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- W924795783 abstract "The genetic disease cystic fibrosis (CF) is a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and results in viscous mucus and impaired mucociliary clearance leading to chronic recurring pulmonary infections. Although extensive experimental research has been conducted over the last few decades, CF lung pathophysiology remains controversial. There are two competing explanations for the observed depletion of periciliary liquid (PCL) in CF lungs. The low volume hypothesis assumes fluid hyperabsorption through surface epithelia due to an over-active epithelial Na+ channel (ENaC), and the low secretion hypothesis assumes inspissated mucins secreted from glands due to lack of serous fluid secreted from gland acini. We present a spatial mathematical model that reflects in vivo fluid recycling via submucosal gland (SMG) secretion, and absorption through surface epithelia. We then test the model in CF conditions by increasing ENaC open probability and decreasing SMG flux while simultaneously reducing CFTR open probability. Increasing ENaC activity only results in increased fluid absorption across surface epithelia, as seen in in vitro experiments. However, combining potential CF mechanisms results in markedly less fluid absorbed while providing the largest reduction in PCL volume, suggesting that a compromise in gland fluid secretion dominates over increased ENaC activity to decrease the amount of fluid transported transcellularly in CF lungs in vivo. Model results also indicate that a spatial model is necessary for an accurate calculation of total fluid transport, as the effects of spatial gradients can be severe, particularly in close proximity to the SMGs." @default.
- W924795783 created "2016-06-24" @default.
- W924795783 creator A5007478932 @default.
- W924795783 creator A5079587534 @default.
- W924795783 creator A5083478373 @default.
- W924795783 date "2015-10-01" @default.
- W924795783 modified "2023-10-16" @default.
- W924795783 title "A spatial model of fluid recycling in the airways of the lung" @default.
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