Ghadiali_10052007

Ghadiali_10052007 - Bioscience in the 21 st Century October...

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Unformatted text preview: Bioscience in the 21 st Century, October 5 th , 2007 Molecular and Biophysical Mechanisms of Lung Cell Injury Samir N. Ghadiali, PhD, Respiratory Biomechanics Laboratory Frank Hook Assistant Professor of Bioengineering Department of Mechanical Engineering and Mechanics Lehigh University Bioscience in the 21 st Century, October 5 th , 2007 Respiratory System Respiratory System Upper Respiratory Airways (Eustachian Tube) Otitis Media (Ear disease) Pulmonary Airways/Alveoli Acute Lung Injury Goal: Utilize engineering, mathematical and biological techniques to understand the pathogenesis of these disorders and develop novel treatments. Bioscience in the 21 st Century, October 5 th , 2007 • Complex bifurcating geometry of pulmonary airways. • Rigid vs. Compliant regions of the lung. • Alveolar contact with circulating blood. Kitoka, Takakai, Suki, JAP 1999 Structure of Pulmonary Airways Structure of Pulmonary Airways Bioscience in the 21 st Century, October 5 th , 2007 Breathing mechanics: • Negative pressure breathing • Contraction of Diaphragm • Deformation of Lung Tissue • Generates negative pressure which “sucks” air in. • Elastic recoil during exhalation Pulmonary Mechanics Pulmonary Mechanics – How do we breath? How do we breath? Alveolar Expansion/Compression Bioscience in the 21 st Century, October 5 th , 2007 Hyaline membranes Lung Immaturity Surfactant Insufficiency Atelectasis Epithelial Injury Alveolar Leakage Fibrosis Infant Respiratory Distress Syndrome Infant Respiratory Distress Syndrome Air bubble • ↑Reopening Pressure → Cell Injury/Fluid Leakage • Surfactant Function → ↓ g and reopening pressure Courtesy, D.P. Gaver, Tulane Univ. Bioscience in the 21 st Century, October 5 th , 2007 S. Ghadiali, Lehigh University Acute Lung Injury Acute Lung Injury • Infections → Necrosis and Detachment of alveolar epithelial cells. • ↑ permeability of alveolar­capillary barrier → Flooding of small airways and alveoli • ↓ gas exchange, severe hypoxia • Standard of care: Mechanical Ventilation • Weaning, Sedation, Ventilator Induced Lung Injury • 30% to 40% mortality rates Ware LB & Matthay MA, New Eng J Med 342(18): 1334­1339 (2000) Courtesy WJ Federspiel, Univ. Pittsburgh Bioscience in the 21 st Century, October 5 th , 2007 Ventilation Induced Lung Injury (VILI) Ventilation Induced Lung Injury (VILI) V P Normal Lower inflection point Ventilated ALI Low Volume Injury (Atelectrauma) ­ Injury due to mechanical stresses exerted during the opening of fluid­filled airways ­ Mechanisms of injury are not well known! High Volume Injury (Volutrauma) • In­vitro cell­culture studies used to identify mechanism of stretch­ induced injury (Tschumperlin, AJRCCM, 2000; Vlahakis, AJPLCMP, 2001, Fisher, AJRCCM, 2004) V T : 12 ml/kg & 6 ml/kg Mortality: 39.8% & 31.0% Bioscience in the 21 st Century, October 5 th , 2007 How do Airways Close during ALI?...
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Ghadiali_10052007 - Bioscience in the 21 st Century October...

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