Cell Injuryand Cell Death课件.pptVIP

Cell Injury and Cell Death Gandi Li, MD, Department of Pathology West China School of Medicine Sichuan University March, 2008 In this Chapter Overview: cellular responses to stress and noxious stimuli Cellular adaptation of growth and differentiation Overview of cell injury and cell death Causes of cell injury Mechanisms of cell injury Reversible and irreversible cell injury Degeneration (so called) Cell death—necrosis and apoptosis Reversible Cell Injury Initially, injury is manifested as functional and morphologic changes that are reversible if the damaging stimulus is removed The hallmarks of reversible injury are reduced oxidative phosphorylation, adenosine triphosphate (ATP) depletion, and cellular swelling caused by changes in ion concentrations and water influx Reversible Cell Injury At this stage, although there may be significant structural and functional abnormalities, the injury has typically not progressed to severe membrane damage and nuclear dissolution These changes are called “ degeneration” in old textbooks of pathology Irreversible Injury Irreversibly injured cells invariably undergo morphologic changes that are recognized as cell death Necrosis Apoptosis When damage to membranes is severe, lysosomal enzymes enter the cytoplasm and digest the cell, and cellular contents leak out, resulting in necrosis Apoptosis, which is characterized by nuclear dissolution without complete loss of membrane integrity Causes of Cell Injury Ischemia/hypoxia (e.g. heart attack) Ischemia ≠ hypoxia Ischemia causes more severe injury than hypoxia Chemical agents (toxins, acid, alcohol) Active oxygen species: free radicals, oxidants, electrophiles Infectious agents Bacterial, virus, fungi, rickettsia, parasite Causes of Cell Injury Immunologic reactions Asthma, autoimmune disorders Genetic defects Down’s syndrome Nutritional imbalances Protein insufficiency, overnutrition-onesity-diabetes Physical agents Trauma, temperature, radiation Iatrogenic causes High concentr