S4: regeneration + repair

Question 1

Describe the differences between labile, stable and permanent tissues and be able to give examples of each.

Answer 1

Labile tissue = continuous replication of cells eg. epithelium, haematopoietic tissue
Stable tissue = normally low level of replication (but can undergo rapid replication if required) eg. liver, kidney, pancreas
Permanent tissue = cells do not replicate eg. neurons, skeletal muscle, cardiac muscle

Question 2

Define stem cells, unipotent, multipotent and totipotent

Answer 2

Stem cells = cells that can differentiate into other cell types and self-renew
Unipotent = produce one cell type eg. epithelial stem cells
Multipotent = produce several cell types eg. haematopoietic stem cells
Totipotent = produce all cell types eg. embryonic stem cells

Question 3

Describe the different ways cells communicate

Answer 3

Autocrine, paracrine & endocrine
Direct cell-cell contact
Local mediators eg. growth factors
Hormones

Question 4

Explain and discuss the processes involved with regeneration, resolution and fibrous repair

Answer 4

Regeneration = regrowth of cells with minimal evidence of injury, only possible with minor injuries, can be physiological (haematopoiesis), requires an intact connective tissue architecture
Fibrous repair = replacement of functioning tissue with a scar

Question 5

Describe the functions of granulation tissue

Answer 5

Fills the gap
Capillaries supply oxygen and nutrients
Contracts and closes the defect

Question 6

Describe the synthesis of collagen, understand the different types and explain some defects of collagen synthesis

Answer 6

Pre-procollagen (in ER of fibroblasts)
Undergoes vitamin C dependent hydroxylation
Procollagen (in cytoplasm of fibroblasts)
C and N terminals of procollagen cleaved
Tropocollagen (in extracellular space)
Tropocollagen crosslinked
Diseases = scurvy, ehlers-danlos syndrome, osteogenesis imperfecta & alport syndrome

Question 7

Explain and distinguish between primary and secondary intention

Answer 7

Primary intention = incised wound, apposed (sutured) edges -> minimal clot and granulation tissues
Epidermis regenerates, dermis undergoes fibrous repair
Secondary intention = significant tissue loss, unapposed edges -> abundant clot, inflammation, granulation tissue
Considerable would contraction required, dermis requires significant repair, epidermis regenerates from edges

Question 8

Discuss the healing processes of bone fractures

Answer 8

1) haematoma surrounds the injury, granulation tissue
2) soft callus, fibrous tissue and cartilage, woven bone
3) hard callus, woven bone gradually organised into lamellar bone
4) remodelling, lamellar bone remodelled to original outline of bone

Question 9

Describe the local and systemic factors influencing the efficacy of healing and repair

Answer 9

Local = size, location, blood supply, local infection & foreign bodies
Systemic = age, anaemia, hypoxia, hypovolaemia, obesity, diabetes, drugs, vitamin deficiencies & malnutrition

Question 10

Describe the complications of fibrous repair

Answer 10

Insufficient fibrosis (wound dehiscence) occurs in obesity, elderly, malnutrition & steroid use
Excessive fibrosis - keloid scar
Adhesions - fibrous bands can cause obstruction of tubes
Loss of function - replacement of specialised tissue by fibrous tissue
Disruption of architecture
Excessive scar contraction - constriction of tubes, fixed flexion deformities (contractures)

Question 11

Describe how a clot forms

Answer 11

1) bleeding and haemostasis - prevention of blood loss
2) inflammation - acute then chronic, digestion of blood clot
3) proliferation - capillaries, fibroblasts, myofibroblasts, extracellular matrix -> granulation tissue
4) remodelling - maturation of scar: reduced cell population, increased collagen, myofibroblasts contract -> fibrous scar

Question 12

Which tissues will undergo regeneration and which will undergo fibrosis?

Answer 12

Regeneration = necrosis of labile/stable tissues + collagen framework intact
Fibrous repair = necrosis of labile/stabile tissues + collagen framework destroyed/on-going chronic inflammation, necrosis of permanent tissues

Question 13

Explain contact inhibition

Answer 13

Isolated cells replicate until they encounter other cells

Cadherins bind between cells, inhibit further proliferation (defective in cancer)

Question 14

Explain the role of growth factors in regeneration

Answer 14

Polypeptides that act on cell surface
Causes cell to enter cell cycle and proliferate (helpful for healing, important in cancer)
Eg. epidermal growth factor, vascular endothelial growth factor

Question 15

Explain regeneration and repair in cardiac muscle

Answer 15

Very limited regenerative capacity and myocardial infarction is followed by scar formation
This can compromise cardiac function

Question 16

Explain regeneration and repair in the liver

Answer 16

A remarkable capacity to regenerate
However, if the architecture is severely damaged as well as the hepatocytes regeneration may not be possible and cirrhosis can result

Question 17

Explain regeneration and repair in the peripheral nerves

Answer 17

The proximal stumps of the degenerated axons sprout and elongate
They use Schwann cells vacated by the distal degenerated axons to guide them back to the tissue that the nerve innervates

Question 18

Explain regeneration and repair in cartilage

Answer 18

Does not heal well as it lacks blood supply, lymphatic drainage or innervation

Question 19

Explain regeneration and repair in the central nervous system

Answer 19

When tissue damage occurs in the CNS the neural tissue is replaced by proliferation of CNS supportive elements (glial cells)