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General Pathology > Repair > Flashcards

Repair Flashcards

1
Q

What is repair?

A

restoring normal structure and function (healing)

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2
Q

What are the two. often interconnected, process of repair?

A

Regeneration and Scar formation

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3
Q

Define Regeneration

A

proliferation and differentiation of new cells from
stem cells to restore native tissue

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4
Q

Define Scar formation

A

deposition of connective tissue (mostly collagen)

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5
Q

Repair is tied to _____________ and must be tightly controlled

A

inflammatory response

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6
Q

If repair is ________ or defective then _________ occurs

A

Insufficient, loss of structure/function

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7
Q

If repair is ________ or defective then _________ occurs

A

excessive (fibrosis), loss of structure/function

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8
Q

The central players in repair are:

A

Macrophages

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9
Q

In terms of proliferative capacity, the tissue can be: (Three types)

A
  • Continuously dividing tissues (labile tissues)
  • Stable Tissues
  • Permanent Tissues
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10
Q

Define Continuously dividing tissues (labile tissues)

A

tissue that is constantly being lost and replaced by maturation from stem cells or mature cells

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11
Q

Examples of Continuously dividing tissues (labile tissues)

A

skin, oral cavity, vagina, cervix,
exocrine ducts, GI tract

(Can often get regeneration in these types of tissues depending on the degree of injury)

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12
Q

Define stable tissue

A
  • Are normally not dividing (quiescent)
  • Can regenerate to a limited degree in response to injury
    Exception: Liver (near
    complete regeneration via
    hyperplasia)
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13
Q

Examples of stable tissue

A

endothelial cells, fibroblasts, smooth muscle, parenchyma (functional part) of most solid organs (kidney, pancreas, liver).

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14
Q

Define permanent tissue

A

Do not proliferate after birth having become fully mature or terminally differentiated

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15
Q

Examples of permanent tissue

A

neurons, cardiac muscle, skeletal muscle

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16
Q

The size of cell populations are tightly regulated by ___________

A

the cell cycle

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17
Q

Upon stimulation by _________ and regulation by ______, cells arrested in the G0 or G1
phase divide then differentiate

A

growth factors, cyclins

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18
Q

What are the five phases of the cell cycle?

A

G0, G1, S, G2, and M

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19
Q

In simple terms, G0 is:

A

quiescent phase (no division)

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20
Q

In simple terms, G1 is:

A

presynthetic growth phase

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21
Q

In simple terms, S is:

A

DNA synthesis phase

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22
Q

In simple terms, G2 is:

A

premitotic growth phase

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23
Q

In simple terms, M is:

A

mitotic phase

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24
Q

Three effects of cyclins on the cell cycle:

A
  • Cyclins are constantly being rapidly produced and degraded
  • Cyclins activate cyclindependent kinases (CDKs) which phosphorylate regulatory proteins leading to cell division
  • Cyclin-dependent kinase (CDK) inhibitors stop the cell cycle
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25
Q

If damage is excessive or if tissues can’t repair by regeneration then they repair by _______________

A

scar formation

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26
Q

Scarring is the:

A

replacement of non-regenerated cells with connective tissue

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27
Q

Define fibrosis

A

excessive collagen deposition
due to chronic inflammation (kidney, lungs, liver) or after necrosis (e.g. myocardial infarction)

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28
Q

What is “organization” in scar formation?

A

fibrosis in a tissue space with an
inflammatory exudate. (e.g. organizing pneumonia)

29
Q

What are the components of scare tissue?

A

capillaries and immature fibroblasts

30
Q

After clot formation occurs immediately after injury, what is the repair sequence? (Day 1, 2, 3-6, 7, and 14)

A

Day 1- Neutrophils migrate in and phagocytose foreign substances and necrotic tissue
Day 2- macrophages enter, granulation tissue (capillaries and immature fibroblasts) starts to form, protected by a fibrin clot
Day 3-6- lymphocytes and plasma cells enter
Day 7- clot digested, initial repair complete
Day 14- fibroblasts mature, collagen remodeled forming scar tissue (dense/white)

31
Q

Blood vessel growth (angiogenesis) is mediated by _________

A

vascular endothelial growth factor (VEGF)

32
Q

migration and proliferation of fibroblasts are mediated by ___________

A

fibroblast growth factor (FGF)

33
Q

By day 3-5 post injury, new _______ and ________ are formed giving a red/pink and granular appearing tissue “________ tissue”

A

blood vessels (capillaries), fibroblasts, granulation

(fibroblasts include specialized fibroblasts with contractile properties called myofibroblasts)

34
Q

Fibroblast maturation/differentiation is stimulated by _________

A

TGF-β

35
Q

Fibroblast maturation/differentiation causes ________ deposit leading to ____________

A

collagen, termination of the
inflammatory response

36
Q

Maturation, reorganization/remodeling into a scar begins ________ after injury and may continue for _________

A

2-3 weeks, months to years

37
Q

What are the types of repair?

A

Primary Intention and secondary Intention

38
Q

Characteristics and example of Primary Intention

A
  • Little loss of tissue occurs with injury.
  • Wound margins are joined closely together.
    (Example: surgical incision)
39
Q

Characteristics and example of Secondary Intention

A
  • Tissue is lost preventing edges of injury from being brought back together. (Example:
    extraction site)
  • increased granulation tissue and scar tissue
40
Q

New vessels are ______ due to VEGF and_________. Thus, granulation tissue is
edematous in its early stages

A

leaky, incomplete
interendothelial junctions

41
Q

Inflammatory cells (e.g. macrophages) make
_________ which causes _________ recruitment and activation to make ___________

A

growth factors, fibroblast, connective tissues

42
Q

Over time, new vessels and proliferating fibroblasts __________ (increase/decrease), while ________ production
increases eventually leading to a __________

A

decrease, collagen, pale avascular
scar

43
Q

Four important growth factors in scar formation:

A

TGF-β, PDGF, FGF, and Cytokines

44
Q

(T/F) TGF-β has different effects depending on cell and tissue
state.

A

True

45
Q

In both acute and chronic inflammation, TGF-β ________
production of and ________ breakdown of ECM

A

stimulates, inhibits

46
Q

TGF-β also had __________ effects where it _______ inflammatory responses

A

anti-inflammatory, ends

47
Q

PDGF stimulates the migration and proliferation of _______ and ________

A

fibroblasts, smooth muscle cells

48
Q

FGF _________ (stimulates/inhibits) fibroblast migration

A

stimulates

49
Q

Cytokines- IL-13 stimulates ___________ and fibroblast migration

A

collagen synthesis

50
Q

(T/F) Connective tissues are modified over time, thus
balancing production and degradation

A

True

51
Q

_______________ are an important player in remodeling

A

Matrix metalloproteinases (MMPs)

52
Q

Talk about Matrix metalloproteinases (MMPs).

A
  • released as inactive precursors (zymogens)
  • activated by proteases at the site of injury (e.g. plasmin)
  • degrade ECM proteins
  • then quickly inhibited by tissue inhibitors of metalloproteinases (TIMPs)
53
Q

What are the eight factors that can prevent or inhibit
normal healing/repair?

A
  • Infection: most important clinical cause
  • Nutrition: protein or vitamin C deficiency
  • Steroid use: anti-inflammatory (may inhibit healing)
  • Poor perfusion: atherosclerosis, diabetes
  • Foreign bodies: impede healing
  • Type and extent of injury: permanent tissues scar
  • Location of injury: resolution of tissue space inflammation
  • Aberration of cell growth: keloids or excessive granulation tissue (pyogenic granuloma)
54
Q

What are stem cells?

A

Undifferentiated cells capable of self-renewal and differentiation into mature (specialized) cells

55
Q

What are the three types of stem cells?

A

Totipotent, Pluripotent, and Multipotent

56
Q

Totipotent stem cells can differentiate into:

A

embryonic and extra-embryonic tissues

57
Q

Pluripotent stem cells includes:

A

embryonic SC and induced pluripotent SC

58
Q

Multipotent stem cells includes:

A

mesenchymal stem cells

59
Q

Embryonic stem cells (ES cells) has ________ capacity to form cells of ___________

A

Pluripotent, 3 germ layers

60
Q

Embryonic stem cells (ES cells) are ____________ and typically cause an __________ when placed in a different person

A

harder to isolate (inner cell layer of the blastocyst), immune response

61
Q

Where are Mesenchymal Stem Cells found?

A

within an organ or tissue with renewal capacity

62
Q

Mesenchymal Stem Cells maintain tissue ___________

A

homeostasis

63
Q

Mesenchymal Stem Cells are Controlled by other cells within the tissue niche. Give two examples.

A
  • Hematopoietic stem cells- can be isolated from blood or bone marrow; and used in bone marrow transplants to treat leukemia/lymphoma
  • Bone marrow also contains mesenchymal stem cells
    (MSC) which give rise to bone, cartilage, fat, and muscle.
64
Q

What are iPS cells?

A

Reprogramed adult cells to acquire
“stem-cell-ness”→ induced pluripotent stem cells (iPS cells) which should engraft and replace damaged cells

65
Q

What are the current applications of iPS cells?

A
  • Being used in clinical trials to treat many diseases including macular degeneration, heart disease, Parkinson disease, spinal cord injury
  • A lot in the future!
66
Q

Dental application of iPS cells?

A

Mesechymal stem cells

67
Q

Clinical trials of Mesechymal stem cells have been very promising. Three of the dental applications are:

A
  • engineer bone for orofacial bone regeneration.
  • tooth root regeneration
  • regeneration of pulp tissue in cleaned root canals with fabricated
    vital dental pulp tissue constructs (future “regenerative” endo treatment)

Fun fact: Multiple companies allow you to bank teeth for future
applications (~$300 + $13/month)

68
Q

Other applications of Mesechymal stem cells:

A

CNS disorders, repair infarcted myocardium, liver disease, autoimmune diseases…so many possibilities

General Pathology (32 decks)

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