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 1.8L.kg^-1, 1.6L.kg^-1 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

Bicarbonate

• CO₂ diffuses freely into erythrocytes, where it can be catalysed by carbonic anhydrase to produce bicarbonate:
  $CO_2 + H_2O \Leftrightarrow H_2CO_3 \Leftrightarrow H^+ + HCO_3^-$
• To maintain bicarbonate production, the products (H⁺ and HCO₃^-) are then removed:
  • H⁺ ions are buffered to haemoglobin
    $HbO_2 + H^+ \Leftrightarrow HHb + O_2$
  • 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:
  $Hb + CO_2 \Leftrightarrow HbCOO^- + H^+$
  • The H⁺ ion is then buffered by another plasma protein (also predominantly haemoglobin)
    $Hb + H^+ \Leftrightarrow HHb$
• 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:

$PACO_2 = {CO_2 \ output \over \dot{V}_A}$

Simplified, PaCO₂ is inversely proportional to alveolar ventilation:

$PACO_2 \propto {1 \over \dot{V}_A}$

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

• 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

References

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