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In the lungs, the Laplace pressure, Δ P = 2 γ / R , would be higher in smaller alveoli than larger alveoli unless the surface tension, γ decreases with alveolar interfacial area, A , such that 2ε > γ in which ε = A (d γ /d A ) is the dilatational modulus. In Acute Respiratory Distress Syndrome (ARDS), lipase activity due to the immune response to an underlying trauma or disease causes single chain lysolipid concentrations to increase in the alveolar fluids via hydrolysis of double-chain phospholpids in bacterial, viral, and normal cell membranes. Increasing lysolipid concentrations decrease the dilatational modulus dramatically at breathing frequencies if the soluble lysolipid has sufficient time to diffuse off the interface, causing 2 ε < γ , thereby potentially inducing the “Laplace Instability”, in which larger alveoli have a lower internal pressure than smaller alveoli. This can lead to uneven lung inflation, alveolar flooding, and poor gas exchange, typical symptoms of ARDS. While the ARDS lung contains a number of lipid and protein species in the alveolar fluid in addition to lysolipids, the surface activity and frequency dependent dilatational modulus of lysolipid suggest how inflammation may lead to the lung instabilities associated with ARDS. At high frequencies, even at high lysolipid concentrations, 2 ε − γ > 0, which may explain the benefits ARDS patients receive from high frequency oscillatory ventilation.
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Inflation instability in the lung: an analytical model of a thick-walled alveolus with wavy fibres under large deformations
Inflation of hollow elastic structures can become unstable and exhibit a runaway phenomenon if the tension in their walls does not rise rapidly enough with increasing volume. Biological systems avoid such inflation instability for reasons that remain poorly understood. This is best exemplified by the lung, which inflates over its functional volume range without instability. The goal of this study was to determine how the constituents of lung parenchyma determine tissue stresses that protect alveoli from instability-related overdistension during inflation. We present an analytical model of a thick-walled alveolus composed of wavy elastic fibres, and investigate its pressure–volume behaviour under large deformations. Using second-harmonic generation imaging, we found that collagen waviness follows a beta distribution. Using this distribution to fit human pressure–volume curves, we estimated collagen and elastin effective stiffnesses to be 1247 kPa and 18.3 kPa, respectively. Furthermore, we demonstrate that linearly elastic but wavy collagen fibres are sufficient to achieve inflation stability within the physiological pressure range if the alveolar thickness-to-radius ratio is greater than 0.05. Our model thus identifies the constraints on alveolar geometry and collagen waviness required for inflation stability and provides a multiscale link between alveolar pressure and stresses on fibres in healthy and diseased lungs.
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- Award ID(s):
- 1910401
- PAR ID:
- 10403138
- Date Published:
- Journal Name:
- Journal of The Royal Society Interface
- Volume:
- 18
- Issue:
- 183
- ISSN:
- 1742-5662
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1098/rsif.2021.0594
