Transport of Carbon Dioxide; Haldane Effect
(Guyton and Hall Textbook of Medical Physiology, 4th South Asia Edition)
Overview
CO2 transport is far less problematic than O2 transport because CO2 can be carried in much larger quantities even under abnormal conditions. Under resting conditions, about 4 mL of CO2 is transported from the tissues to the lungs in each 100 mL of blood. CO2 diffuses out of tissue cells in the dissolved molecular form and is carried in the blood in three forms:
1. Dissolved CO2 (about 7%)
A small fraction remains simply dissolved in the plasma/blood water. Venous PCO2 (45 mm Hg) corresponds to about 2.7 mL/100 mL dissolved CO2, versus 2.4 mL/100 mL at arterial PCO2 (40 mm Hg) - a difference of only 0.3 mL, accounting for roughly 7% of total CO2 transported.
2. As bicarbonate ion (about 70%, the most important form)
- CO2 combines with water inside red blood cells to form carbonic acid (H2CO3), a reaction accelerated about 5000-fold by the enzyme carbonic anhydrase.
- H2CO3 rapidly dissociates into H+ and HCO3-.
- Most H+ is buffered by hemoglobin (a powerful acid-base buffer); HCO3- diffuses out into the plasma in exchange for Cl- entering the red cell via a bicarbonate-chloride carrier protein - the chloride shift.
- This mechanism carries about 70% of total transported CO2. Blocking carbonic anhydrase (e.g., with acetazolamide) raises tissue PCO2 from 45 to as high as 80 mm Hg, showing the importance of this pathway.
3. As carbamino compounds (about 20-30%)
CO2 combines directly with amine groups of the hemoglobin molecule (and to a much lesser extent with plasma proteins) to form carbaminohemoglobin (HbCO2). This is a reversible, loose reaction. It accounts for about 30% of total CO2 carried, though because the reaction is slower, only about 20% is exchanged under normal transport conditions.
Haldane Effect
Just as increased CO2 displaces O2 from hemoglobin in the tissues (the Bohr effect, which aids O2 delivery), the reverse also occurs: binding of O2 with hemoglobin in the lungs tends to displace CO2 from the blood - this is the Haldane effect. Quantitatively, the Haldane effect is even more important for CO2 transport than the Bohr effect is for O2 transport.
Mechanism: When O2 combines with hemoglobin in the pulmonary capillaries, hemoglobin becomes a stronger acid. This more acidic hemoglobin displaces CO2 from the blood in two ways:
- It has less tendency to bind CO2 as carbaminohemoglobin, releasing much of the carbamino-bound CO2.
- Its increased acidity causes it to release excess H+, which combines with HCO3- to form H2CO3, which then dissociates into H2O and CO2 - this CO2 diffuses into the alveoli and is expired.
The opposite happens at the tissue level: as hemoglobin releases O2, it becomes a weaker acid (more alkaline), which allows it to pick up more CO2 and H+ (via the same reactions in reverse), facilitating CO2 loading in the tissues.
Significance: Because of the Haldane effect, the CO2 dissociation curve for oxygenated blood (PO2 = 100 mm Hg, as in lung capillaries) lies below that for deoxygenated blood (PO2 = 40 mm Hg, as in tissue capillaries). This shift allows a much greater quantity of CO2 to be released in the lungs and picked up in the tissues, for any given change in PCO2, than would be possible without this effect - roughly doubling the efficiency of CO2 exchange between the venous and arterial states.
Summary table
| Form | % of total CO2 transported |
|---|
| Dissolved CO2 | ~7% |
| Bicarbonate (HCO3-) | ~70% |
| Carbamino compounds (mainly with Hb) | ~20-30% |
- Guyton and Hall Textbook of Medical Physiology, pp. 528-530