Chloride shift (also known as the Hamburger phenomenon or lineas phenomenon, named after

Hartog Jakob Hamburger Hartog Jakob or Hartog Jacob Hamburger (9 March 1859 – 4 January 1924) was a Dutch physiologist, born in Alkmaar. After completing the Hogere Burgerschool in Alkmaar, Hamburger studied chemistry at Utrecht University, where he received his doc ...

) is a process which occurs in a

cardiovascular system The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

and refers to the exchange of

bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial biochemic ...

(HCO₃⁻) and

chloride The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride salts ...

(Cl⁻) across the membrane of

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

s (RBCs).

Mechanism

Carbon dioxide Carbon dioxide (chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is transpar ...

(CO₂) is produced in tissues as a byproduct of normal metabolism. It dissolves in the solution of blood plasma and into red blood cells (RBC), where

carbonic anhydrase The carbonic anhydrases (or carbonate dehydratases) () form a family of enzymes that catalyze the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions). The active site ...

catalyzes its hydration to carbonic acid (H₂CO₃). Carbonic acid then spontaneously

dissociate Dissociation in chemistry is a general process in which molecules (or ionic compounds such as salts, or complexes) separate or split into other things such as atoms, ions, or radicals, usually in a reversible manner. For instance, when an acid ...

s to form bicarbonate Ions (HCO₃⁻) and a

hydrogen ion A hydrogen ion is created when a hydrogen atom loses or gains an electron. A positively charged hydrogen ion (or proton) can readily combine with other particles and therefore is only seen isolated when it is in a gaseous state or a nearly particle ...

(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 Band 3 anion transport protein, also known as anion exchanger 1 (AE1) or band 3 or solute carrier family 4 member 1 (SLC4A1), is a protein that is encoded by the gene in humans. Band 3 anion transport protein is a phylogenetically-preserved ...

. 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 pCO₂ leads to bicarbonate production in RBCs, which then leaves the RBC in exchange for chloride coming in. The opposite process occurs in the pulmonary capillaries of the lungs when the PO₂ rises and PCO₂ falls, and the

Haldane effect The Haldane effect is a property of hemoglobin first described by John Scott Haldane, within which oxygenation of blood in the lungs displaces carbon dioxide from hemoglobin, increasing the removal of carbon dioxide. Consequently, oxygenated blood ...

occurs (release of CO₂ from hemoglobin during oxygenation). This releases hydrogen ions from hemoglobin, increases free H⁺ concentration within RBCs, and shifts the equilibrium towards CO₂ 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 CO₂ for expiration. The chloride shift may also regulate the affinity of

hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...

for

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...

through the chloride ion acting as an

allosteric In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the ''allosteric site ...

effector.

Reaction

Reaction (as it occurs in the pulmonary capillaries) RBC PLASMA HCO₃⁻ <-- <-- <-- HCO₃⁻ K⁺ Na⁺ Cl⁻ --> --> --> --> Cl⁻ Bicarbonate in the red blood cell (RBC) exchanging with chloride from plasma in the lungs. 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. The net direction of bicarbonate-chloride exchange (bicarbonate out of RBCs in the systemic capillaries, bicarbonate into RBCs at pulmonary capillaries) proceeds in the direction that decreases the sum of the electrochemical potentials for the chloride and bicarbonate ions being transported.

References

{{DEFAULTSORT:Chloride Shift Blood Respiratory physiology