Wound healing dr sumer

wound healing

1. Dr sumer yadav

2. wound
Any violation of live tissue integrity may be regarded
as a wound
Skin is the largest organ of the human body.
Acute wound- orderly and timely reparative
process - laceration, puncture, abrasion, avulsion,
amputation, contusion
Chronic wound – wound not healed in 4 weeks.
Venous and arterial ulcers, diabetic ulcers, pressure
ulcers.

3. Three techniques of wound
treatment
Primary intention- all tissue including skin are closed
with suture material.
Secondary intention – in which wound is left open
and close naturally.
Tertiary intention – in which wound is left open for
number of days and then closed if it found to be
clean.

4. DEFINITION – wound healing
Response of an organism to a physical disruption of a
tissue/organ with an aim to repair or reconstitute the
defect and to re-establish homeostasis.
Can be achieved by 2 processes: scar formation &
tissue regeneration.
Dynamic balance between these 2 is different in
different tissues.

5. Introduction
During healing, a complex cascade of cellular events
occur to achieve resurfacing, reconstitution and
restoration of tensile strength of injured tissue.
3 classic but overlapping phases occur: inflammation,
proliferation & maturation.

6. Phases of Healing
Inflammatory (Reactive)

Haemostasis Inflammation
Proliferative (Regenerative/Reparative)

Epithelial migration proliferation Maturation
Maturational (Remodeling)

Contraction scarring Remodeling

8. Early Wound Healing Events (Days 1-4)
A. Inflammatory or reactive phase
- immediate response to injury
- goals: hemostasis, debridement , sealing of the
wound
Events
1.Increase vascular permeability
2.Chemotaxis
3.Secretion of cytokines
4.Growth factor

9. Inflammatory Phase
Blood vessels are disrupted, resulting in bleeding.
Hemostasis is achieved by formation of platelet plug
& activation of extrinsic(initiation) & intrinsic
clotting(amplification) pathways.
Formation of a provisional fibrin matrix.
Recruitment of inflammatory cells into the wound by
potent chemoattractants.

11. Inflammatory phase
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.

12. Inflammatory cells
PMN
-Migration of PMN stops when wound
contamination has been controlled
-Don’t survive more than 24 hours
-Increase contamination stimulates PMN
resulting to delayed wound healing and
destruction of tissues.
-Not essential for wound healing

13. Inflammatory cells
Macrophages
-Orchestrate release of cytokines/ Process
of wound healing/ release of growth
factors
-24 – 48 hours
-Source of TNF /interleukin 1, 6, 8

14. Macrophage Activities During Wound Healing
Activity Mediators
Phagocytosis Reactive oxygen species
Nitric oxide
Débridement Collagenase, elastase
Cell recruitment
and activation
Growth factors: PDGF, TGF-, EGF, IGF
Cytokines: TNF-, IL-1, IL-6
Fibronectin
Matrix synthesisGrowth factors: TGF-, EGF, PDGF
Cytokines: TNF-, IL-1, IFN-
Enzymes: arginase, collagenase
Prostaglandins
Nitric oxide
Angiogenesis Growth factors: FGF, VEGF
Cytokines: TNF-
Nitric oxide

15. Table 8-2 Growth Factors Participating in
Wound Healing
Stimulates fibroblasts,
keratinocytes,
chondrocytes, myoblasts

Mitogenesis: mesoderm
and neuroectoderm

Stimulation of angiogenesis
(by stimulation of
endothelial cell proliferation
and migration)
Fibroblasts, endothelial
cells, smooth muscle
cells, chondrocytes
Fibroblast
growth
factor
(FGF)
Stimulation of collagen
synthesis

Stimulation of angiogenesis
Mitogenesis: fibroblasts,
smooth muscle cells

Chemotaxis: fibroblasts,
smooth muscle,
monocytes, neutrophils
Platelets,
macrophages,
monocytes, smooth
muscle cells,
endothelial cells
Platelet-
derived
growth
factor
(PDGF)
Cellular and Biological
Effects
Wound Cell OriginGrowth
Factor

16. Table 8-2 Growth Factors Participating in
Wound Healing
Keratinocyte growth
factor (KGF)
Keratinocytes, fibroblastsSignificant homology with
FGF; stimulates keratinocytes
Epidermal growth
factor (EGF)
Platelets, macrophages,
monocytes (also identified in
salivary glands, duodenal
glands, kidney, and lacrimal
glands)
Stimulates proliferation and
migration of all epithelial cell
types
Transforming growth
factor- B (TGF- B
)
Keratinocytes, platelets,
macrophages
Homology with EGF; binds to
EGF receptor
Mitogenic and chemotactic
for epidermal and endothelial
cells
Transforming growth
factor- alpha (TGF-
alpha ) (3 isoforms:

1
,
2
,
3
)

Platelets, T lymphocytes,
macrophages, monocytes,
neutrophils
Stimulates angiogenesis
TGF-
1
stimulates wound
matrix production (fibronectin,
collagen
glycosaminoglycans);
regulation of inflammation

TGF-
3
inhibits scar
formation

21. Late Events in Inflammation
Entry of lymphocytes.
Appearance of mast cell: aberrant scarring?

22. Inflammatory cells
Lymphocytes
-Peak on 7
th
day
-Affects fibroblast
-Stimulate cytokines
-Not essential for acute wound healing

24. B. Proliferative phase
Goal: granulation tissue formation
Events:
1.Angiogenesis
2.Fibroplasia
3.Epithelization

25. Proliferative Phase
Granulation tissue formation (composed of
fibroblasts, macrophages and emdothelial cells).
Contraction.
Re-epithelialization (begins immediately after injury)
Decrease collagen synthesis at 4 weeks after
injury

26. Proliferative phase
Extracellular matrix
-Scaffold for cellular migration
-Composed of fibrin, fibrinogen,
fibronectin, vitronectin
Fibronectin and type 3 collagen = early
matrix
Type 1 collagen – wound strength later

27. Proliferative phase
Hydroxylation results in stable triple
stranded helix
Vitamin C, TGF B, IgF 1, IgF 2- increase
collagen synthesis
Interferon Y , steroids – decreases collagen
synthesis

29. 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.

30. 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.
FGF-1 is most potent angiogenic stimulant
identified. Heparin important as cofactor, TGF-
alpha, beta, prostaglandins also stimulate.

32. 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 5.
Epithelial cells proliferation contributes new cells
to the monolayer. Contact inhibition when edges
come together.
By three keratinocyte functions – migration ,
proliferation and differentiation.

35. Remodeling Phase
Goal: scar contraction with collagen cross-
linking, shrinking and loss of edema
Programmed regression of blood vessels &
granulation tissue.
Wound contraction.
Collagen remodeling.

36. Maturation phase
Wound contraction – centripetal movement
of full thickness of skin
Decreases amount of disorganized scar
Wound contracture, physical restriction,
limitation of function- result of wound
contraction
Appearance of stimulated fibroblast known
as myofibroblast

38. Fetal Wound Healing
Younger the fetus less noticeable is the scar
Fetal fibroblasts even in adult transplantation heals with the
absence of inflammation
Theory: that wound fibroblasts do not become myofibroblasts
until late in gestation.
IL6 is high in adult stimulated fibroblasts compared to fetal
stimulated ones with coincides with increased inflammation in
adults
Thrombospondin 1 decreases with increase in gestation. It
destabilizes matrix contracts in the EC space, facilitates
mitogenesis and chemotaxis. Promotes cell associated protease
and self supports matrix turnover. Thus inflammation would
decrease and there would be less scarring

40. Collagen
19 types identified. Type 1(80-90%) most common,
found in all tissue. The primary collagen in a healed
wound.
Type 3(10-20%) seen in early phases of wound
healing. Type V smooth muscle, Types 2,11 cartilage,
Type 4 in BM.

41. Wound Contraction
Begins approximately 4-5 days after wounding by
action of myofibroblasts.
Represents centripetal movement of the wound edge
towards the center of the wound.
Maximal contraction occurs for 12-15 days, although it
will continue longer if wound remains open.

42. 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.

43. Wound Contraction
Contraction of a wound across a joint can cause
contracture.
Can be limited by skin grafts, full better than split
thickness.
The earlier the graft the less contraction.
Splints temporarily slow contraction.

44. Remodeling
After 21 days, net accumulation of collagen becomes
stable. Bursting strength is only 15% of normal at this
point. Remodeling dramatically increases this.
3-6 weeks after wounding greatest rate of increase, so
at 6 weeks we are at 80% to 90% of eventual strength
and at 6months 90% of skin breaking strength.

45. Remodeling
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 mos, so scar revision
should not be done prematurely.

49. Local Factors
Iscemia
Infection: impairs healing.
Smoking: increased platelet adhesiveness, decreased
O2 carrying capacity of blood, abnormal collagen.
Radiation: endarteritis, abnormal fibroblasts.

50. Systemic Factors
Malnutrition
Cancer
Old Age
Diabetes- impaired neutrophil chemotaxis,
phagocytosis.
Steroids and immunosuppression suppresses
macrophage migration, fibroblast proliferation,
collagen accumulation, and angiogenesis.
Reversed by Vitamin A 25,000 IU per day.

52. Inadequate Regeneration
CNS injuries
Bone nonunion
Corneal ulcers

53. Inadequate Scar Formation
Diabetic foot ulcers.
Sacral pressure sores.
Venous stasis ulcers.

54. Excessive Regeneration
Neuroma
Hyperkeratosis in cutaneous psoriasis
Adenomatous polyp formation.

55. Excessive Scar Formation
Excessive healing results in a raised, thickened
scar, with both functional and cosmetic
complications.
If it stays within margins of wound it is
hypertrophic. Keloids extend beyond the confines
of the original injury.
Dark skinned, ages of 2-40. Wound in the
presternal or deltoid area, wounds that cross
langerhans lines.

56. Keloids and Hypertrophic Scars
Keloids more familial
Hypertrophic scars develop soon after injury, keloids
up to a year later.
Hypertrophic scars may subside in time, keloids
rarely do.
Hypertrophic scars more likely to cause contracture
over joint surface.

57. Keloids and Hypertrophic Scars
Both from an overall increase in the quantity of
collagen synthesized.
Recent evidence suggests that the fibroblasts within
keloids are different from those within normal dermis
in terms of their responsiveness.
No modality of treatment is predictably effective for
these lesions.