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Patho Exam 4 > Svensson- Tissue Renewal, Repair, and Regineration > Flashcards

Svensson- Tissue Renewal, Repair, and Regineration Flashcards

1
Q

Parenchymal cells

A

-functional cells of the organ
-hepatocytes, myocytes, renal tubular cells

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2
Q

Stromal cells

A

-supporting structure of organs
- ECM, blood vessels, connective tissue

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3
Q

Tissue regeneration

A

-replacement of injured tissue with cells of the same type and function

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4
Q

Tissue repair

A

occurs when extent or nature of damage cannot be reversed by regeneration alone

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5
Q

Acute injury

A

-when the stimulus of the damage is removed
-either leads to regeneration or repair

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6
Q

an injury with persistent tissue damage can lead to___

A

fibrosis

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7
Q

What are the four stages of healing after tissue injury?

A

-homeostasis
-inflammation
-proliferation
-remodeling

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8
Q

homeostasis

A

-takes minutes
-results in local vasoconstriction and activation of platelets and clotting factors to form a fibrin clot
-creates the scaffold for migrating cells

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9
Q

inflammation

A

-takes hours
-driven by platelet-derived mediators, bacteria, and secreted chemoattractants
-macrophages and neutrophils

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10
Q

proliferation

A

-takes days
-mediated by macrophage and fibroblast-driven growth factors
-endothelial cells, keratinocytes, fibroblasts

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11
Q

remodeling

A

-takes weeks to months
-transition from type III to type I collagen
-restoring tensile strength of tissue

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12
Q

What is the general model of tissue renewal

A

-in healthy tissue there is little monocyte trafficking or neutrophil efflux into tissues, an intact basement membrane and no scar tissue
-upon tissue damage, there is loss of epithelia, neutrophil influx activation of resident macrophages, and recruitment of inflammatory monocytes, in addition to release of inflammatory factors and activation of pericytes into myofibroblasts
-tissue either goes to tissue regeneration or aberrant tissue repair
-during tissue regeneration there is epithelial proliferation for reconstitution, macrophage activation into a wound0healing phenotype and matrix remodeling. In addition T reg cells are recruited to decrease inflammation
-during aberrant tissue repair, excessive scarring occurs as a result of continued activation of inflammatory cells and impaired epithelial regeneration

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13
Q

What determines regeneration versus repair?

A

-nature of cells injured
-extent of injury
-presence or absence of ongoing inflammation
-underlying disease

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14
Q

nature of cells injured

A

some cells (eg adult cardiac myocytes ) have marginal renewal capacity

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15
Q

Extent of injury

A

the magnitude of injury may exceed regeneration capacity

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16
Q

presence or absence of ongoing inflammation

A

due to concurrent infection or other factors, continued release of inflammatory mediators may disrupt balance toward repair

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17
Q

underlying disease

A

may impair proliferative response or remodeling (eg diabetes)

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18
Q

What are three options for wound treatment

A

-primary intention
-secondary intention
-tertiary intention

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19
Q

primary intention

A

-wound is closed, with surgical intervention
-edges are brought together
-best choice for clean, fresh wounds, in sufficiently vascularized areas

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20
Q

secondary intention

A

-wound is left open and allowed to heal spontaneously
-good for contaminated/infected wounds
-increased scarring

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21
Q

tertiary intention

A

-delayed primary closure
-good for wounds which are contaminated/infected initially

22
Q

What is the mechanism that regulated cell proliferation

A

-driven by proteins that are collectively called growth factors
-production of peptide growth factors, response of cells to these factors, and the ability of tissue cells to five and expand in numbers are all important determinants of the adequacy of the repair process
-cell numbers can be altered by increased or decreased rates of stem cell input, cell death via apoptosis, or change in rates of proliferation or differentiation

23
Q

epidermal growth factor (EGF)

A

-come from activated macrophages, keratinocytes, and many
-function: mitogenic for keratinocytes and fibroblasts; stimulates keratinocyte migration and granulation tissue formation

24
Q

What receptors do EGF use?

A

-utilize surface receptors and transduction pathways
-trigger a protein kinase cascade

25
Q

What does binding of EGF to receptors trigger?

A

-altered gene expression through transcription factor activation

26
Q

What is the benefit of multiple proteins involved in EGF signaling?

A

there are many potential drug targets for modulating EGF signaling and therefore, cell proliferation

27
Q

How does the extracellular matrix affect structural integrity

A

-ECM is related to tissue shape (keeps shape)
-EXM provides tissue specific mechanical properties
-EXM facilitates tissue organization

28
Q

What are cell matrix interactions by the ECM>

A

-ECM provides anchorage for cells through interaction with membrane proteins as integrins
-ECM is related to adhesion and cell spreading
-ECM facilitates cell polarity
-ECM is related to cell migration

29
Q

What are the dynamics and depot role of ECM?

A

-ECM is a growth factor depot and reservoir for other signaling molecules
-constant ECM remodeling through degradation and assembly is regulated by enzymes, like proteases and peptidases

30
Q

What role does ECM play in signals/cell response?

A

-ECM provides signals for homeostasis, proliferation, and differentiation
-cells recognize signals present in ECM through receptors
-ECM is related to autocrine and paracrine signaling

31
Q

What are the major components of the ECM?

A

-basement membrane
-interstitial matrix

32
Q

Basement membrane

A

-Type IV collagen
-laminin
-proteoglycan

33
Q

Integrins

A

-hold the epithelium to the basement membrane
-hold fibroblast to adhesive glycoproteins

34
Q

interstitial matrix

A

-fibrillar collagens (many types of collagen)
-elastin
-proteoglycan and hyaluronan

35
Q

What two mechanisms underly the regulation of cell proliferation?

A

-ECM
-growth factors

36
Q

How does the ECM trigger cell proliferation?

A

upon binding of the extracellular matrix, the actin cytoskeleton on the intracellular side changes in length which releases signals to trigger proliferation

37
Q

When is repair by connective tissue (fibrosis) triggered?

A

When damage is so serve that damaged/dead parenchymal (epithelial or specialized differentiated) cells cannot be regenerated

38
Q

What occurs when damaged cells are unable to be regenerated?

A

-They are replaced by fibroblasts which results in fibrosis (scarring)
-repair begins within 24 hours of injury by the emigration of fibroblasts and the induction of fibroblast and endothelial cell proliferation

39
Q

How many sequential processes are involved in fbrosis?

A

four

40
Q

what are the sequential processes of fibrosis?

A

-formation of new blood vessels at the site of injury- angiogenesis/ neovascularization
-migration and proliferation of fibroblasts at site of injury
-deposition of ECM by firoblasts
-maturation and remodeling of the fibrous tissue- primarily performed by macrophages

41
Q

How are growth factors that regulate fibrosis produced?

A

by endothelial cells and by inflammatory cells, most notably macrophages

42
Q

what are the growth factors that regulate fibrosis?

A

-PDGF (platelet derived growth factor)
-TGF (transforming growth factor)
-FGF-2 (fibroblast growth factor)

43
Q

platelet-derived growth factor (PDGF)

A

migration and proliferation of fibroblasts, smooth muscle cells, and macrophages

44
Q

transforming growth factors (TGF)

A

-potent fibrinogenic factor that stimulates collagen, fibronectin and proteoglycan synthesis
-inhibits collagen degradation
-inhibits lymphocyte proliferation
-has anti-inflammatory effect

45
Q

Fibroblast growth factor (FGF-2)

A

-stimulates proliferation of endothelial cells
-promotes migration of macrophages and fibroblasts to damaged areas

46
Q

Why are the underlying processes of fibrosis regulation viable treatments of disease?

A

many diseases are associated with fibrosis, so the underlying processes are viable targets for treatment

47
Q

Replacement of injured cells with those of the same type and function is know as
A. repair
B. regeneration
C. both A and B

A

A. repair

48
Q

Which stage of healing from tissue injury is largely driven by platelet-derived factors?
A. homeostasis
B. inflammation
C. proliferation
D. Remodeling

A

B. inflammation

49
Q

Name a common disease state that impairs wound healing

A

Diabetes

50
Q

Which of the following is not a key growth factor regulating fibrosis?
A. PDGF
B. PKC
C. TGF
D. FGF-2

A

B. PKC

Patho Exam 4 (6 decks)

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