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Host Defense > Path VIII: cellular proliferation, tissure repair, and would healing > Flashcards

Path VIII: cellular proliferation, tissure repair, and would healing Flashcards

1
Q

What are examples of continuously dividing cells?

A

epithelia of skin, GI tract, bladder, ducts, glands, pancreas, biliary tract
hematopoetic cells

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2
Q

What are examples of quiescent cells?

A

kidney, liver, pancreas, endothelial, mesenchymal

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3
Q

What are five steps to cell division?

A
  1. ligand-receptor binding (GF binds ligand)
  2. receptor actvation (ligand binds receptor and then the receptor is dimerized/phosphorylated/whatever)
  3. signal transduction/secondary messengers (ex. Ras and G protein coupled receptors; phospholipase C)
  4. transcription factors: expression of many growth-regulatory TFs (myc, etc.)
  5. cyclins production: controls entry/progression thru the cell cycle
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4
Q

What are inhibitors of cell growth (4)

A
  1. contact inhibition
  2. TGF-beta
  3. tumor necrosis factor (TNF)
  4. tumor suppressor gene products
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5
Q

What are the three main types of growth factors?

A
  1. those that stimulate growth of numerous cell types
  2. those that stimulate cells of the immune system (cytokines)
  3. stimulate RBCs and WBCs (colony stimulating factor)
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6
Q

For what four processes is repair the outcome (assuming the pt survives)?

A

acute inflammation
chronic inflammation
ischemic necrosis
wounds/bone fractures

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7
Q

What are two important things that must be true in order for regeneration to occur?

A
  1. CT framework is maintained

2. cells are not post-mitotic

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8
Q

What are the four steps of fibrosis?

A

scar formation:

  1. angiogenesis
  2. migration and prolif of fibroblasts
  3. deposition of ECM
  4. organization of collagen
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9
Q

What factor is absolutely essential for scar formation but is not present in the fetus?

A

TGF-beta

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10
Q

What are the 6 steps of wound healing?

A
  1. skin defect occurs
  2. plasma/fibrin clot fills in the defect
  3. epithelium regenerates
  4. granulation tissue forms below the scab.
  5. wound contraction and ECM reorganization
  6. collagen remodeling
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11
Q

What is the purpose of granulation tissue?

A

red, soft, granular surface
provides a support system for new vessel growth.
microenvironment for macrophage phagocytosis of dead tissue and macrophage stimulation of fibroblasts to produce collagen. inflammatory cells also present to prevent infection.

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12
Q

What happens during wound contraction and ECM reorganization

A

fibroblasts turn to myofibroblasts (actin-containg bundles of microfilaments within the cytolasm adjacent to the cell membrane). stimulated by TGF-beta and PDGF

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13
Q

What happens during collagen remodeling?

A

dynamic synthesis and breakdown of collagen

matrix metalloproteinases are proteolytic enzymes. balanced by tissue inhibitors of metalloproteins.

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14
Q

What is the difference between primary intention and secondary intention?

A

primary intetion: sutured wounds- clean edges are joined together
secondary intention: contraction of the would occurs with transformation of fibroblasts into myofibroblasts. intercellular crosslinkage occurs.

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15
Q

What are the four components of the ECM?

A

fibers (collagen, elastin)
cells (fibroblasts, immune cells, endothelial cells)
ground substance: GAGs, proteoglycans
adhesive glycoprotiens: laminin and fibronectin

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16
Q

What is the function of the fibers found in the ECM? What is the structure of collagen?

A

support and elasticity
collagen: triple helix where 1 in every three aas ins glycine. requires hydroxylation of pro and lys through Vitamin C as a cofactor.

17
Q

What is the purpose of ground substance in the ECM? What is its structure?

A

amorphous, gelatinous, supports the ECM. holds water.

mande mostly of sulfated GAGs, proteoglycans, and hyaluronic acid (non-sulfated GAG).

18
Q

What is the purpose of the adhesive glycoproteins? What are the most important adhesive glycoproteins?

A

bind ECM components to each other, esp. cells to the basement membrane.
laminin and fibronectin are key

19
Q

What cells make fibronectin? What does it do?

A

fibroblasts, monocytes, and endothelial cells

RGD sequence recognized by integrins involved in attachement to ECM and cellular migration

20
Q

What does laminin do?

A

most abundant glycoprotein i nthe basement membrane

binds cells to collagen IV and heparan sulfate in the ECM.

21
Q

What are integrins?

A

TM glycoproteins on the cell surface. involved in leukocyte extravasation, platelet aggregation, development, and wound healing. organize actin cytoskeleton and they are receptors that transduce signals form the ECM and help link actin within the cell to fibronectin in the ECM.

22
Q

What are the three initial steps of angiogenesis?

A
  1. proteolysis of vessel basement membrane for capillary sprouts
  2. endothelial cell migration and proliferation
  3. pericyte recruitment
23
Q

What is VEGF?

A

stimulus for angiogenesis
act on the endothelium
incr. vascular permeability

24
Q

What do function do TGF-beta, PDGF, EGF, and FGF have in common?

A

growth factors that cause migration and prolif of fibroblasts in granulation tissue

25
Q

What are the 6 functions of TGF-beta?

A
  1. fibroblast migration and prolif.
  2. incr. collagen synthesis
  3. incr. fibronectin synthesis
  4. decr. degradation of ECM by metalloproteinases
  5. chemotaxis of monocytes
  6. angiogenesis
26
Q

What is the role of fibrinogen and fibronectin in a wound?

A

act as a scaffold for granulation tissue formation during angiogenesis

27
Q

What is one factor over expressed in tissues with chronic fibrotic disease like cirrhosis?

A

TGF-beta

28
Q

On what two factors/processes does net collagen accumulation depend?

A

synthesis by fibroblasts and degradation by matrix metalloproteins

29
Q

What are the 10 steps of angiogenesis?

A
  1. tissue destruction
  2. blot clot to reestablish homeostasis and a temporary ECM
  3. platelets for a plug and secrete PDGF and attract and activate macrophages
  4. macrophages releases acidic and basic FGF
  5. hypoxia continues and VEGF is produced by epidermal keratinocytes
  6. proteolytic enzymes degrade the ECM
  7. fragments of ECM recruit monocytes to the area to become activaed macrophages and release angiogenesis factors
  8. Basic FGF stimulates endothelial cells to release plasminogen activator and procollagenase to digest the basement membrane and cleave collagen
  9. endothelial cells produce angiogenesis factors and cause migration/formation of new blood vessels
  10. apoptosis mediated by thromobspondin, angiostatin, endostatin, and angiopoeitan
30
Q

how do we condense what happens in angiogenesis?

A
  1. injury and blood clot
  2. platets segrete PDGF to get macrophages/platelets
  3. macrophages release acidic and basic FGF
  4. VEGF is produced by epidermal keratinocytes
  5. degradation of the ECM. ECM fragments recruit more macrophages/angiogenesis factors
  6. Basic FGF stimulates endothelial cells: digest basement membrane.
  7. Endothelial cells produce angiogenesis factors: new blood vessels
  8. apoptosis of new blood vessels.
31
Q

What factors mediate apoptosis?

A

thrombospondin, antiostatin, endostatin, angiopoietin

32
Q

What are six functions of matrix metalloproteinases?

A
  1. intrahepatic bile duct formation
  2. small bowel development
  3. mammary gland branching and morphogenesis
  4. salivary gland morphogenesis
  5. wound healing
  6. cycling endometrium
33
Q

What is one critical pathogenic process that involves MMPs?

A

many cancers show overexpression of MMPs.

34
Q

What are 6 diseases in which MMPs have been implicated?

A 
migration of smooth muscle in atherosclerosis
hemorrhagic stroke
MS
periodonatl disease
 corneal ulceration
glomerulosclerosis
35
Q

what are three local causes of impaired wound healing?

A

infection, inadequate blood supply, and foreign bodies

36
Q

What are four systemic causes of poor wound healing?

A

inadequate nutrition, hematologic disorders, diabetes, coritocsteroids

37
Q

What cell has a critical role in the transition from inflammation to repair?

A

macrophage

Host Defense (38 decks)

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