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    Cell Injury-1

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    Nooria Butt
    The document discusses cell injury and the role of free radicals. It describes two types of cell injury - reversible and irreversible. Reversible injury can be repaired when the stimulus is removed, while irreversible injury causes permanent cellular damage and death. Free radicals are highly reactive chemical species that can cause lipid peroxidation, DNA lesions, and protein oxidation, leading to cell injury. The body has antioxidant defenses and enzymatic systems to deactivate free radicals, but an overabundance can overwhelm these protective mechanisms.

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    Cell Injury-1

    Uploaded by

    Nooria Butt
    11 views31 pages
    The document discusses cell injury and the role of free radicals. It describes two types of cell injury - reversible and irreversible. Reversible injury can be repaired when the stimulus is removed, while irreversible injury causes permanent cellular damage and death. Free radicals are highly reactive chemical species that can cause lipid peroxidation, DNA lesions, and protein oxidation, leading to cell injury. The body has antioxidant defenses and enzymatic systems to deactivate free radicals, but an overabundance can overwhelm these protective mechanisms.

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    CELL INJURY-1 (2).ppt

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    The document discusses cell injury and the role of free radicals. It describes two types of cell injury - reversible and irreversible. Reversible injury can be repaired when the stimulus is removed, while irreversible injury causes permanent cellular damage and death. Free radicals are highly reactive chemical species that can cause lipid peroxidation, DNA lesions, and protein oxidation, leading to cell injury. The body has antioxidant defenses and enzymatic systems to deactivate free radicals, but an overabundance can overwhelm these protective mechanisms.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    11 views31 pages

    Cell Injury-1

    Uploaded by

    Nooria Butt
    The document discusses cell injury and the role of free radicals. It describes two types of cell injury - reversible and irreversible. Reversible injury can be repaired when the stimulus is removed, while irreversible injury causes permanent cellular damage and death. Free radicals are highly reactive chemical species that can cause lipid peroxidation, DNA lesions, and protein oxidation, leading to cell injury. The body has antioxidant defenses and enzymatic systems to deactivate free radicals, but an overabundance can overwhelm these protective mechanisms.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    of 31

    1

    "Live as if your were to die


    tomorrow. Learn as if you were
    to live forever."
    CELL INJURY
    IT IS THE RESPONSE OF A CELL TO
    EXCESSIVE PHYSIOLOGIC STRESSES
    OR ADVERSE PATHOLOGIC STIMULI.

    3
    TYPES OF CELL INJURY
    • REVERSIBLE CELL INJURY
    • IRREVERSIBLE CELL INJURY

    4
    REVERSIBLE CELL INJURY
    IT DENOTES PATHOLOGIC CHANGES
    THAT CAN BE REVERSED WHEN THE
    STIMULUS IS REMOVED OR IF THE
    CAUSE OF THE INJURY IS MILD.

    5
    IRREVERSIBLE CELL INJURY

    IT DENOTES PATHOLOGIC CHANGES


    THAT ARE PERMANENT AND CAUSE
    CELLULAR DEATH.

    6
    CAUSES OF CELL INJURY
    • HYPOXIA.
    • PHYSICAL AGENTS.
    • CHEMICAL AGENTS AND DRUGS.
    • INFECTIOUS AGENTS.
    • IMMUNOLOGIC REACTIONS.
    • GENETIC DERANGEMENTS.
    • NUTRITIONAL IMBALANCES.
    7
    MECHANISM OF CELL INJURY

    GENERAL PRINCIPLES

    • CELLULAR RESPONSE.
    • FACTORS GOVERNING CONSEQUENCES.
    • VULNERABLE INTRACELLULAR SYSTEMS.
    • APPEARANCE OF MORPHOLOGIC CHANGES.

    8
    BIOCHEMICAL MECHANISMS
    OF CELL INJURY
    • ATP DEPLETION.
    • OXYGEN DEPRIVED FREE RADICALS.
    • LOSS OF CALCIUM HOMEOSTASIS.
    • DIRECT MEMBRANE DAMAGE.
    • IRREVERSIBLE MITOCHONDRIAL DEMAGE.

    9
    HYPOXIA (REVERSIBLE INJURY)
    ISCHAEMIA

    Mitrochondria (Centre of Aerobic Respiration)

    Oxidative Phosphorilation

    Decreased ATP

    Increased AMP

    Membrane damage Stimulation of Enzymes for Disruption of energy dependent


    Anaerobic Respiration interactions between ER
    Na pump activity
    Membrane and Ribosomes.
    Intracellular Na Increased Glycolysis for
    ATP generation Detachment of Ribosomes
    Osmotic gain of H2O
    Accumolation of Lactic Acid
    Decreased Protein Synthesis
    Cellular swelling ER swelling
    loss of Microvilli Decreased pH
    Lipid deposition
    10
    Bleb formation Mylein Figure Nuclear Chromatin clumping
    HYPOXIA
    IRREVERSIBLE INJURY
    Decreased O2 ISCHAEMIA Inflammation by
    Leukocytes
    Decreased ATP Increased Cytosolic Ca++
    WBC produce
    Decreased Phospholipase Increased Ca toxic Oxygen
    Protease in Mitochondria species
    Phospholipid Activation Activation
    Synthesis
    Poisoning of Memb.
    Increased Damage to
    Mitochondria damage
    Phospholipid Cytoskelatal
    Loss of Memb. degradation filaments anchoring
    Phospholipid Plasma Memb. cell Unable to use O2
    Interior during Respiration
    Lipid breakdown Products

    Formation of
    Memb. damage Detachment of reactive free
    Cell Memb. from Cell Swelling Radicals
    Cell Interior

    Reperfusion
    Rupture of cell Memb.
    Injury 11
    DEDUCTIONS
    • Hypoxia affects Oxidative Phosphorylation
    and Synthesis of ATP.
    • Membrane damage is critical to Lethal Cell
    Injury.
    • Calcium is an important mediator of the
    Biochemical and Morphological alteration
    leading to cell death.
    12
    13
    14
    15
    FREE RADICAL INDUCED CELL INJURY

    DEFINITION:
    THESE ARE EXTREMELY REACTIVE
    CHEMICAL SPECIES THAT HAVE A
    SINGLE UNPAIRED ELECTRON IN THE
    OUTER ORBITAL.

    16
    PRODUCTION OF FREE RADICALS

    • Absorption of radiation energy.


    • Endogenous oxidative reactions.
    • Enzymatic metabolism of exogenous
    chemicals or drugs.

    17
    Mechanisms of action
    • By reacting with inorganic or organic chemicals.
    • By initiating autocatalytic reactions.

    18
    TYPES OF FREE RADICALS
    • THREE MAIN TYPES:
    • Oxygen centered Free Radicals.
    • Carbon centered Free Radicals.
    • Nitrogen centered Free Radicals.

    19
    OXYGEN CENTERED FREE RADICALS

    These are partially reduced toxic


    intermediate oxygen species produced
    intracellularly by the activity of
    oxidative enzymes.

    20
    Intracellular Sites of Production
    • Cystole
    • Mitochondria
    • Lysosomes
    • Plasma Membrane.
    OXIDATIVE ENZYMES INVOLVED
    • Xanthine oxidase
    • Cytochrome P-450 21
    OXYGEN CENTERED FREE RADICALS
    • Superoxide:
    _
    O2 Oxidase
    O2
    • Hydrogen peroxide:
    O2 + O2 + 2H+ SD
    H 2 O2 + O 2
    • Hydroxide Radicals
     Hydrolysis of water by Ionizing Radiations:
    _
    +
    H2O H + OH
     Interaction with Transitional Metals:
    (FENTION REACTION)
    _ _
    ++ +++
    Fe + H2 O Fe + OH + OH 22
    Most of the Iron is in Ferric form
    and it is reduced to Ferrous form
    by Superoxide (Autocatalysis).
    Sources of Iron and Superoxide
    are req for maximum oxidative cell
    damage.

    23
    CARBON CENTERED FREE RADICALS

    Carbon trichloride (CCl3) produced by enzyme


    induced conversion of carbon tetrachloride.
    _ _
    CCl4 + e CCL3 + Cl

    24
    NITROGEN CENTERED FREE RADICALS

    • Nitric Oxide (NO) produced by invading


    Leukocytes.
    • Peroxynitrite anion.

    . _ _
    +
    NO + O2 ONOO + H

    25
    EFFECTS OF FREE RADICALS
    1. Lipid peroxidation of membranes:
    • Attacks double bonds existing within
    unsaturated fatty acids.
    • Peroxides are produced.
    • Reactive species initiating
    autocatalytic reactions.

    26
    2. Lesions in DNA:
    • Reacts with thymine in DNA
    • Causes single strand breaks.
    • Implicated in cell killing and malignant
    transformation.

    27
    3. Oxidative Modifications of Proteins

    • Reacts with labile amino acids, methionine,


    cystein, histidine and lysine.
    • Formation of sulfhydryl mediated cross linkages.
    • Fragmentation of polypeptide chains.
    • Enzymes containing cross linkages are acted
    upon by proteases & gets degraded leading to
    havoc within the cells.

    28
    INACTIVATION OF FREE RADICALS
    1. SPONTANEOUS DECAY
    Example:
    Superoxide into oxygen and H2O2.
    2. NONENZYMATIC INACTIVATION by endogenous
    or exogenous antioxidants.
    Examples:
     Vit E.
     Sulfhydryl containing compounds like cystein and
    glutathione.
     Serum proteins.
    • Albumin.
    • Ceruloplasmin.
    29
    • Transferrin.
    3. ENZYMATIC INACTIVATION OF FREE RADICALS.
    ( i ) Superoxide dismutase:
    Inactivates superoxide by converting it to H 2O2.
    ( ii ) Catalase:
    Inactivates H2O2 by converting it into water.
    ( iii ) Glutathione peroxidase:
    Inactivates hydroxyl ion and hydrogen peroxide by
    .
    releasing hydrogen which then combines with OH or
    H2O2 to form water.

    30
    TYPES OF CELL INJURY EMPLOYING FREE RADICALS

    • Chemical Injury.
    • Radiation Injury.
    • Oxygen toxicity.
    • Cellular aging.
    • Microbial killing.
    • Inflammatory damage.
    • Tumour destruction.
    Final common pathway in most types of
    cell injury.
    31

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