Transcapillary exchange is the movement of fluid and molecules through the porous capillary wall, and is important
in maintaining homeostasis of bodily tissues. The classical view of this process is that of Starling's
hypothesis, in which the forces driving filtration or absorption are the hydrostatic and osmotic pressure
differences across the capillary wall. However, experimental evidence has emerged suggesting the importance of the
capillary wall ultrastructure, and thus rather than the global differences between capillary and tissue, it is the
local difference across a structure lining the capillary wall known as the endothelial glycocalyx that determines
filtration. Hu and Weinbaum presented a detailed cellular level microstructural model of this phenomenon which was
able to explain some experimental discrepancies.
In this Thesis, rather than describing the microstructural details, the capillary wall is treated as a poroelastic
material. The assumptions of poroelasticity theory are such that the detailed pore structure is smeared out and
replaced by an idealized homogeneous system in which the fluid and solid phases coexist at each point. The
advantage of this approach is that the mathematical problem is greatly simplified such that analytical solutions
of the governing equations may be obtained. This approach also allows calculation of the stress and strain
distribution in the tissue. We depart from classical poroelasticity, however, due to the fact that since there are
concentration gradients within the capillary wall, the filtration is driven by both hydrostatic and osmotic
pressure gradients. The model predictions for the filtration flux as a function of capillary pressure compares
favourably with both experimental observations and the predictions of the microstructural models.
An important factor implicated in transcapillary exchange is the endothelial glycocalyx, which was shown
experimentally to protect against edema formation. Using our theory in combination with the experimental
measurements of glycocalyx thickness and pericapillary space dimension (PSD), we make a quantitative comparison
for the excess flow as a result of a deteriorated glycocalyx, which shows reasonably good agreement with the data.
Since many of the parameters in the model are difficult to measure, a sensitivity analysis was performed on the
most important of these. Finally, since there was variation in the measurements of glycocalyx thickness and PSD,
we used probability distributions to represent the data, and performed further calculations to obtain ranges of
likely values for the various parameters. This work could find applications in cardiovascular disease, where the
glycocalyx is degraded or absent, and in cancer research, where the abnormal vasculature is an impediment to the
efficient delivery of anti-cancer drugs.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OWTU.10012/5221 |
| Date | January 2010 |
| Creators | Speziale, Sean |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis or Dissertation |
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