Cell injury 1


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  • 4/12/1432
  • Cell injury 1

    1. 1. Mechanisms of Cell Injury
    2. 2. There are two Patterns Of Cell death Features Necrosis ApoptosisCell Size (Enlarged(swelling (Reduced(shrinkageNucleus Pyknotic  Karyorrhexis Fragmentation into nucleosome size  Karyolysis fragmentsPlasma Disrupted Intact; altered structure, especiallyMembrane orientation of lipidsCellular Enzymatic digestion; may Intact; may be released in apoptoticContent leak out of cell bodiesAdjacent Frequent NoinflammationPhysiologic Often physiologic, means ofand Pathologic eliminating unwanted cells; may berole Invariably pathologic pathologic after some forms of cell injury, especially DNA damage
    3. 3. : ( Oxygen Deprivation (Hypoxia( 1Hypoxia is an extremely important and.common cause of cell injury and cell deathHypoxia is inadequate oxygenation of the( 1.blood due to cardio respiratory failureLoss of the oxygen-carrying capacity of the( 2 blood, as in anemia or carbon monoxidepoisoningDepending on the severity of the hypoxic.state, cells may adapt, undergo injury, or die
    4. 4. Hypoxia. Most common cause of cell injury. Hypoxia : inadequate oxygenation of tissue( 1. MAJOR CAUSES OF HYPOXIA. Ischemia: decreased arterial blood flow to tissues. Most common cause of hypoxiaEx: Atherosclerosis in coronary arteries due to. deposition of lipid in intima of blood vesselsHypoxemia: decrease in the amount of oxygen dissolved in: plasma. Seen inAtelectasis, pulmonary embolus and interstitial fibrosis. of lungHemoglobin related abnormalities AnemiaCarbon monoxide poisoning (CO has high affinity for(. hemoglobinWill get HEADACHES
    5. 5. Causes of cellular injuryPhysical agents: mechanical trauma, burns, frostbite,( 2sudden changes in pressure, radiations, electric shockChemical agents: poisons (toxins), insecticides, CO,( 3asbestos, alcohol, tobacco, glucose, salt, oxygenInfectious agents: Viruses , rickettsiae, bacteria, fungi,( 4parasitesImmunologic reactions: anaphylaxis, autoimmune( 5.diseaseNutritional imbalances: protein calorie deficiency, vitamin( 6(deficiencies, excess food intake (obesity, atherosclerosisGenetic derangements: congenital malformations,( 7abnormal proteins (hemoglobinopathies), abnormal or absent(.enzymes (storage disorders
    6. 6. :By Depletion of ATP( 1Mechanisms of Cell Injurya( The activity of the plasma membrane energy- dependent sodium pump (Na+,K+-ATPase( is reduced. diminished ATP concentration and enhanced ATPase activity, causes sodium to accumulate intracellular and potassium to diffuse out of the cell. isosmotic gain of water, cause cell swelling, & dilation of the endoplasmic reticulum b( oxidative phosphorylation ceases and cells rely on glycolysis for energy glycogen stores are rapidly depleted. accumulation of lactic acid and inorganic phosphates from the hydrolysis of phosphate esters. This reduces the intracellular pH, resulting in decreased activity of many ..cellular enzymes , +c( Failure of the Ca2+ pump leads to influx of Ca2 Damaging effects on numerous cellular components d( detachment of ribosome from the rough endoplasmic reticulum and dissociation of polysomes into monosomes, with a .consequent reduction in protein synthesis e( proteins may become misfolded, the unfolded protein response that may lead to cell .injury and even death
    7. 7. oxidative phosphorylation↓Ischemia ATP↓↓↓ Na pump ↑Glycolysis Ribosomal DetachmentInflux of Na, H2O ↓ Glycogen ↑ Lactic acid ↓ Protein + Ca2& Synthesis Efflux of K ↓ pH Cell Swelling ER swellingLoss of microvilli Nuclear chromatin Membrane blebs clumping
    8. 8. 2) MITOCHONDRIAL DAMAGE Mitochondria are important targets for virtually all types of ,injurious stimuli hypoxia and toxins( 1 a( increases of ,+cytosolic Ca2 b( by oxidative , stress c( by breakdown of phospholipids through the phospholipase A2 and sphingomyelin pathways, and by d(lipid breakdown products
    9. 9. INFLUX OF INTRACELLULAR CALCIUM( 3 AND LOSS OF CALCIUM HOMEOSTASIS The enzymes known to be activated by calcium include a) ATPases (thereby hastening ATP (, depletion b) phospholipases (which cause membrane (, damage c) proteases (which break down both membrane and cytoskeletal proteins(, and d) endonucleases (which are responsible for DNA and chromatin (fragmentation
    10. 10. ACCUMULATION OF OXYGEN-DERIVED FREE RADICALS( 4 (Reactive Oxygen Species (OXIDATIVE STRESSThe reduction-oxidation reactions that occur during normal metabolic **process. During normal respiration, molecular oxygen is sequentially.reduced by the addition of four electrons to generate waterReactive Oxygen Species : toxic intermediates are produced; these include**superoxide anion radical (O2-(, hydrogen peroxide (H2O2(, and hydroxyl ions. (OH(.this free can damage lipids,protiens, and nucleic acids :Cells have defence system against to prevent injury by free radicalsAntioxidants either block the initiation of free radical formation or( 1inactivate and terminate radical damage(scavenging system(. Examples are.the lipid-soluble vitamins E , A , Vit C and glutathione in the cytosolEnzymes: which breaks down H2O2,superoxide O2- helps in protecting ( 2against the bad effects of free radicals e.g. Catalase, Superoxide dismutase,.glutathion peroxidaseAn imbalance between free radical generating and radical scavenging ** .system leads to oxidative stress causing cell injury
    11. 11. :Free Radical- mediated damage are seen inChemical and Radiation Injury( 1Ischemia- Reperfusion Injury( 2Cellular aging and( 3.Microbial Killing by Phagocytes( 4: The effects of these reactive species areLipid peroxidation of membranes results in*extensive membrane, Organellar and cellular damageOxidative modification of proteins resulting protein*.fragmentationLesions in DNA are responsible for aging and *malignant transformation of cells
    12. 12. Mitochondrial dysfunction*Loss of membrane phospholipids *Plasma membrane damage results in loss ofosmotic balance and influx of fluids and ions,as well as loss of proteins, enzymes,coenzymes, and ribonucleic acids. The cellsmay also leak metabolites, which are vital forthe reconstitution of ATP, thus furtherdepleting net intracellular high-energy. phosphatesInjury to lysosomal membranes results in*leakage of their enzymes into the cytoplasmand activation of these enzymes. Lysosomescontain RNases, DNases, proteases,phosphatases, glucosidases, andcathepsins. Activation of these enzymesleads to enzymatic digestion of cellcomponents, resulting in loss ofribonucleoprotein, deoxyribonucleoprotein,, and glycogen.and the cells die by necrosisCytoskeletal abnormalities*