cell injury dr. shoaib raza. cell injury when the adaptive capabilities of the cell are exceeded,...
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CELL INJURY
Dr. Shoaib Raza
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CELL INJURY
When the adaptive capabilities of the cell are
exceeded, the cell is said to be injured
Abnormal homeostasis• Change in the internal environment of the cell
Certain stimulus (triggering agent) is required to
produce such change
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CAUSES OF CELL INJURY
Hypoxia is the most frequent cause • Hypoxic hypoxia
• High altitude
• Ischemic hypoxia• Secondary to ischemia
• Anemic hypoxia• Secondary to anemia
• Histotoxic (Cytotoxic) hypoxia• Cyanide poisoning
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CAUSES OF CELL INJURY
Nutritional disorders• Deficiency:
• Protein Caloric Malnutrition (Kwashiorkor)• Vitamin deficiencies
• Beri beri, Scurvy, Anemia, etc.
• Excess of nutrition:• Hyperlipidemia• Pick wick disorder• Obesity
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CAUSES OF CELL INJURY
Biological agents:• Infection
• Bacteria• Virus• Fungi• Protozoa• Helminths
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CAUSES OF CELL INJURY
Physical agents:• Temperature:
• Increased: Thermal injury, syncope• Decreased: Frost bite
• Pressure:• Trauma
• pH
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CAUSES OF CELL INJURY
Chemical agents:• Corrosive agents• Toxins and poisons• Drugs• Increased or decreased concentration of usual
cellular chemicals• Glucose• Oxygen derived free radicals
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CAUSES OF CELL INJURY
Immunological causes:• Immune system provides defense against foreign
antigens• Autoimmune disorders:
• Immune response against self antigens• Immunodeficiency disorders:
• AIDS, Di-George Syndrome, Hyper IgM Syndrome
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CAUSES OF CELL INJURY
Genetic abnormalities:• Mutation
• Sickle cell anemia, Thalassemia etc
• Chromosomal disorders• Down Syndrome, Klienefelter Syndrome
• Other genetic abnormalities
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CAUSES OF CELL INJURY
Aging:• Telomerase activity
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REVERSIBLE CELL INJURY
In early stages or mild forms of injury, the
functional and morphological changes are reversible
if the stimulus is removed
Hallmark features of hypoxic injury are:• ↓ Oxidative phosphorylation• ↓ ATP synthesis• Cellular swelling• Alterations in intracellular organelles
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HYPOXIA AS A LEADING CAUSE OF CELL INJURY
Deficiency of oxygen impairs oxidative
phosphorylation, this in turn causes:• Deficient aerobic glycolysis• Anaerobic glycolysis
• Accumulation of lactic acid• Reducing pH
• Displacement of ribosomes from RER• Clumping of chromatin network• Inactivation of Na + - K+ pump
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INACTIVATION OF NA + K + PUMP
Na+ K+ pump is ATPase dependent, thus ATP
deficiency leads to inactivation of Na+ K+ pump
Inactivation leads to:• ↑ Na+ influx inside the cell• Intracellular water accumulation
• Cell swelling• Swelling of cytoplasmic organelles
• Mitochondrial swelling• Lysosomal swelling• ER swelling
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REVERSIBLE CELL INJURY
Due to cellular swelling and impaired function of
the cell membrane, certain enzymes (stored in
particular cells) are released and their serum levels
are raised• Lipase, amylase etc during pancreatic cell injury• CK-MB, LDH etc during myocardial injury• AST, ALT, CPK etc during hepatocellular damage
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ANY QUESTION?