%0 PDF %T Mathematical Model of Oxygen Transport in Tuberculosis Granulomas. %A Datta, Meenal. %8 2017-04-20 %R http://localhost/files/sb397m62z %X Abstract: Tuberculosis (TB) is one of the world's most infectious diseases, accounting for approximately 2 million deaths and 2 billion latent infections in 2009. Despite the relative success of first-line anti-TB agents, multi-drug resistant strains of the TB bacillus have become rampant, especially in impoverished nations. This is due in part to the inability of chemotherapeutic agents to reach the TB bacilli trapped by the host immune system within dense cellular masses known as granulomas, in the lungs. It is argued here that granulomas are, in fact, morphologically similar to solid cancerous tumors in that they both share high cell densities, evidence of mechanical stress, abnormal vasculature, and oxygen-starved regions of hypoxia and necrosis where, in the case of TB, the bacilli survive and lie in wait for the host immune system to be compromised. Analogous to similar research in tumors, thus, this Thesis seeks to explore transport limitations within TB granulomas, specifically to better understand how poor oxygen delivery results in hypoxia and necrosis within these abnormal lesions. Chemical engineering principles of transport and reaction were used to investigate oxygen diffusion and cellular consumption within isothermal granuloma spheroids based on Michaelis-Menten (MM) kinetics. An approximate analytical solution to the problem was explored based on dividing the diffusion-limited region into two sub-regions: an outer sub-region A where zero-order approximation of MM kinetics applies as the result of adequate oxygen concentration, and an inner sub-region B of limited oxygen supply where first-order approximation of MM kinetics is assumed, defining the hypoxic region. Cell death ensues below a critical oxygen level that establishes the necrotic core, where the TB bacteria repose. Based largely on a priori parameters, with the main exception of a MM kinetic constant determined from the experimental minimum size of a granuloma with the start of a necrotic core and an estimated oxygen effective diffusivity, the resulting model is able to predict the emergence of hypoxia and necrosis in granulomas. The theoretical sizes of the hypoxic and necrotic regions were found to be in good agreement with experimental results from a rabbit model of TB, carried out at the National Institutes of Health (NIH) as part of a collaboration with Massachusetts General Hospital (MGH). Such quantitative understanding of transport limitations can inform future TB treatment strategies that may, as in tumors, include adjunct therapeutics that mitigate abnormal physiological traits in the granuloma structure and microenvironment to facilitate oxygen, nutrient, and drug delivery.; Thesis (M.S.)--Tufts University, 2013.; Submitted to the Dept. of Chemical and Biological Engineering.; Advisor: Jerry Meldon.; Committee: Rakesh Jain, and Kyongbum Lee.; Keyword: Chemical engineering. %[ 2022-10-12 %9 Text %~ Tufts Digital Library %W Institution