Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology

Abstract

Within the pulmonary acini ventilation and blood perfusion are brought together on a huge surface area separated by a very thin blood-gas barrier of tissue components to allow efficient gas exchange. During ventilation pulmonary acini are cyclically subjected to deformations which become manifest in changes of the dimensions of both alveolar and ductal airspaces as well as the interalveolar septa, composed of a dense capillary network and the delicate tissue layer forming the blood-gas barrier. These ventilation-related changes are referred to as micromechanics. In lung diseases, abnormalities in acinar micromechanics can be linked with injurious stresses and strains acting on the blood-gas barrier. The mechanisms by which interalveolar septa and the blood-gas barrier adapt to an increase in alveolar volume have been suggested to include unfolding, stretching, or changes in shape other than stretching and unfolding. Folding results in the formation of pleats in which alveolar epithelium is not exposed to air and parts of the blood-gas barrier are folded on each other. The opening of a collapsed alveolus (recruitment) can be considered as an extreme variant of septal wall unfolding. Alveolar recruitment can be detected with imaging techniques which achieve light microscopic resolution. Unfolding of pleats and stretching of the blood-gas barrier, however, require electron microscopic resolution to identify the basement membrane. While stretching results in an increase of the area of the basement membrane, unfolding of pleats and shape changes do not. Real time visualization of these processes, however, is currently not possible. In this review we provide an overview of septal wall micromechanics with focus on unfolding/folding as well as stretching. At the same time we provide a state-of-the-art design-based stereology methodology to quantify microarchitecture of alveoli and interalveolar septa based on different imaging techniques and design-based stereology.

Differential effects of two-hit models of acute and ventilator-induced lung injury on lung structure, function, and inflammation

“…The organ-scale mechanical effects of lung injury are driven by alterations in the mechanical function of the alveoli and alveolar ducts that comprise the lung parenchyma ( Knudsen et al, 2023 ). These changes in the structure-function relationship potentiate VILI.…”

Exploring alveolar recruitability using positive end-expiratory pressure in mice overexpressing TGF-β1: a structure–function analysis

“…However, this correlation was relatively weak, indicating that diverse micromechanical mechanisms are involved in size change of the alveolar compartment in the AdCl group. In addition to partial and complete alveolar collapse, shape changes and stretching of the interalveolar septa are mechanisms of alveolar volume change 37 , 38 .…”

“…This suggests that in AdCl alveoli only partially derecruited so that the alveolar entrance remained open and identifiable for stereological counting. The formation of these septal pleats predominantly occurs at the junctions of interalveolar septa and has been suggested to be a physiological mechanism of the alveoli to adapt to volume changes without stretching the vulnerable blood-gas barrier 38 .…”

“…This mechanism has to be distinguished from real stretching, the mechanism of volutrauma, which results in an increase of the surface area of the basal membrane which forms a carpet underneath the alveolar epithelium. To discriminate these two mechanism from each other, electron microscopic quantification of the surface area of the epithelial basal lamina at different Pao would be necessary 38 . Hence, it is difficult to deduce from light microscopic investigation whether or not the reduced surface density of alveoli with higher Pao is really linked to relevant/injurious stretch of the blood-gas barrier as indicated by the lung mechanical properties showing stiffening of lung parenchyma.…”