Wound Healing

Question 1

What is the epidemiology of wounds?

Answer 1

20 million wounds worldwide

annual cost of $125 billion a year

average cost of hospitalization for a wound is $17,845

Question 2

What are the processes of wound healing?

Answer 2

scar and regeneration

Question 3

What are the organs that can heal completely by regeneration?

Answer 3

epithelium, bone, and hepatocytes

Question 4

What are the three different types of wound closure?

Answer 4

primary - wound edges are closely approximated and heal in the absence of complications

secondary - wound edges are not approximated (open woound) and heal by “filling in” with granulation tissue, heal starting from the outside and going in

tertiary - wounds are intentionally left open and allowed to granulate for a finite period of time, then approximated and closed by “primary methods”

Question 5

What are the three phases of primary wound healing?

Answer 5

inflammatory stage (days 0-4)

proliferative stage (days 3-28)

remodeling stage (days 21-365)

Question 6

What are the features of the inflammatory phase of wound healing?

Answer 6

predominantly removal of devitalized tissues and prevention of infection

wounds appear weepy and crusty

PMNs arrive in 24 hours - participate in phagocytosis, clearance of debris takes variable time, depending on amount of debris/baacteria

macrophages appear in 2-3 days and complete the process of removal of all nonessential material - essential for releae of GFs and cytokines

Question 7

What are the features of the proliferative phase of primary wound healing?

Answer 7

days 3-28

replacement of wounded tissue by scarring or regeneration

wound/scar appear raised and erythematous

TGF-beta recruits/activates fibroblasts - ECM collagen production, collagen deposition at 3 weeks, but only 20% strength

EGF stimulates epithelial division and differentiation - cells grow from wound edges and skin appendages

endothelial cells release VEGF to promote angiogenesis

Question 8

What are the features of the remodeling phase of primary wound healing?

Answer 8

days 21-365

begins wiht programmed regression of granulation tissue

replacement of scar to maximize the strength and structural integrity of the wound - replace immature collagen

remodeling of collagen, no net gain in collagen but type III collagen is replaced by type I

wounds become flatter and less erthematous during this time, contraction carried out by myofibroblasts

Question 9

What are some of the common cell types involved in wound healing?

Answer 9

platelets - hemostasis

neutrophils - involved in removing devitalized tissue an dpreventing infection by bacteria

macrophages - major signaling cell of wound healing, TGF-beta, also involved with removal of debris

fibroblast - collagen deposition, myofibroblasts allow for contraction of wounds

keratinocytes - migrate from wound edges to re-establish epithelium

endothelial cells - re-establish blood vessels

Question 10

What are some important growth factors, cytokines, and chemokines involved in wound healing?

Answer 10

TGF-beta - released by platelets, macrophages, and lymphocytes and induces formation of ECM and up-regulates collagen

PDGF - released by platelets and recruits neutrophils, macrophages, and fibroblasts

EGF - released by platelets and macrophages, promotes eCM deposition and epithelial growth

VEGF - released by endothelial cells to promote angiogenesis

Question 11

What is the sequence of wound healing?

Answer 11

vasoconstriction for 5-10 min, then dilation

exposed ECM, TF, and collagen trigger platelet plug formation and coagulation cascade

formation of fibrin matrix for cellular flux - allows other cells to really populate the wound

Question 12

What is granulation tissue?

Answer 12

tissue with high amounts of epithelial activation and blood vessel formation that covers an open wound

Question 13

What are the origins of epithelial cells

Answer 13

wound margins and skin appendages

Question 14

What is the process of epithelialization?

Answer 14

the proess of epithelial regeneration

the rate of healing is critically dependent on the vascularity and health of the underlying granulation tissue (neodermis) across which it migrates

full thickness injuries heal from the skin edges because there are no skin appendages

partial thickness injuries heal from both the wound margin and appendages

rate depends on how clean the granulation bed is

Question 15

How does wound strength progress over the course of healing?

Answer 15

proliferative phase - maximum net collagen deposition, 20% strength at 3 weeks

remodeling phase - no net gain in collagen, 80% wound strength at 6 weeks, can restart full activity

final wound strength is approximately 75% of normal skin

Question 16

secondary wound healing

Answer 16

healing of open wounds

all three phases occur simultaneously

• neutrophils and macrophages constantly clearing environmental debreis (inflammatory)

formation of granulation bed and epithelialization from wound edge (proliferative)

contraction of wound (remodeling)

Question 17

What are the important factors needed for wound healing?

Answer 17

oxygen

nutrition

vitamins and minerals

moisture

Question 18

Why is oxygen important for wound healing?

Answer 18

very energy-taxing procedure

has to be aerobic respiration

largely determined by blood supply

three processes important for good oxygenation:

1) inflow (arterial ulcer can hinder)
2) outflow (venous stasis ulcer can hinder)
3) diffusion (edema can hinder)

Question 19

What kinds of nutrition is important for wound healing?

Answer 19

protein intake for collagen production - normal daily intake should be 1g/kg

large wounds need 2-3x this

albumin is a marker of protein (look at pre-albumin for short term history)

carbohydrate intake to prevent catabolism, and insulin response has overall anabolic effect, also a great source of calories

Question 20

What vitamins and minerals are necessary for wound healing?

Answer 20

vitamin A - essential for epithelial and bone development and differentiation, can also counteract effect of steroids

vitamin C - essential for collagen crosslinking, and deficiency may lead to scurvy

zinc - need a cofactor for many enzymes used in wound healing including those involved in DNA synthesis, cell division, and protein synthesis

Question 21

What is the role of moisture in wound healing?

Answer 21

epithelialization and granulation tissue formation occur best in a moderately moist environment

useful to think of deressings being tailored to the amount of wound exudate

ex. gauze, films, vaseline, hydrogels, hydrocolloids, alginates +/- antimicrobials

Question 22

What are some factors that will negatively affect wound healing?

Answer 22

bacterial colonization or infection

foreign bodies

radiation

glucocorticoids

chemotherapeutics or antimetabolites

smoking

Question 23

What is the difference between bacterial colonization and infection?

Answer 23

infection is the body’s response to bacterial over colonization - prolongs inflammatory phase

all wounds (and skin) are colonized with bacteria

critical coloniztion - effects wound healing when there are 10^5 bacteria/g tissue (will affect epithelialization)

biofilms are a major issue that can impede healing

Question 24

What are radiation wounds?

Answer 24

radiation causes micrvascular thrombosis and fibrosis of the radiation bed

this leads to the decrease in oxygen supply to the wound bed

Question 25

What is delayed wound healing?

Answer 25

one or more of the processes of normal wound healing is deficient

for example, bacterial infection of the wound may lead to a prolonged inflammatory phase or prior radiation

steroids or chemotherapy may slow down to proliferative phase, or local tissue ischemia or advanced age may slow down all processes

Question 26

What are teh basics of care for all wounds?

Answer 26

optimize systemic parameters

debride nonviable tissue

reduce the wound bioburden

optimize blood flow/perfusion

reduce edema

utilize dressings appropriately and consider specific aims and cost effectiveness

Question 27

What are burns?

Answer 27

thermal wounds of the skin

degree of thermal injury is based upon the temprature (>40F) AND time of exposure

Question 28

How are burns classified?

Answer 28

by their depth

determines level of skin dysfunction (water homeostasis, thermoregulation, environmental barrier)

determines ability to heal (partial thickness with wound edges and appendages or full thickness with only wound edges)

Question 29

first degree burns

Answer 29

involves injury to the epidermis

appears as a redness as in a minor sunburn

Question 30

second degree burns

Answer 30

involves injury to the epidermis and part of the dermis

appears as blisters (epidermis separating from dermis) and ar painful

Question 31

third degree burns

Answer 31

involves injury to the epidermis, full thickness of the dermis, and some of the subcutaneous tissue

this includes skin appendages and nerves

appears as a charred, leathery, painless (de-innervated) areas of skin

Question 32

fourth degree burns

Answer 32

involve injury to underlying muscles or burn

Question 33

diabetic wounds

Answer 33

15% of diabetics get these

usually on the feet on areas of pressure

peripheral neuropathy, so wounds go unnoticed

microvascular disease lead to poor circulation and impairs wound healing, also macrovascular problems long term

cellular dysfunction leads to global problems and all cells are less able to do their jobs

Question 34

When do scars appear after wound healing?

Answer 34

only when the injury extends deeper than the superficial dermis

all dermal wounds scar, and all dermal wounds contract

technique, wound care, and genetics will determine how much

Question 35

hypertrophic scars

Answer 35

abundant scar tissues created in response to stress placed on wounds

often confused for keloids

scar remains within the confines of the wound

the wound may stretch along with the scar, but the scar does not extend beyond the border of the wound

normall collagen arrangement

Question 36

keloids

Answer 36

tumor-like growth of scar tissue that extends beyond the margin of the scar

collagen is disorganized

strong genetic components

difficult to treat and are often treated like tumors with re-excision, injction of corticosteroids, chemotherapeutics and subject to radiation

even with these treatments, recurrence rates are high