Carbon dioxide transport

8 min read Last updated April 8, 2026

Clinical relevance / why it matters

  • CO2 carriage determines the relationship between ventilation and PaCO2, and strongly influences acid–base balance.
  • Changes in Hb oxygenation alter CO2 carriage (Haldane effect) and therefore CO2 elimination during oxygen therapy and in lung disease.
  • CO2 is much more soluble than O2, so total CO2 content changes substantially with small changes in PaCO2; this underpins CO2 dissociation curves and buffering.
  • End-tidal CO2 reflects alveolar CO2 only if V/Q and dead space are stable; understanding transport helps interpret capnography in shock/embolism/CPR.

High-yield numbers and proportions

  • Typical arterial values: PaCO2 ≈ 5.3 kPa (40 mmHg); total CO2 content ≈ 48 mL/dL blood (varies with Hb and buffering).
  • Forms of CO2 carriage (approximate): bicarbonate 80–90%, carbamino compounds 5–10%, dissolved CO2 5–10%.
    • Exact fractions vary with oxygenation (Haldane effect), Hb concentration, pH, and PCO2.
  • Solubility: CO2 is ~20× more soluble than O2 in plasma; dissolved CO2 is proportional to PaCO2 (Henry’s law).

1) Forms of CO2 transport

  • Dissolved CO2 in plasma: directly determines PaCO2 (the measured partial pressure).
    • Clinically important because ventilatory control responds to PaCO2 (via central chemoreceptors) rather than total CO2 content.
  • Bicarbonate (HCO3−): main transport form, generated largely inside RBCs via carbonic anhydrase.
  • Carbamino compounds: CO2 binds to terminal amino groups of proteins, especially deoxyhaemoglobin → carbaminohaemoglobin.
    • Binding is favoured by deoxygenated Hb (Haldane effect).

2) Key reactions in tissues and lungs

  • In tissues (high CO2 production): CO2 diffuses into RBC → CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3− (catalysed by carbonic anhydrase).
    • H+ is buffered mainly by deoxyhaemoglobin (Hb acts as a buffer).
    • HCO3− exits RBC in exchange for Cl− (chloride shift / Hamburger phenomenon) to maintain electroneutrality.
  • In lungs (CO2 elimination): reverse occurs; oxygenation of Hb releases H+ (reduced buffering) driving HCO3− + H+ → CO2 + H2O, and CO2 diffuses into alveoli.
    • Chloride shift reverses: HCO3− re-enters RBC as Cl− leaves.

3) CO2 dissociation curve (content vs PCO2)

  • CO2 dissociation curve relates total CO2 content to PCO2; it is more linear over physiological range than the O2 dissociation curve.
  • Deoxygenated blood carries more CO2 at a given PCO2 than oxygenated blood (Haldane effect) → curve shifts upward with deoxygenation.
    • Mechanisms: (1) deoxyHb forms carbamino compounds more readily; (2) deoxyHb buffers H+ better, promoting conversion of CO2 to HCO3−.
  • Clinical implication: giving O2 can reduce CO2 carriage in blood and increase PaCO2 if ventilation cannot rise (important in severe COPD).
    • This is one contributor alongside V/Q changes and reduced hypoxic pulmonary vasoconstriction.

4) Bohr vs Haldane effects (don’t mix them up)

  • Bohr effect: increased CO2/H+ reduces Hb affinity for O2 → facilitates O2 unloading in tissues (right shift of O2 dissociation curve).
  • Haldane effect: oxygenation of Hb reduces its capacity to carry CO2 (and H+), promoting CO2 unloading in lungs.

5) CO2, ventilation, and alveolar gas

  • Alveolar ventilation equation: PaCO2 ∝ VCO2 / VA (for constant CO2 production, PaCO2 inversely proportional to alveolar ventilation).
    • Doubling alveolar ventilation halves PaCO2 (if VCO2 constant).
  • End-tidal CO2 (ETCO2) approximates alveolar CO2 in well-perfused, well-ventilated units; increased dead space widens PaCO2–ETCO2 gradient.
    • Causes: low cardiac output, pulmonary embolism, severe V/Q mismatch, CPR, high PEEP/overdistension.

6) Acid–base link (Henderson–Hasselbalch context)

  • CO2 is the respiratory component of acid–base: pH depends on ratio [HCO3−] / (0.03 × PaCO2) (in mmHg).
    • Transport as HCO3− couples CO2 carriage to buffering and base excess changes over time (renal compensation).
Describe the forms in which carbon dioxide is transported in blood and give approximate proportions.

Structure your answer as dissolved, bicarbonate, and carbamino; then mention what determines PaCO2.

  • CO2 is carried as: (1) dissolved CO2 in plasma (≈5–10%); (2) bicarbonate HCO3− (≈80–90%); (3) carbamino compounds (≈5–10%) mainly on haemoglobin.
  • PaCO2 reflects the dissolved fraction (Henry’s law), not total CO2 content.
  • Relative proportions vary with oxygenation (Haldane effect), pH, Hb concentration, and PCO2.
Explain how CO2 is converted to bicarbonate in the tissues and transported to the lungs.

Walk through diffusion into RBC, carbonic anhydrase, buffering, and chloride shift.

  • CO2 diffuses from tissues into plasma and RBCs down its partial pressure gradient.
  • In RBCs, carbonic anhydrase catalyses: CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3−.
  • H+ is buffered mainly by deoxyhaemoglobin (Hb buffer), limiting fall in intracellular pH and allowing continued HCO3− formation.
  • HCO3− leaves the RBC in exchange for Cl− (chloride shift/Hamburger phenomenon) maintaining electroneutrality; plasma bicarbonate becomes the main transported form.
Describe what happens to bicarbonate and chloride in the pulmonary capillaries (include the effect of oxygenation).

Reverse chloride shift plus Haldane effect-driven CO2 unloading.

  • In lungs, O2 binds Hb, reducing Hb’s ability to buffer H+ and to form carbamino compounds (Haldane effect).
  • HCO3− re-enters RBCs from plasma in exchange for Cl− leaving the RBC (reverse chloride shift).
  • Released H+ combines with HCO3− → H2CO3 → CO2 + H2O (carbonic anhydrase), generating CO2 for exhalation.
Define the Haldane effect and explain its mechanisms and clinical significance.

Definition + two mechanisms + one clinical example (COPD/oxygen therapy).

  • Haldane effect: deoxygenated blood can carry more CO2 (and H+) than oxygenated blood at the same PCO2; oxygenation promotes CO2 unloading in the lungs.
  • Mechanisms: (1) deoxyHb forms carbamino compounds more readily; (2) deoxyHb buffers H+ better, driving CO2 → HCO3− in tissues; oxygenation reverses both.
  • Clinical significance: supplemental O2 may increase PaCO2 in severe COPD if ventilation cannot rise, partly because oxygenated Hb carries less CO2 (plus V/Q effects).
Differentiate the Bohr effect from the Haldane effect.
  • Bohr effect: increased CO2/H+ decreases Hb affinity for O2 → promotes O2 unloading in tissues (right shift of O2 dissociation curve).
  • Haldane effect: oxygenation of Hb decreases CO2 (and H+) carriage → promotes CO2 unloading in lungs (downward shift of CO2 content for a given PCO2).
Describe the CO2 dissociation curve and the factors that shift it.

Mention content vs PCO2, relative linearity, and effect of oxygenation.

  • CO2 dissociation curve plots total CO2 content against PCO2; it is relatively linear over physiological PCO2 compared with the sigmoidal O2 curve.
  • Deoxygenation shifts the curve upward (greater CO2 content at any PCO2) due to the Haldane effect.
  • Curve position also depends on buffering capacity and Hb concentration (anaemia reduces total CO2 carriage capacity at a given PCO2).
Why does PaCO2 reflect ventilation more directly than total CO2 content?
  • PaCO2 is determined by the dissolved CO2 in plasma (partial pressure), which equilibrates rapidly with alveolar gas and is governed by alveolar ventilation relative to CO2 production.
  • Most CO2 is stored as bicarbonate/carbamino; these act as large reservoirs so content can change without immediate proportional changes in PaCO2, depending on buffering and Hb oxygenation.
State and explain the alveolar ventilation equation relating PaCO2 to CO2 production.
  • PaCO2 is proportional to CO2 production divided by alveolar ventilation: PaCO2 ∝ VCO2 / VA (with a constant depending on units).
  • If VCO2 is constant, PaCO2 varies inversely with VA: doubling VA halves PaCO2; halving VA doubles PaCO2.
Explain the chloride shift and why it is necessary.
  • As HCO3− is produced in RBCs, it exits into plasma; to maintain electroneutrality, Cl− enters the RBC via anion exchange (AE1).
  • This permits continued bicarbonate formation and CO2 carriage in plasma; in lungs the process reverses to allow CO2 excretion.
A previous FRCA-style viva: 'Why can giving high-flow oxygen increase PaCO2 in a CO2-retaining COPD patient?' Give a structured answer including CO2 transport.

Aim for 3 main mechanisms; explicitly include the Haldane effect.

  • Haldane effect: oxygenation of Hb reduces CO2 (and H+) binding → CO2 is displaced from blood, increasing dissolved CO2 and therefore PaCO2 if ventilation cannot increase.
  • Worsened V/Q mismatch: reversal of hypoxic pulmonary vasoconstriction increases perfusion of poorly ventilated units → increased dead space/venous admixture and higher PaCO2.
  • Reduced ventilatory drive: in some patients, hypoxic drive contributes; raising PaO2 may reduce minute ventilation (usually smaller contribution than V/Q and Haldane).
A previous FRCA-style written question: 'Describe the transport of CO2 from tissues to alveoli and explain how haemoglobin facilitates this.'

Use a stepwise pathway and explicitly mention buffering, carbamino formation, chloride shift, and Haldane effect.

  • CO2 produced in tissues diffuses into blood and RBCs; a small fraction remains dissolved and determines venous PCO2.
  • Most CO2 enters RBCs and is rapidly converted by carbonic anhydrase to H+ and HCO3−; H+ is buffered mainly by deoxyHb, allowing continued conversion.
  • HCO3− is exported to plasma in exchange for Cl− (chloride shift), so plasma bicarbonate becomes the major transported form.
  • A further portion of CO2 binds directly to deoxyHb as carbaminohaemoglobin; deoxygenation increases this binding (Haldane effect).
  • In pulmonary capillaries, oxygenation of Hb reduces H+ buffering and carbamino binding; HCO3− re-enters RBCs (reverse chloride shift), combines with H+ to form CO2, which diffuses into alveoli and is exhaled.

0 comments