Transport of Carbon Dioxide – Lecture Review

Overview of CO2 Transport

• Carbon dioxide (CO_2) is the metabolic by-product of cellular respiration in every tissue (e.g., even a pig’s farthest big toe).
• Objective: move CO_2 from tissues → venous blood → lungs → atmosphere.
• Transport occurs in three parallel chemical forms within the blood.
• Process is more intricate than O_2 transport due to additional chemical conversions and buffering mechanisms.

Chemical Forms and Percentages

• Dissolved in plasma
  • 7\% of total CO_2.
  • Although CO_2 is only moderately water-soluble, it dissolves far better than O_2.
• Carbamino-hemoglobin (CO_2 bound to Hb)
  • 23\% of total CO_2.
  • CO_2 attaches to amino groups on globin chains, not the heme iron that binds O_2.
• Bicarbonate ion (HCO_3^-)
  • 70\% (the majority) after conversion inside red blood cells (RBCs).
  • Created through hydration of CO_2 followed by dissociation.

Step-by-Step Journey from Tissue to Lungs

1. Diffusion into plasma
   • Tissue P_{CO_2} > plasma P_{CO_2}; CO_2 diffuses into capillary plasma.
2. Entry into RBC (≈93\% of plasma CO_2)
   • CO_2 rapidly crosses the RBC membrane because it is non-polar and small.
3. Partition inside RBC
   • 23 % binds Hb → carbamino-Hb.
   • 70 % reacts with H_2O → H_2CO_3 (carbonic acid) via carbonic anhydrase (CA).
4. Immediate dissociation
   • H2CO3 \rightarrow H^+ + HCO_3^- (spontaneous, fast).
5. Buffering of H^+ by hemoglobin
   • Hb (deoxy form) accepts H^+, preventing dangerous pH shifts.
6. Chloride shift (Hamburger phenomenon)
   • HCO_3^- exits RBC in exchange for Cl^- entering → maintains electroneutrality and osmotic balance.
7. Venous blood arrival at lungs
   • Plasma and RBC P_{CO_2} now exceed alveolar P_{CO_2}; gradients reverse.
8. Exhalation sequence
   • (a) Plasma-dissolved CO_2 diffuses first → alveoli → exhaled.
   • (b) Loss of plasma CO_2 lowers blood P_{CO_2}; carbamino-Hb releases CO_2 (reduced affinity) → plasma → alveoli.
   • (c) Reverse chloride shift: HCO_3^- re-enters RBC, Cl^- exits.
   • (d) Incoming HCO_3^- + H^+ → H_2CO_3 → CO_2 + H_2O (CA catalyzed).
   • CO_2 diffuses → plasma → alveoli → exhaled.

Role of Hemoglobin

• Dual function: gas carrier & chemical buffer.
• Binding sites
  • O_2 ↔ heme iron (Fe^{2+}).
  • CO_2 ↔ terminal amine groups (\epsilon-NH_2 of globin chains).
  • H^+ ↔ histidyl residues; deoxy-Hb is a better proton acceptor.
• Cooperative changes:
  • Binding/release of CO_2 and H^+ shift Hb conformation (Bohr & Haldane effects), modulating O_2 affinity.

Bicarbonate Formation & Buffer Systems

• Main reaction (catalyzed by carbonic anhydrase within RBC):
  CO2 + H2O \xrightleftharpoons[slow]{\text{no\ CA}} H2CO3 \xrightleftharpoons[fast]{ } H^+ + HCO_3^-
• Chemical buffers referenced
  • Phosphate buffer (HPO_4^{2-}/H_2PO_4^-).
  • Hemoglobin buffer (Hb/Hb·H^+).
  • Bicarbonate buffer (HCO_3^-/H_2CO_3).
• Plasma bicarbonate is invaluable for systemic pH regulation; therefore it is exported rather than used to buffer intracellular H^+.

Chloride Shift Mechanism

• Mediated by anion exchanger protein (AE1/Band 3).
• Forward shift (tissues)
  • HCO_3^- leaves RBC; Cl^- enters → balances positive charge of retained H^+.
• Reverse shift (lungs)
  • HCO_3^- re-enters for reconversion to CO_2; Cl^- exits.
• Maintains iso-osmotic conditions; prevents RBC swelling/shrinkage.

Partial Pressure Gradients & Release in Lungs

• Key driving force: $\Delta P = P{blood} - P{alveolus}$ for CO_2.
• Sequence of decreasing P_{CO_2}: RBC interior → plasma → alveolar air → outside air.
• Progressive unloading ensures all three chemical pools eventually surrender CO_2 to be exhaled.

Key Equations & Reactions

• Hydration/dissociation of CO_2: CO2 + H2O \leftrightarrow H2CO3 \leftrightarrow H^+ + HCO_3^-
• Net stoichiometry for majority pathway (tissues):
  CO2{(tissue)} + H2O \rightarrow H^+{(buffered\ by\ Hb)} + HCO3^-{(plasma)}
• Reverse in lungs regenerates CO_2 for expiration.

Comparative Note: CO2 vs O2 Transport

• O_2 is mostly bound to heme (≈98.5\%); only 1.5\% dissolves in plasma.
• CO_2 uses multiple chemical reservoirs, relying heavily on conversion chemistry and membrane transporters.
• Transport complexity underscores why CO_2 carriage is central to acid-base homeostasis.

Practical/Physiological Significance

• Acid-base balance: Exported plasma HCO_3^- is the body’s chief extracellular buffer; alterations manifest as respiratory acidosis/alkalosis.
• Haldane effect: Deoxygenated blood can carry more CO_2 (and H^+)—crucial during exercise and systemic hypoxia.
• Clinical correlation: Disorders of AE1 protein, carbonic anhydrase deficiency, or Hb mutations can impair CO_2 transport and pH regulation.
• Anesthetic & ventilatory management: Understanding partial-pressure gradients and buffering guides ventilation settings to control arterial P_{CO_2}.

Review & Connections

• Connects back to earlier lectures on:
  • Chemical buffering systems (phosphate, bicarbonate, protein).
  • Gas laws (Henry’s & Dalton’s) governing solubility and partial pressures.
  • Hemoglobin structure/function and cooperative binding.
• Ethical/real-world note: Insights into CO_2 transport underpin medical interventions for COPD, traumatic brain injury (where CO_2 modulates cerebral blood flow), and design of blood substitutes.