Wound Repair

Question 1

Regeneration v repair

Answer 1

Regeneration: complete restoration through proliferation of mature cells or adult stem cells may regenerate lost tissue

Repair: combination of regeneration and scar formation

Question 2

Cell categories by proliferating activity

Answer 2

Labile: cont dividing, skin GI hematopoietic
Stable: G0 stage of cell cycle but with growth factor signals at site of injury, liver kidney pancreas
Permanent: terminally differentiated and nonproliferative, neurons, mature skeletal, cardiac muscle

Question 3

Regeneration of liver

Answer 3

Proliferation of surviving hepatocytes after injury is triggered and growth factors
Or
Liver stem cells (oval cells) in niches located in Canal of Hering

The reticulin framework of liver needs to be intact for regeneration to occur, extensive destruction will lead to scarring

Question 4

Skeletal muscle

Answer 4

Does not divide after injury
Satellite cells: reserve pool of stem cells located beneath myocyte basal lamina, ability to generate differentiated myocytes after injury

Question 5

Repair

Answer 5

Scar
Involves ECM
Collagen, elastin, fibronectin, collagen type IV, laminin
Most cells have contact with ECM and contain receptors (integrins) that bind ECM proteins
May store some growth factors for rapid deployment after injury

Question 6

Collagen synthesis

Answer 6

Vitamin c activates prolyl and lysyl hydroxylases which hydroxylate procollagen, otherwise no stage helical configuration
Scurvy: vit C deficiency with poor healing and bleeding tendency, children will have skeletal deformations

Question 7

Three conditions of regeneration

Answer 7

1. Tissue composed of labile or stable cells
2. Area of injury must contain some viable cells capable of undergoing cell division
3. Connective tissue framework, to which tissue cells attached, must be intact to serve as scaffolding for replicating cells

Question 8

Healing by scar formation

Answer 8

Occurs if injured tissue incapable of regeneration, b/c
Tissue consists of permanent non dividing cells
No surviving tissue cells remain
Connect I’ve tissue framework is disrupted or destroyed

Question 9

Three phases of cutaneous wound healing

Answer 9

1. Inflammation: initial injury has clot formation with platelet adhesion and aggregation, acute inflammation
   Activation of coagulation pathways, growth factors, cytokines, chemokines, VEGF (edema due to increased vascular permeability), neutrophils within 24hr
2. Proliferation: formation of granulation tissue, fibroblasts and vascular endothelial cells, re-epithelialization
   Fibroblasts and vascular endothelial cells 24-72hr, 3-7 days, angiogenesis (VEGF and FGF), edema, macrophages, collagen synthesis
3. Maturation and reorganization: ECM deposition, remodeling, wound contraction in large surface wounds
   Epithelialization begins 24-48hr, cell moves from edge of wound along cut margins and deposits basement membrane, meet midline, size determines timeframe, macrophages stimulate fibroblasts to produce FGF-7 and IL-6 to enhance migration and proliferation

Question 10

Macrophages in wound healing

Answer 10

Replace neutrophils in 48-96hr
Key component of tissue repair
Classically activated secrete mediators of inflammation, clear debris, fibrin and other foreign material
Alternatively activated promote angiogenesis, activate fibroblasts, and stimulate collagen synthesis

Question 11

Fibroblasts

Answer 11

TGF-beta most important
Produced by most cells in granulation tissue and causes fibroblast migration and proliferation, increased synthesis of collagen and fibronectin, decreased degradation of ECM mellanoproteinases
At first provisional matrix has fibrin, plasma fibrin, and type III collagen which is replaced by type I as wound healing progresses

Question 12

Tissue remodeling

Answer 12

Replacement of granulation tissue with scar tissue
Involves synthesis and degradation of ECM components
Degraded by MMPs, dependent on zinc for activity

Question 13

Mature scar

Answer 13

Weeks to months
Amount of collagen and ECM proteins increases
Number of fibroblasts and vascularity decreases
Fully mature scar practically avascular, few cells, no dermal appendages, and dense collagen
Trichromatic stain: scar is blue from collagen
Granulation H&E edema, blood vessels

Question 14

Healing by first and second intention

Answer 14

First: wounds with opposed edges

Second: separated edges, more extensive loss of cells and tissue
Wound contraction by myofibroblasts, substantial scar