tissue repair
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Tissue Repair. Kristine Krafts, M.D. Tissue Repair. Tissue repair = restoration of tissue architecture and function after an injury Occurs in two ways: Regeneration of injured tissue Replacement by connective tissue (scarring) Usually, tissue repair involves both processes - PowerPoint PPT PresentationTRANSCRIPT
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Tissue RepairKristine Krafts, M.D.
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• Tissue repair = restoration of tissue architecture and function after an injury
• Occurs in two ways:• Regeneration of injured tissue • Replacement by connective tissue (scarring)
• Usually, tissue repair involves both processes• Involves cell proliferation, and interaction
between cells and extracellular matrix
Tissue Repair
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• Important background facts• Cellular proliferation• Growth factors• The extracellular matrix
• The process of tissue repair• Regeneration• Scarring• An illustration: skin wound healing• Why do good wounds go bad?
Tissue Repair Lecture Outline
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• Important background facts• Cellular proliferation
Tissue Repair Lecture Outline
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• Lots of cells proliferate during tissue repair:• Injured tissue remnants• Vascular endothelial cells• Fibroblasts
• You need to know a few things about:• The cell cycle• The proliferative capacities of different tissues• Stem cells• Growth factors• The extracellular matrix
Cellular Proliferation
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The Cell Cycle
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• Continuously dividing (labile) tissues• Stable tissues• Permanent tissues
Tissues of the body are divided into three groups:
Cellular Proliferation
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• Continuously dividing (labile) tissues• Cells are continuously proliferating• Can easily regenerate after injury• Contain a pool of stem cells• Examples: bone marrow, skin, GI epithelium
Tissues of the body are divided into three groups:
Cellular Proliferation
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Stem cells in skin
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Stem cells in GI epithelium
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• Continuously dividing (labile) tissues• Stable tissues
• Cells have limited ability to proliferate• Limited ability to regenerate (except liver!)• Normally in G0, but can proliferate if injured• Examples: liver, kidney, pancreas
Tissues of the body are divided into three groups:
Cellular Proliferation
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• Continuously dividing (labile) tissues• Stable tissues• Permanent tissues
• Cells can’t proliferate• Can’t regenerate (so injury always leads to scar)• Examples: neurons, cardiac muscle
Tissues of the body are divided into three groups:
Cellular Proliferation
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The Cell Cycle and Different Cell Populations
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• Important background facts• Cellular proliferation• Growth factors
Tissue Repair Lecture Outline
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• Very important in tissue repair.• Actions:
• Stimulate cell division and proliferation• Promote cell survival
• Huge list! Usually have “GF” in name:• EGF (epidermal growth factor)• TGF (transforming growth factor)• PDGF (platelet-derived growth factor)
Growth Factors
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• Important background facts• Cellular proliferation• Growth factors• The extracellular matrix
Tissue Repair Lecture Outline
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• ECM is the network that surrounds cells• Two forms: interstitial matrix and basement
membrane• Does lots of things!
• Sequesters water and minerals• Gives cells a scaffold to adhere to• Stores growth factors
The Extracellular Matrix
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The Extracellular Matrix
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• Bottom line: ECM regulates proliferation, movement, and differentiation of the cells living in it.
• If you screw up your ECM, you can’t regenerate! You’ll form a scar instead.
Extracellular Matrix
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• Important background facts• Cellular proliferation• Growth factors• The extracellular matrix
• The process of tissue repair• Regeneration
Tissue Repair Lecture Outline
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• Occurs all the time in labile tissues • Cells are constantly being lost and replaced• If demand increases, supply increases easily
• Occurs in limited form in stable tissues• Remove one kidney: the other one undergoes
hypertrophy and hyperplasia• Remove half of the liver: it will grow back
• Only occurs if residual tissue is intact!
Regeneration
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Liver before
resection
Liver 1 week after
resection
right lobe to be
resected
left lobenow
enlarged
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• Important background facts• Cellular proliferation• Growth factors• The extracellular matrix
• The process of tissue repair• Regeneration• Scarring
Tissue Repair Lecture Outline
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• If injury is severe, regeneration can’t happen• So, fibrosis (a scar) replaces the injured tissue• Four components to this process:
• New vessel formation (angiogenesis)• Fibroblast proliferation• Synthesis of collagen (scar formation)• Remodeling of scar
Scarring
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• By 24 hours:• Endothelial cells start proliferating• Fibroblasts emigrate
• By 3-5 days:• Granulation tissue present
• Weeks later:• Dense fibrosis (scar)• Scar is remodeled over time
Scarring
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Summary:
1. Make granulation tissue
2. Turn it into a chunk of collagen
Scarring
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Granulation tissue
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Scar
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Q. Is “granulation tissue” the same thing as “granuloma”?
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Q. Is “granulation tissue” the same thing as “granuloma”?
A. No!
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Granuloma
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Q. Is “granulation tissue” the same thing as “granuloma”?
A. No!
Q. Is it the same thing as “chronic granulomatous disease”?
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Q. Is “granulation tissue” the same thing as “granuloma”?
A. No!
Q. Is it the same thing as “chronic granulomatous disease”?
A. No!
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• Important background facts• Cellular proliferation• Growth factors• The extracellular matrix
• The process of tissue repair• Regeneration• Scarring• An illustration: skin wound healing
Tissue Repair Lecture Outline
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• First intention
• Second intention
Skin Wound Healing
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first intention healing
second intention healing
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• Occurs in small wounds that close easily• Epithelial regeneration predominates over
fibrosis• Healing is fast, with minimal scarring/infection• Examples:
• Paper cuts• Well-approximated surgical incisions• Replaced periodontal flaps
Healing by First Intention
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• By 24 hours• By 3-7 days• Weeks later
Healing by First Intention
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• By 24 hours• clot forms • neutrophils come in• epithelium begins to regenerate
Healing by First Intention
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• By 24 hours• By 3-7 days• Macrophages arrive• Granulation tissue is formed• Collagen begins to bridge incision• Epithelium increases in thickness
Healing by First Intention
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• By 24 hours• By 3-7 days• Weeks later• Granulation tissue is gone• Collagen is remodeled• Epidermis is full and mature
(but without dermal appendages)• Eventually, scar forms
Healing by First Intention
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6 hours 24 hours
2 days
1 week
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• 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• Extraction sockets• External-bevel gingivectomies
Healing by Second Intention
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• More inflammation• More granulation tissue• Wound contraction
Second intention healing has:
Skin Wound Healing
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Pressure ulcer of skin
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Skin ulcer: large gap between edges
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Skin ulcer: granulation tissue
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Skin ulcer: re-epithelialization
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• At suture removal: 10%• Rapid increase over next 4 weeks• At third month: 70-80%
Wound strength
Skin Wound Healing
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• Important background facts• Cellular proliferation• Growth factors• The extracellular matrix
• The process of tissue repair• Regeneration• Scarring• An illustration: skin wound healing• Why do good wounds go bad?
Tissue Repair Lecture Outline
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• Extrinsic factors• Infection• Diabetes• Steroids
• Type of tissue injured (labile vs. permanent)• Aberrant cell growth or ECM production
• Keloid scars• Proud flesh
Why do good wounds go bad?
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Keloid scar
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Keloid scar
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Proud flesh
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Proud flesh
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Proud flesh
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• Important background facts• Cellular proliferation• Growth factors• The extracellular matrix
• The process of tissue repair• Regeneration• Scarring• An illustration: skin wound healing• Why do good wounds go bad?
Tissue Repair Lecture Outline
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• Not all injuries result in permanent damage; some are resolved almost completely.
• More often, there is some degree of scarring.• Scarring is usually good (provides a resilient patch)
but occasionally bad (can cause permanent dysfunction)
Tissue Repair Summary
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