Kuliah 8

• Wound healing


  An essential physiological process consisting of the collaboration of many cell replacement of destroyed or damaged tissue by newly produced tissue

  
• Repair (healing)


  Restoration of tissue architecture and function after an injury

  
• Repair of damaged tissues

  • Regeneration by proliferation of residual (uninjured) cells and maturation of tissue stem cells
  • Deposition of connective tissue to form a scar

  
• Regeneration


  Occurs by proliferation of cells that survive the injury and retain the capacity to proliferate
• Tissues with regeneration


  • Epithelia of the skin and intestines, liver, stem cells
• Connective tissue deposition


  If the supporting structures of the tissue are severely damaged, repair occurs by the laying down of connective (fibrous) tissue → scar formation

  
• Tissues with connective tissue deposition

  • Lungs, liver, kidney
• Organization


  Fibrosis in a tissue space occupied by an inflammatory exudate
• Cell and tissue regeneration

  1. Cell proliferation driven by growth factors and dependent on the integrity of the extracellular matrix

  2. Development of mature cells from stem cells
• Tissue types


  • Labile tissues
  • Stable tissues
  • Permanent tissues
• Labile tissues


  Continuously dividing tissue
• Labile tissues


  • Hematopoietic cells, surface epithelia, epithelia of ducts, GI tract epithelia, uterus, fallopian tubes, urinary tract epithelia

  
• Stable tissues


  Quiescent (in the G0 stage of the cell cycle) and have only minimal proliferative activity in their normal state
• Stable tissues


  • Endothelial cells, fibroblasts, smooth muscle cells, liver, kidney, pancreas

  
• Permanent tissues


  Terminally differentiated and non-proliferative
• Permanent tissues


  • Neurons, cardiac myocytes
• Cell proliferation


  1. Driven by signals from growth factors and the extracellular matrix

  2. Macrophages, residual epithelial and stromal cells are activated by damage → growth factors → signaling pathways → cell cycle or block cell cycle

  3. Proliferation of residual cells supplemented by development of mature cells from stem cells
• Restoration of normal tissue architecture can occur only if the residual tissue is structurally intact

  
• If the entire tissue is damaged by infection or inflammation, regeneration is incomplete and is accompanied by scarring

  
• Liver regeneration


  • Proliferation of hepatocytes following partial hepatectomy
  • Liver regeneration from progenitor cells when hepatocyte proliferation is impaired
• Repair by connective tissue deposition

  1. Replacement of injured cells with connective tissue → formation of a scar

  2. Combination of regeneration of some residual cells and scar formation

  
• Scar formation is a response that "patches" rather than restores the tissue

  
• Steps in repair by scar formation

  1. Hemostatic

  2. Inflammation

  3. Cell proliferation

  4. Remodeling

  
• Hemostasis


  1. Vascular spasm (vasoconstriction)

  2. Formation of a platelet plug

  3. Blood clotting (coagulation)

  
• Vasoconstriction


  Endothelial injury causes endothelial cells to secrete von Willebrand factor, which causes platelet adherence during initial clot formation

  
• Platelet plug formation


  Damaged endothelium exposes subendothelial collagen, causing platelets to swell, grow filaments, and aggregate, forming a platelet plug
• Coagulation cascade


  Activated platelets release ADP, serotonin, and thromboxane A2, triggering a cascade of chemical reactions that form a mesh of fibrin to stabilize the platelet plug
• Inflammation


  A response of vascularized tissues to infection and damaged tissues that brings cells and molecules of host defense from the circulation to the sites where they are needed, in order to eliminate the offending agents
• Sequence of events in an inflammatory reaction

  1. Recognition of offending agent by sentinel cells

  2. Recruitment of leukocytes and plasma proteins from circulation

  3. Activation of leukocytes and proteins to eliminate offending agent

  4. Damaged tissue is repaired

  
• Hyperemia


  Microvascular changes in inflammation associated with flush, flare, and weal

  
• Exudation


  Increased passage of protein-rich fluid through vessel wall into interstitial tissue
• Emigration of leukocytes


  Neutrophils and mononuclear cells pass between endothelial cell junctions by amoeboid movement into tissue spaces
• Chemotaxis


  Movement of leukocytes in response to increasing concentration gradient of chemotactic agents

  
• Phagocytosis


  Process by which leukocytes engulf and digest microbes and damaged cells

  
• Steps in scar formation

  1. Angiogenesis

  2. Formation of granulation tissue

  3. Remodeling of connective tissue

  
• Angiogenesis


  Formation of new blood vessels to supply nutrients and oxygen needed for the repair process

  
• Inflammation


  • Caused by slowing of blood flow and by increased 'stickiness' of the endothelial surface

  
• Leucocyte movement after penetration of vessel wall

  1. Controlled by chemotaxis

  2. Cell moves in response to increasing concentration gradient of chemotactic agent

  
• Chemotactic agents


  • Factors derived from Complement system (C3a)
  • Factors derived from Arachdonic acid by the neutrophils → leukotrienes
  • Factors derived from pathogenic bacteria
  • Factors derived from sensitised lymphocytes → cytokines (IL-8)
• INFLAMMATION


  Inflammatory response