The chloride shift is the exchange of intracellular bicarbonate ions (HCO₃⁻) for extracellular chloride ions (Cl⁻) across the red blood cell membrane. It occurs via the anion exchanger protein AE1 (Band 3).
Suggested diagram: Red blood cell showing CO₂ entry, conversion to HCO₃⁻, and the chloride shift across the membrane.
Steps of the chloride shift
Step
Location
Process
1
Peripheral tissue capillaries
CO₂ diffuses into erythrocytes and is hydrated to HCO₃⁻ + H⁺.
2
Inside erythrocyte
HCO₃⁻ is exported to plasma in exchange for Cl⁻ entering the cell (chloride shift).
3
Plasma
HCO₃⁻ travels to the lungs bound to plasma proteins.
4
Lung capillaries
HCO₃⁻ re‑enters erythrocytes, Cl⁻ exits, and HCO₃⁻ is converted back to CO₂ for exhalation.
Importance of the chloride shift
Maintains electrochemical neutrality: The exchange of negatively charged ions prevents a charge imbalance as HCO₃⁻ leaves the cell.
Facilitates CO₂ transport: By moving HCO₃⁻ into plasma, the blood can carry a much larger amount of CO₂ than would be possible by dissolution alone.
Supports efficient gas exchange in the lungs: The reverse shift in the pulmonary capillaries ensures that HCO₃⁻ is rapidly converted back to CO₂, maintaining the gradient for CO₂ diffusion out of the blood.
Regulates blood pH: The interconversion of CO₂, H⁺ and HCO₃⁻, together with the chloride shift, forms a major component of the bicarbonate buffering system.
Key points to remember
The chloride shift is a rapid, reversible ion exchange mediated by the AE1 protein.
It occurs in opposite directions in systemic (tissue) and pulmonary (lung) capillaries.
Without the chloride shift, the capacity of blood to transport CO₂ would be severely limited, and acid–base balance would be disrupted.