Cellular injury; common causes and mechanisms
Cells exist in homeostasis. Where they are subject to stress they attempt to adapt. Where they are unable to adapt they become ‘Injured cells’. Common methods of adaptation include hypertrophy (increase in cellular size), Hyperplasia (increase in cellular number), atrophy (shrinkage of cell by loss of substance) and metaplasia (replacing of cells by different cellular types, think squamous metaplasia of the bronchi in smokers).
Example: Another classic metaplasia is Barrett oesophagus – in chronic acid reflux the squamous epithelium of the lower oesophagus is replaced by intestinal-type columnar epithelium with goblet cells.
The most common cause of cellular injury is Hypoxia, or oxygen deficiency, as it prevents aerobic oxidative respiration, and the conversion of carbohydrates into ATP. Hypoxia can often be caused by Ischemia, lack of blood supply to an affected area, but also as a result of pneumonia (lack of oxygen in blood), anemia (reduction of oxygen carrying capacity of blood) and CO poisoning.
Other important causes include:
- Chemical agents
- Such as high glucose, salt, oxygen, CO or other toxic agents
- Infectious agents
- Immunologic reactions
- Physical agents
- Nutritional imbalances
- Genetic defects
- Aging
These problems cause the cell to become nonfunctional, this dysfunction leads to cellular injury, we’ll now consider the mechanism of cell injury. The following mechanisms of cell injury are the most common, and usually combined:
- Depletion of ATP (failure of energy --- Necrosis)
- Causes; Influx of Sodium and Calcium ions and osmotic swelling due to failure of ATP dependent ion pumps
- ATP depleted cells begin anaerobic metabolism to derive energy from glycogen (Glycolysis)
- Results in decrease of pH, creating acidic environment and damaging enzymes.
- Causes clumping of nuclear chromatin, pyknosis, leading to cellular necrosis.
- Damage to Mitochondria (leads to ATP depletion, high Ca2+ and ROS common causes)
- Influx of calcium (activates enzymes with damaging cellular effects)
- Accumulation of Oxygen-Derived free radicals (Damages membrane and DNA)
- Defects in membrane permeability
- Damage to DNA and proteins
- Disruption to cell membrane