Carbon Dioxide

Describe the oxygen and carbon dioxide stores in the body

Describe the carbon dioxide carriage in blood including the Haldane effect and the chloride shift

Explain the carbon dioxide dissociation curve

Describe the movement of carbon dioxide from blood to the atmosphere

CO2 is produced in the mitochondria during the citric-acid cycle as a product of metabolism.

  • There is ~120L of carbon dioxide in the body
    A total of, of which is in relatively inaccessible compartments.
  • Normal elimination (and, at steady state, production) of carbon dioxide is 200ml.min-1

Carbon Dioxide in Blood

In blood, CO2 is stored as:

  • Bicarbonate (90%)
  • Dissolved gas
  • Carbamino compounds
Form Arterial Blood Additional CO2 in venous blood
Bicarbonate 90% 60%
Dissolved 5% 10%
Carbamino compounds 5% 30%


  • CO2 diffuses freely into erythrocytes, where it can be catalysed by carbonic anhydrase to produce bicarbonate:
  • To maintain bicarbonate production, the products (H+ and HCO3-) are then removed:
    • H+ ions are buffered to haemoglobin
    • Intracellular HCO3- is then exchanged with extracellular Cl- via the BAND3 membrane protein
      • This is called the Hamburger, or Chloride Shift
      • Chloride entering the cell draws water in along its osmotic gradient, increasing the haematocrit of venous blood relative to arterial blood

Dissolved Gas

  • As per Henry's Law, the amount of carbon dioxide dissolved in blood is proportional to the PaCO2
  • As carbon dioxide is 20x as soluble as oxygen in water, dissolved carbon dioxide contributes much greater proportion of carbon dioxide content than dissolved oxygen does to oxygen content

Carbamino Compounds

  • CO2 can bind directly to proteins (predominantly haemoglobin), which displaces a H+ ion:
    • The H+ ion is then buffered by another plasma protein (also predominantly haemoglobin)
  • Bound CO2 does not contribute to the partial pressure gradient
  • Carbamino compounds are only a small contributor to overall CO2 carriage, but contribute about one third of the arterio-venous CO2 difference due to the Haldane effect
    The Haldane effect states that deoxyHb binds CO2 more effectively than oxyHb. This is because:
    • DeoxyHb is a better buffer of H+
      pKa of deoxyHb is 8.2, compared to that of oxyHb which is 6.6.
      • Enhanced buffering contributes ~30% of the Haldane effect
    • DeoxyHb forms carbamino compounds more easily Deoxy-Hb has 3.5x the affinity for CO2 than Oxy-Hb.
      • This forms ~70% of the Haldane effect

CO2 Dissociation Curve

This curve plots PCO2 against blood CO2 content in ml.100ml-1.

Key points:

  • Mixed venous CO2 content is 52ml.100ml-1, at a PCO2 of 46mmHg
  • Arterial CO2 content is 48ml.100ml-1, at a PCO2 of 40mmHg
  • Approximately 50% of the arterial-mixed venous difference occurs due to the upwards shift of the curve, which is due to the Haldane effect
    This is the mechanism for changes in PO2 affecting the CO2 dissociation curve.

Comparison Curve

Comparison of gas content of both oxygen and carbon dioxide per 100mL of blood:

Removal of CO2

CO2 dissolves from pulmonary arterial blood into the alveolus down a concentration gradient. As inspired CO2 is negligible, PACO2 is a function of alveolar ventilation and CO2 output, given by the equation:

Simplified, PaCO2 is inversely proportional to alveolar ventilation:

Distribution of Carbon Dioxide

CO2 in the body can be considered as a three-compartment model:

  • Well-perfused (blood, brain, kidneys)
  • Moderately-perfused (resting muscle)
  • Poorly-perfused (bone, fat))

  • Each of these tissues has a different time-constant, such that a mismatch of ventilation with metabolic activity may take 20-30 minutes to equilibrate across compartments

  • Therefore hypoventilation and hyperventilation have different effects on PCO2:
    • Hyperventilation causes a rapid decrease in PCO2 in blood, subsequent (slower) redistribution from peripheral compartments
    • Hypoventilation causes a rise in PaCO2, the rate of which is determined both by production and distribution into plasma
      • With no ventilation, PCO2 rises at 3-6mmHg.min-1
        • Due to the Haldane effect the PaCO2 will rapidly increase during passage through the pulmonary capillary (despite the fact that carbon dioxide content is unchanged) as the proportion of OxyHb increases
      • Therefore:
        • PaO2 is more sensitive at detecting early hypoventilation provided PAO2 is normal
        • Steady-state PCO2 gives the best indication of adequacy of ventilation
          • In acute hypoventilation, produced CO2 is preferentially stored in tissues, decreasing CO2 elimination
          • In acute hyperventilation, CO2 is mobilised from tissues resulting in increased CO2 elimination

CO2 Cascade

Region Value (mmHg)
Mixed Venous 46
Alveolar 40
(Arterial) 40
Mixed-expired 27
  • Venous CO2 diffuses into the alveolus, reaching equilibrium with arterial PCO2
  • Alveolar CO2 is then diluted by dead space gas, resulting in a lower ME'CO2


  1. Lumb A. Nunn's Applied Respiratory Physiology. 7th Edition. Elsevier. 2010.
  2. FRCA: Anaesthesia Tutorial of the Week - Respiratory Physiology
Last updated 2021-08-23

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