Wound Healing Flashcards
Name 4 phases of wound healing (human articles + Dong, 2023, Lux 21)
1.Hemostasis/coagulation
2. inflammatory
3. Repair/proliferation/granulation and contraction
4. Remodeling and scar formation
How damaged keratinocytes end endothelium respond to an injury ?
-release vasoactive compounds- catecholamines, histamine, serotonin and PG
-create transient constriction= decrease blood flow from wound
+ and then vasodilatation=fluids and cells could pass from vessel and lymphatics to fill and clean the site of injury
Intrinsic blood clot results from?
1.surface activation of Hageman factor XII
2. Tissue procoagulant released from damaged cells
3. Coagulation factors expressed on activated platelets and endothelial cells
What does the fibrin clot contains?
-cross-linked fibronectin, activated factor XIII, fibrin
What is the function of fibronectin?
- allows binding of fibroblasts to ECM
-enhances fibroblast activity
When is the clot formation terminated ?
When the stimuli for the formation are removed / diluted from the system
What does the clot formation provides in wound healing process?
-scaffold for movement and organization of cells at the injury site
=fibrin, fibronectin, vitronectin =provisional Matrix (1. ECM that fills the wound )
-provides a pathway for the influx of monocytes, fibroblasts , and newly forming vessels
+ hemostasis
+barrier to micro-organisms
How is classical and alternative complement pathway activated?
By the initiation of coagulation cascade and activation of Hageman factor that create fragments of bradykinin (vasoactive agent)
What will activation of complement cascade result in ?
-release of C3a and C5a
-they will increase the blood vessel permeability
+ will attract neutrophils and monocytes at cite of injury
+they will release other vasoactive amines - histamine, LTC4, LTD4 (MC) and active oxygen products (from neutrophils and macrophages)
Function of platelets in wound healing
-platelets degranulate and release growth factor and cytokines
-They initiate wound healing process by leukocyte recruitment
-signal cellular movement for re-epithelialization, wound contraction and the angiogenic response
-cause vasoconstriction = by releasing serotonin, and forming thromboxane A2 (TXA2)
What substances does the platelet release?
-serotonin, thromboxane A2, adhesive proteins like fibrinogen, fibronectin, von Willebrand-factor VIII
What are the functions of thromboxane A2 (released from dense granules)?
-vasoconstriction
-amplifies platelet activation
+ additional platelet recruitment
What does the alpha granules of platelets release ?
-adhesive proteins like fibrinogen, von Willebrand’s factor, factor V
-it stimulates more platelet aggregation= platelet plug
Platelet activation, adhesion and aggregation are triggered by
Exposure at the wound site to thrombin and fibrillar collagen
Who limits the size of the clot to the size of defect?
Intact adjacent endothelial cells who provide factors: prostacyclin (PC) and anti-thrombin III
What does the prostacyclin do?
Inhibits platelet aggregation
How is clot lysis initiated?
By the release of plasminogen activator and convert plasminogen to plasmin
What are the chemoattractants for neutrophils in wound healing?
IL-8, Gro, kallikrein, fibrinogen degradation products (FDP), fibrinopeptides (from fibrin degradation) , cytokines (from activated platelets) and FORMYL METHIONYL PEPTIDES (cleaved from bacterial proteins)
Another name for apoptotic neutrophils
Effete
Which cells play a pivotal role in the transition between inflammation and repair
Monocytes/ macrophages
Name hallmark of the inflammatory phase (clinically)
Exudate, which can be septic or non septic
Acute- contains growth factors, leukocytes, chemotactic factors
Chronic- higher levels of damaging proteases
Purulent debris is composed of what ?
-wound fluid
-products by neutrophils-proteases, reactive and toxic oxygen species (degrade injured cells, denatured ECM, bacterial products)
-reflection of inflammatory process
Name 2 types of macrophages and their function?
M1-traditional, kill bacteria and scavenge debris
M2-suppress the immune system and aid in tissue repair
Name role of the macrophages during wound repair
- Phagocytosis and antimicrobial function
- Wound debridement
- Cell recruitment and activation
- Angiogenesis
- Matrix synthesis regulation