Lecture Notes: General Pathology - Cell Injury and Cell Death

Introduction to General Pathology

• Focus on exam-relevant topics
• Clinical integration with examples
• Chapter: Cell Injury

Types of Cell Injury

1. Reversible Cell Injury
2. Irreversible Cell Injury

Cell Injury Process

• Normal Cell: Under homeostasis
• Stressed Cell: Adaptation occurs
  • Failure to Adapt: Leads to cell injury
• Types:
  • Reversible Cell Injury: Minor damage; cell can return to normal
  • Irreversible Cell Injury: Severe damage; leads to cell death (necrosis or apoptosis)

Reversible Cell Injury

• Causes: Hypoxia (most common)
  • Hypoxia: Decreased oxygen
  • Ischemia: Decreased blood supply (most common cause of hypoxia)
• Cellular Changes:
  • Mitochondrial dysfunction
  • Decreased ATP production
  • Sodium-potassium pump failure
  • Cellular swelling (hydropic change)
  • Loss of microvilli
  • Cytoplasmic blebs
  • Myelin figures
  • Clumping of chromatin
  • Ribosomal detachment leading to decreased protein synthesis

Irreversible Cell Injury

• Key Features:
  • Severe membrane damage
  • Mitochondrial damage
  • Calcium influx leading to activation of destructive enzymes
  • Formation of large amorphous flocculent densities in mitochondria
• Nuclear Changes:
  • Pyknosis (condensation)
  • Karyorrhexis (fragmentation)
  • Karyolysis (dissolution)

Types of Cell Death

1. Necrosis
2. Apoptosis

Necrosis

• Always Pathological
• Types:
  • Coagulative Necrosis: Most common; architecture preserved (heart, kidney, spleen)
  • Liquefactive Necrosis: Found in brain and pancreas
  • Caseous Necrosis: Cheesy appearance, seen in TB
  • Fat Necrosis: Seen in breast tissue, pancreatic fat (chalky white appearance)
  • Fibrinoid Necrosis: Seen in vasculitis (e.g., polyarteritis nodosa)
  • Gangrene: Dry (coagulative) and wet (liquefactive)
  • Zenker's Degeneration: Waxy degeneration of skeletal muscles (e.g., typhoid)

Apoptosis

• Programmed Cell Death: Can be physiological or pathological
• Characteristics:
  • No inflammation
  • Caspase-dependent
  • Active process using ATP
• Pathways:
  • Extrinsic Pathway: Death receptor-mediated (e.g., CD95/Fas ligand)
  • Intrinsic Pathway: Mitochondrial pathway (e.g., cytochrome C release)
• Execution: Activation of caspases leading to cell breakdown

Other Types of Cell Death

1. Necroptosis: Combination of necrosis and apoptosis; caspase-independent

• Seen in pancreatitis, steatohepatitis, neurodegenerative diseases
• Key Enzymes: RIPK1, RIPK3, MLKL

2. Pyroptosis: Inflammatory form of cell death

• Key Enzymes: Caspase-1, Gasdermin
• Outcome: Inflammation and fever (IL-1, IL-18)

Cellular Adaptations

1. Hypertrophy: Increase in cell size

• Examples: Muscle (exercise), heart (outflow obstruction), breast (pregnancy/puberty), uterus

2. Hyperplasia: Increase in cell number

• Examples: Endometrial hyperplasia, benign prostatic hyperplasia

3. Atrophy: Decrease in cell size and number

• Examples: Disuse atrophy, malnutrition, ischemic atrophy, denervation atrophy

4. Metaplasia: Change in cell type

• Examples: Barrett’s esophagus, smoker's lung

5. Dysplasia: Disorganized growth; precancerous

• Reversibility: Irreversible

Intracellular Accumulations

1. Pigments: Melanin

• Seen in skin and substantia nigra
• Stains: Mason Fontana, HMB-45, dopa oxidase

2. Iron: Hemosiderin

• Seen in hemochromatosis
• Stains: Prussian blue, Pearl’s stain

3. Copper: Wilson’s Disease

• Stains: Rhodanine, rubeanic acid

4. Lipids: Fatty liver, cholesterolosis

• Stains: Oil Red O, Sudan Black B

5. Glycogen: Seen in diabetes mellitus

• Stains: PAS (Periodic Acid-Schiff)

Summary

• Cell injury can be reversible or irreversible, leading to different types of cell death
• Cellular adaptations occur in response to stress
• Intracellular accumulations can indicate underlying diseases
• Focus on understanding mechanisms, examples, and clinical relevance