inflammation and repair 2

  1. Describe the details of cellular events in acute inflammation.
    • 1. cytokines activates the endothelium in actue inflammation.
    • 2. activated endothelium expresses adhesion molecules such as endothelial leukocytes adhesion molecules 1 (ELAM-1), intercellular adhesion molecules 1 (ICAM-1), CD34, and P-selectin that allow neutrophil adhesion. Adhesion+aggregation = margination.
    • 3. neutrophils emigrate through the wall to damage area in response to chemotactic factors (complement fragments C5a, bacterial components)
    • 4. Neutrophil's main job is to phagocytose foreign/noxious agents. a. it has membrane receptors for the Fc portion of antibodies, complement bound to foreign particles, and bacterial polysacchardies. Neutrophils can then bind and engulf. b. Phagasome (phagocytosed injurious agent) fuse with neutrophilic granules (which contains lysomal enzymes) to break it down = oxygen-independent mechanisms. Another way of killing is production of superoxide and hydrogen peroxide = oxygen-dependent mechanism. c. phagocytosed material is reduce to residual body = harmless junk.
  2. What are the 3 outcome of acute inflammation?
    • 1. a desired outcome of acute inflammation - Resolution.
    • 2. The less desirable outcome of acute inflammation - Healing by scarring.
    • 3. The worse case scenario is progression to chronic inflammation.
  3. what happens in resolution?
    • a. injurious agent gets removed before extensive damage.
    • b. acute inflammatory exudate is removed by liquefaction and phagocytosis.
    • c. functional cells regenerate, resulting in restoration of tissue/organ function.
  4. what happens in "healing by scarring"?
    • a. extensive scarring to supportin stroma. a number of events happen in the injured, acutely infalmed area that is known as organization. Organization => reapiar by formation of collagenous scar => permanent loss of specialized cells => loss of function
    • 1. macrophages remove debris from injured area.
    • 2. vascular granulation tissue: macrophages secrete fibrogenic and angiogenic factors. Capillaries bud into the damaged area and fibroblasts and myofibroblasts start to proliferate.
    • 3. fibrovascular granulation tissue: fibroblasts and myofibroblasts continue to grow and vessles become sparser.
    • 4. Creation of fibrous granulation tissue and eventually a collagenous scar (avascular).
  5. Abscess formation. Extensive tissue necrosos caused by pus-forming bacteria will result in the formation of a mass of necrotic tissue containing what?
    neutrophils and the products of tissue breakdown
  6. What are the 3 circumstances that create chronic inflammation?
    • 1. following acute inflammation if the inciting stimulus persists or interference of healing process
    • 2. repeated events of acute inflammation
    • 3. most commonly! gradual low grade, smoldering response that does not follow the classic acute inflammation (persistent infection like TB...)
  7. in chronically inflamed tissue necrosis, ______ and ____ occur simultaneously.
    a. organization and repair
  8. When a damaging stimulus persists, the immune system becomes increasingly ______. Thus ___________ will be found at a site of chronic inflammation in addition to necrotic cellular debris, acute inflammatory exudate, granulation tissue, macrophages and collagenous scar tissue.
    • a. vigilant
    • b. activated lymphoid cells (lymphocytes and plasma cells)
  9. Healing in chronic inflammation occurs by ______.
  10. What activates macrophages?
    How does macrophags play in a role in chronic inflammation?
    • activated by lymphokines or by nonimmune factors like endotoxins
    • primary role
    • phagocytic and secretes a number of chemokines that influence the immune response
  11. When does granulomatous inflammation occurs and what happens? What are the agents that lead to this?
    • occurs when neutrophil phagocytosis is ineffective
    • hallmark of this = granuloma, which is discrete cluster of macrophages and lymphocytes
    • agents are certain bacteria (M. tuberculosis and Mycobacterium species), foregin material in tissue, some fungi, and unknown factors.
    • granulomas evoked by M. tuberculosis has special necrosis = caseous necrosis. one of the necrotic granulomas is termed a tubercle
  12. what is regeneration?
    • replacement of ijured tissue by cells of the same type
    • cells are divided to 3 groups depend on their abiity to regenerate: labile, stable, permanent cells.
  13. what are labile cells?
    • cells that are continuously proliferating througout life
    • ex. epithelial cells, hematopoeitic cells
  14. what are stable cells?
    • normally have a low replication level but can undergo rapid division
    • ex. liver, CT
  15. What are permanent cells?
    • cells that do not regenerate
    • ex. nerve cells, skeletal, and cardiac muscle
  16. What are the two distinct processes of healing and repair?
    regeneration and replacement by CT
  17. What occurs in replacement by CT?
    • occurs by formation of granulation tissue
    • main histological features of which are the proliferation of small blood vessels (neovascularization & angiogenesis)
  18. what is healing by primary intention?
    The adjacent surfaces of a cleanly incised wound are apposed and held together (e.g. by sutures).
  19. what is healing by secondary intention?
  20. what are the steps to wound healing in primary and secondary intention?
    • A. 0 hours: the incision is filled with clot
    • B. Day 1: The appearance of neutrophils heralds the onset of the acute inflammatory response.
    • Epithelial cells start to divide and migrate across the wound.
    • C. Day 2: Macrophages start to clean up fibrin; a
    • continuous layer of epithelium bridges the wound.
    • D. Day 3: Granulation tissue starts for form; the bridging epithelium thickens.
    • E. Day 5: Vascular granulation tissue fills the incision
    • space; the epithelium achieves normal thickness.
    • F. Day 7 – Day 30: Continued fibroblast proliferation and collagen deposition leads to progressive strengthening of the wound.
    • G. 3 months: Healing is largely achieved with minimal scar tissue formation.
  21. what are the mechanisms involved in repair?
    • 1. Growth factors (e.g. Epidermal growth factor EGF, platelet derived growth factor PDGF, fibroblast growth factor FGF)
    • 2. Cell-cell and cell-matrix interaction (e.g. cell stop dividing when injury has healed)
    • 3. Collagenization and wound strength (e.g. collagen of granulation tissue is type III which is weak and later replaced by collagen I). Wound strength at the end of the 1st week is 10% and by the end of third month it is 80%
  22. List 8 factors that adversely affect wound healing.
    • A. Ischemia.
    • B. Poor nutrition (vitamin C, protein).
    • C. Infection
    • D. Foreign material retained at the site of damage
    • E. Steroids.
    • F. Radiation
    • G. Diabetes.
    • H. Denervation.
Card Set
inflammation and repair 2
inflammation and repair, pathology, Dr. Said