Cell injury: causes, pathogenesis, Morphology of reversible cell injury

3. NORMAL CELL
(HOMEOSTASIS)
STRESS
ADAPTATION CELL INJURY
INABILITY
TO
ADAPT
REVERSIBLE INJURY
MILD
TRANSIENT
SEVERE
PROGRESSIVE
IRREVERSIBLE INJURY
NECROSIS APOPTOSISCELL
DEATH

4. Learning objectives
• General mechanisms of cell injury
• Causes of cell injury
• Pathogenesis of cell injury
• Free radical induced cell injury
• Examples of reversible cell injury

5. Cell Injury – General Mechanisms
• Four very interrelated cell systems are
particularly vulnerable to injury:
– Membranes (cellular and organellar)
– Aerobic respiration
– Protein synthesis (enzymes, structural
proteins, etc)
– Genetic apparatus (e.g., DNA, RNA)

6. What causes cell injury?
• Hypoxia

7. • Hypoxia
– Reduced blood flow [ischemia]
– Inadequate oxygenation of the blood due to
cardiorespiratory failure
– Decreased oxygen carrying capacity of the
blood as in anemia and CO poisoning
– Severe blood loss

8. • Physical agents
• Chemical agents
• Infectious agents
• Immunologic reactions
• Genetic causes
• Nutritional
• Iatrogenic
• Idiopathic

9. Pathogenesis
• Basic principles
• Nature of injury, duration and severity
• Type , state and adaptability of the injured cell
• Biochemical mechanisms acting on several
essential cellular components.

10. The principal mechanisms of cell injury, and
their biochemical and functional effects

11. REVERSIBLE

12. IRREVERSIBLE

13. FREE RADICAL MEDIATED
CELL INJURY

14. • These are the chemical species that have
single unpaired electron in their outer
orbit.
• Highly reactive, unstable chemicals
• Associated with cell injury
– Chemicals/drugs, reperfusion injury,
inflammation, irradiation, oxygen toxicity,
carcinogenesis

16. Free radicals
• Superoxide oxygen
• Hydroxyl radical
• Hydrogen peroxide
• Nitric oxide
• Peroxynitrite
• Hypochlorous acid

17. Antioxidant mechanisms
• Catalase
• Superoxide dismutase
• Glutathione peroxidase

18. Antioxidants
• Endogenous or exogenous substances
which inactivate free radicals
– Vitamins A, C , E
– Sulphydryl containing compounds
• Cysteine and glutathione
– Serum proteins
• Ceruloplasmin and transferrin

19. Hydroxyl free radical
( the most reactive)
Lipid
peroxidation
Protein
oxidation
DNA
damage
Cytoskeletal
damage
Cell death
Mechanism of injury

20. Morphology of cell injury

21. Reversible Irreversible

23. Hydropic change
• Accumulation of water in the cytoplasm
• Cloudy swelling, vacuolar degeneration
• Appears when cells are incapable of
maintaining ionic and fluid homeostasis
• It is the first manifestation of almost all
forms of cell injury
• Reversible cell injury
• Due to impaired regulation of sodium &
potassium on cell membrane.

26. Hydropic swelling. A needle biopsy of the liver of a patient with toxic hepatic
injury shows severe hydropic swelling in the centrilobular zone. The affected
hepatocytes exhibit central nuclei and cytoplasm distended (ballooned) by excess
fluid.

27. Ultrastructural changes in reversible cell injury

28. Summary
• General mechanisms of cell injury
• Causes of cell injury
• Pathogenesis of cell injury
• Free radical induced cell injury
• Examples of reversible cell injury

29. Thank you