Pathoma ch 1-3

• Growth adaptations


  1. Increase in stress leads to increase in organ size

  2. Decrease in stress leads to decrease in organ size

  3. Change in stress leads to change in cell type
• Hypertrophy


  • Increase in size of cells
  • Involves gene activation, protein synthesis, and production of organelles
• Hyperplasia


  • Increase in number of cells
  • Occurs via production of new cells from stem cells
• Hyperplasia and hypertrophy


  Generally occur together
• Permanent tissues (cardiac muscle, skeletal muscle, nerve) can only undergo hypertrophy, not hyperplasia
• Pathologic hyperplasia


  Can progress to dysplasia and cancer
• Benign prostatic hyperplasia (BPH) does not increase risk of prostate cancer
• Atrophy


  • Decrease in size and number of cells
  • Occurs via apoptosis and ubiquitin-proteosome degradation/autophagy
• Metaplasia


  • Change in cell type to better handle new stress
  • Occurs via reprogramming of stem cells
• Barrett esophagus


  • Squamous epithelium changes to columnar epithelium to handle acid reflux
• Metaplasia is reversible with removal of driving stressor
• Persistent metaplasia


  Can progress to dysplasia and cancer
• Vitamin A deficiency


  • Causes metaplasia of conjunctiva to keratinizing squamous epithelium (keratomalacia)
• Mesenchymal (connective) tissues can also undergo metaplasia, e.g. myositis ossificans
• Metaplasia


  Reversible change in which one adult cell type is replaced by another adult cell type
• Metaplasia is reversible, in theory, with removal of the driving stressor
• Example of metaplasia reversing


  • Treatment of gastroesophageal reflux may reverse Barrett esophagus
• Under persistent stress, metaplasia


  Can progress to dysplasia and eventually result in cancer
• Example of metaplasia progressing to cancer


  • Barrett esophagus may progress to adenocarcinoma of the esophagus
• Apocrine metaplasia of breast carries no increased risk for cancer
• Vitamin A deficiency


  Can also result in metaplasia
• Vitamin A


  Necessary for differentiation of specialized epithelial surfaces such as the conjunctiva covering the eye
• Keratomalacia


  Change in vitamin A deficiency where the thin squamous lining of the conjunctiva undergoes metaplasia into stratified keratinizing squamous epithelium
• Mesenchymal (connective) tissues can also undergo metaplasia
• Example of mesenchymal metaplasia

  • Myositis ossificans - connective tissue within muscle changes to bone during healing after trauma
• Dysplasia


  Disordered cellular growth, most often refers to proliferation of precancerous cells
• Example of dysplasia


  • Cervical intraepithelial neoplasia (CIN) represents dysplasia and is a precursor to cervical cancer
• Dysplasia often arises from longstanding pathologic hyperplasia or metaplasia


  e.g. endometrial hyperplasia, Barrett esophagus
• Dysplasia is reversible, in theory, with alleviation of inciting stress
• If stress persists, dysplasia

  Progresses to carcinoma (irreversible)
• Aplasia


  Failure of cell production during embryogenesis
• Example of aplasia


  • Unilateral renal agenesis
• Hypoplasia


  Decrease in cell production during embryogenesis, resulting in a relatively small organ
• Example of hypoplasia


  • Streak ovary in Turner syndrome
• Apoptosis


  1. Mediated by caspases

  2. Caspases activate proteases

  3. Proteases break down cytoskeleton

  4. Caspases activate endonucleases

  5. Endonucleases break down DNA
• Caspase activation


  1. Multiple pathways

  2. Intrinsic mitochondrial pathway

  3. Extrinsic receptor-ligand pathway

  4. Cytotoxic CD8 T cell-mediated pathway
• Intrinsic mitochondrial pathway


  • Cellular injury, DNA damage, or decreased hormonal stimulation leads to inactivation of Bcl2
  • Lack of Bcl2 allows cytochrome c to leak from inner mitochondrial matrix into cytoplasm and activate caspases
• Extrinsic receptor-ligand pathway


  • FAS ligand binds FAS death receptor (CD95) on target cell, activating caspases
  • Tumor necrosis factor (TNF) binds TNF receptor on target cell, activating caspases
• Cytotoxic CD8 T cell-mediated pathway


  • Perforins secreted by CD8 T cell create pores in membrane of target cell
  • Granzyme from CD8 T cell enters pores and activates caspases
  • CD8 T-cell killing of virally infected cells is an example
• Free radicals


  Chemical species with an unpaired electron in their outer orbit