Question 6

Describe the carriage of carbon dioxide (CO2) in blood

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College Answer

For a good answer candidates were expected to mention values for CO2 content in blood as 
well as the various ways it is carried (e.g. dissolved, as bicarbonate, combined with 
haemoglobin, etc) and a description of these modes. Wherever possible candidates are 
encouraged to illustrate their answer, in particular if those illustrations are core knowledge. 
Candidates who didn’t, were not penalised if they were still able to provide the required 
responses. However, candidates who did appeared to better synthesize a response. 
Candidates are reminded to include, and know, what are the appropriate units for any 
values they mention.


CO2 is transported by three (maybe, four) major mechanisms:

  • As bicarbonate (HCO3), 70-90% of total blood CO2 content
    • Combined with water, COforms carbonic acid, which in turn forms bicarbonate:
      CO2 + H2O ⇌ H2CO⇌ HCO3- + H+
    • This mainly happens in RBCS
    • The rise in intracellular  HCO3- leads to the exchange of bicarbonate and chloride, the chloride shift. Chloride is taken up by RBCSs, and bicarbonate is liberated.
    • Thus chloride concentration is lower in systemic venous blood than in systemic arterial blood
  • As carbamates, the conjugate bases of carbamino acid (about 10-20%)
    • Dissociated conjugate bases of carbamino acids, which form in the spontaneous reaction of R-NHand CO2.
    • Intracellular (RBC) carbamino stores are the greatest: haemoglobin, particularly deoxygenated haemoglobin, has a high affinity for CO2, whereas most other proteins do not
  • As dissolved CO2 gas, about 10%
    • Henry's law states that the amount of dissolved gas in a liquid is proportional to its partial pressure above the liquid
    • Thus, for every 1 mmHg of pCO2 the blood concentration increases by about 0.03 mmol/L
    • Thus, CO2 is 10-20 times more soluble than oxygen 
  • Carbonic acid: 
    • A miniscule proportion of total carbon dioxide exists in this form, i.e. it is not a major contributor to CO2 transport

There is a difference between arterial and venous CO2 content:

  • Mixed venous blood has a total CO2 content of  about 22.5 mmol/L
    (or 520 mL/L)
  • Arterial blood has a total CO2 content of about 20.5 mmol/L 
    (or 480ml/L)
  • Much of this difference is due to the increase in bicarbonate concentration (85%)
  • Some of this difference is also due to the Haldane effect:
    • Deoxyhaemoglobin has about 3.5 times the affinity for CO2 when compared to oxyhaemoglobin
    • This increases the CO2 binding capacity of venous blood
    • Deoxyhaemoglobin is also a better buffer than oxyhaemoglobin, which increases the capacity of RBCs to carry HCO3-


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Cherniack, NEIL S., and G. S. Longobardo. "Oxygen and carbon dioxide gas stores of the body." Physiol Rev 50.2 (1970): 196-243.

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Groeneveld, AB Johan. "Interpreting the venous-arterial PCO2 difference." Critical care medicine 26.6 (1998): 979-980.