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38 Cards in this Set
- Front
- Back
What is the difference between regeneration and healing?
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Regeneration = tissue repaired to normal state
Healing = Repair occurs by lying down connective tissue; scar formation |
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What is fibrosis?
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Deposition of collagen in tissues that occurs as a consequence of chronic inflammation, infarction, etc.
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What is organization?
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When fibrosis develops in a tissue space occupied by an inflammatory exudate
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What are CDKs?
What is the effect of growth factors on CDKs? |
Cyclin-dependent kinases, promote cell cycle progression
Growth factors release the inhibition of CDKs, allowing G1 to progress |
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What are continuously dividing tissues?
2 Examples? |
Tissues whose cells are constantly being lost and regenerated from stem cells --> readily regenerate after injury
Hematopoietic cells in bone marrow Surface epithelia |
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What are stable tissues?
4 examples? |
Cells are normally in G0, but can proliferate to perform limited regeneration after injury
Parenchyma of most solid tissues Endothelial cells Fibroblasts Smooth muscle cells |
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What are permanent tissues?
2 examples? |
Cells are terminally differentiated, non-proliferative --> regeration is scar formation
Cardiac myocytes Neurons |
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What are 2 essential properties of stem cells?
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1. Self-renewal capacity
2. Asymmetric replication - produce differentiated and undifferentiated progeny |
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Epidermal Growth factor (EGF)
a. Source b. Function |
a. Activated macrophages, salivary glands, keratinocytes, other cells
b. Mitogens for keratinocytes and fibroblasts; keratinocyte migration and granulation tissue formation |
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Transforming Growth Factor alpha (TGF a)
a. Source b. Function |
a. Activated macrophages, T lymphocytes, keratinocytes, other cells
b. Similar to EGF, stimulates replication of hepatocytes and epithelial cells |
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VEGF
a. Source b. Function |
a. Mesenchymal cells
b. Increases vascular permeability, mitogenic for endothelial cells |
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PDGF
a. Source b. Function |
a. Platelets, macrophages, endothelial cells, keratinocytes, smooth muscle
b. Chemotactic, mitogenic, activators for PMNs, macrophages, fibroblasts, and smooth muscle Stimulates angiogenesis and wound remodeling; regulates integrin expression |
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TGF-b
a. Source b. Function |
a. Platelets, T lymphcytes, macrophages, endothelial cells, keratinocytes, smooth muscle, fibroblasts
b. Chemotactic for PMN, macrophage, lymphocytes, and fibroblasts Inhibits matrix metalloproteinase; regulates integrin expression |
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What are 6 roles of ECM?
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1. Mechanical support
2. Control cell growth - signal through integrin receptors 3. Maintain cell differentiation 4. Scaffolding for tissue renewal 5. Establish tissue microenvironments 6. Storage and presentation of regulatory molecules (growth factors) |
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What are the 3 basic components of ECM? General duties of each?
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1. Collagen and elastin - tensile strength and recoil
2. Proteoglycans and hyaluronan - resilience and lubrication 3. Adhesive glycoproteins - connect matrix elements to one another and to cells |
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What are fibrils?
Role? |
Collagen whose triple helices has been cross-linked laterally
Fibrillin collagens = connective tissue in healing wounds and scars |
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What is elastin?
Structure? |
Component of ECM, gives recoil ability
Central core of elastin surrounded by meshwork of fibrillin |
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What is the defect in Marfan syndrome?
What does this cause? |
Defect in fibrillin synthesis --> skeletal abnormalities, weakened aortic walls
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What are proteoglycans? roles?
Hyaluronan? |
Hydrated, compressible gels of long polysaccharides around a protein core --> confer resilience and lubrication, reservoir for growth factors, membrane proteins
Hyaluronon is long string of disaccs without protein core |
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What are the roles of adhesive glycoproteins?
What are the two types? |
Adhesion between cells and ECM
Fibronectin and laminin |
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What are 2 types of fibronectin and what are their roles?
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1. Tissue fibronectin = forms fibrillar aggregates at wound healing sites
2. Plasms fibronectin = binds fibrin to form clot of a wound --> substratum for ECM deposition, re-epithelialization |
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What is laminin?
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Basement membrane glycoprotein, attaches cells to ECM basement membrane components like Collagen IV and heparan sulfate
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What are integrins?
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Transmembrane glycoproteins on cells that act as cellular receptors for ECM components (fibronectins and laminins)
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What is granulation tissue? When does it appear?
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Fibroblasts, new capillaries in a loose ECM
Appears 3-5 days after wound |
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What are 4 steps of repair by connective tissue deposition?
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1. Angiogenesis
2. Migration and proliferation of fibroblasts 3. Deposition of ECM (scar formation) 4. Maturation and reorganization of fibrous tissue (remodeling) |
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What are 3 functions of a blood clot in inflammation?
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1. Hemostasis (keeps blood in vessels)
2. Release inflammatory mediators 3. Matrix to support cell migration into the wound |
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How are macrophages and fibroblasts attracted to a wound site?
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PDGF (platelets), coagulation and complement components, Injured parenchymal cells
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What happens to a wound after...
a. 24 hrs b. 3 days |
a. Neutrophils remove debris
b. Neutrophils extruded to surface Monocytes respond to TGF-B, bind integrin receptors --> become reparative Fibroblasts deposit collagen |
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What do reparative macrophages express in inflammation? (3)
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1. CSF-1 promotes macrophage longevity
2. TNF-a augments inflammation 3. PDGF chemoattractant and mitogen for fibroblasts |
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What is healing by first intention?
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Healing of a clean incision made by a surgical cut
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First intention healing
a. 24 hrs b. 3 - 7 days c. Weeks |
a. Neutrophils migrate to fibrin clot, basal epidermal cells undergo mitosis, epithelial cells lay down basement membrane
2. Macrophages and granulation tissue invade; high vascularization --> granulation tissue fills space 3. Epilthelium covers connective tissue, little vascularization |
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What is healing by second intention?
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Healing of an extensive wound, abcess formation, or ulceration
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How is healing by second intention different from primary intention?
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1. Larger clot, rich in fibrin and fibronectin
2. More intense inflammation 3. More granulation tissue formed 4. Wound contraction - myofibroblasts help contract the wound |
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What are matrix metalloproteinases?
What secretes them? |
Degrade collagen during transition from granulation tissue to scar
Macrophages, endothelial cells, keratinocytes, and fibroblasts |
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What are 5 pathological conditions that inhibit wound repair?
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1. Infection --> increased inflamm response --> delay repair
2. Vit C deficiency --> Inhibits collagen synth 3. Steroids --> anti-inflamm, anti-fibrosis 4. Foreign bodies --> granulomatous inflamm 5. Poor perfusion --> ulcers |
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What is exuberant granulation? Why is it bad?
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Granulation tissue protrudes above edges of the wound
Can inhibit migration of epidermal cells , stops wound closing |
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What are keloids?
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Overproduction of fibroblasts --> overproduction of collagen --> raised scars
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What occurs in Marfan's syndrome?
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Mutation in fibrillin-1 (ECM protein that helps form elastin) sequesters TGF-B in elastin-rich tissues --> low grade inflammation --> degeneration of aortic wall, rupture
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