Hemoglobin exhibits cooperative binding of oxygen, producing a sigmoid saturation curve that shifts rightward with decreased pH, increased CO₂, increased temperature, and increased 2,3-DPG—all markers of high metabolic demand. Oxygen delivery (cardiac output × hemoglobin × arterial saturation) exceeds resting tissue demand, providing a safety margin. Oxygen extraction by tissues depends on the arterial-venous oxygen content difference and local oxygen demand.
From your study of respiratory mechanics and cardiac anatomy, you know that breathing gets oxygen into the alveoli and the heart pumps blood through the pulmonary capillaries to pick it up. But how much oxygen actually reaches tissues, and how do tissues extract what they need? These questions require combining three concepts you have already built: ventilation (getting O₂ to the alveolar surface), cardiac output (the pump's delivery rate), and hemoglobin's cooperative binding behavior (the saturation curve).
Oxygen delivery (DO₂) is the total amount of oxygen delivered to the body per minute. The formula is: DO₂ = cardiac output (CO) × arterial oxygen content (CaO₂). Arterial oxygen content is dominated by hemoglobin — each gram of hemoglobin carries 1.34 mL of O₂ when fully saturated, so CaO₂ ≈ Hb (g/dL) × 1.34 × SaO₂. The small contribution of dissolved oxygen (0.003 × PaO₂) matters mainly in hyperbaric contexts. At rest, a healthy adult delivers roughly 1,000 mL of O₂ per minute to tissues that consume only about 250 mL — a 4:1 safety margin. This reserve means that mild anemia, reduced saturation, or reduced cardiac output can each be individually tolerated; it is only when multiple factors fall simultaneously that delivery becomes critically inadequate.
The Bohr effect is the mechanism that matches O₂ unloading to metabolic demand at the tissue level. You know from hemoglobin cooperativity that the oxyhemoglobin saturation curve is sigmoid because of cooperative binding — but the key point here is that this curve is not fixed. In metabolically active tissues, CO₂ rises, pH falls (due to lactic acid and carbonic acid), temperature rises, and 2,3-DPG increases. Each of these factors shifts the curve rightward — hemoglobin's affinity for oxygen decreases, causing it to release more O₂ at the same partial pressure. The more a tissue is working, the more conditions favor O₂ release exactly there. This self-regulating unloading is elegant: no neural signal is needed, because the tissue's own metabolic byproducts provide the signal.
Oxygen extraction describes what tissues actually take from the blood that passes through. The oxygen extraction ratio (OER) = (CaO₂ − CvO₂) / CaO₂, where CvO₂ is venous oxygen content. At rest, venous blood still carries about 75% of the oxygen it arrived with — only 25% was extracted. During intense exercise or sepsis, extraction can rise to 60–70% as tissues pull more oxygen from each unit of blood. When delivery falls (from low cardiac output or anemia) and extraction is already maxed out, tissue hypoxia results. This is why clinicians monitor both delivery and extraction together: a high extraction ratio in a critically ill patient signals that delivery has become insufficient and the body is compensating to its limit.