Healing + Repair

Question 1

What is the regenerative ability of the following 3 cell types?
Liable
Stable
Permenant

Answer 1

Liable= continuously dividing 
Stable= can re-enter cell cycle from G0 to proliferate 
Permanent= no regeneration capability i.e. unable to divide

Question 2

Give examples of labile, stable and permanent cells

Answer 2

LABILE:
Squamous epithelium
Columnar epithelium
Urothelium

STABLE:
Hepatocytes 
Pancreatic acinar cells 
Fibroblasts 
Endothelium 
SM

PERMANENT
Cardiac myocytes
Neurons
Skeletal muscle

Question 3

Which growth factors are associated with epithelial cells and what are their sources?

Answer 3

Epidermal growth factor (EGF)
Source= activated macrophages/salivary glands/kerantinocytes

Hepatocyte growth factor (HGF)
Source= Fibroblasts/liver stromal cells/ endothelial cells

Keratinocyte growth factor (KGF)
Source- fibroblasts

Transforming growth factor alpha (TGF-alpha)
Source= activated macrophages/keratinocytes

Question 4

Which growth factors are associated with mesenchymal cells and what are their sources?

Answer 4

Vascular endothelial growth factor (VEGF)
Source= mesenchymal cells

Fibroblast growth factors (FGFs)
Source= Macrophages/mast cells/endothelial cells

Transforming growth factor beta (TGF-beta)
Source= platelets/T-lymphocytes/ macrophages/endothelial cells/epithelial cells/ SM/ fibroblasts

Question 5

Which growth factors are associated with liver regeneration and what is their function?

Answer 5

HGF:
Released from damaged hepatocytes to stimulate stable hepatocytes to re-enter cell cycle

VEGF:
Enables sinusoidal pathways to form in regenerative tissue

Question 6

How does bone regeneration differ from regeneration seen in liver?

Answer 6

Bone regeneration relies on REMODELLING + DEPOSITION of osteoid rather than just cell regeneration

Question 7

What are the 2 calluses involved in bone regeneration and what is the process of their formation?

Answer 7

Soft callous

• provides structure for other cells to enter
• Inflammatory markers (PDGF/TNF-beta/FGF) released from platelets and inflammatory cells
• Markers act on osteoclasts to resorb bone, osteoblasts to lay osteoid and chondrocyte differentiation from progenitor

Hard callous

• fibrin mesh work replaced with immature woven bone via endochondrial ossification
• immature bone matures to lamellar bone at 3 weeks- months

Question 8

Why do scars form and what are their key characteristics?

Answer 8

When damage cannot be repair by regeneration

CT deposition

Question 9

What are the 4 stages of scar formation? Give brief details of what is occurring at each stage

Answer 9

1. Haemorrhage
   - fibrin and platelets deposited to form fibrin plug
2. Acute inflammation
3. Cell proliferation
   - granulation tissue formation from endothelial,fibroblasts, loose fibrous tissue and inflammatory cells
   I.e. acts as provisional ECM to provide structural integrity whilst cell proliferates
   -Angiogenesis from endothelial cells proliferating in response to VEGF
4. Connective tissue deposition/fibroplasia
   - scar tissue formed from collagen and prosteoglycans produced by fibroblasts
   - TGF-beta (from M2 macrophages) = key regulator
   - increases structural integrity of damaged tissue

Question 10

What is involved in the process of scar remodelling?

Answer 10

Matrix metalloproteinases control extent of remodelling

• Collagen fibres remodel
• Myofibroblasts can forms i.e. have SM properties to enable contraction of the wound to facilitate wound healing

Question 11

Skin can heal via primary and secondary intention. When does each occur and what is the difference?

Answer 11

Primary:

• small defects where only epidermis and basement membrane damaged
• can be close with sutures

Secondary:

• large defects following severe trauma
• 1st= Re-epithelialisation at base of wound
• more fibroplasia, granulation tissue and inflammation
• fibroblasts mediate contraction
• cannot be closed

Question 12

What are the systemic and local factors effecting wound healing?

Answer 12

Systemic:

• nutrition
• metabolic status i.e. diabetes can effect the blood supply
• circulatory status i.e. assess for ischaemia
• hormones

Local:

• local BS
• infection
• foreign body
• mechanical factors

Question 13

Give examples of pathological healing of the skin?

Answer 13

Keloid scar- associated with thick keloidal collagen
Contractures- prevents movement of hands
Chronic leg ulcer- due to compromised angiogenesis and vascular supply i.e. can be associated with diabetes

Question 14

What is the name of the pathological healing process which occurs in the liver? How is it characterised?

Answer 14

Cirrhosis

Nodules of regenerating hepatocytes surrounding fibrous tissue

Question 15

What factors affect the development of liver cirrhosis?

Answer 15

1. Injury time course
   - response to prolonged severe injury
   Eg chronic alcoholism
2. Site of injury
   - Classical cirrhosis i.e. damage to parenchyma mediate by sinusoidal Stella the cells
   - Portal-biliary cirrhosis (PBC) i.e. biliary pattern of cirrhosis affecting portal structure

Question 16

What are the 2 types of liver cirrhosis (based on anatomy)?

Answer 16

Classical= parenchyma 
PBC= portal tracts

Question 17

What are the clinical consequences of liver cirrhosis?

Answer 17

Jaundice 
Spider naevi 
Plamar erythema 
Gynaecomastia 
Splenomegaly 
Flapping tremor 
Impaired protein/hormone/clotting factor synthesis + drug processing 
Portal hypertension 
Encephalopathy 
Spontaneous bacterial peritonitis 
Hepatocellular caricinoma (HCC)