Hemoglobin Loads and Unloads Oxygen by Demand

Here is something remarkable about hemoglobin: it does not behave like a simple sponge that soaks up oxygen evenly. It is a smart, cooperative molecule — and that cooperation is exactly why you can survive a sprint. Each hemoglobin molecule has four subunits, and each subunit carries one heme group that can bind one oxygen molecule. When the first O2 binds, it slightly changes hemoglobin's shape, making the second binding site easier to fill. Each binding event makes the next one easier still. This cooperative binding is what gives the oxygen-hemoglobin dissociation curve its characteristic S-shape — or sigmoidal shape — instead of a simple diagonal line. Now look at the two key regions of that curve. In the lungs, alveolar PO2 is roughly 100 mmHg. At that partial pressure, hemoglobin is about 98% saturated — nearly every binding site is loaded with O2. Notice that the curve is relatively flat at the top: even if PO2 drops to around 60 mmHg (as it does at moderate altitude), saturation stays above 90%. This flat plateau is a safety buffer. Down in an actively working muscle, PO2 can fall to 20–40 mmHg. Drop down the steep part of the S-curve to that range and saturation plummets — hemoglobin gives up a large fraction of its oxygen right where it is needed most. The steep middle section of the curve means that small PO2 changes drive large unloading. That is not a flaw; it is the design. Three signals from active tissues push the dissociation curve to the right — meaning hemoglobin releases even more oxygen at any given PO2. Two of these signals — rising CO2 and falling pH (more acidic conditions) — define what physiologists call the Bohr effect. CO2 produced by working muscles lowers blood pH, and both changes reduce hemoglobin's affinity for oxygen. Think of it as the tissue broadcasting: "We are working hard — send more O2." Hemoglobin listens and lets go. A third signal, elevated temperature from muscle activity, independently reduces hemoglobin's affinity and reinforces the right shift. Temperature acts separately from the Bohr effect, but in exercising muscle all three forces — CO2, lower pH, and heat — work together to maximize oxygen delivery exactly when demand is highest. The dissociation curve actually does shift — to the right during exercise and more modestly to the left in pulmonary capillaries where CO2 is exhaled and pH is slightly higher. Both the PO2 difference and these curve shifts together explain the full loading-and-unloading story. A left shift means higher affinity — hemoglobin holds on tighter — and it occurs when CO2 is low and pH is higher, as in the lungs. However, the primary reason pulmonary hemoglobin reaches near-full saturation is the high alveolar PO2, which keeps the blood operating on the flat plateau of the curve; the modest leftward shift adds to that advantage but is secondary.