Cell injury is the starting point of almost every disease. It means the cell is unable to maintain normal structure or function because the stress it faces is beyond its capacity to adapt. If the cause is removed early, the cell may recover. If damage continues, the cell dies.
Types of Cell Injury
A) Reversible Cell Injury
This is the early and mild stage of damage. If the harmful stimulus is removed, the cell can return to normal. In this stage, the cell may swell, show mild functional disturbance, but the membrane and nucleus are still intact.
B) Irreversible Cell Injury (Cell Death)
When damage is severe, the cell cannot recover and dies. There are two major types of cell death:
- Necrosis: Uncontrolled cell death due to severe damage. The membrane breaks, enzymes leak out, and inflammation occurs.
- Apoptosis: Programmed cell death. It is regulated, energy-dependent, and does not cause inflammation.
Necrosis
Necrosis is the “messy” form of cell death. It occurs in ischemia (lack of blood supply), trauma, toxins, and infections. The cell swells, membrane ruptures, and contents leak out, producing inflammation.
Apoptosis
In apoptosis, the cell activates a self-destruction program. The membrane remains intact but becomes recognizable to phagocytes. The cell breaks into small fragments which are cleared without inflammation. It is normal in many physiological processes and also seen in some diseases.
Causes of Cell Injury
Cell injury can occur due to several reasons:
1. Oxygen Deprivation (Hypoxia)
Hypoxia reduces ATP production and is a common cause of cell death. It may occur due to anemia, blood loss, ischemia, respiratory failure, or carbon monoxide poisoning.
2. Physical Agents
- Heat and cold
- Radiation
- Mechanical trauma
- Electricity
- Pressure changes
3. Chemicals and Drugs
Excess salt, glucose, poisons like arsenic, cyanide, mercury, air pollutants, insecticides, and therapeutic drugs can injure cells.
4. Microbial Agents
Bacteria, viruses, fungi, protozoa, and parasites cause infection and injury.
5. Immunologic Reactions
Autoimmune diseases, allergies, and hypersensitivity reactions can damage tissues.
6. Nutritional Imbalance
Deficiency (e.g., starvation, anemia) or excess (e.g., obesity, atherosclerosis) can disturb cellular function.
7. Psychological Factors
Stress, smoking, alcohol, drug abuse can lead to metabolic and structural changes.
8. Genetic Causes
Chromosomal defects, enzyme deficiencies and inherited disorders can make cells more vulnerable to injury.
Pathogenesis of Cell Injury
Cell injury can be reversible or irreversible depending on the type, intensity, and duration of the insult.
The outcome also depends on the cell type and its ability to adapt. For example, heart cells die within 20–30 minutes of ischemia, while skeletal muscle can tolerate hours.
Mechanisms of Reversible Cell Injury
Major mechanisms include:
1. ATP Depletion
Low ATP affects membrane pumps, leading to sodium and water accumulation, cell swelling, and reduced protein synthesis.
2. Mitochondrial Damage
Mitochondria fail to generate ATP. If permeability pores open, ATP production stops and necrosis starts. Leakage of cytochrome-C triggers apoptosis.
3. Calcium Influx
Failure of calcium pumps causes calcium accumulation. This activates enzymes that damage membranes, proteins, and DNA.
4. Membrane Damage
Caused by phospholipid loss, phospholipase activation, free radicals, and cytoskeletal damage.
5. Protein Misfolding
Stress, toxins or hypoxia may lead to misfolded proteins, triggering the unfolded protein response and cell injury.
Mechanisms of Irreversible Cell Injury
Once damage cannot be reversed, the following occur:
- Mitochondrial failure with no ATP generation
- Severe membrane damage leading to massive calcium influx
- Lysosomal enzyme leakage causing digestion of cell components
- Nuclear changes like pyknosis, karyorrhexis, and karyolysis
Hypoxia-Induced Cell Injury
Hypoxia affects oxidative phosphorylation first. ATP falls rapidly, pumps fail, ions accumulate, and the cell swells. If hypoxia continues, membranes rupture and cell death occurs.
Free Radical–Induced Injury
Free radicals (ROS) damage membranes, proteins, DNA, and mitochondria. They arise from radiation, chemicals, inflammation, and normal metabolism.
Protective mechanisms include antioxidants like Vitamin E, catalase, SOD and glutathione peroxidase. Deficiency increases susceptibility to injury.
Adaptive Changes of Cells
When exposed to stress, cells try to survive by adapting:
1. Hypertrophy
Increase in cell size (e.g., skeletal muscle in exercise, heart muscle in hypertension).
2. Hyperplasia
Increase in the number of cells (e.g., uterine lining during pregnancy).
3. Atrophy
Decrease in cell size due to disuse, reduced blood supply or loss of nerve input.
4. Metaplasia
One adult cell type is replaced by another better suited to handle stress (e.g., smokers’ respiratory epithelium).
5. Dysplasia
Disordered cell growth. It is reversible but may progress to cancer if the stimulus continues.
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