Session 4-Healing:Regeneration And Repair Flashcards
Which processes are involved in wound healing? (3)
1) Haemostasis
2) Inflammation
3) Regeneration and repair
What is regeneration?
Restitution with no, or minimal, evidence that there was a previous injury
What is the difference between an abrasion and an ulcer?
Abrasion-lose top few layers of cells, only affecting mucosa
Ulcer-injury goes into submucosa, more severe form of abrasion
Which cells replicate in regeneration?
New differentiated cells are mainly derived from stem cells
What are stem cells?
Prolonged proliferative activity and show asymmetric replication
Whereabouts in the epidermis are the stem cells?
Basal layer adjacent to basement membrane
Whereabouts in the intestinal mucosa are the stem cells?
Bottom of crypts
Whereabouts in the liver are the stem cells?
Between hepatocytes and bile ducts
What are the three types of stem cells?
1) unipotent
2) multipotent
3) totipotent
What are unipotent stem cells?
Most adult stem cells which only produce one type of differentiated cell eg. Epithelia
What are multipotent stem cells?
Produce several types of differentiated cell eg haematopoeitic stem cells
What are totipotent stem cells?
Embryonic stem cells which can produce any type of cell and therefore any tissues of the body
What are blood cells derived from?
Multipotent stem cells in bone marrow
Can all tissues regenerate?
No
Give examples of labile tissues and describe what they contain
Surface epithelia, haematopoeitic tissues
Contain short-lived cells that are replaced from cells derived from stem cells
Give examples of stable tissues
Liver parenchyma
Bone
Fibrous tissue
Endothelium
True or false: stable tissues have a low level of replication but if necessary can undergo rapid proliferation
TRUE
Give examples of permanent tissues
Neural tissue
Skeletal muscle
Cardiac muscle
Which type of cells are continuously cycling in the cell cycle?
Labile cells
In what circumstances can regeneration take place?
If damage occurs in labile or stable tissue
If tissue damage is not extensive
What is fibrous repair?
Healing with formation of fibrous connective tissue (scar)
When does fibrous repair occur?
With significant tissue loss and if permanent or complex tissue is injured
Which type of injury is repaired by regeneration?
Necrosis of labile or stable tissues if collagen framework is intact
Which injuries involve fibrous repair?
Necrosis of labile or stable tissues when collagen framework is destroyed or when there is ongoing chronic inflammation
OR
Necrosis of permanent tissues
During which period of scarring are stitches removed from wounds?
Between 7 and 10 days (early scarring)
When does granulation tissue form?
3 days
What does granulation tissue consist of?
Developing capillaries
Fibroblasts and myofibroblasts
Chronic inflammatory cells
What are the functions of granulation tissue?
Fills the gap
Capillaries supply oxygen, nutrients and cells
Contracts and closes the hole
What are the stages of scar formation? (6)
1) haemostasis
2) acute inflammation
3) chronic inflammation
4) granulation tissue forms
5) early scar
6) scar maturation
Which inflammatory cells are involved in fibrous repair?
1) Neutrophils and macrophages-phagocytosis
2) Lymphocytes and macrophages-production of chemical mediators
How are endothelial cells involved in fibrous repair?
They proliferate and result in angiogenesis
How are fibroblasts and myofibroblasts involved in fibrous repair?
1) Produce extracellular matrix proteins eg collagen
2) Responsible for wound contraction-contraction of fibrils within myofibroblasts
Why do scars become white?
No regeneration of melanocytes
Why do scars tend to stretch with time?
Fibroblasts/myofibroblasts cannot lay down elastin
Why does hair not grow on a scar?
Hair follicles cannot regenerate
Which type of collagen is the most common and where is it found?
Type I
In hard and soft tissue (bones, tendons, ligaments, skin, sclera, cornea, blood vessels)
What does type IV collagen make up?
Basement membrane
Where are the polypeptide alpha chains of collagen synthesised?
In the ER of fibroblasts and myofibroblasts
Which vitamin is needed for hydroxylation in collagen formation?
C
What produces the tensile strength of collagen?
Cross-linking between molecules
What causes scurvy?
Vitamin C deficiency
Which collagen does scurvy affect most?
Collagens supporting blood vessels
Why can scurvy lead to tooth loss?
Collagen in periodontal ligament has short half life and normal collagen is replaced by defective collagen
What is Ehlers-Danlos syndrome a defect in?
Conversion of procollagen to tropocollagen
Why can skin recoil in Ehlers-Danlos syndrome?
Elastic fibres are normal, just missing the tethering effect of normal collagen fibres
Describe the joints of a patient with Ehlers-Danlos syndrome
Hypermobile
Predisposition to joint dislocation
Why do patients with osteogenesis imperfecta have blue sclerae?
Too little collagen within them and they are translucent
True or false: Alport syndrome is an X-linked disease
TRUE
What abnormality results in Alport syndrome?
Type IV collagen abnormality
How does Alport syndrome present in children/adolescents?
Haematuria progressing to renal failure
Neural deafness
Eye disorders
Why are growth factors important?
Wound healing
What are growth factors coded by?
Proto-oncogenes
What do growth factors do in the cell cycle?
Bind to specific receptors, stimulate transcription of genes that regulate entry of cell into cell cycle and cell’s passage through it
Apart from cell proliferation, what other effects can growth factors have?
Inhibition of division Locomotion Contractility Differentiation Viability Activation Angiogenesis
Which cells produce growth factors?
Platelets
Macrophages
Endothelial cells
What is contact inhibition?
1) signalling through adhesion molecules
2) inhibits proliferation in intact tissue, promotes proliferation in damaged tissues
What do cadherins do?
Bind cells to each other
What do integrins do?
Bind cells to extracellular matrix
Describe the type of wound in primary intention
Incised, closed and non-infected and sutured wounds (typical surgical wound)
What is healing by primary intention?
Disruption of basement membrane continuity but death of only small number of epithelial and connective tissue cells
True or false: there is minimal clot and granulation tissue in primary intention
TRUE
What occurs in healing by primary intention?
1) epidermis regenerates
2) dermis undergoes fibrous repair
3) minimal contraction and scarring
Describe the type of wound in secondary intention
Excisional wound, wounds with tissue loss and separated edges, infected wounds eg infarct, ulcer, abscess
What happens to the wound in secondary intention?
Open wound filled by abundant granulation tissue - grows in from wound margins
True or false: circular scars heal better than rectangular ones
FALSE - other way round
True or false: healing by primary intention takes longer than healing be secondary intention
FALSE - secondary takes longer
Which local factors can influence wound healing? (5)
1) type, size and location of wound
2) mechanical stress
3) blood supply
4) local infection
5) foreign bodies
Which general factors influence wound healing?
1) age
2) anaemia, hypoxia and hypovolaemia
3) obesity
4) diabetes
5) genetic disorders
6) drugs
7) vitamin deficiency
8) malnutrition
What are the complications of fibrous repair? (6)
1) insufficient fibrosis
2) formation of adhesions
3) loss of function due to replacement of specialised functional parenchymal cells by scar tissue
4) disruption of complex tissue relationships within an organ
5) overproduction of fibrous scar tissue
6) excessive scar contraction
What is a keloid scar?
Lots of collagen within the dermis so excessive fibrous scar tissue is produced
