Wound healing

A presentation about Wound Healing.

1. WOUND HEALING WOUND HEALING
PRESENTED BY
DR NOBODY
MS RESIDENT
GYNAE & OBS, UNIT 2
X MEDICAL

2. DEFINITION
Wound healing refers to the body’s
replacement of destroyed tissue by living
tissue.
Can be achieved by 2 processes: tissue
regeneration &scar formation.
Dynamic balance between these 2 is different
in different tissues.

3. Introduction
During healing, a complex cascade of cellular
events occur to achieve resurfacing,
reconstitution and restoration of tensile strength
of injured tissue.
Wound healing occurs in 3 phases
1.Inflammatory phase
2.Proliferative phase
3.Remodeling phase

4. Stages of wound healing

5. I. Inflammatory phase
A.Immediate to 2-5 days
B.Hemostasis
1.Vasoconstriction – damaged blood vessels
constrict
2.Hemostasis is achieved by formation of platelet
plug & activation of extrinsic & intrinsic clotting
pathways.
3.Formation of a provisional fibrin matrix
C. Recruitment of inflammatory cells into the
wound by potent chemoattractants

6. Early Events in Inflammation
Fibrin and fibronectin form a lattice that
provides scaffold for migration of
inflammatory, endothelial, and mesenchymal
cells.
Neutrophilic infiltrate appears: removes dead
tissue & prevent infection.
Monocytes/macrophages follow neutrophils:
orchestrated production of growth factors &
phagocytosis.

7. Late Events in Inflammation
Entry of lymphocytes.
Appearance of mast cell

8. II. Proliferative phase
A.2 days to 3 weeks
B.Granulation tissue formation (composed of
fibroblasts,macrophages and endothelial cell)
C.Angiogenesis
D.Contraction
I.Wound edges pull together to reduce the
defect
E.Epithelialization
I.Epithelial cells migrate across the new tissue to
form a barrier between the wound and the
environment

9. Mesenchymal cell proliferation
Fibroblasts are the major mesenchymal cells
involved in wound healing, although smooth
muscle cells are also involved.
Macrophage products are chemotactic for
fibroblasts. PDGF, EGF, TGF, IL-1,
lymphocytes are as well.
Replacement of provisional fibrin matrix with
type III collagen.

10. Angiogenesis
Angiogenesis reconstructs vasculature in
areas damaged by wounding, stimulated by
high lactate levels, acidic pH, decreased O2
tension in tissues.
Recruitment & assembly of bone marrow
derived progenitor cells by cytokines is the
central theme.
EGF-1 is most potent angiogenic stimulant
identified. Heparin is also an important as
cofactor, TGF- alpha, beta, prostaglandins
also stimulate.

12. Epithelialization
Basal cell layer thickening, elongation,
detachment & migration via interaction with
ECM proteins via integrin mediators.
Generation of a provisional BM which includes
fibronectin, collagens type 1 and 3
Epithelial cells proliferation contributes new
cells to the monolayer. Contact inhibition when
edges come together.

13. III. Remodeling phase
A.3 weeks to 2 years
B.New collagen forms which increases the
tensile strength of the wound
C.19 types identified. Type 1(80-90%) most
common, found in all tissue. The primary
collagen in a healed wound.
D.Type 3(10-20%) seen in early phases of
wound healing. Type V smooth muscle,
Types 2,11 cartilage, Type 4 in BM.

14. Remodelling
The number of intra and intermolecular cross-
links between collagen fibers increases
dramatically.
A major contributor to the increase in wound
breaking strength
Quantity of Type 3 collagen decreases
replaced by Type 1 collagen
Remodeling continues for 12 months, so scar
revision should not be done prematurely.

15. Wound Contraction
Begins approximately 4-5 days after wounding
by action of myofibroblasts.
Generally occurs in large surface wounds.
Represents centripetal movement of the
wound edge towards the centre of the wound.
Maximal contraction occurs for 12-15 days,
although it will continue longer if wound
remains open.

16. Wound contraction
The wound edges move toward each other at
an average rate of 0.6 to .75 mm/day.
Wound contraction depends on laxity of
tissues, so a buttock wound will contract faster
than a wound on the scalp or pretibial area.
Wound shape also a factor, square is faster
than circular.

17. Wound Strength
Skin wounds
At the end of first week,wound strength is
approximately 10% of unwounded skin
Wound strength increases rapidly over next 4
weeks and then slows down at approximately
at third month,reaches a plataue at about 70-
80% of the tensile strength of unwounded skin
Scar tissue is never as strong as the original
tissue !!

18. Important Growth factors
responsible for wound healing
Platelet derived growth factor:
Promotes migration and proliferation of fibroblasts
Is chemotactic for monocytes
Epidermal growth factor
Promotes growth of endothelial, epithelial cells
and fibroblasts

19. Growth factors in wound
healing
Fibroblast growth factor:
Promotes synthesis of ECM proteins including
fibronectin.
Chemotactic for fibroblasts and endothelial cells
Promotes angiogenesis
Vascular Endothelial Growth Factor (VEGF)
Angiogenesis
Macrophage derived growth factors
IL-1 and TNF
Promote proliferation of fibroblasts and endothelial cells.

20. Wound healing
Wound healing is accomplished in one of the
following two ways:
1.Healing by first intention (primary union)
2.Healing by second intention (secondary
union)

21. Healing by first intention (primary
union)
Occurs in clean, incised wounds with good
apposition of the edges – particularly planned
surgical incisions
(clean wounds – no infections or foreign bodies)
The incision causes only focal disruption of
epithelial basement membrane continuity and
death of a relatively few epithelial and
connective tissue cells.
As a result, epithelial regeneration
predominates over fibrosis

22. Healing by first
intention:
Sequence of events

23. Immediate
The narrow
incisional space
rapidly fills with
fibrin clotted blood
Dehydration at the
surface produces a
scab to cover and
protect the healing
repair site

24. Within 24 hrs
Movement and
proliferation of
epithelial cells across
the wound resulting
in a thin, but
continuous epithelial
layer
Early inflammation
close to the edges
(neutrophils)

25. 2-3 days
Neutrophils
replaced by
macrophages
Macrophages
remove the blood
clot
Proliferation of
epithelial cells
Fibroblastic activity

26. 10-14 days
Scab loose (aka dry
clot)
Epithelial covering
complete
Fibrous union of
edges
Wound still weak
vascularization

27. By the end of the first month
Scar comprises of a
cellular connective
tissue devoid of
inflammatory infiltrate,
covered by intact
epidermis
Dermal appendages
destroyed in the line of
incision are
permanently lost
Tensile strength of the
wound increases and
reaches maximum

28. Healing by second intention
(secondary union)
This occurs in open wounds, particularly when
there has been significant loss of tissue,
necrosis or large wounds with irregular margins
Regeneration of parenchymal cells cannot
completely reconstitute the original architecture
Abundant granulation tissue grows in from the
margin to complete the repair
Granulation tissues consists of:
ECM fibroblasts
Macrophages, neutrophils
New blood vessels

29. Healing by second
intention
(secondary union)
sequence of events

30. Early

31. A few days

32. 1 week
Epithelial
proliferation
Capillary loops
(granulations)
Scab shed
Loose connective
Tissue formed by
fibroblasts

33. 2 weeks onwards

34. Months
Full thickness of
Epithelium restored
Varying depth of
Surface depression
Thick collagenous
Scar tissue becoming
Less vascular

36. Secondary union differs from
primary union in several
respects
1.inflammatory reaction is
more intense
2.larger amounts of
granulation tissue formation
3.larger scar
4.***wound contraction
Myofibroblasts: modified
fibroblasts with feature of
SMC
defect significantly
decreases in size as wound
heals.

37. Factors that influence healing
Classified as
A.Systemic
and
B.Local

38. Systemic Factors that Delay/Retard
Wound Healing
Nutrition
Protein deficiency, Vitamin C deficiency
inhibit collagen synthesis
Zn deficiency (cofactor in type III collagenase)
Metabolic status
diabetes mellitus:
Susceptibility to infection caused by impaired
circulation and increased glucose.
Circulatory status
inadequate blood supply
atherosclerosis, vascular defects
Hormones
glucocorticoids inhibit collagen synthesis, decrease
inflammation

39. Local Factors that Delay/Retard
Wound Healing
Infection
most important cause of delayed wound healing
Persistent injury and inflammation
Mechanical factors
motion early in healing
Foreign material - like suture material and foreign bodies
Size, location & type of wound
wounds in ↑ vascularized areas (face) heal faster than
in poorly vasc areas (tendon, feet)
small wounds heal faster than larger
incisions faster than blunt trauma (contusions)

40. Complications of wound healing
1.Deficient scar formation
2.Excessive formation of repair
components
3.Exaggerated contraction

41. Deficient scar formation
Can lead to two types of complications:
A. Wound Dehiscence (rupture of wound)
most common after abdominal surgery
coughing, vomiting,
B. Ulceration - defect in the continuity

42. Wound Dehiscence

43. Excessive formation of repair
components
1.Keloid / hypertrophic scar (excess collagen)
2.Exuberant granulation or proud flesh
(excessive granulation tissue that protrudes
above the level of the surrounding skin and
impairs the growth of epithelium)

44. Keloid / hypertrophic scar
Raised scars due to accumulation of excess
amounts of collagen ( type III – type I)
Hypertrophic scars do not grow beyond the
boundaries of the original wound
Keloids grow beyond the boundaries of the
original wound (more serious)

45. Keloid

46. Exuberant granulation (proud
flesh)
Excessive granulation
tissue
Protrudes above
surrounding skin
Prevents re
-epithelialization

47. Exaggerated contraction
deformation of
surrounding tissue or
wound
Can compromise the
movement of joints.
most common on
palms, soles, anterior
thorax following
severe burns