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Physiology Objectives 40 1. Diffusion in the alveolus: diffusion in the alveolus is driven by partial pressure differences; the O2 partial pressure difference is 100-40 = 60 mmHg into the bloodstream, while the CO2 partial pressure difference is 40-45 = 5 mmHg into the lung. a. Diffusion rate and gas characteristics: Graham’s Law states that diffusion rate is inversely proportional to the square root of the density of the gas. Thus, denser gases will diffuse more slowly. b. Gas phase vs. membrane/liquid phase: using the Fick equation, gas diffuses more slowly with smaller area, lower solubility, lower driving pressure, and a thicker membrane 2. Optimization of diffusion using Fick’s Law: the alveoli are extremely thin (0.5 microns) and have a large cross-sectional area (80-100 m2) which optimizes diffusion across its membrane. 3. Perfusion limited gas exchange: complete gas exchange that is only limited by the amount of blood available for exchange Examples: rapid saturation in the bloodstream (low solubility), high driving pressure, fast diffusion rate Diffusion limited gas exchange: incomplete gas exchange that is limited by the ability of the gas to diffuse into the bloodstream Examples: slow saturation in the bloodstream (high solubility), low driving pressure, low diffusion rate 4. Factors causing diffusion limited gas exchange: thickening of the alveolar capillary membrane, high altitude, low FIO2, increased blood flow 5. Measurement of diffusing capacity: gas flow/pressure change Use of CO to measure diffusing capacity: since CO is diffusion limited, it can easily measure the CO being taken in by the body; also, since CO is rapidly and irreversibly bound by hemoglobin, there is no pressure back into the alveoli and therefore, the driving pressure is only the partial pressure of CO in the alveoli Limitations of DLCO: since hemoglobin uptake of CO plays a major role in determining the driving pressure of CO, patients with high or low hemoglobin counts will have a skewed DLCO. To normalize this, we factor the hemoglobin reaction rate resistance in with the membrane resistance to diffusion rate.