Irreversible cell injury

IRREVERSIBLE CELL INJURY

• Persistent ischemia or hypoxia results in irreversible cell injury which leads to cell death.
• Irreversible cell injury has two phenomenon consistently-

1. Inability to reverse mitochondria dysfunction.
2. Development of disturbances in membrane function.

 Features of irreversible cell injury- 

1. Calcium influx → Mitochondrial damage 

• Due to hypoxia, cytosolic influx of calcium ions occurs —>  excess of calcium ions —> mitochondria & its function damage.
• Mitochondria damage results in formation of large flocculent mitochondrial densities.

2. Activated phospholipases-

• Damage to plasma membrane & its function, is the most important event in irreversible cell injury.
• Increased calcium influx → activates phospholipase → cell membrane damage.

3. Intracellular proteases  → damages cytoskeleton of the cell → membrane injury.

4. Activated endonucleases → DNA or nucleoproteins are damaged.

• Damage to nucleus can be of three forms-

1. Pkynosis- nuclear shrinkage & chromatin condensation and clumping.
2. Karyorrhexis- Nuclear fragmentation.
3. Karyolysis- decreased basophilia due to dissolution of nucleus.

5. Lysosomal hydrolytic enzymes-

• Lysosomal membranes are damaged → lysosomal hydrolytic enzymes leakage → enzymatic digestion of cell component → cells die by necrosis.

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