Carbon dioxide can be transported through the blood via three methods. It is dissolved directly in the blood, bound to plasma proteins or hemoglobin, or converted into bicarbonate.

The majority of carbon dioxide is transported as part of the bicarbonate system. Carbon dioxide diffuses into red blood cells. Inside, carbonic anhydrase converts carbon dioxide into carbonic acid (H2CO3), which is subsequently hydrolyzed into bicarbonate (HCO3−) and H+. The H+ ion binds to hemoglobin in red blood cells, and bicarbonate is transported out of the red blood cells in exchange for a chloride ion. This is called the chloride shift.

Bicarbonate leaves the red blood cells and enters the blood plasma. In the lungs, bicarbonate is transported back into the red blood cells in exchange for chloride. The H+ dissociates from hemoglobin and combines with bicarbonate to form carbonic acid with the help of carbonic anhydrase, which further catalyzes the reaction to convert carbonic acid back into carbon dioxide and water. The carbon dioxide is then expelled from the lungs.

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