What is the Haldane Effect
The Haldane effect describes how deoxygenated hemoglobin has an increased capacity to bind CO₂ and H⁺ ions compared to oxygenated hemoglobin, facilitating CO₂ removal from metabolically active tissues and its transport to the lungs. 1
Physiological Mechanism
The Haldane effect operates through a reciprocal relationship between oxygen and carbon dioxide binding to hemoglobin:
When oxygen is released from hemoglobin in peripheral tissues, the deoxygenated hemoglobin becomes a better buffer for H⁺ ions and can bind more CO₂, enhancing CO₂ removal from metabolically active tissues 1
This effect is distinct from but complementary to the Bohr effect, which describes how increased CO₂ and H⁺ ions cause hemoglobin to release oxygen more readily 1, 2
The Haldane effect plays a far greater physiological role in CO₂ transport than the reciprocal influence of CO₂ on oxygen transport (the classical Bohr effect) 3
Clinical Significance in Oxygen Therapy
The Haldane effect has important clinical implications when administering supplemental oxygen:
Increasing 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, 1
The Haldane effect is ranked as the third most important mechanism (after V/Q mismatch and loss of hypoxic ventilatory drive) causing hypercapnia when supplemental oxygen is administered to patients with chronic respiratory disease 4, 2
When high-concentration oxygen is given, hemoglobin becomes more saturated with oxygen, reducing its ability to carry CO₂ away from tissues and potentially leading to CO₂ accumulation 2
Quantitative Considerations
The magnitude of the Haldane effect varies based on several physiological parameters:
The Haldane coefficient (change in total CO₂ concentration per unit change in total O₂ concentration at constant PCO₂) depends significantly on plasma pH, 2,3-DPG concentration, PCO₂ level, initial hemoglobin O₂ saturation, and hematocrit 5
The dependency of the Haldane coefficient on O₂ saturation and PCO₂ can increase the O₂-linked CO₂ flux across the alveolar membrane by more than 30% in patients with respiratory insufficiency 5
Under conditions of hyperoxic apnea (a "closed" system), the Haldane effect can cause arterial PCO₂ to actually exceed mixed venous PCO₂, with documented arterial-venous CO₂ gradients of 2.8 ± 1.8 mmHg 6
Clinical Pitfalls
When managing patients receiving oxygen therapy, clinicians should recognize:
Do not assume hypercapnia on oxygen is solely due to loss of hypoxic drive—V/Q mismatch and the Haldane effect are more important contributors 2
The Haldane effect independently decreases hemoglobin's CO₂ buffering capacity, contributing to CO₂ retention even when ventilatory drive is maintained 2
Monitor arterial blood gases within 30-60 minutes after initiating oxygen therapy in at-risk patients to detect CO₂ retention early 2