Cell injury and adaptation.pdf

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1. CELL INJURY
AND
ADAPTATION
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2. Cell injury and adaptation
•Injury-any noxious (unpleasant) internal or
external stimuli that can disrupt the cell
homeostasis.
•Adaptation-changes made by the cell in its
functioning to survive in the altered
environment.
Cells can adapt to a certain limit in response to
stress.
If the stress become persistent or excessive it can
lead to cell injury
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3. HIMANSHU AGGARWAL

4. Cellular responses to injury
•Altered physiology
–Increased demands
–Decreased nutrients/
use
–Chronic irritation
•Reduced O
2supply
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5. Types of cell injury
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6. Reversible injury
•Reduced ATP sysnthesis
•Reduced Na/K ATPasepump
functioning
–Influx of Na and water
–Cell swelling
–ER swelling
•Glycolysis
–Depletion of cytoplasmic
glycogen
–Increased lactic acid
production
–Decreased cellular pH
•Decreased protein synthesis
–Ribosomesdetach from rER
•Plasma membrane blebs
Irreversible injury
•Severe membrane damage
–Massive Ca influx
–Efflux of cellular proteins and enzymes
•Severe mitochondrial dysfunction
–Ceased ATP synthesis
–Mitochondrial swelling
–Irrepairabledamage to oxidative
phosphorylationpathway
•Lysosomalrupture
–Release of lysosomalenzymes in the
cytosol
–Autolysis
•Nuclear changes
–Pyknosis(irreversible condensation ofchromatin)
–Karyorrhexis(destructive fragmentation of the nucleus)
–Karyolysis(complete dissolution of the chromatin)
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7. Causes of cell injury
•Chemicals
–Drugs, poisons, pollution, smoking, alcoholism, drug abuse
•Infectious agents
–Parasites, infection of cells, toxins, inflammatory responses
•Physical
–Trauma, burns, radiation, pressure
•Immunologic reactions
–Hypersensitivity, auto immune
•Genetic defects
•Hypoxia
–Ischemia, cardiopulmonary failure, anemia, shock
•Nutritional imbalance
–PEM, atherosclerosis (MI), obesity
–Vitamin deficiency
•Aging
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8. Morphologic Changes
•Morphologicchangesrefertothestructural
alterationsincellsortissuesthatareeither
characteristicofadiseaseordiagnosticofan
etiologicprocess
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9. Cellular responses during injury
1)Hypertrophy
2)Atrophy
3)Hyperplasia
4)Metaplasia
These responses depend on several factors
1)Type of injury
2)Duration
3)Severity
4)Type of cell being injured
5)Cell’s metabolic state
6)Cell’s ability to adapt
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10. HIMANSHU AGGARWAL

11. Why does injury occurs?
•Ifthelimitsofadaptiveresponsesareexceededor
•ifcellsareexposedtoinjuriousagentsorstress,
deprivedofessentialnutrients,or
•becomecompromisedbymutationsthataffect
essentialcellularconstituents
a sequence of events follows that is termed cell injury
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12. HIMANSHU AGGARWAL

13. Major cellular components susceptible to
injury
•DNA(genetic material)
•Production of ATP(essential for cell survival
and physiological processes)
•Cell membranes(maintaining cell integrity)
•Protein synthesis(cell signaling and
maintenance)
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14. Mechanisms of cell injury
1) Damage to
–DNA
–Proteins
–Membranes
–Circulating lipids by free radicals
Eg. Superoxide anion
Hydroxyl radical
Hydrogen peroxide
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15. 2) ATP depletion
3) Increased membrane permeability
4) Ca
2+
accumulation
-Second messenger
-Enzyme activation
-Proteases
-ATPases
-Phospholipases
-Endunucleases
5) Mitochondrial dysfunction
-reduced ATP production
-release of cytc
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16. Mitochondrial dysfunction
Failure to generate ATP
leading to necrosis
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17. Ca influx
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18. Altered membrane permeability
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19. Morphological consequences of the cell
injury
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20. •Cellular Adaptations
•Hypertrophy
•Atrophy
•Hyperplasia
•Metaplasia
•Causes of cell injury
•Mechanisms of cell injury
•ATP depletion
•Mitochondrial damage
•Calcium influx
•Membrane permeability
•Free radicals
•Damage to DNA and proteins
Revisit the cell injury
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21. Types of cell injury
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22. Reversible injury
•Reduced ATP sysnthesis
•Reduced Na/K ATPasepump
functioning
–Influx of Na and water
–Cell swelling
–ER swelling
•Glycolysis
–Depletion of cytoplasmic
glycogen
–Increased lactic acid
production
–Decreased cellular pH
•Decreased protein synthesis
–Ribosomesdetach from rER
•Plasma membrane blebs
Irreversible injury
•Severe membrane damage
–Massive Ca influx
–Efflux of cellular proteins and enzymes
•Severe mitochondrial dysfunction
–Ceased ATP synthesis
–Mitochondrial swelling
–Irrepairabledamage to oxidative
phosphorylationpathway
•Lysosomalrupture
–Release of lysosomalenzymes in the
cytosol
–Autolysis
•Nuclear changes
–Pyknosis(irreversible condensation ofchromatin)
–Karyorrhexis(destructive fragmentation of the nucleus)
–Karyolysis(complete dissolution of the chromatin)
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23. Types of cell injury (examples)
•Ischemia hypoxia injury
•Ischemia reperfusion injury
•Chemical injury
•Free radical mediated injury
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24. HIMANSHU AGGARWAL

25. Cell death
After irreversible cell injury cell under goes
either of the two destruction pathways
1)Necrosis-sudden cell death
2)Apoptosis-programmed cell death
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26. Morphological differences between
apoptosis and necrosis
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27. Difference between Apoptosis and Necrosis
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28. •Apoptosisisapathwayofcelldeaththatis
inducedbyatightlyregulatedsuicideprogram
inwhichcellsdestinedtodieactivateintrinsic
enzymesthatdegradethecells’ownnuclear
DNAandnuclearandcytoplasmicproteins.
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32. Necrosis
•Types of necrosis
1)Coagulative
2)Liquefactive
3)Caseous
4)Fat
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33. Coagulativenecrosis
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34. Liquefactive
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35. Caseousnecrosis
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36. Fat necrosis
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