D LCO-related parameters have higher sensitivity to detecting abnormalities in pulmonary microcirculation than those in the alveolocapillary membrane. Pulmonary diffusing capacity for CO (D LCO) and the value corrected for alveolar volume (V AV), i.e., D LCO/V AV (K CO), are thought to be crucial for diagnosing alveolar-wall damages. However, one should be aware that although alveolar-arterial P O2 difference sensitively detects moderately low ventilation-perfusion regions causing hypoxemia, it is insensitive to abnormal gas exchange evoked by very low and high ventilation-perfusion regions. Therefore, effective alveolar-arterial P O2 difference is considered useful for assessing gas-exchange abnormalities in lung periphery. Changes in effective alveolar P O2, the most important parameter in classical gas-exchange theory, are coherent with those in mixed alveolar P O2 decided from the multiple inert-gas elimination technique. Based on anatomical and physiological perspectives, the multiple inert-gas elimination technique is thought to be highly effective for predicting ventilation-perfusion heterogeneity between acini of Aschoff under steady-state condition. Although it is difficult to define functional gas-exchange unit in a way entirely consistent with anatomical structures, acinus of Aschoff may serve as a functional gas-exchange unit in a first approximation. Acinus of Loeschcke is taken as an anatomical gas-exchange unit. Model A of Weibel in which dichotomously branching airways are incorporated should be used for analyzing gas mixing in conducting and acinar airways. In the present review, we highlighted these uncertain issues from a variety of anatomical and physiological viewpoints. Many problems regarding structure-function relationships have remained unsolved in the field of respiratory physiology.
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