Healing and Repair

Question 1

Where does complete restoration of tissues occur and where does greater tissue destruction occur?

Answer 1

acute inflammation

chronic inflammation

Question 2

What is regeneration and what is repair?

Answer 2

replacement with functional differentiated cells

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

Question 3

What determines regeneration or repair?

Answer 3

severity and location of damage

Question 4

What tissues cannot regenerate if damaged?

Answer 4

brain
heart

Question 5

What are the cell types and what are their characteristics?

Answer 5

• Labile cells;
  – Normal state is active cell division
  – Rapid regeneration
• Stable cells (conditional renewal cells); – variable rates of regeneration
  – Rapid proliferation in response to injury
• Permanent cells;
  – unable to divide
  – unable to regenerate

Question 6

What cells are present in heart?

Answer 6

permanent cells

Question 7

What are examples of labile cells?

Answer 7

epithelial cells
hematopoietic stem cells

Question 8

Where are there stable cells?

Answer 8

liver
kidneys

Question 9

What are the four stages of healing?

Answer 9

1- coagulation
2 - inflammation
3 - proliferation
4 - maturation

Question 10

What happens in the coagulation phase (homeostasis)?

Answer 10

– Clot formation
– Mitosis of labile/stable cells (e.g., epithelial cells)

Question 11

What happens in the inflammation phase?

Answer 11

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

Question 12

What happens in the proliferative phase?

Answer 12

– Formation of granulation tissue
– Fibroblasts are key players
– New connective tissue (rich in collagen)
– Angiogenesis (new blood vessels)
– Growth factors are essential

Question 13

What are essential in the proliferative phase?

Answer 13

growth factors

Question 14

What are the two phases of the granulation tissue?

Answer 14

1st - vascular granulation tissue
2nd - fibrous granulation tissue

Question 15

What are the characteristics of vascular granulation tissue?

Answer 15

– Mix of proliferating capillaries, fibroblasts, immune cells
– New capillaries are relatively ‘leaky’ allowing cells and fluid into tissue

Question 16

What are the characteristics of fibrous granulation tissue?

Answer 16

– Overtime capillaries regress and immune cells return to blood
– Mature fibroblasts lay down collagen

Question 17

What is angiogenesis?

Answer 17

formation of new capillaries (blood vessels)

Question 18

What are the two mechanisms in which blood vessels are formed?

Answer 18

sprouting (sprouting from existing vessels)
intussusceptive (splitting)

Question 19

What growth factor is associated with angiogenesis?

Answer 19

vascular endothelial growth factor (VEGF)

Question 20

What is VEGF produced by?

Answer 20

in extracellular matrix produced by epithelial cells, macrophages and fibroblasts

Question 21

What occurs if there is a VEGF gradient?

Answer 21

endothelial cells move towards gradient (sprouting)

Question 22

What occurs if there is no VEGF gradient?

Answer 22

lumen of existing blood vessel enlarges until central areas fuse together leading to splitting of vessel.

Question 23

What do growth factors do?

Answer 23

• Promote or inhibit cell growth and
  differentiation
• Bind receptors on cell surfaces

Question 24

What are the functions of growth factors?

Answer 24

• Promote cell survival
• Locomotion
• Contractility
• Differentiation
• Angiogenesis

Question 25

What is fibrosis?

Answer 25

the extensive deposition of collagen and fibrous connective tissue

Question 26

What is fibrosis driven by?

Answer 26

fibroblasts (and M2 macrophages)

Question 27

What macrophage subtype is responsible for healing and repair?

Answer 27

M2 macrophages

Question 28

What growth factors are produced during fibrosis by macrophages?

Answer 28

TFG - BETA
PDGF

Question 29

What happens during maturation phase?

Answer 29

– Disorganized granulation tissue remodeled by remaining cells
– Collagen fibres are cross linked along tension lines
– Re-epithelization (growth factors)
– Regain of tensile strength (up 80% of
pre-injury strength)
– Fibrous scar remains (in repair)
– Tissue remodeling

Question 30

What is the difference between primary and secondary intentions?

Answer 30

primary - regeneration
secondary - regeneration and repair

Question 31

What intention causes a difference in tissue appearance?

Answer 31

secondary

Question 32

What does the inflammatory stage (48 hours) of hard tissue repair include?

Answer 32

• Blood clot formation at fracture
• Acute inflammatory response
• Death of bone cells

Question 33

What happens to bone cells in the inflammatory stage that are deprived of oxygens?

Answer 33

die off

Question 34

What does the repairing stage 1 (weeks) of hard tissue repair include?

Answer 34

• Capillaries form into hematoma
• Fibroblasts produce collagen fibers and osteoblasts form spongy bone
• Granulation tissue forms and becomes the soft callus

Question 35

What do osteoblasts form in repairing stage 1?

Answer 35

spongy bone

Question 36

What does the repairing stage 2 (months) of hard tissue repair include?

Answer 36

• Chondrocytes and osteoblasts produce cartilage and bone
• Formation of hard bone callus at fracture site (known as Fracture Callus or woven bone)

Question 37

What does the remodelling stage (months-years) of hard tissue repair include?

Answer 37

• Osteoclasts and osteoblasts remodel the hard bone callus (resorption vs deposition of bone)
• Cortical bone replaces woven bone.
• Angiogenesis essential in bone regeneration and repair