Wound Healing (Dong NAVDF) Flashcards

1
Q

Wound HEALING vs wound REPAIR

A

Healing = regeneration. Back to OG. Keratinocytes + endothelial cells

Repair = scarring. Compromised function. Fibroblasts

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2
Q

4 phases of wound healing

A

1) Hemostasis/coagulation
2) Inflammation (neutrophils, then macs)
3) Repair/granulation phase
4) Remodeling/scar formation

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3
Q

Order of cells involved in wound healing (plt, mac, fibro, neut)

A

1) PLATELETS ARE FIRST
2) Neutrophils
3) Macrophages
4) Fibrocytes

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4
Q

Which are the FIRST cells in wound healing

A

Platelets

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5
Q

What allows platelets to bind to each other

A

Thromboxane

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6
Q

What mediates linkage of platelets with exposed collagen

A

von wilibrand factor

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7
Q

What marks the END of the coagulation phase

A

Fibrin clot

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8
Q

Factors of intrinsic coagulation cascade

A

Factors 11, 9, 8

Not $12, but $11.98

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9
Q

Factors of common coagulation cascade

A

Factors 10, 1 (aka fibrinogen)

“Small change = $10, $1”

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10
Q

Factors of the extrinsic cascade

A

Factor 7

Uses tissue factor to convert to factor 1, aka fibrinogen

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11
Q

What mediates conversion of fibrinogen to fibrin

A

Thrombin

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12
Q

What do damaged cells release to initiate hemostasis

A

Histamine
Serotonin
Catecholamines

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13
Q

3 “stages” platelets go through during hemostasis

A

1) Aggregation
2) Platelet plug
3) Fibrin clot

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13
Q

What happens to the blood vessels during hemostasis? (Vasoconstriction vs vasodilation)

A

Initially: Vasoconstriction to stop bleeding

Later: Vasodilation to recruit WBC

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14
Q

Platelet activation pathway

A

1) Tissue injury
2) Exposed collagen recruits platelets (VWB F)
2) Coagulation cascade –> fibrinogen to fibrin via thrombin
3) Quiet platelet becomes activated via exposure to collagen, thrombin, ADP, TXA2
4) Active platelet releases DENSE granules (ADP, ATP, Serotonin) and TXA2 to activate more platelets
4) Active platelet releases ALPHA granules (fibrinogen, fibronectin, PDGF, P-selectin) to attract more neutrophils, macrophages
5) Platelets release stores of TGF-B, which induces fibrocyte activity, recruits more neut/mac

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15
Q

Contents of Dense Granules (Platelets)

A

1) Serotonin
2) ADP
3) ATP

Induce aggregation of platelets
*Construction and adherence

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16
Q

Contents of Alpha Granules (Platelets)

A

1) Fibrinogen
2) Fibronectin
3) PDGF
4) P-selectin

*Fibrin clot factors
*Chemokines for neut/mac/fibroblasts

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17
Q

More important thing STORED in platelets, functions

A

TGF B

Activates neut/mac
Stimulates fibroblasts to myofibroblasts

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18
Q

Cells that stores TGF B

A

Platelets

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19
Q

Factors involved in LYSIS of fibrin clot (4)

A

1) Plasminogen activator (initiates lysis)
2) Antithrombin III
3) Protein C (factor 5, 8)
4) Prostacyclin C (limit platelet aggregation)

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20
Q

Timeframe for neutrophils to come to wound

A

Minutes to 72hr

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21
Q

Adhesion molecules involved in neutrophils ROLLING

A

Selectins

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22
Q

Which Selectins on which cell types?

A

P selectin- platelets
E selectins - endothelial cell
L selectin- leukocytes

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23
Q

Adhesion molecules involved in neutrophil ADHESION/activation

A

Integrins (ICAM, VCAM)

hold neutrophils TIGHTLY

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24
Q

What binds to ICAM on endothelial cells

A

LFA-1 on neutrophil

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25
Q

What binds to VCAM on endothelial cells

A

VLA on neutrophil

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26
Q

Which adhesion molecules allow diapedesis? (3)

A

1) PECAM1
2) JAM-1 (tight junctions)
3) VE-cadherin (adherens junctions)

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27
Q

When do macrophages enter wound healing site?

A

24-48hr

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28
Q

Which TYPE of macrophage is involved in wound healing?

A

M2

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29
Q

What are M1 macrophages

A

Phagocytize bacteria + neuts, induce inflammation, scavenge debris

Stimulated by TNF alpha

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30
Q

TNFalpha will induce which TYPE of macrophage

A

M1

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31
Q

What are M2 macrophages

A

Repair, help with wound healing. Suppress immune system

Stimualted by TGF Beta

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32
Q

TGF B will induce which TYPE of macrophage

A

M2

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33
Q

Time frame of REPAIR phase of wound healing

A

2-10d

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34
Q

4 “steps” of Repair Phase

A

1) Granulation tissue formation (3-4d)
2) Fibroplasia, wound contraction (triggered by hypoxia. Fibroblasts respond to TGF-B)
3) Angiogenesis
4) Re-epithelialization

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35
Q

What stimulates fibroblasts to turn into myofibroblasts for wound contracture

A

TGF B
PDGF

Increases collagen integrin receptor alpha-2 expression

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36
Q

Type of Collagen INITIALLY in wound healing, granulation tissue

A

Collagen 3, less strong

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37
Q

Type of Collagen in MATURE wound healing, remodeling phase

A

Collagen 1, stronger

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38
Q

Type of collagen in vessels and hypertrophic scars

A

Collagen 5

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39
Q

Most abundant type of collagen in basement membrane

A

Collagen 4

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40
Q

When does wound contraction peak?

A

2 weeks

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41
Q

What type of collagen is present in scar tissue

A

Collagen 1

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42
Q

What type of collagen is present in granulation tissue

A

Collagen 3

43
Q

Which 2 growth factors stimulation wound contracture

A

1) PDGF (induce fibroblast to myofibroblast)
2) TGF-B1 (stim fibroblast contraction, myofibroblast differentiation, production of HA and RHAMM)

44
Q

What is the receptor for HA

A

RHAMM

45
Q

What is the function of GAGs in wound healing

A

Moist environment

46
Q

What is the fastest and most abundant GAG in wound healing

A

HA

47
Q

Where in cells is HA synthesized

A

Plasma membrane

48
Q

When does angiogenesis start after wounding

A

Day 2

49
Q

What stimulates angiogenesis (4)

A

1) Macrophage-released cytokines
2) Decreased O2
3) Lactic acid
4) Growth factors (VEGF, bFGF)

50
Q

What are the 2 growth factors that stimulate angiogenesis

A

VEGF
bFGF (basic fibroblast GF)

51
Q

Where do keratinocytes for re-epithelialization come from?

A

*Neighboring keratinocytes
*Hair follicle stem cells (bulge)
*Sebaceous glands
*Claws

52
Q

If there is a full thickness wound, what to keratinocytes NEED to migrate over?

A

Granulation tissue

53
Q

How do keratinocytes re-epithelialize with partial thickness wound?

A

Leap frog

54
Q

What are lamellipodia

A

How keratinocytes migrate; little projections

55
Q

Process of lamellipodia migration

A

1) Focal adhesion
2) Extension –> forms lamellipodia
3) Adhesion –> new focal adhesion at tip of lamellipodia
4) Translocation –> Contraction, cell body moves to the new focal adhesion
5) De-adhesion –> lets go of old focal adhesion

56
Q

Stimulation of lamellipodia formation

A

Low Ca2+
High Mg2+

57
Q

What are keratinocytes able to migrate over?

A

1) COL 1, 3, 5
2) Fibronectin
3) Fibrin
4) Tenascin
5) Vitronectin

58
Q

Can keratinocytes cross the BMZ directly?

A

NO.
MMP degrades the BMZ, so keratinocytes can reach it once GRANULATION tissue is formed

59
Q

What is “contact inhibition”

A

When keratinocytes reach each other, they know to stop migration.

60
Q

What is the final strength of the scar compared to original, healthy skin

A

70% strength

61
Q

What signal helps with remodeling and scar formation

A

TGF-B

62
Q

Which species has delayed collagen synthesis

A

Cats

Forms day 19. “pseudo-healing”. Indolent pocket wounds.

63
Q

Where does granulation tissue begin in cats

A

Periphery of wound

64
Q

Which species has an early inflammatory response

A

Dogs

65
Q

Where does granulation tissue begin in dogs

A

Center of the wound

Day 7.5
More direct cutaneous vessels

66
Q

Which species has weak/prolonged inflammation phase

A

Horses

67
Q

Which species has exuberant granulation tissue

A

Horse –> proud flesh

68
Q

Which disease in horses is equivalent to keloids in people

A

Proud flesh

-Increased TGF beta
-Mast cell hyperplasia

69
Q

T or F: Proud flesh can invade healthy skin

A

T

70
Q

Which scar is characterized by NO myofibroblasts

A

Proud flesh

71
Q

Which scar is characterized by ABUNDANT myofibroblasts

A

Hypertrophic scars

Noninvasive
Widely spaced collagen

72
Q

Acronym to assess complications in wound healing= TIME. What does this mean?

A

TIME

T= nonviable tissue
I = inflammation, infection. Inflammation phase should be done in 3d, so if persistent, check for infection
M= moisture
E= epithelialization

73
Q

Which growth factor is overexpressed in proud flesh. Which cell is hyperplastic in proud flesh?

A

TGF-B1

Mast cell hyperplasia

74
Q

What is the difference between a wound DRESSING and wound BANDAGE

A

BANDAGE: Control swelling, immobilization

3 Layers
1) Dressing
2) Absorb deleterious factors
3) Hold layers together

DRESSING: Cover + protection
*Absorb excess exudate
*Stimulate repair (non-antigenic, not too moist, occludes dead space)

75
Q

In which phase of wound healing is honey a good dressing?

A

Inflammatory + Repair phase

76
Q

Functions of honey dressing

A

-Debridement
-Hyperosmotic effects
* -Dehydrates microorganisms + Manuka factor (uMF)
* -Reduces tissue edema
-Stimulates granulation tissue

77
Q

Functions of granulated sugar

A

*Hyperosmotic effects

Inferior option:
No antiinflammatory /wound healing effects

Needs to be 1 cm thick
Painful

78
Q

Function of fish skin (tilapia, cod)

A

-Excellent skin adherence
-Induces growth factors (EpidermalGF, FGF)
-Antimicrobial activity
-OFA 3: bacterial barrier, pain modulating

79
Q

Function of negative pressure wound therapy

A

-Debridement
-Aids in contraction
-Increased perfusion
-Decreased edema
-Removes detrimental cytokines

80
Q

Contraindications for negative pressure wound therapy

A

-Exsanguination
-Neoplasia
-Necrotic tissue/eschar

81
Q

Benefits of HBOT (3)

A

-Hyper-oxygenation
-Leukocyte oxidative killing capacity (Mac ROS)
-Synergistic with antibiotics/antifungals

82
Q

Which medications are synergistic with HBOT (4)

A

1) Fluoroquinolones
2) Aminoglycosides
3) Beta-lactams
4) Amphotericin B

83
Q

Contraindications for HBOT (3)

A

-Pneumothorax
-Seizures, uncontrolled
-Unconscious patient, coma

84
Q

Effect of serotonin and thromboxane A2 from platelet dense granules

A

Vasoconstriction
Amplify platelet activation/recruitment

85
Q

Effect of Fibrinogen, vWF, factor V from platelet alpha granules

A

Stimulate more platelet aggregation –> platelet plug

86
Q

Where in platelets are PDGF, TGF-B, VEGF made/stored?

A

Alpha granules

87
Q

Which phase of wound healing would you expect to see exudate (septic or nonseptic)

A

Inflammatory phase

(neutrophils getting eaten up by macs)

88
Q

Predominant cell type in repair phase

A

1) M2
2) Fibroblasts
3) Endothelial cells
4) Keratinocytes

**Marked increased in fibro, endo, KC during “proliferation” phase

89
Q

What do fibroblasts bind to, to make scar?

A

Fibronectin of provisional ECM

90
Q

Structural proteins of scar

A

Collagen, elastin

91
Q

Adhesive proteins of scar

A

Fibronectin

92
Q

Ground substance in scar

A

Hyaluron (HA), Proteoglycans (PG)

93
Q

Which cell types of repair phase secrete proteases?

A

All of them (M2, fibloblasts, KC, endothelial cells)

94
Q

Members of MMP family (3)

A

-Collagenases
-Gelatinases
-Stromelysins

95
Q

What breaks down old blood vessels?

A

MMP
Heparinase

From endothelial cells

96
Q

Inhibitors of angiogenesis (3)

A

Angiostatin
Endostatin
Antithrombin III

97
Q

Risk factors for poor wound healing (6)

A

1) Infection
2) Medications
3) Comorbidities (age, endocrine, liver/kidney, neoplasia, immune-med)
4) Nutrition (need Glu, protein, Mg, Vit A)
5) Location
6) Radiation tx

98
Q

How do wounds heal for rats/mice

A

Contraction

99
Q

How do wounds heal for pigs?

A

Re-epithelialization

Since skin is tightly adhered to underlying structures, limited ability for contracture

100
Q

Where on body is proud flesh most common

A

Distal limb wounds

101
Q

Who has more wound contraction: horses or ponies?

A

Ponies –> less proud flesh than horses

102
Q

Collagen dressing

A

-Hydrophilic: maintain moist wound environment
-Scaffold for fibroblasts

103
Q

Platelet-derived products dressing

A

*Enhance fibroblast proliferation
*accelerate epithelial differentiation

Indication: decubital ulcers in dogs, horses

104
Q

Mesenchymal stem cell dressing

A

*Make many SC lines
*Anti-inflammatory, pain modulating
*Immunmodulation

105
Q

Bioelectric dressing

A

*Mimics physiologic currents at wound edge across wound surface
*Use AFTER inflammatory phase
*Antimicrobial, prevent biofilm
*Moist environment
*Increases epithelialization