Cell Injury
REVERSIBLE CELL INJURY (RCI):
If ischemia or hypoxia is for short period of time, the cell can be reverting back to its normal condition which is known as RCI. In coronary arteries, myocardial contractility is reversed if circulation is quickly restored.
It also depends upon the organ which undergoes hypoxia. Ex, skeletal muscle can with stand for half an hour with cell injury but brain cells can undergo permanent damage within 10 minutes.
The pathogenesis of RCI is described below.
- Decrease supply of oxygen, decreases cells aerobic respiration by mitochondria due to decrease ATP generation.
- To maintain the supply of energy to the cell anaerobic glycolysis takes place to generate ATP.
- Decreases glycogen level. This result in increase accumulation of lactic acid. Thus, decreases intracellular pH.
- This causes clumping of nuclear chromatin.
- Decrease ATP causes failure of energy requiring Na-pump. There by causing accumulation of Na and diffusion of K outside the cell resulting in cellular swelling.
- If hypoxia continues, intracellular protein synthesis decreases due to damage to ribosomes and polysomes.
- Continue hypoxia causes cytoskeleton changes with loss of microvilli and formation of blebs on the surface of the cell.
- This swelling results in swelling at mitochondria and ER (endoplasmic reticulum). If reperfusion at this stage, changes can be reverse otherwise results in irreversible cell injury.
In RCI,
Decreased generation of cellular ATP: The first point of attack of hypoxia is the cells aerobic respiration. ATP is essentially requires for variety of cellular functions such as ion transport, protein synthesis, lipid synthesis and phosphor lipid metabolism. ATP in human derived from two sources, aerobic respiration or oxidative phosphorylation in mitochondria and anaerobic glycolytic pathway.
ATP is also generated from creatine phosphate through action of creatinine kinase.
Reduced intracellular pH: Due to decrease aerobic respiration by mitochondria results in anaerobic glycolytic pathway for generation of ATP for energy requirement. This result in rapid depletion of glycogen and accumulation of lactic acid which lowering the intracellular pH. Early fall in intracellular pH results in clumping of nuclear chromatin.
Damage plasma membrane Na+ pump: Normally, Na+ is kept lower intracellular than extracellularly. Na+/K+ pump (Na/K Atpase). This Na+/K+ pump regulates active transport of Na to outside the cell(by using ATP) and diffusion of K in to the cell. By decrease supply of ATP, failure of Na/K Atpase takes place which cause accumulation of Na+ inside the cell with diffusion of K+ outside the cell.
Increase accumulation of Na+ leads to increase intracellular water level for maintain isoosmotic condition which leads to cellular swelling and dilation of ER (Hydropic swelling).
Reduce protein synthesis: As continued hypoxia, ribosomes are detached from granular ER and polysomes are degraded to monosomes. Thus causing reduction in protein synthesis.
Functional Coseqences: RCI may result in functional disturbances like myocardial contractility ceases within 60 sec of coronary occulation but can be reverse if circulation is restored.
Ultra structural changes:
They are as follow,
ER: detachment of membrane bounded polysomes from surface of rough ER.
Mitochondria: mitochondrial swelling and phospholipid rich amorphous densities.
Plasma Membrane: loss of microvilli and projection of blebs take place.
Nucleus: segregration of granular and fibillar components of nucleolus and decrease synthesis of ribosomal RNA.
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