The role of three-dimensionality and alveolar pressure in the distribution and amplification of alveolar stresses

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.

Progression of regional lung strain and heterogeneity in lung injury: assessing the evolution under spontaneous breathing and mechanical ventilation

“…Lung injury promoters are responsible for the amplification of damage injured lungs, even when MV parameters are within standard safety limits (non-harmful). The concept of stress raisers has been introduced to explain the amplification of damage in areas of high inhomogeneity [ 24 , 25 ], linking the biological response in the lung parenchyma to the regional deformation in localized areas of the lung. The regional analysis showing inhomogeneity in the SB-group suggests that injurious patterns of ventilation in subjects without MV (spontaneous breathing), such as tidal recruitment, anisotropic inflation, and Pendelluft phenomena, among others, can be associated with progression of injury, although the method we used cannot accurately characterize them.…”

A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection

“…The term stress raisers refer to those additional regional factors capable of intensifying the damage. Stress raisers produce amplification of the stress applied in certain localized regions of the lung, like the areas of high inhomogeneity of ventilation [ 19 – 22 ]. The deleterious effects of high regional strain in the lung was confirmed recently in a swine model of injurious MV, where lung zones of increased regional strain had a spatial correlation with areas of tissue inflammation [ 23 ].…”

Estimation of changes in cyclic lung strain by electrical impedance tomography: Proof‐of‐concept study

“…Although strain threshold able to damage baby lung using EELV as the reference volume was reached (ie, strain values above ~0.20), we did not measure neither biomarkers nor metabolic activity in the ventilated lung; our aim was to test if EIT monitoring is able to predict the changes in global cyclic strain when we increase the level of PEEP. In addition, global strain does not capture the inherent heterogeneity in lung deformation, where regional strain amplifications usually arise, 20,21,33,34 which may be obtained using strain based on biomechanical CT method.…”