Wound Healing Flashcards
What are the 3 phases of wound healing?
1) inflammation
2) proliferation
3) maturation and remodeling
The inflammatory phase consists of 2 responses, what are they?
1) vascular
2) cellular
Immediately following injury, the body responds in 3 ways to try and control blood loss. What are they?
1) injured blood vessel walls allow transudate to leak out of the vessels and into the interstitial space causing edema
2) local blood vessels reflexively constrict for several minutes after injury to further reduce blood loss
3) platelets aggregate at the site of injury and are activated by contact with damaged endothelial cells lining vessel walls and exposed collagen
The exposed collagen activates the platelets to release what 3 chemical mediators? What does each do?
- Cytokines: signal proteins
- Growth factors: control cell growth, differentiation, and metabolism
- Chemotactic agents: attract cells for wound repair to the area
Within __ minutes of the initial vasoconstriction that occurs following injury blood vessels begin to vasodilate pushing more fluid into the interstitial space and allowing more growth factors and inflammatory cells to reach the injured area.
30
This mixture of fluid, proteins, and WBCs within the interstitial space is now called what?
exudate
The histamine that is released during the vascular response of the inflammatory phase acts to do what?
increase vessel wall permeability allowing for short term vasodilation
The prostaglandins that are released during the vascular response of the inflammatory phase acts to do what?
provide a more Long-term vasodilation
What are the 5 cardinal signs of inflammation?
- Swelling
- Redness
- Warmth
- Pain
- Decreased function
What is the Latin word for swelling?
tumor
What is the Latin word for redness?
rubor
What is the Latin word for warmth?
calor
What is the Latin word for pain?
dolor
What is the Latin word for decreased function?
functio laesa
Increased vessel wall leakiness causes a decrease in local blood volume which slows the flow of circulating WBCs traveling within the capillaries and arterioles. This is known as the _____ response.
cellular
What WBCs are the first to reach the site of injury?
Polymorphonuclear neutrophils (PMNs)
Describe the 3 step process by which PMNs reach the site of injury.
1) diapedesis
2) margination
3) chemotaxis
PMNs reach the site of injury within how long?
12-24 hours
Once present, PMNs secrete chemotactic agents and mediators of inflammation. What do these substances then do?
- attract more inflammatory cells to the injured area
- stimulate fibroblasts migration
- induce new vascular growth
What are the next cells to arrive after PMNs?
circulating monocytes, or macrophages once in the interstitium
What role do macrophages play in wound healing?
They signal the extent of the injury, attracting more inflammatory cells to the area as needed
Mast cells also help with wound healing during the cellular response, what role do they play?
They produce chemical mediators that attract and activate inflammatory cells
In healthy individuals it is possible for the proliferative phase of healing to begin within __ hours of injury
48
The proliferative phase consists of 4 crucial events, what are they?
1) angiogenesis
2) granulation tissue formation
3) wound contraction
4) epithelialization
Define angiogenesis
the formation of new blood vessels
What cells form the new blood vessels?
angioblasts
What do matrix metalloproteases (MMPs) do during granulation tissue formation?
they degrade the debris formed during the inflammatory phase leaving a defect that must be filled in order for healing to progress
What is granulation tissue?
a temporary latticework of vascularized connective tissue that fills the void left behind from the MMPs
What cells fill the spaces between the collagen and elastic fibers in the granulation tissue forming an extracellular matrix?
Fibroblasts
What does the extracellular matrix allow for?
Fibroblasts and other cells to advance across the wound bed by providing a scaffolding on which they can migrate
Surface cells receptors, called ______, help cells recognize and reversibly bind to the extracellular matrix allowing this migration
integrins
What eventually replaces granulation tissue?
scar tissue
Some fibroblasts within the wound bed are transformed in ______ which cause wound contraction
myofibroblasts
What type of wound contracts the fastest? Slowest?
linear wounds
circular wounds
Is wound contraction greater in full or partial thickness wounds? Why?
Full, due to the increased amount of granulation tissue formation required for deeper wounds
What type of cells reepithelialize the wound surface?
keratinocytes
Describe the process by which keratinocytes reepithelialize the wound
They elongate, extend pseudopods across the extracellular matrix, and then pull their parent cells with them as they advance
What can slow the process of epitheltialization?
low oxygen tension and thick debris
When examining a wound what 2 things are indicative of the proliferative phase?
- small endothelial buds within the wound bed, indicating angiogenesis
- pale pink epithelial cells at the wound edge which is evidence of epithelialization
- wound contraction
After the prolifertive phase the granulation tissue matrix must continue to strengthen and reorganize itself to fit the surrounding tissue which requires continued collagen synthesis. The old collagen is broken down by what?
collagenases
How can you tell the differnece between a scar that is remodeling and one that is fully remodeled?
A rosy, pink scar is still in the remodeling phase, whereas a scar that is pale or more closely approximates the surrounding tissue color is fully remodeled
Describe the change collagen fibers make during the remodeling phase
They change from immature Type III collagen to mature type I collagen and reorient along the line of stress
Remodeling continues up to _ years following wound closure, with the greatest amount occurring when?
2
6-12 months
Even once fully remodeled, scar tissue is at most only __% of the original tissue’s strength and elasticity
80
What are the 3 types of wound closures?
- primary
- secondary
- delayed
Describe primary wound closure
It is the simplest and fastest type of wound closure as it occurs when the wound edges are able to be approximated with little or no granulation tissue formation
Give an example of a primary wound closure
a surgical incision
How long should a wound take to close via primary intention?
1-14 days
Describe secondary wound closure
Requires the body to make a matrix of granulation tissue to fill the wound defect
Describe delayed primary wound closure
It is a combination of primary and secondary closure that may be used in patients with large wounds that are initially infected or that fait to successfully close by secndary closure
A wound that is closed via delayed primary closure should be closed within how many weeks?
1-2
What characterizes a chronic wound?
Senescent cells, which are mitotically active but minimally responsive
Chronic wounds have higher levels of MMPs and lower levels of TIMPs which leads to what?
degradation of the extracellular matrix
In what type of patient can a reduced or absent inflammatory response be seen?
- pts taking high doses of steroids
- patients who are malnourished
- patients who are elderly
- patients with immune system disorders (HIV, AIDS, etc.)
Cellulary, chronic inflammation is characterized by an increase in what?
macrophages and fibroblast proliferation
What are the 3 common causes of chronic inflammation?
- Presence of foreign body in wound bed
- Repetitive mechanical trauma
- Cytotoxic agents
A wound that is _____ fails to build enough granulation tissue to fill the wound defect, resulting in a pothole-type wound. In the end what does this result in?
hypogranular
the epithelial cells cannot bridge the gap to achieve wound closure and repair is suspended
What is the cause of wound epibole?
The epithelial tissue migrates
down sides of the wound instead of across. Edges that roll over will ultimately cease in migration secondary to contact inhibition once epithelial cells of the leading edge come in contact with other epithelial cells.
In what type of patients do hypogranular wounds seem to occur more frequently in?
those with diabetes or malnutrition
How can hypogranular wounds be managed?
by gently wiping the wound edges with gauze with each dressing change
How can hypergranulation be prevented?
by protecting the fragile epithelital cells from trauma
Once present, hypergranulation can be resolved in 3 ways. What are they?
1) pressure over the hypergranular tissue
2) silver nitrate applied to the hypergranular tissue cauterizing the tissue
3) surgical excision
What is hypertrophic scarring due to?
the overproduction of immature collegen during the proliferative and maturation/remodeling phases of healing
What do hypertrophic scars look like?
red, raised, fibrous lesions that stay within the confines of the original wound
What type of wounds are more likely to result in hypertrophic scarring?
in wounds that cross lines of tension in the skin or in wounds with prolonged inflammatory phase, such as large or infected wounds
Hypertrophic lesions are often associated with what?
contractures, because of the random overproduction of collagen
How can hypertrophic scars be managed?
- compression garments worn 23 hours per day
- silicone gel sheets over the scarred areas
- scar mobilization to alter the scar tissue
- repeated steroid injections to modify the scar
- topical agents
- surgery
How do keloid scars differ from hypertrophic scars?
Keloids extend beyond the confines of the original wound and rarely regress independently
What are keloids associated with?
- laceration
- tattoo
- surgery
- ear piercing
- burns
What do keloids look like?
nodular masses of collagen randomly arranges in swirls or clusters of collagen fibers
How are keloid scars managed?
steroid injections with or without surgical excision
What is a contracture?
a pathological shortening of scar tissue resulting in deformity
When are contractures most likely to form?
in wounds crossing a joint
What is dehiscence?
the separation of wound margins due to insufficient collagen production or tensile strength
