Cell Growth

Question 1

What are the 5 phases of cell growth?

Answer 1

G0
G1
S
G2
M

Question 2

What occurs in G0?

Answer 2

sleeping

Question 3

What occurs in G1?

Answer 3

centrosome replication

Question 4

What occurs in S?

Answer 4

DNA synthesis; chromosome replication

• a point of no return

Question 5

What occurs in G2?

Answer 5

pre-mitotic

Question 6

What occurs in M?

Answer 6

mitosis + cell devision

Question 7

what are the x2 systems which control the cell cycle?

Answer 7

cyclins + cyclin dependent kinase

checkpoints; G1/S and G2/M

Question 8

what occurs at the G1/S checkpoint?

Answer 8

checks for DNA damage

Question 9

what occurs at the G2/M checkpoint?

Answer 9

check to make sure DNA copies are correct

Question 10

how do cells know when to divide?

Answer 10

growth factor -> + expression of proto-oncogene
-> increase division

Question 11

what are the x3 receptors growth factors can bind to?

Answer 11

receptors with kinase activity
e.g. epidermal growth factor, fibroblast growth factor

receptors with no intrinsic kinase activity
e.g. cytokines

G-protein linked receptors
e.g. chemokines, adrenaline, glucagon

Question 12

what are the x5 main signal transduction pathways?

Answer 12

1. mitogen activated protein (MAP) pathway
2. phosphoinositdie 3 (PI3) kinase pathway
3. inositol-lipid pathway (IP3) pathway
4. cAMP pathway
5. JAK/STAT pathway

Question 13

what is transforming growth factor (TGF-B) produced by?

Answer 13

platelets
endothelial cells
T cells
macrophages

Question 14

what does transforming growth factor (TGF-B) do?

Answer 14

major growth inhibitor for epidermal cells

Question 15

how does transforming growth factor (TGF-B) induce fibrosis?

Answer 15

increasing fibroblast chemotaxis
increasing collagen and fibronectin synthesis
decreasing collagen degradation

Question 16

why does growth induction in normal cells usually begin as a cytokine interaction with a specific surface receptor on the target cell?

Answer 16

because

cytokine growth factors are highly RECEPTOR SPECIFIC and NOT CELL SPECIFIC

Question 17

What doe the extracellular matrix consist of?

Answer 17

collagen
adhesive glycoproteins
proteoglycans + hyaluronom

Question 18

what type of collagen is skin made from?

Answer 18

type 1

Question 19

what type of collagen is interstitial tissue and basement membranes made from?

Answer 19

types 4,5,6

Question 20

what types of collagen is fribrillar collagens made from?

Answer 20

1,2,3

Question 21

what produces collagen?

Answer 21

fibroblasts

Question 22

what is the sequence of events that occurs when repairing by connective tissue?

Answer 22

1. damage
   - necrosis, haematoma, abscess
2. acute inflammation
3. demolition
   - macrophage influx + phagocytosis
4. granulation tissue ingrowth
   - angiofibrogenesis
5. matrix deposition
6. remodelling
   - amount of collagen does not increase but strength does

Question 23

what are the x4 recognised steps in angiogenesis?

Answer 23

1. breaking down parent basement membrane
2. endothelial migration and formation of capillary spout
3. proliferation and maturation of endothelial cells
4. recruitment of peri-endothelial cells to support tubes

Question 24

what causes cell migration and formation of capillary spout in angiogenesis?

Answer 24

VEGF
angiopoietin

Question 25

what is angiogenesis?

Answer 25

new vessel formation

Question 26

what is angiogenesis a feature of?

Answer 26

chronic inflammation metastatic cancer

Question 27

what factors initiate extra-cellular migration e.g. chemotaxis?

Answer 27

Vascular endothelial growth factors - FGF, TGF-alpha, EGF Fibronectin Laminin

Question 28

what factors initiate extra-cellular proliferation?

Answer 28

VEGF-R1

Question 29

what factor initiates extra-cellular tabulation?

Answer 29

VEGF-R2

Question 30

what factor initiates extra-cellular maturation?

Answer 30

Ang2-Tie2

Question 31

what is fibroplasia?

Answer 31

formation of fibrous connective tissue part of wound healing process fibroblasts create collagen-rich matrix

Question 32

what plays an important role in chronic inflammatory fibrosis?

Answer 32

TGF-b

Question 33

in the formation of granulation tissue, endothelial cell migration is mediated by?

Answer 33

cytokine growth factors fibronectin

Question 34

what is the role of myofibroblasts in granulation tissue?

Answer 34

cause wound contraction - contains contractile cytoplasmic filaments secretes collagen

Question 35

what are myofibroblasts developed from?

Answer 35

fibroblast progenitor cells

Question 36

what plays an important role in newly healing wounds?

Answer 36

fibronectin

Question 37

what is found in the newly formed collagen of newly healing wounds?

Answer 37

high content of soluable collagen

Question 38

what does tissue remodelling mean?

Answer 38

replacing granulation tissue with scars

Question 39

what do fibroblasts and leukocytes secrete to initiate tissue remodelling?

Answer 39

matrix metalloproteinases (MMPs)

Question 40

what are fibroblasts and leukocytes inhibited by when attempting tissue remodelling?

Answer 40

TGF-b

Question 41

what do matrix metalloproteinases (MMPs) consist of?

Answer 41

interstitial collagenases - breaks down collagen type 1, 2, and 3 gelatinases - breaks down collagen type 4 stromelysins - breaks down proteoglycans, laminin, fibronectin

Question 42

what are the x6 steps in wound healing?

Answer 42

1. induction of acute inflammatory response 2. regeneration of parenchymal cells 3. migration and proliferation of both parenchymal and connective tissue cells 4. synthesis of ECM proteins 5. remodelling of connective tissue and parenchymal components 6. collagenisation and acquisition of wound strength

Question 43

What occurs at 0hr of wound healing?

Answer 43

incision filled with clot

Question 44

what occurs at 3-24 hours of wound healing?

Answer 44

neutrophils infiltrate clot mitosis begins at epithelial base cells epithelial closure takes place at 24-48 hours

Question 45

what occurs at day 3 of wound healing?

Answer 45

neutrophils are replaced with macrophages granulation tissue begin to appear

Question 46

what occurs at day 5 of wound healing?

Answer 46

incision space is filled with granulation tissue neovascularisation is maximal collagen fibrils begin to appear epithelial proliferation is now maximal

Question 47

what occurs at week 2 of wound healing?

Answer 47

proliferation of fibroblasts and continued collagen accumulation to produce scar collagen replacement from type 3 to type 1 inflammation + newly formed vessels have disappeared

Question 48

what occurs at month 2 of wound healing?

Answer 48

scar now consists of connective tissue devoid of inflammation covered by intact epidermis

Question 49

what are the main differences between healing by primary and secondary intention?

Answer 49

haematoma is bigger acute inflammation is more intense volume of granulation tissue is greater wound contraction is more evidence

Question 50

what is the wound strength at the end of 1st week?

Answer 50

approx 10% of normal

Question 51

what is the wound strength by month 3?

Answer 51

70-80% - may persist for life

Question 52

when does wound contraction occur?

Answer 52

day 7-10 completed by day 14

Question 53

how much does the size of the wound reduce by in wound contraction?

Answer 53

may be reduced by 30-80%

Question 54

what is wound contraction delayed by?

Answer 54

corticosteroids administration glucocorticoid therapy anabolic steroids skin grafting changes occurring in a burn X-radiation

Question 55

what does wound contraction during the first 2 weeks following injury result from?

Answer 55

actions of ingrowing myofibroblasts

Question 56

what does wound contraction during the first 2 weeks following injury NOT result from?

Answer 56

not from epithelial ingrowth into wound or enzyme induced contraction of type IV collagen

Question 57

How can wound wound repair be disrupted?

Answer 57

deficient scar too much scar contracture