Lecture 1: Introduction and Basics of Pathology

Overview

• Series of 30 lectures to cover the entire pathology syllabus needed for exams.
• Focus on exam-relevant content and clinical examples.

General Pathology

Cell Injury

• Types of Cell Injury:
  • Reversible Cell Injury
  • Irreversible Cell Injury
• Types of Cell Death:
  • Necrosis: Pathological, passive process, always caused by external stress.
  • Apoptosis: Programmed cell death, can be physiological or pathological.

Reversible Cell Injury

• Causes:
  • Most common cause: Hypoxia
  • Hypoxia often caused by ischemia (decreased blood supply).
• Cell Changes:
  • Adaptation failure leads to cell injury.
  • Reversible injury can return cell to normal if stress is removed.
• First Changes:
  • Mitochondrial dysfunction reduces ATP, leading to reversible injury.
  • Sodium-potassium ATPase pump failure causes sodium and water influx, leading to cellular swelling and hydropic change.
  • Chromatin clumping due to lactic acid from anaerobic respiration.
  • Ribosomal detachment causes decreased protein synthesis.

Irreversible Cell Injury

• Characteristics:
  • Severe membrane damage and mitochondrial damage are key indicators.
  • Calcium influx activates phospholipases and proteases, degrading cell membranes and cytoskeletal proteins.
  • Nuclear changes include pyknosis (condensation), karyorrhexis (fragmentation), and karyolysis (dissolution).
• Indication: Presence of large flocculent densities in mitochondria indicates irreversible injury.

Necrosis

• Types of Necrosis:
  • Coagulative Necrosis:
    • Most common, preserves architecture.
    • Seen in heart, kidneys, spleen due to infarction.
    • Ghost cells present.
  • Liquefactive Necrosis:
    • Tissue architecture not preserved.
    • Seen in brain and pancreas.
  • Caseous Necrosis:
    • Cheese-like appearance, combination of coagulative and liquefactive necrosis.
    • Associated with TB and some fungal infections.
  • Fat Necrosis:
    • Occurs in breast and pancreatitis.
    • Saponification (calcium binding with fatty acids) leads to chalky white appearance.
  • Fibrinoid Necrosis:
    • Seen in vasculitis and rheumatic heart disease.
    • Fibrin-like pink deposits in vessel walls.

Apoptosis

• Characteristics:
  • Both physiological and pathological.
  • No inflammation, as cell membrane remains intact.
  • Active process involving caspases (cysteine-aspartic proteases).
• Pathways:
  • Extrinsic Pathway: Triggered by external signals (e.g., Fas ligand binding to CD95).
  • Intrinsic Pathway: Triggered by internal stress, involves cytochrome C release from mitochondria.
• Execution:
  • Activation of executioner caspases (3, 6, 7) leads to cellular breakdown into apoptotic bodies.
  • Phagocytosis of apoptotic bodies facilitated by 'eat me' signals (e.g., phosphatidylserine).

Differences Between Necrosis and Apoptosis

• Necrosis affects groups of cells, causes inflammation, and results in cellular swelling.
• Apoptosis affects single cells, is inflammation-free, and results in cell shrinkage.

Conclusion

• Reversible cell injury is often a precursor to irreversible injury if stress persists.
• Necrosis and apoptosis are distinct pathways of cell death, each with unique features and implications.
• Understanding these processes is crucial for recognizing pathological changes and developing therapeutic strategies.