Cell Injury

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
    • hypothermia can mitigate hypoxic injury by decreasing cellular metabolism and slowing reperfusion 
  • ischemia
  • toxin-induced (e.g., ethanol and cigarette smoking)
  • infectious agents
  • genetic abnormalities
  • aging
  • imbalances in nutrition
  • physical causes (e.g., trauma)