Download Cell Injury and Cell Death

LO
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At the end of session student should
be able to
Enlist causes of cell injury
Identify effect of injurious agents on
cell cytoplasm and nucleus
Causes of Cell Injury
Oxygen Deprivation
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Hypoxia – deficiency of oxygen
Ischemia – loss of blood supply
(arterial flow or reduced venous
drainage)
Causes of Cell Injury
Physical Agents
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Mechanical trauma
Extremes of temperature – burns,
deep cold
Radiation
Electric shock
Causes of Cell Injury
Chemical Agents and Drugs
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Hypertonic concentration of salt –
deranging electrolyte homeostasis
Poisons – arsenic, cyanide, or
mercuric salts
Insecticides and Herbicides
Air pollutant – carbon monoxide
Occupational hazard – asbestos
Alcohol and Narcotic drugs
Causes of Cell Injury
Infectious Agents
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Parasites
Fungi
Bacteria
Rickettsiae
Viruses
Causes of Cell Injury
Immunologic Reactions
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Anaphylactic reaction to foreign
protein or drug
Reactions to endogenous selfantigens – autoimmune diseases
Causes of Cell Injury
Genetics Derangements
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Congenital malformation – Down
syndrome
Decreased life of red blood cell –
Thalassemia, Sickle cell anemia
Inborn errors of metabolism
Causes of Cell Injury
Nutritional Imbalances
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Protein-calorie deficiencies
Vitamin deficiencies
Anorexia nervosa
Excesses of lipids – Obesity,
Atherosclerosis
Metabolic diseases – Diabetes
Mechanisms of Cell Injury
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Depletion of ATP
Mitochondrial Damage
Influx of Intracellular Calcium and Loss
of Calcium Homeostasis
Accumulation of Oxygen-Derived free
radical (Oxidative stress)
Defects in Membrane Permeability
Mechanisms of Cell Injury
Depletion of ATP
Causes
Hypoxia, Ischemia
Chemical Injury
Membrane
transport
ATP
Na+K+ATPase (Na-pump),
Ca2+Mg2+ATPases (Ca-pump)
Protein synthesis,
Lipogenesis etc
Mechanisms of Cell Injury
Depletion of ATP
Na+
Ca2+
K+
Mechanisms of Cell Injury
Mitochondrial Damage
Causes
Hypoxia, Toxins
Cytosolic Ca2+
Oxidative stress
Lipid breakdown product
Mechanisms of Cell Injury
Mitochondrial Damage
• Mitochondrial permeability transition of inner
membrane (formation of high-conductance
channel)
Mitochondrial Oxidative Phosphorylation
ATP production
• Leakage of Cytochrome c into cytosol
Mechanisms of Cell Injury
Mitochondrial
Damage
Mechanisms of Cell Injury
Influx of Intracellular Calcium
and Loss of Calcium
Homeostasis
Mechanisms of Cell Injury
Mechanisms of Cell Injury
Accumulation of OxygenDerived Free Radicals
(Oxidative Stress)
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The Oxidation-Reduction reaction
(normal metabolic processes)
-superoxide anion (O2 )
-hydrogen peroxide (H2O2)
-hydroxyl ion (OH )
Mechanisms of Cell Injury
Accumulation of OxygenDerived Free Radicals
(Oxidative Stress)
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Absorption of radiant energy
(ultraviolet light: UV, X-ray)
Ionizing radiation
H20
OH
H
Mechanisms of Cell Injury
Accumulation of OxygenDerived Free Radicals
(Oxidative Stress)
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Transition Metals – iron, copper
“Fenton reaction”
H202
Fe2+
Fe3+
OH
OH-
Mechanisms of Cell Injury
Accumulation of Oxygen-Derived Free
Radicals (Oxidative Stress)
Effects of the free radicals on cell injury
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Lipid peroxidation of Membranes
- Plasma membrane
- Organellar membrane
Double bonds in unsaturated fatty acids
membrane damage
Mechanisms of Cell Injury
Accumulation of Oxygen-Derived Free
Radicals (Oxidative Stress)
Effects of the free radicals
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Oxidative modification of proteins
-Oxidation of amino acid side chains
Protein-protein cross-linkages
-Oxidation of the protein backbone
Protein fragmentation
Mechanisms of Cell Injury
Accumulation of Oxygen-Derived Free
Radicals (Oxidative Stress)
Effects of the free radicals
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Lesions in DNA
Reaction with Thymine
DNA single-stranded break
DNA fragmentation
Superoxide dismutase
(SOD)
Mechanisms of Cell Injury
Defects in Membrane
Permeability
Mechanism of Membrane damage in Cell Injury
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Mitochondrial Dysfunction
-Decreased phospholipid synthesis
-Phospholipase activation
Loss of Membrane phospholipid
Mechanisms of Cell Injury
Defects in Membrane
Permeability
Mechanism of Membrane damage in Cell Injury
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Cytoskeletal Abnormality
Cytosolic Ca+
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protease
Reactive Oxygen species
Lipid breakdown products
(detergen effect on membrane)
Cellular and biochemical
sites of damage in cell
injury
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