglobin dissociation curve

Oxygen–hemoglobin dissociation curve: P50 38.5 mmHg 0204060801000255075100PO₂ (mmHg)Hb saturation (%)P50 3953 %93 %

P50 38.5 mmHgArterial blood 93 %Mixed venous blood 53 %O₂ given up to the tissues 40 %

Right shift (P50 38.5 mmHg): Hb has less affinity and gives up more O₂ in the tissues. Acid, CO₂, heat and 2,3-BPG cause it.

  • Current curve
  • Normal curve (pH 7.40 · 37 °C)
  • Arterial blood (PO₂ 100)
  • Mixed venous blood (PO₂ 40)
  • O₂ given up to the tissues
More CO₂ and lower pH in active tissue: the curve shifts right.

Equations

Henderson–Hasselbalch (bicarbonate)pH = 6.1 + log ( HCO3- / (0.03 × PCO2) )
6.1
pKa of the carbonic acid/bicarbonate system
0.03
CO₂ solubility, mmol/L per mmHg

If PCO₂ rises with no change in bicarbonate, pH falls.

Reference values

ParameterValueNote
PaCO₂ (sea level)35–45 mmHgBogotá ≈ 30–35 mmHg
Mixed venous PvCO₂≈ 45–46 mmHg
Arterial HCO₃⁻22–26 mEq/Lsomewhat lower at altitude
CO₂ solubility≈ 20 times that of O₂

Approximate values for a healthy adult at rest; each laboratory sets its own ranges.

Forms of CO₂ transport

FormShare (arterial)Detail
Bicarbonate≈ 70%Made in the red cell, carried in plasma
Carbamino (mostly Hb)≈ 20–23%Bound to globin amino groups; more on deoxygenated Hb
Dissolved≈ 7–10%The fraction that sets the measured PCO₂

Clinical notes

  • COPD on high-flow O₂: PaCO₂ can rise, partly through the Haldane effect and partly through worsening V/Q.
  • Acute respiratory acidosis: PaCO₂ rises and pH falls before the kidney can retain bicarbonate.
  • Carbonic anhydrase inhibitors lower plasma bicarbonate and cause a mild metabolic acidosis.

Test yourself

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

Why does venous blood carry more CO₂ than arterial blood at the same PCO₂?

The Haldane effect: deoxyhemoglobin buffers more H⁺ and forms more carbamino, so it accepts more CO₂.

Which ion enters the red cell in tissue capillaries, and why?

Chloride: it comes in as bicarbonate goes out, keeping the cell electrically neutral (band 3 exchanger).

Why is venous hematocrit slightly higher than arterial?

As Cl⁻ enters and more solute forms inside the red cell, water follows by osmosis and the cell swells slightly.

Which enzyme limits bicarbonate formation in plasma, and why is it slow there?

Carbonic anhydrase: plasma has almost none, so the conversion happens inside the red cell.

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See it in 3D

The structures of Durgical's 3D anatomy where it happens.

In Biochemistry

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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); Respiratory acidosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2024); Chronic Obstructive Pulmonary Disease (COPD) (StatPearls (NCBI Bookshelf), 2024); 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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