Pathology Chapter: Necrosis and Apoptosis

Cell Response to Injury

• Learning outcomes include: enumerating causes and types of cell response to injury; describing different mechanisms of cell injury; comparing reversible and irreversible cell injury; defining different types of cell injury; describing gross and microscopic pictures of injury types; describing the pathogenesis and fate of reversible cell injury; comparing necrosis and apoptosis; and comparing different types of necrosis.

Causes of Cell Injury

• Causes include physical factors, infection, hypoxia, chemicals, and immunological factors.

Mechanisms of Cell Injury

• Mechanisms of cell injury include ATP depletion, membrane damage, increases in intracellular calcium, and formation of oxygen-derived free radicals. A injurious stimulus initiates these events.

Mechanisms of Cell Injury - Hypoxia

• Hypoxia is a key cause of cell injuries, often due to ischemia.
• The processes involved include: loss of energy-dependent cellular function; oxidative phosphorylation decreases and thus ATP; Na pump dysfunction; influx of Ca++, H₂O, and Na+; loss of K+; ER and cellular swelling; loss of microvilli and blebs; anaerobic glycolysis; glycogen clumping; nuclear chromatin clumping; protein synthesis decreases; lipid deposition; and general detachment of ribosomes.

Mechanisms of Cell Injury - Other factors

• Other mechanisms include membrane damage; enzymatic digestion of cellular components, leading to cell death; comparing pro-apoptotic vs. anti-apoptotic proteins and their effect on survival signals; and intracellular Ca2+ increase leading to activation of multiple intracellular enzymes (e.g., ATPase, phospholipase, protease, endonuclease), which can disrupt membranes and cytoskeletal proteins, leading to nuclear damage.
  • Formation of reactive oxygen species (ROS), such as superoxide (O2-) and hydrogen peroxide (H2O2), is another factor.

Effect of Cell Injury

• The effect of cell injury is dependent on the nature, duration, severity, and type of cell affected.

Reversible vs. Irreversible Cell Injury

• Reversible injury is mild and short in duration, while irreversible injury is severe and long in duration.
• Active parenchymal cells, with a higher metabolic rate, are more affected than supporting stroma cells during injury.

Types of Reversible Cell Injury

• Types of reversible cell injury include cloudy swelling, hydropic swelling, and fatty change.

Cloudy Swelling

• Definition: A reversible cell injury characterized by cell swelling due to water accumulation and cytoplasmic granularity.
• Causes: Physical factors, infection, hypoxia, or chemical/immunological factors.
• Pathogenesis: Ischemia hinders oxidative phosphorylation; anaerobic glycolysis increases; lactic acid accumulation increases pH; and osmotic load increases. Na/K pump failure disrupts cellular water balance.
• Gross and microscopic findings: Clinical changes include no significant change; proteinuria and dilation and decreased contractility; in section, there are enlarged, swollen cells with a cloudy, granular appearance.
• Fate: If the injury stops, the cell returns to normal; if injury continues, proceeds to hydropic swelling.

Hydropic Swelling

• Definition: A reversible cell injury involving morphological swelling and vacuoles in cell cytoplasm due to excess water accumulation.
• Causes and pathogenesis are similar to cloudy swelling.
• Gross and microscopic findings: Affected cells are swollen, with vacuoles appearing in the cytoplasm.
• Fate: If injury stops, cell returns to normal; if injury continues, leads to irreversible damage.

Fatty Change

• Definition: Reversible cell injury involving pathological fat accumulation in cells.
• Causes: Excess fat intake and viral hepatitis, among other causes detailed below
• Pathogenesis: Fat produced or carried to injured cells cannot be metabolized due to limited enzyme activity which accumulates in the cytoplasm, leading to the appearance of vacuoles.
• Gross and microscopic findings: Patchy or diffuse fat accumulation is observed, sometimes resembling a "nutmeg liver" appearance.
• Fate: If injury stops, cell returns to normal; if injury continues leads to irreversible injury.

Necrosis

• Definition: Local death of a large group of cells or tissues within a living body due to direct or consequential injury from reversible injury.
• Causes: Physical, infection, hypoxia, or chemical/immunological factors.
• Gross findings: Surrounded by a red area due to inflammatory hyperemia.
• Microscopic findings:
  • Nuclear: Pyknosis (nuclear shrinkage), karyorrhexis (nuclear fragmentation), and karyolysis (nuclear dissolution);
  • Cytoplasmic: Cytomegaly (cell swelling), indistinct cell membrane, Ca2+ deposition, cytoplasmic eosinophilia in H&E (due to loss of cytoplasmic RNA and denatured cytoplasmic proteins), and a glassy homogenous appearance (loss of glycogen particles).
• Types include: coagulative, liquefactive, caseative, fat, and fibrinoid.
• Fate: Small areas heal by macrophage engulfment of solid debris, fluid drainage, and tissue regeneration. Large areas result in a fibrous capsule and dystrophic calcification.

Apoptosis

• Definition: Energy-dependent, programmed cell death essential for eliminating unwanted cells, critical for normal development.
• Causes: Normal cell turnover, embryogenesis, hormone-dependent involution, cellular damage.
• Pathologic examples include, DNA damage, infections (viral hepatitis).
• Gross findings: Microscopic.
• Microscopic findings: Cell shrinkage, dense cytoplasm, tightly packed organelles, chromatin condensation, surface blebbing, formation of membrane-bound apoptotic bodies.
• Fate: Phagocytosis of apoptotic bodies by macrophages and degradation of cell contents by lysosomal enzymes.

This quiz explores key concepts in pathology, particularly focusing on necrosis and apoptosis. Test your knowledge on the various types of necrosis, their microscopic characteristics, and the processes associated with cell death. Understand the differences between necrosis and apoptosis, along with their underlying mechanisms.