Wound Healing

Question 1

DEFINITION of healing

Answer 1

: Healing is the body response to injury in an attempt to restore normal structure and function .

Question 2

Regeneration

Answer 2

:- Complete restoration of the original tissues.

Question 3

Repair

Answer 3

:- When the healing take place by proliferation of connective tissue element resulting in fibrosis and scarring.

Question 4

Repair occurs in the following steps

Answer 4

1. Injury induces acute inflammation
2. Parenchymal cells regenerate
3. Both parenchymal and connective tissue cells migrate and proliferate
4. Extracellular matrix is produced
5. Parenchyma and connective tissue matrix remodeling.
6. Increase in wound strength due to collagen deposition.

Question 5

What is Granulation tissue?

Answer 5

Hallmark of healing
Term comes from soft, pink, granular appearance when viewed from the surface of a wound
Histology: Proliferation of small blood vessels and fibroblasts; tissue often edematous

Question 6

Processes of wound healing include

Answer 6

→ Induction of acute inflammation
→ Regeneration of parenchymal cells (labile, quiescence or stable cells)
→ Migration and proliferation of parenchymal and CT cells (Depends on Growth factors such EGF, TGF, PDGF PDR; cytokines
→ Synthesis of ECM proteins – collagens
→ Remodeling of CT and parenchymal components (depends on collagen degradation due to metalloproteinases that is ZINC dependent)
→ Collagenisation and acquisition of wound strength (X-linking of collagen). Depends on collagen synthesis and degradation
- In synthesis of Collagen -Vitamin C is required Hydroxylation of collagen propeptide
- Defect in collagen structures (Enhlers-Danlos Syndrome, osteogensis imperfecta, Alport Syndrome (Hereditary Nephritis, deafness dislocation of lens, cataract.

Question 7

SOFT TISSUE REPAIR
• Involves two processes:

Answer 7

Regeneration → replacement of injured cells by cells of the same type (No residual trace)
Replacement by CT.→ Permanent scar.

Question 8

Repair involves

Answer 8

Cell migration
Cell proliferation
Cell differentiation
Cell-matrix interaction.

Question 9

Labile cells

Answer 9

-have high replicative capacity include surface epithelium of the skin, oral cavity, vagina, and cervix, the lining mucosa of salivary glands, pancreas, biliary tract,the columnar epithelium of the GI tract and uterus; the transitional epithelium of the urinary tract, and cells of the bone marrow and hematopoietic tissues.

Question 10

QUIESCENT OR STABLE CELL

Answer 10

–Have replication capcityinclude parenchymal cells of liver, kidneys, and pancreas; mesenchymal cells such as fibroblasts and smooth muscle; vascular endothelial cells; and lymphocytes and other leukocytes.

Question 11

PERMANENT CELL

Answer 11

–Replicate only in postnatal life include CNS, skeletal and cardiac muscle cells.

Question 12

TYPES OF WOUND HEALING

Answer 12

1. PRIMARY UNION
2. Secondary UNION

Question 13

PRIMARY UNION

Answer 13

PRIMARY UNION or Healing by 1st intention → involves healing of a clean uninfected, surgical incision, approximated by surgical sutures. Minimal death of epith. Cells, and CT. cells.
- Minimal disruption of epithelial BM continuity.
- The narrow incisional space fills with clotted blood containing, fibrin and blood cells → formation of Scab that covers the wound.

Question 14

Steps involved in primary wound healing: first 24 hours

Answer 14

1. Hemostatic plug which stops bleeding and supports migrating cells into the injured site
2. Within 24 hours: acute inflammation begins
   - Neutrophils appear at the margins of incision.
   - The epidermis of its cut edge thickens due mitotic activity of basal cells.

3) 24 – 28 hours → spurs of epithelial cells migrate and grow along the cut margins of the dermis → depositing BM components.
→ Fuse at the centre producing a continuous but thin layer of epithelium.

By 3rd Day → Neutrophils replaced by macrophages
→ Granulation tissue invades the incision space
→ Collagen fibres are now present in the margins
→ Epitheliazation continues → thickening

By Day 5 → Incision space filled with granulation tissue → Pink, soft granular appearance Histologically characterized by proliferation of new small BV (Angiogenesis or Neovascularization) and fibroblasts.
Neovascularization is maximal
Epidermis mature with surface keratinizing

2nd Week → Accumulation of collagen
Proliferation of fibroblasts
Regression of vascular channels, oedema and leukocytes

By 1st month → Scar formation
compose of a cellular CT devoid of inflammatory cells.
Tensile strength of the wound increases.
Takes months for tensile strength to get to maximum.

Question 15

SECONDARY UNION OR HEALING BY SECOND INTENTION.

Answer 15

• Occurs where there is more extensive loss of cells and tissue e.g. infarction, inflammations, ulceration, abscess formation, surface wound that create large defects (severe Burns, cancrumoris)

Here the process is more complicated
-The large defect must be filled
- Regeneration cannot completely reconstitute the original architecture
- Abundant granulation tissue grows in from the margin to complete the repair.

Question 16

Differences b/w primary and secondary UNIONS

Answer 16

1. Large tissue defects with more fibrin and more necrotic tissue and exudates
2. Inflammatory Rxn is more intense
3. Much large amounts of granulation tissue are formed.
4. Wound contraction occurs → Reduction in size of the area
5. Healing starts from the base rather that edges

Question 17

Mechanism of wound healing-

Answer 17

1. Induction of an acute inflammatory process
2. Regeneration of parenchymal cells ( Labile, Quiescent or stable and permanent?)
3. Migration and proliferation of both Parenchymal and CT cells.
4. Synthesis of Extracellular matrix proteins
5. Remodeling of CT and parenchymal components
6. Collagenization
7. Acquisition of would strength

Question 18

BONE HEALING
Stages

Answer 18

1. Haematoma formation – follows injury if periosteum is torn
2. Acute Inflammation – Fibrin-rich exudates, increased WBC – Hyperaemia

3.Demolition – Invasion by macrophages and osteoclasts – removing fibrin, RBC, Exudates, debris

4. Formation of granulation tissue – Ingrowth of capillaries and mesenchymal cells
5. Woven bone and Cartilage formation – mesenchymal cells differentiated to form woven bone or cartilage – forms hard material uniting the fractured ends – CALLUS
6. Collagen and ground substance are laid down to form OSTEOID
   Undergo calcification to form Woven bone (In fractures that are immobilized like long bone)

In ribs, the mesenchymal cells behave like chondrocytes to form cartilage
Occurs by 10th day
In many fractures, both woven and cartilage are formed – serves to unite the ends

7.?Formation of lamellar bone – Adult bone
Woven bone is removed by osteoclasts – Vascular invasion
Cartilage disintegrates and are invaded by BV & osteoclasts
The provisional Callus is removed, osteoclasts laid down OSTEOID
Calcifies to form BONE
Collagen are arranged in orderly lamellar fashion (Haversian system)

8. Remodeling – involves
   Continued osteoclastic removal and osteoblastic laying down of bone
   External callus – is slowly removed
   Intermediate callus – converted to compact bone with Haversian system
   Internal Callus – hallowed out to Marrow cavity

Question 19

ABNOMALITIES OF FRACTURE HEALING

Answer 19

I. FIBROUS UNION - the fracture is stabilized by a fibrous connective tissue, rather than a bony union.
Common when there is free movement of fracture

1. Fibrous tissue dominates: Fibroblasts and collagen fibers predominate at the fracture site.
2. Limited bony formation: Minimal or no bony callus formation.
3. Instability persists: Fracture remains unstable, with some degree of movement.

II. MALUNION – Angulation/shortening
Fracture heals in an abnormal position or alignment.

III. NON-UNION – interposition of soft parts into the fracture, preventing haematoma formation
1. Complete failure to heal: Fracture does not heal, and the bone remains separated.
2. Pseudarthrosis: A false joint forms at the fracture site, leading to chronic instability.

IV. DELAYED UINON:
1. Slowed healing process: Fracture takes longer than expected to heal.
2. Inadequate callus formation: Insufficient or weak callus formation, leading to delayed stability.

Question 20

AFFECTING WOUND HEALING:
Systemic

Answer 20

FACTORS AFFECTING WOUND HEALING
Systemic
1) Nutrition → lack of protein and vitamin C, def of Zinc → inhibit collagen synthesis and retard wound healing

2) Administration of glucocorticoids (have anti inflammatory effects while anabolic steroids enhance healing

3) Anaemia (inadequate leukocytes – Neutropenia) – delay wound healing

4) Age and Sex – old age and female sex – slower healing

5) Systemic diseases – DM

Question 21

FACTORS AFFECTING WOUND HEALING
Local

Answer 21

Local factors
1) Infection – delays wound healing

2) Mechanical factors e.g. increased abnormal pressure → may cause rupture abdominal wound (wound dehiscence), adhesion, movement.

3) Poor BS usually from arteriosclerosis or venous abnormalities – impairs healing, site (facial wounds have better blood supply Vs pretibial wounds with poorer blood supply)

4) Foreign Bodies – sutures (non absorbable) or fragments of steel or glasses or bone → impair healing.

5) Location: eg of the wound is over the joints is will take longer to heal due to consistent mobility

Question 22

COMPLICATIONS OF WOUND HEALING

Answer 22

1. Infection
2. Wound dehiscence (reopening)
3. Cicatrisation → scarring, stricture, stenosis
4. Reduced Tensile strength → permanent weakness/recurrent hernias
5. Hypertrophy scar → keloid Accumulation of excessive collagen → tumourous scar. Common in certain individuals, blacks, females more than males
6. Excess granulation tissue → protrusion above normal level → EXUBERANT GRANULATION
7. Painful scar e.g. Neuromas
8. Pigmented changes
9. Epidermoid /implantation cyst
10. Malignant transformation – SCC from scar- RARE