Healing and Repair Flashcards

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1
Q

what type of inflammation is regeneration or restoration of infected tissue associated with?

A

acute inflammation

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2
Q

what type of inflammation is tissue repair associated with?

A

chronic inflammation

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3
Q

what is regeneration?

A

replacement with functional differentiated cells

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4
Q

what is repair?

A

production of a fibrous scar and changes in tissue structure/architecture

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5
Q

what does regeneration or repair depend on?

A

severity and location of damage - some tissues have better regenerative capacities than others

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6
Q

what are the 3 different types of cells?

A

labile, stable and permanent cells

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7
Q

what are labile cells?

A

normal state is active cell division and rapid regeneration

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8
Q

what are stable cells

A

variable rates of regeneration, rapid proliferation in response to injury

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9
Q

what are permanent cells?

A

unable to divide or regenerate

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10
Q

what are the four stages of healing?

A

clotting phase, inflammation phase, proliferative phase and maturation phase

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11
Q

what happens during the clotting phase of healing?

A

clot formation and mitosis of labile/stable cells

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12
Q

what happens in the inflammation phase of healing?

A

macrophages/neutrophils phagocytose and degrade infectious agent, stimulation of certain cells (e.g. keratinocytes and fibroblasts) to start regenerating and/or repairing tissue

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13
Q

what happens in the proliferative phase of healing?

A

formation of granulation tissue, fibroblasts are key players, new connective tissue, angiogensis and growth factors are essential too

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14
Q

what is the first phase of the proliferative phase?

A

vascular granulation tissue

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15
Q

what is the second phase of the proliferative phase?

A

fibrous granulation tissue

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16
Q

what happens during the vascular granulation tissue phase of the prolfierative phase?

A

mix of proliferating capillaries, fibroblasts, immune cells, new capillaries are relatively leaky allowing cells and fluid into the tissue

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17
Q

what happens during the fibrous granulation tissue phase of the proliferative phase?

A

over time capillaries regress and immune cells return to blood, mature fibroblasts lay down collagen

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18
Q

what is angiogenesis?

A

the formation of new capillaries

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19
Q

how does the new capillaries from angiogenesis form?

A

from existing vasculature by either sprouting or the intussusceptive mechanism

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20
Q

what is angiogenesis driven by

A

growth factors - vascular endothelial growth factor (VEGF)

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21
Q

what are the steps of the sprouting mechanism of angiogenesis?

A

VEGF gradient, 1 - tip vs stalk selection, 2 - abluminal sprouting, 3 - elongation and bridging, 4 - sprout fusion and lumenisation

22
Q

what are the steps of the intussusceptive mechanism of angiogenesis?

A

no VEGF gradient, 1 - vascular enlargement, EITHER 2a - protrusion of opposing capillary walls OR 2b - intraluminal sprouting, 3 - intraluminal pillar formation, 4 - splitting

23
Q

what happens when there is a VEGF gradient?

A

VEGF found in extracellular matrix and produced by epithelial cells, macrophages and fibroblasts, endothelial cells move towards gradient (sprouting)

24
Q

what happens when there is no VEGF gradient?

A

lumen of existing blood vessel enlarges until central areas fuse together leading to splitting of vessel (intussusceptive)

25
Q

what growth factors play key roles in the proliferative phase?

A

cytokines and hormones

26
Q

what do growth factors do in the proliferative phase?

A

promote or inhibit cell growth and differentiation, bind receptors on cell surfaces, homeostatic production

27
Q

what does an alteration in the balance of growth factors cause?

A

dysregulated cellular proliferation and survival of abnormal cells

28
Q

what are the multiple functions of growth factors?

A

promote cell survival, locomotion, contractility, differentiation, angiogenesis

29
Q

what are the receptors of growth factors?

A

they are specific on the target cells

30
Q

what is fibrosis?

A

the extensive deposition of collagen and formation of excess fibrous connective tissue

31
Q

what is fibrosis driven by?

A

fibroblasts (and macrophages)

32
Q

what controls fibroblast function?

A

macrophages (M1 and M2 subtypes)

33
Q

what are M2 macrophages essential in?

A

the process of healing and reapir

34
Q

what do M2 macrophages in the healing and repair process?

A

engulf/degrade and produce growth factors: TGF-beta and PDGF, VEGF and EGF

35
Q

what does TGF-beta do?

A

stimulates fibroblast proliferation and collagen synthesis and controls epithelial regeneration

36
Q

what does PDGF do?

A

mitogenic and chemotactic for fibroblasts and smooth muscle cells

37
Q

what happens in the maturation phase of healing?

A

disorganised granulation tissue remodelled by remaining cells, collagen fibres are cross linked along tension lines, re-epithelisation, regain of tensile strength, fibrous scar remains, tissue remodelling

38
Q

what happens in the first 24 hours of primary intention healing?

A

scab forms, neutrophils rush to the site of trauma and a clot forms

39
Q

what happens in 3-7 of primary intention healing?

A

mitoses, granulation tissue forms, macrophages and fibroblasts present and new capillaries form

40
Q

what happens in the weeks of primary intention healing?

A

fibrous union

41
Q

what are the differences between primary and secondary intention healing?

A

in secondary intention there is a larger scab, inflammation more intense because there is more necrotic debris exudate and fibrin to remove, larger amounts of granulation tissue - larger defect, involves wound contraction

42
Q

what determines whether primary or secondary healing takes place?

A

the extent of the damage

43
Q

summarise what is present in secondary intention and not in primary intention

A

longer repair and healing time, greater chances of scarring, increased chance of infections

44
Q

what happens in the inflammatory stage of fracture of healing?

A

haematoma formation at fracture, occurs within 48 hours, acute inflammatory response - inflammatory infiltrate scavenge debris and dying tissue, bone cells deprived of oxygen /blood supply die off

45
Q

what happens in the first repairing stage of fracture healing?

A

capillaries form into haematoma, occurs within weeks, fibroblasts produce collagen fibres, osteoblasts form spongy, granulation tissue forms, granulation tissue becomes the fibrocartilage callus (soft callus)

46
Q

what is fibrocartilage callus?

A

the temporary material surrounding a fractured bone and is composed of fibroblasts and chondroblasts

47
Q

what happens in the second repairing stage in fracture healing?

A

chondrocytes and osteoblasts produce cartilage and bone, remaining granulation tissue is ossified (turned to bone), formation of hard bone callus at fracture site (known as fracture callus or woven bone), occurs within months

48
Q

what happens in the remodelling stage of fracture healing?

A

osteoclasts and osteoblasts remodel the hard bone callus (resorption vs deposition of bone), cortical bone replaces woven bone, takes between months and years, angiogenesis essential in bone regeneration and repair

49
Q

what is woven bone

A

hard bone callus at the fracture site which gets replaced with cortical bone later on

50
Q

what type of tissue and inflammation does fibrosis occur in?

A

repair tissue (chronic inflammation)

51
Q

what are the stages of fracture healing?

A

inflammatory, repairing (1 and 2) and remodelling