Wound Healing (Dong NAVDF) Flashcards
Wound HEALING vs wound REPAIR
Healing = regeneration. Back to OG. Keratinocytes + endothelial cells
Repair = scarring. Compromised function. Fibroblasts
4 phases of wound healing
1) Hemostasis/coagulation
2) Inflammation (neutrophils, then macs)
3) Repair/granulation phase
4) Remodeling/scar formation
Order of cells involved in wound healing (plt, mac, fibro, neut)
1) PLATELETS ARE FIRST
2) Neutrophils
3) Macrophages
4) Fibrocytes
Which are the FIRST cells in wound healing
Platelets
What allows platelets to bind to each other
Thromboxane
What mediates linkage of platelets with exposed collagen
von wilibrand factor
What marks the END of the coagulation phase
Fibrin clot
Factors of intrinsic coagulation cascade
Factors 11, 9, 8
Not $12, but $11.98
Factors of common coagulation cascade
Factors 10, 1 (aka fibrinogen)
“Small change = $10, $1”
Factors of the extrinsic cascade
Factor 7
Uses tissue factor to convert to factor 1, aka fibrinogen
What mediates conversion of fibrinogen to fibrin
Thrombin
What do damaged cells release to initiate hemostasis
Histamine
Serotonin
Catecholamines
3 “stages” platelets go through during hemostasis
1) Aggregation
2) Platelet plug
3) Fibrin clot
What happens to the blood vessels during hemostasis? (Vasoconstriction vs vasodilation)
Initially: Vasoconstriction to stop bleeding
Later: Vasodilation to recruit WBC
Platelet activation pathway
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
Contents of Dense Granules (Platelets)
1) Serotonin
2) ADP
3) ATP
Induce aggregation of platelets
*Construction and adherence
Contents of Alpha Granules (Platelets)
1) Fibrinogen
2) Fibronectin
3) PDGF
4) P-selectin
*Fibrin clot factors
*Chemokines for neut/mac/fibroblasts
More important thing STORED in platelets, functions
TGF B
Activates neut/mac
Stimulates fibroblasts to myofibroblasts
Cells that stores TGF B
Platelets
Factors involved in LYSIS of fibrin clot (4)
1) Plasminogen activator (initiates lysis)
2) Antithrombin III
3) Protein C (factor 5, 8)
4) Prostacyclin C (limit platelet aggregation)
Timeframe for neutrophils to come to wound
Minutes to 72hr
Adhesion molecules involved in neutrophils ROLLING
Selectins
Which Selectins on which cell types?
P selectin- platelets
E selectins - endothelial cell
L selectin- leukocytes
Adhesion molecules involved in neutrophil ADHESION/activation
Integrins (ICAM, VCAM)
hold neutrophils TIGHTLY
What binds to ICAM on endothelial cells
LFA-1 on neutrophil
What binds to VCAM on endothelial cells
VLA on neutrophil
Which adhesion molecules allow diapedesis? (3)
1) PECAM1
2) JAM-1 (tight junctions)
3) VE-cadherin (adherens junctions)
When do macrophages enter wound healing site?
24-48hr
Which TYPE of macrophage is involved in wound healing?
M2
What are M1 macrophages
Phagocytize bacteria + neuts, induce inflammation, scavenge debris
Stimulated by TNF alpha
TNFalpha will induce which TYPE of macrophage
M1
What are M2 macrophages
Repair, help with wound healing. Suppress immune system
Stimualted by TGF Beta
TGF B will induce which TYPE of macrophage
M2
Time frame of REPAIR phase of wound healing
2-10d
4 “steps” of Repair Phase
1) Granulation tissue formation (3-4d)
2) Fibroplasia, wound contraction (triggered by hypoxia. Fibroblasts respond to TGF-B)
3) Angiogenesis
4) Re-epithelialization
What stimulates fibroblasts to turn into myofibroblasts for wound contracture
TGF B
PDGF
Increases collagen integrin receptor alpha-2 expression
Type of Collagen INITIALLY in wound healing, granulation tissue
Collagen 3, less strong
Type of Collagen in MATURE wound healing, remodeling phase
Collagen 1, stronger
Type of collagen in vessels and hypertrophic scars
Collagen 5
Most abundant type of collagen in basement membrane
Collagen 4
When does wound contraction peak?
2 weeks
What type of collagen is present in scar tissue
Collagen 1