Cell Injury and Cell Death. LO At the end of session student should be able to At the end of session...
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Transcript of Cell Injury and Cell Death. LO At the end of session student should be able to At the end of session...
LOLO
At the end of session student should At the end of session student should be able tobe able to
Enlist causes of cell injuryEnlist causes of cell injury Identify effect of injurious agents on Identify effect of injurious agents on
cell cytoplasm and nucleuscell cytoplasm and nucleus
Oxygen DeprivationOxygen Deprivation
Hypoxia – Hypoxia – deficiency of oxygendeficiency of oxygen Ischemia – Ischemia – loss of blood supplyloss of blood supply
(arterial flow or reduced venous (arterial flow or reduced venous drainage) drainage)
Causes of Cell InjuryCauses of Cell Injury
Physical AgentsPhysical Agents
Mechanical traumaMechanical trauma Extremes of temperature – Extremes of temperature – burnsburns, ,
deep colddeep cold RadiationRadiation Electric shockElectric shock
Causes of Cell InjuryCauses of Cell Injury
Chemical Agents and DrugsChemical Agents and Drugs
Hypertonic concentration of salt – Hypertonic concentration of salt – deranging electrolyte homeostasisderanging electrolyte homeostasis
PoisonsPoisons –– arsenic, cyanide, or arsenic, cyanide, or mercuric saltsmercuric salts
Insecticides and HerbicidesInsecticides and Herbicides Air pollutant – Air pollutant – carbon monoxidecarbon monoxide Occupational hazard – Occupational hazard – asbestosasbestos Alcohol and Narcotic drugsAlcohol and Narcotic drugs
Causes of Cell InjuryCauses of Cell Injury
Infectious AgentsInfectious Agents
ParasitesParasites FungiFungi BacteriaBacteria RickettsiaeRickettsiae VirusesViruses
Causes of Cell InjuryCauses of Cell Injury
Immunologic ReactionsImmunologic Reactions
Anaphylactic reaction to Anaphylactic reaction to foreign foreign proteinprotein or or drugdrug
Reactions to endogenous self-Reactions to endogenous self-antigens – antigens – autoimmune diseasesautoimmune diseases
Causes of Cell InjuryCauses of Cell Injury
Genetics DerangementsGenetics Derangements
Congenital malformation – Congenital malformation – Down Down syndromesyndrome
Decreased life of red blood cell – Decreased life of red blood cell – Thalassemia, Sickle cell anemiaThalassemia, Sickle cell anemia
Inborn errors of metabolismInborn errors of metabolism
Causes of Cell InjuryCauses of Cell Injury
Nutritional ImbalancesNutritional Imbalances
Protein-calorie deficienciesProtein-calorie deficiencies Vitamin deficienciesVitamin deficiencies Anorexia nervosaAnorexia nervosa Excesses of lipids – Excesses of lipids – ObesityObesity, ,
AtherosclerosisAtherosclerosis Metabolic diseasesMetabolic diseases –– Diabetes Diabetes
Causes of Cell InjuryCauses of Cell Injury
Mechanisms of Cell InjuryMechanisms of Cell Injury Depletion of ATPDepletion of ATP Mitochondrial DamageMitochondrial Damage Influx of Intracellular Calcium and Loss of Influx of Intracellular Calcium and Loss of
Calcium HomeostasisCalcium Homeostasis Accumulation of Oxygen-Derived free Accumulation of Oxygen-Derived free
radical (radical (Oxidative stressOxidative stress)) Defects in Membrane PermeabilityDefects in Membrane Permeability
Mechanisms of Cell InjuryMechanisms of Cell Injury
Depletion of ATPDepletion of ATP
Na+K+ATPase (Na-pump), Ca2+Mg2+ ATPases (Ca-pump)
CausesCauses
Hypoxia, Ischemia
Chemical Injury
Membrane transport
Protein synthesis, Lipogenesis etc
ATP
Na+
K+
Ca2+
Mechanisms of Cell InjuryMechanisms of Cell Injury
Depletion of ATPDepletion of ATP
Mitochondrial DamageMitochondrial DamageMechanisms of Cell InjuryMechanisms of Cell Injury
CausesCauses
Hypoxia, Toxins
Cytosolic Ca2+
Oxidative stress
Lipid breakdown product
Mitochondrial DamageMitochondrial DamageMechanisms of Cell InjuryMechanisms of Cell Injury
• Mitochondrial permeability transition of inner membrane (formation of high-conductance high-conductance channelchannel)
• Leakage of Cytochrome cCytochrome c into cytosol
ATP productionATP production
Mitochondrial Oxidative Phosphorylation
Mechanisms of Cell InjuryMechanisms of Cell Injury
Mitochondrial Mitochondrial DamageDamage
Influx of Intracellular Calcium Influx of Intracellular Calcium and Loss of Calcium and Loss of Calcium
HomeostasisHomeostasis
Mechanisms of Cell InjuryMechanisms of Cell Injury
Mechanisms of Cell InjuryMechanisms of Cell Injury
Accumulation of Oxygen-Accumulation of Oxygen-Derived Free Radicals Derived Free Radicals
(Oxidative Stress)(Oxidative Stress) The Oxidation-Reduction reaction The Oxidation-Reduction reaction
(normal metabolic processes)(normal metabolic processes)
-superoxide anion (O-superoxide anion (O22--))
-hydrogen peroxide (H-hydrogen peroxide (H22OO22))
-hydroxyl ion (OH )-hydroxyl ion (OH )
Mechanisms of Cell InjuryMechanisms of Cell Injury
Accumulation of Oxygen-Accumulation of Oxygen-Derived Free Radicals Derived Free Radicals
(Oxidative Stress)(Oxidative Stress) Absorption of radiant energy Absorption of radiant energy
(ultraviolet light: UV, X-ray)(ultraviolet light: UV, X-ray)
Mechanisms of Cell InjuryMechanisms of Cell Injury
HH2200
Ionizing radiationIonizing radiation
OHOH HH
Accumulation of Oxygen-Accumulation of Oxygen-Derived Free Radicals Derived Free Radicals
(Oxidative Stress)(Oxidative Stress) Transition Metals – Transition Metals – ironiron, , coppercopper
Mechanisms of Cell InjuryMechanisms of Cell Injury
HH220022 OHOH--OHOHFe3+Fe2+
“Fenton reaction”
Lipid peroxidation of MembranesLipid peroxidation of Membranes
- Plasma membrane- Plasma membrane
- Organellar membrane- Organellar membrane
Accumulation of Oxygen-Derived Free Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress)Radicals (Oxidative Stress)
Mechanisms of Cell InjuryMechanisms of Cell Injury
Effects of the free radicals on cell injuryEffects of the free radicals on cell injury
Double bonds in Double bonds in unsaturated fattyunsaturated fatty acids acids
membrane damagemembrane damage
Accumulation of Oxygen-Derived Free Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress)Radicals (Oxidative Stress)
Mechanisms of Cell InjuryMechanisms of Cell Injury
Effects of the free radicalsEffects of the free radicals Oxidative modification of proteinsOxidative modification of proteins --Oxidation of amino acid side chainsOxidation of amino acid side chains
Protein-protein cross-linkagesProtein-protein cross-linkages --Oxidation of the protein backboneOxidation of the protein backbone
Protein fragmentationProtein fragmentation
Accumulation of Oxygen-Derived Free Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress)Radicals (Oxidative Stress)
Mechanisms of Cell InjuryMechanisms of Cell Injury
Effects of the free radicalsEffects of the free radicals Lesions in DNALesions in DNA
Reaction with Reaction with ThymineThymine
DNA single-stranded breakDNA single-stranded break
DNA fragmentationDNA fragmentation
Superoxide dismutase Superoxide dismutase (SOD)(SOD)
Defects in Membrane Defects in Membrane PermeabilityPermeability
Mitochondrial DysfunctionMitochondrial Dysfunction
-Decreased phospholipid synthesis-Decreased phospholipid synthesis
-Phospholipase activation-Phospholipase activation Loss of Membrane phospholipidLoss of Membrane phospholipid
Mechanisms of Cell InjuryMechanisms of Cell Injury
Mechanism of Membrane damage in Cell Injury
Cytoskeletal AbnormalityCytoskeletal Abnormality
Reactive Oxygen speciesReactive Oxygen species
Lipid breakdown productsLipid breakdown products
(detergen effect on membrane)(detergen effect on membrane)
Defects in Membrane Defects in Membrane PermeabilityPermeability
Mechanisms of Cell InjuryMechanisms of Cell Injury
Mechanism of Membrane damage in Cell Injury
Cytosolic Ca+ proteaseprotease
Cellular and biochemical Cellular and biochemical sites of damage in cell sites of damage in cell
injuryinjury
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