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Oxygen Transport, Diffusion, and the Oxygen-Haemoglobin Dissociation Curve

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I. FORMS OF OXYGEN TRANSPORT IN BLOOD

1. Dissolved O₂ (Physical Solution)

• Oxygen dissolves directly in plasma and intracellular fluid of RBCs.
• Amount dissolved = 0.003 mL O₂ per 100 mL blood per 1 mmHg PO₂
• At arterial PO₂ of 100 mmHg → only ~0.3 mL O₂/100 mL blood — grossly insufficient to meet tissue demands.
• However, dissolved O₂ is physiologically critical: it is the only form that diffuses across alveolar-capillary membranes and RBC membranes; haemoglobin cannot traverse membranes itself.

2. O₂ Bound to Haemoglobin (Chemical Combination)

• Each haemoglobin (Hb) molecule (MW ~68,000) carries 4 haem groups, each binding one O₂.
• At Hb = 15 g/100 mL blood, ~20 mL O₂/100 mL blood can be carried — approximately 60–100× more than dissolved alone.
• Binding is reversible and cooperative: binding of the first O₂ increases affinity for subsequent O₂ molecules — this produces the characteristic sigmoid (S-shaped) curve.
• O₂ binds to the ferrous (Fe²⁺) iron of haem; this is oxygenation, not oxidation.

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II. DIFFUSION OF O₂ — ALVEOLI TO BLOOD TO TISSUES

Fick's Law of Diffusion

A. Alveolar to Pulmonary Capillary

• Pressure gradient driving O₂ into blood = 64 mmHg initially.
• O₂ equilibration occurs within 0.2–0.4 s; transit time through pulmonary capillary at rest = ~0.75 s → full equilibration well within available time.
• During heavy exercise (transit time ↓ to ~0.3 s), equilibration is still usually achieved, though it may become diffusion-limited in disease.

B. Pulmonary Capillary to Red Cell

• O₂ diffuses through plasma, crosses the RBC membrane, then diffuses inside the cell.
• Inside the RBC, high Hb concentration makes the cytoplasm 3× more viscous than water, reducing the O₂ diffusion coefficient to one-third of its aqueous value.
• Despite the short distances (few microns), significant diffusion gradients may exist within the RBC interior.

C. Systemic Capillary to Tissue Cells

• Gradient of ~55 mmHg drives O₂ out of capillary into interstitium, then into cells.
• Tissue cells are usually ≤50 µm from a capillary; greater distance causes diffusion-limited O₂ delivery.
• Intracellular PO₂ of just >1 mmHg is sufficient for normal oxidative phosphorylation — below this, metabolism becomes O₂-limited.

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III. THE OXYGEN-HAEMOGLOBIN DISSOCIATION CURVE

Key Features of the Sigmoid Curve

Physiological Significance of the Sigmoid Shape

1. Upper flat portion (PO₂ 60–100 mmHg): Hb remains ~90–97% saturated despite large drops in alveolar PO₂ — protective against hypoxia at altitude or in lung disease. This is why patients maintain near-normal SaO₂ until PO₂ falls below ~60 mmHg.
2. Steep middle portion (PO₂ 20–60 mmHg): Small drops in PO₂ cause large O₂ release — ideal for unloading O₂ at the tissue level where PO₂ is 40 mmHg.
3. Cooperative binding (quaternary structure): Deoxygenated Hb (T-state, tense) has low affinity; as O₂ binds, Hb shifts to R-state (relaxed), increasing affinity for subsequent O₂ — produces the positive cooperativity reflected in the sigmoid shape.

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IV. FACTORS SHIFTING THE DISSOCIATION CURVE

Right Shift (↑P50 = decreased affinity = more O₂ unloaded to tissues)

Left Shift (↓P50 = increased affinity = less O₂ released)

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V. ROLE OF 2,3-BISPHOSPHOGLYCERATE (2,3-BPG)

• Produced in RBCs via the Rapoport-Luebering shunt of glycolysis.
• Normal BPG maintains a tonic rightward shift of the ODC, facilitating O₂ delivery.
• In chronic hypoxia (altitude, anaemia, cardiorespiratory disease), BPG levels rise within hours, shifting the curve further right — this is a key adaptive mechanism allowing O₂ release at up to 10 mmHg higher tissue PO₂ than without BPG.
• Stored blood (bank blood) loses BPG → curve shifts left → O₂ not readily released to tissues (corrected within ~24 hours of transfusion).

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VI. THE BOHR EFFECT

• In metabolically active tissues: CO₂ and H⁺ are produced → local acidosis → right shift → Hb releases more O₂ exactly where needed.
• In pulmonary capillaries: CO₂ is lost to alveoli → local pH rises → left shift → Hb picks up more O₂.
• This tissue-specific modulation of Hb affinity is the Bohr effect — a self-regulating, demand-driven O₂ delivery mechanism.

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VII. O₂ DELIVERY AND UTILISATION

• 1.34 mL O₂ is bound per gram of fully saturated Hb.
• At rest: DO₂ = 5 L/min × 20 mL/dL = ~1000 mL O₂/min
• Resting consumption (VO₂) = ~250 mL/min
• O₂ extraction ratio = VO₂/DO₂ = ~25% at rest (can rise to ~75% during maximal exercise)

• Intracellular PO₂ only needs to exceed ~1 mmHg for normal mitochondrial function; O₂ usage is primarily controlled by ADP concentration (energy demand), not O₂ availability under normal circumstances.
• Cells ≤50 µm from capillaries receive adequate O₂ by diffusion; greater distances lead to diffusion-limited O₂ delivery.

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VIII. CLINICAL CORRELATIONS

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Summary Table

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