Overview Forms of Carbon Dioxide (CO2) in the Blood Dissolved CO2 Bicarbonate (HCO3-) Carbaminohemoglobin ~5-10% of total CO2 content 70% of total CO2 content 20-25% of total CO2 content CO2 bound to N-terminus amino group of hemoglobin (Hb) Stabilizes taut form of Hb → right-shift of O2-Hb dissociation curve (Bohr effect) → favors O2 release Transport of CO2 in blood (peripheral tissues → RBC → lungs) peripheral tissues metabolically active tissues produce CO2, which diffuses across the cell membrane and eventually into the RBC at the level of the capllaries RBC carbaminohemoglobin ↑ pCO2 is produced in peripheral tissues this facilitates CO2 binding to Hb, forming carbaminohemoglobin (CO2-Hb) in turn, the Taut (T) state of Hb is stabilized Bohr effect enhanced release of O2 in the presence of low pH or increased pCO2 CO2-Hb → ↓ Hb affinity for O2 → ↑ O2 unloading into tissues right shift in the hemoglobin-oxygen (Hb-O2) dissociation curve H+ produced by converting CO2 + H2O to HCO3- + H+ via carbonic anhydrase (CA) which contributes in lowering the pH protonated Hb stabilizes the T state, facilitating O2 release into tissues (oxyhemoglobin) HbO2 + H+ ↔ HbH + O2 (deoxyhemoglobin) Haldane effect at low pO2 levels, the carrying capacity of CO2 increases in other words, there is an increase affinity for CO2 when there is less O2 bound to hemoglobin bicarbonate (HCO3-) CA reversibly catalyzes the formation of HCO3- from the hydration of CO2 this reaction is reversible, thus CA is also involved in the dehydration of H2CO3 CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- the produced H+ remains in the RBC, where it is buffered by deoxyhemoglobin deoxyhemoglobin is a better H+ buffer than oxyhemoglobin the produced HCO3- is transported into the plasma via a chloride-bicarbonate (Cl-HCO3) exchanger (AE1 or band three protein) this describes the chloride (or Hamburger) shift lung the reactions mentioned above occur in reverse inside the lung carbaminohemoglobin Bohr effect in lungs (low PCO2), CO2 dissociates from hemoglobin and stabilizes high O2 affinity Relaxed (R) state hemoglobin-oxygen dissociation curve left shifts → ↑ hemoglobin affinity for O2 → ↑ O2 loading Haldane effect O2 loading → ↓ hemoglobin affinity for CO2 → ↑ CO2 unloading bicarbonate HCO3- is exchanged for Cl- (chloride shift) across RBC membranes HCO3- enters RBCs Haldane effect O2 loading → ↓ hemoglobin affinity for H+→ ↑ H+ unloading H+ + HCO3- → H2CO3 → CO2 + H2O ↑ H+ drives equilibrium reactions to right (CO2 formation).