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Pathology and Immunity > Healing and Repair > Flashcards

Healing and Repair Flashcards

1
Q

what are the four stages of soft tissue healing

A

coagulation
inflammation
proliferative
maturation

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2
Q

what occurs in the proliferative phase

A

angiogenesis and fibrosis

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3
Q

what are the stages of hard tissue healing

A

bone remodelling
fracture healing

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4
Q

what type of inflammation leads to healing and repair

A

both acute and chronic

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5
Q

what is regeneration

A

replacement with functional, differentiated cells

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6
Q

what is repair

A

production of a fibrous scar and changes in tissue structure

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7
Q

what determines if there will regeneration or repair

A

this depends on the severity or location of tissue damage

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8
Q

how does a fibrous scar arise

A

from fibrosis by fibroblasts which produce collagen
scar will remain in tissue and change its struture and function

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9
Q

which form of inflammation is associated with a fibrous scar

A

chronic inflammatory diseases

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10
Q

what are the three cell types involved in healing and repair

A

labile cells
stable cells
permanent cells

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11
Q

what are labile cells

A

these are cells that have active cell division and rapid regeneration

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12
Q

what is an example of labile cells

A

oral keratinocytes

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13
Q

what is an example of stable cells

A

fibroblasts

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14
Q

what characterises stable cells

A

these have variable rates of regeneration and proliferation in response to injury

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15
Q

what is an example of permanent cells

A

nerve fibres

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16
Q

what characterises permanent cells

A

unable to divide and unable to regenerate

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17
Q

why is nerve damage permanent

A

nerve cells cannot regenerate or divide

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18
Q

where are oral keratinocytes found

A

in the periphery of gingival tissue

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19
Q

what happens in the coagulation phase of healing

A
  • clot formation through coagulation cascade
  • in parallel with the fibrinolytic system
  • platelets are weaved together by fibrin
  • mitosis of labile and stable cells
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20
Q

are the stages of healing and repair isolated

A

no they all occur at the same time

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21
Q

describe the inflammation stage of healing and repair

A

innate immune cell recruitment to site
immune cells will phagocytose and degrade infectious agents or damaged cells
stimulation of cells to start tissue repair and regeneration
fibroblasts drive fibrosis

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22
Q

what are the main points of inflammation phase

A

cell recruitment and fibrosis

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23
Q

what occurs in the proliferation phase

A

this has an early and late phase
forms granulation tissue
growth factors
fibroblasts
angiogenesis
myofibroblasts

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24
Q

what is angiogenesis

A

the formation of new blood vessels

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25
Q

what is granulation tissue rich in

A

collagen

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26
Q

why are myofibroblasts involved in healing

A

they aid in the closure of a wound

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27
Q

why are wounds bright red

A

there are new blood vessels being formed during proliferation phase

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28
Q

what is the first phase of proliferation

A

this phase is rich in vasculature and is a mix of newly formed capillaries, immune cells, fibroblasts and leaky capillaries

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29
Q

what occurs in the second phase of proliferation

A

this stage is rich in collagen as there is fibrous granulation tissue
the capillaries will regress and mature fibroblasts will create collagen

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30
Q

when is granulation tissue first formed

A

during proliferation phase

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31
Q

how does granulation tissue appear histologically

A

circular cells that are macrophages to control fibroblast action
new capillaries appear as red dots
fibroblasts are long and spindle shaped cells

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32
Q

what are matrix metalloproteinases

A

these are produced by different immune cells and that remodel the extracellular matrix, help with cellular migration and aid the process of angiogenesis

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33
Q

how do MMPs work

A

they target collagen to help cellular migration, getting the cells out of circulation itno the tissue and then aiding angiogenesis
create a way into the tissue to the new capillaries can be formed
produce cytokine growth factors and these enzymes will aid in cellular migration and angiogenesis

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34
Q

what are growth factors

A

these are signalling molecules that promote or inhibit cell growth and differentiation.
they bind receptors on the cell surface
they are normally produced but if there is an alteration in the balance of their production then there is dysregulated cellular proliferation

35
Q

when are growth factors released as effector responses

A

following microbial recognition and cytokine signalling

36
Q

what are the two growth factors to notr

A

TGF
VEGF

37
Q

what is TGF

A

transforming growth factor
functions in driving the formation of new tissue and stimulates fibroblasts to produce collagen

38
Q

what is VEGF

A

this is vascular endothelial factor that functions in driving angiogenesis

39
Q

what is angiogenesis in healing

A

formation of new capillaries
formed by existing vasculature by sprouting or splitting
the process is driven by VEGF

40
Q

what is sprouting

A

VEGF will produce a gradient and endothelial cells lining existing vasculature will move toward the gradient and as they move they will form a new capillary stemming from the original vasculature

41
Q

what does splitting mean

A

this is intersusception of existing vasculature
this is when there is no VEGF gradient and the endothelial cells will move and increase the size of the lumen of the existing vasculature until it forms new vasculature through splitting

42
Q

how are new blood vessels formed when there is a VEGF gradient

A

sprouting

43
Q

how are new blood vessels formed when there is no VEGF gradient

A

splitting

44
Q

what is fibrosis

A

this is the deposition of collagen and the formation of fibrous connective tissue
it is driven by fibroblasts
during substantial or repeated damage ie in chronic inflammation

45
Q

what controls fibroblasts function

A

M1 and M2 macrophages

46
Q

where are fibroblasts found

A

within the connective tissue underlying the epidermis and epithelial tissue

47
Q

which macrophages are the main drivers of fibrosis and angiogenesis

A

M2

48
Q

which macrophage is antiinflammatory

A

m2

49
Q

which macrophages are pro inflammatory

A

m1

50
Q

what does the balance between the m1 and m2 subsets of macrophages lead to

A

tissue injury or tissue repair

51
Q

which molecule drives tissue remodelling

A

prostaglandins

52
Q

do prostaglandins increase or decrease the activity of fibroblasts

A

they decrease it

53
Q

what is the maturation phase of healing

A

this is when disorganised granulation tissue is remodelled by remaining cells
collagen fibres are cross linked and there is repeithelialisation
they regain tensile strength
fibrous scar will remain
tissue remodelling is required

54
Q

which molecules reduce fibroblast activity

A

prostaglandins

55
Q

what is osteoblastogenesis

A

the formation of bone

56
Q

what is osteoclastogenesis

A

the resorption of bone

57
Q

how often do we get a new skeleton

A

every ten years

58
Q

is there net loss of bone during normal formation and resorption

A

no

59
Q

what is bone resorption mediated by

A

osteoclasts

60
Q

what do osteoclasts differentiate from

A

macrophages

61
Q

what is RANKL

A

receptor activator of nuclear factor Kappa-B Ligand

62
Q

what produces RANKL

A

osteoblasts

63
Q

what does RANKL activate

A

RANK on osteoclasts

64
Q

why is there not normally unbalanced bone resorption

A

the production of RANKL is normally controlled

65
Q

what mediates bone formation

A

osteoblasts

66
Q

what do osteoblasts secrete alongside RANKL

A

OPG - osteoprotogerin

67
Q

what inhibits RANKL

A

osteoprotogerin

68
Q

what is the RANKL/OPG ratio important for

A

modulating processes in health

69
Q

what is an excessie immune respone associated with

A

an increase in the RANKL/OPG ratio

70
Q

what is an example of a disease that leads to an imbalance in RANKL/OPG ratio

A

periodontal disease

71
Q

what is the keystone pathogen for periodontal disease

A

p gingivails

72
Q

how does p gingivalis cause periodontal disease

A

they target osteoblasts and stimulate the production of RANKL which leads to an imbalance in the ratio to cause excessive bone resorption

73
Q

what is the periosteum

A

this is the sheath outside the bone that supplies it with blood immune cells and plasma proteins

74
Q

what are the stages of fracture healing

A

hematoma to callus to the original shape

75
Q

what occurs in the coagulation phase for fracture healing

A

formation of a hematoma

76
Q

what is a hematoma

A

blood clot within tissue/bone

77
Q

what occurs in the inflammatio phase of fracture healing

A

recruitment of immune cells and removal of debris and dying tissue
cells produce soluble mediators to drive later healing responses

78
Q

describe the proliferation phase of fracture healing

A

formation of granulation tissue that is similar to soft tissue
this granulation tissue becomes the fibrocartilage callus and is comopsed of osteoblasts, fibroblasts and chondrocytes
it is then ossified

79
Q

what does woven bone do during fracture healing

A

forms a tempoary scaffold for new bone development

80
Q

describe the maturation phase of fracture healing

A

osteoclasts and osteoblasts will remodel the bone callus
cortical replaces woven bone
can take between months and years
angiogenesis is essential for bone regeneration and repair

81
Q

why does bone remodelling occur

A

to restructure the bone back to its original shape

82
Q

describe the steps to sprouting

A
  • tip vs stalk selection
  • abluminal sprouting
  • elongation and bridging
  • sprout fusion and lumenisation (ie formation of a lumen)
83
Q

describe the steps to splitting

A
  • vascular enlargement
  • protrusion of opposing capillary walls, intraluminal sprouting
  • intraluminar pillar formation
  • splitting
84
Q

what is another name for capillary splitting

A

intussusception

Pathology and Immunity (16 decks)

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