describe the chloride shift and explain the importance of the chloride shift

Transport of Oxygen and Carbon Dioxide – The Chloride (Hamburger) Shift

Learning Outcomes

• Describe the three ways in which O₂ is transported in the blood and give the quantitative proportions.
• Describe the three forms in which CO₂ is transported, state their relative contributions and explain why bicarbonate dominates.
• Explain the role of carbonic anhydrase in rapid CO₂ ↔ HCO₃⁻ interconversion.
• Describe the mechanism and direction of the chloride shift in systemic and pulmonary capillaries.
• Explain the Bohr effect and interpret the oxygen‑dissociation curve (ODC), including the factors that shift the curve.
• Recall key quantitative values (P₅₀, normal arterial pH and pCO₂, % O₂ and % CO₂ carried by each form).

1. Oxygen Transport in Blood

• Hb‑bound O₂ (≈ 98 % of total O₂)
  • Each haemoglobin (Hb) molecule can bind four O₂ molecules:
    $$\text{Hb}+4\text{O}_2\;\rightleftharpoons\;\text{Hb(O}_2)_4$$
  • Binding is cooperative – the first O₂ binds with lower affinity, the fourth with highest affinity.
• Dissolved O₂ in plasma (≈ 2 % of total O₂)
  • Follows Henry’s law: concentration ∝ partial pressure (Pₒ₂).
• Haemoglobinic acid (HHb)
  • When O₂ is released, deoxy‑Hb binds H⁺:
    $$\text{Hb}+\text{H}^+\;\rightleftharpoons\;\text{HHb}$$
  • Formation of HHb reduces Hb’s affinity for O₂ – a central component of the Bohr effect (see §5).

2. Carbon Dioxide Transport in Blood

2.1 Forms of CO₂ and Their Relative Contributions

2.2 Role of Carbonic Anhydrase

• Located inside red blood cells (RBCs).
• Catalyses the rapid, reversible conversion:
  $$\text{CO}_2+\text{H}_2\text{O}\;\xrightleftharpoons[\text{CA}]{} \text{H}_2\text{CO}_3\;\rightleftharpoons\;\text{H}^+ + \text{HCO}_3^-$$
• The enzyme is not consumed; it simply accelerates the reaction ~10⁴‑fold, allowing CO₂ loading in tissues and unloading in the lungs to keep pace with metabolic rates.
• The direction of the reaction is driven by the partial pressures of CO₂ in the surrounding fluid (tissue vs. alveolar air).

3. The Chloride Shift (Hamburger Phenomenon)

3.1 Mechanism – Anion Exchanger AE1 (Band 3)

AE1 mediates an electroneutral exchange of intracellular bicarbonate (HCO₃⁻) for extracellular chloride (Cl⁻) across the RBC membrane.

3.2 Step‑by‑Step Process

3.3 Direction of the Shift

• Systemic capillaries (tissues): outward movement of HCO₃⁻, inward movement of Cl⁻.
• Pulmonary capillaries (lungs): inward movement of HCO₃⁻, outward movement of Cl⁻ (reverse shift).

3.4 Diagram (Suggested)

Two labelled diagrams of a single RBC:

1. RBC in a systemic capillary – show CO₂ entry, carbonic anhydrase reaction, HCO₃⁻ exiting, Cl⁻ entering.
2. RBC in a pulmonary capillary – show reverse exchange, HCO₃⁻ entry, Cl⁻ exit, conversion back to CO₂.

4. The Bohr Effect

• In metabolically active tissues:
  1. ↑ CO₂ → ↑ HCO₃⁻ + H⁺ (via carbonic anhydrase).
  2. H⁺ binds to deoxy‑Hb → HHb, lowering Hb’s affinity for O₂.
  3. Result: right‑ward shift of the O₂‑dissociation curve → O₂ released where it is needed.
• In the lungs:
  1. CO₂ is expelled → ↓ [H⁺] (pH rises).
  2. Hb regains high O₂ affinity → left‑ward shift of the ODC → O₂ uptake.

5. Oxygen‑Dissociation Curve (ODC)

5.1 Key Features

• Sigmoidal shape – reflects cooperative binding of O₂ to the four subunits of Hb.
• P₅₀ – the partial pressure of O₂ at which Hb is 50 % saturated; for normal adult Hb, P₅₀ ≈ 26 mm Hg (≈ 3.5 kPa).

5.2 Factors Shifting the Curve

6. Quantitative Facts (Exam‑type Recall)

1. ≈ 98 % of O₂ is Hb‑bound; ≈ 2 % is dissolved in plasma.
2. ≈ 70 % of CO₂ is transported as plasma bicarbonate, ≈ 23 % as carbamino‑Hb, ≈ 7 % dissolved.
3. One molecule of CO₂ yields one H⁺ and one HCO₃⁻; the H⁺ is largely buffered by Hb (forming HHb).
4. Normal arterial blood pH = 7.40 ± 0.02.
5. Normal arterial P₍CO₂₎ ≈ 5.3 kPa (40 mm Hg).
6. P₅₀ for adult haemoglobin ≈ 26 mm Hg (≈ 3.5 kPa).

7. Links to Other Topics (Cross‑References)

• Haemoglobin structure – see Topic 6 (Nucleic acids & protein synthesis) for the quaternary structure that underlies cooperative O₂ binding.
• 2,3‑BPG synthesis – covered in Topic 12 (Energy & respiration); its concentration in RBCs modulates the ODC.
• Acid‑base balance – the bicarbonate buffer system is revisited in Topic 13 (Homeostasis).

8. Summary of the Whole Process

1. In tissues:
   • CO₂ diffuses into RBCs.
   • Carbonic anhydrase converts CO₂ + H₂O → H⁺ + HCO₃⁻.
   • HCO₃⁻ leaves the cell via the chloride shift (AE1); Cl⁻ enters.
   • H⁺ binds to deoxy‑Hb → HHb (Bohr effect).
2. Transport in plasma: HCO₃⁻ (≈ 70 % of total CO₂) is carried dissolved in plasma, dramatically increasing the blood’s CO₂‑carrying capacity.
3. In the lungs:
   • Reverse chloride shift brings HCO₃⁻ back into RBCs; Cl⁻ exits.
   • Carbonic anhydrase reconverts HCO₃⁻ + H⁺ → CO₂ + H₂O.
   • CO₂ diffuses into alveoli and is exhaled.
   • Fall in P₍CO₂₎ and rise in pH restore Hb’s high O₂ affinity (left‑ward ODC shift) → O₂ uptake.

Suggested Diagram for Revision