Lecture 5: Tissue Repair Flashcards
Elements of tissue repair
- Injury
- Inflammation
- Regen. or fibrosis
Categories of cellular regenerative potential
- Labile (always in cell cycle)
- Stable (quiescent, divide in response to stim.)
- Permanent (rare/nondividing)
Stem cells
Undifferentiated cells w/ prolonged self-renewal + asymmetric replication capacity
Steps in tissue repair
- Inflammation
- Cell proliferation/migration
- ECM synthesis
- ECM remodeling
Layers of tissue repair process
- Necrosis, acute inflam. exudate
- Granulation tissue
- Granulation tissue + ECM
- Fibrous scar
Tissue elements of layer 1
Necrosis, acute inflammation
- Fibrin, PMNs, macrophages, platelets
Molecular elements of layer 1
Necrosis, acute inflammation
- Cytokines (ILs, IFNs, TNF) and GFs (PDGF, FGF)
Cellular elements of layer 2
Cell proliferation + migration
- Capillaries, fibroblasts, macrophages
Molecular elements of layer 2
Cell proliferation + migration
- EGF, TGF-α, PDGF, FGF, VEGF, TGF-β, angiopoietins
Angiogenesis in tissue repair - steps/paths
From bone marrow EPC mobilization or pre-existing vessels
1. Vasodilation (NO, VEGF)
2. Sprouting + proliferation
3. Migration + recruitment
4. Suppression
Growth factors
Peptides that stim. cell proliferation, synthetic capacity, migration, and differentiation through auto/para/endocrine signaling
Layer 3 ECM functions
ECM synthesis
- Tissue texture (turgor, elasticity, rigidity)
- GF reservoir
- Substratum/matrix for cell adherence/migration
2 domains of ECM
- Basal membrane
- Interstitial matrix
Role of basal membrane
Produced by epithelial/mesenchymal cells; allows epithelial adherence/movement
Role of interstitial matrix
Fills space between cells, predominant CT element
3 elements of ECM
- Fibrous structural proteins (collagens, elastins)
- Cell Adhesion Molecules (CAMs; cadherins, integrins, fibronectin, laminin)
- ECM gel (proteoglycans, hyaluronan)
Fibronectin
Large glycoprotein from fibroblasts, endothelium, monocytes; has specific binding domains
Laminin
Most abundant glycoprotein in basement membrane; cross shaped cross-linking of specific receptors to collagen IV, heparan sulfate
Proteoglycans
Core protein linked w/ hydrated disaccharide polymers e.g. heparan/chondroitin sulfate; regulate ECM structure and permeability
Hyaluronan
Large repeating disaccharide that binds H2O for turgor and assoc. w/ varying proteins/receptors. Abundant in migrating cell matrices
Layer 4 features
ECM remodeling
- MMP degradation of collagens/other proteins
- Form. of collagen plates along physical stress lines
MMPs
Matrix metalloproteases; collagen-/gelatinases, stromelysins
Events of layer 4
ECM remodeling
- ECM remodeling, collagen plate formation
- Wound contraction (myofibroblasts)
- Blood vessel regression
Cutaneous wound healing by 1st intention
- small, shallow, clean wounds
- Small clot + granulation tissue -> fibrous union (scab)
- Can be primary union or secondary
1st intention wound healing - primary union
Physical wound closure (sutures, staples, etc.)
1st intention wound healing - secondary union
Healing by wound contracture via myofibroblasts
Cutaneous wound healing by 2nd intention
Larger wound w/ some infection -> wound contracture
Local factors that affect wound healing
- Perfusion
- Denervation
- Tissue type
- Foreign body/infection
- Necrosis
- Mechanical stress
- etc.
Systemic factors that affect wound healing
- Diabetes
- Nutrition
- Hypoxia
- Uremia
- Vit. C levels
Aberrations in wound healing
- Hypertrophic scar
- Keloid scar
Hypertrophic scar
Excess granulation tissue/collagen production
Keloid scar
Large raised scar w/ excess collagen
