In the lungs, the Laplace pressure, ΔP = 2γ/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(dγ/dA) 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 2ϵ < 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, 2ϵ - γ > 0, which may explain the benefits ARDS patients receive from high frequency oscillatory ventilation.
Bibliographical noteFunding Information:
The authors express their gratitude to Todd Squires and Alan Waring for helpful discussions and Amit K. Sachan for his initial work on the microtensiometer. Research reported in this publication was supported by the National Heart, Lung, & Blood Institute of the National Institutes of Health under grant numbers R01HL135065 and R01HL51177 and National Science Foundation Grants CBET 170378 and CBET 1437864.
© The Royal Society of Chemistry.
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