Session 4 Flashcards
What three processes are involved in wound healing?
Haemostasis
Inflammation
Regeneration and/or Repair
What is haemostasis?
The stopping of a flow of blood
What is regeneration?
Restitution with no, or minimal evidence that there was a previous injury
What is ulceration?
More severe form of an abrasion that includes damage to the submucosa
What is an abrasion?
Where top few layers of cells is lost with damage to the mucosa
Which types of cells replicate in regeneration?
Mainly stems cells
What are stem cells?
Cells with prolonged proliferation activity
What type of replication due stem cells show?
Asymmetrical replication
What is meant by asymmetrical replication? Which cells show this?
During replication - one mature cell is formed and one cell remains as a stem cell
Stem cells
Where are stem cells found in tissues?
Varies between tissues
Where are stem cells typically found in the…
I) Epidermis
II) Intestinal mucosa
III) Liver
In the basal layer adjacent to basement membrane
At the bottom of crypts
Between hepatocytes and bile ducts
Stem cells can be of which 3 types? Most adult stem cells are of which type?
Unipotent (most adult stem cells)
Multipotent
Totipotent
What are unipotent stem cells? Give an example.
Stem cells that only produce one type of differentiated cell
Epithelia
What are multipotent stem cells? Give an example
Stem cells that produce several types of differentiated cell
Haematopoietic stem cells
What are totipotent stem cells? Give an example
Stem cells that can produce any type of cell
Embryonic stem cells
Tissues can be grouped into which three categories based on their ability to regenerate?
Labile
Stable
Permanent
Give two examples of labile tissues
Surface epithelia
Haematopoietic tissues
What are labile tissues?
Tissues with short-lived cells that are replaced from cells derived from stem cells
Give two examples of stable tissues
Liver parenchyma
Bone
What happens in stable tissues?
There is normally a low level of replication, if necessary can undergo rapid proliferation by stem cells and mature cells
Give two example of permanent tissues
Skeletal muscle
Cardiac muscle
What are permanent tissues?
Tissues that contain mature cells that can’t undergo mitosis - no stem cells present
In which tissues can regeneration take place?
For regeneration to take place what is also essential?
In labile or stable tissues
The tissue damage not to be extensive - regeneration requires intact connective tissue scaffold
What is fibrous repair?
Healing with formation of fibrous connective tissue (scar)
When does fibrous repair take place? (2)
Significant tissue loss
Injury of a permanent or complex tissue
When does fibrous repair take place as opposed to regeneration? (2)
If the damage is in permanent tissues
If the collagen framework is destroyed
What are the 6 stages of formation of a scar following injury? What are the timescales of each stage?
Haemostasis (secs - mins) Acute inflammation (mins - hrs) Chronic inflammation (1-2 days) Granulation tissue (3 days) Early scar (7-10 days) Scar maturation (weeks - years)
What is the significance of the early scar stage of scar formation?
Stitches are taken out of wounds at this point
Which cell infiltrates and digests the blood clot formed during fibrous repair?
Neutrophils
Vessels sprout in the area of damaged tissue during fibrous repair, what cells are recruited?
What is their function?
Myofibroblasts
Fibroblasts
Secrete collagen to form the scar
What does granulation tissue consist of? (3)
Developing capillaries
Fibroblasts/Myofibroblasts
Chronic inflammatory cells
What are three functions of granulation tissue?
Fills the gap
Contracts and closes the hole
Capillaries supply oxygen, nutrients and cells
What are 3 types of cells involved in fibrous repair?
Inflammatory cells
Endothelial cells
Fibroblasts/myofibroblasts
What is the function of inflammatory cells in fibrous repair? (2)
Phagocytosis of debris - neutrophils/macrophages
Production of chemical mediators - lymphocytes/macrophages
What is the function of endothelial cells in fibrous repair?
Proliferation results in angiogenesis
What is the function of fibroblasts/myofibroblasts in fibrous repair? (2)
Produce collagen
Help with wound contraction
Why do old scars often appear white?
There are no melanocytes in the area
What happens to scars as they get older?
They stretch as they can only produce collagen and not elastin
Name two structures that can’t be regenerated in scars/fibrous repair
Sweat glands
Hair follicles
What is the structure of a collagen molecule?
Composed of triple helices of alpha polypeptide chains
What types of collagen can be described as fibrillar collagens? What is their function?
Types I - III
Tissue strength
What types of collagen can be described as amorphous collagens? Give an example of where these collagens are found in the body
Types IV - VI
Basement membrane
What is the most common type of collagen? Where in the body is it found?
Type I collagen
Bones, tendons, ligaments, skin
Which cells secrete type IV collagen? What does it make up?
Epithelial cells
Basement membrane
Where are the polypeptide alpha chains that make up collagen synthesised in a cell?
In the ER
What role does vitamin C play in the production of collagen fibres?
Cofactor for enzyme that hydroxylate residues on polypeptide alpha chain
How is a procollagen triple helix molecule formed from alpha chains?
Chains align and cross-link to form procollagen triple helix
What happens to the procollagen that gets secreted?
Cleaved to tropocollagen
How does tropocollagen form collagen fibres?
Tropocollagen polymerises to form microfibrils and then fibrils
Bundles of fibrils —> Fibres
What feature of collagen gives it tensile strength?
Cross-linking
What causes scurvy?
Vitamin C deficiency
What consequence does scurvy have on collagen production?
Inadequate vitamin C dependent hydroxylation of procollagen alpha chains —> Reduced cross-linking —> Defective helix formation
What are three symptoms of scurvy?
Poor wound healing Poor bone function Tendency to bleed Tooth loss Old scars break down and open up as fresh wounds
Why does scurvy often result in teeth loss?
Collagen that holds teeth in place has a short half life and so normal collagen is replaced by weak defective collagen
Are Ehlers-Danlos syndromes inherited/acquired?
Inherited disorders
What happens in Ehlers-Danlos syndromes?
Defective conversion of procollagen to tropocollagen = collagen fibres lack tensile strength
What are three symptoms of Ehlers-Danlos syndromes
Poor wound healing
Hyper-extensible skin (increased fragility)
Hyper-mobile joints (increased risk of dislocation)
Spontaneous rupture of colon, large arteries or cornea
Retinal detachment
Osteogenesis imperfecta is also known as…
Brittle bone disease
What happens in osteogenesis imperfecta?
There is too little bone tissue, resulting in severe, progressive deformation of long bones
What are three symptoms of osteogenesis imperfecta?
Blue sclerae
Hearing impairment
Dental abnormalities
How is Alport syndrome acquired?
It is inherited - x-linked recessive
What happens in alport syndrome?
There is abnormal type IV collagen —> Dysfunction of (glomerular) basement membrane
What can alport syndrome present with? Name another symptom of alport syndrome
Haematuria - indicating renal failure
Deafness
Eye disorders
Which local mediators play an important role in wound healing?
Growth factors
What are growth factors? Which genes code for them?
Polypeptides that act on cell surface receptors
Proto-oncogenes
Growth factors bind to…
And have what effect?
Specific cell surface receptors
Stimulate transcription of genes that regulate entry of cell into the cell cycle
Name two different type of growth factors
Epidermal growth factor
Tumour necrosis growth factor
Growth factors are produced by cells such as…
Platelets
Macrophages
Endothelial cells
Name another effect of growth factors apart from stimulating the transcription of genes that regulate entry of the cell into the cell cycle
Angiogenesis
What property of cells inhibits proliferation in intact tissue and promotes proliferation in damaged tissues?
This property is altered in which sorts of cells…
Contact inhibition
Malignant cells
What is contact inhibition?
Where proliferation of cells stops when two cells touch each other
Which two molecules are involved in contact inhibition and adhesion of cells to each other?
Cadherins
Integrins
Cadherins bind…
Cells to one another
Integrins bind…
Cells to the ECM
When does healing by primary intention take place?
For incised, closed, non-infected and sutured wounds
When there is only death of a small number of epithelial/connective tissue cells
In healing by primary intention, how much granulation tissue and how much of a clot is formed?
Minimal clot and granulation tissue
Describe the process of healing by primary intention
Epidermis regenerates - epidermal cells deposit basement membrane and fuse beneath the scab
Dermis undergoes fibrous repair
Minimal contraction and scarring
When does healing by secondary intention take place?
For excisional wounds
For wounds with tissue loss, separated edges and infected wounds
How much granulation tissue is formed in healing by secondary intention?
Abundant granulation tissue which fills the open wound
What is the process of healing by secondary intention?
Is it a longer or shorter process than healing by primary intention?
Same as healing by primary intention but with considerable wound contraction to close the wound and substantial scar formation
Longer
How does the donor site heal in spit skin grafts?
What happens to the skin taken for a skin graft?
The skin taken is split quite superficially, structures such as hair follicles/sweat glands remain
Skin taken is meshed to cover a large wound
What are the 6 stages involved in the healing of bone?
Haematoma Granulation tissue Soft callus Hard callus Lamellar bone Remodelling
What does a hard callus in bone consist of?
Woven bone (weaker/less organised than lamellar bone)
What function does a haematoma play in bone healing?
Fills the gap and surrounds the injury
What role does granulation tissue play in bone healing?
Contains cytokines that activate osteoprogenitor cells
What are some local factors that can affect wound healing?
Type, size and location of wound Mechanical stress Blood supply Local infection Foreign bodies
What are some general factors that can affect wound healing?
Age Anaemia Obesity Diabetes Vitamin Deficiency
How do steroid drugs affect wound healing?
They interfere with collagen synthesis
What complications can result from insufficient fibrosis in fibrous repair?
Wound rupture, hernia and ulceration
What complications can result from overproduction of fibrous scar tissue in fibrous repair?
Keloid scars
What complications can result from excessive scar contraction as a result of fibrous repair? When is this usually seen?
Obstruction of tubes/disfiguring scars
Following burns
Predicting the type of healing that will occur depends on which three factors?
The type of tissue
The extent of injury
The presence of persistent infection
