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Bohr effect and haldane effect for 5 marks

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Bohr Effect and Haldane Effect

Bohr Effect

Definition: The Bohr effect describes how an increase in CO2 and H+ concentration (fall in pH) shifts the oxygen-hemoglobin (Hb-O2) dissociation curve to the right, decreasing hemoglobin's affinity for O2 and promoting O2 release to the tissues.
Mechanism: Deoxyhemoglobin has a greater affinity for H+ than oxyhemoglobin. When CO2 enters the blood from metabolically active tissues, it is hydrated to carbonic acid (H2CO3), which dissociates to release H+ ions. These H+ ions bind to specific ionizable groups on Hb - particularly histidine residues (His-146 of the beta chain is most important) whose pKa rises in the deoxy state. This protonation:
  • Forms ionic bonds (salt bridges) that stabilize the T (tense/deoxy) conformation of hemoglobin
  • Lowers O2 affinity - the curve shifts right (increased P50)
This can be summarized as:
HbO2 + H+ ⇌ HbH+ + O2
There are two components:
  1. pH-Bohr effect (dominant) - direct effect of falling pH
  2. CO2-Bohr effect (minor) - CO2 directly combines with terminal amino groups of Hb to form carbamino compounds, also stabilizing the T form
Physiological Significance:
  • At active tissues: high CO2/low pH → Hb releases more O2 (right shift)
  • At the lungs: low CO2/high pH → Hb binds O2 more avidly (left shift)
  • The effect is amplified during strenuous exercise due to lactic acid production
  • Deoxyhemoglobin is a stronger base (better H+ buffer), so the Bohr effect also minimizes the pH drop in venous blood by ~50%
  • Fishman's Pulmonary Diseases and Disorders
  • Lippincott Illustrated Reviews: Biochemistry, 8e, p. 105

Haldane Effect

Definition: The Haldane effect states that oxygenation of hemoglobin reduces its ability to carry CO2 - conversely, deoxygenation increases CO2-carrying capacity. Oxygenated blood at any PCO2 carries less CO2 than deoxygenated blood at the same PCO2.
Mechanism: When O2 binds hemoglobin in the lungs, Hb becomes a stronger acid (HbO2 is more acidic than deoxy-Hb). This displaces CO2 from the blood in two ways:
  1. Carbamino displacement: OxyHb has less tendency to form carbaminohemoglobin (Hb-NH-COO-), so CO2 previously carried as carbamino is released
  2. Bicarbonate displacement: More acidic oxyHb releases excess H+; these H+ ions bind HCO3- to form carbonic acid (H2CO3), which dissociates to H2O + CO2, which is then exhaled
This can be summarized as:
Deoxy-Hb + CO2 ⇌ Oxy-Hb + CO2 (released)
Physiological Significance (Quantitative): The diagram below from Guyton & Hall illustrates this effect:
CO2 dissociation curves showing the Haldane effect - at PO2 40 mmHg (tissues, dashed line) blood carries more CO2 than at PO2 100 mmHg (lungs, solid line)
At PCO2 of 45 mmHg in tissues (point A), blood carries 52 vol% CO2. In the lungs, oxygenation shifts the curve down - CO2 content falls to 48 vol% (point B) instead of 50 vol%. Thus the Haldane effect roughly doubles CO2 transport in both directions.
  • The Haldane effect accounts for 40-50% of total CO2 exchange in the lung
  • Equal contributions come from changes in bicarbonate and carbamino concentrations
Quantitative importance: The Haldane effect is quantitatively far more important in promoting CO2 transport than the Bohr effect is in promoting O2 transport.
  • Guyton and Hall Textbook of Medical Physiology

Bohr-Haldane Interrelationship

These two effects are complementary and synergistic:
LocationBohr EffectHaldane Effect
Tissues↑CO2/↑H+ → right shift → O2 releasedDeoxygenation → Hb picks up more CO2 & H+
Lungs↓CO2/↓H+ → left shift → O2 loadedOxygenation → Hb releases CO2 & H+
In essence:
  • CO2 entering the blood at tissues facilitates O2 unloading (Bohr effect)
  • O2 loading in the lungs facilitates CO2 unloading (Haldane effect)
Both effects arise from the same conformational change in the hemoglobin molecule - the shift between the R (relaxed/oxy) and T (tense/deoxy) states - and together they make gas exchange far more efficient than simple diffusion alone.
  • Fishman's Pulmonary Diseases and Disorders; Guyton and Hall Medical Physiology; Lippincott Biochemistry, 8e
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