wound healing Flashcards
1
Q
healing
A
Follows tissue damage
- attempt to restore integrity to an injured tissue (back to how they were)
- follows the inflammatory process (often overlaps)
2
Q
resolution
A
return to normal
3
Q
regeneration
A
lost tissue replaced by same type of tissue to restore tissue
4
Q
repair
A
tissue lost replaced by firbois scare (via granulation tissue)
5
Q
regeneration vs repair headings for comparision
A
cell type involved
tissue architecture
amount of tissue lost
6
Q
cell type involved (regeneration vs repair )
A
labial continual cell division vs stable infrqeuen cell divison
7
Q
tissue architecture regeneration vs repair
A
simple vs complex tissue
8
Q
amount of tissue lost regeneration vs repair
A
small vs large
9
Q
steps for repair
A
1) endotheoal cells and fibroblasts at edges (form loose meshwork/bridge)
2) these migrate into area forming loose connective tissue, granulation tissue
3) increase in blood vessels and collagen
4) vascularity decreases and fibrous scar formed
10
Q
cells involved in the repair process
A
- macrophages (phagocytosis any debris cell ect and secretion to promote wound healing
- fibroblasts (collagen and other tissue support)
- endothelial cells (nutrition)
11
Q
what does slough contain
A
neutrophuils
12
Q
granulation tissue conposition
A
- Inflammatory
- endothelial cells
- fibroblasts
13
Q
phases of wound healing
A
1) haemostasis
2) inflammation
3) proliferation
4) remodelling
14
Q
haemostasis
A
vessel rupture, bleeding
- activation of coagulation cascade
- vasoconstriction (5-10 mins serotonin, adrenaline)
- thrombus formation, fibrin and fibrinogen glue would together
15
Q
cells involved in inflamamtion
A
neutrophls
macrophages
16
Q
neutrophils inflammation
A
- recruited from circulation (why we need vasodilation)
- remove bacteria and forign material
- phagocytosis and enzymes
- short live (2 days)
17
Q
macrophages inflammation
A
- recruited from blood monocytes (circulation) and those already resident in the tissue, proliferate locally
- phagocytose of remaining debris
Further secretion cytokines and growth factors by both (secret further cytokines) - both follow the chemoattracts to where they are needed
18
Q
proliferation step in wound healing key cells and roles
A
key cell- fibroblast
- proliferate, migrate and become myofibroblast (change phenotype, gives them some contractile properties to pull wound together)
- synthesis of matrix proteins eg collagen
- proliferation and migration of cells over wound bed
Key cell – keratinocyte
- re epithelialisation
- angiogenesis (new blood vessel formation)
19
Q
remodelling in wound healing steps
A
- provisional matrix remodelled
- reduction in cell and capillary density (less red)
- protases (collagenases) required for remodelling ECM (Scaffold and chemical signalling matrix)
- wound contraction (using proteins within the cytoskeleton to pull together)
- type III collagen replaced by bundles of type I
- strength relies on cross linked collagen I (vitamin C)
- 7-10 days wound = 10% strength (provisional matrix)
- 2-3 months 70-80%
20
Q
types of intention on how to treat the wound
A
primary
secondary
21
Q
primary intention
A
- wound edges are apposed (brought together) and held in place by mechanical means (eg sutrues, glue)
- actively helping process
- wound that is clean straight
- no tissue lost
- just split open due to pressure of tissue
- bring together with stiches
- minimal scaring
22
Q
secondary intention
A
- wound left open
- edges come together natural by means of granulation and contraction
- heal by itself
23
Q
secondary intention type of wound
A
- bigger wound
- deeper
- wider
- tissue has been lost
- even if you brought it together on the surface, there would be missing skin underneath so the extra pressure would not help healing
- leave to heal on its own
- healing will take longer, more like repair, fibroblastic response, more scarring
24
Q
bone fracture healing
A
- don’t get granulation tissue but similar tissue which forms a bridge/scaffold
- follows by immature then mature bone
- resolution process, extra bits of bone taken away by macrophages
25
socket healing steps
- inflammation
- proliferation
- remodelling
granulation tisseu formation is then replaced by fibroblasts
26
oral and skin wound healin g is best acheived by
primary intention
27
factors influencing wound healing (systemic and local)
1) Local
- type(eg clean cut), size and location of wound
- movement within wound
- infection (barrier function of the epithelium) is gone
- presence of forgein/necrotic material
- irradiation (damage cells ability to proliferate)
- poor blood supply (cant bring inflammatory cells in)
2) systemic
- age (longer to heal)
- nutrition
- (vitamin C and Zinc)
- systemic disease – circulatory, diabetes
- drugs (esp steroids, antiinflammaory healing stage interrupted)
28
signals involved in the healing process
- from cells or blood
- growth factors
- cytokines and chemokines
- O2, nutrients etc
- extracellular matrix
29
cells involved in healing process
- different types (WBC, bone cells, epithelail cells ect interact with each other and the ECM)
- cell to extracellular matrix interactions (integrins) – sense type of ECM they are in
- cell- cell interactions
- correct position of cells
30
mitogenic growth stimuli in epithelail cells
- loss of contact inhibition (cells are tightly packed and normally don’t grow, loss of contact tells epithelial cells they need to grow to replace)
- growth factor mediated (from platelets and damaged endothelial cells)
31
control of epithelila cell movment
Migration of existing cells at wound edge (fibronectin) – proliferating cells move over the wound bed
- migration stops when cells meet
- stratification (differentiation) finally occurs
- basement membrane proteins reappear (between dermis and epidermis)
32
control of neutrophils and macrophages
1) margination
- cells line up against the vessel wall
- neutrophils line up against endothelium
2) adhesion
- adhesion molecule expression on endothelium changed
- receptors that respond to this signal
3) emigration
- pseudopodia push through gaps in endothelium
4) chemotaxis
- movement along a chemical gradient
- released in local areas, to bring in blood cells
- bacteria products(exogenous)
- complement
- fragments
- prostaglandins
- leukotrienes
- cytokines
5) phagocytosis and degranulation
- free radicals
- lysozyme (digest and kill bacteria)
- proteolytic enzymes in lysosomes
33
angiogenesis
ingrowth of new blood vessels
34
steps for angiogeneiss
- budding from intact vessels at wound edge
- macrophages secrete angiogenic
- macrophages secrete angiogenic factors in response to low oxygen (hypoxic, to relief that environment)
- fibroblast GF and VEGF stimulate protease secretion and growth of endothelial cell
- anti- angiogenic factors limit vessel formation (towards end of would healing)
- as inflammation subsides, apoptosis occurs
35
what are fibroblasts activated to form
myofibroblasts
change phenotype, express contractile protein
- fibroblast and smooth muscle features
- gives fibroblast cell ability to contract
- pull wound together
36
what is migrtion stimulated by for fibroblasts
fibronectin
Chemoattraction by macrophages
secretion of collagen and fibronectin and TGF beta (affects other cells)
37
proliferation of fibroblasts
- PDGF, FGF, TGFalpha, c5a from macrophages, platelets and endothelial cells
- grow within granulation tissue
38
why is healing complicated
- multiple cell types
- multpiple control points
- control is key
- lots of chemokines
- all processes are crutial for healing, needs to be tightly regualted
39
dysregulated healing leads to
cancer
40
scar
macroscopic disturbance of the normal structure and function of the skin architecture resulting from the end product of a healed wound
41
cancer steps in wound healing
- keratinocyte proliferation and migration
- fibroblast activation
- angiogenesis
- proteases unregulated
- integrin expression altered
42
problems with healing
- burns (lose ECM, can get the repair back by filling the gap but don’t get tissue architecture back)
- hypertrophic scars (where wound healing takes longer to stop not when it should, scars with stick out of the wound further than they should)
- contracture
- keloids
- neuroma
- loss of function
- cosmetic (collagen, fibroblasts)
43
hypertrophic scaring
increased incidence of hypertrophic/keloid in those with darker skin
44
contractures
Muscle/tendon shortening
45
keloid scar
- thick bundles of collagen with high levels of type III
- abnormal cross linkage and high turnover
- altered cytokine levels
46
neuroma
scar tissue around nerves
- nerve bruised or pulled
- can form scar tissue around it
- may reduce condition and alter sensation
- eg may be tingly lower lip
47
chronic wounds and characteristics
Stuck in inflammatory phase
- beyond 3 months
- increased proteases (destroy ECM)
- reduced GFs (PDGF, FGF, EGF)
- fibrin cuffs
- underling disease (venous insufficiency, diabetes)
- infection
- necrosis
48
foetal wounds and mechaism
wounds almost scarless and dissolve immediately
- reduced inflammation, fewer neutrophils
- fibroblast phenotype different to adults (ECM synthesis, cytokine production, RTK signalling)
- prompt disappearance of PlatletderivedGF (stimulates the next phase)
- VEGF increased (more rapid angiogenesis) and FGF – quicker to give nutrients
- homeobox genes (transcription factors)
49
chronic wounds
- don’t heal due to underlying disease
- adult skin scarring lasts almost forever
- can create sig defect in the OC, but will heal without scar (secondary healing without sutres)
50
oral vs skin healing
Enviroment
- saliva has antibacterial properties
- protected from other elements
Fibroblasts are heterogeneous
- different in underlying tissue in mouth vs skin
- oral have increased ability to contract
- younger phenotype (telomerase)
- increased secretion of growth factors, change in profile of the messengers, different levels in oral vs skin (KGF, HGF, VEGF)
- increased keratinocyte proliferation, can cover a wound are in a shorter length of time
51
assisted wound healing
- dressings
- hyperbaric oxygen (can encourage wound healing, cells able to take up oxygen better)
- maggots and leeches (maggots eat dead things, debride the wound, encourage remaining tissue to grow back, leech good for grafts to encourage circulation
- negative pressure/vaccum therapy (creates a seal around the wound, vaccum keeps dry and sealed also keeps the wound together)
52
new research into wound healing
TGFB
| alter ratio of isoforms
