Abstract
Alveolar stresses are fundamental to enable the respiration process in mammalians and have recently gained increasing attention due to their mechanobiological role in the pathogenesis and development of respiratory diseases. Despite the fundamental physiological role of stresses in the alveolar wall, the determination of alveolar stresses remains challenging, and our current knowledge is largely drawn from 2D studies that idealize the alveolar septal wall as a spring or a planar continuum. Here we study the 3D stress distribution in alveolar walls of normal lungs by combining ex-vivo micro-computed tomography and 3D finite-element analysis. Our results show that alveolar walls are subject to a fully 3D state of stresses rather than to a pure axial stress state. To understand the contributions of the different components and deformation modes, we decompose the stress tensor field into hydrostatic and deviatoric components, which are associated with isotropic and distortional stresses, respectively. Stress concentrations arise in localized regions of the alveolar microstructure, with magnitudes that can be up to 27 times the applied alveolar pressure. Interestingly, we show that the stress amplification factor strongly depends on the level of alveolar pressure, i.e, stresses do not scale proportional to the applied alveolar pressure. In addition, we show that 2D techniques to assess alveolar stresses consistently overestimate the stress magnitude in alveolar walls, particularly for lungs under high transpulmonary pressure. These findings take particular relevance in the study of stress-induced remodeling of the emphysematous lung and in ventilator-induced lung injury, where the relation between transpulmonary pressure and alveolar wall stress is key to understand mechanotransduction processes in pneumocytes.
Highlights
The biomechanical behavior of pulmonary alveoli, the basic ventilatory unit of the lung, plays a fundamental role in the respiratory physiology of mammalians
There is wide clinical consensus that organ-level deformation measures are not discriminant enough to detect the early-stage onset of harmful pulmonary conditions during mechanical ventilation therapy[7], which has motivated the development of novel regional tissue biomarkers that can better represent the effect of mechanical ventilation on the strains and stresses acting on lung tissue[8,9]
By imposing static equilibrium in the continuum domain representing the alveolar sac under different levels of alveolar pressure, they were able to resolve the deformed state and the stress distribution in the sample, concluding that local stresses can concentrate in localized regions of the parenchyma, a phenomenon that is amplified in emphysematic lungs
Summary
The biomechanical behavior of pulmonary alveoli, the basic ventilatory unit of the lung, plays a fundamental role in the respiratory physiology of mammalians. Spatial 3D representations of the pulmonary acinus constructed from μ-CT have been reported in the literature, where tetrahedral meshes have been constructed from μ-CT images to visualize and study the intricate alveolated 3D architecture of acini[19] Such geometrical representation of the acinus has motivated the development of structural models of the lung parenchyma by means of 3D continuum finite-element (FE) simulations[20,21,22], which have allowed for a detailed account of the distribution of local strains in the alveolar walls of a rat acinus sample. We hypothesize that the consideration of 3D alveolar geometries and the use of continuum stress analysis on deformed configurations deliver 3D distributions of stresses that will enhance our current knowledge of the distribution and amplification of alveolar stresses, established predominantly from previous 2D studies To this end, we develop a combined experimental-computational technique to assess the 3D stress distribution in alveolar walls of rat acini. We characterize our results in statistical terms, and contrast them to current alveolar stress states reported in the literature
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