2. Outline
• Proliferative capacity of cell
• Types of healing process
• Factors affecting healing
• Complications of Wound Healing
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3. Wound
Definitions
Wound is a disruption of the normal structure and
function of the skin and underlying soft tissue.
Regeneration refers to growth of cells and tissues to
replace lost structures.
Healing is usually a tissue response to;
A wound (commonly in the skin),
Inflammatory processes in internal organs, and
Cell necrosis in organs incapable of regeneration.
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4. Types of wounds
Acute vs. chronic
Open vs. close
Tidy vs. untidy
Tidy vs untidy wounds
Tidy Untidy
Incised -Crushed or avulsed
Clean - Contaminated
Healthy tissues -Devitalized tissues
Seldom tissue loss - Often tissue loss
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5. • The body's ability to repair and replace injured/dead cells and
tissues after inflammation is critical to survival
Healing refers to the body’s replacement of destroyed tissue
• Involves two distinct processes:
1. Regeneration: replacement of lost tissue by similar tissues
2. Repair (healing by scaring)
– the restoration of tissue architecture and function by granulation
tissue which matures to form scar tissue
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6. • The repair process is influenced by many factors,
including:
- The tissue environment and the extent of tissue
damage
- The intensity and duration of the stimulus
- Adequacy of blood supply
- presence of foreign bodies
- Systemic diseases that inhibit repair
- Steroid therapy
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7. Types of cells based on proliferative capacity
1. Continuously Dividing(Labile cells)
– cells which have a continuous turn over by programmed
division of stem cells after injury as long as the pool of stem
cells is preserved
– They are found in the surface epithelium of the skin, GIT,,
urinary tract, uterus, lymphoid
– Has excellent regenerative capacity
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8. 2. Stable cells (Quiescent)
• Cells are quiescent and have few stem cells with only minimal
replicative activity in their normal state
• However, these cells are capable of proliferating in response to
injury or loss of tissue mass
– E.g.. mesenchymal cells such as smooth muscle cells,
fibroblasts, osteoblasts and endothelial cells , Liver, endocrine
glands and renal tubular epithelium
– Their chances of regeneration are good
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9. 3. Permanent cells
– They are terminally differentiated cells(non-dividing) in
postnatal life
– Once permanent damaged, cannot be replaced
– For example: adult neurons, striated muscle cells, and cells of
the lens, cardiac myocytes
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10. Healing by regeneration
• Regeneration is the renewal of a lost tissue in which the lost cells are
replaced by identical ones
• The capacity of a tissue for regeneration depends on its:
– proliferative ability
– degree of damage to stromal framework
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11. Repair (Healing by connective tissue)
• lost tissue is replaced by a scar
– If tissue injury is severe or chronic that extend through the
basement membrane, stromal framework, to the parenchymal
cells
– Healing by fibro proliferative response "patches" rather than
restores a tissue
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12. • Repair begins within 24 hours of injury by the emigration of
fibroblasts and the induction of fibroblast and endothelial cell
proliferation
• By 3 to 5 days, a specialized type of tissue that is called
granulation tissue is apparent
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13. Granulation tissue
• Term derives form its red pink (new capillary loops), soft, moist &
granular appearance on the surface of wounds
• Components
Newly growing blood vessels: provide nutrients, take away
cellular wastes, & transport new leukocytes
Proliferating fibroblasts: new matrix synthesis(collagen initially
type III later type I)
Inflammatory cells e.g., macrophages, neutrophils
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14. granulation-tissue formation pass through three phases
1. Phase of inflammation
– inflammatory exudate containing polymorphs, platelet
aggregation and fibrin deposition
2. Phase of demolition
– macrophage infiltrate and ingest particulate matter.
– proteolytic enzymes degrade inflammatory cells
3. Ingrowth of granulation tissue
– characterized by proliferation of fibroblasts and In growth of
new blood vessels with a variable number of inflammatory cell
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16. • Repaire consists of four sequential processes:
– Formation of new blood vessels (angiogenesis)
– Migration and proliferation of fibroblasts
– Deposition of ECM (scar formation)
– Maturation and reorganization of the fibrous tissue
(remodeling)
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17. Angiogenesis
• Blood vessels are assembled by two processes:
• Vasculogenesis: primitive vascular network is assembled from
angioblasts during embryonic development; and
• Angiogenesis or neovascularization: in which preexisting vessels
send out capillary sprouts to produce new vessels
• Angiogenesis is critical to chronic inflammation and fibrosis,
tumor growth, and vascularization of ischemic tissues
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18. Angiogenesis (Neovascularization)
• Vascular proliferation starts 48 to 72 hours after injury and lasts for
several days
It occurs because of:
• the branching and extension of adjacent blood vessels
– endothelial cells from these vessels become motile and
proliferate to form capillary beds
• recruitment of endothelial progenitor cells (EPCs) from the bone
marrow which can differentiate and form mature network by
linking with preexisting vessels
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20. Migration of Fibroblasts and ECM Deposition (Scar Formation)
• Scar formation builds on the granulation tissue framework of new
vessels and loose ECM that develop early at the repair site
• It occurs in two steps:
1. migration and proliferation of fibroblasts into the site of injury
2. deposition of ECM by these cells
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21. • As healing progresses, the number of proliferating fibroblasts and
new vessels decreases but fibroblasts increase the synthesis and
deposition of ECM
• collagen synthesis by fibroblasts begins early in wound healing
(days 3 to 5) and continues for several weeks
• the granulation tissue evolves into a scar composed of largely
inactive, spindle-shaped fibroblasts, dense collagen, fragments of
elastic tissue, and other ECM components
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22. ECM and Tissue Remodeling
• The outcome of the repair process is a balance between ECM
synthesis and degradation
• degradation of collagens and other ECM components is
accomplished by a family of matrix metalloproteinase (MMPs)
• MMPs include collagenases(MMP-1,-2 and -3); gelatinases
(MMP-2 and 9) and stromelysins (MMP-3,10, and 11)
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23. • MMPs are produced by a variety of cell types (fibroblasts,
macrophages, neutrophils, synovial cells, and epithelial cells)
• their synthesis and secretion tightly controlled regulated by
growth factors and cytokines and inhibited by TGF-β and
suppressed by steroids
• elaborated as inactive precursors and activated collagenases can
be rapidly inhibited by specific TIMPs
• They are essential in the debridement of injured sites and in the
remodeling of the ECM
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24. Wound Healing
• In very superficial wounds, the epithelium is reconstituted and
there may be little scar formation
• Epidermal appendages do not regenerate, and there remains a
connective tissue scar
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26. Phases of wound healing
• events in wound healing overlap to a great extent and cannot be
completely separated from each other
1. Coagulation phase
induced immediately following injury
characterized by vaso-constriction, clot formation and release
of platelets and other substances necessary for healing and
help as a bridge between the two edges
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27. 2. Inflammatory phase:
takes place from time of wounding up to three days
characterized by classical inflammatory response,
vasodilatation and pouring out of fluids, migration of
inflammatory cells and leukocytes and rapid epithelial growth
3. Proliferate Phase(phase of fibroplasia)
starts around the 3rd day of injury and stays for about three
weeks
characterized by fibroblast, epithelial and endothelial
proliferation, Collagen synthesis, and ground substance and
blood vessel production
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28. Maturation phase(phase of remodeling)
takes the longest period which may extend for up to one year
Equilibrium between protein synthesis and degradation
leading to slow and continuous increase in tissue strength
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29. based on the nature of the wound, Skin wounds heal by
– primary intention
–secondary intention or
– Healing by third intention
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30. Healing by first intention (primary union)
• The incision causes only focal disruption of epithelial basement
membrane and death of a few epithelial & connective tissue cells
• the wounds are sealed immediately with simple suturing, skin
graft placement, or flap closure, such as closure of the wound at
the end of a surgical procedure
• epithelial regeneration predominates over fibrosis
• A small scar is formed, but there is minimal wound contraction
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31. • dehydration of the surface clot forms the well-known scab that
covers the wound
– E.g. healing of a clean, uninfected surgical incision
approximated by surgical sutures
The healing process follows a series of sequential steps:
• Within 24 hrs.
– neutrophils appear
• In 24 to 48 hours
– spurs of epithelial cells move from the wound edges
– They fuse in the midline beneath the surface scab, producing a
continuous thin epithelial layer that closes the wound
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32. • By day 3
– the neutrophils largely replaced by macrophages
– Granulation tissue progressively invades the incision space
– Collagen fibers are now present in the margins of the incision
but do not bridge the incision
• By day 5
– the incisional space is filled with granulation tissue
– Neovascularization is maximal
– type III collagen fibrils become more abundant but by day 7 to
8, type I is prominent and becomes the major collagen of
mature scar tissue
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33. • During the 2nd wk
– continued collagen accumulation and fibroblast
proliferation
– The leukocyte infiltrate, edema, and increased vascularity
are substantially diminished
• By the end of the first month
– the scar is made up of a cellular connective tissue devoid of
inflammatory infiltrate, covered by intact epidermis
– The dermal appendages in the line of the incision are
permanently lost
• Tensile strength of the wound increases thereafter, but it may
take months for the wounded area to obtain its maximal strength
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35. Wound contraction
it is a mechanical reduction in the size of the defect
wound is reduced approximately by 70-80% of its original size
If contraction is prevented, healing is slow and a large ugly scar is
formed
Causes of contraction
• It is said to be due to contraction by myofibroblasts which have
the features intermediate between those of fibroblasts and smooth
muscle cells
• Two to three days after the injury they migrate into the wound and
their active contraction decrease the size of the defect
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36. Healing By Second Intention(secondary union )
• occurs in wounds with widely separated edges, contaminated with
abscess formation which are not primarily closed
• Healing takes place by granulation tissue formation, tissue
contraction and epithelialization
• Closure by secondary, or spontaneous, intention involves no active
intent to seal the wound
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37. • Secondary healing differs from primary healing in several
respects:
• more intense inflammatory reaction( more necrotic debris
and exudate)
• abundant granulation tissue development
• larger fibrin clot that fills the defect
• formation of a large scar
• the wound contracts
• takes much longer time
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38. Healing by third intention:
- This occurs in wounds which are left open initially for various
reasons and closed later (delayed primary closure)
- contaminated wound is initially treated by repeated
débridement, or antibiotics for several days to control infection
- Once the wound is being ready for closure approximation will
be performed
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39. Wound Strength
• Carefully sutured wounds have approximately 70% of the strength
of unwounded skin
• When sutures are removed= strength is approximately10% but
this increases rapidly over the next 4 weeks
• Wound strength reaches approximately 70% to 80% of normal by
3 months but usually does not substantially improve beyond that
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40. Factors affecting healing
Local factors
• Infection
• Mechanical factors: early motion
• Foreign bodies: sutures, steel, etc
• Size, location
• type of wound
• Adhesions
• Radiation
Systemic factors
• Age
• Nutrition
– Protein, Vitamin C, Zinc
deficiency
• DM
• Circulatory status
• Corticosteroids:
• Granulocytopenia
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41. Complications In Cutaneous Wound Healing
• Complications in wound healing can arise from abnormalities in
any of the basic components of the repair process
• These aberrations can be grouped into three general categories:
1) Deficient scar formation,
2) Excessive formation of the repair components, and
3) Formation of contractures
Others
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42. • Inadequate formation of granulation tissue or assembly of a scar
can lead to two types of complications:
wound dehiscence and ulceration
• Dehiscence or rupture of a wound is most common after
abdominal surgery and is due to increased abdominal pressure
• The accumulation of excessive amounts of collagen may give rise
to a raised scar known as a hypertrophic scar; if the scar tissue
grows beyond the boundaries of the original wound and does not
regress, it is called a keloid.
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44. Hypertrophic scar
• Occurs anywhere in the
body
• It is limited to the scar
tissue only and It will not
extend to normal skin.
• Not genetically
predisposed
• Growth usually limits up
to 6 months
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45. Keloid
• Grows beyond the
boundaries of the original
wound & does not regress
• Frequently seen on earlobes,
shoulders, upper back and
anterior chest
• Other sites are upper arm,
chest wall, lower neck in
front
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