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WOUND HEALING
© UST Medicine
CHRONIC WOUNDS
• does not proceed to a restoration of functional integrity • initial intense local vasoconstriction of arterioles and
• prolonged due to inflammatory phase capillaries vasodilation and increased vascular
• does not proceed to closure permeability
I. INFLAMMATORY PHASE
• activated platelets membrane phospholipids bind
clotting factor V interaction with clotting factor X
A. Hemostasis and Inflammation membrane-bound prothrombinase activity
• represents tissue's attempt to limit damage by: thrombin production
Growth Factors
MAJOR EFFECT
• Stimulate fibroblast, endothelial cell and keratinocyte proliferation (important in Proliferative Stage)
CYTOKINE
SOURCE FUNCTIONS
(Growth Factors)
Chemotactic for PMNs, macrophages, fibroblasts and smooth
Platelets, macrophages,
Platelet-derived growth muscle cells; Activates PMNs, macrophages and fibroblasts;
endothelial cells,
factor mitogenic for fibroblasts, endothelial cells; stimulates angiogenesis
keratinocytes
and wound contraction; remodelling
Platelets, T lymphocytes, Chemotactic for PMNs, macrophages, lymphocytes, fibroblasts;
Transforming growth factor- macrophages, endothelial stimulates TIMP synthesis, keratinocyte migration, angiogenesis,
beta cells, keratinocytes, and fibroplasias; inhibits production of MMPs and keratinocyte
fibroblasts proliferation; induces TGF-β production
Mitogenic for keratinocytes and fibroblasts; stimulates keratinocyte
Epidermal growth factor Platelets, macrophages
migration
Keratinocyte growth factor Fibroblasts Stimulates keratinocyte migration, proliferation and differentiation
2 types: 3. IL-4
→ fibroblast proliferation, collagen synthesis
T- lymphocytes
-appear in significant numbers (5th day) Inhibitory cytokines
-peak occurrence( 7th day ) 1. TGF-β (Transforming Growth Factor – beta)
→ inhibits keratinocyte proliferation (but
B- lymphocytes chemotactic to fibroblasts and causes
- no significant role in wound healing fibroplasia)
Fibroblasts 2. IFN-γ
- cells that makes the structural fibers and ground → retards and suppresses collagen synthesis and
substance of connective tissue. cross-linking ( collagenase
activity)
Keratinocyte
-the major cell type of the epidermis, making up about II. PROLIFERATIVE PHASE
90% of epidermal cells.
characterized by the formation of granulation tissue which
consists of:
T-lymphocytes’ effect is the production of: • capillary bed
• fibroblasts
Stimulatory cytokines • macrophages
1. IL-2
SURGERY WOUND HEALING Wound Manipulation 3
• loose arrangement of collagen capillary maturation
• fibronectin
• hyaluronic
Refer to the diagram below:
• acid
• Following injury, the endothelium is exposed to
1. ANGIOGENESIS soluble factors and comes in contact with RBC.
process of new blood vessel formation which is necessary • This results in the upregulation of the expression of
to support a healing wound environment cell surface adhesion molecules such as vascular cell
surface adhesion molecule (VCAM-1). Matrix
overview: degrading enzymes are also released and activated,
Injury degrading the endothelial basement membrane.
↓activated endothelial cells • Fragmentation of the basement membrane allows
degradation of basement membrane of postcapillary venules endothelial cell migration to the wound and this is
↓ promoted by fibroblast growth factor (FGF), platelet
migration of cells derived growth factor (PDGF) and TGF-β.
↓division • Integrinαvβ3 – facilitates endothelial cell migration to the
tubule or lumen formation wound
↓ • PECAM-1 – modulates their interaction as they
deposition of basement membrane migrate to the wound
↓
A f te r in j u r y :
e n d o t h e l i u m e x p o s e d t o s o l u b le f a c t o r s a n d R B C
V C A M -1 m a t r i x - d e g r a d i n g e n z y m e s ( p l a s m i n , m e t a l lo p r o t e i n a s e s )
d e g ra d e s b a s e m e n t m e m b ra n e
F G F , P D G F , T G F -B
in te g r in
P E C A M -1
e n d o th e li a l c e ll m i g r a ti o n t o t h e w o u n d
• Attachment proteins (Fibrin and fibronectin) provide attachment to ECM by binding to cell surface integrin receptors
Collagen
• Found in all multicellular proteins • Type I
• Long, stiff triple-stranded helix composed of 3 – Fibrin-forming collagen
collagen polypeptide alpha chain – forms superhelix – Secreted into ECM Collagen Fibrils
• Proline and Glycine-rich Collagen Fibers
– Pro – provides stability
– Gly – allows tight packing • Other types:
• Main constituents of CT are – Type I, II, III, V, XI – Type IX & XII – fibril-associated collagens;
– Type I – most common; skin and bones found on surfaces of fibril to connect them to
– Type III – increased expression in early one another and to the ECM
wound healing – Type IV & VII – network-forming
GAG’S AND PROTEOGLYCANS •Function: mediated by both their core proteins and GAG
chains.
Glycosaminoglycans •GAGs sulfonation
Enter as Pro-alpha chains with Amino-terminal signal peptides and Propetides at N & C-terminal ends
Amino-terminal signal direct Pro-alpha chains towards ER
Collagen Fibrils
Therapeutic Intervention
structurally related enzymes that can
▫ Antagonist of TGF-B and receptor degrade ECM components
▫ Inhibition of collagen and ECM synthesis differentiated by their substrate specificity
▫ Cell cycle inhibitor degrade the adhesive substrates for cell
▫ IFN-y – supress collagen synthesis migration and signaling molecules (GF &
cytokines)
CHRONIC WOUNDS
- irregular
Development to squamous cell carcinoma in - raised above the surface
- chronic burn scars - white, pearly discoloration
- Osteomyelitis
- Pressure sores Pseudoepitheliomatous hyperplasia pre malignant state
- Venous stasis ulcer if this is
- Hidradenitis reported on biopsy, the biopsy should be
repeated because there may be squamous
Wounds appear cell carcinoma present in other areas
DRUGS
*alcayde Diabetes
Wound Infection
Diabetic patients are prone to:
Intact epithelium- prevents the bacterial contaminants •Tissue ischemia
normally present in the skin to gain entry into deep tissues •Repetitive trauma
•Infection
Antibiotic prophylaxis- most effective when adequate conc.
are present during time of incision Lymphocyte & Leukocyte function are impaired-
increases collagen degradation and decrease collagen
Repeated Dosing- essential in decreasing postoperative deposition
wound
Ionizing Radiation
Additional dose of Antibiotics-given for 24 hrs
postoperatively in lengthy cases with prosthetic implants Endothelial Cell Injury causing atrophy, fibrosis and delayed
tissue repair
AGING
Bacterial count >105/g tissue or if a B-hemolytic strep
are present- wound will not heal by any means including flap Elderly patients
closures, skin graft replacement nor primary sutures
• Surgical wound rupture
Most common organisms responsible for wound infections • Delayed healing
are (in decreasing order): • Slower healing
• Collagen: qualitative and quantitative
Staph. Aureus changes
Coagulase (-) Strep • Dermal collagen content decreases
Enterococci • Aging collagen: distorted architecture and
E.coli
organization
Contamination- presence of bacteria w/o multiplication • Reduced re-epithelialization, decreased
collagen synthesis, impaired angiogenesis
Colonization-multiplication w/o host response • Decreased Multiple growth factors
including factors FGF-2 and VEGF
Infection-presence of host response in reaction to deposition
and multiplication
• Altered early inflammatory period –
impaired macrophage activity, decreased
phagocytosis and delayed infiltration of