1. After injury
    • the tissue works to eliminate the offending agent
    • contain the damage
    • prepare surviving cells for replication
  2. Healing
    • combination of regeneration on fibrosis (scarring)
    • heart and brain are not able to regenerate so they scar
    • Extensive exudate with fibrin will cause scarring
  3. Regeneration
    • tissue growth that replaces lost structures
    • must have intact connective tissue scaffold
  4. what regulates adult cell populations
    • cell proliferation
    • differentation
    • apoptosis
  5. Proliferation
    • physiologic;hormaonal
    • pathologic; injury, cell death
    • signals may inhibit or stimulate
    • can recruit cell into the cell cycle
  6. Cell cycle
    • G1, presynthesis
    • S DNA synthesis
    • G2 Premitotic
    • M mitosis
    • G0 resting state
  7. continuesly dividing tissues
    • cells proliferate throughout life replacing dead cells
    • surface epithelium, the intestinal tract, bone marrow
  8. quiescent cells
    low level replication but still capable of dividing in response to stimuli; liver, kidney, fibroblasts, smooth muscle, endothelial cells
  9. Nondividing cells
    neurons, skeletal muscle, cardiac muscle
  10. Stem cells
    • prolonged self renewal capacity
    • asymetric replication
  11. What do you use in knockout experiments
    embryonic stem cells
  12. Adult stem cells
    • located in niches
    • restricted differentiation capability
    • liniage specific
  13. Where in the liver are stem cells
    • canals of Hering; junction of hepatocyte and bile duct
    • only differentiate if direct hepatocyte proliferation is not possible
  14. MAin VEGF receptor
  15. Epidermal growth factor
    • Source; platelets, macrophages, saliva, urine , milk, plasma
    • Function; stimulates keritinocytes and fibroblasts to proliferate
  16. Transforming growth factor alpha
    • source; macrophages, T cells,
    • function; stimulates replication of hepatocytes, and epithelial cells
  17. Hepatocyte growth factor
    • source; mesechymal cells
    • function; stimulates epithelial, endothelial, and hepatocyte proliferation
    • stimulates mobility
  18. Vascular endothelial growth factor
    • source; mesenchymal cells
    • function; increase vascular permeability, endothelial cell proliferation
  19. PDGF
    • source; platelets, macrophages, smooth muscle, endothelial cells
    • chemotactic; PMNs, macrophages, fibroblasts, smooth muscle cells,
    • activation of all cells
    • mitogenic for fibroblasts, endothelial cells, smooth muscle
    • stimulates production of, proteases, fibronectin,
    • angiogenisis and would contraction
    • inhibits platelet aggrigation
    • regulates integrin expression
    • alpha granuals
  20. FGF
    • source; macrophages, mast cells, t cells, endothelial cells,
    • chemotactic for fibroblasts
    • mitogenic for fibroblasts and keritocytes
    • wound contraction
    • angiogenesis
    • centrally involved in would repair
    • form resivoirs of inactive factors
  21. TGF beta
    • source; platelets, t cells, macrophages, smooth muscle, fibroblasts
    • chemotactic ; macrophages, neutrophils, lymphocytes, fibroblasts,
    • stops proteasis; tissue inhibitor of proteases
    • down regulates intigrins
    • anti-inflammatory effect
    • promotes fibrosis by stimulation chemotaxis
  22. keratinocyte growth factor
    • fibroblasts
    • stimulates keratinocyte migration, differentation, and proliferation
  23. ILGF
    source; macrophages, fibroblasts
  24. TNF
    • macrophages, mast cells, lymphocytes
    • activates macrophages, regulates the cytokines
  25. interlukins
    • macrophages, mast cells, lymphocytes
    • many functions
  26. interferons
    • lymphocytes, fibroblasts
    • activates macrophages,
    • inhibits fibroblast proliferation and synthesis of MMPs
  27. Tyrosine kinase
    • most growth factors
    • Ras
    • PI3
    • phospholipase C
    • activated Ras binds to Raf and then activates a MAP kinase
    • PLC leads to IP3 and DAG, increased cytosol calcium
  28. JAK / STAT
    • cytokines
    • stats are transcription factors
  29. G protein receptors
    • glucogon, epi, chemokines, ACTH
    • generates cAMP
  30. steroid hormaone recptors
    • diffuse directly into membrane
    • intranuclear trascription factors
  31. p53
    cell cycle inhibitor gene
  32. Transcription factor response time
    • the rapid response time needed by the cell does not permit for new synthesis, it rather relys on post transcriptional modification that allows migration into the necleus
    • modification; dimerization, phosphorilation, release of inhibitors
  33. cell cycle regulation
    • CDKs; protein kinases become active after binding cyclin
    • each step needs different kinases
    • CDKs are regulated by catabolism or inhibitors
    • p53 works by expressing cyclin inhibitor, this stops the cell cycle until the damage is corrected or can induce apoptosis
  34. Function of hypertrophy and hyperplasia
    the restore functional capacity, not reconstruct original anatomy
  35. after nephrotmy
    the other kidney will hypertrophy to make up for the lost one
  36. collagen
    • skin and bone; type 1
    • cartilage; type 2
    • basment membrane; type 4
    • elastin type 3
    • formed as individual alpha chain, form a triple helix
  37. Defect in marfans
    fibrilin 1
  38. classic ehlers-danlos
    collogen v
  39. vascular ehlers danlos
    collogen III
  40. osteogenesis imperfecta
    collegen I
  41. type II collegen
    • catillage
    • any grooming disorder
    • arachnidactyl
  42. four cell adhesion proteins
    • immunoglobins
    • cadherins; calcium dependent
    • intigrins, cell-cell adhesion as well as cell to to ECM
    • selectins
  43. what two cell adhesion molecules are transmembrane
    cadherins and intigrins
  44. fibronectin
    • lots of adhesion
    • in hemidesmosoms
  45. most abundant glycoprotein in the BM
  46. an angiogenesis inhibitor
  47. proteoglycans and hyaluronic acid
    • bind large amounts of water and GAGs
    • give turner and resists compression
  48. scarring
    a fibroproliferative response that pathces rather then restores
  49. fibrosis
    ECM depositing at a site of injury
  50. the sequence of healing
    • inflammatory response to eliminate stimulus and remove injured tissue
    • proliferation and migration of parechymal and connective tissue
    • angiogenisis; new blood vessels
    • synthesis of ECM proteins
    • tissue remodeling
    • wound contraction
    • granulomas are a hallmark of healing
  51. monocyte chemotaxis
  52. Fibroblast migration
  53. fibroblast proliferation
  54. angiogenesis
  55. collagen synthesis
  56. collagenase secretion
    PDGF, FGF, EGF, TNF, TGF-b inhibits
  57. embryonic vessel development
  58. branching of pre-existing blood vessels
  59. steps of angiogenesis
    • NO dialates preexisting vessel
    • VEGF induces increased permeability
    • metalloprotinases degrade BM
    • plasminogen activator disrupts cell cell interaction
    • ECs migrate to angiogenic stimulus
    • EC mature into capillary tubes
    • periendothelial cells are recruited
  60. Growth factor receptors in angiogenesis
    • VEGF and the angiopoetins
    • VEGFR2; tyrosine kinase receptor
  61. recruits smooth muscle
  62. stabilizes newly formed vessels
  63. Three stapes to scar formation
    • Fibroblast migration and proliferation
    • ECM deposition and scar formation
    • Tissue remdeling
  64. Type III collogen in in granulation tissue then is replaced by type I
  65. MMPs cofacter
  66. Gelatinases
    degrade amorphous collagen
  67. TIMP
    tissue inhibitor metalloproteinases
  68. cutaneous Wound healing
    • epidermal appendages do not regenerate
    • induction of inflammation
    • granulation tissue formation, type III collagen
    • ECM deposit and remodeling with wound contraction
  69. First intention wound healing
    • opposed edges, clean surgical cut
    • 0 hours; incision is filled with blood
    • 3-24 hours; meutrophils infiltrate
    • day 3; macrophages replace neutrophil;s
    • day 5; granuloma fills incision space, neovasculation
    • week 2; inflammation and edema are done
    • month 2; scar is now connective tissue devoid of inflammation covered by epidermis. strength will continue to accrue
  70. second intention wound healing
    • greater inflammation response
    • more scaring
    • thinner epidermis
    • thicker granuloma
    • most significantly wound healing is characterized by contraction; myofibriblassts
  71. wound strength
    • 1 week 10%
    • within 3 months 70-80%
  72. Excessive repair with large scar
  73. palmer contracture
    too much contractor in the healing process from inflammation
  74. glucocorticoids
    inhibit collegen synthesis
Card Set
robbins chapter 3