Oxygen Transport to the Tissues

Overview of Oxygen Transport

• Oxygen must move from the external environment (atmosphere) to every cell, including low-demand tissues (e.g., skin) and high-demand tissues (e.g., skeletal muscle during exercise, neurons).
• Only about 2 % of total blood O$_2$ is transported physically dissolved in the water-rich plasma; ≈ 98 % is carried bound to hemoglobin (Hb) inside red blood cells (RBCs).
• Hemoglobin structure reminder (from prior lecture): four globin chains, each containing one heme; the central Fe$^{2+}$ atom of each heme reversibly binds one O$2$ molecule → up to four O$2$ per Hb tetramer.
• Because O$2$ is poorly soluble in water, hemoglobin is indispensable for adequate O$2$ delivery.

Step-by-Step Pathway of Oxygen Movement

• Atmosphere → Alveoli
  • Gases move down partial-pressure gradients.
  • P{O2\,(atm)} > P{O2\,(alveoli)} → O$_2$ diffuses into alveolar air spaces.
• Alveoli → Blood Plasma
  • P{O2\,(alveoli)} > P{O2\,(plasma\,at\,lung)} → O$_2$ enters the plasma.
• Plasma → RBC (Hemoglobin binding)
  • P{O2\,(plasma)} > P{O2\,(RBC)} → ~98 % of incoming O$_2$ crosses the RBC membrane and binds Hb.
  • Remaining ~2 % stays dissolved in plasma and travels with the blood.
• Systemic Capillaries (Plasma → Interstitial Fluid → Cells)
  • Metabolically active tissues continuously lower their intracellular and interstitial P{O2}.
  • Dissolved O$2$ (2 %) leaves the plasma first; the resulting fall in plasma P{O2} pulls O$2$ off Hb (facilitated by factors below) → Hb-bound O$_2$ diffuses out, replenishing plasma, then into tissues.

Key Chemical & Metabolic Context

• Cellular respiration (constantly occurring in tissues):
  \text{C}6\text{H}{12}\text{O}6 + 6\,O2 \;\longrightarrow\; 6\,CO2 + 6\,H2O + \text{heat} + \text{ATP}
• Rising CO$_2$ and heat are direct indicators of elevated ATP production (metabolic demand).
• Carbonic acid / bicarbonate equilibrium (links CO$2$ to pH changes): CO2 + H2O \;\rightleftharpoons\; H2CO3 \;\rightleftharpoons\; HCO3^- + H^+
  • More CO$_2$ → more H$^+$ → lower pH (more acidic).

Factors Promoting O$_2$ Release From Hemoglobin at Tissues

• 1. Low tissue P{O2} (high gradient)
  • Primary driver; Hb unloads O$2$ whenever surrounding plasma/tissue P{O_2} falls.
• 2. Elevated P{CO2}
  • High CO$2$ signals active metabolism → Hb changes conformation (Bohr effect) → lower O$2$ affinity → easier release.
• 3. Decreased pH (↑[H$^+$])
  • Mechanistically tied to CO$_2$ rise via carbonic-acid reaction.
  • Acidic environment stabilizes the "tense" (T) state of Hb → O$_2$ dissociates more readily.
• 4. Increased Temperature
  • Heat is another byproduct of ATP generation; higher local temperature likewise shifts Hb toward lower O$_2$ affinity.
• 5. Increased 2,3-Bisphosphoglycerate (2,3-BPG)
  • 2,3-BPG is a glycolytic intermediate; concentration surges when cells rely more on anaerobic glycolysis (low O$_2$ availability).
  • Binds deoxygenated Hb, stabilizing T state → enhances O$_2$ unloading.
• Interrelation: All four tissue factors (CO$_2$, H$^+$, temperature, 2,3-BPG) tend to rise together in metabolically active or hypoxic tissues, perfectly tuning Hb delivery to need.

Functional & Clinical Significance

• The described shifts constitute the Bohr effect (though not named in the transcript), ensuring O$_2$ is preferentially unloaded where metabolism is highest.
• Hb’s responsiveness allows efficient global distribution despite uniform arterial O$_2$ content.
• Understanding these modulators is critical for interpreting blood-gas analyses, managing patients with respiratory disorders, high-altitude acclimatization, and designing transfusion or blood-storage protocols (stored blood gradually loses 2,3-BPG → impaired O$_2$ unloading).

Transition to Upcoming Topic

• Oxygen transport is comparatively straightforward because O$_2$ is carried primarily in one form (Hb-bound).
• CO$_2$ transport (next lecture) is more complex, involving dissolved gas, bicarbonate ions, and carbamino-hemoglobin.