describe and explain the oxygen dissociation curve of adult haemoglobin

Transport of Oxygen and Carbon Dioxide

Learning Objective

Describe and explain the oxygen‑dissociation curve of adult haemoglobin (HbA) and the main mechanisms by which red blood cells (RBCs) transport O₂ and CO₂.

1. Role of Red Blood Cells & Haemoglobin in O₂ Transport

  • RBCs are packed with haemoglobin – about 33 % (w/w) of the cell.

  • Each Hb molecule = 4 polypeptide sub‑units (2 α + 2 β) each containing a heme‑iron centre that can bind one O₂ molecule → 4 O₂ per Hb.

  • Binding of O₂ to one sub‑unit increases the affinity of the remaining sites – cooperative binding. This gives the characteristic sigmoidal O₂‑Hb relationship.

2. Structural Basis of Cooperative Binding

In the deoxy (T) state the sub‑units are relatively rigid. When O₂ binds, the iron atom moves into the plane of the heme and pulls the attached globin chain, converting the molecule to the relaxed (R) state. This conformational change stabilises O₂ at the other sites, producing the sigmoidal curve.

3. The Oxygen‑Haemoglobin Dissociation Curve

  • Plots percentage haemoglobin saturation (% HbSat) against the partial pressure of oxygen (pO₂).

  • The S‑shaped (sigmoidal) form reflects cooperative binding.

3.1 Hill Equation

The relationship can be expressed mathematically as:

\$\theta = \frac{pO2^{\,n}}{P{50}^{\,n}+pO_2^{\,n}}\$

  • θ = fractional saturation (0–1)

  • n = Hill coefficient (≈ 2.8 for adult HbA – indicates positive cooperativity)

  • P₅₀ = pO₂ at 50 % saturation (≈ 26 mm Hg for HbA)

3.2 Typical Values for Adult Haemoglobin (HbA)

pO₂ (mm Hg)% Hb Saturation
205 %
4025 %
6050 %
8090 %
10098 %

3.3 Linking Curve Shape to Physiology

  • High‑affinity (steep left‑hand) region: At alveolar pO₂ ≈ 100 mm Hg the curve is steep, so a small rise in pO₂ produces a large increase in saturation – >95 % of Hb becomes loaded with O₂ in the lungs.

  • Low‑affinity (right‑hand) region: In active muscle pO₂ may fall to 20–40 mm Hg; the curve flattens, so a small fall in pO₂ releases a large amount of O₂ to the tissues.

4. Factors that Shift the Curve (Change Haemoglobin Affinity)

Anything that stabilises the T‑state shifts the curve to the right (lower affinity); anything that stabilises the R‑state shifts it to the left (higher affinity).

FactorEffect on CurvePhysiological Consequence
pH (Bohr effect)↓ pH (↑ H⁺) → right‑shiftFacilitates O₂ release in metabolically active, acidic tissue.
pCO₂↑ pCO₂ → ↑ H⁺ (via H₂CO₃) → right‑shiftSame as Bohr effect; high CO₂ in exercising muscle enhances unloading.
Temperature↑ temperature → right‑shift; ↓ temperature → left‑shiftWarm active muscle releases O₂ more readily.
2,3‑Bisphosphoglycerate (2,3‑BPG)↑ 2,3‑BPG binds β‑chains → stabilises T‑state → right‑shiftAdaptation to chronic hypoxia (e.g., high altitude) or anaemia.
Fetal haemoglobin (HbF)Higher intrinsic O₂ affinity → left‑shiftEnsures efficient transfer of O₂ from mother to fetus.

5. Why the Sigmoidal Curve Is Important

  • Lung loading: At alveolar pO₂ ≈ 100 mm Hg the curve’s steep left side means >95 % of Hb becomes saturated with only a modest increase in pO₂.

  • Tissue unloading: In exercising muscle pO₂ may drop to 20–40 mm Hg; the flatter right side means a small fall in pO₂ releases a large amount of O₂.

  • Rapid response to metabolic change: The Bohr shift, rise in temperature and increase in 2,3‑BPG during exercise all move the curve rightward, further enhancing O₂ delivery where it is needed most.

6. Transport of Carbon Dioxide

CO₂ is removed from tissues and carried back to the lungs by three complementary mechanisms.

6.1 Enzymatic Conversion – Carbonic Anhydrase

Inside RBCs:

\$\text{CO}2 + \text{H}2\text{O} \;\xrightleftharpoons[\text{CA}]{\text{catalysed}}\; \text{H}2\text{CO}3 \;\rightleftharpoons\; \text{H}^+ + \text{HCO}_3^-\$

  • Carbonic anhydrase (CA) accelerates the reaction >10⁴‑fold.

  • ≈ 70 % of CO₂ is transported as bicarbonate (HCO₃⁻) in plasma.

6.2 Direct Binding – Carbamino‑haemoglobin

  • CO₂ binds reversibly to the terminal –NH₂ groups of the globin chains, forming carbamino‑Hb (≈ 10 % of total CO₂).

  • This binding is favoured when O₂ affinity is lowered (Bohr effect).

6.3 Dissolved CO₂

  • ~20 % of CO₂ remains physically dissolved in plasma (≈ 0.03 vol % at normal pCO₂).

6.4 Chloride Shift (Hamburger Shift)

  • To maintain electroneutrality, HCO₃⁻ produced in the RBC leaves the cell in exchange for Cl⁻ from plasma.

  • In the lungs the reverse occurs: Cl⁻ exits, HCO₃⁻ re‑enters, is converted back to CO₂ and is exhaled.

6.5 Role of Plasma

  • Plasma is the medium for dissolved CO₂ and the major carrier of HCO₃⁻.

  • The bicarbonate buffer system (CO₂/H₂CO₃/HCO₃⁻) also helps regulate blood pH.

7. Summary

The oxygen‑dissociation curve of adult haemoglobin illustrates how Hb’s affinity for O₂ varies with pO₂ and is modulated by pH, temperature, CO₂, 2,3‑BPG and haemoglobin type (HbA vs HbF). Its cooperative, sigmoidal shape enables efficient loading of O₂ in the high‑pO₂ environment of the lungs and rapid unloading in the low‑pO₂, acidic, warm conditions of active tissues. CO₂ is removed mainly as bicarbonate (catalysed by carbonic anhydrase), with smaller contributions from carbamino‑Hb and dissolved CO₂; the chloride shift ensures charge balance during this transport.

Suggested diagram: Oxygen‑haemoglobin dissociation curve showing (i) normal position, (ii) right‑shift (low affinity – Bohr effect, high temperature, high 2,3‑BPG) and (iii) left‑shift (high affinity – HbF, low temperature, low 2,3‑BPG).