Healing and repair

Question 1

How does healing and repair arise?

Answer 1

following acute or chronic inflammation

Question 2

What type of healing occurs after acute inflammation?

Answer 2

complete restoration of tissues (resolution of structure and function)

Question 3

What type of healing occurs following chronic inflammation?

Answer 3

healing associated with tissue damage (e.g. fibrosis) - no restoration

Question 4

Regeneration definition

Answer 4

new functional, differentiated cells replace the damaged tissue (healing)

Question 5

Repair definition

Answer 5

production of a fibrous scar and changes in tissue structure and function

Question 6

What factors determine whether inflamed tissues undergo regeneration or repair?

Answer 6

tissue type and severity of damage (e.g. acute vs chronic inflammation)

Question 7

What type of healing may occur after a mild, superficial injury?

Answer 7

regeneration

Question 8

What type of healing may occur following severe injury?

Answer 8

repair (fibrosis)

Question 9

Which cells are involved in healing and repair?

Answer 9

immune cells and labile, stable and permanent cells

Question 10

What are labile cells?

Answer 10

cells whose normal state is active cell division and therefore undergo rapid regeneration

Question 11

Examples of labile cells

Answer 11

immune cells and non-professional immune cells e.g. keratinocytes (epithelial cells)

Question 12

What are stable cells?

Answer 12

cells that undergo variable rates of regeneration

Question 13

When do stable cells proliferate/regenerate?

Answer 13

in response to injury

Question 14

Example of stable cells

Answer 14

fibroblasts

Question 15

What are permanent cells?

Answer 15

cells that are unable to divide or regenerate

Question 16

Example of permanent cells

Answer 16

neurones and certain myocytes

Question 17

What happens as a result of a minor cut to the skin periphery?

Answer 17

rapid regeneration occurs as only epithelial (labile) cells are involved

Question 18

What happens as a result of a deeper cut involving the connective tissue underlying the epithelium?

Answer 18

regeneration occurs but at a slower rate due to the involvement of stable cells (e.g. fibroblasts in CT)

Question 19

What happens as a result of an aggressive cut affecting nerve endings?

Answer 19

Repair occurs as permanent cells are unable to regenerate (collagen deposition and scarring results)

Question 20

What are the 4 stages of healing for soft and hard tissues?

Answer 20

1. coagulation phase
2. inflammation phase
3. proliferation phase
4. maturation phase

Question 21

What is the first stage of healing in soft tissues?

Answer 21

coagulation (hemostasis) phase

Question 22

When does the coagulation phase of healing take place?

Answer 22

within minutes to hours of the injury

Question 23

Which plasma system forms blood clots?

Answer 23

coagulation system

Question 24

Which two plasma systems work alongside each other to balance excess bleeding or clotting?

Answer 24

coagulation and fibrinolytic systems

Question 25

What forms the stable blood clot?

Answer 25

activated platelets weaved together by fibrin

Question 26

Which phase of healing involves labile and stable cells dividing to replace dying cells?

Answer 26

coagulation (hemostasis) phase

Question 27

What is the second stage of healing?

Answer 27

Inflammation phase (occurs at the same time as coagulation phase)

Question 28

When does the inflammation stage of healing occur?

Answer 28

within hours to days of injury

Question 29

What occurs during the inflammation stage?

Answer 29

diapedesis of immune cells which perform phagocytosis, antigen presentation (MHCI-TCR CD8+), increased fibroblast activity

Question 30

Which molecules drive the inflammatory phase?

Answer 30

kinins, complement proteins, cytokines

Question 31

Which plasma systems are involved in the inflammatory phase?

Answer 31

kinin and complement

Question 32

Which molecule stimulates increased fibroblast activity in the inflammation phase?

Answer 32

cytokines

Question 33

What is the role of fibroblasts in healing?

Answer 33

they are non-professional immune cells that play an important role in proliferation stage

Question 34

What is the third stage of healing?

Answer 34

proliferative phase

Question 35

What happens in the first stage of the proliferative phase?

Answer 35

red new tissue forms that is rich in vasculature (angiogenesis)

Question 36

Why are capillaries 'leaky' during the first phase of the proliferative phase?

Answer 36

to allow for: - diapedesis - action of plasma factor systems - movement of soluble mediators - nutrient supply

Question 37

Why are immune cells present in the proliferative phase?

Answer 37

there is an overlap with inflammation phase

Question 38

What happens during the second stage of proliferative phase?

Answer 38

deposition of collagen and formation of fibrous CT

Question 39

What is the name of the tissue that forms in the second phase of the proliferative phase?

Answer 39

fibrous granulation tissue

Question 40

What happens to the capillaries in the second stage of the proliferative phase?

Answer 40

capillaries regress and are replaced by fibrous granulation tissue

Question 41

Which protein makes up the majority of fibrous granulation tissue in the second phase of proliferation?

Answer 41

collagen

Question 42

Which cells drive fibrosis (collagen deposition)?

Answer 42

fibroblasts (stable cells)

Question 43

What is fibrosis?

Answer 43

deposition of collagen and the formation of fibrous CT

Question 44

Which stage of healing involves fibrosis?

Answer 44

the second stage of the proliferative phase

Question 45

What type of injury results in fibrosis?

Answer 45

severe or repeated damage (e.g. chronic inflammation)

Question 46

Which cells control fibroblast function?

Answer 46

macrophages

Question 47

What are the 2 subsets of macrophages?

Answer 47

M1 - pro-inflammatory M2 - anti-inflammatory

Question 48

Function of M1 macrophages

Answer 48

drive inflammation

Question 49

Function of M2 macrophages

Answer 49

drive tissue repair

Question 50

Which subset of macrophages drive angiogenesis and fibrosis?

Answer 50

M2 (tissue repair)

Question 51

Which cell type drives contraction of surrounding tissues for healing?

Answer 51

myofibroblasts

Question 52

Which soluble mediators are essential in the proliferative phase?

Answer 52

growth factors and matrix metalloproteinases (MMPs)

Question 53

Which cells release soluble mediators?

Answer 53

immune cells

Question 54

Which cells produce MMPs?

Answer 54

different immune cells

Question 55

What is the ECM composed of?

Answer 55

protein fibres (mainly collagen)

Question 56

Function of matrix metalloproteinases

Answer 56

remodel ECM by cleaving through collagen to enable angiogenesis

Question 57

Angiogenesis definition

Answer 57

formation of new blood vessels

Question 58

What are growth factors?

Answer 58

signalling molecules that bind to receptors on cell surface to promote cell growth/differentiation

Question 59

What happens if there is an imbalance of growth factors?

Answer 59

dysregulated cellular proliferation occurs

Question 60

Which growth factor drives angiogenesis?

Answer 60

vascular endothelial growth factor (VEGF)

Question 61

Which cells does VEGF target?

Answer 61

endothelial cells

Question 62

What are the 2 ways angiogenesis can occur?

Answer 62

Sprouting or splitting

Question 63

What happens during sprouting angiogenesis?

Answer 63

New endothelial cells grow from blood vessels towards an increasing vascular endothelial growth factor (VEGF) gradient

Question 64

What happens during splitting angiogenesis?

Answer 64

endothelial cells grow into blood vessel lumen to split the blood vessel in 2. No VEGF gradient

Question 65

Which type of angiogenesis requires vascular endothelial growth factor?

Answer 65

sprouting

Question 66

What is the final stage of healing?

Answer 66

Maturation phase

Question 67

What is the aim of the maturation phase of healing?

Answer 67

tissue remodelling (of disorganised granulation tissue) to regain tensile strength

Question 68

How is tissue remodelled in the maturation phase?

Answer 68

collagen fibres are cross-linked, re-epithelization occurs with aid from myofibroblasts, fibrous scar remains in repair

Question 69

Which chemical mediator is involved in the maturation phase of healing?

Answer 69

prostaglandins

Question 70

Function of prostaglandins in tissue remodelling

Answer 70

decrease fibroblast activity

Question 71

Re-epithelization definition

Answer 71

Process by which wounds are replaced by new keratinocytes (epithelial cells)

Question 72

Which cells aid re-epithelization?

Answer 72

myofibroblasts (found in muscle cells - contract to bring epithelium together)

Question 73

What forms in the coagulation phase of hard tissue healing?

Answer 73

hematoma

Question 74

What a hematoma?

Answer 74

a blood clot within the bone and surrounding tissue

Question 75

What is the name of the granulation tissue formed during the proliferation phase of hard tissue healing?

Answer 75

fibrocartilage callus

Question 76

What is the name of the granulation tissue formed during the proliferation phase of soft tissue healing?

Answer 76

fibrous granulation tissue

Question 77

Which cells make up a fibrocartilage callus?

Answer 77

fibroblasts, chondroblasts and osteoblasts

Question 78

What happens during the maturation phase of hard tissue healing?

Answer 78

the fibrocartilage callus becomes ossified and requires constant remodelling

Question 79

Which cells drive bone remodelling (production and degradation of bone?

Answer 79

osteoblasts, osteocytes, osteoclasts

Question 80

Which stem cells are osteoblasts and osteocytes (matured osteoblasts) derived from?

Answer 80

mesenchymal stem cells (osteoprogenitor cells)

Question 81

Which stem cells are osteoclasts derived from?

Answer 81

haemopoietic stem cells

Question 82

What cells form osteoclasts?

Answer 82

monocyte/macrophage lineage precursor cells fuse together to form osteoclasts

Question 83

What is the term for bone formation?

Answer 83

osteoblastogenesis

Question 84

What is the term for bone resorption?

Answer 84

osteoclastogenesis

Question 85

Approximately how many years does it take for a new skeleton to be formed?

Answer 85

new skeleton is formed every ten years (bone is constantly being remodelled)

Question 86

What is the relationship between formation and resorption of bone in health?

Answer 86

formation and resorption are in equilibrium (no net bone loss)

Question 87

Structural feature of osteoclasts

Answer 87

long protrusions on cell surface that allows the release of mediators to degenerate bone

Question 88

What happens during osteoclastogenesis?

Answer 88

osteoblasts produce RANKL which activates the RANK receptor on osteoclasts resulting in osteoclast maturation

Question 89

How is bone resorption controlled?

Answer 89

by the controlled production of RANKL from osteoblasts

Question 90

What happens during osteoblastogenesis?

Answer 90

osteoblasts secrete osteoprotogerin (OPG) which inhibits RANKL (prevents osteoclast development therefore inhibiting osteoclastogenesis)

Question 91

Examples of diseases in which there is an imbalance of bone remodelling

Answer 91

osteoporosis and periodontitis

Question 92

Which molecule is secreted (on membrane) by osteoblasts during osteoclastogenesis?

Answer 92

RANKL

Question 93

Which molecule is secreted by osteoblasts during osteoblastogenesis?

Answer 93

Osteoprotogerin (OPG)