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44 Cards in this Set

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  • Back
What 2 factors determine the restitution of normal tissue or a scar?
Extent of damage to the tissue framework, and the regenerative capacity of the cells in the injured tissue
Members of a family of proteins that increase and decrease at various phases of the cell cycle to trigger transitions from one phase to the next.
How do cyclins become active?
They combine with cyclin dependent kinases (CDK) and these enzymes phosphorylate other protein substrates.
What types of intracellular changes can they cause?
CDK-cyclin complexes activate/deactivate: other enzymes, protein-protein interactions, protein-DNA binding, and protein catabolism.
What occurs to CDK1 during G2?
CDK1 remains inactive until the cells enters G2, when cyclin B is produced. The two complex, and CDK becomes active after phosphorylation, causing the G2 to M transition..
What does the activation of the above result in?
spindle formation, depolymerization of the nuclear membrane, and chromatin condensation.
What is the function of p53 in terms of DNA damage?
p53 activates p21, a CDK inhibitor. This causes the cell to remain in G1 or G2 for repair. If DNA can’t be repaired, p53 triggers apoptosis
Define labile, stable, and permanent cells.
labile cells have a steady rate of proliferation and death, stable cells are normally quiescent, but may return to the cell cycle in response to injury, permanent cells can’t reenter the cell cycle (cardiac monocytes and neurons)
Growth factors influence the expression of _____ _____.
What happens to the above if they are altered to become oncongenes?
they allow uncontrolled cell growth
_____ ______ allow for the transmission of soluble mediators.
gap junctions
What is the difference between autocrine, paracrine, synaptic, and endocrine signaling?
autocrine: mediators produced by one cell act on that cell (ex. Hyperplasia after hepatectomy), paracrine: mediators act on cells that are nearby (ex. Chemokines), synaptic: neural tissues’ use ot neurotransmitters at synapses, endocrine: regulatory substances secreted by one cell into the blood stream targets cells that are far away.
Where are intracellular receptors usually located?
associated with DNA
What type of receptor can cause in influx of a given ion, and a downstream activation of enzymatic activities?
ion channel receptors
What are two receptors with intrinsic kinase activity?
FGF and EGF receptors result in phosphorylation of the receptor itself, then tyrosine kinase activity
What type of receptors do cytokines bind to?
receptors without intrinsic enzyme activity, which become associated with kinases.
What fills the spaces between the cells of connective tissue?
interstitial matrix
The region where the interstitial matrix is more organized adjacent to epithelial, endothelial, and smooth muscle cells.
basememt membrane
What is the major role of the ECM?
to provide mechanical support for cell adhesion, forms microclimate
Which collagens crosslink?
Collagen I, III, IV, V, crosslink: a) I,III,V form fibrils in the ECM. B) IV is in the basement membrane.
Which ECM component imparts recoil to connective tissue?
What is the glycoprotein that surrounds elastin?
What condition results from a defect in the above molecule?
Marfan’s Syndrome: defects in fibrillin results in disorganized elastin fibers
What is heparin sulfate?
a hydrated gel formed by long polysaccharides (GAG).
An example of a polysaccharide gel without a protein core?
What is syndecan?
Membrane protein that binds GFs and connects to the cytoskeleton
How long after an injury does the repair process begin?
within 24 hours
What is angiogenesis?
the process of making new blood vessels from existing ones
What is the first step of angiogenesis?
proteolytic enzymes degrade the basement membrane of the parent vessel.
What two compounds, secreted by endothelial cells in response to injury, initiate this initial digestion?
VEGF and bFGF.
What is the second step of angiogenesis?
Migration: cells from the original capillary migrate to the site of angiogenic stimulus (the place where the injured cells are released VEGF and bFGF.
What is the third step of angiogenesis?
proliferation of endothelial cells (due to growth factors)
What is the fourth step of angiogenesis?
endothelium matures into effective tubes, there is also recruitment of supportive cells
What cell is primarily responsible for scar formation?
fibroblasts secrete ECM components from day 3-5 through a couple of weeks.
What are metalloproteinases?
collagenases I, II, III, IV (that digest collagen), stromelysins to degrade proteoglycans, etc., .
After scar formation, the collagen produced by fibroblasts is digested by metalloproteinases. What is the original form in which these enzymes are found?
The enzymes area originally zymogens, and are activated by substances that are released during injury (HOCl radicals, plasmin, etc).
What guards against the effects of metalloproteinases?
TIMPS (tissue inhibitors of metalloproteinases) protect against unregulated digestion of the matrix:
What are the roles of bFGF and VEGF?
GF: 1) bFGF: has an affinity for heparin sulfate and recruits cells to the site of injury. Also stimulates the proliferation of fibroblasts and endothelial cells (contributing to angiogenesis and collagen deposition). 2) VEGF: strong activator of angiogenesisà increases vascular permeability.
What is TGFβ?
Stimulates fibroblasts and collagen production, but inhibits the growth of many cell types
What is granulation tissue? Fibrosis?
Repair: 1) Granulation tissue: unorganized ECM, fibroblasts, and angiogenesis, which precedes fibrosis or clean resolution (pathologically predominates in proud flesh) 2) Fibrosis: scar tissue: collagen is deposited and organized by fibroblasts, then remodeled by metalloporeinases.
What is meant by healing by first intent?
In a clean cut regeneration occurs instead of fibrosis.
What is the sequence of events for healing by first intention?
1st Intention a) Within 24 hours: fibrin clot fills incision, and neutrophils migrate to the clot. Basal epidermal cells migrate medially, from both sides of the cut, to meet each other. B) Within 3-7 days: neutrophils are replaced by macrophages and granulation tissue replaces the fibrin clot. C) 2nd week: edema resolves, fibroblasts secrete collagen to increase tensile strength.
What is the sequence of events for healing by second intention? How does 2nd intention differ from first intention?
2nd Intention: Too much damage
What is wound strength after 1 week? 3 months?
1 week: 10%, 3 months : 70-80%.