| Popis: |
This thesis focuses on the development and analysis of mathematical models of the acute inflammation. These models were developed to understand multiple organ dysfunction syndrome (MODS) in ICU patients. MODS is characterized by sequential organ failure caused by an overactive immune system. Therefore, our modeling focused on the acute immune response, which is the generic initial immune response. Understanding the complex interaction during this response will facilitate the development of effective treatments for MODS. We first derived a small scale model for the acute inflammation to understand simple dynamics between pro- and anti-inflammation. More specifically, we use this reduced model to explore the effects of anti-inflammatory mediators, which were once hypothesized as a treatment for MODS with less success than predicted. After the analysis of this reduced model, my research has involved expanding this model into two more complex models. The first includes specific measurable immune mediators, unlike the four variable model. This model also takes in account the interaction between the tissue and blood, which are essential during an inflammatory response. It is a minimum model for an organ and we used it to explore the spread of inflammation between organs. The second models the effects of inflammation on gas exchange in the lung. The lung is typically the first organ to fail during MODS. We developed a model for a single respiratory unit (~25 alveoli). Linking the respiratory units under various anatomical conditions we model the full lung. Methods were developed in order to reduce computation times of the single unit model, allowing the implementation of more accurate ventilation perfusion mismatch in the full model. |
