Auer Ch 5 Wound Healing

Front 1

Define clean wound:

Back 1

surgical wounds under aseptic conditions

Front 2

Define clean-contaminated wound:

Back 2

surgical wounds entering respiratory, gi, urogenital tract entered under controlled conditions without unusual contamination

Front 3

Define contaminated wound:

Back 3

open, acute, accidental or surgical wounds with major break in sterile technique

Front 4

Define infected wound:

Back 4

wounds with old, devitalized, or have gross contamination with foreign debris

Front 5

What are wound classifications based on time?

Back 5

I- less than 6 hrs with minimal contamination II- 6-12 hrs with significant contaminiation III- longer than 12 hrs with gross contaminiation

Front 6

What are the phases of wound healing?

Back 6

Inflammatory (lag) , proliferative, remodeling (maturation)

Front 7

What is initiated immediately in the inflammatory phase?

Back 7

Hemostasis (via vasoconstriction, platelet aggregation, fibrin deposition)

Front 8

What mediated the reflex vasoconstriction during the inflammatory phase?

Back 8

Release of endothelin and thromboxane A2 from injured vessels and serotonin released from platelets results in smooth muscle contraction

Front 9

How long does reflex vasoconstriction of vessels last in the inflammatory phase?

Back 9

5-10 min

Front 10

What occurs after reflex vasoconstriction early in the inflammatory phase?

Back 10

Vasodilation; diapedesis of cells, fluid and protein into the wound

Front 11

What is the provisional wound matrix?

Back 11

Early wound clot consisting of polymerized fibrin fibers

Front 12

What occurs at the wound if it is left unbandaged?

Back 12

Clot dessicates, provisional wound matrix is replaced by granulation tissue beneath scab

Front 13

What amplifies the early inflammatory phase?

Back 13

Activated platelets within the fibrin plug

Front 14

What mediators are released by activated platelets to amplify the early inflammatory phase?

Back 14

Platelet derived growth factor, transforming growth factor B

Front 15

What are the 1st cell types to enter the wound in large numbers?

Back 15

PMN

Front 16

What is the role of neutrophils in early inflammatory phase?

Back 16

Remove damaged tissue & bacteria; release chemoattractants to augment inflammatory response

Front 17

What are the principal degradative proteins released by PMN in inflammatory phase?

Back 17

Cathepsin G, neutrophil specific interstitial collagenase, neutrophil elastase

Front 18

When do monocytes enter the wound?

Back 18

24 hours after wounding

Front 19

What cells are the major inflammatory cells regulating wound repair?

Back 19

Macrophages

Front 20

How do macrophages regulate wound repair in the inflammatory phase?

Back 20

Release ROS, cytokines, growth factors; remove necrotic tissue & bacteria; tissue debridement via release of proteinases

Front 21

What proteinases are released by macrophages in the inflammatory phase?

Back 21

Elastase, collagenase, plasminogen activator

Front 22

What initiates the proliferation phase?

Back 22

Release of tissue growth factors by macrophages

Front 23

When does the proliferation phase begin?

Back 23

Approximately 3rd day after wounding

Front 24

What processes occur during the proliferation phase?

Back 24

Angiogenesis, fibrous & granulation tissue formation, collagen deposition, epithelialization, wound contraction

Front 25

What initiates angiogenesis?

Back 25

Decreased oxygen tension, increased lactate, low pH within wound

Front 26

What does vascular outgrowth during angiogenesis require?

Back 26

Endothelial cell proliferation

Front 27

What mediators regulate neovascularization during angiogenesis?

Back 27

Vascular endothelial growth factor, basic fibroblast growth factor

Front 28

When does production of angiogenic factors stop?

Back 28

When macrophages/ GF producing cells are no longer in hypoxic, lactic acid environment

Front 29

What cells mediate fibrous and granulation tissue formation in the proliferation phase?

Back 29

Fibroblasts

Front 30

When do fibroblasts arrive at the wound during the proliferation phase?

Back 30

2nd day after wounding

Front 31

When do fibroblast populations peak within the wound during the proliferation phase?

Back 31

7-14 days after wounding

Front 32

What mediates fibroblast migration to the wound in the proliferation phase?

Back 32

Platelet derived growth factor, transforming growth factor B, basic fibroblast growth factor

Front 33

What are the roles of fibroblasts in early proliferation phase?

Back 33

Proliferate and migrate within wound

Front 34

What are the roles of fibroblasts in later proliferation phase?

Back 34

Synthesize and reconstruct components to replace provisional wound matrix

Front 35

What products do fibroblasts synthesize and secrete in the proliferation phase?

Back 35

Collagen, GAGs (HA), glycoproteins, proteoglycans, proteases (MMPs)

Front 36

When does collagen production begin in the proliferation phase?

Back 36

2-3 days after wounding

Front 37

When does collagen production peak in the proliferation phase?

Back 37

1-3 weeks after wounding

Front 38

What type of collagen is initially most abundant in the proliferation phase?

Back 38

III

Front 39

When does epithelialization begin in the proliferation phase?

Back 39

Immediately after wounding

Front 40

How does epithelialization begin in the proliferation phase?

Back 40

Resident keratinocytes begin migration and phagocytosis

Front 41

What enables keratinocyte migration in the proliferation phase?

Back 41

Phenotypic change resulting from loss of contact inhibition, exposure to cellular products (NO)

Front 42

What effect do keratinocytes have on fibroblasts in the proliferation phase?

Back 42

Stimulate fibroblasts to release GF, cytokines

Front 43

How do keratinocytes migrate in the proliferation phase?

Back 43

Detach from neighbor cells, develop pseudopods with actin filaments, attach via integrins on pseudopods to ECM, actin filaments pull cell

Front 44

What interferes with keratinocyte migration in the proliferation phase?

Back 44

Fibrin, inflammatory products, exuberant granulation tissue

Front 45

What stops keratinocyte migration?

Back 45

Contact with other keratinocytes

Front 46

How does new epidermis differ from uninjured skin during the proliferation phase?

Back 46

Lacks rete pegs, lacks dermal layer in full thickness wounds

Front 47

What is a rete peg?

Back 47

Anchor epidermis to underlying connective tissue matrix

Front 48

When does contraction begin in the proliferation phase?

Back 48

2nd week after wounding (full thickness)

Front 49

What is necessary for contraction in the proliferation phase?

Back 49

Differentiation of fibroblasts to myofibroblasts

Front 50

Contraction rate (loose skin):

Back 50

0.75mm/day

Front 51

What are the primary mediators of fibroblast differentiation to myofibroblasts in the proliferation phase?

Back 51

TGFB released by macros & keratino; fibroblast density, mechanical tension on fibroblasts

Front 52

What signifies fibro → myofibroblast differentiation in the proliferation phase?

Back 52

Acquisition of alpha smooth muscle actin microfilament system

Front 53

When does contraction stop in the proliferation phase?

Back 53

Wound edges meet; tension of surrounding skin is equal to or greater than contraction; # of myofibroblasts becomes low

Front 54

What begins the maturation phase?

Back 54

Wound defect filled; homeostasis between collagen production & degradation; reduction of macrophases & fibroblasts by apoptosis

Front 55

How does collagen content change in the maturation phase?

Back 55

No net gain in content but haphazard arrangement changes to formation of bundles, cross-linking, and alignment along lines of tension

Front 56

How does tensile strength of the wound change during the maturation phase?

Back 56

Gradual gain, 20% of normal tissue at 3 weeks, 50% of normal within 3 months, 70-80% of normal at conclusion

Front 57

Why do ponies heal faster than horses?

Back 57

Quicker & more intense inflammatory response

Front 58

What are some reasons for delayed wound healing?

Back 58

Wound expansion, motion, exposed bone, infection

Front 59

What are the negative effects of soil?

Back 59

Reduce WBC effectiveness, decrease humoral defences, neutralize antibodies

Front 60

Why do distal limb wounds heal more slowly that trunk wounds?

Back 60

Slower epithelialization & contraction because of motion, infection, exuberant granulation tissue

Front 61

What are reasons for development of exuberant granulation tissue on distal limb wounds?

Back 61

Inefficient inflammatory response, imbalance in collagen homeostasis, profibrotic environment, microvascular occlusion, inappropriate cell apoptosis

Front 62

What mediated the profibrotic environment resulting in exuberant granulation tissue?

Back 62

Imbalance of TNFa, IL1, IL6, PDGF, TGFB, basic fibroblast GF

Front 63

What effect does TGFB have on creating a profibrotic environment?

Back 63

Enhances migration and proliferation of fibroblasts, delays fibroblast apoptosis

Front 64

What is microvascular occlusion?

Back 64

Occlusion of small capillaries within granulation tissue

Front 65

What is the effect of microvascular occlusion on the formation of exuberant granulation tissue?

Back 65

Results in local hypoxia which stimulates angiogenic and fibroblastic signals

Front 66

What general factors affect wound healing?

Back 66

Age, nutritional status, type of injury,tissue perfusion, hemostasis & hematoma formation, debridement, wound closure, topical therapy, pharmaceuticals

Front 67

What are the negative effects of seroma or hematoma formation?

Back 67

Impede healing by mechanical distraction of wound edges, reduce capillary perfusion (pressure on vessels), increases risk of infection

Front 68

what are the effects of TAO/ SSD on wound healing?

Back 68

Increase epithelialization but decrease wound contraction

Front 69

What are the effects of nitrofurazone on wound healing?

Back 69

Decreases epithelialization, delays wound contraction, carcinogen

Front 70

What is the benefit of ketanserin?

Back 70

Blocks serotonin-induced macrophage suppression and vasoconstriction during inflammatory phase (strengthens inflammatory response)

Front 71

What is the benefit of aloe vera?

Back 71

Stimulates macrophages to release fibrogenic and angiogenic cytokines during inflammatory phase and early proliferation phase (will increase granulation tissue formation over bone)

Front 72

What is the active agent in aloe vera?

Back 72

Acemannan

Front 73

What are the effects of NSAIDs on wound healing?

Back 73

Inhibit inflammatory response (decreased fibroblasts proliferation, protein synthesis, wound contraction, inhibition of keratinocyte GF, reduced angiogenesis)

Front 74

Function of PMN (neutrophils) in wound healing:

Back 74

phagocytosis of microbes, macrophage activation, amplify inflammatory response, stimulate repair processes

Front 75

Function of macrophages in wound healing:

Back 75

phagocytosis of PMN, damaged tissue and microbes, amplify repair process, stimulate angiogenesis & fibroplasia, fibrolysis

Front 76

Function of mast cells in wound repair:

Back 76

control vascular permeability, control influx of PMN, regulate tissue remodeling

Front 77

PMN mediators:

Back 77

ROS, eicosinoids, TNFa, IL1B, IL6, VEGF, IL8

Front 78

Macrophage mediators:

Back 78

TNFa, IL1B, IL6, PDGF, VEGF, bFGF, TGFa, TGFB, tPA, uPA

Front 79

Mast cell mediators:

Back 79

histamine, chymase, tryptase

Front 80

Source of colony stimulating factor (CSF):

Back 80

macrophage, lymphocyte, fibroblast, endothelial cell

Front 81

Function of CSF:

Back 81

differentiation & maturation of hematopoietic stem cells

Front 82

Source of interferon:

Back 82

monocytes, macrophage, lymphocyte, mesenchymal cell

Front 83

Function of interferon(INF):

Back 83

proinflammatory, release other cytokines to inhibit fibrosis

Front 84

Source of interleukin (IL):

Back 84

all nucleated cells (mostly macrophage & lymphocyte)

Front 85

Function of interleukin:

Back 85

proinflammatory, enhances epithelialization, angiogenesis, remodeling

Front 86

Source of tumor necrosis factor (TNF):

Back 86

macrophage, lymphocyte, mast cell

Front 87

Function of TNF:

Back 87

proinflammatory, enhance angiogenesis, epithelialization, and remodeling

Front 88

Source of connective tissue growth factor:

Back 88

fibroblast

Front 89

Function of connective tissue growth factor:

Back 89

mediate TGFb activity (cell proliferation, ECM accumulation)

Front 90

Source of epidermal growth factor (EGF):

Back 90

platelet, saliva

Front 91

Function of epidermal growth factor:

Back 91

epithelialization, chemotactic & mitogenic to fibroblast, protein & MMP synthesis

Front 92

Source of transforming growth factor a (TGFa):

Back 92

macrophage, epithelial cell

Front 93

Function of TGFa:

Back 93

epithelialization, chemotactic & mitogenic to fibroblast, protein & MMP synthesis, angiogenesis

Front 94

Source of fibroblast GF:

Back 94

inflammatory cell, fibroblast, endothelial cell

Front 95

Function of FGF:

Back 95

chemotactic and mitogenic to fibroblast and epithelial cell, protein synthesis, angiogenesis

Front 96

Source of insulin-like growth factor (IGF):

Back 96

liver, platelet

Front 97

Function of IGF:

Back 97

chemotactic & mitogenic to epithelial cell, migration of epithelial cell, fibroblast proliferation, protein & GAG synthesis

Front 98

Source of keratinocyte GF (KGF):

Back 98

fibroblast

Front 99

Function of KGF:

Back 99

chemotactic & mitogenic to epithelial cell

Front 100

Source of PDGF:

Back 100

platelet

Front 101

Function of PDGF:

Back 101

chemotactic to inflammatory cell & fibroblast, mitogenic to mesenchymal cell, protein synthesis

Front 102

Source of TGFB:

Back 102

platelet, lymphocyte, mast cell, monocyte, macrophage, endothelial cell, epithelial cell, fibroblast

Front 103

Function of TGFB:

Back 103

chemotactic to inflammatory & mesenchymal cell, fibroblast proliferation, protein synthesis, ECM deposition, inhibition of MMP, induction of TIMP, wound contraction

Front 104

Source of VEGF:

Back 104

macrophage, fibroblast, endothelial cell, epithelial cell

Front 105

Function of VEGF:

Back 105

angiogenesis