explain the importance of the oxygen dissociation curve at partial pressures of oxygen in the lungs and in respiring tissues

Transport of Oxygen and Carbon Dioxide (Cambridge AS & A‑Level Biology 9700)

Learning Objective

Explain the importance of the oxygen‑haemoglobin dissociation curve at the partial pressures of oxygen in the lungs and in respiring tissues, and describe the main mechanisms by which red blood cells (RBCs) transport O₂ and CO₂.

Key Concepts Overview

• Partial pressure (P_O₂, P_CO₂) determines how much gas dissolves in plasma and how much binds to haemoglobin.
• Haemoglobin (Hb) is the principal carrier of O₂; its affinity for O₂ is expressed by the oxygen‑haemoglobin dissociation curve.
• CO₂ is carried as dissolved gas, as carbamino‑haemoglobin, and mainly as bicarbonate (HCO₃⁻) in plasma.
• RBC enzymes (carbonic anhydrase) and membrane transporters (anion exchanger AE1 – “chloride shift”) enable rapid inter‑conversion of CO₂ and HCO₃⁻.

1. Oxygen Transport

1.1 Forms of O₂ in Blood

• Dissolved O₂ – ≈1.5 mL O₂ · L⁻¹ blood at a P_O₂ of 100 mm Hg (≈0.3 % of total O₂).
• Oxy‑haemoglobin (HbO₂) – ≈98 % of O₂ is bound to the four heme groups of haemoglobin.
• Minor plasma‑protein binding – <1 % of O₂ is loosely bound to albumin and other plasma proteins (not required for the syllabus but shows completeness).

1.2 The Oxygen‑Haemoglobin Dissociation Curve

The curve relates the % saturation of haemoglobin (Y) to the partial pressure of oxygen (P_O₂). Its characteristic sigmoidal shape** reflects cooperative binding: the binding of each O₂ molecule increases the affinity of the remaining sites.

P₅₀ – the PO₂ at which haemoglobin is 50 % saturated – is ≈ 26 mm Hg for adult human Hb. This value shifts left or right in response to physiological factors (see Section 3).

Figure suggestion: A single curve showing the plateau at high PO₂ (lungs) and the steep portion at low PO₂ (tissues), with arrows indicating right‑shift (↑CO₂, ↑H⁺, ↑T, ↑2,3‑BPG) and left‑shift (↓CO₂, ↓H⁺, ↓T, ↓2,3‑BPG).

1.3 Why the Curve Matters in the Lungs

1. Alveolar P_O₂ ≈ 100 mm Hg places arterial blood on the flat (plateau) part of the curve → haemoglobin is already ≈ 98 % saturated.
2. The plateau means that a small fall in P_O₂ (e.g., mild hypoventilation) causes only a minor loss of saturation, ensuring efficient loading.
3. High P_O₂ drives the formation of HbO₂, minimising the amount of free dissolved O₂ required to meet tissue demand.
4. Left‑shifting factors in the lungs (low temperature, high pH, low 2,3‑BPG) further increase Hb affinity, maximising uptake.

1.4 Why the Curve Matters in Respiring Tissues

1. Active muscle P_O₂ may fall to 20–40 mm Hg, a region where the curve is steep – a small decrease in PO₂ produces a large fall in Hb saturation, promoting O₂ release.
2. Bohr effect (right shift): ↑ CO₂, ↑ H⁺ (lower pH), ↑ temperature and ↑ 2,3‑BPG reduce Hb affinity for O₂, enhancing unloading precisely where it is needed.
3. Haldane effect: De‑oxygenated Hb has a higher affinity for CO₂ and H⁺, so O₂ release simultaneously increases CO₂ uptake by the blood.
4. The steep portion therefore provides a tight match between O₂ delivery and metabolic demand.

1.5 Quantitative Relationships (AO1 & AO2)

2. Carbon‑Dioxide Transport

2.1 Forms of CO₂ in Blood

• Dissolved CO₂ – ≈ 5 % of total CO₂; directly proportional to P_CO₂.
• Carbamino‑haemoglobin – CO₂ binds reversibly to the amino groups of the globin chains (≈ 5–10 % of total CO₂).
• Bicarbonate ion (HCO₃⁻) – ≈ 80–85 % of CO₂ is carried as bicarbonate, primarily in plasma after being formed inside the RBC.

2.2 The Carbonic Anhydrase Reaction (inside RBCs)

CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻  (catalysed by carbonic anhydrase)

• In tissues: CO₂ diffuses into RBCs, is hydrated to H₂CO₃, which dissociates to H⁺ and HCO₃⁻.
• In the lungs: The reaction runs in reverse, converting HCO₃⁻ + H⁺ back to CO₂ for exhalation.
• Most H⁺ is buffered by de‑oxygenated haemoglobin, forming haemoglobinic acid and limiting a fall in blood pH.

2.3 Chloride Shift (Hamburger‑Freund Mechanism)

1. HCO₃⁻ produced in the RBC diffuses out into plasma.
2. To maintain electrical neutrality, Cl⁻ moves from plasma into the RBC via the anion exchanger AE1.
3. In the lungs the process reverses: HCO₃⁻ re‑enters the RBC, combines with H⁺, and Cl⁻ exits.

2.4 Haldane Effect

De‑oxygenated haemoglobin has a higher affinity for CO₂ and H⁺ than oxygenated haemoglobin. Consequently:

• When O₂ is released in tissues, Hb binds more CO₂ (enhancing CO₂ transport).
• When O₂ binds in the lungs, Hb releases CO₂, facilitating its exhalation.

2.5 CO₂ Release in the Lungs

• Alveolar P_CO₂ ≈ 40 mm Hg creates a diffusion gradient that drives CO₂ out of blood.
• Carbonic anhydrase catalyses the reverse reaction (HCO₃⁻ + H⁺ → CO₂ + H₂O).
• O₂ binding to Hb displaces carbamino‑CO₂ (the “Haldane effect”), further increasing CO₂ removal.

2.6 Summary of CO₂ Transport Pathways

3. Factors Shifting the O₂‑Hb Dissociation Curve

3.1 Right‑Shift (Bohr Effect – promotes unloading)

3.2 Left‑Shift (facilitates loading in the lungs)

4. Integrating O₂ and CO₂ Transport

• In the lungs: Blood arrives with high P_O₂ (≈ 100 mm Hg) and low P_CO₂ (≈ 40 mm Hg). The left‑shifted O₂ curve allows ≈ 98 % Hb saturation, while the Haldane effect releases CO₂ from de‑oxygenated Hb and converts plasma HCO₃⁻ back to CO₂ for exhalation.
• In systemic circulation: Tissue metabolism lowers P_O₂ and raises P_CO₂. The right‑shifted O₂ curve (Bohr effect) promotes O₂ unloading; simultaneously, de‑oxygenated Hb binds more CO₂ (Haldane effect), and carbonic anhydrase rapidly forms HCO₃⁻ for transport.
• The coordinated shifts ensure that O₂ delivery matches metabolic demand and that CO₂ removal is maximised.

5. Quick Revision Box

• O₂ loading (lungs): High PO₂ → plateau of the curve → ~98 % Hb saturation; left‑shift factors (low CO₂, high pH, low temperature, low 2,3‑BPG) enhance loading.
• O₂ unloading (tissues): Low PO₂ (20–40 mm Hg) → steep part of the curve → rapid release; right‑shift (Bohr) factors (↑CO₂, ↑H⁺, ↑T, ↑2,3‑BPG) further lower affinity.
• CO₂ transport: 5 % dissolved, 5–10 % carbamino‑Hb, 80–85 % as HCO₃⁻ in plasma; carbonic anhydrase and the chloride shift accelerate conversion.
• P₅₀: ~26 mm Hg – the PO₂ at which haemoglobin is 50 % saturated.
• Bohr effect: ↑CO₂/H⁺ → right shift → easier O₂ release.
• Haldane effect: De‑oxygenated Hb binds more CO₂; oxygenated Hb releases CO₂.

Suggested Diagram

Combined oxygen‑haemoglobin dissociation curve showing (i) the plateau at alveolar PO₂ ≈ 100 mm Hg, (ii) the steep region at tissue PO₂ ≈ 30 mm Hg, and (iii) arrows indicating right‑shift factors (↑CO₂, ↑H⁺, ↑T, ↑2,3‑BPG) and left‑shift factors (↓CO₂, ↑pH, ↓T, ↓2,3‑BPG).