The micromechanics of lung alveoli: structure and function of surfactant and tissue components

Abstract

The mammalian lung´s structural design is optimized to serve its main function: gas exchange. It takes place in the alveolar region (parenchyma) where air and blood are brought in close proximity over a large surface. Air reaches the alveolar lumen via a conducting airway tree. Blood flows in a capillary network embedded in inter-alveolar septa. The barrier between air and blood consists of a continuous alveolar epithelium (a mosaic of type I and type II alveolar epithelial cells), a continuous capillary endothelium and the connective tissue layer in-between. By virtue of its respiratory movements, the lung has to withstand mechanical challenges throughout life. Alveoli must be protected from over-distension as well as from collapse by inherent stabilizing factors. The mechanical stability of the parenchyma is ensured by two components: a connective tissue fiber network and the surfactant system. The connective tissue fibers form a continuous tensegrity (tension + integrity) backbone consisting of axial, peripheral and septal fibers. Surfactant (surface active agent) is the secretory product of type II alveolar epithelial cells and covers the alveolar epithelium as a biophysically active thin and continuous film. Here, we briefly review the structural components relevant for gas exchange. Then we describe our current understanding of how these components function under normal conditions and how lung injury results in dysfunction of alveolar micromechanics finally leading to lung fibrosis.

Keywords: Acinus; Acute lung injury; Connective tissue; Fibrosis; Surfactant; Type II alveolar epithelial cell.

Fig. 1

Transmission electron microscopy. Human lung. Inter-alveolar septum with type I (AEC1) and type II (AEC2) alveolar epithelial cell. Note surfactant-storing lamellar bodies (LB) in type II cell. Arrowheads mark tight junctions between type II cell and neighbouring type I cell extensions. Collagen fibrils (col) are present in the interstitium. Alv alveolar lumen, Cap capillary lumen, Endo capillary endothelial cell. Scale bar 2 µm

Fig. 2

Transmission electron microscopy. Human lung. Inter-alveolar septum with collagen fibrils (col) and elastic fibers (el). The alveolar epithelium (thin type I cell extension marked by arrowheads) is covered with a lining layer containing intra-alveolar surfactant (Surf). Alv alveolar lumen. Scale bar 1 µm. Inset shows tubular myelin, a surface-active intra-alveolar surfactant subtype, at higher magnification. Scale bar 0.5 µm

Fig. 3

Transmission electron microscopy. Human lung. Inter-alveolar septum with free edge (right) indicating the opening into an alveolar lumen (Alv). Note reinforced entrance ring with elastic fibers (el) at the alveolar opening where the axial fibers are connected to the septal fibers. col collagen fibrils, Fb fibroblast extensions, bl alveolar epithelial basal lamina, arrowhead tight junction between type I alveolar epithelial cells. Scale bar 1 µm

Fig. 4

The stress-bearing elements of acinar airspaces. In a previous study (Knudsen et al. 2018), healthy rat lungs were fixed in vivo at airway opening pressure (Pao) of 1 (a) and 10 cm H₂O (b). At low pressure, the alveolar ducts are narrow and the inter-alveolar septal walls are characterized by foldings and pleats. The septal walls protrude into the alveolar duct and are connected to the duct via the alveolar entrance. By drawing a straight line between the edges of the septal walls, alveolar and ductal airspaces were separated from each other (fine dashed lines). The axial network of elastic and collagen fibers is concentrated at the edges of alveolar septa and coils the alveolar duct. Here, this system is illustrated as springs spanning the alveolar duct (red springs). At low Pao (or lung volume), the elastic fibers are only slightly stretched (a, b). The fibers exert pulling forces on the alveolar edges/entrance rings in the direction of the ductal lumen (red arrows in a, c) and counteract the surface tension forces (green arrows in a, c) which would pull the septal wall away from the duct and result in a piling up and finally collapse of airspaces. At Pao = 10 cm H₂O the alveolar duct is widened, the axial fiber system stretched (red springs in c and d). The forces which are responsible for inflation of the lung are related to the pressure gradient between the pleural space (P_Pl) and the alveolar space (P_alv). The outward forces (F_O) are transmitted to the fiber system in the septal walls and correspond here to the inward forces (F_i). Depiction is based on models of Wilson and Bachofen (1982) and Mead et al. (1970). Scale bar 100 µm

Fig. 5

Mechanisms of alveolar micromechanics during the deflation limb of a pressure–volume curve. Four mechanisms have been suggested (Gil et al. 1979): (1) Alveolar derecruitment, (2) Isotropic (balloon-like) destretching, (3) Shape changes and (4) Folding of alveolar walls. In vivo, the lung volume usually does not drop below the functional residual volume which is above the inferior infliction point. The occurrence of alveolar derecruitment is unlikely in this range of pressures but can be observed at very low lung volumes, e.g. with negative airway opening pressures. The other 3 mechanisms are likely to occur throughout the partial PV relationship above FRC although there is good evidence that folding dominates at lower volumes while destretching is most prominent at larger volumes. Shape changes have been described to be very dominant at intermediate volumes. This depiction is based on the observations of Gil et al. (1979), Bachofen et al. (1987), Tschumperlin and Margulies (1999) and Knudsen et al. (2018). The light microscopic images were taken from histological sections of a previous study (Knudsen et al. 2018). The description provided in this image is based on evaluations of lungs fixed at different pressures during the PV loop. Isolated phenomena occurring in the septal walls such as folding, shape change or stretching have never been observed in exactly the same alveolus directly. Scale bar 50 µm