<P> Chloride shift (also known as the Hamburger shift or lineas phenomenon, named after Hartog Jakob Hamburger) is a process which occurs in a cardiovascular system and refers to the exchange of bicarbonate (HCO) and chloride (Cl) across the membrane of red blood cells (RBCs). </P> <P> Carbon dioxide (CO) is generated in tissues as a byproduct of normal metabolism . It dissolves in blood plasma and into red blood cells (RBC), where carbonic anhydrase catalyzes its hydration to carbonic acid (H CO). Carbonic acid then spontaneously dissociates to form bicarbonate (HCO) and a hydrogen ion (H). In response to the decrease in intracellular pCO, more CO passively diffuses into the cell . </P> <P> Cell membranes are generally impermeable to charged ions (i.e. H, HCO) but RBCs are able to exchange bicarbonate for chloride using the anion exchanger protein Band 3 . Thus, the rise in intracellular bicarbonate leads to bicarbonate export and chloride intake . The term "chloride shift" refers to this exchange . Consequently, chloride concentration is lower in systemic venous blood than in systemic arterial blood: high venous pCO leads to bicarbonate production in RBCs, which then leaves the RBC in exchange for chloride coming in . </P> <P> The opposite process occurs in the pulmonary capillaries of the lungs when the PO rises and PCO falls, and the Haldane effect occurs (release of CO from hemoglobin during oxygenation). This releases hydrogen ions from hemoglobin, increases free H concentration within RBCs, and shifts the equilibrium towards CO and water formation from bicarbonate . The subsequent decrease in intracellular bicarbonate concentration reverses chloride - bicarbonate exchange: bicarbonate moves into the cell in exchange for chloride moving out . Inward movement of bicarbonate via the Band 3 exchanger allows carbonic anhydrase to convert it to CO for expiration . </P>

When bicarbonate ion diffuses out of red blood cells into plasma