Wound Healing

Question 1

What is wound healing?

Answer 1

Physiology by which the body replaces and restores function to damaged tissues
-Tortora and Grabowski 1996

The wound in all cases has a tendency to produce the deposition and the means of a cure
-John Hunter (1728-1793)

Question 2

What are the 3 phases of wound healing?

Answer 2

1. Haemostasis &Inflammation
2. Proliferation
3. Maturation

Question 3

What happens in the Haemostasis and Inflammation phase?

Answer 3

●This takes about 4-6 days to complete
●Exposed collagen activates clotting cascade and inflammatory phase
●Fibrin clot provides scaffolding and it concentrates cytokines and growth factors

Question 4

The role of Granulocytes (neutrophils)e

Answer 4

●Arrives at the crime scene around 48 hours
● After being alerted by Complement, IL-1, TNF-ă, Platelet factor 4 (PF-4), bacterial products etc)
●Non-specific, like beat cops 👮‍♂️
●Role: phagocytosis of bacteria and debris
●Also produce free radicals like
The main free radicals produced by neutrophils are:
1. Superoxide radical (O2•-)
2. Hydrogen peroxide (H2O2)
3. Hypochlorous acid (HOCl)
4. Hydroxyl radical (•OH)

These radicals can also damage 💔 the host

♤They then call the FBI, The Monocytes,

Question 5

The role of macrophages

Answer 5

These are called Monocytes (in blood),and transform into macrophages so that they can infiltrate the crowd at the crime scene
●Reminder: They’re attracted to the area by complement.
☆These special agents are activated by:
1. Fibin
2. Foreign body material
3. Exposure to hypoxic and acidotic environment
●Peak at about 48-96 hours
●Remains at the area for weeks
Their main functions:
1. Mediates: Angiogenesis & Fibroplasia: matrix synthesis and regulation, Cell recruitment and activation; Wound debridement, Phagocytosis and antimicrobial function
2. Synthesise: Nitric oxide
3. Secrete: Collagenases
They’re essential for progression onto the Proliferation Phase

Question 6

The T- Lymphocytes

Answer 6

The guest from the White House
●Peak at 1 week
♤ Bridges the transition from inflammatory to proliferative phase
● Precise role not fully defined
■ Modulates the wound environment

Question 7

EVIDENCE OF INFLAMMATION
“Quintus Tumor,”

Answer 7

Rubor (Redness)
Calor (Heat)
Tumor (Swelling)
Dolor (Pain)
Functio laesa (Impaired function)

Question 8

PROLIFERATIVE PHASE

Answer 8

●Day 4 through 14
1. Epithelialization: the beginning of everything!!
2. Angiogenesis
3. Provisional Matrix Formation
■Hallmark of the proliferative phase: Production of Collagen
●Can be in the wound from Day 7 to 6 weeks

Question 9

Epithelializaton

Answer 9

1. Basal epithelial cells at the wound margin flatten (mobilise) and migrate into the open wound
2. Marginal cells multiply horizontally by mitosis
3. Cells behind the margin grows vertically (differentiation)

Question 10

Epithelializaton

Answer 10

1. Basal epithelial cells at the wound margin flatten (mobilise) and migrate into the open wound
2. Marginal cells multiply horizontally by mitosis
3. Cells behind the margin grows vertically (differentiation)

Question 11

Fibroblasts: The work horse of wound repair

Answer 11

Produce Granulation tissue:
●Signals: Platelet derived growth factor (PDGF) and Epidermal growth factor (EGF)
Produces
■Collagen type III
■Glycoseaminoglycans
■Fibronectin
■Elastin fibers
Transforming Growth Factor ɓeta- 1(TGF-ɓ1) induces tissue fibroblasts to become Myofibroblasts, needed for contractility

Question 12

The Endothelial Cell

Answer 12

■TNF-ą, TNF-ɓ and VEGF stimulate the migration of endothelial cells from neighbouring venules into the wound
■This leads to extensive formation of new capillaries

Question 13

THE MATURATION PHASE

Answer 13

●Day 8 through years
●The previously random fibrils are organised to a linear fashion
●Type III collagen is replaced by Type I
Wound may increase in strength for upto 2 years after injury (When a wound is covered by epithelium, it doesn’t mean it has comlpleted healing, there is a lot going on, including Collagen organisation and Cross linking)

Question 14

WOUND CONTRACTION

Answer 14

●Pulling of wound edges towards the centre, making it smaller
●This is mediated by myofibroblasts, which have contractile properties
●As a result of central pulling of the wound edges, the surrounding skin is stretched and thinned.
However, the dermal thickness is maintained.
Increasing collagen I increases the wound breaking strength 💪

Question 15

What if the healing process don’t go according to the plan:
Aberrations of wound healing

Answer 15

There is formation of:
1. Hypertrophic scar
2. Keloid
N.B: This are histologically identical on hematoxylin & eosin (H/E) staining

Question 16

HYPERTROPHIC SCAR

Answer 16

●Limited to the margins of the original wound
●Raised and firm
●Can be itchy and painful

♧Naturally, it would eventually regress

Question 17

HYPERTROPHIC SCAR

Answer 17

●Limited to the margins of the original wound
●Raised and firm
●Can be itchy and painful

♧Naturally, it would eventually regress

Question 18

KELOID SCAR

Answer 18

●Extends beyond the original bounds of the wound
●Raised and firm (like the hypertrophic scar)
□More common in dark skinned races
●Predilection for sternum, mandible, and deltoid
●Rarely occurs distal to wrist or knee
On electron microscope, it differs from a hypertrophic scar in the following ways:
1. Rate of collagen synthesis is increased
2. Water content is higher
3. Increased glycosaminoglycans

Question 19

Treatment of hypertrophic scar and Keloid scar

Answer 19

Aim: modulates the chemistry in the scar. None of these measures works 100%, sometimes combining them could be more effective.
1. Corticosteroids: decrease inflammation in the scar
2. Pressure dressings
3. Silicone dressings absorb moisture from the scar
4. Laser therapy
5. Chemotherapy: Bleomycin
6. Cryotherapy
7. Surgery

Question 20

Factors that affect wound healing

Answer 20

To treat the wound, you have to treat the patient

Local factors:
●Foreign bodies
●Haematoma
●Ischaemia
●Oedema

Systemic factors

Secondary Immunosuppression:
●Aging (immunosenescence)
●Lifestyle factors:
- Malnutrition or nutritional deficiencies (e.g., protein, vitamin, and mineral deficiencies)
- Excessive alcohol consumption
- Smoking
- Chronic stress

●Co-morbid conditions:
- Diabetes mellitus
- Chronic kidney disease
- Liver disease
●Acquired immune deficiencies:
- HIV/AIDS
- Malignancies affecting the immune system (e.g., leukemia, lymphoma)

●Medication-related factors:
- Immunosuppressant drugs (e.g., corticosteroids, chemotherapeutic agents, biologics)
Ionising radiation

●Autoimmune disorders:
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Sjögren’s syndrome
- Inflammatory bowel diseases (e.g., Crohn’s disease, ulcerative colitis)
Connective tissue disorders:
1. Ehlers-Danlos syndrome (EDS)
2. Marfan syndrome
3. Cutis laxa

Primary Immunodeficiencies:
1. Genetic disorders:
- Severe combined immunodeficiency (SCID)
- DiGeorge syndrome
- Wiskott-Aldrich syndrome
- Ataxia-telangiectasia
- Common variable immunodeficiency (CVID)

Question 21

WOUND DRESSINGS
Desired characteristics of wond dressings

Answer 21

1. Promote wound healing (maintain moist environment)
2. Conformability
3. Pain control
4. Odor control
5. Non-allergic and non-irritating
6. Permeability to gas (O2 in, Co2 and others out)
7. Safety (shouldn’t cause more harm to the patient)
8. Non-traumatic removal
9. Cost-effectiveness
10. Convenience

Question 22

Why is wound dressing so important?

Answer 22

1. Mimic epithelial barrier: protect the site from bacteria, covering of nerve endings reduces pain
2. Compression provides haemostasis and reduces oedema
3. Occlusion controls hydration and allows for oxygenation/gaseous diffusion
4. Occlusion (controlled hypoxia) stimulates collagen synthesis and epithelial cell migration

Question 23

Classification of dressings

Answer 23

1. Primary Dressing
   ● Placed directly on the wound and may provide absorption of fluids and prevent dessication, infection, adhesion of a secondary dressing.
2. Secondary Dressing:
   ●Placed on the primary dressing for further protection, absorption, compression, and occlusion

Question 24

Types of dressings

Answer 24

1. Absorent:
   ● Absorbs excess wound fluid to prevent maceration (softening and breakdown of the skin due to prolonged exposure to moisture or excess wound exudate) and bacterial overgrowth
2. Non- Adherent:
   ● Impregnated with paraffin, petroleum jelly (vaseline) or water-soluble jelly [
   ☆Requires 2⁰ dressing to seal edges & prevent dessication/ infection
3. (Semi)occlusive:
   ●Film dressing good for minimally exudative wounds
   ●Waterproof, impervious to microbes, permeable to water vapour and oxygen
4. Hydrophilic: aid in fluid absorption
5. Hydrophobic: waterpoof, prevents absorption (Good for a wound that is prone to dryness)
6. Hydrocolloid
   ● Absorption of exudates
   ▪︎Leaves a gellatinous mass after dressing
   ▪︎Removal is atraumatic since the hydrocolloids can be washed off
7. Hydrogels:
   ☆Useful for burns because they allow for a high rate of evaporation without decreasing wound hydration
8. Alginate:
   ●Derived from brown algae
   They’re polysaccharide polymers with a high absorbency
   Good for skin loss, open surgivak wounds with medium exudation, and full thickness chronic wounds
9. Medicated:
   ● Benzoyl peroxide, Zinc oxids, neomycin, bacitracin-zinc
   ☆Used to treat infections
   ☆Increase epithelialization
10. Mechanical dressing
    • Vacuum-assisted closure system applies a negative presstobthe surface and margiof the wound via a foam dressing
    ■■Over days to weeks, it slowly draws the edges o the wound together, in a process called macrodeformation, making the wound smaller
    ■It also pulls up granulation tissue into the wound (microdeformation) and increase the chances of granulation
    ■Pressure Ulcers■
    • Good for exudate absorption and odour control
    • Very effective for chronic ulcers, trauma, flaps/grafts, dehiscent incisions