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The pathophysiology of sepsis can be regarded as a series of steps, beginning with the invasion of normally sterile tissue by microbes and the elaboration of various pro-inflammatory mediators. The final common pathway is often the development of the multiple organ dysfunction syndrome (MODS). Whereas a great deal has been learned during the past quarter century about the inflammatory processes associated with sepsis (and other related conditions, such as ischemia/reperfusion injury), our understanding is far less developed with respect to the pathophysiological events that lead to organ dysfunction under these conditions. Nevertheless, efforts by both clinical and laboratory scientists are leading to new knowledge in this area. The chapters in this volume provide a state-of-the-art overview of many aspects of the pathophysiology of organ dysfunction in critical illness.
Mitochondrial Biology.- Cellular Responses to Hypoxia: Role of Oxidant Signal Transduction.- The Mitochondrial Permeability Transition: A ‘Pore ‘Way to Die.- Cytopathic Hypoxia in Circulatory Shock: The Role of Poly (ADP-Ribose) Synthetase Activation.- Derangements in Cellular Oxygen Metabolism.- Pharmacologic and Metabolic Mitochondrial Rescue.- Leukocytes and Cell Signaling Mechanisms in Inflammation.- Role of Leukocytes in Sepsis and Lung Injury.- Dysregulated Neutrophil Apoptosis in the Pathogenesis of Organ Injury in Critical Illness.- Does Apoptosis Play a Role in the Development of Sepsis-Induced Myocardial Dysfunction?.- The Intracellular Signaling Pathways of Inflammatory Stress.- Pro-Inflammatory Cytokines: Double-Edged Swords in the Pathogenesis of Bacterial Infection.- Organ-Organ Interactions in Multiple Organ Failure.- Microcirculatory Dysfunction.- Endothelial Cell Dysfunction and Abnormal Tissue Perfusion.- The Microcirculation in Sepsis.- Lung and Kidney.- Pulmonary Vascular Dysfunction.- Pulmonary Epithelial Injury: Clinical and Experimental Evidence for a Major Role in Acute Lung Injury and Multiple Organ Dysfunction.- Ischemia-Induced Derangements in the Actin Cytoskeleton: Mechanisms and Functional Significance.- Multiple Organ Failure and the Kidney.- Apoptosis in Renal Ischemia-Reperfusion Injury.- Gastrointestinal Tract.- Local Muscularis Inflammatory Mechanisms of Ileus.- Mechanisms Responsible for Intestinal Barrier Dysfunction in Critical Illness.- Liver Dysfunction: Nitric Oxide, Carbon Monoxide, and Reactive Oxygen Species.- Brain Injury.- Polyamine Oxidase and 3-Aminopropanal in the Pathogenesis of Cerebral Ischemia.- Key Mechanisms of Secondary Neuronal Damage After Brain Trauma.- Cerebral Ischemia: Pathophysiology and Neuroprotection.- Organ Dysfunction: Detection and Intervention.- Redistribution of Microvascular Oxygen Pressures in the Pig Intestine in Hemodilution and Sepsis.- Influence of Mechanical Ventilation on Organ Dysfunction.- Coagulation Abnormalities in Critical Illness.- Multiple Organ Failure: Clinical Syndrome.