2. Introduction
The body's ability to replace injured or dead
cells &
To repair tissues after inflammation is critical to
survival.
When injurious agents damage cells and
tissues, the host responds by setting in motion
a series of events that serve
To eliminate these agents,
Contain the damage, and
Prepare the surviving cells for replication.
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4. Cont…
A. Regeneration -proliferation of cells and
tissues to replace lost structures
E.g. -liver growth after partial resection or
necrosis, but these processes consist of
compensatory growth rather than true
regeneration.
5. Cont…
B. Repair - most often consists of a combination
of regeneration and scar formation by the
deposition of collagen
Relative contribution of regeneration and
scarring in tissue repair depends on the ability of
the tissue to regenerate and the extent of the
injury
6. Cont…
Scar formation is the predominant healing process
that occurs when the extracellular matrix (ECM)
framework is damaged by severe injury
ECM components are essential for wound
healing, because
They provide the framework for cell migration,
Maintain the correct cell polarity for the re-assembly of
multilayer structures, and
Participate in the formation of new blood vessels
(angiogenesis).
7. Cont…
cells in the ECM (fibroblasts, macrophages, and
other cell types) produce growth factors,
cytokines, and chemokines that are critical for
regeneration and repair.
9. Proliferative Capacities of Tissues
The ability of tissues to repair themselves is critically
influenced by their intrinsic proliferative capacity.
Based on this criterion, the tissues of the body are
divided into three groups.
A. Continuously Dividing Tissues(Labile tissues)
Continuously being lost and replaced by maturation
from stem cells and by proliferation of mature cells
E.G.
1. Hematopoietic cells in the bone marrow
10. Labile Tissues..
2. Surface epithelia, such as the stratified squamous
surfaces of the skin, oral cavity, vagina, and cervix;
3. Cuboidal epithelia of the ducts draining exocrine organs
E.g., Salivary glands, pancreas, biliary tract);
4. The columnar epithelium of the gastrointestinal tract,
uterus, and fallopian tubes
5. Transitional epithelium of the urinary tract.
These tissues can readily regenerate after injury as long
as the pool of stem cells is preserved.
11. B. Stable Tissues
Cells of these tissues are quiescent (in the G0 stage of the
cell cycle) and have only minimal replicative activity in
their normal state.
However, these cells are capable of proliferating in
response to injury or loss of tissue mass.
Stable cells constitute the parenchyma of most solid
tissues, such as liver, kidney, and pancreas.
They also include endothelial cells, fibroblasts, and
smooth muscle cells; the proliferation of these cells is
particularly important in wound healing.
With the exception of liver, stable tissues have a limited
capacity to regenerate after injury.
12. C. Permanent Tissues
The cells of these tissues are considered to be terminally
differentiated and non proliferative in postnatal life.
The majority of neurons and cardiac muscle cells belong
to this category.
Thus, injury to brain or heart is irreversible and results
in a scar, because neurons and cardiac myocytes do not
divide.
13. Regeneration
Regeneration refers to growth of cells and tissues to
replace lost structures.
In mammals, whole organs and complex tissues rarely
regenerate after healing, and the term is usually applied
to processes such as liver and kidney growth after,
respectively, partial hepatectomy and unilateral
nephrectomy.
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14. Regeneration …
Tissues with high proliferative capacity, such as the
hematopoietic system and the epithelia of the skin and
gastrointestinal tract, renew themselves continuously and
can regenerate after injury, as long as the stem cells of
these tissues are not destroyed.
Regeneration involves the restitution of tissue
components identical to those removed or killed.
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15. Repair by Healing, Scar Formation, & Fibrosis
By contrast, healing is a fibro proliferative response.
If tissue injury is severe or chronic, and results in
damage of both parenchymal cells and the stromal
framework of the tissue, healing can not be
accomplished by regeneration.
Under these conditions, the main healing process is
repair by deposition of collagen and other ECM
components, causing the formation of a scar
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16. Repair …
It is a complex but orderly phenomenon involving a number
of processes:
Induction of an inflammatory process in response to the
initial injury
1. Proliferation and migration of parenchymal and
connective tissue cells
2. Formation of new blood vessels (angiogenesis) and
granulation tissue
3. Synthesis of ECM proteins and collagen deposition
4. Tissue remodeling
5. Wound contraction
6. Acquisition of wound strength
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17. Repair by connective tissue
Occurs when repair by parenchymal
regeneration alone cannot be accomplished
Involves production of Granulation Tissue-
Replacement of parenchymal cells with
proliferating fibroblasts and
Vascular endothelial cells.
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18. Cont…
The repair process is influenced by many factors including
The tissue env”t and extent of tissue damage
Intensity and duration of tissue damage
Conditions that affect tissue repair like foreign body,
decreased blood supply
Various diseases that inhibit repair
E.g. DM, and treatment with steroids
19. Cutaneous Wound Healing…
Cutaneous wound healing is generally divided into three
phases:
1. Inflammation (early and late);
2. Granulation tissue formation and re-epithelialization
3. Wound contraction, ECM deposition, & remodeling.
These phases overlap, and their separation is somewhat
arbitrary
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20. Phases Cont…
The initial injury causes platelet adhesion and aggregation
and the formation of a clot in the surface of the wound,
leading to inflammation.
In the proliferative phase there is formation of granulation
tissue, proliferation and migration of connective tissue
cells, and reepithelialization of the wound surface
Maturation involves ECM deposition, tissue remodeling,
and wound contraction.
23. Healing by first intention (wounds with opposed
edges)
Skin wounds are classically described to heal by primary
or secondary intention.
This distinction is based on the nature of the wound
rather than the healing process itself.
The least complicated example of wound repair is the
healing of a clean, uninfected surgical incision
approximated by surgical sutures.
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24. Pattern of wound healing cont…
Such healing is referred to as primary union or
healing by first intention.
The incision causes death of a limited number of
epithelial and connective tissue cells as well as
disruption of epithelial basement membrane
continuity.
….
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25. Sequence of events in primary wound healing
Day1. Neutrophils appear at the margin of the incision,
move towards the Fibrin clot
Day 2. Epithelial cells move from the wound edge
along the cut margins of dermis and deposit
basement membrane
Day3.
neutrophils are replaced by macrophages
Granulation tissue formation
Collagen fiber formation begin
Epithelial cell proliferation thickens the epidermal
26. Day5 .
the incisional space is filled with granulation tissue
Maximal neovascularization
More abundant collagen fibers which start to bridge the
incision
The epidermis recovers its normal thickness
Week 2.
continuous accumulation of collagen and proliferation of
fibroblasts
Leukocyte infiltration , edema, and increased vascularity
subside
End of first month; the scar is made up of a cellular
connective tissue devoid of inflammatory infiltrates
27.
28. Healing by First Intention
-Focal disruption of basement
membrane and loss of only a few
epithelial cells
E.g. Surgical Incision
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29. Healing by second intention (wounds with separated edges)
When there is more extensive loss of cells and tissue, as in
surface wounds that create large defects, the reparative
process is more complicated.
Regeneration of parenchymal cells cannot completely
restore the original architecture, and hence abundant
granulation tissue grows in from the margin to complete the
repair.
This form of healing is referred to as secondary union or
healing by second intention.
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30. Second intention…
Secondary healing differs from primary healing in several respects:
The inflammatory reaction is more intense.
Much larger amounts of granulation tissue are formed.
Wound contraction, perhaps the feature that most clearly
differentiates primary from secondary healing.
Contraction of these cells at the wound site decreases the gap
between the dermal edges of the wound.
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31. Healing by Second Intention
-Larger injury, abscess,
infarction
-Process is similar but
-Results in much larger scar
and then contraction
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32. Factors affecting Healing:
Systemic
Nutrition
Vitamin def.(particularly vit c)
Age
Immune status
Metabolic status (e.g DM)
Circulatory status (e.g in
arteriosclerosis, varicose vein)
Hormones (e.g glucocorticoids)
inhibit collagen synthesis
Other diseases
Local
necrosis
Infection
apposition
Blood supply
Mobility
Foreign body
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34. Complications in cutaneous wound healing/
Pathologic aspects of healng
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 (wound dehiscence, ulcers)
2. Excessive formation of the repair components
(hypertrophic scar, Keloid, exuberant granulation)
3. Abnormal remodeling. … 34
35. Deficient scar formation
Inadequate formation of granulation tissue or assembly of
a scar can lead to two types of complications:
1.Wound dehiscence and
2.Ulceration
Dehiscence or rupture of a wound- is most common
after abdominal surgery and is due to increased abdominal
pressure.
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36. Excessive formation of the repair components
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.
Keloid formation appears to be an individual
predisposition, and for unknown reasons this aberration
is somewhat more common in african-americans.
…
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37. Note
Contraction in the size of a wound is an important
part of the normal healing process.
An exaggeration of this process is called a
contracture and results in deformities of the wound
and the surrounding tissues.
Contractures are particularly prone to develop on
the palms, the soles, and the anterior aspect of the
thorax.
Contractures are commonly seen after serious
burns and can compromise the movement of joints.
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