oxygen-hemoglobin dissociation curve
Summary
The oxygen-hemoglobin dissociation curve is a sigmoidal graph depicting the relationship between partial pressure of oxygen (PaO2) and hemoglobin oxygen saturation (SaO2). It reflects hemoglobin's cooperative binding of O2, with the sigmoidal shape arising from positive cooperativity between the four heme subunits. Shifts of the curve left or right indicate changes in hemoglobin's affinity for oxygen, which are clinically important for understanding oxygen delivery to tissues.
Detail
Hemoglobin is a tetramer with four oxygen-binding sites; binding of O2 to one subunit induces a conformational change (T to R state) that increases affinity of the remaining subunits—positive cooperativity—producing the characteristic sigmoid curve rather than a hyperbolic one (as seen with myoglobin, which has no cooperativity). The P50 (PaO2 at which Hb is 50% saturated) is normally ~27 mmHg and serves as a marker of Hb affinity.
RIGHT SHIFT (decreased affinity, easier O2 unloading to tissues): Increased temperature, increased 2,3-BPG (produced during glycolysis, elevated in chronic hypoxia/high altitude), increased CO2, decreased pH (Bohr effect—Haldane/Bohr), exercise. Mnemonic: "CADET, face Right!" (CO2, Acid, 2,3-BPG, Exercise, Temperature).
LEFT SHIFT (increased affinity, harder O2 unloading, Hb holds onto O2 tighter): Decreased temperature, decreased 2,3-BPG, decreased CO2, increased pH, carbon monoxide poisoning (CO has ~200x affinity for Hb versus O2, and also causes leftward shift plus decreases O2-carrying capacity), methemoglobin, fetal hemoglobin (HbF has lower affinity for 2,3-BPG, so it holds O2 more tightly than adult Hb, facilitating placental transfer).
Clinical significance: Right shift facilitates O2 unloading at tissues (beneficial during exercise/hypoxia). Left shift impairs O2 unloading despite normal PaO2, seen in CO poisoning and methemoglobinemia, causing tissue hypoxia even with normal-appearing oxygen saturation on some monitors (pulse oximetry may be falsely normal in CO poisoning). Bohr effect: increased CO2/H+ in tissues shifts curve right, promoting O2 release; in lungs, low CO2/H+ shifts curve left promoting O2 loading—works together with Haldane effect (oxygenation of Hb promotes CO2 unloading) for efficient gas exchange.
High-yield exam associations: 2,3-BPG deficiency (rare) causes tissue hypoxia due to left shift; chronic anemia and high altitude increase 2,3-BPG causing right shift (adaptive); sickle cell Hb (HbS) polymerizes when deoxygenated, and curve shifts can be relevant in sickle cell crises management.
Sources
- Guyton and Hall Textbook of Medical Physiology
- First Aid for the USMLE Step 1
- Costanzo Physiology
- Boron & Boulpaep Medical Physiology
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