Cell Injury and Cell Death

Cell Injury and Cell Death

  • Topics Covered:
    • Agents causing cell injury
    • Reversible vs. irreversible cell injury
    • Stages of cell damage
    • Adaptations to cell injury
    • Mechanisms of cell death
    • Necrosis vs. apoptosis
    • Types and causes of necrosis
    • Pathological calcification

Reversible vs. Irreversible Cell Injury

  • Cell injury can be reversible or irreversible.
  • Reversible Injury:
    • Stress is small in magnitude or short in duration.
    • Cell restores homeostasis and recovers original form/function.
  • Irreversible Injury:
    • Stress is larger in magnitude or longer in duration.
    • Results in cell death (necrosis).
    • Intracellular proteins are denatured.
    • Damage to cell nucleus.
    • Autolysis (cell swells, ruptures, and releases contents).
    • Lysosomal enzymes damage surrounding healthy cells.
    • Irreversible cell injury = cell death.
  • Reversible cell injury process:
    • Increase in intracellular ions.
    • Interstitial fluids merge into the cytosol and cell organs.
    • Cell volume increases.
    • Cell membrane starts to bleb.
    • Swelling of organelles.

Causes of Cell Injury

  • Main causes (covered generally):
    • Ischemia
    • Infections
    • Chemical factors
    • Physical factors
    • Nutritional factors
    • Psychosocial factors

Ischemia

  • Insufficient blood flow to maintain homeostasis and metabolic functions (hypoxia or anoxia).
  • Causes: circulatory, metabolism, inadequate respiratory transport, and inadequate transport in the cardiovascular system.
  • Loss of aerobic metabolism, reduction in ATP synthesis, accumulation of ions and fluid intracellularly, all cause cells to swell and their function is compromised.

Infections

  • Types: bacterial, viral, and immune reactions.
  • Bacterial Infections:
    • Invade the host after penetrating the body.
    • First line of defense: skin, mucosal membranes (barriers of the host).
    • Inflammatory response leads to cell injury and death in the local area of infection.
    • Endotoxins induce synthesis of cytokines (tumor necrosis factor and interleukins) causing systemic manifestations of sepsis.
    • Exotoxins damage host cells directly or disrupt normal cellular processes.
  • Viral Infections:
    • Direct or indirect effect depending on RNA or DNA viruses.
    • RNA viruses (direct cytopathic effects) disrupt the integrity of the cell.
    • DNA viruses signal the cell to be destroyed by the host’s body.

Chemical Factors

  • Examples: carbon monoxide, ammonia, heavy metals (mercury, aluminum), alkylating agents in pharmaceutical drugs, and free radicals.
  • Carbon monoxide and ammonia are the cause of most injuries and death in this category.
  • Free radical formation: unstable byproduct of oxidation that destroys cell membranes.
    • Associated with cancer, atherosclerosis, Alzheimer’s, and Parkinson’s.

Physical Factors

  • Examples: blunt trauma, temperature extremes (hypothermia, hyperthermia), radiation, and electricity.
  • Mechanical factors depend on the characteristics of the load and tissue tolerance.
  • Physical injury can damage cell membranes or intracellular structures.
  • Controlled increase in physical stress from exercise increases tissue tolerance (muscle hypertrophy).

Nutritional Factors

  • Vitamin B12 deficiency: neuropathy (nerve death or injury).
  • Calcium deficiency: poor bone quality.
  • Protein malnutrition: weight loss and edema due to low protein levels in the blood, diminished capacity for activities and tasks.

Psychosocial Factors

  • Fear, tension, anxiety, depression, or isolation impact activity and participation levels.
  • Influence and impact thresholds for tissue adaptation and injury.

Inflammation

  • Clinical manifestations: redness, swelling, increased temperature, pain, and decreased function.
  • Acute inflammation subsides when the agent is removed or resolved.
  • If little cell death, structure and function remain intact.
  • Examples: blisters, cuts, scratches, and links to pathologies like atherosclerosis, diabetes, and obesity.

Cardinal Signs of Inflammation (Local Signs and Symptoms)

  • Rubor (Redness):
    • Due to vasodilation.
    • Increase in blood flow due to histamine and prostaglandins.
    • Vascular permeability causes protein and cellular components (exudate) to seep out, leading to edema.
  • Calor (Heat):
    • Increased blood flow from the core of the body.
  • Tumor (Swelling):
    • Capillary fluid shift mechanism.
    • Capillaries become more permeable, movement of protein and water from circulation into interstitial spaces.
  • Dolor (Pain):
    • Mechanical pain: swelling or edema causes pressure on tissue.
    • Biochemical pain: inflammatory mediators (substance P, ions, prostaglandins, and bradykinin) irritate bare nerve endings.

Cell Death

  • Necrosis:
    • End point of a pathological process.
    • Occurs when there is cell injury and is an irreversible cell injury.
  • Apoptosis:
    • Programmed cell death.
    • Genetically mediated (like leaves falling off a tree in autumn).
    • No activation or trigger.
    • Cells shrink or shrivel.
    • Components are recycled or absorbed by phagocytes.

Necrosis Types: Example

  • Yellow, soft, granular, cheesy appearance.
  • Due to the release of lipids from the cell walls of mycobacterium tuberculosis.
  • Lipases break down lipids and combine with calcium, magnesium, and sodium ions, creating soaps (saponification).
  • Opaque and chalk like substances are observed within the necrotic tissue.