Allometric Relationships of Cell Numbers and Size in the Mammalian Lung

Abstract Allometric studies have shown that lung volume, alveolar surface area, and diffusing capacity increase proportionally with body weight across a broad range of mammalian species. Changes in the number of cells and in average cell size and surface areas with increasing body weight have not been defined. We speculated that cell size is determined more by cell function than by species and body weight. To test this hypothesis, nine species ranging in size from shrew (2 to 3 g) to horse (510 kg) were studied. Random sites from the distal alveolar region of each species were analyzed using morphometric techniques. Six to 10 nuclei from each of the major classes of parenchymal lung cells were three-dimensionally reconstructed to determine their average diameter, volume, and surface area. To calculate the cell density, nuclear profiles were counted using electron microscopy. The number of cells per lung increased with body mass and lung volume with a slope of 1.01 (r2 = 0.99). The lung is unique among organs in the diversity and function of individual cell types, such as mechanical, sensory, secretory, transporting, and circulating cells. Excluding the circulatory cells, the lung has 60 different cell types, making it an ideal organ for examining the varieties in cell characteristics across different species. Up to 6-fold differences in size were found between different lung cell types within a single species; however, for cells having secretory functions, such as type II cells, there was no detectable change in cell size with increasing lung surface area or body mass. Even for cells having a surface lining role, such as alveolar epithelial type I and endothelial cells, there was no substantial increase in size with increasing body mass. A maximum of a 2-fold change in the average size of an alveolar type I cell occurred over a 200,000-fold increase in body mass. In general, a larger alveolar surface area is constructed with more, not necessarily larger, cells. The average alveolus in the inflation-fixed lungs of the rats we studied had a surface area of 20,800 µm2 and was covered by only four type I and six type II cells. In contrast, the average human alveolus had a surface area of 206,900 µm2 and was covered by 40 type I and 67 type II cells. These data support the hypothesis that cell size and surface area are determined by cell function and not by species size.