Cell Injury

• Four aspects of a disease

  • Cause (etiology)
  • Biochemical and molecular mechanisms of its development (pathogenesis)
  • Structural alterations induced in the cells and organs of the body (morphologic changes – gross and microscopic)
  • Functional consequences of these changes (clinical manifestations)
• Two classes of etiology or cause

  • Genetic (e.g. inherited mutations and disease-associated gene variants, or polymorphisms)
  • Acquired (e.g. infectious, nutritional, chemical, physical)
• Pathogenesis


  Sequence of cellular, biochemical, and molecular events that follow the exposure of cells or tissues to an injurious agent
• The study of pathogenesis is a central focus of pathology
• Morphologic changes


  Structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process
• Clinical manifestations


  The end results of changes in cells and tissues are functional abnormalities that lead to the symptoms and signs of disease, as well as its progression

  
• Homeostasis


  The normal cell is able to handle physiologic demands, maintaining a steady state
• Adaptations

  • Increase in the size (hypertrophy) and functional activity of cells
  • Increase in cell number (hyperplasia)
  • Decrease in the size and metabolic activity of cells (atrophy)
  • Change in the phenotype of cells (metaplasia)
• When the stress is eliminated, the cell can return to its original state without having suffered any harmful consequences
• Causes of cell injury


  • Oxygen deprivation or hypoxia
  • Physical agents
  • Chemical agents and drugs
  • Infectious agents
  • Immunologic reactions
  • Genetic derangements
  • Nutritional imbalances
• Reversible cell injury


  In early stages or mild forms of injury, the functional and structural alterations are reversible if the damaging stimulus is removed
• Features of reversible cell injury

  • Cellular swelling
  • Fatty change
• Cell injury is reversible up to a certain point, but if the stimulus persists or is severe enough from the beginning, the cell suffers irreversible injury and ultimately undergoes cell death
• Phenomena characterizing irreversibility


  • Inability to reverse mitochondrial dysfunction (lack of oxidative phosphorylation and ATP generation)
  • Profound disturbances in membrane function
• Two principal pathways of cell death

  • Necrosis
  • Apoptosis
• Necrosis


  Denaturation of cellular proteins, unable to maintain membrane integrity and their contents often leak out, a process that may elicit inflammation in the surrounding tissue
• Nuclear changes in necrotic cells

  • Karyolysis – basophilia of chromatin may fade
  • Pyknosis – nuclear shrinkage and increased basophilia
  • Karyorrhexis – pyknotic nucleus undergoes fragmentation