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Gas exchange at the alveolar-capillary membrane and at peripheral tissues is governed by Fick's law: diffusion rate is proportional to surface area and partial pressure gradient, and inversely proportional to membrane thickness. Atmospheric O2 (PO2 ~160 mmHg) equilibrates with alveolar air (~104 mmHg) and then diffuses into pulmonary capillary blood (~40 mmHg) until equilibration. Hemoglobin's sigmoidal oxygen-dissociation curve enables cooperative O2 loading in high-PO2 lung capillaries and efficient unloading in low-PO2 tissues. The Bohr effect — increased CO2, acidity, and temperature shift the curve rightward — enhances O2 delivery to metabolically active tissues. CO2 is transported primarily as bicarbonate ion in plasma (70%), with the remainder as dissolved CO2 and carbaminohemoglobin.
Draw the oxygen dissociation curve and annotate the pulmonary capillary operating point (PO2 ~100 mmHg, near-saturation) and the tissue operating point (PO2 ~40 mmHg, significant unloading). Explain why a rightward shift (Bohr effect) is beneficial in exercising muscle: acidic, warm, high-CO2 environment promotes O2 release exactly where it is most needed.
Gas exchange is fundamentally a diffusion problem, and everything about the respiratory and circulatory systems is organized to make diffusion work as efficiently as possible. Fick's law tells you the key variables: diffusion rate increases with surface area and partial pressure gradient, and decreases with membrane thickness. The alveoli provide an enormous surface area (~70 m²), the alveolar-capillary membrane is only ~0.5 µm thick, and the partial pressure gradient between alveolar air (PO2 ~104 mmHg) and incoming venous blood (PO2 ~40 mmHg) is steep. These three factors together make O2 uptake fast enough to nearly fully equilibrate within the brief time a red blood cell spends traversing a pulmonary capillary.
Once O2 crosses into the blood, it faces a transport problem: only ~3 mL of O2 per liter of blood dissolves in plasma — far too little to supply tissues. Hemoglobin solves this by binding O2 cooperatively. The oxygen-dissociation curve is sigmoidal, not linear, because each O2 bound increases the affinity for the next. The flat top of the curve (around PO2 100 mmHg in the lungs) means that hemoglobin remains ~97-98% saturated even if alveolar PO2 drops somewhat. The steep middle portion (PO2 20–60 mmHg) covers the range found in tissues: small drops in PO2 trigger large O2 release. This shape is not accidental — it is precisely the range where delivery is most needed.
The Bohr effect fine-tunes this delivery. In actively metabolizing tissues, CO2 production lowers local pH and raises PCO2 and temperature. Each of these shifts the dissociation curve to the right — hemoglobin's O2 affinity falls, so even more O2 is released at a given PO2. In the lungs, the reverse occurs: CO2 is exhaled, pH rises, and hemoglobin's affinity increases, promoting O2 loading. The system is elegant because the same metabolic signals that create O2 demand also trigger enhanced delivery.
CO2 transport runs in parallel but is mechanistically different. When CO2 enters red blood cells from tissues, carbonic anhydrase converts it to carbonic acid (H2CO3), which dissociates to bicarbonate (HCO3-) and a proton. The bicarbonate exits into plasma in exchange for chloride (the chloride shift), and it is in this bicarbonate form that ~70% of CO2 is carried to the lungs. The proton released in this reaction is buffered largely by hemoglobin itself — and this proton binding is what causes the Bohr effect. The CO2 and O2 transport systems are therefore biochemically coupled: unloading O2 in tissues simultaneously facilitates CO2 loading, and vice versa in the lungs.