Chapter 9 Wound Healing Flashcards
What are the 7 main cellular components of wound healing?
- Platelets
- Neutrophils
- Macrophages
- Endothelial cells
- Fibroblasts
- Myofibroblasts
- Keratinocytes
(+ lymphocytes)
What are the three phases of wound healing?
- Inflammatory
- Proliferative
- Maturation
What are the three main types of signalling molecule?
- Growth factors (=proteins that bind to cell surface receptors with primary result being activation of cellular proliferation/differentiation)
- Cytokines (=small signalling proteins that have growth, differentiation and activation functions. Secreted primarily by leukocytes)
- Chemokines (=subset of cytokines with mainly chemotactic function. *Chemotactic = movement in response to chemical stimulus)
What is early extracellular matrix vs late ECM composed of?
Fibrin initially –> collagen later
Phases of wound healing are broken down into inflammatory, proliferative and maturation. How is inflammatory further sub-divided?
- Haemostasis: reflex vasoconstriction can prevent haemorrgahe from arterioles up to 5mm in diameter. Platelets + coagulation cascade activated. Thomboxane from platelet = powerful vasoconstrictor. Neutrophils, macrophages endothelial cells and fibroblasts attracted.
- Early inflammatory: Establishes immune barrier. Serotonin + histamine –> vasodilation & increased permeability –> extravasation of plasma + leukocyte migration. 24-48 hours.
- Late inflammatory: Establishes macrophages –> debridement + cytokines. Clinically characterised by erythema and oedema. 3-5d after injury
By which time point have macrophages usually become predominant leukocyte in wound?
2-5d
List 4 funtions that neutrophils in a wound
- Killing bacteria (release reactive oxygen species. Dependent of high PO2 - inhibited if PO2 <40 mmHg. )
- Breakdown ECM (release proteloytic enzymes)
- Phagocytosis of debris
- Release of cytokines to prolong inflammatory phase
When does the proliferative phase typically occur and how is it characterised?
4-12d
Angiogenesis, fibroplasia, contraction, epithelialisation. Appearance of granulation tissue
Predmoinant cell types: macrophages, fibroblasts, endothelial cells, epithelial cells
VEGF has potent angiogenic activity. By which cells in wound is it predominantly secreted?
Keratinocytes on wound edge.
Quiscent mesenchymal stem cells differentiate into fibroblasts 3-5d after wounding and begin synthesysing major comonents of definitve ECM - what are definitive componend to ECM.
What proportions of these are present in unwounded dermis, vs in wounded dermis?
(Pro-) collagen I and III
Unwounded dermis = 80% type I collagen, 20% type III.
In healing wound, type III collagen predominates (after maturation final scar contains around 10% type III)
Which signalling molecule is responible for transformation of fibroblasts to myofibroblasts?
Transforming Growth Factor ß (TGF-ß)
Myofibroblasts –> increased alpha-smooth muscle actin (day 6 after wounding). Orientate linearly along lines of tension + attach to ECM –> wound contraction.
Which molecule type is predominantly responisble to ECM breakdown?
Matrix metalloproteinases
How long does it take for strenght of healing skin wound to plateau?
At what % unwounded strenght does healed tissue plateau?
12-18 months
Approx 70-80%
What proportion of various collagens is present in GI submucosa?
68% Type I
20% Type III
12% Type V
How long does it take for bladder mucosa to re-epithelialise?
How long does it take a bladder wound to reach near original strength?
2-4 days
3 weeks
In the GI tract, which cells predominantly produce collagen?
Smooth muscle cells (vs fibroblasts in skin)
What is responisble for reduced GI wound strenght around 2d post-op?
Collagenase. (N.B. activity increased during sepsis)
List ways that GI wound healing differs from skin
- Increased intraluminal pressure during peristalisis –> shear forces.
- Polymicrobial, aerobic and anaerobic GI flora. Cant reduce by cleaning unlike skin
- Vascular perfusion more sensitive e.g. during shock (hypotension identified as associated with spetic peritonitis and death)
How big a drop in pcv can be tolerated (i.e. GI wound healing not affected) if cardiac output maintained?
15% below normal PCV
What are the three prinicples re fascial healing on which a consensus has been reached?
- Faliure often due to early, high mechanical force.
- Healing optimized by using continuous non-/slowly absorbable monofilament
- Sutures placed >3mm from edge, outside active zone of inflammation.
BMPs part of TGF-ß family. How do BMPs work?
Stimulate undifferentiated mesenchymal stem cells in periosteum, marrow, endosteum and surrounding muscle to become chondroblasts and osteoprogenitor cells.
How long does the maturation phase of bone last?
>1 year
In experimental study, how ong did it take for granulation tissue to appear in dog vs cat?
And time until complete granualtion tissue bed?
Dog 4.5 days
Cat 6.3 days
Dog 7.5d
Cat 19d
What hormones have been implicated in negatively impacting wound healing?
Androgens
List 6 local factors and 3 systemic factors that influence wound healing:
- Wound perfusion
- Tissue viability
- Wound fluid accumulation
- Wound infection
- Mechanical factors
- Envenomation
- Impaired immune function (endocrinopathy, steroids, ?blood transfusion etc)
- Cancer
- Age
