Wound Healing Flashcards
Describe the difference between autocrine and paracrine signaling.
Autocrine is the production of signaling molecules by a specific cell and the molecules act only on that cell type. Paracrine molecules act on a range of cells.
Name 4 functions of neutrophils in the wound.
Killing of bacteria with reactive oxygen species, phagocytosis of bacteria, release of additional cytokines, breakdown of extracellular matrix via proteolytic enzymes.
Neutrophil killing of bacteria within the wound is dependent upon what?
High partial pressure of oxygen (40mmHg)
After approximately 48 to 96 hours after wounding, what is the primary leukocyte in the wound?
Macrophage
Name 4 cytokines and 4 growth factors released by Macrophages
AND 4 enzymes!
IL-1,6,8,TNF-alpha and FGF, EGF, TGF-beta, PDGF; MMP1, 2, 3, and 9
What’s the predominant cell type in the proliferative phase?
Fibroblast
The proliferation phase from day____ to day _____.
4-12
Wound contraction is a function of transforming ___________ into ________________ in response to signaling from ________________.
Fibroblasts , myofibroblasts, TGF-beta
Grossly, the proliferative phase of healing is characterized by the development of ____________.
Granulation tissue
During the maturation phase of healing, the early granulation tissue is composed of primarily type ____collagen and as the phase continues and tension is applied to the wound the type of collagen switches to the more robust type ____.
III,I
The mucosa of the GI is composed of three layers. Name them
Epithelium, lamina propria, and muscularis mucosa
The esophagus does not have a serosal layer. Instead it’s outer layer is called the __________.
Adventitia
The submucosa is composed of what three types of collagen? Which type predominates and provides the majority of the tensile strength?
I, III, V and type I (68%)
Intra-abdominal sepsis can be responsible for the increased production of _____________which will result in the increased breakdown of mature collagen and the decreased production of new collagen.
Collagenase.
How does fascial healing times compare to skin healing times?
2x’s
Bladder regains 100% of its unwounded strength in _____days
21
4 Steps of wound healing
3 Stages: Inflammation, Proliferation, and Maturation. 4 steps: 1-Formation of a fibrin-platelet clot. 2-Recruitment of WBCs. 3-Neovascularization and cellular proliferation. 4-Tissue remodeling
3 phases of wound healing
inflammation, proliferation, maturation
3 classifications of burns and what separates them?
Partial (subdivided into -superficial partial (only epidermal) and -deep partial (epidermal and partial dermal)
& full thickeness
With respect to contamination and time, What is the threshold for developing an infection?
10 to 5th (10^5) colony-forming units per gram of tissue has long been considered the threshold for developing an infection with the time frame of this occurring in 6 hours or more
How many classes of wounds are there? And what are they?
Class I: 0-6 hrs old, minimal contamination and tissue trauma
Class II: 6-12 hrs old, microbial burden may not have reached a critical level
Class III: > 12 hrs old, microbial replication may have reached the critical level consistent with the development of an infection
Types of wound closure?
Primary (1st intention)
Delayed primary
2nd intention (healing by contraction and epithelialization)
Secondary closure ("3rd intention")Characteristics of Primary wound closure
Wound edges are apposed and allowed to heal with minimal gap with sutures, tissue glue, staples, a bandage or application of a graft soon after injury.
Class I wounds are considered amenable to primary closure. Class II wounds can be closed primarily if wound contamination/tissue trauma is minimal.
Characteristics of delayed primary closure
Appositional closure 3-5 days after wounding but before granulation tissue has been produced in the wound bed.
Indicated for mildy contaminated, minimally traumatized wounds that require some cleansing, debridement, and open management prior to closure.
Class II wounds
Characteristics of 2nd intention healing
Wound is left to heal through contraction and epithelialization. Drawbacks - New epithelium is fragile and easily abraded, wound contraction can be excessive, or wounds may fail to completely reepithelialize, leaving exposed or proliferative granulation tissue in the center of the wound. Indicated for dirty, contaminated, traumatized wounds in which cleansing and debridement is necessary but primary or delayed closure is prohibited.
Burn wound: 3 concentric zones?
Zone of destruction or coagulation; Zone of stasis; zone of hyperemia
A __________ area separates completely devitalized tissue from undamaged tissue
transition area
Zone of destruction or coagulation?
Excessive heat results in denaturation of cellular proteins and coagulation of blood vessels; Zone closest to heat source; Irreversible damage
Zone of stasis?
reduced blood flow and intravascular sludging; potentially reversible; further damage from hypoperfusion, edema, hypoxia, or infection can convert marginal tissues to nonviable tissue; Some vessels completely thrombosed→Thromboxane A2 produced → further vasoconstriction
Zone of hyperemia?
minimal tissue damage, complete healing follows; Zone is peripheral to and deep to the zone of stasis.
Burn wound: loss of proteins into the extracellular space is the greatest in the first __ to __ hours.
8-12
In dogs, partial-thickness burns of 20% of BSA resulted in __% loss of plasma volume in 1st 6 hours
28%
Carbon monoxide poisoning: CO has ___ to ___ times the affinity of hemoglobin than oxygen (Displaces oxygen from Hg → hypoxia)
210-240
Thermal burns: Cardiac Output decreases soon after injury. 50% scalding burn causes a __ % to __ % decrease in CO within minutes. Then a __ % to __ % further decrease during the first hour
40-50%-minutes
10-20%- within first hour
Decreased cardiac output is due to what?
peripheral vascular responses and direct myocardial effects
direct myocardial effects; Note that previous literature talks about myocardial depressant factor. Tobias does not mention MDF. Tobias talks about…..
increased Ca++ and Na+ in cytoplasm of the cardiac myocytes. See p 1294
I would know both just in case.
Decreased wound healing with steroids can be inhibited by _______.
Vitamin A
What is chalone?
???
Wound healing: What do platelets produce?
PDGF, TGF-beta, EGF, thromboxane A2, serotonin, leukotrienes, PG’s, histamine, kinins
Wound healing: What do macrophages produce?
IL-1, 6, and 8; TNF-alpha; EGF, FGF, TGF-beta, PDGF, IGF-1; MMP 1, 2, 3, and 9
Wound healing: What do endothelial cells produce?
PDGF, FGF, TGF, and endothelin (Endothelin causes vasoconstriction)
Wound healing: What do fibroblasts produce?
Type III Colagen, GAG’s, and fibronectin, FGF-1 and 2, IGF-1
Proliferation phase of wound healing predominant cells?
Fibroblasts, endothelial cells and epithelial cells
Proliferation Phase: What 3 main things are happening?
1-capillary ingrowth (VEGF), 2-wound contraction, 3-collagen production
Proliferation Phase: When does TGF-beta peak? What does it do? (at least 2)
TGF-beta peaks at day 7-14; increases synthesis of Type I collagen and stimulates conversion of fibroblasts to myofibroblasts
Maturation phase: Granulation tissue composed of __% Type III collagen? compared to ultimate scar, which will be __ % type III collagen.
30% to 10% type III collagen
PSIS vs. control effects on wounds paper
Schallberger etal. Effect of porcine small intestine submucosa on acute full thickness wounds in dogs. VetSurg 2008
PSIS increased acute inflammation, slower contraction, and decreased epithelialization
Rochat paper? Duraprep vs. Povidone Iodine?
duraprep equally effective? check paper
Mitsui A. etal. Effects of fascial abrasion, fasciotomy, and fascial excision, on cutaneous wound healing in cats. AJVR 2009
Time to appearance of granulation tissue and coverage of wound base w gran tissue was shorter for tx group.
No diff with regard to epithelialization and contraction
Name 4 non-enzymatic debridement dressings and their
effect on micro-organisms?
effect on wound?
Hypertonic saline (20%), sugar, honey, dextran-soaked Effect on micro-orgs: Hypertonic nature of dressings = dehydration of micro-orgs, cidal and inhibitory effect on their growth Effect on wound: draws exudate and debris out of the wound and can reduce surrounding adema
When do you want to use a non-enzymatic debridement dressing?
inflammatory and early repair.
According to Tobias what is considered the std of care for open wound mgt?
Fostering a moist wound environment to facilitate debridement, granulation tissue formation, and epithelialization.
What is the underlying principle of moist wound healing
Application of hydrophilic dressings
Good bandage choice for a -
dry to minimally exudative wound
Hydrogel.
How does burn wound fluid differ from normal surgical wound fluid with respect to healing cytokines?
Burn wound fluid has less than 5% of normal levels of FGF-2 and none of the capillary endothelial chemotactic and proliferative activity seen in normal surgical wounds
3 toxic effects of carbon monoxide
1) decreases Hgb O2 carrying capacity by preferentially binding to Hgb
2) that results in a left shift of oxyHgb dissociation curve = decreased O2 delivery at tissues
3) reduced O2 availability to muscle by binding w myoglobin
How do cats differ from dogs with respect to blood supply to the skin?
Cats have lower density of collateral subcutaneous tissues
and a smaller number with a wider distribution of perforators
Wound strengths of sutured incision as a % of normal skin (in dogs) at 14 days _____, 3-4 weeks _______, and ultimate strength______
5-10%, 25% and 70-80%
How do cats differ from dogs with respect to skin perfusion following wounding?
Lower skin perfusion in the first 7 days but then higher in the following 7 days to equilibrate by day 14
How do cats differ from dogs with respect to wound strength at 1 week post op
Significantly lower wound breaking strength
