L65 Cell Injury 1 eOx .pdf

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. Accumula...

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 4. DNA damage • Exposure of cells to: • • • • Radiation or chemotherapeutic agents Intracellular generation of ROS Acquisition of mutations Severe may trigger apoptotic death. 5. Inflammation • • Elicited by pathogens, necrotic cells, and dysregulated immune responses (autoimmune diseases and allergies) Inflammatory cells secrete products that evolved to destroy microbes but also may damage host tissues (Hypersensitivity) 03 Describe the morphologic alterations in reversible and irreversible cell injury Reversible vs irreversible cell injury ● ● ● Reversible injury : Within limits, the cell can compensate for the derangements and, if the injurious stimulus stops , will return to normalcy Irreversible : Persistent or excessive injury, causes irreversible injury And when does the cell actually die? 1. 2. The inability to reverse mitochondrial dysfunction The development of profound disturbances in membrane function. Morphology – Reversible Injury • • On light microscopy • Hydropic Swelling • Fatty Change Ultrastructural changes: • Changes are seen by EM Morphology – Irreversible Injury • On light microscopy • Plasma membrane damage • Lysosomal rupture • Autolysis • Increase mitochondrial permeability • Changes of the nucleus • • • Pyknosis (Nuclear shrinkage) Karyorrhexis (Nucleus undergoes fragmentation) Karyolysis (Chromatin fade) 03 Describe the morphology of the patterns of necrosis with suitable examples Necrosis Spectrum of morphologic changes that follow cell death in living tissues , resulting from the progressive degradative action of enzymes on the lethally injured cells which then invokes inflammatory response TYPES OF NECROSIS Coagulative necrosis Fat necrosis 1 Liquefactive necrosis 2 6 Fibrinoid necrosis 3 5 4 Gangrenous necrosis Caseous necrosis 1. COAGULATIVE NECROSIS • Most common necrosis • Form of tissue necrosis where the component cells are dead but underlying tissue architecture is preserved for at least several days • All solid organs except the brain. Gross Morphology: Firm texture, pale, & slightly swollen. With progression: more yellowish, softer & shrunken COAGULATIVE NECROSIS (Cont.) Protein Blocking the proteolysis of the dead cells structure & enzymes denatured MAY PERSIST FOR DAYS/WEEKS Cellular debris removed by phagocytosis Leukocytes are recruited to the site of necrosis Digested by the action of lysosomal enzymes WHICH ONE IS COAGULATIVE NECROSIS? B A Microscopic view of coagulative necrosis 2. LIQUEFACTIVE NECROSIS Due to bacterial and, occasionally, fungal infections Dead cells are completely digested. Transform of tissue into liquid viscous mass. Remove by phagocytes acute inflammation (bacterial infection) frequently creamy yellow (pus) Gross Morphology The affected area is soft with liquefied centre containing necrotic debris Cyst wall is performed Microscopical Morphology Demonstrates many macrophages at the right which are cleaning up the necrotic cellular debris 3. GANGRENOUS NECROSIS Body part lost blood supply/serious bacterial infection Undergo coagulative necrosis (multiple tissue layers) Superimposed bacterial infection Change morphologic appearance to liquefactive necrosis Destructive contents of the bacteria Attracted leukocytes • Example: DM, Frost bite, Raynaud’s disease, Escharotic drugs Gross Morphology Microscopical Morphology Dry gangrenous necrosis Wet gangrenous necrosis Inflammation extending beneath the skin involve soft tissue (fat and connective tissue at the right) and bone (at the left). 4. CASEOUS NECROSIS Coagulative necrosis + Liquefactive necrosis Gross Morphology Foci of caseous necrosis, friable yellow-white appearance of the area of necrosis. Microscopical Morphology Collection of fragmented or lysed cells with an amorphous granular pink appearance in H&E stained tissue sections. 5. FAT NECROSIS Acinar cell injury Saponification (Chalky features) Calcium + Fatty acid LIPASES Split triglyceride ester Gross Morphology Microscopical Morphology A Soft and chalky white areas B Microscopical Morphology A B 6. FIBRINOID NECROSIS • A special form of necrosis. • Associated with vascular damage & the exudation of plasma. • Characterised by deposition of fibrin-like material which has the staining properties of fibrin. • Cannot be identified grossly. • Example of immunologic tissue injury: • • • 1. Immune complex vasculitis 2. Autoimmune diseases 3. Arthus reaction