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    Cell Injury and Cell Death: Mahmud Ghaznawie

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    This document summarizes mechanisms of cell injury and death. It discusses general mechanisms, ischemic injury caused by lack of oxygen, injury from free radicals, and morphological changes in reversible versus irreversible injury. It describes the differences between necrosis and apoptosis, the mechanisms of apoptosis, and subcellular changes to lysosomes, the endoplasmic reticulum, mitochondria, and cytoskeleton during injury. Causes of injury include hypoxia, free radicals, physical and chemical insults, infection, and inflammation. The morphology of necrotic cells and apoptosis are also detailed.

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    Cell Injury and Cell Death: Mahmud Ghaznawie

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    LIEBERKHUN
    51 views48 pages
    This document summarizes mechanisms of cell injury and death. It discusses general mechanisms, ischemic injury caused by lack of oxygen, injury from free radicals, and morphological changes in reversible versus irreversible injury. It describes the differences between necrosis and apoptosis, the mechanisms of apoptosis, and subcellular changes to lysosomes, the endoplasmic reticulum, mitochondria, and cytoskeleton during injury. Causes of injury include hypoxia, free radicals, physical and chemical insults, infection, and inflammation. The morphology of necrotic cells and apoptosis are also detailed.

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    Cell Injury

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    Cell Injury

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    This document summarizes mechanisms of cell injury and death. It discusses general mechanisms, ischemic injury caused by lack of oxygen, injury from free radicals, and morphological changes in reversible versus irreversible injury. It describes the differences between necrosis and apoptosis, the mechanisms of apoptosis, and subcellular changes to lysosomes, the endoplasmic reticulum, mitochondria, and cytoskeleton during injury. Causes of injury include hypoxia, free radicals, physical and chemical insults, infection, and inflammation. The morphology of necrotic cells and apoptosis are also detailed.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    51 views48 pages

    Cell Injury and Cell Death: Mahmud Ghaznawie

    Uploaded by

    LIEBERKHUN
    This document summarizes mechanisms of cell injury and death. It discusses general mechanisms, ischemic injury caused by lack of oxygen, injury from free radicals, and morphological changes in reversible versus irreversible injury. It describes the differences between necrosis and apoptosis, the mechanisms of apoptosis, and subcellular changes to lysosomes, the endoplasmic reticulum, mitochondria, and cytoskeleton during injury. Causes of injury include hypoxia, free radicals, physical and chemical insults, infection, and inflammation. The morphology of necrotic cells and apoptosis are also detailed.

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    © All Rights Reserved
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    of 48

    Cell Injury and Cell Death

    Mahmud Ghaznawie
    Dept Pathology
    Medical Faculty
    Hasanuddin University
    * General mechanism of cell death (C2)
    * Ischemic injury (C3)
    * Injury due to free radicals (C3)
    * The morphology of reversible vs
    irriversible injury (C4)
    * Necrosis vs apoptosis (C4)
    * Mechanism of apoptosis (C3)
    * Subcellular changes due to injury
    * Lisosomes (C2)
    * ER (C2)
    * Mitochondria (C2)
    * Cytoskeleton (C2)
    Plasma Membrane

    Nucleus
    Golgi Apparatus Mitochondria

    Lisosome & peroxisome


    The rough endoplasmic reticulum

    The smooth endoplasmic reticulum


    Cytoskeleton
    Intermediate
    Actin filaments Microtubules filaments
    Adaptation

    Reversible
    injury
    Normal
    cell

    Cell death
    Causes of cell injury
    • Hypoxia
    • Free radicals
    • Physical injury
    • Chemical injury
    • Infection
    • Immune reaction
    Inflammation Hypoxia
    Reperfusion
    Radiation

    Ischemia
    Aging
    Chemical
    Ischemic/hypoxic injury

    Oxygen 

    Oxydative phosphorilation 

    ATP production 

    Sodium pump  Ribosome detachment


    Glycogenolysis
    Ischemic/hypoxic injury

    Oxygen 

    Oxydative phosphorilation 

    ATP production 

    Sodium pump  Ribosome detachment


    Glycogenolysis
    Sodium pump 

    Influx Ca ++ Na+ Retension Efflux K+

    • Cell swollen
    • Microvilli disappear
    • Bleb formation
    • ER swollen
    • Myelin bodies
    Ischemic/hypoxic injury

    Oxygen 

    Oxydative phosphorilation 

    ATP production 

    Sodium pump  Ribosome detachment


    Glycogenolysis
    Glycogenolysis 

    Lactic acid and inorganic


    phosphate

    pH 

    Chromatin clumps
    Ischemic/hypoxic injury

    Oxygen 

    Oxydative phosphorilation 

    ATP production 

    Sodium pump  Ribosome detachment


    Glycogenolysis
    Detachment of ribosomes

    Protein production 

    Intracellular osmotic pressure 

    Cell edema
    Blebs Myelin figures

    Cell swelling

    ER swelling
    Chromatin Ribosomes
    clumps detachment

    Mitochondrial
    Autophagy swelling

    Small
    densities
    C
    A
    Irreversible
    Normal

    B
    Reversible
    Mechanisms membrane damage
    (made simple)
    ATP  Ca++ 

    Phospolipase Protease
    activation activation

    Phospholipid synthesis  Phospholipid Cytoskeletal


    degradation damage

    Membrane damage
    Rupture of Membrane
    lysosomes
    defects

    Myelin figures
    Nucleus
    pyknosis

    Lysis of ER

    Mitochondrial
    swelling

    Large densities
    Inflammation Hypoxia
    Reperfusion
    Radiation

    Iskemia
    Aging
    Chemical
    Injury due to Free Radicals
    • Free Radicals: atoms or molecules
    possesing unpaired electron in an outer
    orbit
    • Characteristics of free radicals:
    – react with any organic / inorganic substance
    – the results will form a new free radicals  new
    reaction chain
    – the reaction will cease by itself or by enzymatic
    reaction
    • Three important free radicals:
    – Superoxide anion radical (O2÷)
    – Hydrogen peroxide (H2O2)
    – Hydroxyl ions(OH•)
    • Effects of free radicals on cell membrane:
    – Membrane lipid peroxidation (especially by OH•)
    – Protein damage: cross-linking of amino acids,
    increase protease activation
    – DNA damage: single helix formation followed by
    cell death of even malignant transformation
    (cancer)
    De-activation of free radicals
    • Spontaneous, because of its instability
    • Endogenous/exogenous antioxidant
    – Vitamine E, C and A
    – Binding to storage & transport proteins (lactoferrin,
    ceruloplasmine, dan trasferrin)
    • Enzymatic
    – Superoxide dismutase (SOD)
    – Catalase
    – Glutathione peroxidase
    S.O.D,
    Catalase,
    and Gluthation peroxidase
    are free radical-scavenging
    enzymes
    Chemical injury
    • Water soluble
    – Act directly (by combining with some critical
    molecular component or cellular organelle)
    – E.g: HgCl, cyanide, antibiotics, and
    chemotherapy
    – Mercury binds to the sulfhydryl groups of the cell
    membrane  increased membrane permeability
    and inhibit ATPase-dependent transport
    – Cyanide poisons mitochondrial cytochrome
    oxidase and block oxidative phosphorylation
    Chemical injury (cont)
    • Lipid soluble
    – Indirect effects (converted to reactive toxic
    metabolites, which then act on target cells)
    – E.g: CCl4
    CCl4

    CCl3•

    Lipid peroxidation

    RER damage Membrane damage

    Permeability Na, H2O, Ca++


    Polysome detachment

    Cell swelling and


    Apoprotein synthesis massive influx of Ca++

    Fatty liver Protein denaturation


    Cell Death
    • Could be necrosis or apoptosis
    • Necrosis
    – Cell death in association to a living tissue
    – When due to lisosomal enzymes: autolysis,
    due to enzymes of immigrant cells: heterolysis.
    – Autolysis  coagulative necrosis; heterolysis
     liquefactive necrosis
    – Morphological changes occure within hours
    The morphology of necrotic cells
    • Cytoplasm:
    – Eosinophillic (reaction to denatured proteins)
    – Glassy appearance (due to loss of glykogen particles)
    – Vacuolated (due to digestion of organelles)
    – Calcification
    • Nucleus: (3 possibilities)
    – Karyolisis (basophilia of the chromatine fades)
    – Pyknosis (due to nuclear shrinkage)
    – Karyorhexis (fragmentation of the pyknotic nucleus)
    Normal Necrosis
    The cytoplasm
    is more eosinophillic
    Nuclei partially lysis
    H & E staining
    to show edema of the
    myocardial fibres

    LDH enzyme staining


    to area unstained areas
    Morphology of necrosis
    Coagulative necrosis:
     The cell outlines are maintained
     Characteristic to hypoxic necrosis
    exept on the brain.

     Occur because the


    lysosomal enzymes we
    also damaged
    Liquefactive necrosis:
     Due to autolysis or
    heterolysis
     Characteristic to bacterial
    infection (pus) and hypoxic
    necrosis to the brain

     Gangrenous necrosis:
    infected coagulative
    necrosis (may then turns to
    liquefactive necrosis)
    Caseous necrosis
     Special form of coagulative necrosis,
    spesific to tbc
     Macroscopically looks like “cheese”
     Microscopic:
    amorphous mass,
    granular, surrounded by
    inflammatory cells
    Enzymic fat
    necrosis

     Destruction of fat due to pancreatic


    lipase
     Fatty acid formed will bind to calcium
     Microscopic: necrotic area, calcium
    deposition (blue), and inflammation of the
    surrounding tissue
    Apoptosis
    • Could be physiological or pathological
    – “Programmed cell death” in embryogenesis,
    involusion of hormon dependent organs, cell death in
    cancer, etc)
    • Morphology:
    – Shrinkage
    – Chromatin condensation
    – Formation of blebs and apoptotic bodies
    – Phagocytosis of apoptotic bodies
    Perubahan subseluler
    Lisosome
    Autophagy dan
    heterophagy

    Autophagy
    Smooth endoplasmic reticulum

    Massively enlarged
    Mitochondria

    Enlarged
    Conclusion
    • Cell injury in the basis of any
    pathologic processes
    • It could be reversible or irreversible
    (ended with cell death)
    • The morphological changes are so
    characteristic
    • The mechanism of cell injury should
    be beared in mind in your further
    study of BMD and medicine
    – Exam Questions on cell injury
    – http://peir2.path.uab.edu/bmp/article_6.shtml
    Mahmud Ghaznawie

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