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CO₂ Transport, Diffusion, and Dissociation Curve
1. Overview
CO₂ is produced continuously in tissue cells as a byproduct of oxidative metabolism. Under resting conditions, 4 mL of CO₂ is transported from tissues to lungs per 100 mL of blood. Unlike O₂, CO₂ combines with chemical substances in the blood that amplify its transport 15–20-fold.
2. Diffusion of CO₂ — From Tissues to Blood
CO₂ transport begins with simple diffusion driven by partial pressure gradients:
| Site | PCO₂ | Direction |
|---|
| Tissue cells | ~46 mm Hg | → into capillaries |
| Venous blood | 45 mm Hg | → toward lungs |
| Alveolar air | 40 mm Hg | CO₂ diffuses out |
| Arterial blood | 40 mm Hg | equilibrates with alveoli |
- In tissue capillaries: PCO₂ rises from 40 → 45 mm Hg as CO₂ diffuses in
- In pulmonary capillaries: PCO₂ falls from 45 → 40 mm Hg as CO₂ diffuses out into alveoli
- CO₂ is 20× more soluble in body fluids than O₂, so diffusion is rarely a limiting factor
3. Chemical Forms of CO₂ Transport
CO₂ is transported in three forms:
A. Dissolved CO₂ — 7%
- CO₂ dissolves directly in plasma as molecular CO₂
- Venous blood: 2.7 mL/100 mL; arterial: 2.4 mL/100 mL
- Net transport: 0.3 mL/100 mL → ~7% of total CO₂
B. Bicarbonate Ion (HCO₃⁻) — 70% ★ Most Important
This is the dominant pathway. The sequence inside red blood cells (RBCs):
CO₂ + H₂O →[carbonic anhydrase]→ H₂CO₃ → H⁺ + HCO₃⁻
Key steps:
- CO₂ enters RBCs and reacts with H₂O via carbonic anhydrase (5000× faster than in plasma)
- H₂CO₃ dissociates into H⁺ and HCO₃⁻ almost instantaneously
- H⁺ is buffered by hemoglobin (powerful acid-base buffer)
- HCO₃⁻ diffuses out into plasma in exchange for Cl⁻ via the bicarbonate-chloride carrier protein
- This exchange is called the Hamburger Shift (Chloride Shift)
In the lungs, the entire process reverses: HCO₃⁻ re-enters RBCs, recombines with H⁺ (released from oxyhemoglobin) → H₂CO₃ → CO₂ + H₂O → CO₂ exhaled
C. Carbamino Compounds — 23% (Carbaminohemoglobin)
- CO₂ reacts directly with –NH₂ (amino) groups of hemoglobin and plasma proteins
- Forms carbaminohemoglobin (also called carbhemoglobin):
Hb–NH₂ + CO₂ ⇌ Hb–NH–COOH (carbaminohemoglobin)
- This reaction is rapid but smaller in capacity than the bicarbonate pathway
- Deoxygenated Hb (in tissues) binds more CO₂ than oxygenated Hb
- Carries ~20–23% of total CO₂ transport
4. Summary Table: Proportions of CO₂ Transport
| Form | % Transported | Location |
|---|
| Dissolved CO₂ | ~7% | Plasma |
| Bicarbonate (HCO₃⁻) | ~70% | Plasma (formed in RBCs) |
| Carbaminohemoglobin | ~23% | RBCs |
5. CO₂ Dissociation Curve
The CO₂ dissociation curve plots total blood CO₂ (all forms) vs. PCO₂:
CO₂ dissociation curve — normal operating range highlighted between 40–45 mm Hg. — Guyton & Hall, Fig. 41.14
Key Features:
| Feature | Detail |
|---|
| Shape | Steep, nearly linear (unlike O₂ sigmoid curve) |
| Normal PCO₂ range | 40 mm Hg (arterial) → 45 mm Hg (venous) |
| Total CO₂ in blood | ~50 vol% |
| CO₂ exchanged per cycle | ~4 vol% (rises from 48 → 52 vol% in tissues) |
| No plateau at physiological range | Blood can keep absorbing CO₂ even at high PCO₂ |
Comparison with O₂ Dissociation Curve:
| Feature | O₂ Curve | CO₂ Curve |
|---|
| Shape | S-shaped (sigmoid) | Steep, almost linear |
| Binding molecule | Hemoglobin (heme) | Multiple (HCO₃⁻, Hb amino, dissolved) |
| Plateau | Yes (above ~70 mm Hg) | No plateau in physiological range |
| Factors shifting curve | Bohr effect | Haldane effect |
6. The Haldane Effect ★★ (High-Yield Exam Topic)
Haldane effect: At PO₂ = 40 mm Hg (tissues), blood carries more CO₂ at any given PCO₂ (Point A) than at PO₂ = 100 mm Hg (lungs, Point B). — Guyton & Hall, Fig. 41.15
Definition: Oxygenation of hemoglobin in the lungs promotes CO₂ release from blood.
Mechanism:
- When O₂ binds Hb in the lungs → Hb becomes a stronger acid (oxyhemoglobin is more acidic)
- More acidic Hb has less affinity for CO₂ → carbamino-CO₂ is displaced from Hb
- More acidic Hb releases excess H⁺ → H⁺ + HCO₃⁻ → H₂CO₃ → CO₂ + H₂O → CO₂ exhaled
Clinical significance: The Haldane effect is quantitatively more important than the Bohr effect. At tissues, deoxygenated Hb picks up more CO₂; in the lungs, oxygenated Hb dumps CO₂.
7. The Bohr Effect (Related — Exam Favorite)
- Increased CO₂ (↑ PCO₂) and decreased pH → O₂ dissociation curve shifts RIGHT
- Hb releases O₂ more readily to tissues
- The Haldane and Bohr effects are complementary and reinforce each other
8. Factors Affecting the CO₂ Dissociation Curve
| Factor | Effect on Curve |
|---|
| ↑ Oxygenation (PO₂) | Shifts curve DOWN (less CO₂ carried) — Haldane effect |
| ↓ Oxygenation (PO₂) | Shifts curve UP (more CO₂ carried) |
| ↑ Temperature | ↑ CO₂ release from blood |
| ↑ 2,3-DPG | Slight effect |
9. CO₂ Transport — Tissue vs. Lung Summary
| Event | Tissues | Lungs |
|---|
| PCO₂ gradient | Cell > capillary → CO₂ enters blood | Blood > alveolus → CO₂ leaves blood |
| Carbonic anhydrase | CO₂ + H₂O → H₂CO₃ | H₂CO₃ → CO₂ + H₂O |
| Chloride shift | Cl⁻ into RBC; HCO₃⁻ out | HCO₃⁻ into RBC; Cl⁻ out |
| Hb state | Deoxy-Hb (better CO₂ carrier) | Oxy-Hb (releases CO₂) |
| Net CO₂ movement | Into blood | Out of blood |
10. Clinical Correlations
- Hypercapnia (↑ PCO₂): impaired CO₂ transport → respiratory acidosis
- Carbonic anhydrase inhibitors (e.g., acetazolamide): slow HCO₃⁻ formation → used in altitude sickness, glaucoma
- Carbon monoxide poisoning: Hb occupied by CO → less carbaminohemoglobin formation, impaired CO₂ transport
- Shock/hypoperfusion: stagnant blood → CO₂ accumulates in tissues
Sources: Guyton and Hall Textbook of Medical Physiology (Ch. 41 — Transport of O₂ and CO₂ in Blood and Tissue Fluids)