2 - Principles of Wound Healing

Question 1

Wound healing

Answer 1

• Incision by a blade, trauma from a bullet and tissue death from a myocardial infarction all undergo a similar and predictable reparative process
• Understanding how the body repairs damaged tissue is vital to treating and preventing wounds

Question 2

Phases of wound healing from the “wound module”

Answer 2

• Injury (not always included)
• Inflammatory phase
• Proliferative phase
• Maturation

Question 3

Mechanisms of wound repair

Answer 3

o Connective tissue deposition
o Epithelization
o Contraction

Question 4

Types of woundn closure

Answer 4

o Primary intention
o Secondary intention
o Delayed primary closure
o Partial thickness (scratch or superficial abrasion)

Question 5

Inflammatory phase

Answer 5

• Characterized by hemostasis and inflammation
• Collagen exposure during wound deformation activates the clotting cascade –> IMPORTANT
  o Damaged cells release thromboxane A2 and prostaglandin 2-alpha (vasoconstrictors)
  o Initial response limits the hemorrhage

Question 6

Capillary vasodilation of the inflammatory phase

Answer 6

• Capillary vasodilatation occurs as well in response to histamine release
  o This causes inflammatory cells to migrate to the wound bed
  o Vasodilation occurs to counteract the vasoconstriction –> “checks and balances”

Question 7

1st and 2nd cells to show up during inflammatory phase

Answer 7

• Platelets are “first response cells” and neutrophils are “second response cells”

Question 8

Platelets during the inflammatory phase - 3 things they release

Answer 8

1st = Platelets (first response cell) release 3 things:
o Epidermal growth factors (EGF) –> regulates cell growth, proliferation, differentiation
o Platelet Derived Growth Factors(PDGF) –> regulates cell growth, blood vessels division
o Histamine

* During the inflammatory phase, the wound is stabilized through clot formation*

Question 9

Neutrophils during inflammatory phse

Answer 9

Neutrophils (second response cell) migrate to the wound for complement mediated opsonization of bacteria (“packaging and getting rid of bacteria”)
o Vessel adherence (pavementing, margination)
o Diapedesis (movement through vessel walls)
o Chemotaxis (chemical directive to injury site)
o Phagocytosis (opsonization)

Question 10

Macrophages during inflammatory phase

Answer 10

Macrophages are most essential cell for wound healing
o Initially you need neutrophils to “clean up,” but eventually you need macrophages to start initiating wound healing and regrowth of tissue
o Macrophages release Tumor Necrosis Factor (TNF) which stimulates fibroblasts (collagen) and angiogenesis

Question 11

Other events promoting healing and new growth during inflammatory phase

Answer 11

o Transforming Growth Factor (TGF) will be present, which stimulates keratinocytes
o Increased blood flow and congestion is evident by the increased number of red cells
o The increase in neutrophils (dark segmented cells) is also evident as well as the increased protein exudates (pink substance)

Question 12

3 stages of proliferative phase of wound healing

NEED TO KNOW

Answer 12

o **Epithelization
o **Angiogenesis
o ***Collagen deposition (granulation tissue formation)

Note that there is some overlap between these stages

Question 13

Epithelialzation

Answer 13

Stage 1 of proliferative phase
o If basement membrane is intact, cells will migrate in a normal pattern (Example: 1st degree skin burn) - Normal layers of epidermis will be restored in 2-3 days
o If basement membrane destroyed, wound is re-epithelialized from cells in the periphery (Example: 2nd or 3rd degree burns)

Question 14

Angiogenesis

Answer 14

Stage 2 of proliferative phase
o Stimulated by TNF-alpha
o Endothelial cell migration and capillary formation
o Maintains the granular bed
o Migration of capillaries (new capillary formation) delivers nutrients to the wound bed

Question 15

Collagen deposition (granulation tissue formation)

Answer 15

Stage 3 of proliferative phase

Fibroblasts differentiate and lay down collagen fibers in varying patterns

• Organized collagen = STRONG, disorganized, random collagen = WEAK
• Collagen is much thicker during proliferative phase, thinner during maturation

Cytokines involved: IGF (insulin like growth factor), PDGF

Question 16

Maturation phase

Answer 16

• Begins 1-2 weeks after injury
• Increased collagen and vascularity occur, wound contraction begins
• At the beginning of the maturation phase the tensile strength of the skin is 30% of normal skin
  o Wound will not reach maximum strength until one year
• Increased collagen deposition, increased blood flow, new capillaries

Question 17

Graph on phases of wound healing

Answer 17

• Here you can see the three phases (inflammation,
  proliferation, maturation)
• Note the specific cells that are present during each
  phase and the significant overlap that is present
• Oxygen availability is important here –> during the
  inflammatory phase, there really is no oxygen available,
  but as we progress through maturation, oxygen becomes
  available due to extensive angiogenesis

Question 18

Tensile strength graph

Answer 18

• This graph shows the types of cells present in each
  phase as well, but in this graph focus on the tensile
  strength in each of the phases
• Tensile strength continuously increases following injury
• During fibroblastic phase there is a jump in strength that
  continues through maturation
• At day 21 (beginning of maturation phase), the tensile
  strength is only at about 30%

Question 19

Collagen deposition graph

Answer 19

• Same thing for tensile strength – from 0-21 days, you
  reach about 30% of normal tissue strength
• Note that the collagen is deposited in a random
  orientation from 0-21 days, leading to significantly
  thicker collagen
• This collagen then gets reorganized during the
  maturation phase and it becomes thinner
• Don’t need to know specific dates, but know the
  ballpark time periods for these events

Question 20

LOCAL factors that affect wound healing

Answer 20

• Blood Supply
• Denervation
• Hematoma (collection of blood)
• Seroma (collection of serous fluid)
• Infection
• Mechanical Stress
• Surgical Technique
• Irrigation
• Dressing materials

Question 21

GENERAL factors that affect wound healing

Answer 21

• Age
• Anemia
• Anti-inflammatory drugs (controversial)
• Corticosteroids
• Malnutrition
• Diabetes
• Vitamin deficiency

Question 22

Wound healing principles

Answer 22

Things you need to address

• Vascular perfusion
• Bacterial balance
• Nutritional balance
• Control contributing factors (anything that contributed to trauma or breakdown)

Question 23

wound dehiscene

Answer 23

o Surgical site opens up and there is parting of the layers of the surgical wound

Question 24

Cause of wound dehiscence

Answer 24

o Infection, hematoma, seroma, poor surgical technique, inappropriate closure technique, excessive motion at the surgical site, patient non-compliance

Question 25

Primary intention

Answer 25

o Side to side closure of the wound with sutures | o Reapproximation of skin edges

Question 26

Considerations for primary intention

Answer 26

o Sutures can be placed under ideal circumstances o Need to prep the skin o Incision in the line of election for elective wounds o Dermis has tensile strength, but tensile strength is not regained for several weeks o Inflammation causes scarring o Place epidermal sutures superficial

Question 27

Secondary intention

Answer 27

- Wound is left open to granulate to closure

Question 28

Delayed primary closure

Answer 28

- Wound is left open for a period of time and then primarily closed - Typically done when you have contamination/infection at the site

Question 29

Wound repair and closure

Answer 29

- These are the RELATIVE contribution of the three principle mechanisms of wound healing in the different types of wounds

Question 30

Epithelialization

Answer 30

- You have a breakdown of the superficial skin, but no penetration through basement membrane - Following debridement of the area, you see healthy granular base which will eventually heal on its own with ***NO SCAR*** since there was no damage to the basement membrane or dermis - The difference between epithelization and secondary intention is that the basement membrane has NOT been breached in epithelization and it HAS been breached in secondary intention - Note that since secondary intention involves a breach in basement membrane, a scar WILL form

Question 31

Chart on healing process for primary, secondary and partial thickness wound healing

Answer 31

- Sutured = primary intention - Open = secondary intention - Partial thickness = epithelialization Each of these will be assessed in terms of contraction, epithelialization and connective tissue deposition

Question 32

Sutured (primary intention)

Answer 32

- No contraction - Slight epithelialization - High connective tissue deposition

Question 33

Open (secondary intention)

Answer 33

- High contraction - Slight epithelialization - Moderate connective tissue deposition

Question 34

Partial thickness (epithelialization)

Answer 34

- NO Contraction - HIGH epithelialization - NO connective tissue deposition NOTE - the ONLY wound healing mechanism in play during partial thickness epitheliazatoin is the epithelialization itself ***

Question 35

Keloid

Answer 35

o Abnormal scar that extends beyond the boundary of the original skin injury o Raised, thickened growth associated with pruritus and pain - pathophysiology unknown

Question 36

Histology of a keloid

Answer 36

o Scanning electron microscopy reveals randomly organized collagen fibers in a dense connective tissue matrix

Question 37

Location of keloids

Answer 37

o Sternum, deltoid area, upper back have increased susceptibility because these areas have elevated levels of muscle and skin tension o Earlobes and posterior portion of the neck are also common place

Question 38

Trends in keloids

Answer 38

o More common in African American, Hispanics, Asians (as high as 16%) o Familial predisposition is also noted -> Ask patient about history and family history

Question 39

Treatment for keloid

Answer 39

o 50% recurrence rate | o Compressive dressings, intralesional corticosteroid injections, cryosurgery, laser ablation

Question 40

Hypertrophic scars

Answer 40

o Defined as a widened or unsightly scar that does not extend beyond the original boundaries of the wound Different from keloid with DOES extend beyond initial scar boundary

Question 41

Trends in hypertrophic scars

Answer 41

o Usually reach a certain size and then stabilizes or begins to regress o No racial or familial preponderance noted