Anion Transport

There are −106 copies of the band 3 protein per normal human red blood cell [1]. The principal function of this transport protein is to mediate the rapid exchange of extracellular chloride (Cl“) and intracellular bicarbonate (HCO₃ ^~) i°ns during the red blood cell’s passage through the capillaries of the tissue, and the reverse exchange during their transit through the alveolar capillaries. This rapid exchange is of central importance in the physiology of CO₂ transport. Hamburger has been credited with first proposing, in 1892, that Cl and HCO₃ are exchanged across the red blood cell membrane [2]. This “Hamburger shift” is the classical mechanism that explains the observation that venous plasma Cl is 1–2 mM lower than arterial plasma Cl concentration. The overall mechanism (Figure 1) was first clearly described by Jacobs and Stewart [3]. As the erythrocyte enters a tissue capillary, it encounters a higher pCO₂ (46 mm Hg) than in the arterial circulation (40 mm Hg). The pCO₂ of the plasma and intraerythrocyte compartments rises rapidly to 46 mm Hg, and takes CO₂ and carbonic acid (H₂CO₃) out of equilibrium. As part of reestablishing the equilibrium, some CO₂ is hydrated to carbonic acid, which instantaneously dissociates to bicarbonate and protons. The hydration reaction occurs much more rapidly within the erythrocyte than in the plasma because of intracellular carbonic anhydrases (EC 4.2.1.1). The new protons are mostly buffered by hemoglobin and this protonation reaction facilitates oxygen unloading because protonated hemoglobin Figure 1 Erythrocyte uptake of CO₂ in peripheral capillaries. Tissue CO₂ is transported as dissolved CO₂ (8%) in both cytoplasm and plasma, as carbamino hemoglobin (HbNHCOO”, 11%) in the cytoplasm and as bicarbonate (81%) in cytoplasm (24%) and plasma (57%). This latter bicarbonate is the result of intra-cellular hydration catalyzed by carbonic anhydrase (C. A.) followed by dissociation into a proton and bicarbonate and its exchange with extracellular chloride on band 3. A proton is produced by each CO₂ not carried as dissolved CO₂ and these protons are largely buffered by oxyhemoglobin (HbO₂) and promote O₂ dissociation and delivery to the tissue https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781003066118/04df0481-596a-4660-8298-7640562170ee/content/fig1_19.tif"/> 564 565has a decreased affinity for O₂ (Bohr shift). The new bicarbonate ions accumulate within the cell and would remain there were not band 3 present to export them in exchange for plasma chloride. The removal of this bicarbonate from the cells allows the chain of reactions including the hydration of CO₂ and the subsequent dissociation of carbonic acid to continue until the plasma bicarbonate reaches equilibrium as well. By carrying HCO₃ in the plasma as well as the cytoplasm, the blood greatly increases its total CO₂ carrying capacity (see below).