Ch.5 Wound Healing Flashcards
Which wounds are clean, clean contaminated, contaminated and dirty
Clean - created under aseptic conditions
<1 x 10^5 (100,000) bacteria/g tissue
Clean contaminated - Surgical wounds of respiratory/ailimentay/urogenital entered under controlled conditions w/o min contamination
<1 x 10^5 (100,000) bacteria/g tissue
Contaminated - open, acute, accidental, major break in aseptic technique
>1 x 10^5 (100,000) bacteria/g tissue
Dirty - old, devitalized tissue, gross contamination, foreign debris
Describe the 3 classes of wounds
Class 1 <6hrs duration w min contamination
Class 2 6-12hrs duration w significant contamination
Class 3 >12hrs duration w gross contamination
What are the phases of the healing process?
1 - Inflammatory or lag phase - hemostasis and acute inflam
2 - Proliferative phase - tissue formation
3 - Remodeling phase - healing tissue regains strength
When is a delayed primary closure performed
Clean contaminated w edema/questionable tissue viability
2 - 5 days after injury
When is a secondary closure performed
Contaminated or infected wound
At least 5 days after injury
What are the functions of PMN (polymorphonuclear cells) in tissue repair
- Phagocytosis of microbes
- Macrophage activation
- Amplify inflammatory response
- Stimulate repair process
- Mediators - reactive oxygen species, cationic peptides, eicosanoids, proteases
TNF Alpha
IL-1Beta IL-6
VEGF, IL-8
What are the functions of macrophage in tissue repair
- Phagocytosis of PMN, damaged tissue and microbes
- Amplify repair process
- Stimulate angiogenesis and fibroplasia
Fibrolysis
What is the early wound clot known as
Provisional wound matrix
Activated platelets within the provisional wound matrix direct and amplify the early inflammatory phase of healing through the release of what
Wound repair mediators most importantly
1) PDGF - Platelet derived growth factor
2) TGF-Beta - Tissue growth factor Beta
What activates Leukocyte migration into the wound?
- Exposed collagen
- Elastin breakdown products
- Complement factors
- Cytokines
- Changes in mechanical tension
What are the first cells to enter the wound in large numbers and are the hallmark of acute skin injury
PMNs polymorphonuclear cells
On what day do PMN polymorphonuclear cells numbers peak
Day 2 and decline as debris is cleared from the site
What are the roles of the neutrophils in the wound
- Remove damaged tissue and bacteria by phagocytosis
- Release chemoattractant to further augment the early cellular inflammatory response
At what stage after injury do circulating monocytes enter the wound and differentiate into macrophages
24 hours
What proteinases are released by the macrophages in the wound
Elastase
Collagenase
Plasminogen activator
What initiates the proliferative phase of wound repair
Tissue growth factors released by macrophages
After how long is the proliferative phase of wound repair active
Day 3
What is the proliferative phase of wound repair characterised by
- Angiogenesis
- Fibrous and granulation tissue formation
- Collagen deposition
- Epithelialization
- Wound contraction
What initiates the process of angiogenesis
Decreased oxygen tension
High lactate levels
Low pH
The endothelial cells at the tips of capillaries adjacent to the wound grow at what rate
0.4 - 1.0 mm/day
What growth factors play a significant role in neovascularization?
VEGF - Vascular Endothelial Growth Factor
bFGF - basic Fibroblast Growth Factors
What do MMPs (matrix metalloproteinases) do?
Reduce migration and proliferation of endothelial cells
When do fibroblasts arrive in the wound
Day 2
What are the major cell type in the wound bed by day 4
Fibroblasts
On what day does the fibroblast number peak
7-14 days
What regulates fibroblast migration and proliferation
PDGF - platelet derived growth factor
TGF-Beta - transforming growth factor
bFGE - basic fibroblast growth factor
What do fibroblasts synthesise and release
1.Collagen
- Glycosaminoglycans - hyaluronan
- Glycoproteins - fibronectin and laminin
- Elastin
- Proteoglycans
- Proteases including MMPs (matrix metalloproteinases)
When does collagen production begin in a wound
Day 2-3
When does collagen production reach peak production
1-3 weeks
Which type of collagen do wound fibroblasts produce
Type 1 collagen
30-40% of collagen found in the acute wound will be what type of collagen
Type III
Why is the relationship between keratinocytes and fibroblasts important
Keratinocytes stimulate fibroblasts to synthesize and release growth factors and cytokines which in turn stimulate keratinocyte proliferation
How do keratinocytes clear a path across the wound surface
They synthesize and release collagenases, MMPs and plasminogen activator
How long before new epidermis is evident at the wound edges
4-5 days
How does new epidermis differ from that found in uninjured skin
It lacks retepegs which anchor it to the underlying connective tissue matrix
In full thickness wounds it lacks a dermal layer without which there is a loss in tissue strength and elasticity
When does contraction begin in full thickness wounds
2nd week following injury
How much does contraction reduce the wound surface in full thickness wounds
40-80%
What is the rate of contraction in areas with loose skin
0.75mm/day
What is responsible for fibroblasts to form myofibroblasts
TGF-B1 released from macrophages and keratinocytes
What signifies the change from fibroblast to myofibroblast
Acquisition of an alpha smooth muscle actin microfilament system
Function of the actin microfilament system
Wound contraction
How does scar tissue strength compare to original tissue strength
15 - 20% weaker
What does the remodelling and maturation phase begin with
Begins with the replacement of Hyaluronan in provisional matrix by proteoglycans in the ECM
when does the remodelling and maturation phase begin and end
Begins 2 weeks after injury - continues for 1-2 years
What is the strength of scar tissue at 3 weeks vs original tissue
20%
At what stage is scar tissue 50% of original tissue strength
3 months
What % of wounds closed by primary intention are thought to dehisce
59-74%
How does wound healing in horses differ greatly from other species
Marked diff btw species ie horse vs pony
Varied healing rate depending on location
Exuberant granulation tissue
How does wound healing in ponies differ from horses
Faster
More intense inflammatory response - less infection
Myofibroblasts are organised and orientated parallel to the wound surface for optimal healing at 2 weeks
Less bone proliferation
In exp study 7-9 week repair in pony vs 12 in horse
What is the reported rate of re-epithelialization in distal limb wounds in horses
0.09mm/day
What is the reported rate of contraction in distal limb wounds in horses vs body
Distal limb .2mm/day
Body 0.8 - 1mm/day
Contamination with how many microorganisms in the presence of soil can result in infection
100
What are the most common wound isolates
Pseudomonas aeruginosa
Staphylococcus spp
What is believed to be the cause of exuberant granulation tissue in horses
PMNs stay higher in horses for a longer period of time resulting in chronic inflammation - imbalance of mediators released from PMNs - tumour necrosis factor alpha, IL-1, IL-6, PDGF, TGF-B and bFGE contributes to profibrotic state.
TGF-B1 enhances migration and proliferation of fibroblasts and subsequent collagen production and delays fibroblast apoptosis
Why more excessive granulation tissue in distal limb
Tissue hypoxia as a result of microvascular occlusion of the small capillaries within the granulation tissue found to be 3 times higher in distal limb
Potentially bandaging - lowers cutaneous temp due to dc blood flow - stimulates angiogenesis and wound debris on bandage provides constant source of inflammatory mediators.
Wound dressing guidelines
Occlusive dressing in clean wounds until healthy bed of granulation tissue develops then switch to semi occlusive
Dirty wounds - adherent hydrophilic or antimicrobial dressings until healthy granulation tissue forms then switch to semi-occlusive
Effect of shockwave on distal limb wounds
Decreases TGF-B1
How does protein deficiency delay wound healing
Suppresses fibroblast proliferation, angiogenesis, collagen synthesis and remodelling
Role of Vit E in wound healing
Antioxidant
Augments antimicrobial action against MRSA
Role of B Vitamins in wound healing
Important cofactors in collagen cross linking reactions
How should fluids be applied to a wound for debridement
At an oblique angle
Pressure of 7-15lbs per square inch
1L bag - pressurised to 300mmHg - 16-22G needle
How is autolytic debridement achieved
Placing an occlusive dressing over the wound, trapping the body’s own proteases within the wound to liquefy necrotic tissue
What are the ingredients in Granulex used for chemical debridement
Trypsin
Peruvian balsam
Castor oil
Which fly larvae are used in maggot debridement
Lucilia sericata
How much necrotic tissue can maggot consume per day
75mg
Suture tension above what pressure leads to tissue necrosis
> 30-40mmHg (above capillary pressure)
How dilute should chlorohex be to use on wound
0.05%
Add 25ml of 2% chlorohex to 975ml saline
How dilute should povidone-iodine be to use on wound
0.1-0.2%
10-20ml of 10% Pov-Iod to 980/990ml saline
What % hydrogen peroxide is toxic to fibroblasts
3% but 1%cream - faster healing
What additional benefits does SSD possess over triple abx
Effective against pseudomonas and fungi
Draw backs of nitrofurazone
Decrease epithelialisation
Decrease wound contraction
Carcinogenic
Benefits of honey on wound healing
Efficacious against 10 common pathogens inc MRSA
Decrease distal limb wound retraction
Improves wound healing up to day 21
Which growth factor has been approved for topical use
PDGF -Platelet derived growth factor
What does PRP contribute to wound healing
Rich in:
TGF-B
PDGF -platelet derived growth factor
Epidermal growth factor
Transforming growth factor alpha
VEGF - vascular endothelial growth factor
Serotonin
Histamine
Secrete:
fibrin,
fibronectin
vitronectin which act as a matrix providing a surface for epithelial migration
Benefit of using Acemannan
Active ingredient of aloe vera
accelerates the production of granulation tissue over exposed bone
What proregenerative cytokines are secreted from stem cells
VEGF, EGF, KGF, IGE