Question

What is the chloride shift and why does it occur?

Answer 1

Definition: 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 (HCO₃^?) and chloride (Cl^?) across the membrane of red blood cells (RBCs).

Reason: Carbon dioxide (CO₂) 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 form carbonic acid (H₂CO₃). Carbonic acid then spontaneously dissociates to form bicarbonate (HCO₃^?) and a hydrogen ion (H⁺). In response to the decrease in intracellular pCO₂, more CO₂ passively diffuses into the cell.

Cell membranes are generally impermeable to charged ions (i.e. H⁺, HCO₃^? ) 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.

The underlying properties creating the chloride shift are the presence of carbonic anhydrase within the RBCs but not the plasma, and the permeability of the RBC membrane to carbon dioxide and bicarbonate ion but not to hydrogen ion. Continuous process of carbonic acid dissociation and outflow of bicarbonate ions would eventually lead to a change of intracellular electric potential because of lasting H+ ions. Inflow of chloride ions maintains electrical neutrality of a cell.