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38 Cards in this Set

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  • Back
What is the difference between regeneration and healing?
Regeneration = tissue repaired to normal state

Healing = Repair occurs by lying down connective tissue; scar formation
What is fibrosis?
Deposition of collagen in tissues that occurs as a consequence of chronic inflammation, infarction, etc.
What is organization?
When fibrosis develops in a tissue space occupied by an inflammatory exudate
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
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
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
What are permanent tissues?

2 examples?
Cells are terminally differentiated, non-proliferative --> regeration is scar formation

Cardiac myocytes
Neurons
What are 2 essential properties of stem cells?
1. Self-renewal capacity
2. Asymmetric replication - produce differentiated and undifferentiated progeny
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
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
VEGF
a. Source
b. Function
a. Mesenchymal cells
b. Increases vascular permeability, mitogenic for endothelial cells
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
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
What are 6 roles of ECM?
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)
What are the 3 basic components of ECM? General duties of each?
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
What are fibrils?

Role?
Collagen whose triple helices has been cross-linked laterally

Fibrillin collagens = connective tissue in healing wounds and scars
What is elastin?

Structure?
Component of ECM, gives recoil ability


Central core of elastin surrounded by meshwork of fibrillin
What is the defect in Marfan syndrome?

What does this cause?
Defect in fibrillin synthesis --> skeletal abnormalities, weakened aortic walls
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
What are the roles of adhesive glycoproteins?

What are the two types?
Adhesion between cells and ECM

Fibronectin and laminin
What are 2 types of fibronectin and what are their roles?
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
What is laminin?
Basement membrane glycoprotein, attaches cells to ECM basement membrane components like Collagen IV and heparan sulfate
What are integrins?
Transmembrane glycoproteins on cells that act as cellular receptors for ECM components (fibronectins and laminins)
What is granulation tissue? When does it appear?
Fibroblasts, new capillaries in a loose ECM

Appears 3-5 days after wound
What are 4 steps of repair by connective tissue deposition?
1. Angiogenesis
2. Migration and proliferation of fibroblasts
3. Deposition of ECM (scar formation)
4. Maturation and reorganization of fibrous tissue (remodeling)
What are 3 functions of a blood clot in inflammation?
1. Hemostasis (keeps blood in vessels)
2. Release inflammatory mediators
3. Matrix to support cell migration into the wound
How are macrophages and fibroblasts attracted to a wound site?
PDGF (platelets), coagulation and complement components, Injured parenchymal cells
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
What do reparative macrophages express in inflammation? (3)
1. CSF-1 promotes macrophage longevity
2. TNF-a augments inflammation
3. PDGF chemoattractant and mitogen for fibroblasts
What is healing by first intention?
Healing of a clean incision made by a surgical cut
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
What is healing by second intention?
Healing of an extensive wound, abcess formation, or ulceration
How is healing by second intention different from primary intention?
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
What are matrix metalloproteinases?

What secretes them?
Degrade collagen during transition from granulation tissue to scar

Macrophages, endothelial cells, keratinocytes, and fibroblasts
What are 5 pathological conditions that inhibit wound repair?
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
What is exuberant granulation? Why is it bad?
Granulation tissue protrudes above edges of the wound

Can inhibit migration of epidermal cells , stops wound closing
What are keloids?
Overproduction of fibroblasts --> overproduction of collagen --> raised scars
What occurs in Marfan's syndrome?
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