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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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4. Cellular responses to injury
• Altered physiology
– Increased demands
– Decreased nutrients/
use
– Chronic irritation
• Reduced O2 supply
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5. Types of cell injury
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6. Reversible injury
• Reduced ATP sysnthesis
• Reduced Na/K ATPase pump
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
– Ribosomes detach 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
– Irrepairable damage to oxidative
phosphorylation pathway
• Lysosomal rupture
– Release of lysosomal enzymes in the
cytosol
– Autolysis
• Nuclear changes
– Pyknosis (irreversible condensation of chromatin)
– Karyorrhexis (destructive fragmentation of the nucleus)
– Karyolysis (complete dissolution of the chromatin)
HIMANSHU AGGARWAL

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
• Morphologic changes refer to the structural
alterations in cells or tissues that are either
characteristic of a disease or diagnostic of an
etiologic process
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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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11. Why does injury occurs?
• If the limits of adaptive responses are exceeded or
• if cells are exposed to injurious agents or stress,
deprived of essential nutrients, or
• become compromised by mutations that affect
essential cellular constituents
a sequence of events follows that is termed cell injury
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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)
HIMANSHU AGGARWAL

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) Ca2+ accumulation
- Second messenger
- Enzyme activation
- Proteases
- ATPases
- Phospholipases
- Endunucleases
5) Mitochondrial dysfunction
-reduced ATP production
-release of cyt c
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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
HIMANSHU AGGARWAL

21. Types of cell injury
HIMANSHU AGGARWAL

22. Reversible injury
• Reduced ATP sysnthesis
• Reduced Na/K ATPase pump
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
– Ribosomes detach 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
– Irrepairable damage to oxidative
phosphorylation pathway
• Lysosomal rupture
– Release of lysosomal enzymes in the
cytosol
– Autolysis
• Nuclear changes
– Pyknosis (irreversible condensation of chromatin)
– 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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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. • Apoptosis is a pathway of cell death that is
induced by a tightly regulated suicide program
in which cells destined to die activate intrinsic
enzymes that degrade the cells’ own nuclear
DNA and nuclear and cytoplasmic proteins.
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32. Necrosis
• Types of necrosis
1) Coagulative
2) Liquefactive
3) Caseous
4) Fat
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33. Coagulative necrosis
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34. Liquefactive
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35. Caseous necrosis
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36. Fat necrosis
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