Healing Flashcards
What 3 processes are involved in wound healing
- haemostasis
- inflammation
- regeneration
Why does haemostasis occur
As the vessels are open
What is regeneration
Restitution with no or minimal evidence that there was previous injury - healing by primary intention
What is the alternative to regeneration
Fibrous repair (organisation)
What is an abrasion
Heeling by regeneration to the superficial layer of the skin (epidermis)
What is an ulcer
Injury to the mucosa (deep layers)
Which cells replicate in regeneration
Stem cells
What are stem cells
Cells that have a prolonged proliferative activity and show asymmetric replication
What is asymmetric replication
When they divide into daughter cells and 1 cells remains as a stem cell whereas the other differentiates into a mature cells
What tissues are stem cells found in
- epidermis (basal layer)
- intestinal mucosa (bottom of the crypts)
- liver (between hepatocytes and bile ducts)
What does unipotent mean
Stem cells which only differentiate into 1 type of cell e.g. Epithelia
What are mulitpotent cells
Stem cells which can differentiate into several different types of cells e.g. Haematopoietic cells
What are totipotent stem cells
Stem cells which which can differentiate into any type of cell in the body e.g. Embryonic stem cells
What type of stem cells do blood cells derive from
Multi potent stem cells in the bone marrow
What types of tissue can regenerate
Labile and stable tissue
What type of tissue doesn’t regenerate
Permanent tissue
What are labile tissues
Tissues which contain short-lived cells that are replaced by stem cell derived cells e.g. Surface epithelia and haematopoietic cells
What are stable tissues
Cells which normally have low levels of replication but can undergo rapid proliferation of stem cells and mature cells when needed e.g. Liver, bone, endothelium and fibrous tissue
What are permanent tissues
Tissues made up of mature cells that cant undergo mitosis and don’t have stem cells present e.g. Neural tissue, skeletal muscle and cardiac muscle
When does regeneration take place
- if there’s damage in labile or stable tissue
- if tissue damage is not extensive so the connective tissue scaffold is not damaged
What is fibrous repair (organisation regeneration)
The healing causing the formation of fibrous connective tissue to give a scar
Healing by secondary intention
When does fibrous repair occur
- significant tissue loss
- if permanent or complex tissue is damaged
After how long may stitches be taken out from a wound and why
After 7-10 days as an early scar has formed and so the wound wont fall apart
How long does scar maturation take
Can take up to 2 year
What is granulation tissue
Tissue which consists of capillaries, fibroblasts, myofibroblasts and chronic inflammatory cells giving a granular appearance
What are the functions of granulation tissue
- fills the gaps in wounds
- the capillaries supply oxygen, nutrients and cells
- allows contraction to close the hole
Outline fibrous repair
- a blood clot forms in a wound
- neutrophils infiltrate and digest clot
- macrophages and lymphocytes arrive and secrete chemicals which causes capillaries to bud
- capillaries grow and the myo/fibroblasts make glycoproteins
- collagen synthesised, lots of capillaries and macrophage number reduced
- lot of collagen, cell number reduces and the wound contracts and remodels
What cells are involved in fibrous repair
- inflammatory cells (neutrophils, macrophages and lymphocytes)
- endothelial cells
- fibroblasts and myofibroblasts
What do endothelial cells do in fibrous repair
Their proliferation results in angiogenesis
What is angiogenesis
The growing of new blood vessels
What are myofibroblasts
Fibroblasts which can also contract like smooth muscle cells so are responsible for wound contraction
What do fibroblasts do
Produce the extracellular matrix protein collagen
Why do scars form on the head and sweat glands
Hair follicles and sweat glands are complex tissues so cant regenerate so must undergo fibrosis repair
What does collagen do
Provided the extracellular framework to give cells their shape, hold the body of the cell together
What are the fibrillar collagens
Types I-III
This are responsible for strength
What are the amorphous collagens
Type IV-VI
These make up the basement membrane
Where is type 1 collagen mostly found
Bones, tendons, ligaments, skin, sclera, blood vessels
What cells secrete type IV collagen
Epithelial cells
Outline the production of fibrillation collagen
- polypeptide alpha chains are produced in the ER of fibroblasts and myofibroblasts
- enzymatic modification
- cross linkage between the alpha chains forming procollagen triple helix
- pro collagen secreted and cleaved to give tropocollagen
- tropocollagen polymerises to give fibrils which then bundle to form fibres
- remodelling
What enzymes allow remodelling of collagen
Collengases
What does crosslinkage of collagen cause
Gives tensile strength
What is vitamin C need for in collagen production
Hydroxylation which allows for cross linkages
Give an example of an acquired collagen synthesis disease
Scurvy
What is scurvy
Deficiency in vitamin C reducing the cross linkages in the helix structure so there’s less strength and is vulnerable to enzymatic degradation
What are the symptoms of scurvy
- poor wound healing
- tendency to bleed
- tooth loss (normal collagen replaced by defective collagen)
- old scars break down
What is ehlers-danlos syndrome
Defective conversion of procollagen to collagen so they lack tensile strength
What are the symptoms of ehlers-danlos
- poor wound healing
- hyper-extensible, thin, fragile skin
- hypermobile and joint predisposed to dislocation
- rupture of colon, arteries
Why can the skin in ehlers-danlos recoil
The skin still contains elastin
What is osteogenesis imperfecta
Defective collagen so there’s little bone tissue and so the bones are very fragile
What are the symptoms of osteogenesis imperfecta
- repeated fractures
- blue sclera (too little collagen makes then translucent)
What is Alport syndrome
- abnormal type IV collagen
- gives disfunction of glomerular basement membrane, cochlea of ear and lens of eye
What inheritance pattern is Alport syndrome
X linked
What controls regeneration and fibrous repair
- hormones
- local mediators (growth factors)
- direct cell to cell or cell to stroma contact
What are growth factors
Polypeptides which act on cell surface receptors to stimulate transcription of genes that regulate entry of the cell into the cell cycle
What genes code for growth factors
Proto-oncogenes
What are the affects of growth factors
- proliferation
- inhibition of division
- contractility
- differentiation
- angiogenesis
Giver 4 examples of growth factors
- epidermal growth factor
- vascular endothelial growth factor
- platelet derived growth factor
- tumour necrosis factor
What produces growth factors
Platelets, macrophages and endothelial cells
What is contact inhibition
Signalling through adhesion molecules where the Cadherins on cells allow them to bind and they grow up until the integrins of the outer cells bind to the extracellular matrix. Grow to fill the space
What happens if there is a loss of contact inhibition
Proliferation will continue after the space is filled so they will proliferate onto of eachother
What is healing by primary intention
Where there is disruption to the basement membrane but there’s only death of a small number of epithelial and connective tissue cells.
What type of intention are surgical wounds healed by
Primary intention
What occurs in primary intention
- epidermis regenerates (basal epidermal cells at the edge of cut and fuses beneath scab)
- dermis has fibrous repair
- minimal contraction and scarring with good strength
What is healing secondary intention
When an open wound (which has tissue loss and separated edges or infected wounds) is filled by abundant granulation tissue
Outline healing by secondary intention
- same as primary but more so
- more contraction to close wound
- substantial scar formation
- takes longer
Outline bone healing
- haematoma forms
- granulation tissue forms
- soft callus forms
- hard callus forms
- lamellar bone
What things can influence wound healing
- type, size and location of wound
- mechanical stress
- blood supply
- local infection
- foreign bodies
What are complications of fibrous repair
- insufficient fibrosis
- formation of adhesions (fibrotic tissue which surrounds or is found inbetween organs) which can comprise function and block tubes
- loss of function (when specialised functional tissue is replaced by fibrotic tissue)
- overproduction
- excessive contraction
What type of scar is produced from overproduction of fibrous scar tissue
Keloid scar
When may excessive scar contraction occur
Following burns