educational purpose

1. Wound Healing
ABDI SOLOMON(GSR 1)
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2. Outlines
 Definition
 Phases of Wound healing
 Healing in specific tissue
 Factors affecting healing
 Abnormal wound healing
 types of wound healing
 Reference
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3. Definition
 Any violation of live tissue integrity may be regarded
as a wound.
 Wound healing is a complex cellular and biochemical cascade
that leads to restitution of integrity and function
 Can be achieved by two processes: scar formation and tissue
regeneration.
 Dynamic balance between these two is different in different tissues
and organs.
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4. Phases of Wound healing
 Normal wound healing follows a
predictable pattern that can
be divided into overlapping phases defined by
characteristic cellular populations and
biochemical activities:
1. hemostasis and inflammation
2. Proliferation
3. maturation and remodeling
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5. Hemostasis
 includes vasoconstriction by the smooth muscle of the blood vessels,
platelets adhesion and aggregation and activation of coagulation cascade.
 The component of injured tissue , fibrillar collagen and tissue factor , act
to activate the extrinsic clotting cascade and prevent ongoing hemorrhage.
 The end result of coagulation cascade is fibrin matrix ,which provides
scaffold for cell migration required during a later phase of wound healing.
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7. inflammation
 Cellular infiltration after injury follows a characteristic
predetermined sequence
 For the first two days PMNs infiltrate into the fibrin matrix
,whose primary role is to remove dead tissue by phagocytosis
and prevent infection by oxygen dependent and independent
killing mechanism.
 By the third day monocytes & macrophages are predominant
,involved in phagocytosis of debris,& bacteria. Also produce
growth factor important for production of extracellular matrix
by fibroblast and new blood vessels.
 Mast cells degranulate, releasing histamine and other mediators
of vasodilation and cellular migration.
 The lymphocyte , the last cell to enter wound between 5 to 7
days, although its functionis not fully defined. but, declares the
start of the proliferative phase.
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T lymphocytes:
play an active role in the modulation of the wound environment
and truly bridge the transition from the inflammatory to the proliferative phase of healing

9. A wound at Inflammatory Phase
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10. Proliferative phase
 The proliferative phase is the second phase of wound healing
 and roughly spans days 3 through 21 .
 It is during this phase that tissue continuity is re=established.
 Mainly mediated by fibroblasts, endothelial & epithelial cells
 Characterized by
 Epithelialization
 Fibroplasia &
 Vascularization
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11.  Wound vascularization may be achieved by
angiogenesis or vasculogenesis.
 Angiogenesis represents sprouting of
capillaries from existing blood vessels in the
wound edge tissue.
 Vasculogenesis relies on the formation of
new blood vessels by mobilization of bone
marrow-derived endothelial stem cells
 .TNF &,TGF-β, TGF- α, bFGF, PDGF, and
VEGF play a key role in driving wound
angiogenesis.
Vascularization
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12. Fibroplasia
 Upon entering the wound environment, recruited fibroblasts first need to
proliferate, and then become activated, to carry out their primary function of
matrix synthesis remodeling.
 the strongest chemotactic factor for fibroblasts is PDGF.
 Production of collagen is hallmark of proliferative phase
 Other chemokines involved in stimulation of fibroblasts are EGF, IGF-I, TGF-β,
 produce glycoprotein and mucopolysaccharides, which make up ground
substance.
 fibroblasts acquire smooth-muscle cell characteristics and differentiate into
contractile myofibroblasts.
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13. Epithelialization
 Involves a sequence of changes in wound
keratinocytes—detachment, migration,
proliferation, differentiation, and
stratification.
 Absence of neighboring cells at the wound
margin and expression of EGF, TGF-α, and
KGF stimulate epitheliazation
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The epithelial cells move in leapfrog and
tumbling fashion until the edges establish
contact. If the basement membrane zone is
not intact, it will be repaired first

14. Collagen Cross Linking, Collagen Remodeling, and Wound Contraction
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15. Cont…
 During the remodelling phase there is no net increase in collagen (state of
collagen homeostasis).
 The extensive capillary network produced in the proliferative phase begins to
involute.
 The collagen fibres, which are initially laid down in a haphazard manner, become
arranged in a more organized manner.
 The rate of collagen synthesis declines after 4 weeks and eventually balances
the rate of collagen destruction by collagenase (MMP-1). At this point, the
wound enters a phase of collagen maturation
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16. Collagen
 the most abundant protein in the body,
 plays a critical role in the successful completion of adult wound healing.
 Its deposition, maturation, and subsequent remodeling are essential to the
functional integrity of the wound.
 Although there are at least 18 types of collagen described, the main ones of
interest to wound repair are types I and III.
 Principal amino acids that make up collagen are glycine, proline,
hydroxyproline and hydroxylysine
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17. Cont…
 Wound strength and mechanical integrity in the fresh wound are determined
by both the quantity and quality of the newly deposited collagen.
 The deposition of matrix at the wound follows xic pattern:
 Fibronectin and collagen lll—early
 GAGS and proteoglycans—next
 Collagen l—last
 Scar remodeling continues for many (6 to 12) months postinjury, gradually
resulting in a mature, avascular, and acellular scar.
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18. Collagen Cross Linking and
Collagen Remodeling
 Type III collagen in the early proliferative phase will be replaced by Type I
and fibril formation and fibril cross-linking occurs which result in decreased
collagen solubility, increased strength, and increased resistance to enzymatic
degradation.
Fibril cross linking
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19. Wound contraction
 Response to injury that is aimed at juxtaposing the edges of an open wound.
 early phase of wound closure appears to be mediated by a contractile
“purse-string” force produced by a circumferentially arranged band of
fusiform-shaped epidermal cells situated in the wound margin.
 Fibroblasts acquire smooth-muscle cell characteristics and differentiate into
contractile myofibroblasts.
 intact epidermal barrier is enabled through wound epithelializatio
 Reorganization of the cytoskeleton
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20. Remodeling phase
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21. Healing In Specific Tissues
GIT
 Healing begins with a surgical or mechanical reaposition of bowel ends
 Injuries to all parts of the GIT under go the same sequence of healing as
cutaneous wounds
 There are some differences:
1. Mesothelial or serosal and mucosal healing can occur with out scarring
2. Collagenase activity occurs early in the healing process and during the
first 3-5ds collagen break down far exceeds collagen synthesis
3. Collagenase is much more marked in the colon compared to SB.
 Failure of healing results in dehiscence,leaks and fistulas.
 Excessive healing results in stricture and stenosis.
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22. Bone healing
 The phases of bone healing are similar to those of wound healing.
1. Hematoma formation
2. Inflammation
3. Soft callus formation:three to 4 days after injury, characterized by the end of
pain and inflammatory signs
 Periosteal proliferation occurs on the outer aspect of the cortex.
 Endosteal proliferation occurs on the inner aspect of the cortex.
4. Hard Callus formation: may take up to 2 to 3 months
 Callus consists of immature woven bone composed of osteoid laid down by osteoblasts.
 This osteoid is mineralized with hydroxyapatite.
5. Remodeling
 The cortical structure and medullary cavity are restored.
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23. Cartilage healing
 Superficial wound
 Slow to heal and often results in persistent structural defects.
 Deep wound
 Healing is fast and complete
Why such a difference?
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24. Tendon
 Tendons and ligaments subjected to a variety of injuries
such as laceration,rupture and contusion
 Tenocytes are very active metabolically and retain a large
regenerative potential
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25. Nerve
 There are three types of nerve injuries:
 neurapraxia =focal demyelination
 axonotmesis =interruption of axonal continuity but preservation of Schwann cell
basal lamina
 neurotmesis =complete transection
 Following all types of injury, the nerve ends progress through a predictable
pattern of changes involving three crucial steps:
(a) survival of axonal cell bodies;
(b) regeneration of axons that grow across the transected nerve to reach the
distal stump; and
(c) migration and connection of the regenerating nerve ends to the appropriate
nerve ends or organ targets 3/3/2024 25

26. Fetal Wound Healing
 The main characteristic that distinguishes the healing of fetal wounds from
that of adult wounds is the lack of scar formation.
 characteristics that may influence the differences between fetal and adult
wounds; wound environment, inflammatory responses, differential growth
factor profiles, and wound matrix.
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This so-called “transition wound”
occurs at the beginning of the third trimester
1. absence of TGF
2. sterile, temperature-stable fluid
3. Reduced fetal inflammation due to the immaturity of the fetal immune system
but collaen & matrix synthesis
4. excessive and extended hyaluronic acid production

27. Factors Affecting Healing
 Local :
 Ischemia and decreased O2 tension
 FB
 Infection
 Irritation by urine or fecal matter
 Mov’t
 Irradiation
 Site of wound
 Mechanism of injury
 Loss of tissue
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28. Cont’d
Systemic
 Age
 Malnutrition(under and over nutrition)
 Ds like DM,cirrhosis,renal failure, malignancies….
 Medications:steroids,cytotoxic agent
 Imminodef(HIV/AIDS)
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29. Abnormal wound healing
1 Chronic wounds
 wounds that have failed to proceed through the orderly process that
produces satisfactory anatomic and functional integrity
 The majority of wounds that have not healed in 3 months are considered
chronic.
 Chronic wounds can be broadly classified into three major categories:
venous and arterial ulcers, diabetic ulcers, and pressure ulcers.
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30. Cont’d
Venous ulcers
 are wounds that are thought to occur due to improper
functioning of venous valves, usually of the legs.
 They are the major cause of chronic wounds, occurring in 50–70% of
chronic wound cases.
 Venous ulcers develop mostly along the medial distal leg, and can be
very painful.
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31. Cont’d
Arterial ulcers
 Because both arterial and venous ulcers typically occur on the lower leg,
differrentiating between them is difficult
 The most common cause of arterial ulcers is atherosclerosis.
 Risk factors for the develop-ment of atherosclerosis include age, smoking,
diabetes mellitus, hypertension, dyslipidemia, family history, obesity, and
sedentary lifestyle
Diabetic ulcers
 In diabetics, the effects of peripheral neuropathy, peripheral vascular
disease, and infection often combine to facilitate the development of
diabetic ulcers that can lead to gangrene and amputation.
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32. Cont’d
Pressure ulcers
 is a localized injury to the skin or underlying tissue,usually
over a bony prominence, as a result of unrelieved pressure.
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33. Excess healing
 Hypertrophic scar
 Keloids
 Contractures
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34.  Hypertrophic scar
 Excessive scar tissue that does not
extend beyond the boundary of the
original incision or wound.
 Usually occur across areas of
tension and flexor surfaces,
which tend to be at right angles to
joints or skin creases.
 Usually develop within 4 weeks
after trauma.
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35.  Keloids
 Excessive scar tissue that extends beyond the
boundaries of the original incision or wound.
 Keloids tend to occur 3 months to years
after the initial insult.
 Certain body sites have a higher incidence of
keloid formation, including the skin of the
earlobe as well as the deltoid, presternal, and
upper back regions.
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36. Contractures
 Where scars cross joints or flexion creases, a
tight web may form restricting the range of
movement at the joint.
 can cause hyperextension or hyperflexion
deformity
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37. Types of Wound healing
 Three basic types of healing
 Primary
 Secondary
 Delayed Primary or Tertiary- healing
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38.  Primary
 Wound surfaces opposed
 Healing without complications
 Minimal new tissue
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39.  Secondary healing
 Surfaces not
approximated
 Defect filled by
granulation
 Covered with
epithelium
 Less functional
 More sensitive to
thermal and
mechanical injury
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40. Secondary Wound Healing
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41.  Delayed primary healing
 Left open initially
 Edges approximated 4-6 days later
 For contaminated wounds
 skin Grafts and flaps may be reqiured
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42. References
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43. THANKS !!!!
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