Updated: 1/19/2019

Cell Injury

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Overview

 
Introduction
  • Cells constantly interact with their environment and try to maintain homeostasis
    • cells respond to stress (e.g., physiologic and toxic) via adaptation to maintain viability and function
      • cell injury results when the cell can no longer adapt to the stress, which can be
        • reversible
          • implies that once the stress is removed the cell can return to its original state
        • irreversible
          • when the stressful stimuli is excessive or persistent the cellular damage becomes irreversible and cells undergo
            • cell death
  • General mechanism of cell injury
    • ATP depletion leads to 
      • reduced Na+/K+ ATPase activity causing
        • cellular and endoplasmic reticulum swelling
      • anaerobic glycolysis which subsequently leads to
        • glycogen depletion
        • lactic acid
      • reduced calcium pump activity which
        • alters calcium homeostasis and activates proteins
      • reduced protein synthesis
    • mitochondrial damage can result from hypoxia, reactive oxygen species (ROS), and intracellular calcium levels and leads to
      • increased mitochondrial permeability which causes
        • impaired oxidative phosphorylation resulting in
          • the production of ROS (damages lipids, proteins, and nucleic acid)
          • leakage of apoptotic proteins (e.g., cytochrome C and caspases) into the cellular cytoplasm
    • DNA damage that is irreparable results in
      • apoptosis
        • apoptosis can also result in misfolded proteins
  • Etiologies of cell injury includes
    • hypoxia
    • ischemia
    • toxin-induced (e.g., ethanol and cigarette smoking)
    • infectious agents
    • genetic abnormalities
    • aging
    • imbalances in nutrition
    • physical causes (e.g., trauma)
 
Findings in Reversible and Irreversible Cellular Injury
Reversible
Irreversible
  • Morphological findings
    • cellular swelling
    • nuclear chromatin clumping
    • ribosomal detachment
      • secondary to decreased protein synthesis
    • membrane blebbing
    • fatty change
  • Morphological findings
    • plasma membrane damage
    • lysosomal rupture
    • autolysis
    • mitochondrial permeability
    • changes of the nucleus include 
      • pyknosis
      • karyorrhexis  
      • karyolysis
 

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