Chloride shift (also known as the Hamburgers shift or Hamburger's phenomenon, named after Hartog Jakob Hamburger) is a process which occurs in a cardiovascular system and refers to the exchange of bicarbonate (HCO3-) and chloride (Cl-) across the membrane of red blood cells (RBCs).
Carbon dioxide (CO2) generated in tissues passively diffuses into capillaries via the interstitial fluid. Once in circulation, CO2 enters red blood cells (RBCs) to balance the intracellular and extracellular CO2 concentrations. RBCs contain appreciable quantities of carbonic anhydrase, an enzyme which converts CO2 to carbonic acid and which is not highly expressed in interstitial fluid and plasma. RBC carbonic anhydrase converts dissolved CO2 and intracellular water to carbonic acid (H2CO3), which spontaneously dissociates to form bicarbonate (HCO-3) and a hydrogen ion (H+). In response to the fall of intracellular CO2, more CO2 passively diffuses into the cell.
Red blood cells are impermeable to hydrogen ions but are able to exchange bicarbonate ions for chloride ions using the exchanger protein Band 3. A rise in intracellular bicarbonate causes chloride intake and bicarbonate export. The term "chloride shift" refers to this exchange. As a result, blood chloride concentration is lower in systemic venous blood than in systemic arterial blood or in pulmonary circulation because the levels of CO2 and therefore bicarbonate are higher in systemic venous blood, providing less of a driving force for exchange.
The opposite process occurs when blood O2 concentrations rise and the Haldane effect occurs (release of CO2 from hemoglobin). Release of hydrogen ions from hemoglobin increases H+ concentration within RBCs, shifting the equilibrium towards CO2 and water formation from bicarbonate. The subsequent decrease in intracellular bicarbonate concentration reverses chloride-bicarbonate exchange. Inward movement of bicarbonate across Band 3 allows carbonic anhydrase to convert it to CO2 for expiration.
Reaction (as it occurs in the lung)
HCO3- --> --> --> HCO3- Na+ K+
Cl- <-- <-- <-- <-- Cl-
Bicarbonate in the red blood cell (RBC) exchanging with chloride from plasma.
The underlying properties creating the chloride shift are the presence of carbonic anhydrase within the red blood cell but not the blood, and the permeability of the blood to bicarbonate but not to hydrogen. Exchange of bicarbonate for chloride ions across the erythrocyte cell membrane maintains the electrical neutrality of the cell. Bicarbonate moves against its concentration gradient: erythrocyte [HCO3] is about 15 mmol/L; plasma [HCO3] is about 24 mmol/L. Chloride moves down its concentration gradient. This active transport is facilitated by the Band 3 anion exchanger protein.
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