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The primary function of the respiratory system is to oxygenate blood and eliminate carbon dioxide, which requires that blood come into virtual contact with fresh air to facilitate diffusion of respiratory gases between blood and gas. This process occurs in the lung alveoli, where blood flowing through alveolar wall capillaries is separated from alveolar gas by an extremely thin membrane of flattened endothelial and epithelial cells, across which respiratory gases diffuse and equilibrate. Blood flow through the lung is unidirectional via a continuous vascular path, along which venous blood absorbs oxygen from and loses CO2 to inspired gas. The path for airflow, in contrast, reaches a dead end at the alveolar walls; as such, the alveolar space must be ventilated tidally, with inflow of fresh gas and outflow of alveolar gas alternating periodically at the respiratory rate (RR). To achieve an enormous alveolar surface area (typically 70 m2) for blood-gas diffusion within the modest volume of a thoracic cavity (typically 7 L), nature has distributed both blood flow and ventilation among millions of tiny alveoli through multigenerational branching of both pulmonary arteries and bronchial airways. As a consequence of variations in tube lengths and calibers along these pathways, and of the effects of gravity, tidal pressure fluctuations, and anatomic constraints from the chest wall, there is variation among alveoli in their relative ventilations and perfusions. Not surprisingly, for the lung to be most efficient in exchanging gas, the fresh gas ventilation of a given alveolus must be matched to its perfusion.

For the respiratory system to succeed in oxygenating blood and eliminating carbon dioxide, it must be able to ventilate the lung tidally to freshen alveolar gas; it must provide for perfusion of the individual alveolus in a manner proportional to its ventilation; and it must allow for adequate diffusion of respiratory gases between alveolar gas and capillary blood. Furthermore, it must be able to accommodate severalfold increases in the demand for oxygen uptake or CO2 elimination imposed by metabolic needs or acid-base derangement. Given these multiple requirements for normal operation, it is not surprising that many diseases disturb respiratory function. Here, we consider in greater detail the physiologic determinants of lung ventilation and perfusion, and how their matching distributions and rapid gas diffusion allow for normal gas exchange. We also discuss how common diseases derange these normal functions, and thereby impair gas exchange—or at least raise the work of the respiratory muscles or heart to maintain adequate respiratory function.

It is useful to think about the respiratory system as having three independently functioning components—the lung including its airways, the neuromuscular system, and the chest wall; the latter includes everything that is not lung or active neuromuscular system. As such, the mass of the respiratory muscles is part of the chest wall, while the force they generate is part of the neuromuscular system; the abdomen (especially an obese abdomen) and the heart (especially an enlarged heart) are, ...

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