How Oxygen Enters the Bloodstream: From Alveoli to Hemoglobin

Oxygen transfer from air to blood occurs in four steps:

1. Ventilation: Air reaches alveoli (tidal volume ~500 mL).
2. Diffusion: O₂ crosses alveolar‑capillary barrier (Type I pneumocyte → basement membrane → capillary endothelium → plasma → RBC membrane). Driven by partial pressure gradient (PAO₂ ~100 mmHg → PaO₂ ~95 mmHg).
3. Binding: O₂ binds heme iron on hemoglobin (Hb). Each Hb tetramer carries 4 O₂. Cooperative binding → sigmoidal dissociation curve.
4. Transport: Cardiac output delivers oxygenated blood via arteries → capillaries → tissues.

Key Factors Affecting Loading

• Ventilation‑perfusion (V/Q) matching.
• Hemoglobin concentration (anemia reduces O₂ content despite normal PaO₂).
• pH, CO₂, temperature, 2,3‑BPG (Bohr effect – right shift enhances unloading).
• Diffusion barrier thickening (edema, fibrosis) impairs equilibration.

Clinical Relevance

• Pulse oximetry measures SpO₂ (Hb saturation), not PaO₂.
• Shunt (e.g., pneumonia, ARDS) causes hypoxemia refractory to O₂ therapy.
• Carbon monoxide binds Hb with 240× affinity → functional anemia.

Understanding this cascade is fundamental to respiratory physiology, critical care, and exercise science.