L65 Cell Injury 1.pdf

01 List the causes of cell injury with appropriate examples Hypoxia & Ischemia Toxins Infectious agents Immunologic reactions Causes of Cell Injury Genetic abnormalities Nutritional imbalance Physical agents Aging Hypoxia & Ischemia Hypoxia: Oxygen deficiency (blockage) Ischemia: Reduce...

01 List the causes of cell injury with appropriate examples Hypoxia & Ischemia Toxins Infectious agents Immunologic reactions Causes of Cell Injury Genetic abnormalities Nutritional imbalance Physical agents Aging Hypoxia & Ischemia Hypoxia: Oxygen deficiency (blockage) Ischemia: Reduced blood supply • Most common causes of cell injury • Resulting from: • Arterial obstruction • Disease affecting lung • Anaemia • Carbon monoxide (CO) • poisoning • Toxins Infectious agents Immunologic Reactions Immune responses elicit inflammatory reactions Genetic Abnormalities Can result in pathologic changes as conspicuous as the congenital malformations Nutritional Imbalance Physical Agents Aging Results in a diminished ability of cells to respond to stress and, eventually, the death of cells and of the organism. 02 Explain the mechanism of cell injury General Principles of Cell Injury Cellular response to injury depends on Targets that are suseptible to cell injury Type of injury Cell membranes Duration Production of ATP via aerobic respiration Severity of injury Type of cell injured Protein synthesis DNA Mechanism of Cell Injury 1. Loss of energy (ATP Depletion) • • Deficiency of oxygen leads to failure of many energydependent metabolic pathways, and ultimately to death of cells by necrosis. Associated with both hypoxic and chemical (toxic) injury 1. Loss of energy (ATP Depletion) Hypoxia and Ischemia • • Persistent or severe hypoxia and ischemia ultimately lead to failure of ATP generation and depletion of ATP in cells. Loss of this critical energy store has deleterious effects on many cellular systems 1. Loss of energy (ATP Depletion) Ischemia-Reperfusion Injury • • • Restoration of blood flow to ischemic but increased cause of cell injury. Mechanisms of cell injury exacerbation New damage may be initiated during reoxygenation by • • Increased generation of ROS Inflammation due to ischaemic injury may increase with reperfusion because it enhances the influx of leukocytes and plasma proteins 2. Increase oxidative stress • • Cellular abnormalities that are induced by ROS, which belong to a group of molecules known as free radicals. Produced by two major pathways: • • Small amounts in all cells during the reduction-oxidation (redox) reactions Phagocytic leukocytes, mainly neutrophils and macrophages Free radicals • • They are chemical species with a single unpaired electron in the outer orbit. They are chemically unstable and so they react with other molecules causing damage If they are not neutralized they can damage cells by • Lipid peroxidation of membranes • DNA fragmentation • Protein cross linking Defects in plasma membrane permeability • • Can also be damaged directly by certain bacterial toxins, viral proteins, lytic complement components, and a variety of physical and chemical agents. Membrane damage affect the mitochondria, the plasma membrane, and other cellular membranes 3. Accumulation of misfolding protein • • • Can stress compensatory pathways in the ER and lead to apoptosis. May be caused by abnormalities that increase the production of misfolded proteins or reduce the ability to eliminate them May cause disease by creating a deficiency of an essential protein or by inducing apoptosis