Posted in Pathology

Cellular injury


  • Autophagy involves sequestration of cellular organelles into cytoplasmic autophagic vacuoles. (autophagosomes) that fuse with lysosomes and digest the enclosed material. 
  • Autophagy is an adaptive response that is enhanced during nutrient deprivation, allowing the cell to cannibalize itself to survive. 
  • Autophagosome formation is regulated by more than a dozen proteins that act in a coordinated, and sequential manner. 
  • Dysregulation of autophagy occurs in many disease states including cancers, inflammatory bowel diseases, and new rodegenerative disorders. Autophagy plays a role in host defense against certain microbes. 

Abnormal Intracellular Depositions and Calcifications 

    • Abnormal deposits of materials in cells and tissues are the result of excessive intake or defective transport or catabolism. 
    • Deposition of lipids :
    1. Fatty change: Accumulation of free triglycerides in cells, resulting from excessive intake or defective transport (often because of defects in synthesis of transport proteins); manifestation of reversible cell injury 
    2. Cholesterol deposition: Result of defective catabolism and excessive intake; in macrophages and smooth muscle cells of vessel walls in atherosclerosis 
    • Deposition of proteins: Reabsorbed proteins in kidney tubules; immunoglobulins in plasma cells 
    • Deposition of glycogen: In macrophages of patients with defects in lysosomal enzymes that break down glycogen (glycogen storage diseases) 
    • Deposition of pigments: Typically indigestible pigments, such as carbon, lipofuscin (breakdown product of lipid peroxidation), or iron (usually due to overload, as in hemosiderosis) 
    • Pathologic calcifications :
    1. Dystrophic calcification: Deposition of calcium at sites of cell injury and necrosis 
    2. Metastatic calcification: Deposition of calcium in normal tissues, caused by hypercalcemia (usually a consequence of parathyroid hormone excess) 

    Cellular Aging 

      • Cellular aging results from a combination of accumulating cellular damage (e.g., by free radicals), reduced capacity to divide (replicative senescence), reduced ability to repair damaged DNA, and defective protein homeostasis 
      • Accumulation of DNA damage: Defective DNA repair mechanisms; conversely, caloric restriction activates DNA repair and is known to prolong aging in model organisms 
      • Replicative senescence: Reduced capacity of cells to divide secondary to progressive shortening of chromosomal ends (telomeres) 
      • Defective protein homeostasis: Resulting from impaired chaperone and proteasome functions. 
      • Nutrient sensing system: Caloric restriction increases longevity. Mediators may be reduced lGF-1 signaling and increases in sirtuins. 

        ©Robbins Basic Pathology, Ninth edition

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