Overview

As bicarbonate≈70%

As carbamino compounds≈20–23%

Dissolved≈7–10%

In systemic capillaries CO2 diffuses into plasma and erythrocytes. A little stays dissolved (≈7–10%). Some combines with terminal amino groups of globin to form carbaminohaemoglobin (≈20–23%). Most (≈70%) is hydrated inside red cells by carbonic anhydrase: CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3−. The H+ is buffered by deoxyhaemoglobin (a better buffer than oxyhaemoglobin), and HCO3− leaves the cell in exchange for Cl− through the band 3 anion exchanger (chloride or Hamburger shift); osmotically active particles accumulate, so venous red cells are slightly larger. In the lungs every step reverses: HCO3− re-enters the cell, Cl− leaves, and CO2 is regenerated and exhaled.

The Haldane effect is the increased CO2-carrying capacity of deoxygenated blood: in tissues, O2 unloading helps CO2 loading; in the lungs, oxygenation of Hb releases H+ and carbamino CO2, accounting for roughly half of the CO2 unloaded. Its counterpart, the Bohr effect, describes the effect of CO2/H+ on O2 binding. The CO2 dissociation curve is nearly linear and much steeper than the O2 curve in the physiological range, which is why hyperventilating healthy lung regions can compensate for underventilated ones for CO2, but not for O2.

Location: Erythrocytes and plasma.

Function

Carries ≈200 mL CO2/min from tissues to lungs.
Provides the bicarbonate–CO2 buffer system central to acid–base balance.

Physiology: Henderson–Hasselbalch: pH = 6.1 + log([HCO3−]/(0.03 × PaCO2)) = 6.1 + log(24/1.2) ≈ 7.40. Acute changes in PaCO2 alter pH within minutes; the kidneys compensate over 2–5 days by adjusting HCO3−.

Clinical significance

Respiratory acidosis and alkalosis

Hypoventilation (COPD exacerbation, opioid overdose, neuromuscular weakness) raises PaCO2 and lowers pH; hyperventilation (anxiety, PE, early salicylate toxicity, altitude) lowers PaCO2, causing alkalosis, tingling and carpopedal spasm (fall in ionised calcium).

Carbonic anhydrase inhibitors

Acetazolamide causes renal bicarbonate loss and a mild metabolic acidosis that stimulates ventilation — used to prevent acute mountain sickness.

Test yourself

In what form is most carbon dioxide transported in venous blood?

Dissolved in plasma
Bound to the haem iron of haemoglobin
As carbaminohaemoglobin
As bicarbonate ions

Answer: As bicarbonate ions

≈70% of CO2 travels as HCO3− formed by carbonic anhydrase inside red cells; ≈20–23% as carbamino compounds (bound to terminal amino groups of globin, not to the haem iron); ≈7–10% dissolved.

What exchanges with bicarbonate across the erythrocyte membrane during the "chloride shift"?

Chloride, via the band 3 anion exchanger
Sodium, via the Na+/K+-ATPase
Hydrogen ions, via carbonic anhydrase
Potassium, via ROMK channels

Answer: Chloride, via the band 3 anion exchanger

In systemic capillaries HCO3− generated inside the red cell leaves in exchange for Cl− through band 3 (AE1), maintaining electroneutrality. The direction reverses in pulmonary capillaries.