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.

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.

Diffusion into plasma
- Tissue P_{CO_2} > plasma P_{CO_2}; CO_2 diffuses into capillary plasma.
Entry into RBC (≈93\% of plasma CO_2)
- CO_2 rapidly crosses the RBC membrane because it is non-polar and small.
Partition inside RBC
- 23 % binds Hb → carbamino-Hb.
- 70 % reacts with H_2O → H_2CO_3 (carbonic acid) via carbonic anhydrase (CA).
Immediate dissociation
- H2CO3 \rightarrow H^+ + HCO_3^- (spontaneous, fast).
Buffering of H^+ by hemoglobin
- Hb (deoxy form) accepts H^+, preventing dangerous pH shifts.
Chloride shift (Hamburger phenomenon)
- HCO_3^- exits RBC in exchange for Cl^- entering → maintains electroneutrality and osmotic balance.
Venous blood arrival at lungs
- Plasma and RBC P_{CO_2} now exceed alveolar P_{CO_2}; gradients reverse.
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.

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.

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^+.

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.

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.

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.

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.

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}.

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.