Lec4 Would Healing and Repair Flashcards
Regeneration vs Healing
Regeneration: restore lost tissues
- occurs with superficial wounds, some inflammatory process, intact tissue framework
- ex. liver regeneration, superficial skin wound, resorption exudate in pneumonia
Healing: restore original structure but collagen formation and scar formation
- occurs with damaged tissue framework, deep wounds
- ex. deep excisional wound, MI
Fibrosis
Tissue scar formation when persistent tissue damage
- ex. chronic inflammatory disease - cirrhosis, chronic pancreatitis, pulmonary fibrosis
Early state of healing
- 0-3 days
- thrombosis
- inflammation [neutrophils + macrophages]
- re-epithelialization [this new epidermis above scar]
in order:
0-4 hrs: fibrin clot forms
1-3 days: phagocytosis
1-4 days: chemoattraction and migration of inflammatory cells to wound
fibronectin
in early wound healing:
- helps fibroblasts bind fibrin to form fibrin clot
- promotes phagocytosis
Migration in wound healing
- occurs days 1-4
- monocytes [macrophages, neutrophils] are recruited and adhere to site of injury
- produce cytokines including: PDGF [platelet derived growth factor] and TGF-B
- — stimulate proliferation + migration + matrix production
What is PDGF?
- Platelet derived growth factor
- mitogenic cytokine
- released by platelets and endothelial cells
- mitogen for formation of fibroblasts, smooth muscle, connective tissue
- part of early wound repair?
What is FGF?
- Fibroblast growth factor
- mitogenic cytokine
- has many types and isoforms
- produced by macrophages and fibroblasts
- stimulates fibroblast proliferation and new vessel growth
4 Markers of Organizing wound??
Organizing = wound undergoing repair
- secondary change in thrombus
- dissolution of clot
- formation new vessels
- deposition of stroma
Mid State of Wound Healing
1-10 days
- early formation new collagen III matrix, dissolution of clot and phagocytosis [2-4 days]
- More collagen III and matrix molec [2-5 days]
- Granulation tissue
Granulation tissue
- part of mid stage of wound healing
- components
- – macrophages, myofibroblasts, fibroblasts, capillaries
- angiongenesis via canalization and connection of capillaries
2 mitogenic cytokines
PDGF - platelet derived growth factor
FGF - fibroblast growth factor
2 Fibrogenic cytokines
TGF-B [transforming growth factor -B]
IL-4 [interleukin-4]
What is TGF-B?
- fibrogenic cytokine
- secreted by lymphocytes, macrophages, platelets
- chemoattractant for inflammatory cells
- inhibits inflammatory response
What is IL-4?
- fibrogenic cytokine
- effects many cell types [B and T]
- modulates inflammatory response [TH2]
- essential in fibrosis along with TGF-B
What is VEGF?
- angiogenic cytokine
- vascular endothelial growth factor
- promotes growth of blood vessels
- binds receptors on endothelial cells
What is EGF?
- epithelial proliferation cytokine
- produced by keratinocytes and macrophages
- promotes epidermal migration and proliferation
Metalloproteinases
- aid in remodeling extracellular matrix activation and inhibition
Late stage of wound healing
3-30 days and more
- formation of definitive collagen I matrix
Content of extracellular matrix
- collagens I, III, IV
- glycosaminoglycans
- elastin
- microfibrils
- fibronectin
- integrins
Myofibroblast
- expresses antigens of smooth muscle
- responds to agents that contract smooth muscle
- responsible for wound contraction
Wound strength
Elastic fibers are not replaced in scar tissue
- after 1 wk: 10% strength
- after 2 months: 50% strength
- after 3 months: 70-80% strength
Re-epithelialization
- source is stem cells from hair follicle
- must reform protective barrier
- close wounds by migration or purse string
- differentiate again
- role of basement membrane
Mechanisms of re-epithelialization
- leap-frog method
- keratinocyte B leap frogs over keratinocyte A - train method
- keratinocyte A puls keratinocyte B and C
3 Types of proliferative cells
Labile: rapidly dividing
ex. epidermis, GI tract epithelium
Stable/quiescent: slowly dividing unless stimulus
- ex. liver
permanent: incapable of dividing
- ex. neurons, cardiac myocytes
stem cells
- cell capable of self-renewal and production of another cell for differentiated phenotype-assymetric replication
- embryonic + adult
Local factors influence wound healing
- type, size, location of wound
- adequacy blood supply
- presence infection
- exposure to ionizing radiation
- exposure to ultraviolet light
Systemic factors influence wound healing
- circulatory status [age]
- metabolic status
- presence infection, diabetes, neaplasia
- adequate levels Vic C, AA [met]
- hormones: corticoids, ACTH, estrogens, growth hormone
Complications of wound healing
- deficient scar formation: ulceration, dehiscence
- excessive scar formation: keloids, hypertrophic scar
- excessive contraction: contracture or cicatrisation
- excessive regeneration
- painful scar
- pigmentary change
Healing by primary vs secondary intention
primary intention: wounds with apposed edges
– approximation surgical wounds, minimal wound contraction, good esthetic result
secondary intention: wounds with separated edges
–non-approximation wound edges, massive contraction, poor esthetic resutl
would dehiscence
would ruptures along surgical suture
