General Pathology Lecture Notes

Introduction to Cell Injury

• Chapter Focus: Cell Injury
  • Types of Cell Injury: Reversible and Irreversible
  • Types of Cell Death: Necrosis and Apoptosis

Basic Concepts of Cell Injury

• Normal Cell Condition: Homeostasis
• Cell Stress: Microbiological or radiological stress leads to:
  • Adaptation: Initial response to stress.
  • Injury: If adaptation fails, cell injury occurs.
    • Reversible Cell Injury: Minor damage, cell can return to normal.
    • Irreversible Cell Injury: Severe damage, leads to cell death.

Types of Cell Injury

1. Reversible Cell Injury

• Initial Changes:

  • Mitochondrial Dysfunction: Leads to decreased ATP production.
  • Cellular Swelling (Hydropic Change): Increase in sodium influx and water retention.
  • Endoplasmic Reticulum Swelling: Organelles swell.
  • Loss of Microvilli: Flattening of cellular projections.
  • Cytoplasmic Blebs: Small protrusions form on the membrane.
  • Myelin Figures: Laminate appearances in cytoplasm from damaged membranes.

• Other Changes:

  • Lactic Acidosis: Due to anaerobic respiration when oxygen is low.
  • Clumping of Chromatin: Nuclear changes reflecting cell injury.
  • Decrease in Protein Synthesis: Due to ribosomal detachment from the endoplasmic reticulum.

2. Irreversible Cell Injury

• Severe Membrane Damage: Leads to cell death.
• Calcium Influx: Activates enzymes that damage cell components.
  • Key Enzymes: Phospholipases, proteases, nucleases.
• Nuclear Changes:
  • Karyolysis: Dissolution of nucleus.
  • Karyorrhexis: Fragmentation of nucleus.
  • Pyknosis: Nuclear shrinkage.

Cell Death Mechanisms

1. Necrosis

• Pathological Process: Cells die due to external stress.
• Types of Necrosis:
  • Coagulative Necrosis: Architecture preserved, example: myocardial infarction.
  • Liquefactive Necrosis: Tissue architecture not preserved, example: brain infarcts.
  • Caseous Necrosis: Characteristic cheesy appearance, seen in tuberculosis.
  • Fat Necrosis: Associated with traumatic injuries and pancreatitis.
  • Fibrinoid Necrosis: Seen in conditions like vasculitis.
  • Gangrene: Dry (coagulative) and wet (liquefactive) gangrene.

2. Apoptosis

• Programmed Cell Death: Physiological and pathological.
• Key Features:
  • No inflammation, cell membrane remains intact.
  • Caspase-dependent process: Initiator caspases (8, 9, 10) and executioner caspases (3, 6, 7).
  • Mechanisms:
    • Extrinsic Pathway: Signal from outside activates death receptors.
    • Intrinsic Pathway: Stress signals lead to mitochondrial damage.

Cellular Adaptations

1. Hypertrophy

• Definition: Increase in cell size due to increased protein synthesis.
• Examples:
  • Exercise-induced muscle hypertrophy.
  • Left ventricular hypertrophy due to aortic stenosis.

2. Hyperplasia

• Definition: Increase in the number of cells due to mitosis.
• Examples:
  • Endometrial hyperplasia due to estrogen.
  • Benign prostatic hyperplasia (BPH).

3. Atrophy

• Definition: Decrease in cell size and number.
• Mechanism: Ubiquitin-proteasome degradation pathway.
• Examples:
  • Muscle wasting due to disuse.
  • Ischemia leading to organ atrophy.

4. Metaplasia

• Definition: Change from one cell type to another.
• Examples:
  • Barrett's esophagus due to chronic acid exposure.
  • Squamous metaplasia in smokers' lungs.
  • Myositis ossificans.

5. Dysplasia

• Definition: Disorganized growth of cells, often precancerous.
• Key Note: Not a reversible adaptation.

Intracellular Accumulations

1. Pigments

• Melanin: Found in skin and substantia nigra; stains: Mason Fontana, HMB-45.
• Iron: Hemochromatosis; stain: Prussian Blue.
• Copper: Wilson's disease; stains: Rhodanine, Rubinic acid.
• Lipofuscin: Accumulates with age; stain: Oil Red O.
• Glycogen: Seen in diabetes mellitus; stain: PAS.

Conclusion

• Understanding cell injury, death, and adaptations provides a foundation for pathology and clinical applications.