2 – Basic Wound Healing

Question 1

What are the 4 stages of wound healing?

Answer 1

1. Inflammation phase
   a. Vascular phase (ex. hemorrhage)
2. Debridement phase
3. Repair phase
4. Maturation phase

Question 2

Acute vascular phase

Answer 2

• Hemorrhage
• Vasoconstriction
  o Immediate hemostasis
  o <10 minutes
• Endothelial injury
• Cellular adhesion (leukocytes, platelets, RBC)
• Coagulation

Question 3

Cellular players: roles

Answer 3

• Mast cells, macrophages, platelets
  o Growth factors or cytokines=initiate and maintain proliferative phase of healing
• Begins immediately after injury and last ~5 days
• WBCs: initiate debridement phase

Question 4

What are some vasoactive substances? (inflammation phase)

Answer 4

• Histamine
• Serotonin
• Kinins
• Prostaglandins
• Chemotactic agents

Question 5

Histamine (inflammation phase)

Answer 5

• Early permeability increase
• <30 mins

Question 6

Serotonin (inflammation phase)

Answer 6

• Endothelial cell swelling
• Induces lysyl oxidase=important for inflammation to occur

Question 7

Chemotaxic agents: examples (2) (inflammation phase)

Answer 7

• Prostaglandins
• Cytokines

Question 8

Prostaglandins (inflammation phase)

Answer 8

• Permeability changes
• Vasoactive
• Chemotaxis
• Stimulate mitosis

Question 9

Granulocyte characteristics (inflammation phase)

Answer 9

• pH sensitive
• antibacterial
• collagenase
• proteolytic enzymes

Question 10

Macrophages (inflammation phase)

Answer 10

• ‘custodial staff’
• Mitogenic factors
• Cytokines: (TGF-alpha, TFG-beta, IGF-1)

Question 11

Debridement phase: timeline

Answer 11

• 6-12 hrs after injury

Question 12

Chemoattract: debridement phase

Answer 12

• Neutrophils
• Monocytes

Question 13

Exudate: debridement phase

Answer 13

• WBC
• Dead tissue
• Wound fluid

Question 14

Neutrophils: debridement phase

Answer 14

• Increase for 2-3 days
• Prevent infection
• Phagocytize organisms and debris

Question 15

Degenerating neutrophils: debridement phase

Answer 15

• Release enzymes
  o Breakdown bacteria, extracellular debris and necrotic material
  o *stimulate monocytes

Question 16

**Monocytes: debridement phase

Answer 16

• **ESSENTIAL FOR WOUND HEALING (neutrophils are not)
• Major secretory cells
  o Synthesis GF for tissue formation and remodelling
  o Secrete collagenases: remove necrotic tissue, bacteria, foreign material
  o Recruite mesenchymal cells
  o Stimulate angiogenesis
  o Modulate matrix production
• Become macrophages in wounds: 24-48hrs

Question 17

Lymphocytes: debridement phase

Answer 17

• Appear later than neutrophils and monocytes
• Secrete soluble factors
  o Stimulate or inhibit migratory and protein synthesis by other cells

Question 18

What severely impairs healing?

Answer 18

• Macrophage function (ex. monocytes)
• Ex. neutropenia and lymphopenia do NOT inhibit healing or development of wound tensile strength

Question 19

Repair phase timeline

Answer 19

• 3-5 days after injury

Question 20

Fibroblasts: repair phase

Answer 20

• Transforming GF to produce fibronecrotic
  o Cell binding and fibroblast movement
• Platelet-derived GF and basic fibroblast GF
• Originate from undifferentiated mesenchymal cells
  o Migrate to wounds along fibrin strands in fibrin clot
  o *just before new capillary buds as inflammatory phase subsides
• **synthesize and deposit collagen, elastin, and proteoglycans=fibrous tissue
• Haphazard orientation until day 5
  o Tension causes them to orient parallel
  o *wound fibrin disappears and collagen is deposited

Question 21

Collagen: repair phase

Answer 21

• Wound tensile strength
• As wound maturation
  o Type I (mature) increases
  o Type III (immature) decreases
• Reaches max within 2-3 weeks post-injury
• *Increased collagen leads to decreased fibroblasts=end of repair stage

Question 22

If there are no macrophages, what is delayed?

Answer 22

• Fibroblast migration and proliferation
• Collagen production
• Capillary ingrowth

Question 23

Angiogenesis

Answer 23

• Capillaries invade wounds behind migrating fibroblasts
• Interaction of ECM with cytokines
  o Migration of endothelial cells
  o Proliferation of endothelial cells
• New capillaries, fibroblasts, fibrous tissue
  o Bright red, fleshy granulation tissue
  o **3-5 days after injury

Question 24

Granulation tissue

Answer 24

• Fills defect and protects wound
• Barrier for infection
• Surface for epithelial migration
• *source of myofibroblasts
• *formed at wound edge at rate of 0.4 to 1mm/day

Question 25

Granulation is a source of myofibroblasts (special fibroblasts)

Answer 25

- Wound contraction: actin and myosin - Not found in normal tissue, incised and coated wounds OR tissue surrounding contracting wounds

Question 26

Epithelialization: timeline

Answer 26

- Begins almost immediately in sutured wounds (24-48hrs) o Primary closure healing - Begins in open wounds when granulation bed has formed (4-5 days) o Second intention healing - *visible 4-5 days after injury

Question 27

Epithelialization

Answer 27

- Mobilization, migration, proliferation, differentiation - *guided by collagen fibers - Contact with epithelial cells on all side INHIBIT further cell migration o Only one cell thick initially, gradually thickens as new layers added - Occurs along suture tracts (would result in scars) - Moist environments help the process o Does NOT occur over non-viable tissue

Question 28

First intention healing

Answer 28

- Primary closure - Ex. suture incision - Tissue apposition: NO granulation bed

Question 29

Second intention healing

Answer 29

- Open wound healing o Granulation: pale pink o Contraction o Epithelization

Question 30

Epithelization: basal cells at wound edge

Answer 30

- Microvilli and extend broad pseudopodia over exposed surface of collagen bundles - Epithelial cells migrate over them until they contact wound surface - **Do this over scabs by producing collagenase that dissolve the scabs (otherwise they can’t do it)

Question 31

Epithelialization: energy

Answer 31

- Energy dependent - Related to oxygen tension o Needs to find a happy medium - *anoxia prevents epithelial migration and mitosis

Question 32

Wound contraction

Answer 32

- Reduces size of wounds o Subsequent to fibroblasts o Reorganizing collagen in granulation tissue o Myofibroblast contraction at wound edges - Occurs simultaneously with granulation and epithelialization o **Independent of epithelization - *wounds may be noticeable smaller by 5-9 days - *centripetal (outside to middle)

Question 33

Why does wound contraction stop?

Answer 33

- Wound edges meet - Tension is excessive - Myofibroblasts are inadequate

Question 34

Maturation phase

Answer 34

- Collagen has been adequately deposited - 17-20 days o may continue for years - functionally oriented fibers become thicker - type III collagen decreases while type I collagen increases

Question 35

Timeline of wound strength

Answer 35

- most rapid gain: 7-14 days o collagen rapidly accumulates in wound - 20% strength o First 3 weeks after injury - Slow increase, but normal tissue strength will NEVER be regained o 80% of original strength may be regained

Question 36

Serum scald:

Answer 36

- From the serum and everything draining - *can be reduce by putting Vaseline on skin

Question 37

What are some systemic factors affecting wound healing?

Answer 37

- Age - Nutrition (ex. low protein=hard time healing, obese) - Concurrent disease - Corticosteroids, NSAIDs, immunosuppression

Question 38

What are 2 main local wound factors?

Answer 38

- Surgeon - Wound environment

Question 39

Surgeon factors

Answer 39

- Tissue handling - Procedure duration - Suture material - Suture tension - Hematoma or seroma formation

Question 40

Wound environment

Answer 40

- Infection - Foreign body - Microenvironment o Oxygen tension o Temperature o pH o topical medications