1 Cell injury - etiology and pathogenetic mechanisms.
Cell injury refers to a state in which the cell is unable to maintain normal homeostasis due to harmful stimuli, leading to structural and functional changes. It can be reversible (if the stimulus is mild or short-lived) or irreversible (leading to cell death).
Etiology (Causes of Cell Injury)
- Hypoxia and Ischemia
- Hypoxia: Decreased oxygen availability (e.g., severe anemia, carbon monoxide poisoning).
- Ischemia: Reduced blood supply to a tissue (e.g., thrombus or embolus in an artery).
- Physical agents
- Mechanical trauma (e.g., blunt force injury).
- Extreme temperatures (burns, frostbite).
- Radiation (ionizing and non-ionizing).
- Electric shock.
- Chemical agents and drugs
- Poisons (cyanide, arsenic).
- Environmental pollutants.
- Alcohol, narcotics.
- Therapeutic drugs in excessive or inappropriate doses.
- Infectious agents
- Viruses, bacteria, fungi, parasites.
- Can directly damage cells or induce immune-mediated injury.
- Immunologic reactions
- Autoimmune diseases (e.g., lupus).
- Allergic reactions (hypersensitivity).
- Genetic defects
- Congenital malformations.
- Enzyme deficiencies (e.g., sickle cell anemia, storage diseases).
- Nutritional imbalances
- Protein-calorie deficiencies.
- Vitamin deficiencies or excess.
Pathogenetic Mechanisms of Cell Injury
Cellular injury occurs when stress exceeds the cell’s adaptive capacity. The main mechanisms include:
- ATP depletion
Causes
- Hypoxia/ischemia.
- Mitochondrial damage.
Consequences
- Failure of Na/K ATPase pump → intracellular Na increases, K decreases → cell swelling.
- Increased anaerobic glycolysis → lactic acidosis → decreased pH → clumping of nuclear chromatin.
- Detachment of ribosomes → decreased protein synthesis.
- Mitochondrial damage
Causes
- Increased cytosolic Ca².
- Oxidative stress.
- Ischemia.
Consequences
- Loss of membrane potential → ATP depletion.
- Leakage of pro-apoptotic proteins (e.g., cytochrome c) → apoptosis.
- Influx of intracellular calcium and loss of calcium homeostasis
- Ischemia and toxins cause increased cytosolic Ca².
Consequences
- Activation of phospholipases → membrane damage.
- Activation of proteases → cytoskeletal damage.
- Activation of endonucleases → nuclear damage.
- Activation of ATPases → further ATP depletion.
- Accumulation of reactive oxygen species (ROS) —Oxidative stress
Sources
- Mitochondrial respiration.
- Inflammatory cells (e.g., neutrophils, macrophages).
- Radiation exposure.
Effects
- Lipid peroxidation → membrane damage.
- Protein modification → enzyme inactivation, misfolding.
- DNA damage → mutations, apoptosis.
- Defects in membrane permeability
Targets
- Lysosomal membranes → leakage of enzymes → autolysis.
- DNA and protein damage
Causes
- Radiation, ROS, toxins.
Effects
- Activation of p53 → cell cycle arrest or apoptosis.