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Tissue cells that are metabolically active produce carbon dioxide that diffuses into erythrocytes in the systemic capillaries. Carbon dioxide combines with water in the erythrocytes to produce a weak acid called carbonic acid. This reaction is facilitated by the enzyme carbonic anhydrase, which acts to speed up the reaction. Carbonic acid dissociates into a bicarbonate ion and a proton. The proton binds to haemoglobin, forming protonated haemoglobin, or HHb. The bicarbonate ion diffuses down its concentration gradient into the blood, taking along its negative charge.
To balance the charge in the erythrocyte, chloride ions, which are also negatively charged, move into the erythrocytes from the blood in a process known as the chloride shift. The reverse chemical reaction takes place in erythrocytes that move into the capillaries of the lungs. Bicarbonate from the blood moves into the erythrocyte and chloride leaves to balance the charge.
Haemoglobin donates a proton, which combines with bicarbonate ions to produce carbonic acid. Carbonic anhydrase catalyses the conversion of carbonic acid into carbon dioxide and water, allowing the reaction to take place quickly. Carbon dioxide then diffuses down its concentration gradient across the alveolar walls and is exhaled.