Oxygen Transport to the Tissues

Overview

• Oxygen must be delivered from the external environment to every cell; tissues with higher metabolic rates (e.g., working skeletal muscle, neurons) demand proportionally more O_2.

• Transport relies largely on hemoglobin (Hb) because O_2 is poorly soluble in water-based plasma.

• Only 2\% of total arterial O_2 is dissolved directly in plasma; roughly 98\% is reversibly bound to the iron atom in hemoglobin’s heme group.

• Framework to remember: the cellular respiration equation—\text{Glucose} + 6\,O2 \rightarrow 6\,CO2 + 6\,H2O + \text{ATP} + \text{Heat}—dictates why and where O2 is needed and what by-products influence its release.

Oxygen Solubility & Hemoglobin Binding

• Water (and therefore plasma) has a low O_2 solubility ➔ necessitates a carrier molecule.

• Hemoglobin contains four heme groups; each can bind one O_2 molecule by coordinating its iron (Fe^{2+}).

• Binding is cooperative—binding of one O_2 increases affinity for the next, but local environment can reverse this to promote unloading.

Step-by-Step Journey of Oxygen

1. Atmosphere → Alveoli
   • O2 diffuses down its partial-pressure gradient (ΔP{O_2}) from atmospheric air into alveolar air sacs.

2. Alveoli → Plasma
   • In healthy lungs, P{O2,\,alveoli} \gt P{O2,\,plasma}, so O_2 dissolves into plasma.

3. Plasma → Red Blood Cell (RBC)
   • ~98\% of the freshly dissolved O_2 binds Hb inside RBCs; ~2\% remains dissolved in plasma.

4. Bulk Flow → Systemic Capillaries
   • Blood transports Hb-bound and dissolved O_2 to tissues.

5. Plasma → Tissues
   • The dissolved 2\% diffuses first, lowering local P{O2} in plasma. Yes, the dissolved 2\% of oxygen in the plasma diffuses into the tissues first. This initial diffusion lowers the local partial pressure of oxygen (P*{O*2})) in the plasma, which then triggers the release of more oxygen from hemoglobin.

6. Hb → Plasma → Tissues
   • Decreased plasma P{O2} triggers Hb to release more O_2, sustaining diffusion into cells.

Detailed Mechanism of Oxygen Release from Hemoglobin

The following factors shift the Hb-O2 dissociation curve right, favoring O2 unloading:

1. Partial Pressure Gradient of Oxygen

• Primary driver: when P{O2,\,plasma} \lt P{O2,\,tissue}, Hb releases O_2 to restore equilibrium.

2. Increased CO$_2$ (Bohr Effect)

• Metabolically active tissues produce CO2 ➔ raises local P{CO_2}.

• CO2 binds to Hb (forming carbamino-Hb) and indirectly lowers pH (see below), both reducing Hb affinity for O2.

3. Decreased pH (H$^+$ Concentration)

• Reaction: CO2 + H2O \rightleftharpoons H2CO3 \rightleftharpoons HCO_3^- + H^+.

• Elevated H$^+$ (lower pH) protonates Hb, stabilizing the T-state (tense, low-affinity form) ➔ promotes unloading.

4. Increased Temperature

• Heat is a by-product of intense ATP synthesis.

• Higher temperature alters Hb conformation, again stabilizing the T-state.

5. 2,3-Bisphosphoglycerate (2,3-BPG)

• A glycolytic intermediate generated during anaerobic metabolism.

• Low O_2 supply ➔ cells switch to anaerobic glycolysis ➔ [2,3-BPG] rises.

• 2,3-BPG binds β-globin chains of Hb, reducing O_2 affinity, especially critical at high altitude, chronic hypoxia, or anemia.

Integrated View: Cellular Respiration Link

• Every factor in sections 2-4 stems from the cellular respiration equation:
  • More ATP demand ➔ more O2 consumed ➔ more CO2, H$^+$, and heat produced.
  • These by-products feed back to ensure O_2 delivery matches metabolic need.

• Conceptual mnemonic: "CO2, H+, Temp, 2,3-BPG" all yell "Drop the O2!" at Hb.

Quantitative / Numerical References

• O_2 carriage: \approx 98\% Hb-bound, \approx 2\% dissolved.

• Hb can bind 4 O2 molecules ➔ 1 RBC can carry ≈10^8 O2 molecules (context from prior lecture).

• Dissociation curve shift: a right-shift at pH 7.2 vs. 7.4 can lower Hb saturation by ~15\% at P{O2}=40 mmHg (not explicitly stated but inferred for completeness).

Practical & Clinical Implications

• Exercise physiology: skeletal muscle produces CO2, H$^+$, heat, and 2,3-BPG ➔ enhanced O2 release supports work output.

• High altitude: chronic hypoxia elevates 2,3-BPG to improve O2 unloading despite reduced arterial P{O_2}.

• Anemia or hypoxic lung disease: compensatory rise in 2,3-BPG partially offsets reduced O_2 carrying capacity.

• Acid-base disorders: metabolic or respiratory acidosis lowers blood pH ➔ may exacerbate tissue O_2 delivery or, conversely, precipitate Hb desaturation.

Connections & Preview

• Prior lecture: detailed structure of the human globin molecule (α and β chains, heme, Fe^{2+} center).

• Next lecture will address CO$2$ transport, which involves dissolution, carbamino-Hb formation, and bicarbonate chemistry—mechanistically more complex than O2 transport.