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Chapter 4
Tissue renewal and
repair
1
Course outlines
 Describe the process of tissue repair
Specify the patterns of wound healing
 List the factors that influence wound
healing
Discuss the complications of wound
healing
 Understand fracture healing
2
Definition of tissue repairing
•Repair sometimes is called healing
• Refers to the restoration of tissue
architecture and function after an injury
3
Process of healing
• Occurs by two types of reactions
• 1. Regeneration – the replacement of loss tissue
by tissues similar in type.
• Occurs in tissues with high proliferative
capacity.
• Such as: - hematopoietic system→BM
- epithelia of the skin
4
Ctd...
2. Healing by scar formation – the replacement of
loss tissue by granulation tissue which matures to
form scar tissue.
• E.g. In skin, superficial wounds heal by
regeneration but deep wounds (dermis) heal by
scar formation.
• Fibrosis - the extensive deposition of collagen
that occurs in the lungs, liver, kidney and other
organs as a consequence of chronic
inflammation.
5
6
7
Control of normal cell
proliferation
• In adult tissues, the size of the cell population is
determined by the:
 rates of cell proliferation
differentiation &
death by apoptosis
• Cell proliferation can be stimulated by physiologic &
pathologic conditions.
8
Ctd...
• Pathologic conditions such as injury, cell death &
mechanical alteration of tissues stimulate cell
proliferation.
• Cell proliferation is largely controlled by signals
(soluble or contact dependant) from the
environment which may stimulate or inhibit cell
proliferation.
9
Types of cells
• Based on their proliferative capacity there are three
types of cells:
1. labile cells
• These are cells which have a continuous turn over
by programmed division of stem cells.
• They are found in the surface epithelium of the GI
tract, urinary tract or the skin.
10
Ctd...
• cells of lymphoid & haemopoietic systems are
further examples of labile cells.
• The chances of regeneration are excellent.
2. Stable cells
• Tissues which have such type of cell have normally
a much lower level of replication & there are few
stem cells.
11
Ctd...
• However, the cells of such tissues can undergo
rapid division in response to injury.
• Example – mesenchymal cells such as smooth
muscle cells, fibroblasts, osteoblasts & endothelial
cells are stable cells which can proliferate
• Liver, endocrine glands & renal tubular
endothelium has also such type of cells which can
also regenerate
12
3. Permanent cells
• These are non dividing cells.
• If lost, permanent cells cannot be replaced.
• Example – adult neurons, striated muscle cells,
myocytes & cells of the lens
13
HEALING BY REGENERATION
• Definition: - regeneration (generare = bring to life)
is the renewal of a lost tissue or part in which the
lost cells are replaced by identical ones.
• It involves two processes
1. Proliferation of surviving cells to replace lost
tissue
2. Migration of surviving cells in to the vacant
spaces
14
Ctd...
• The capacity of tissue regeneration depends on its:
1. Proliferative ability
2. degree of damage to stromal frame work
3. on the type & severity of the damage
• Tissues formed from labile & stable cells can
regenerate if and only if stromal frame work are
intact
15
16
Repair by Scarring
• If repair cannot be accomplished by regeneration
alone, it occurs by replacement of the injured cells
with connective tissue, leading to the formation of
a scar, or by a combination of regeneration of some
residual cells and scar formation.
• happen if the tissue injury is severe or chronic and
results in damage to parenchymal cells and
epithelia as well as to the connective tissue
framework, or if non dividing cells are injured.
• In contrast to regeneration, which involves the
restitution of tissue components, scar formation is
a response that “patches” rather than restores the
tissue. 17
Steps in Scar Formation
• Repair by connective tissue deposition consists of a
series of sequential steps that follow tissue injury.
1.haemostatic plug comprised of platelets is formed,
stops bleeding , occurs within minutes after injury,.
2.Inflammation
Macrophages are the central cellular players in the
repair process.
18
3.Cell proliferation takes up to 10 days.
Epithelial cells migrate over the wound to cover
it.
Endothelial and other vascular cells proliferate
to form
new blood vessels(angiogenesis).
Fibroblasts- lay down collagen fibers (begins 3 –
5 days after injury) form the scar.
• The combination of proliferating fibroblasts, loose
connective tissue, new blood vessels and scattered
chronic inflammatory cells, forms a type of tissue
that is unique to healing wounds and is called
granulation tissue.
19
20
21
22
Wound healing
• Two types of wound healing
• described depending on the amount of tissue
damage.
• These are essentially the same process varying only
in amount.
• These include healing by first intention & healing by
second intention.
• Whether a wound heals by primary or secondary
union is determined by the nature of the wound,
rather than by the healing process itself !!
23
24
Healing by First Intention:
Timeline
• Occurs in wounds that close easily.
• Epithelial regeneration predominates over fibrosis.
• Healing is fast, with minimal scarring/infection
• Examples:
• Paper cuts
• Well-approximated surgical incisions
25
Healing by First Intention:
Timeline
• By 24- 48 hours
• Wound space is filled with blood & fibrin clots.
• Fibrin clot dries.
• Neutrophils come in
• Epithelium begins to regenerate.
26
• By 3-7 days
• Macrophages come in
• Granulation tissue is formed
• new blood vessels
• fibroblasts
• Collagen begins to bridge incision
• Epithelium increases in thickness
27
Weeks later
• Granulation tissue gone
• Collagen is remodeled
• Epidermis full, mature.
• (but without dermal appendages!)
• Eventually, scar forms
28
29
Healing by second intention
• Occurs in larger wounds that have gaps between
wound margins
• Fibrosis predominates over epithelial regeneration
• Healing is slower, with more inflammation and
granulation tissue formation, and more scarring
• Examples: Infarction,Large burns and ulcers, Large
devitalized tissue
• Regeneration of parenchymal tissues can not
completely restore original architecture.
30
• Differs from primary union in several ways:
- More fibrin, more debris more intense
inflammation
- More granulation tissue is formed
- Wound contraction aided by myofibroblasts
31
24 hrs
• Wound space is filled
with blood & fibrin
clots.
• Fibrin clot dries
3 to 7 days
• Initial acute
inflammatory response.
• Proliferation of
epithelial tissues
32
By weeks
• Due to the presence of
myofibroblasts
contraction of wound
occurs
33
Wound contraction
• is a mechanical reduction in the size of the defect.
• The wound is reduced ≈ by 70-80% of its original
size.
• Contraction results in much faster healing.
• It is said to be due to contraction by
myofibroblasts.
34
Ctd...
• Myofibroblasts have the features intermediate b/n
those of fibroblasts & smooth muscle cells.
• 2-3 days after injury they migrate in to the wound
& their active contraction decrease the size of the
defect
35
Wound strength
• Wound healing is initially largely dependent on
suturing.
• When the sutures are removed (typically at 1
week), wound strength is only about 10% of the
normal.
• At the end of 3 months 70- 80% of normal.
• This is due to increased collagen synthesis than
collagen degradation.
36
Factors that influence healing
Local factors
• Type, size & location of the wound
stable and labile cells- Complete repair.
wounds on the face heal fast(rich
vascularization)
small injuries heal faster
• Mechanical stress- pressure areas long
time.
• Foreign bodies
Infection-is the single most important
cause of delay in healing
persistent tissue injury and
inflammation.
37
Ctd...
Systemic factors
• Nutrition - vitamin C, proteins
• Circulatory status.
• Metabolic status – diabetes mellitus
E.g-poorly controlled DM delayed wound healing
• Hormones – steroids/glucocorticoids
E.g.- corticosteroids -impair wound healing
-decreased collagen synthesis
-anti-inflammatory effect..... result in weak
scars
diminish fibrosis
38
Complications in wound healing
1. Infection
2. Deficient scar formation
a. wound dehiscence
b. incisional hernias
• dehiscence occurs in 0.5-5% of abdominal surgeries
• can be due to:-inappropriate surgical techniques,
stress, increased pressure or infection.
c. ulceration
• trophic or neuropathic ulcers-in varicose, DM,
leprosy, 30 syphilis (spinal involvement
39
Excessive Scarring
• Excessive formation of the components of the repair
process can give rise to hypertrophic scars and
keloids.
• failure in 'maturation arrest' or block in the healing
process.
• hypertrophic scar- often grow rapidly and contain
abundant myofibroblasts, but they tend to regress
over several months.
• Thermal and traumatic injury
• Keloid- If the scar tissue grows beyond the
boundaries of the original wound and does not
regress.
40
41
42
Fracture healing
43
• Step 1:
• Immediately after the fracture, extensive bleeding
occurs. Over a period of several hours, a large
blood clot, or fracture hematoma, develops.
• Bone cells at the site become deprived of nutrients
and die. The site becomes swollen, painful, and
inflamed.
44
• Step 2:
• Granulation tissue is formed as the hematoma is
infiltrated by capillaries and macrophages, which
begin to clean up the debris.
• Some fibroblasts produce collagen fibers that span
the break , while others differentiate into
chondroblasts and begin secreting cartilage matrix.
• C. Osteoblasts begin forming spongy bone.
• D. This entire structure is known as a fibro
cartilaginous callus and it splints the broken bone.
45
• Step 3:
• Bone trabeculae increase in number fibro
cartilaginous callus
• bony callus of spongy bone
• Typically takes about 6-8 weeks for this to occur.
46
• Step 4:
• During the next several months, the bony callus is
continually remodeled.
• Osteoclasts work to remove the temporary
supportive structures
• Osteoblasts rebuild the compact bone and
reconstruct the bone so it returns to its original
shape/structure.
47
48
49
•QUESTIONS?
50

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4. Pathology -midwifery stu-Tissue repair(1).ppt

  • 2. Course outlines  Describe the process of tissue repair Specify the patterns of wound healing  List the factors that influence wound healing Discuss the complications of wound healing  Understand fracture healing 2
  • 3. Definition of tissue repairing •Repair sometimes is called healing • Refers to the restoration of tissue architecture and function after an injury 3
  • 4. Process of healing • Occurs by two types of reactions • 1. Regeneration – the replacement of loss tissue by tissues similar in type. • Occurs in tissues with high proliferative capacity. • Such as: - hematopoietic system→BM - epithelia of the skin 4
  • 5. Ctd... 2. Healing by scar formation – the replacement of loss tissue by granulation tissue which matures to form scar tissue. • E.g. In skin, superficial wounds heal by regeneration but deep wounds (dermis) heal by scar formation. • Fibrosis - the extensive deposition of collagen that occurs in the lungs, liver, kidney and other organs as a consequence of chronic inflammation. 5
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  • 8. Control of normal cell proliferation • In adult tissues, the size of the cell population is determined by the:  rates of cell proliferation differentiation & death by apoptosis • Cell proliferation can be stimulated by physiologic & pathologic conditions. 8
  • 9. Ctd... • Pathologic conditions such as injury, cell death & mechanical alteration of tissues stimulate cell proliferation. • Cell proliferation is largely controlled by signals (soluble or contact dependant) from the environment which may stimulate or inhibit cell proliferation. 9
  • 10. Types of cells • Based on their proliferative capacity there are three types of cells: 1. labile cells • These are cells which have a continuous turn over by programmed division of stem cells. • They are found in the surface epithelium of the GI tract, urinary tract or the skin. 10
  • 11. Ctd... • cells of lymphoid & haemopoietic systems are further examples of labile cells. • The chances of regeneration are excellent. 2. Stable cells • Tissues which have such type of cell have normally a much lower level of replication & there are few stem cells. 11
  • 12. Ctd... • However, the cells of such tissues can undergo rapid division in response to injury. • Example – mesenchymal cells such as smooth muscle cells, fibroblasts, osteoblasts & endothelial cells are stable cells which can proliferate • Liver, endocrine glands & renal tubular endothelium has also such type of cells which can also regenerate 12
  • 13. 3. Permanent cells • These are non dividing cells. • If lost, permanent cells cannot be replaced. • Example – adult neurons, striated muscle cells, myocytes & cells of the lens 13
  • 14. HEALING BY REGENERATION • Definition: - regeneration (generare = bring to life) is the renewal of a lost tissue or part in which the lost cells are replaced by identical ones. • It involves two processes 1. Proliferation of surviving cells to replace lost tissue 2. Migration of surviving cells in to the vacant spaces 14
  • 15. Ctd... • The capacity of tissue regeneration depends on its: 1. Proliferative ability 2. degree of damage to stromal frame work 3. on the type & severity of the damage • Tissues formed from labile & stable cells can regenerate if and only if stromal frame work are intact 15
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  • 17. Repair by Scarring • If repair cannot be accomplished by regeneration alone, it occurs by replacement of the injured cells with connective tissue, leading to the formation of a scar, or by a combination of regeneration of some residual cells and scar formation. • happen if the tissue injury is severe or chronic and results in damage to parenchymal cells and epithelia as well as to the connective tissue framework, or if non dividing cells are injured. • In contrast to regeneration, which involves the restitution of tissue components, scar formation is a response that “patches” rather than restores the tissue. 17
  • 18. Steps in Scar Formation • Repair by connective tissue deposition consists of a series of sequential steps that follow tissue injury. 1.haemostatic plug comprised of platelets is formed, stops bleeding , occurs within minutes after injury,. 2.Inflammation Macrophages are the central cellular players in the repair process. 18
  • 19. 3.Cell proliferation takes up to 10 days. Epithelial cells migrate over the wound to cover it. Endothelial and other vascular cells proliferate to form new blood vessels(angiogenesis). Fibroblasts- lay down collagen fibers (begins 3 – 5 days after injury) form the scar. • The combination of proliferating fibroblasts, loose connective tissue, new blood vessels and scattered chronic inflammatory cells, forms a type of tissue that is unique to healing wounds and is called granulation tissue. 19
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  • 23. Wound healing • Two types of wound healing • described depending on the amount of tissue damage. • These are essentially the same process varying only in amount. • These include healing by first intention & healing by second intention. • Whether a wound heals by primary or secondary union is determined by the nature of the wound, rather than by the healing process itself !! 23
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  • 25. Healing by First Intention: Timeline • Occurs in wounds that close easily. • Epithelial regeneration predominates over fibrosis. • Healing is fast, with minimal scarring/infection • Examples: • Paper cuts • Well-approximated surgical incisions 25
  • 26. Healing by First Intention: Timeline • By 24- 48 hours • Wound space is filled with blood & fibrin clots. • Fibrin clot dries. • Neutrophils come in • Epithelium begins to regenerate. 26
  • 27. • By 3-7 days • Macrophages come in • Granulation tissue is formed • new blood vessels • fibroblasts • Collagen begins to bridge incision • Epithelium increases in thickness 27
  • 28. Weeks later • Granulation tissue gone • Collagen is remodeled • Epidermis full, mature. • (but without dermal appendages!) • Eventually, scar forms 28
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  • 30. Healing by second intention • Occurs in larger wounds that have gaps between wound margins • Fibrosis predominates over epithelial regeneration • Healing is slower, with more inflammation and granulation tissue formation, and more scarring • Examples: Infarction,Large burns and ulcers, Large devitalized tissue • Regeneration of parenchymal tissues can not completely restore original architecture. 30
  • 31. • Differs from primary union in several ways: - More fibrin, more debris more intense inflammation - More granulation tissue is formed - Wound contraction aided by myofibroblasts 31
  • 32. 24 hrs • Wound space is filled with blood & fibrin clots. • Fibrin clot dries 3 to 7 days • Initial acute inflammatory response. • Proliferation of epithelial tissues 32
  • 33. By weeks • Due to the presence of myofibroblasts contraction of wound occurs 33
  • 34. Wound contraction • is a mechanical reduction in the size of the defect. • The wound is reduced ≈ by 70-80% of its original size. • Contraction results in much faster healing. • It is said to be due to contraction by myofibroblasts. 34
  • 35. Ctd... • Myofibroblasts have the features intermediate b/n those of fibroblasts & smooth muscle cells. • 2-3 days after injury they migrate in to the wound & their active contraction decrease the size of the defect 35
  • 36. Wound strength • Wound healing is initially largely dependent on suturing. • When the sutures are removed (typically at 1 week), wound strength is only about 10% of the normal. • At the end of 3 months 70- 80% of normal. • This is due to increased collagen synthesis than collagen degradation. 36
  • 37. Factors that influence healing Local factors • Type, size & location of the wound stable and labile cells- Complete repair. wounds on the face heal fast(rich vascularization) small injuries heal faster • Mechanical stress- pressure areas long time. • Foreign bodies Infection-is the single most important cause of delay in healing persistent tissue injury and inflammation. 37
  • 38. Ctd... Systemic factors • Nutrition - vitamin C, proteins • Circulatory status. • Metabolic status – diabetes mellitus E.g-poorly controlled DM delayed wound healing • Hormones – steroids/glucocorticoids E.g.- corticosteroids -impair wound healing -decreased collagen synthesis -anti-inflammatory effect..... result in weak scars diminish fibrosis 38
  • 39. Complications in wound healing 1. Infection 2. Deficient scar formation a. wound dehiscence b. incisional hernias • dehiscence occurs in 0.5-5% of abdominal surgeries • can be due to:-inappropriate surgical techniques, stress, increased pressure or infection. c. ulceration • trophic or neuropathic ulcers-in varicose, DM, leprosy, 30 syphilis (spinal involvement 39
  • 40. Excessive Scarring • Excessive formation of the components of the repair process can give rise to hypertrophic scars and keloids. • failure in 'maturation arrest' or block in the healing process. • hypertrophic scar- often grow rapidly and contain abundant myofibroblasts, but they tend to regress over several months. • Thermal and traumatic injury • Keloid- If the scar tissue grows beyond the boundaries of the original wound and does not regress. 40
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  • 44. • Step 1: • Immediately after the fracture, extensive bleeding occurs. Over a period of several hours, a large blood clot, or fracture hematoma, develops. • Bone cells at the site become deprived of nutrients and die. The site becomes swollen, painful, and inflamed. 44
  • 45. • Step 2: • Granulation tissue is formed as the hematoma is infiltrated by capillaries and macrophages, which begin to clean up the debris. • Some fibroblasts produce collagen fibers that span the break , while others differentiate into chondroblasts and begin secreting cartilage matrix. • C. Osteoblasts begin forming spongy bone. • D. This entire structure is known as a fibro cartilaginous callus and it splints the broken bone. 45
  • 46. • Step 3: • Bone trabeculae increase in number fibro cartilaginous callus • bony callus of spongy bone • Typically takes about 6-8 weeks for this to occur. 46
  • 47. • Step 4: • During the next several months, the bony callus is continually remodeled. • Osteoclasts work to remove the temporary supportive structures • Osteoblasts rebuild the compact bone and reconstruct the bone so it returns to its original shape/structure. 47
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