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1 Path Unit > 6 Inflammation & Repair III - Repair > Flashcards

6 Inflammation & Repair III - Repair Flashcards

1
Q

What is the term for the systemic effects of inflammation?

A

Acute phase reaction (or system inflammatory response)

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2
Q

What are the most important mediators of systemic inflammation? Be specific.

A

Cytokines

TNF, IL-1, & IL-6 (same trio as in the local acute inflammatory response)

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3
Q

What blood tests can be used to show an acute phase reaction is happening in a patient? Will the levels be elevated or depressed?

A

C-reactive protein (CRP)

erythrocyte sedimentation rate (ESR)

Both elevated

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4
Q

What are all the systemic manifestations of an acute phase reaction?

A
  • Fever
  • Elevated plasma levels of acute-phase proteins
  • Increased WBC count
  • Increased HR & BP
  • Chills, rigors
  • Anorexia, somnolence, & malaise
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5
Q

What is/are the key mediator(s) for fever?

A

TNF

IL-1

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6
Q

What is the basic process causing a fever?

A

It is in response to pyrogens which stimulate prostaglandin synthesis

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7
Q

What is/are the key mediator(s) for elevated plasma levels of acute-phase proteins?

A

IL-6

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8
Q

What is/are the key mediator(s) for increased WBC count?

A

TNF

IL-1

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9
Q

T/F

The population of WBCs increased in an acute phase reaction is neutrophils (PMNs).

A

False

The population of WBCs increased varies

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10
Q

What is another term for systemic inflammatory response syndrome? What are the presenting signs of this?

A

Sepsis

  • Hypotension
  • Poor organ perfusion
  • Disseminated intravascular coagulation (May progress to shock and multiorgan failure)
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11
Q

What are the mediators of systemic inflammatory response syndrome?

A

TNF (most important)

IL-1

IL-12

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12
Q

What cytokines contributes to these local and systemic inflammatory effects?

  • Increased permeability of blood vessels (local)
  • Increased expression of adhesion molecules by vascular endothelium (local)
  • Leukocyte production (systemic) & activation (local)
  • Fever (systemic) -Low cardiac output (systemic)
  • Increased clot formation (systemic)
  • Insulin resistance in multiple tissues (systemic)
  • Shock (systemic) (top mediator in this effect)
A

TNF

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13
Q

What cytokines contributes to these local and systemic inflammatory effects?

  • Increased expression of adhesion molecules by vascular endothelium (local)
  • Leukocyte production (systemic) & activation (local)
  • Increased chemokine production
  • Fever (systemic)
  • Insulin resistance in multiple tissues (systemic)
  • Shock (systemic)
A

IL-1

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14
Q

What cytokines contributes to these local and systemic inflammatory effects?

  • Increased chemokine production
  • Fever
  • Increased production of acute phase proteins
  • Increased leukocyte production
A

IL-6

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15
Q

What anti-inflammatory mediators downregulate acute inflammation?

A

Increased lipoxin

NO production by endothelium

Anti-inflammatory cytokine secretion (eg TGF)

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16
Q

What are the 3 possible outcomes of acute inflammation?

A

1-Complete restitution - no permanent damage and function regained

2-Healing by tissue replacement - fibrosis

3-Progression to chronic inflammation persistence of injurious agent interference with healing process autoimmunity

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17
Q

What are the 2 possible outcomes of chronic inflammation?

A

1-Resolution - inflammation subsides and repair occurs

2-Progressive tissue damage, repair, & scar formation (simultaneous)

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18
Q

The inflammatory response not only serves to eliminate the insult and tissue damage, but also sets into motion the process of ___________.

A

Repair

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19
Q

What are the 2 mechanisms of tissue repair (healing)?

A

Regeneration

Scar formation

-Often both mechanisms contribute to repair

20
Q

What is regeneration (mechanism of tissue repair)?

A

Tissues that are able to replace damaged cells return to a normal state.

21
Q

What is scar formation (mechanism of tissue repair)?

A

Occurs when the injured tissue is incapable of regeneration or if the supporting structures (eg basement membrane) are severely damaged. Process of deposition of fibrous tissue

22
Q

What tissues are capable of regeneration?

A

Skin, GI epithelium, liver

23
Q

What basic factors are necessary for regeneration to occur?

A

Cell proliferation

Growth factors

Integrity of extracellular matrix

24
Q

What cell types proliferate during tissue repair?

A

Remnants of injured tissue

Vascular endothelial cells

Fibroblasts

25
Q

What are the 3 types of tissues (based on proliferative capacity)? What is an example of each?

A

1) Labile tissues - readily regenerate - hematopoietic cells in bone marrow, surface epithelia, GI epithelium
2) Stable tissues - minimal replicative activity (normally quiescent) - parenchyma of most solid organs, endothelial cells, fibroblasts, smooth muscle
3) Permanent tissues - non-proliferative - most neurons, cardiac muscle

26
Q

Stem cells are characterized by & found in:

A

Characterized by self-renewal & asymmetric replication

Found in labile tissues

27
Q

What are growth factors?

What cells produce growth factors related to tissue repair?

A
  • Proteins that stimulate the survival and proliferation of particular cells; may also promote migration, differentiation, and other cellular responses
  • Many produced by macrophages and lymphocytes; others by parenchymal or stromal cells in response to cell injury
28
Q

Name the growth factors involved in repair (list from PP).

A

EGF

TGF-beta

HGF

VEGF

PDGF

FGFs

29
Q

What are the 2 forms of extracellular matrix? What does each contain?

A

Interstitial matrix - fibrillar collagens, elastin, proteoglycan, and hyaluronan

Basement membrane - type IV collagen, laminin, and proteoglycan

30
Q

What are the functions of the extracellular matrix?

A
  • Provides mechanical support to tissues
  • Acts as a substrate for cell growth and formation of tissue microenvironments
  • Regulates cell proliferation and differentiation
  • Required for tissue regeneration (otherwise scar formation occurs)
31
Q

What is the process of regeneration in labile tissues? What signaling molecules are involved?

A

Injured cells are rapidly replaced by proliferation of residual cells and differentiation of tissue stem cells provided that the underlying basement membrane is intact

No known growth factors

32
Q

What is the process of regeneration in stable tissues? What signaling molecules are involved?

A

Liver has the greatest ability to regenerate. After damage remaining hepatocytes proliferate.

Initiated by cytokines (TNF, IL-6) & mediated by growth factors (HGF, EGF, TGF-beta)

33
Q
A

;)

34
Q

What is the time course of inflammation and repair?

A

Inflammation 0.1 - 3 days

Granulation tissue 0.3 - 10 days

Wound contraction 3 - 30 days

Collagen accumulation/remodeling 3 - 100 days

35
Q

What are the essential processes involved in scar formation?

A
  • Inflammatory cell infiltration
  • Angiogenesis
  • Fibrogenesis (migration and proliferation of fibroblasts with deposition of extracellular matrix - mainly collagen; formation of granulation tissue)
  • Maturation & remodeling (sometimes re-epithelialization)
36
Q

Angiogenesis involves what processes?

What growth factors are necessary?

A

extracellular matrix interactions; endothelial cell migration, proliferation, and differentiation

VEGF (vascular endothelial growth factor), bFGF (basic fibroblast growth factor), Ang1, & Ang2

37
Q

New vessels are leaky.

What is the result of leaky vessels?

What growth factor contributes to this?

A

Edema

VEGF

38
Q

What are the 2 steps of fibrogenesis?

A
  1. migration & proliferation of fibroblasts
  2. deposition of ECM by fibroblasts
39
Q

What growth factors are involved in fibrogenesis?

A

TGF-beta (transforming growth factor beta)

PDGF (platelet derived growth factor)

FGF (fibroblast growth factor)

cytokines - IL-1, IL-13

40
Q

What is granulation tissue?

A

highly vascular tissue composed of small vessels, fibroblasts, few inflammatory cells

41
Q

What is a granuloma?

A

inflammation characterized by epitheloid macrophages and giant cells

42
Q

What is involed in tissue remodeling?

A
  • balance of collagen synthesis and degradation
  • synthesis of fibroblasts
  • degradation by metalloproteinases
  • collagenases, gelatinases, and stromelysins
  • produced by fibroblasts, leukocytes, and some epithelial cells
  • tightly controlled by growth factors, plasmin, and tissue inhibitors of metalloproteinases (TIMPs)
43
Q

What 8 factors influence tissue repair?

A

Infection - most important cause of delay in healing

Nutrition

Glucocorticoids - anti-inflammatory effects -> weaker scar

Mechanical variables - pressure, torsion

Poor perfusion

Foreign bodies

Location of injury

Abberations of cell growth (keloid)

44
Q

What is the difference between first intention and second intention healing?

A

First intention - eg surgical incision; leads to less prominent scar

Seconf intention - eg trauma, ulcer; leads to more significant scar

45
Q

What are the 5 Rs of the inflammatory response?

A
  • Recognition of the injurious agen
  • Recruitment of leukocytes
  • Removal of the agent
  • Regulation of the response
  • Resolution (repair)
46
Q

What is the hallmark of inflammation?

A

Infiltration of tissue with any of the classes of leukocytes

  • neutrophils - acute inflammation
  • lymphocytes & monocytes - chronic inflammation

1 Path Unit (16 decks)

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