What is the Bohr effect?

The Bohr Effect

The Bohr effect is the physiological mechanism by which increased hydrogen ions (H+) and carbon dioxide in metabolically active tissues cause hemoglobin to decrease its affinity for oxygen, thereby facilitating oxygen release precisely where it is most needed. 1, 2

Molecular Mechanism

The Bohr effect operates through specific molecular interactions:

• H+ ions bind to specific amino acid residues on hemoglobin (known as Bohr groups), causing allosteric conformational changes in the hemoglobin molecule that reduce its affinity for oxygen 1, 2
• This binding shifts the oxygen dissociation curve to the right, meaning that at any given partial pressure of oxygen, hemoglobin releases more oxygen to the tissues 1, 3
• The magnitude of this effect is quantified by the Bohr factor, which measures the change in oxygen affinity per unit change in pH 3, 4

Physiological Context

The Bohr effect is intimately linked to tissue metabolism:

• In metabolically active tissues, increased CO₂ production leads to formation of carbonic acid (H₂CO₃), which dissociates to bicarbonate (HCO₃⁻) and H+ ions according to the reaction: CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻ 1, 2
• The resulting increase in H+ concentration (lower pH) triggers the Bohr effect, enhancing oxygen release precisely where oxygen demand is highest 1, 2
• This creates an elegant feedback system where tissues that are metabolically active and producing more CO₂ automatically receive more oxygen 1

Magnitude and Clinical Importance

Recent modeling studies have revealed that the Bohr effect is far more important than historically appreciated:

• The Bohr effect profoundly influences both the shape and position of the oxygen equilibrium curve, not just causing a simple rightward shift 3, 4
• Abolishing the Bohr effect dramatically increases oxygen affinity (decreasing P50 from 26 mmHg to as low as 6 mmHg in modeling studies), making oxygen delivery to tissues severely impaired 3, 4
• The P50 and the Bohr factor are directly related - varying the number of Bohr groups from 0 to 8 per hemoglobin tetramer results in P50 values ranging from 6 to 46 mmHg 4
• Contrary to century-old teaching, the Bohr effect's influence on oxygen delivery is actually more important than its influence on CO₂ uptake (the Haldane effect) 3, 4

Clinical Applications and Pitfalls

Understanding the Bohr effect is essential for several clinical scenarios:

• The Bohr effect is essential for efficient oxygen delivery, particularly during exercise or in metabolically active tissues where acid production increases 1
• Conditions causing alkalosis (decreased H+ concentration) impair oxygen unloading by shifting the curve left, potentially causing tissue hypoxia despite normal oxygen saturation readings 1, 5
• Conversely, acidosis enhances oxygen unloading through the Bohr effect, which can be beneficial for tissue oxygen delivery but problematic if severe enough to impair other physiological functions 1
• Understanding the Bohr effect is crucial when interpreting blood gas results, especially in patients with acid-base disturbances 1

Relationship to Other Oxygen Affinity Modulators

The Bohr effect works in concert with other factors:

• 2,3-DPG (2,3-diphosphoglycerate) also decreases hemoglobin's oxygen affinity and works additively with the Bohr effect 1, 2, 6
• Temperature affects oxygen affinity independently - hypothermia causes a left shift (increased affinity), while hyperthermia causes a right shift (decreased affinity) 2, 5
• In methemoglobinemia, where iron is oxidized to the ferric (Fe³⁺) state, the oxygen dissociation curve shifts left, impairing oxygen release despite the Bohr effect and resulting in "functional anemia" 1, 5

Special Considerations

• The full extent of the Bohr effect cannot be appreciated by comparing oxygen equilibrium curves at constant PCO₂ or pH, but only by comparing curves at constant proton saturation of the Bohr groups, because it is the protons bound to the Bohr groups that directly influence hemoglobin-oxygen binding 3
• Novel allosteric modifiers of hemoglobin (such as ITPP) can augment the Bohr effect without abrogating it, providing additive effects on oxygen delivery 6
• Carbon monoxide binding to hemoglobin affects the Bohr effect differently than oxygen, with the fixed acid Bohr factor increasing in magnitude as carboxyhemoglobin concentration increases 7