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42 Cards in this Set
- Front
- Back
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Cellular response and consequences to injurious stimuli will depend on? |
Type of injury/insult Duration of the injurious agent's effect Severity, extent of injury, concentration in tissue Type of cell and its Current status |
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Cell injury occurs when a cell... |
Can no longer maintain a steady state |
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"The point of no return" occurs when.. |
the injury reaches a certain limit whereby the cell can't recover and progresses to irreversible cell injury |
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Tissue Sensitivity to hypoxia depends on... |
Energy demands of the cell and/or its ability to utilize anaerobic glycolysis as a source of energy |
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Tissue Sensitivity to hypoxia: high |
Neurons
*only 3-5mins to irreversible cell injury |
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Tissue Sensitivity to hypoxia: intermediate |
Hepatocytes, Myocardium, Renal epithelium
*30 mins to 2 hours to irreversible cell injruy |
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Tissue Sensitivity to hypoxia: low |
Fibroblasts, Epidermis, Skeletal Muscle
*Many hours to irreversible cell injury |
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Brain, heart and renal tubular cells are sensitive to.. |
Hypoxia and Ischemia |
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Liver cells are susceptible to... |
Injury by drugs and chemicals |
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5 intracellular systems that are particularly vulnerable |
Cell membrane Aerobic respiration Protein synthesis Cytoskeleton Genetic apparatus |
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Aerobic respiration includes |
Mitochondrial oxidative phosphorylation / ATP production |
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Biochemical mechanisms of cell injury |
ATP depletion Free radical induced injury (Oxidative Stress) Intracellular Ca and loss of Ca homeostasis Mitochondrial damage Defects in membrane permeability |
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ATP Depletion |
Consequence of both ischemic & toxic injury ATP required for membrane transport, osmotic balance, protein synthesis, protein stability, lipogenesis |
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What are free radicals? |
Molecules with a single unpaired electron (extremely unstable) that react with organic or inorganic chemicals, avidly attack and degrade nucleic acids and membrane molecules |
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Free radical induced injury occurs when... |
free radial generation overwhelms radical-scavenging defence mechanisms |
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Main sites of free radical damage |
Damage of membranes (lipid peroxidation) Damage of proteins Damage to DNA |
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Protective Mechanisms against free radical damage |
Storage and transport proteins Antioxidants Enzymes that scavenge free radicals |
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Protective Mechanisms: Storage and transport proteins |
Iron and copper *Catalyze formation of reactive O2 forms and are bound to storage and transport proteins |
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Protective Mechanisms: Antioxidants |
Block formation of free radicals or inactivate them Vitamins A & E, C and Glutathione
*GSH reacts with H2O2 or OH --> Oxidized glutathione (GSSG) and H20 |
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Protective Mechanisms: Enzymes that scavenge free radicals |
Glutathione peroxidase - Se containing enzyme which catalyzes GSH to GSSG Superoxide dismutase (SOD) - catalyze conversion of O2- to H2O2 Catalase - breaks down H2O2 to O2 and H20 |
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Normal Ca balance |
Cytosolic Ca at low concentration compared to extracellular Ca due to energy-dependent pumps and sequestration within mitochondria and ER |
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What causes increased cytosolic Ca? |
Influx of Ca across plasma membrane and release of Ca from ER and mitochondria due to Ischemia and toxins |
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Increased cytosolic Ca causes activation of numerous enzymes... What are they and what do they do? |
ATPases (ATP depletion) Phospholipases (membrane damage) Proteases (breakdown of membrane & cytoskeletal proteins) Endonucleases (DNA/Chromatin damage) |
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Mitochondrial damage by... |
Directly - certain toxins (ex. cyanide)
Indirectly - (ex. increased cytosolic Ca, free radicals, phospholipases) |
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Types of damage to membrane permeability and how? |
Direct - Free radicals, physical agents, chemical agents, bacterial toxins, viruses, lytic component Indirect - ATP depletion and Ca activation of phospholipases, proteases
*Lysosomal membrane damage causes leakage of enzymes which will digest most components |
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Morphologic changes of cell injury |
Acute cell swelling - Occurs within mins Cell death - 20-60 mins Ultrastructual (EM) & Histochemical changes and release of enzymes within 2 hours Light microscopy in 4-12 hours Gross changes in 12-24 hours |
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Main type of reversible cell injury recognized by light microscopy is? |
Acute Cell Swelling or Hydropic Degeneration |
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Acute Cell Swelling: definition |
Acute cell swelling is an early, sub-lethal manifestation of cell damage, characterized by increased cell size and volume |
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Acute Cell Swelling: pathogenesis |
Overload of intracellular water due to alterations in electrolyte transport across plasma membrane and ER |
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Failure of osmotic homeostasis results in... |
Diffuse disintegration of organelles and cytoplasmic proteins |
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Acute Cell Swelling: Etiology |
Causative agents (disrupting cellular homeostasis) -Physical, mechanical injury -Hypoxia -Toxins -Free radicals -Viruses -Bacteria -Immune mediated injury |
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Acute Cell Swelling: Gross Appearance |
Affected organ slightly swollen, rounded edges Paler than normal Affected tissue bulges / no correct apposition Seem heavier than normal |
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Acute Cell Swelling: Histologic appearance |
Water uptake dilutes the cytoplasm and affected cells appear enlarged, with pale cytoplasm, nucleus often in normal position |
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Severity of Acute Cell Swelling |
Cloudy Swelling Hydropic (vacuolar) degeneration Ballooning degeneration |
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Cloudy Swelling |
Mild cell swelling Cells have pale, slightly granular appearance |
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Hydropic degeneration |
Intermediate cell swelling Cells markedly swollen and many vacuoles of variable size appear in cytoplasm |
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Ballooning degeneration |
Severest cell swelling Cells enlarge and eventually rupture
*seen in certain viral diseases |
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Acute Cell Swelling: Ultrastructural changes in plasma membrane |
Loss of microvilli, blebbing, myelin figures, loosening of intracellular attachments |
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Acute Cell Swelling: Ultrastructural changes in endoplasmic reticulum |
Dilation of cisternae (fluid accumulation) detachment and disintegration of polysomes |
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Acute Cell Swelling: Ultrastructural changes in mitochondria |
Swelling, appearance of small densities |
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Acute Cell Swelling: Ultrastructural changes in nucleus |
Clumping of chromatin, disintegration of granular and fibrillar components |
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Acute Cell Swelling: Prognosis |
Early stage corresponds to reversible cell injury Abundant accumulation of intracellular water occurring in vacuolar degeneration and ballooning degeneration results in lysis of affected cell - irreversible cell injury |
