Oxygen-Hemoglobin Dissociation Curve, Bohr Effect, and Haldane Effect Simplified
The Oxygen-Hemoglobin Dissociation Curve
The oxygen-hemoglobin dissociation curve is an S-shaped (sigmoidal) curve that shows how hemoglobin picks up oxygen in the lungs and releases it to tissues, with two key protective features: a flat upper portion that maintains near-complete saturation despite falling oxygen pressure, and a steep middle portion that ensures continued oxygen delivery to tissues even as saturation drops. 1
Key Features of the Curve Shape
Upper flat portion (plateau): When arterial oxygen pressure (PaO2) is above 8 kPa (60 mm Hg), hemoglobin saturation (SaO2) remains near 100% even if PaO2 drops significantly—this protects you during mild hypoxemia 1
Steep middle portion: As saturation falls rapidly in this zone, the PaO2 remains relatively preserved, facilitating continued oxygen delivery to metabolically active tissues 1
The sigmoidal shape reflects the cooperative effect—once one oxygen molecule binds to hemoglobin, the next ones bind more easily 2, 3
Practical Clinical Correlations
The relationship between PaO2 and SaO2 is not linear, which has critical implications 1:
- PaO2 of 8 kPa (60 mm Hg) = SaO2 of ~90%
- PaO2 of 10 kPa (75 mm Hg) = SaO2 of ~95%
- PaO2 of 13 kPa (97.5 mm Hg) = SaO2 of ~98%
Target oxygen therapy to maintain PaO2 ≥8 kPa or SpO2 ≥90% in most patients, which corresponds to the flat portion of the curve where small decreases in PaO2 don't produce large reductions in saturation. 4
The Bohr Effect
The Bohr effect is the mechanism by which increased hydrogen ions (H+) and CO₂ in metabolically active tissues cause hemoglobin to release oxygen more readily by shifting the dissociation curve to the right—essentially, acidic and CO₂-rich tissues get more oxygen exactly when and where they need it. 4, 5
How It Works Mechanistically
In metabolically active tissues, increased CO₂ production leads to formation of carbonic acid (H₂CO₃), which dissociates to bicarbonate (HCO₃⁻) and H+ ions 5
H+ ions bind to specific amino acid residues on hemoglobin (Bohr groups), causing allosteric conformational changes that decrease hemoglobin's affinity for oxygen 4, 5
This rightward shift enhances oxygen release precisely where oxygen demand is highest 4
Factors That Shift the Curve RIGHT (Enhanced Oxygen Release)
A rightward shift facilitates oxygen unloading to tissues and occurs with: 1, 6
- Increased H+ ions (acidosis/low pH)
- Increased CO₂ (hypercapnia)
- Increased temperature (fever)
- Increased 2,3-DPG (chronic hypoxemia, stored blood after transfusion)
Factors That Shift the Curve LEFT (Impaired Oxygen Release)
A leftward shift increases oxygen capture in the lungs but hinders tissue release, creating "functional anemia" where tissues experience hypoxia despite normal hemoglobin and SpO2: 6, 5
- Decreased H+ ions (alkalosis/high pH)
- Decreased CO₂
- Decreased temperature (hypothermia)
- Decreased 2,3-DPG (stored blood)
- Methemoglobinemia
Critical Clinical Pitfall
Normal SpO2 can mask significant tissue hypoxia in patients with a left-shifted curve—always obtain arterial blood gas with co-oximetry when suspecting CO poisoning, methemoglobinemia, or severe alkalosis, as standard pulse oximeters cannot differentiate these conditions. 6
The Haldane Effect
The Haldane effect describes how deoxygenated hemoglobin has increased capacity to bind CO₂ and H+ ions, facilitating CO₂ removal from tissues and transport to the lungs—this is the flip side of the Bohr effect. 4, 7
Mechanism and Physiological Importance
When oxygen is released from hemoglobin in peripheral tissues, the deoxygenated hemoglobin becomes a better buffer for H+ ions and can bind more CO₂ 4
This enhances CO₂ removal from metabolically active tissues where CO₂ production is high 4
The Haldane effect plays a far greater physiological role than the reciprocal influence of CO₂ on oxygen transport (the classical Bohr effect) 7
Clinical Consequence in Oxygen Therapy
Increasing inspired oxygen (FiO₂) decreases the carbon dioxide buffering capacity of hemoglobin through the Haldane effect, which can contribute to CO₂ retention in patients with limited ventilatory reserve. 4
This is why target oxygen saturation of 88-92% in COPD patients reduces mortality compared to high-concentration oxygen 4, 6
Excessive oxygen can worsen hypercapnia through multiple mechanisms including the Haldane effect 4
Putting It All Together: Clinical Algorithm
For Oxygen Therapy Targets:
- Standard patients (no hypercapnia risk): Target SpO2 94-98% 6
- COPD or chronic CO₂ retention: Target SpO2 88-92% 4, 6
- Goal: Maintain PaO2 ≥8 kPa (60 mm Hg) or SpO2 ≥90% minimum 4
When Suspecting Left Shift (Impaired Oxygen Release):
- Obtain arterial blood gas with co-oximetry to measure PaO2, SaO2, pH, carboxyhemoglobin (COHb), methemoglobin (MetHb) 6
- Measure body temperature 6
- Correct alkalosis if present by treating the primary cause 6
- Normalize temperature in hypothermic patients 6
- Treat methemoglobinemia with methylene blue if MetHb >20-30% or symptomatic 6
- Consider higher SpO2 targets than standard range 6
When Suspecting Right Shift:
- Evaluate if it is compensatory (chronic anemia, chronic lung disease, high altitude) 6
- Do not correct if physiologically appropriate 6
- Optimize other components of oxygen delivery (cardiac output, hemoglobin level) 6
Special Consideration for Transfusion:
Stored blood has depleted 2,3-DPG levels causing a leftward shift, but 2,3-DPG returns to ~50% of normal after 6 hours post-transfusion and normalizes completely within 48 hours. 1, 6