Wound Healing Flashcards

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1
Q

T/F: During normal homeostasis, hair follicles contribute to the epithelia.

A

False - normally do NOT, but during wound healing they do

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2
Q

What is a foam dressing?

A

polyurethane or silicone foam; vapor permeable but provide thermal insulation to the wound; hydrophilic wound contact layer and a hydrophobic backing – highly absorbent

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3
Q

What is the function of granulocyte/macrophage colony stimulating factor in wound healing?

A

stimulates proliferation and differentiation of osteoblasts; synergizes with Epogen in proliferation of BM progenitor cells; strong chemoattractant for neutrophils

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4
Q

What is an alginate?

A

produced from the calcium and sodium salts of alginic acid found in seaweeed; partially dissolved on contact with wound fluid –> forms a hydrophilic gel; can absorb 15-20 times their weight in fluid – excellent for highly exudative wounds

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5
Q

What is the purpose of semi-permeable films?

A

impermeable to fluids and bacteria but permeable to air and water vapor

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6
Q

What are differences between equine exuberant granulation tissue and keloids?

A

Exuberant granulation tissue lacks epithelial cover (keloids have); TGF-beta1 is increased –> induces general protein synthesis

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7
Q

What is the role of prostaglandins in wound healing?

A

increased vascular permeability, sensitize pain receptors, increased synthesis of glycosaminoglycans

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8
Q

What is the function of platelets that form the initial clot during wound healing?

A

maintain hemostasis, provide a matrix for migration of cells involved in wound healing, secrete cytokines to direct wound healing

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9
Q

What role does hypoxia play in wound healing?

A

activates fibroblasts and endothelial cells, stimulates macrophages to release angiogenic factors (TGF-beta1)

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10
Q

Indications for a semipermeable film (wound dressing)?

A

flat, shallow wounds with medium exudate; may be left in place for several days; useful secondary dressing; no cushion; provides moist environment and doesn’t adhere to wound

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11
Q

T/F: Migrating keratinocytes cannot bind to denatured collagen or denatured fibrin.

A

True - results in wound dissection and peeling off of the eschar

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12
Q

What cytokines and growth factors do activated platelets release?

A

platelet-derived growth factor, transforming growth factor beta-1 (TGF-beta-1), platelet activating factor, platelet-derived epidermal growth factor, fibronectin and serotonin

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13
Q

What are the processes that occur in scar tissue formation and tissue remodeling?

A

1) Fibrinolysis, 2) Removal of excessive extracellular matrix, 3) Contraction/scar formation, 4) Remodeling the collage and vasculature and further effects of matrix metalloproteinases

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14
Q

______ is new vascular tissue in granular form on an ulcer or the healing surface of a wound.

A

granulation tissue

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15
Q

What proteins do activated platelets release?

A

adenosine diphosphate (ADP), fibrinogen, fibronectin, thrombospondin; von Willebrand factor VIII

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16
Q

What is the function of platelet-derived growth factor in wound healing?

A

fibroblast proliferation, chemotaxis and collagen metabolism; angiogenesis; A & B isoforms are potent mitogens for fibroblasts, arterial smooth muscle cells, chondrocytes and epithelial cells; potent chemoattractant for hematopoietic and mesenchymal cells, fibroblasts and muscle cells, stimulates chemotaxis toward a gradient of PDGF; activates TGF-beta, stimulates neutrophils and macrophages, mitogenesis of fibroblasts and smooth muscle cells, collagen synthesis, collagenase activity and angiogenesis

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17
Q

What type of collagen is increased during neovascularization and in highly vascular hypertrophic scars?

A

collagen V

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18
Q

characteristics of hypertrophic scars

A

non-invasive, decreased collagen lysis –> abundance of collagen I, problem with remodeling phase

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19
Q

What is the role of kinins (e.g. bradykinin) in wound healing?

A

increased vascular permeability (through activation of complement cascade)

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20
Q

How are neutrophils removed from the wound?

A

with the wound eschar or are phagocytosed by activated tissue macrophages

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21
Q

What phenotypic changes occur in keratinocytes to allow migration to take place?

A

retract tonofilaments; dissolve desmosomes and hemidesmosomes; increase gap junctions (enhanced cellular communication); peripheral actin filaments and formation of lamellipodia (motor apparatus); express keratin 5, 14, 6, 16; express serine proteases and matrix metalloproteinases; express integrins that allow attachment to provisional matrix

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22
Q

What is the function of tumor necrosis factor in wound healing?

A

promotes inflammation

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23
Q

Migrating cells use what type of receptors that recognize the matrix components of the provisional matrix (fibrin, fibrinonectin, vitronectin)?

A

integrin receptors (mostly beta-2 integrins)

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24
Q

What is the second provisional matrix in wound healing?

A

granulation tissue

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25
Q

What is the most important growth factor in angiogenesis? What cell(s) release(s) it?

A

fibroblast growth factor - released by macrophages (and keratinocytes)

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26
Q

Why are neutrophils present in the wound earlier and in greater numbers than macrophages?

A

are present in the circulation in greater numbers

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27
Q

Indications for antimicrobial dressings?

A

can be used in all locally infected wounds

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28
Q

T/F: After wound healing, a scar reaches its original tissue strength.

A

False - only reaches 70% of original tissue strength

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29
Q

characteristics of keloids

A

invasive, abundance of collagen III, problem with proliferative phase (stuck in proliferative phase)

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30
Q

What are the known receptors for hyaluronic acid?

A

1) CD44 – involved with attachment, uptake and breakdown of HA, 2) RHAMM - found on macrophages and fibroblasts

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31
Q

What is the function of histamine in wound healing?

A

causes increased vascular permeability

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32
Q

Where are the most macrophages present in granulation tissue (what zone)?

A

zone of capillary sprouts and arches

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33
Q

What is the function of keratinocyte growth factor in wound healing?

A

keratinocyte proliferation - most potent growth factor for keratinocytes, playing a role in tissue repair following skin injuries; promotes wound healing via proliferation, differentiation, angiogenesis and cell migration; mitogen for many epithelial cells but not for fibroblasts and endothelial cells

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34
Q

In full thickness wounds, where does epithelialization start from?

A

wound’s edge

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35
Q

What is present in granulation tissue that gives wounds a “glisteny” appearance?

A

hyaluronic acid

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36
Q

Indication for a low adherent dressing?

A

flat, shallow wounds with low exudate

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37
Q

What are the primary collagens involved in wound repair?

A

Collagen III (present first) and then collagen I

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38
Q

What is the role of complement in wound healing?

A

increased vascular permeability, increased phagocytosis, enhanced bacterial lysis, mast cell and basophil activation

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39
Q

What is the function of connective tissue growth factor in wound healing?

A

fibroblast proliferation, chemotaxis and collagen metabolism; induces proliferation, migration, and tube formation of vascular endothelial cells and angiogenesis; potent stimulator for the proliferaiton and differentiation of osteoblasts, stimulates the matrix mineralization

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40
Q

What is the function of plasminogen activator in clot formation?

A

limits the clot formation by activating plasmin (converts plasminogen to plasmin) – plasmin causes clot lysis

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41
Q

What is a major chemoattractant for monocytes in wound healing?

A

TGF-beta-1

42
Q

What replaces hyaluronic acid as a wound matures?

A

glycosaminoglycans

43
Q

What cells are involved in coagulation/inflammation?

A

1) Platelets (coagulation), 2) Neutrophils (inflammation), 3) Growth factors (coagulation & inflammation), 4) Fibrin clot (coagulation), 5) Matrix metalloproteinases (coagulation & inflammation)

44
Q

_____ refers to a reorganization of the tissue to accommodate the processes of healing.

A

Remodeling

45
Q

What cytokine is thought to be involved in the development of keloids?

A

IL-6

46
Q

How are macrophages removed from the wound?

A

apoptosis

47
Q

What is a hydrogel?

A

matrix of insoluble polymers with up to 96% water content –> can donate water molecules to the wound surface; facilitate natural autolysis

48
Q

What are the processes that occur during coagulation/inflammation?

A

1) Bleeding with resultant tissue hypoxia, 2) Platelet activation/aggregation and coagulation, 3) Recruitment of leukocytes, 4) Debridement of damaged tissue, 5) Formation of first provisional matrix = fibrin clot

49
Q

What is the orientation of vessels in granulation tissue to the wound surface?

A

perpendicular

50
Q

What is the first provisional matrix in wound healing?

A

fibrin clot

51
Q

What is the function of IL-1 in wound healing?

A

fibroblast proliferation; proinflammatory; inhibits the growth of endothelial cells and hepatocytes

52
Q

What is a hydrocolloid?

A

colloids such as sodium carboxymethylcellulose, gelatin, pectin, elastomers, and adhesives bonded to a carrier of a semi-permeable film on a foam sheet –> produces a flat, occlusive adhesive dressing that forms a gel on the wound surface. Water and air impermeable and used to rehydrate dry, necrotic eschar and promote autolytic (self) debridement

53
Q

What cells are involved in tissue formation (migration/proliferation)?

A

macrophages, fibroblasts, keratinocytes, integrins, growth factors, enzymes (serine proteases and matrix metalloproteinases)

54
Q

What cells would CD18 deficient mice lack in their wounds?

A

neutrophils – CD18 is a marker for integrins (needed for diapedesis of neutrophils)

55
Q

What is the primary enzyme involved in collagen lysis?

A

matrix metalloproteinase-1 (collagenase-1) - ZINC depedent

56
Q

How soon after the initial wound do macrophages replace neutrophils as the predominant cell type?

A

within 24-48 hours

57
Q

What is the function of vascular endothelial growth factor in wound healing?

A

angiogenesis; vascular permeability; macrophage chemotaxis; induces synthesis of metalloproteinase – which degrades interstitial collagen types I, II, III

58
Q

What do mast cells produce that lead to nerve stimulation?

A

histamine, serotonin, nerve growth factor

59
Q

What effect would blocking plasminogen have on wound healing?

A

knockout mice show delayed re-epithelialization; plasminogen is converted to plasmin, which helps to limit the size of the clot that is formed

60
Q

What is the function of epidermal growth factor in wound healing?

A

keratinocyte proliferation and migration; stimulates the proliferation of epidermal and epithelial cells, fibroblasts, and embryonic cells; chemoattractant for fibroblasts and epithelial cells; stimulates re-epithelialization, augments angiogenesis; influences the synthesis and turn-over of extracellular matrix

61
Q

T/F: Scar tissue and grafts regain the innvervation of the original tissue

A

FALSE - healing wounds are associated with HYPERinnervation

62
Q

What cells are involved in scar tissue formation and tissue remodeling?

A

myofibroblasts, enzymes (serine proteases and matrix metalloproteinases), growth factors

63
Q

What is the function of insulin-like growth factor 1 in wound healing?

A

keratinocyte proliferation and differentiation; growth factor for normal fibroblasts; promotes the synthesis of collagenase and prostaglandin E2 in fibroblasts; stimulates collagen and matrix synthesis by bone cells, regulating metabolism of joint cartilage

64
Q

What cleaves fibrinogen into fibrin?

A

thrombin

65
Q

What do keratinocytes need to be in contact with in the provisional matrix in order to migrate?

A

collagen I, III or V, fibronectin, fibrin, tenascin, or vitronectin

66
Q

What is the function of fibroblast growth factor in wound healing

A

fibroblast and epithelial cell proliferation; matrix deposition, wound contraction; angiogenesis

67
Q

What is the purpose of a low-adherent dressing?

A

allow exudate to pass through a secondary dressing while maintaining a moist wound bed – designed to prevent the dressing form adhering to the wound

68
Q

What is the role of serotonin in wound healing?

A

stimulates fibroblast proliferation, involved in cross-linking of collagen molecules

69
Q

Indications for alginates (wound dressing)?

A

for highly exudative undermined wounds. Highly absorbent and needs a secondary dressing

70
Q

Indications for a hydrocolloid (wound dressing)?

A

Sheets: cavity or flat, shallow wounds with low-medium exudate; absorbent; comfortable; good in difficult area; Paste: debriding agent - can cause maceration; Hydrofiber: like sheets but can handle higher exudate; can be left in place for several days but needs secondary dressing

71
Q

T/F: Histology of keloids and hypertrophic scares usually reveals mast cell hyperplasia.

A

True - this is in contrast to normal rapid disappearance of perilesional mast cells

72
Q

What is the function of IL-8 in wound healing?

A

supports angiogenesis, mitogenic for epidermal cells

73
Q

What do mast cells produce after exposure to fibronectin and type III collagen that break down the extracellular matrix

A

proteases chymase and typtase

74
Q

Why does fetal repair result in no scarring?

A

lack of inflammatory response

75
Q

T/F: Endothelial cells produce their own extracellular matrix and basement membrane.

A

True- extracellular matrix is fibronectin and proteoglycans

76
Q

What are the components of intrinsic blood clotting?

A

surface activation of Hageman Factor XII, tissue procoagulant released from damaged cells, coagulation factors expressed on activated platelets and endothelial cells

77
Q

What are the processes that occur during tissue formation (migration/proliferation)?

A

1) Granulation tissue formation (second provisional matrix), 2) Cell migration and proliferation, 3) Final extracellular matrix production, 4) Fibroplasia/angiogenesis

78
Q

Migrating keratinocytes contain what products normally found in the stratum corneum?

A

involucrin and transglutaminase

79
Q

What cell(s) release vascular endothelial growth factor?

A

platelets, keratinocytes, macrophages, neutrophils

80
Q

On what type of wound should semi-permeable films NOT be used?

A

highly exudative wounds

81
Q

Hypertrophic scars and keloids result from persistance of what cell type?

A

fibroblasts (myofibroblasts)

82
Q

What are chemoattractant factors for neutrophils?

A

IL-8, kallikrein, Gro (growth-related oncogene-alpha), fibrinogen degradation products, fibrinopeptides, cytokines released by activated platelets

83
Q

What is the primary signal that stops keratinocyte migration?

A

reconstitution of laminin within the BMZ

84
Q

What is the function of the complement cascade in clot formation?

A

results in release of anaphylatoxins C3a and C5a –> increase vessel permeability and attract neutrophils and monocytes to site of injury

85
Q

Lymphocyte function associated-antigen, a beta-2 integrin present on activated neutrophils, binds to what on endothelial cells to facilitate neutrophil diapedesis?

A

I-CAM

86
Q

In partial thickness wounds, where does epithelialization start from?

A

both the wound edge and from adnexal structures within the wound bed

87
Q

Why could bandaging an equine leg increase the amount of granulation tissue produced?

A

bandaging results in a condition of hypoxia –> leads to stimulation of fibroblasts, endothelial cells, macrophages

88
Q

What is the function of hepatocyte growth factor in wound healing?

A

keratinocyte proliferation

89
Q

Where are the most neutrophils present in granulation tissue (what zone)?

A

Zone of necrotic debris

90
Q

T/F: Hair follicles are not necessary to close a wound, only to initiate rapid re-epithelialization.

A

TRUE

91
Q

What is the function of IL-10 in wound healing?

A

fibroblast proliferation; anti-inflammatory

92
Q

What proteoglycans are important in wound healing?

A

serglycine (produced by mast cells and endothelial cell membranes –> involved in coagulation); chondroitin-4-sulfate and dermatan sulfate (produced by mature scar fibroblasts –> structural components); versican (promotes cell migration by decreasing adhesion); decorin (inhibits growth of cells in vitro); syndecan family

93
Q

What is the primary role of neutrophils in the wound site?

A

phagocytosis and intracellular killing o fcontaminating bacteria

94
Q

What is the most important storage factor for transforming growth factor beta-1 (TGF-beta-1)?

A

platelets

95
Q

What are the four zones of granulation tissue?

A

Deepest –> superficial: 1) Zone of mature connective tissue, 2) Zone of capillary proliferation, 3) Zone of capillary sprouts and arches, 4) Zone of necrotic debris (“scab” or “crust”)

96
Q

What is the function of transforming growth factor-beta in wound healing?

A

fibroblast proliferation, chemotaxis and collagen metabolism; angiogenesis; immunomodulation; decreases dermal scarring;

97
Q

______ is the formation of granulation tissue and subsequent re-collegenation of the dermal matrix.

A

fibroplasia

98
Q

What are the phases of wound healing?

A

1) Coagulation, 2) Inflammation, 3) Migration/Proliferation, 4) Remodeling

99
Q

What is the function of transforming growth factor-alpha in wound healing?

A

keratinocyte proliferation and migration; resembles EGF (binds to the same receptor); stimulates mesenchymal, epithelial, and endothelial cell growth, endothelial chemotaxis, controls the epidermal development; stimulates the proliferaiton of endothelial cells (more potent than EGF); promotes the generation of osteoblasts - influencing them to lay down bone matrix during osteogenesis; affects bone formation and remodeling by inhibition fo the synthesis of collagen and release of calcium

100
Q

Indications for foam dressings?

A

sheets: flat, shallow wounds - gives some cushioning. Can be left in for 2-3 days, needs secondary dressing; cavity foam: for medium to highly exudative cavitated wounds

101
Q

What growth factors do macrophages release?

A

transforming growth factor beta-1; fibroblast growth factor; platelet-derived growth factor; vascular endothelial growth factor; hepatocyte growth factor

102
Q

Indications for hydrogels (wound dressing)?

A

moisturizes dry, flat, cavitated or sinus wounds; good for necrotic, sloughing wounds - but can cause maceration. Needs a secondary dressing