Cell Injury Overview

Cell Injury 1

• Learning outcomes include listing causes of cell injury with examples, explaining mechanisms, describing morphologic alterations in reversible and irreversible cell injury, and describing the morphology of necrosis patterns.

Causes of Cell Injury

• Hypoxia & Ischemia: Oxygen deficiency (hypoxia) and reduced blood supply (ischemia). Caused by arterial obstruction, lung disease, anemia, and carbon monoxide poisoning.

• Toxins: Examples include ethanol, various drugs, heavy metals, and environmental pollutants.

• Infectious agents: Viruses, bacteria, fungi.

• Immunologic reactions: Immune responses can trigger inflammation.

• Genetic abnormalities: Result in various conditions, including congenital malformations.

• Nutritional imbalance: This can lead to malnutrition conditions like Kwashiorkor and Marasmus.

• Physical agents: Trauma, extreme temperatures, radiation.

• Aging: Cells lose responsiveness to stress, leading to eventual death.

Mechanism of Cell Injury

• General principles: Cellular response depends on the type, duration, severity of injury, and type of cell. Key targets susceptible to injury include cell membranes, ATP production (aerobic respiration), protein synthesis, and DNA.

• Mechanism of cell injury: Injury mechanisms include energy failure (ATP depletion), increased oxidative stress, DNA damage, and inflammation.

• Loss of energy (ATP depletion): Oxygen deficiency results in failure of many metabolic pathways and ultimately cell death via necrosis.

  • Ischemia-reperfusion injury exacerbates damage during reoxygenation. Free radical generation is also involved.
  • Hypoxia and ischemia lead to failure of ATP generation and depletion--affecting many cellular systems.

• Increase oxidative stress: ROS (reactive oxygen species) are induced frequently during injury. Free radical damage can lead to lipid peroxidation of membranes, DNA fragmentation, and protein cross-linking if not neutralized.

• DNA damage: Exposure to radiation, chemotherapeutic agents, or ROS generation results in DNA damage, sometimes triggering apoptotic death.

• Defects in plasma membrane permeability: Toxins, viruses, bacterial toxins and physical or chemical agents can damage the plasma membrane directly leading to membrane damage.

• Accumulation of misfolded proteins: Stress can cause compensatory pathways in the ER (endoplasmic reticulum) and lead to apoptosis. Misfolded proteins increase which reduces the ability to eliminate abnormal proteins leading to the disease.

• Inflammation: Pathogens, necrotic cells, dysregulated immune responses (autoimmune diseases/allergies) can elicit inflammation. Inflammatory cells create products to destroy microbes but can harm normal tissues.

Types of Necrosis

• Coagulative necrosis: Most common type. Cell components are dead, and tissue structure is preserved. Examples include heart attacks, infarct of kidneys, & solid organs except brain.

• Liquefactive necrosis: Dead cells digested completely. Cells are transformed into liquid viscous mass (pus). Common in brain infections.

• Gangrenous necrosis: Involves multi-layered cells that undergo coagulative necrosis and is often superimposed by bacterial activity. This leads to a change in morphology to liquefactive necrosis commonly seen in extremities.

• Caseous necrosis: Mixture of coagulative and liquefactive necrosis. Example: Tuberculosis. The appearance of dead tissue is often described as "cheesy."

• Fat necrosis: Lipases split triglycerides into fatty acids and calcium, leading to chalky areas. Occurs in the pancreas, for example.

• Fibrinoid necrosis: Deposition of fibrin-like material that results from vascular damage. Associated commonly with immune complex vasculitis and autoimmune diseases.

Reversible vs Irreversible Cell Injury

• Reversible cell injury: A compensation for disturbances and return to normalcy when the injurious stimulus stops.

• Irreversible cell injury: Persistent or excessive injury that leads to cell death. Usually involves mitochondrial dysfunction or profound disturbance in membrane function.

Reversible and Irreversible Injury Morphology

• Reversible: Light microscopy shows hydropic swelling and fatty changes. Ultrastructural changes seen by electron microscopy.

• Irreversible: Plasma membrane damage, lysosomal rupture, autolysis. Changes in nucleus: pyknosis, karyorrhexis, and karyolysis are seen. Also mitochondrial permeability increase.

This quiz covers various aspects of cell injury, including its causes, mechanisms, and morphological changes associated with both reversible and irreversible cell injury. You'll also explore different patterns of necrosis and the impact of factors like hypoxia, toxins, and aging on cell health.