MoD Healing and Repair

Question 1

Define regeneration

Answer 1

The replacement of dead or damaged cells by functional differentiated cells.

Question 2

Whats the difference between regeneration and repair?

Answer 2

In regeneration the normal structure is restored whereas in repair the normal structure is permanently altered - e.g. fibrosis.

Question 3

Give examples of labile, stable and permanent cell populations, and what are the differences between each?

Answer 3

They vary on their ability to regenerate.

Labile - continuously dividing, normal state is active cell division e.g. epithelial and haematopoietic cells

Stable - they are usually in the resting state (G0) and only regenerate when stimulated (slow) e.g. hepatocytes, osteoblasts, fibroblasts

Permanent - permanently in the G0 state with no ability to divide or regenerate e.g. neurones, cardiac myocytes

Question 4

What is the role of stem cells?

Answer 4

They are the the internal repair system to replace lost or damaged cells.

Question 5

What are the 3 types of stem cell?

Answer 5

Unipotent: can only produce one type of differentiated cell e.g. epithelia
Multipotent: can produce several types of differentiated cells e.g. haematopoietic
Totipotent: can produce any type of cell e.g. embryonic stem cells

Question 6

What controls regeneration and repair?

Answer 6

Growth factors (can be hormones such as oestrogen, GH or proteins e.g. VEGF, PDGF)
They promote proliferation of the stem cells and promote expression of genes controlling the cell cycle. 

Adhesion molecules that signal between basement membranes and adjacent cells. “Contact inhibition” occurs when tissue is intact however loss of contact promotes proliferation (can lead to cancer).

Question 7

What is the difference between fibrous repair and regeneration/resolution?

Answer 7

Fibrous repair occurs in necrosis of permanent cell populations and necrosis of labile and stable cell populations where the collagen framework has been destroyed. Fibrous repair results in scarring.

Question 8

Outline the 3 key steps in fibrous repair

Answer 8

1. Cell migration
2. Angiogenesis (new blood vessel formation)
3. EC matrix production and remodelling

Question 9

In cell migration (step 1 of fibrous repair), what cell types are involved and what is their function?

Answer 9

Inflammatory cells
Neutrophils and macrophages phagocytose debris
Lymphocytes and macrophages act as chemical mediators by attracting other cells

Endothelial cells
Needed for angiogenesis

Fibroblasts and myofibroblasts
Make EC matrix proteins, wound contraction

Question 10

Outline the function and process of angiogenesis in fibrous repair

Answer 10

A blood supply is vital to wound healing - it provides access to the wounds for cells eg inflammatory cells and fibroblasts, and delivers O2 and nutrients.

Angiogenesis is initiated by VEGF and other growth factors

Preexisting BV sprout new vessels

Question 11

Outline the function and process of extracellular matrix production in fibrous repair

Answer 11

Function - supports and anchors cells, secretes and stores growth factors, allows communication between cells

Made up of glycoproteins, proteoglycans, and elastin

Question 12

What are the different types of collagen? (broad)

Answer 12

Fibrillar collagens (I-III) eg dermis, bone
Uninterrupted helices form fibrils

Amorphous collagens (IV-VI) eg 
Interrupted so form sheets

Question 13

Outline the synthesis of fibrillar collagens

Answer 13

Alpha chains synthesised in ER
Vit C dependent hydroxylation
Alpha chains cross link to produce procollagen triple helix
Soluble procollagen secreted
Procollagen cleaves to give tropocollagen
Tropocollagen forms fibrils then fibres

There can be slow remodelling by specific collagenases

Question 14

Describe what can happen if there is a defect in collagen synthesis

Answer 14

Vit C deficiency: inadequate hydroxylation produces defective helices (weak). Particularly affects collagens supporting blood vessels so can result in haemorrhage. Skeletal changes in infants

Ehlers-Danlos syndrome: defective conversion from procollagen to tropocollagen. Results in hypermobile joints and skin stretch

Osteogenesis imperfecta: brittle bones

Question 15

What is healing by primary intention?

Answer 15

Occurs when there is a clean, smooth incision with apposed edges. There is minimal clotting and granulation tissue. The scar is minimal and has good strength

Possible complication: sutures can trap infection inside causing an abscess

Question 16

What is healing by secondary intention?

Answer 16

Occurs when there is a skin wound such as infarct, ulcer, or abscess (all have extensive loss of cells). The wound edges are unapposed, a large clot forms a stab and the repair process forms a lot more granulation tissues.

Takes longer to heal and there is a larger scar.

Question 17

Outline the healing of bone fractures

Answer 17

Haematoma forms 
Necrotic tissue removed
Capillaries develop
Soft callus forms 
Hard callus forms 
Bone remodelling in the direction of mechanical stress

Question 18

What factors affect healing and repair?

Answer 18

Local factors:
Type, size and location of wound
Apposition and lack of movement
Blood supply
INFECTION (most important)
Foreign material

General factors:
Age
Drugs e.g. steroids inhibit collagen formation
Dietary deficiencies
General state of health e.g. diabetes, RA
General cardiovascular status

Question 19

What are some complications of fibrous repair?

Answer 19

Insufficient fribrosis - the wound can herniate and ulcerate (esp abdomen)

Excessive fibrosis - cosmetic issues, keloids, cirrhosis

Excessive wound contraction - can obstruct tubes and channels (strictures), can limit joint movement (contractures)

Question 20

What happens during healing of the myocardium?

Answer 20

Regeneration capacity is almost none, resulting in scar formation which may compromise cardiac function.

Question 21

What is special about liver regeneration?

Answer 21

The liver has a remarkable capacity to regenerate. Part of the liver can be removed and there is compensatory growth of liver tissues. Almost all hepatocytes replicate during regeneration.

Question 22

What occurs in peripheral nerve regeneration?

Answer 22

There is wallerian degeneration of the axons of a severed nerve. The axons then regenerate at a rate of 1-3mm per day. Schwann cells guide the growing axons to the tissue they innervate.

Question 23

What is the regenerative capacity of cartilage?

Answer 23

Very little - lacks blood supply, lymphatic drainage and innervation.

Question 24

What happens when there is damage to the central nervous system?

Answer 24

Neural tissue is permanent therefore the neural tissue is replaced by glial cells.