W12 Cell Death 1-Necrosis

Introduction

  • Topic: Cell Death and Pathology

  • Presenter: Michael M. Yakubovskyy, MD, PhD

Learning Objectives

  1. Types of Cell Death

    • Define and differentiate necrosis from apoptosis.

  2. Causes and Mechanisms

    • Correlate causes with the mechanisms of necrosis.

  3. Features of Necrosis

    • Describe and recognize gross and microscopic features of necrosis.

  4. Morphologic Patterns

    • Discriminate between common morphologic patterns of necrosis.

Fate of Cells in Multicellular Organisms

  • Proliferation:

    • Cell division to maintain a pool of stem/progenitor cells (e.g., hematopoietic cells).

  • Senescence:

    • Cell aging and replicative senescence.

  • Dormancy:

    • Cells remain alive but with slowed functions (e.g., dormant stem cells post-embryonic period).

  • Death:

    • Various forms of cell death, including necrosis and apoptosis.

Types of Cell Death

  • Necrosis

  • Apoptosis

  • Other Types:

    • Necroptosis, pyroptosis, ferroptosis, NETosis, anoikis, and more.

Necrosis vs Apoptosis

  • Necrosis:

    • Morphologic changes due to irreversible cell injury.

    • Affects groups of cells ("cellular homicide").

    • Only observed in pathologic conditions.

    • Induces acute inflammatory responses (neutrophil influx).

  • Apoptosis:

    • Morphologic changes from programmed cell death.

    • Affects individual cells ("cellular suicide").

    • Occurs in both physiological and pathological conditions.

    • Apoptotic bodies are cleared by macrophages.

Causes and Mechanisms of Cell Injury and Necrosis

Causes

  1. Hypoxia and ischemia

  2. Microorganisms

  3. Chemicals and drugs

  4. Physical agents (heat, cold, radiation, trauma)

  5. Immunologic reactions

  6. Genetic derangements

  7. Nutritional imbalances

Mechanisms

  1. ATP depletion

  2. Mitochondrial damage

  3. Free radical generation

  4. Reperfusion injury

  5. Membrane damage

  6. Calcium influx

  7. DNA damage

Necrosis: Types of Nuclear Changes

  1. Karyolysis:

    • Nuclear dissolution.

  2. Pyknosis:

    • Nuclear shrinkage and increased basophilia (can also start apoptosis).

  3. Karyorrhexis:

    • Fragmentation of the pyknotic nucleus (nuclear dust).

Clinico-Morphologic Patterns of Necrosis

  • Types of Necrosis:

    • Coagulative, liquefactive, gangrenous, caseous, fat, fibrinoid.

Coagulative Necrosis

  • Definition:

    • Preservation of cellular outlines and tissue architecture.

  • Mechanism:

    • Calcium influx, denaturation of proteins, no proteolysis.

  • Common Cause:

    • Ischemia leading to infarction.

Coagulative Necrosis: Morphology

  • Histology:

    • Anuclear cells, eosinophilic cytoplasm, recognizable outlines.

  • Gross Appearance:

    • Dense, dry tissue; white-grey cut surface.

  • Outcome:

    • Inflammatory response with enzymatic digestion by neutrophils and clearance by macrophages.

Liquefactive Necrosis

  • Definition:

    • Loss of cell outlines and tissue architecture.

  • Causes:

    • Ischemia (e.g., cerebral infarct), infections (bacterial/fungal).

  • Mechanism:

    • Inflammatory response causing lysis of structural proteins.

  • Outcome:

    • Cavity formation or abscess filled with pus.

Gangrenous Necrosis

  • Definition:

    • Necrosis of organs in contact with the environment (e.g., skin).

  • Characteristics:

    • Generally black in color due to iron sulfide accumulation.

Caseous Necrosis

  • Definition:

    • A distinct form with loss of architecture but firm consistency.

  • Etiology:

    • M. tuberculosis, Histoplasma.

  • Gross Appearance:

    • White, granular, and friable (cheese-like).

Enzymatic Fat Necrosis

  • Definition:

    • Fat destruction due to abnormal release of pancreatic enzymes.

  • Etiology:

    • Acute pancreatitis leading to cell injury.

Traumatic Fat Necrosis

  • Affected Organ:

    • Female breast.

  • Causes:

    • Trauma or needling procedures.

  • Mechanism:

    • Cell injury and necrosis of adipose tissue followed by inflammation.

Fibrinoid Necrosis

  • Definition:

    • Extracellular degeneration with fibrinoid accumulation in blood vessel walls.

  • Causes:

    • Severe hypertension, immune-mediated vasculitis.

Conclusion

  • Summary of presented types of cell death, their mechanisms, causes, and histological features to aid in understanding cellular pathology.