Overview Oxygen-hemoglobin dissociation curve sigmoidal shape is characteristic of positive cooperativity binding of 1 O2 molecule to 1 subunit of deoxyhemoglobin increases affinity for O2 in adjacent subunits P50 is PO2 at which hemoglobin is 50% saturated ↑ P50 → ↓ hemoglobin affinity for O2 50% saturation achieved at higher-than-normal P50 ↓ P50 → ↑ hemoglobin affinity for O2 50% saturation achieved at lower-than-normal P50 Loading and unloading of oxygen in lungs PaO2 ≈ 100 mm Hg hemoglobin % saturation ≈ 100% facilitates maximal O2 loading into arterial blood in lungs in peripheral tissues PvO2 ≈ 40 mm Hg hemoglobin % saturation ≈ 75% facilitates O2 unloading into peripheral tissues Shift to right mechanism ↑ P50 → ↓ hemoglobin affinity for O2 → ↑ O2 unloading causes ↑ PCO2, ↓ pH (Bohr Effect) ↑ PCO2 → ↑ H+ → ↓ pH CO2 + H2O → H2CO3 → H+ + HCO3- ↑ PCO2 → equilibrium reaction shifts right Le Chatelier's principle ↑ CO2, ↑ H+ bind hemoglobin and stabilize low O2 affinity T (taut) state ↓ hemoglobin affinity for O2 → ↑ O2 unloading e.g., exercise → ↑ PCO2, ↓ pH ↑ O2 unloading ensures O2 delivery meets O2 demand in skeletal muscle ↑ temperature e.g., ↑ tissue metabolism → ↑ temperature ↑ 2,3-bisphosphoglycerate (2,3-BPG) high altitude → hypoxemia → ↑ synthesis of 2,3-BPG Also seen in heart failure, anemia, morbid obesity, etc. ↑ 2,3-BPG binds hemoglobin and stabilizes low O2 affinity T (taut) state ↓ hemoglobin affinity for O2 → ↑ O2 unloading Shift to left mechanism ↓ P50→ ↑ hemoglobin affinity for O2 → ↓ O2 unloading causes ↓ PCO2, ↑ pH (Bohr Effect) ↓ PCO2 → ↓ H+ → ↑ pH ↓ CO2, ↓ H+ → stabilizes high O2 affinity R (relaxed) state ↑ hemoglobin affinity for O2 → ↑ O2 loading conversely, ↑ O2 decreases Hb affinity for CO2/H (Haldane effect) ↓ temperature ↓ tissue metabolism → ↓ temperature ↓ 2,3-bisphosphoglycerate (2,3-BPG) hemoglobin F fetal hemoglobin 2 α subunits and 2 γ subunits (α2γ2) ↑ affinity for O2, ↓ affinity for 2,3-BPG facilitates O2 delivery from mother to fetus