Cell Injury and Cell Death

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Cell Injury and Cell Death
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LO

• 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

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Oxygen Deprivation
Causes of Cell Injury

• Hypoxia deficiency of oxygen
• Ischemia loss of blood supply (arterial flow or
  reduced venous drainage)

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Physical Agents
Causes of Cell Injury

• Mechanical trauma
• Extremes of temperature burns, deep cold
• Radiation
• Electric shock

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Chemical Agents and Drugs
Causes of Cell Injury

• 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

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Infectious Agents
Causes of Cell Injury

• Parasites
• Fungi
• Bacteria
• Rickettsiae
• Viruses

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Immunologic Reactions
Causes of Cell Injury

• Anaphylactic reaction to foreign protein or drug
• Reactions to endogenous self-antigens
  autoimmune diseases

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Genetics Derangements
Causes of Cell Injury

• Congenital malformation Down syndrome
• Decreased life of red blood cell Thalassemia,
  Sickle cell anemia
• Inborn errors of metabolism

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Nutritional Imbalances
Causes of Cell Injury

• Protein-calorie deficiencies
• Vitamin deficiencies
• Anorexia nervosa
• Excesses of lipids Obesity, Atherosclerosis
• Metabolic diseases Diabetes

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Mechanisms of Cell Injury

• 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

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Depletion of ATP
Mechanisms of Cell Injury
Causes Hypoxia, Ischemia Chemical Injury
Membrane transport
ATP
NaKATPase (Na-pump), Ca2Mg2ATPases (Ca-pump)
Protein synthesis, Lipogenesis etc
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Mechanisms of Cell Injury
Depletion of ATP
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Mitochondrial Damage
Mechanisms of Cell Injury
Causes Hypoxia, Toxins Cytosolic Ca2
Oxidative stress Lipid breakdown product

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Mitochondrial Damage
Mechanisms of Cell Injury

• Mitochondrial permeability transition of inner
  membrane (formation of high-conductance channel)
• Leakage of Cytochrome c into cytosol

Mitochondrial Oxidative Phosphorylation
ATP production
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Mechanisms of Cell Injury
Mitochondrial Damage
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Influx of Intracellular Calcium and Loss of
Calcium Homeostasis
Mechanisms of Cell Injury
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Mechanisms of Cell Injury
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Accumulation of Oxygen-Derived Free Radicals
(Oxidative Stress)
Mechanisms of Cell Injury

• The Oxidation-Reduction reaction (normal
  metabolic processes)
• -superoxide anion (O2-)
• -hydrogen peroxide (H2O2)
• -hydroxyl ion (OH )

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Accumulation of Oxygen-Derived Free Radicals
(Oxidative Stress)
Mechanisms of Cell Injury

• Absorption of radiant energy (ultraviolet light
  UV, X-ray)

Ionizing radiation
H20
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Accumulation of Oxygen-Derived Free Radicals
(Oxidative Stress)
Mechanisms of Cell Injury

• Transition Metals iron, copper

Fenton reaction
H202
OH-
Fe3
Fe2
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Effects of the free radicals on cell injury
Mechanisms of Cell Injury
Accumulation of Oxygen-Derived Free Radicals
(Oxidative Stress)

• Lipid peroxidation of Membranes
• - Plasma membrane
• - Organellar membrane

• Double bonds in unsaturated fatty acids
• membrane damage

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Mechanisms of Cell Injury
Accumulation of Oxygen-Derived Free Radicals
(Oxidative Stress)
Effects of the free radicals

• Oxidative modification of proteins
• -Oxidation of amino acid side chains
• Protein-protein cross-linkages
• -Oxidation of the protein backbone
• Protein fragmentation

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Mechanisms of Cell Injury
Accumulation of Oxygen-Derived Free Radicals
(Oxidative Stress)
Effects of the free radicals

• Lesions in DNA
• Reaction with Thymine
• DNA single-stranded break
• DNA fragmentation

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Superoxide dismutase (SOD)
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Defects in Membrane Permeability
Mechanisms of Cell Injury
Mechanism of Membrane damage in Cell Injury

• Mitochondrial Dysfunction
• -Decreased phospholipid synthesis
• -Phospholipase activation
• Loss of Membrane phospholipid

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Defects in Membrane Permeability
Mechanisms of Cell Injury
Mechanism of Membrane damage in Cell Injury

• Cytoskeletal Abnormality
• Reactive Oxygen species
• Lipid breakdown products
• (detergen effect on membrane)

protease
Cytosolic Ca
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Cellular and biochemical sites of damage in cell
injury
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• Thanks