Lecture 4 - Healing and Repair

Question 1

what is fibrous repair?

Answer 1

replacement of functional tissue by scar tissue

Question 2

what are the key components of fibrous repair?

Answer 2

1. cell migration
2. blood vessels - angiogenesis
3. ecm production/remodelling

Question 3

how does cell migration contribute to fibrous repair?

Answer 3

inflammatory cells - phagocytosis of debris and chemical mediators
endothelial cells - angiogenesis
fibroblasts/myofibroblasts - ecm proteins and wound contraction

Question 4

how does angiogenesis contribute to fibrous repair?

Answer 4

development of new blood supply is vital to wound healing to provide access for cells and deliver o2 and nutrients
endothelial proliferation induced by proangiogenic factors such as vegf
preexisting vessels sprout new ones
endothelial proteolysis of basement membrane
migration of endothelial cells by chemotaxis
endothelial proliferation
endothelial maturation and tubular remodelling
recruitment of periendothelial cells

Question 5

how does ecm contribute to fibrous repair?

Answer 5

supports and anchors cells
separates tissue compartments
sequesters growth factors
allows communication between cells
facilitates cell migration

Question 6

what are the three stages of fibrous repair?

Answer 6

1. inflammatory cell infiltrate
2. clot replaced by granulation tissue
3. maturation

Question 7

describe inflammatory cell infiltrate

Answer 7

blood clot forms
ai around edges
ci - macrophages and lymphocytes migrate into the clot

Question 8

describe the clot being replaced by granulation tissue

Answer 8

angiogenesis
fibroblasts/myofibroblasts migrate and differentiate
ecm produced by myo/fibroblasts

Question 9

describe maturation

Answer 9

comparatively long lasting
cell population falls
collagen increases, matures and remodels
myofibroblasts contract - reduces volume of defect
vessels differentiate and are reduced
left with fibrous scar

Question 10

what is regeneration?

Answer 10

replacement of dead or damaged cells by functional, differentiated cells

Question 11

describe stem cells

Answer 11

potentially limitless proliferation

daughter cells remain as stem cells or diffferentiate to a specialised cell type

Question 12

what is a unipotent cell?

Answer 12

can only produce one type of differentiated cell

eg epithelia

Question 13

what is a multipotent cell?

Answer 13

can produce several types of differentiated cell

eg haemotopoietic

Question 14

what is a totipotent cell?

Answer 14

can produce any type of cell

eg embryonic stem cell

Question 15

what is a labile cell?

Answer 15

normal state is active cell division: g1-m-g1
usually rapid proliferation
eg epithelial or haematopoietic cells

Question 16

what is a stable cell?

Answer 16

resting state: g0
speed of regeneration variable
eg hepatocytes, osteoblasts, fibroblasts

Question 17

what is permanent cell?

Answer 17

unable to divide: g0
unable to regenerate
eg neurones, cardiac myocytes

Question 18

how do growth factors control regeneration?

Answer 18

promote proliferation of stem cells
promote expression of genes controlling cell cycle
hormones and proteins
autocrine, paracrine and endocrine release from many cell types

Question 19

how does contact between basement membrane and adjacent cells control regeneration?

Answer 19

signalling through adhesion molecules
inhibits proliferation in intact tissue - contact inhibition
loss of contact promotes proliferation
exploited in cancer

Question 20

describe healing by primary intention

Answer 20

incised wound
apposed edges
minimal clot and granulation tissue
epidermis regenerates
dermis undergoes fibrous repair
sutures out at 5-10 days - approx 10% strength
maturation of scar continues up to 2 years
minimal contraction and scarring, good strength
risk of trapping infection leading to abscess

Question 21

describe healing by secondary intention

Answer 21

infarct, ulcer, abscess or any large wound
unapposed edges
large clot dries to form scab
epidermis regenerates from base up
repair process produces much more granulation tissue

Question 22

how does secondary intention compare with primary intention?

Answer 22

produces more contraction to reduce volume of defect
produces a larger scar but not necessarily weaker
takes longer

Question 23

what local factors influence the efficacy of healing and repair?

Answer 23

1. type, size, location of wound
2. apposition, lack of movement
3. blood supply - venous or arterial
4. infection
5. foreign material including necrotic tissue
6. radiation damage

Question 24

what general factors influence the efficacy of healing and repair?

Answer 24

1. age
2. drugs and hormones
3. general dietary deficiencies eg protein
4. specific dietary deficiencies eg vitamin c or essential amino acids
5. general state of health eg chronic diseases
6. general cardiovascular status

Question 25

how does cardiac muscle undergo healing and repair?

Answer 25

fibrosis

Question 26

how does bone undergo healing and repair?

Answer 26

callus formation

Question 27

how does the liver undergo healing and repair?

Answer 27

acute damage - regeneration
chronic damage - cirrhosis
hepatocytes have some regenerative capacity but architecture does not regenerate - imbalance leads to cirrhosis and nodules

Question 28

how do peripheral nerves undergo healing and repair?

Answer 28

wallerian degeneration

proximal degeneration, distal proliferation (1mm/day)

Question 29

how do central nerves undergo healing and repair?

Answer 29

no regenerative capacity

glial cells can proliferate - gliosis

Question 30

how does muscle undergo healing and repair?

Answer 30

cardiac and smooth are permanent - replaced by a scar
vascular smooth muscle has some limited regeneration
skeletal has limited regenerative capacity due to satellite cells