dc.contributor.advisor |
Sneyd, J |
en |
dc.contributor.advisor |
Crampin, E |
en |
dc.contributor.advisor |
Donovan, G |
en |
dc.contributor.author |
Sharp, Katie |
en |
dc.date.accessioned |
2015-05-11T02:42:17Z |
en |
dc.date.issued |
2015 |
en |
dc.identifier.citation |
2015 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/25457 |
en |
dc.description.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 conditions. The 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 develop a spatial mathematical model that reflects in vivo fluid recycling via submucosal gland (SMG) secretion, and absorption through surface epithelia. We test the model in CF conditions by increasing ENaC open probability and decreasing SMG flux whilst 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 deplete the serous fluid above CF surface epithelia 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 SMG. |
en |
dc.publisher |
ResearchSpace@Auckland |
en |
dc.relation.ispartof |
PhD Thesis - University of Auckland |
en |
dc.relation.isreferencedby |
UoA99264800208002091 |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ |
en |
dc.title |
A Steady State Model of Fluid Flow in Airways |
en |
dc.type |
Thesis |
en |
thesis.degree.discipline |
Applied Mathematics |
en |
thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Doctoral |
en |
thesis.degree.name |
PhD |
en |
dc.rights.holder |
Copyright: The Author |
en |
pubs.elements-id |
486971 |
en |
pubs.record-created-at-source-date |
2015-05-11 |
en |
dc.identifier.wikidata |
Q111963670 |
|