Response to Injury I: Overview of Cellular&Tissue Responses

• Give an example of a labile, stable & permanent cell.

  Labile (continuously in cell cycle): epidermal/oral epithelial cells

  
  

  Stable (temporarily entered the cell cycle): hepatocytes

  
  

  Permanent (terminally differentiated): axons, cardiac myocytes
• What is a general cellular response to injury and what does it depend on?

  1. Stimulus : Type, Duration and Severity

  2.Cell: Type, status, capability and genetic makeup

  3.response:

  
• What changes can be seen after cell injury?

  Molecular/genetic changes-->functional changes-->structural changes-->signs & symptoms

  
• What may adaptive responses result from?

  Either physiological or pathological stimuli

  
• What are some different cellular adaptive responses?

  Hyperplasia

  Hypertrophy

  Atrophy

  Metaplasia

  Dysplasia

  
• What is hyperplasia?

  Increase in number of cells, not associated with increase in size of cells
• What is an example of physiological hyperplasia?

  Proliferation of glandular tissue in female breast, either during puberty or pregnancy
• What is an example of pathological hyperplasia?

  Prostate during hormonal imbalance

  Chronic hyperplastic candidosis

  
• What is hypertrophy?

  Increase in cell size, without increase in number of cells
• Which cells would usually undergo hypertrophy and hyperplasia?

  Hypertrophy- in cells that can undergo cell division

  Hyperplasia- in cells that can't undergo cell division
• What is atrophy?

  Decrease in cell size
• What is an example of physiological atrophy?

  Vaginal epithelium during menopause

  
• What is an example of pathological atrophy?

  Buccal mucosa epithelium during lichen planus

  
• What is metaplasia?

  A change from one differentiated cell type to another
• What is an example of metaplasia?

  Oral cavity: as a result of trauma/recent surgery, some ductal epithelial cells undergo metaplasia from cuboidal epithelium to stratified squamous epithelium
• What is dysplasia?

  Disordered stratification & maturation
• What could possibly happen after cell injury?

  Adaptation or Death

  
• Are hyperplasia, hypertrophy, atrophy, metaplasia, & dysplasia all reversible?

  Yes, when the stimulus is gone, it will reverse back to its original state

  
• What are the causative agents of cell damage?


  Physicale.g. trauma, radiation, thermal

  Chemicale.g. CO, cigarette smoke, ethanol

  Infectiouse.g. toxins, metabolic products, lysis,DNA damage

  Oxygen deprivatione.g. hypoxia, ischaemia

  Immunologice.g. complement activation, cell mediated cytotoxicity, autoimmune
• What are some mechanisms of cell injury?

  Disruption of metabolism (one of the most important)

  
  

  Nutrient/growth factor deprivation

  
  

  Free radical/ROS formation

  
  

  DNA damage

  
  

  Membrane disruption

  
  

  Inflammation

  
• By what mechanisms can cell death occur?

  Apoptosis

  Necrosis
• Apoptosis vs. Necrosis

  Necrosis causes cells to swell and burst, whereas apoptotic cells shrink and condense
• What is necrosis characterised by?

  Increased eosinophilia or increased pinkness of the cell
• What is pyknosis, karyorrhexis and karyolysis?

  1. Nuclear shrinkage

  2. Nucleus undergoes fragmentation

  3. DNA is digested by DNase and the nucleus disappears
• What is the most common type of necrosis?

  Coagulative necrosis
• What is coagulative necrosis?

  When the structural pattern of the necrotic tissue is maintained
• What are common causes of coagulative necrosis?

  Ischaemia

  Infarction
• What is liquefactive necrosis?

  Transformation of tissue into a liquid viscous mass (characterised by digestion of the dead cells)
• In what tissues is liquefactive necrosis common?

  Central nervous tissue (or in places where there is bacterial or fungal infection)
• What is caseous necrosis?

  A form of coagulative necrosis in which a thick, yellowish, cheesy substance forms

  Very common in TB infection
• What is apoptosis?

  Regulated & targeted programmed cell death
• What is an example of physiological apoptosis?

  Embryogenesis
• What is an example of pathological apoptosis?

  DNA damage, viral infection, protein misfolding
• What is the extrinsic mechanism/death receptor-mediated pathway for apoptosis?


  Death ligand binds to death receptor which, upon activation, causes the activation of downstream apoptosis intermediates (caspases)

  
  

  Caspase 8 activates caspase 3 which then causes apoptosis

  
• What is the intrinsic mechanism/mitochondrial dependent pathway for apoptosis?

  Release of cytochrome C causes downstream activation of caspase 9 which then causes activation of caspase 3 which ultimately leads to apoptosis

  
• What are several morphological stages in apoptosis characterised by?

  1. Early stages: shrinkage of nucleus & cytoplasm

  
  

  2. Middle stages: formation of membrane bound bodies containing organelles (apoptotic bodies)

  
  

  3. Later stages: phagocytosis of apoptotic bodies by inflammatory cells, including macrophages

  
• Differentiate between necrosis & apoptosis.

  
• What is autophagy?


  The cell recycles its own organic material

  Lysosome will surround it and eat it, allowing its building blocks to be something else