Path Tissue Renewal and Repair

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Path Tissue Renewal and Repair
2011-10-18 00:39:43
Pathology tissue renewal repair

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  1. Regenerative tissues
    • High proliferative capacity: epithelium, bone marrow
    • Stable tissues: liver, kidney

    Requires intact ECM
  2. Labile tissues
    • Continuous proliferation throughout life
    • ex: epithelial linings, bone marrow, epidermis
  3. Stabile tissues
    • Normally low levels of replication
    • Can replicate rapidly in response to stimuli
    • Ex: parenchymal cells of kidney, liver, pancreas, bribroblasts, sm m, endothelium, chondrocytes, osteocytes
  4. Permanent tissues
    • Cell unable to undergo mitotic division in postnatal life
    • Ex: neurons, skel m, cardiac m
  5. Stem cell ex's
    • Liver - canals of hering, make oval cells
    • Brain - olfactory bulb and hippocampus
    • Skeletal m - Replication of satellite cells
    • Epitheial
  6. EGF
    • Epidermal growth factor
    • EGF R = HER-2
    • Mitogenic for epithelial cells, hepatocytes, fibroblasts
    • Produced by keratinocytes, macrophages, inflammatory cells
  7. Hepatocyte GF
    • =Scatter F
    • Mitogenic for epithelial cells
  8. VEGF
    • Vascular endothelial
    • Induces bl vessel formation
    • More in tumors, chronic inflammation, healing wounds
  9. Platelet-derived GF
    • Stored in platelet a granules, relseased on activation
    • Cause migration and prolif of fibroblasts, sm m cells/monocytes
  10. FGF
    • Fibroblast GF
    • Wound repair
    • Differentiation
  11. TGF-B
    • Growth inhibition of epithelium and leukocytes
    • Stim prolif of fibroblasts adn sm m cells
    • Fibrogenic agent
  12. Liver Regeneration
    • Restores functional mass not form
    • All hepatocytes participate in regen
    • TNF and IL-6 transition G0-G1 (priming)
    • HGF and TGFa (proliferation)
    • TGFb (growth cessation)
  13. Collagen
    • #1 prot
    • 27 types (4 is nonfibrillar in basement memb)
    • Defect: Ehlers-Danlos, osteogenesis imperfecta
  14. Elastin
    • Tissue recoil
    • Elastic fibers then surrounded by fibrillin
    • Defect: Marfan
  15. Angiogenesis
    • Granulation tissue is hallmark of healing
    • From endothelial precursor cells (stored in bone marrow)
    • From pre-existing vessels (vasodil, -basement memb, endothelial migration, recruit periendothelial cells)
    • VEGF, angiopoietin, PDGF, TGFb
  16. Scar formation
    • Fibroblast migration/prolif
    • TGFb!!
    • Lots of collagen 3-5 days after injury
    • Matrix metalloproteinases degrade ECM and remodel
  17. Healing by primary intention
    • Surgical wounds
    • Least complicated, clean, uninfected, edges re-approximated
    • Immediate healing, space fills with blood, dehydration forms scab
    • W/i 24h neurtrophils at margin, begin re-epithelialization
    • Day 3: Neutrophils replaced by macrophages, granulationtissue
    • Day 5: Max neovascularization, collagen fibers bridge incision
    • Day 10: More collagen, less inflammation
    • Day 30: no inflam, tensile strength increasing
  18. Healing by second intention
    • Not well re-approx
    • More intense inflamm due to large fibrin clot, more necrotic material
    • More granulation tissue
    • Wound contraction myofibroblasts
  19. Complications in wound healing
    • Deficient scar (dehiscence and ulceration)
    • Excesive repair (keloid, exuberant granulation, desrnoid
    • Formation of contractures
  20. Persistence of initial stimulus or dev of chronic immune reactions
    • Cirrhosis (alcholism, chronic viral hepatitis)
    • Pneumoconiosis (coal, asbestos, silica)
    • Post-radiation therapy
    • Chronic pancreatitis