Reversible and irreversible injury

1. Cell Injury
- Etiology
- Reversible & irreversible injury
Dr Saket Kumar.

2. Cell Injury
• Effects of a variety of stresses due to etiologic agents a cell
encounters resulting in changes in its internal and external
environment.

3. • Cellular response to stress depends on –
- Host factors
- Factors pertaining to injurious agent

5. TIMELINE

6. Etiology of Cell Injury
• Hypoxia and Ischaemia
• Physical agents
• Chemical agents
• Microbial agents
• Immunologic agents
• Nutrition derangements – Deficieny and Excess
• Ageing

7. Pathogenesis
• Reversible / Irreversible injury –
- Duration and severity of injurious agent
- Type and adaptability of target cell
- Mitochondrial damage
- Cell membrane damage

8. Ischaemic and hypoxic injury
• REVERSIBLE CELL INJURY
- Short duration of ischaemia and hypoxia
- Biochemical and ultrastructural changes:
1) Decreased generation of cellular ATP
ATP generation – Aerobic (Oxidative phosphorylation)
Anaerobic ( Glycolytic oxidation)
Hypoxia – Anaerobic respiration – reversible cell injury
Ischaemia – No glucose is available for anaerobic – irreversible
cell injury

9. 2) Intracellular lactic acidosis – Nuclear clumping
3) Damage to plasma membrane pumps – Hydropic swelling
Damage of Na+/K+ pump
Failure of Ca2+ pump

10. 4) Reduced protein synthesis – dispersed ribosomes
5) Ultrastructural changes – loss of microvilli, focal projections of
cytoplasm(blebs)

11. • IRREVERSIBLE CELL INJURY
- Persistence of ischaemia and hypoxia
- 2 important phenomena
a) Inability to reverse mitochondrial dysfunction
b) Disturbance of cell membrane function (plasma membrane,
lysosomal membrane damage causes liberation of lysosomal
enzymes).

12. - Biochemical and ultrastructural changes:
1) Calcium influx – mitochondrial damage
2) Activated phospholipase – membrane damage
3) Activation of proteases – cytoskeleton damage

13. 4) Activated endonuclease – Nuclear damage (DNA or nucleoproteins)
Pyknosis
Karyorrhexis
Karyolysis
- Dead cell is eventually replaced by masses of phospholipids, called
myelin figures which are phagocytosed.

14. - Liberated enzymes through damage cell membrane into serum can be
estimated and used as marker of cell death.

15. Sequence of events in pathogenesis of reversible & irreversible cell injury

17. Thank You