Development of Alveolar Septa and Cellular Maturation within the Perinatal Lung

Abstract

Abstract To quantitate fetal lung cellularity and regional variation in alveolar maturation, guinea pig lungs were studied at 55, 60, and 65 d of gestation or within 2 h of birth (term = 68 d), and the data were analyzed for intralobar, interlobar, and age-group differences. Nine blocks from each left cranial and caudal lobe were all measured for volume, numerical, and surface densities in tissue (Vv(i,t), Nv(i,t), and Sv(i,t)), and total volumes, numbers, and surface areas per lung (V, N, and S) of type I and type II epithelia, presumptive progenitor epithelium (cuboidal cells lacking lamellar bodies [LB]), interstitium, and endothelium. Total fixed lung volume, VL, increased 3-fold from day 55 through birth. At each age, there were no consistent intralobar or interlobar differences in Vv(i,t), Nv(i,t), or Sv(i,t) for any cell type. Within a septal tissue volume of 580 to 670 µl at all ages, the N and V of type I cells did not vary with age, although their S increased from 1,240 cm2 at day 55 to 3,967 cm2 at birth. The N of morphologic type II cells per lung increased 7-fold from day 55 to day 60 and was constant thereafter, while the N of cuboidal cells decreased proportionally; type II cells contained only 4.8% (vol/vol) of LB at 55 d compared to 18.0% at birth. The N and V of interstitium did not vary by age. While endothelial V was constant over these ages, endothelial S increased from 897 cm2 to 3,398 cm2, and the V of capillary blood and the V of alveolar airspace each increased 4-fold. Arithmetic mean barrier thickness decreased from 5.6 µm at day 55 to 1.4 µm in newborn animals. Thus, from day 60 until birth there was little cellular proliferation or addition of structural mass to the septal parenchyma but uniform and continuous thinning of the epithelial, interstitial, and capillary endothelial surface layers. Further production of LB within type II cells and very large increases in both alveolar airspace and capillary blood volumes paralleled the elaboration of septal surfaces.