L8- repair & Regeneration

Question 1

Two types of Healing:

Answer 1

1) Regeneration: Damaged cells replaced by like Tissue returns to normal (still has its specialised function)
2) Repair: Damaged cells cannot be replaced by like Fibrosis and scarring (loss of specialised function)

Question 2

What are Labile cell populations

Answer 2

High normal turnover

Active stem cell population

Excellent regenerative capacity - eg Epithelia

(“S” stage of mitosis)

Question 3

What are Stable (quiescent) cell populations

Answer 3

Low physiological turnover

Turnover can massively increase if needed

Good regenerative capacity- eg liver, renal tubules

(Enter at g1 of mitosis?)

Question 4

What are Permanent cell populations

Answer 4

No physiological turnover

Long life cells

No regenerative capacity (nb recent stem cell research)- eg neurons, muscle cells

(Exit after Mitosis before g1)

Question 5

Stem cells

Answer 5

Survival of stem cells crucial to regeneration

Destruction of stem cells can occur in: full thickness burns, radiation

Question 6

Control of regeneration

Answer 6

Proliferation of stem cell / amplifying cell compartments

Covering of defect

Contact inhibition

Complex control by growth factors, cell-cell and cell-matrix interactions

Question 7

Regeneration - summary

Answer 7

Restoration of normal structure / function

Depends on tissue cell kinetics, architecture

Depends of stem cell survival

Question 8

Repair

Answer 8

Normal structure cannot be replaced

Healing by non-specialised fibrous tissue (‘Scar’)

Can have Functional consequences

Question 9

Organisation

Answer 9

Basic stereotyped pathological process

Repair of specialised tissue by formation of fibrous scar

Granulation tissue

Question 10

Granulation tissue

Answer 10

New capillary loops

Phagocytic cells

• Neutrophils
• Macrophages

(Myo)fibroblasts

Question 11

Why do granulotamous tissue contract?

Answer 11

Proliferation and migration of myofibroblasts

Synthesise collagen and ECM

Acquire myofibrils and contractile ability

—> Leading to wound contraction

Question 12

Local Factors inhibiting healing

Answer 12

Infection

Haematoma

Blood supply

Foreign bodies

Mechanical stress

Question 13

Systemic Factors inhibiting healing

Answer 13

Age

Drugs (eg steroids)

Anaemia

Diabetes

Malnutrition

Catabolic states

Vitamin C deficiency

Trace metal deficiency

Question 14

Healing by first intention

Answer 14

Clean, uninfected surgical wound

Good haemostasis

Edges apposed eg with sutures or staples

Question 15

Healing by second intention

Answer 15

Wound edges not apposed:

• Extensive loss of tissue
• Apposition not physically possible
• Large haematoma
• Infection
• Foreign body

More florid granulation tissue reaction (“leaving a wound to granulate”)

More extensive scarring

Question 16

Fracture healing

Answer 16

Haematoma is organised

Removal of necrotic fragments

Osteoblasts lay down woven bone (=callus)

Remodelling according to mechanical stress

Replacement by lamellar bone

Question 17

Non-union of fractures

Answer 17

Misalignment

Movement

Infection

Interposed soft tissue

Pre-existing bone pathology= ‘pathological fracture’

Question 18

Healing in the brain

Answer 18

Neurons are terminally differentiated

Supporting tissue is glial cells rather than collagen and fibroblasts etc

Hence damaged tissue is removed, often leaving cyst

Gliosis rather than scarring

Question 19

Epidermal growth factor a

Answer 19

Mitogenic for keratinocytes and fibroblasts. Stimulates granulation tissue formation

Question 20

Tumor necrosis factor

Answer 20

Activates macrophages; regulates other cytokines; multiple functions

Question 21

Vascular endothelial cell growth factor

Answer 21

Increases vascular permeability; mitogenic for endothelial cells