Wound healing Flashcards

1
Q

Wound healing

A
Essential
Trauma, injury or surgery
Most commonly skin
Research
Cosmetic industry
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Wound healing cost

A

£180M - £2 billion per year to NHS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Healing

A

Follows tissue damage
An attempt to restore integrity to an injured tissue
Follows (often overlaps) the inflammatory process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Resolution definition

A

Return to normal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Regeneration definition

A

Lost tissue replaced by same type to restore tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Repair definition

A

Tissue lost replaced by fibrous scar via granulation tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Regeneration vs repair: what determines the type of healing?

A
  1. Cell type involved
  2. Tissue architecture
  3. Amount of tissue lost
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Regeneration vs repair: cell type involved

A

Labile: continual cell division
Stable: infrequent cell division, but can increase e.g. liver cells in injury
Permanent: no cell division possible e.g. nerve cells, cardiac cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Regeneration vs repair: tissue architecture

A

Simple tissues

Complex tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Regeneration vs repair: amount of tissue lost

A

Small

Large - especially if basement membrane/ ECM lost

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Repair: organisation: the formation of a fibrous scar via granulation tissue

A

Endothelial cells and fibroblasts at edges
These migrate into area, forming loose CT - granulation tissue
> in BVs and collagen (number of blood vessels eventually decreases again)
Vascularity < and fibrous scar formed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Granulation tissue do not confuse this with granuloma

A

Named such due its appearance in skin
Cells in repair process
-macrophages (phagocytosis & secretion)
-fibroblasts (collagen and other tissue support)
-endothelial cells (nutrition)
Often chronic inflammation is concurrent
!! histology on slides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Shape of fibroblasts

A

Spindle shaped

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Macrophages histology

A

Larger, pale staining

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Endothelial cells histology

A

BVs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

3 layers of wound healing

A

Surface: fibrin slough and acute inflammatory cells (blood forms on surface for protection)
Granulation tissue, mostly macrophages and endothelial cells
More mature granulation tissue, more fibroblasts
histology on slides
-over time more macrophages at surface

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Phases of wound healing

A
haemostasis
inflammation
proliferation
remodelling
!! pictures on slides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Haemostasis

A

•vessel rupture, bleeding
•activation of coagulation cascade
•vasoconstriction (5-10 mins. serotonin, adrenaline etc.)
•thrombus formation, fibrin & fibrinogen glue wound together
Key cell: Platelets (trapped within clot)
•cytokines & growth factors released (PDGF, TGFβ)
•act as chemo-attractants
•vasodilation (prostaglandins, leukotrienes, histamine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Inflammation

A
Key cell (early): Neutrophil
•recruited from circulation
•remove bacteria and foreign material
•phagocytosis and enzymes
•short lived (2 days)
Key cell: Macrophage
•recruited from blood monocytes &amp; those already resident
in tissue, proliferate locally
•phagocytosis of remaining debris
Further secretion cytokines &amp; growth factors by both
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Proliferation

A

Granulation tissue formation
Key cell: Fibroblast
-proliferate, migrate & become myofibroblast
Synthesis of matrix proteins e.g. collagen
Proliferation & migration of cells over wound bed
Key cell: Keratinocyte
Re-epithelialisation
Angiogenesis (new BV formation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Remodelling

A

Provisional matrix remodelled
< in cell & capillary density (less red)
Proteases (collagenases) required for remodelling
Wound contraction
Type III collagen replaced by bundles of type I
Strength relies on cross-linked collagen I (Vitamin C)
7-10 days wound = 10% strength
2-3 months=70-80%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Phases overlap

A
Inflammation (early): 0.1-3 days
Inflammation (late): 0.3-10 days
Granulation tissue formation; 3-30 days
Matrix formation and remodelling: 5-100+ days (in which time amount of collagen decreases)
*!*! graph on slide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Primary intention

A

Wound edges are
apposed (brought together) & held in place
by mechanical means (sutures etc.)
-wound is clean, in straight line, with little loss of tissue
-usually rapid healing with minimal scarring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Secondary intention

A

Wound left open,
edges come together naturally by means
of granulation and contraction
-large wound with considerable tissue loss
-healing takes longer and results in more scarring
-can’t stitch it up, too big and would cause a lot of stress on the tissue
E.g. tooth extraction, wound on palate (tightly bound mucosa)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Intention
If you are actively going to do something to help the healing process
26
Socket healing
``` Same principles as fracture healing -inflammation -proliferation -remodelling No calus ```
27
Tooth socket over time
Day 4: residual clot Day 8: granulation tissue Day 52: bony infill Osteoclast rebsorption
28
Factors influencing wound healing
1. Local - type, size and location of wound - movement within wound - infection - presence of foreign/ necrotic material - irradiation - poor blood supply 2. Systemic - age - nutrition (VitC, zinc) - systemic disease - circulatory, diabetes - drugs (esp steroids)
29
How is the healing process controlled?
``` Different types of cells -cell-to-ECM interactions (integrins) -cell-cell interaction -correct position of cells Signals (multiple) -from cells or blood -growth factors -cytokines and chemokines -O2, nutrients etc -ECM ```
30
Control of epithelial cells
``` New cells are required: stimulation of stem cells in the basal layer Mitogenic (growth) stimuli are: -loss of contact inhibition -growth factor mediated (from platelets and damaged endothelial cells): -> platelet derived growth factor (PDGF) -> epidermal growth factor (EGF) -> keratinocyte growth factor (KCD) ```
31
Control of epithelial cells
``` New cells are required: stimulation of stem cells in the basal layer Mitogenic (growth) stimuli are: -loss of contact inhibition -growth factor mediated (from platelets and damaged endothelial cells): -> platelet derived growth factor (PDGF) -> epidermal growth factor (EGF) -> keratinocyte growth factor (KCD) ```
32
Control of epithelial cells - movement
``` Migration of existing cells at wound edge (fibronectin) Migration stops when cells meet Stratification (differentiation) finally occurs Basement membrane proteins re-appear ```
33
Control of neutrophils and macrophages
``` Margination Adhesion Emigration Chemotaxis Pagocytosis and degranulation ```
34
Margination
Cells line up against the vessel wall
35
Adhesion
Adhesion molecule expression on endothelium changed
36
Emigration
Pseudopodia push through gaps in endothelium
37
Chemotaxis
Movement along a chemical gradient | -bacterial products (exogenous), complement fragments, prostaglandins, leukotrienes, cytokines
38
Phagocytosis and degranulation
Free radical, lysozyme
39
Control of angiogenesis
``` Ingrowth of new BVs Budding from intact vessels at wound edge Macrophages secrete angiogenic factors in response to low oxygen Fibroblast growth factor (FGF) & VEGF stimulate protease secretion & growth of endothelial cells Anti-angiogenic factors limit vessel formation As inflammation subsides, apoptosis occurs ```
40
Control of fibroblasts
'Activated' to come myofibroblasts (TGFβ) -fibroblast & smooth muscle features Proliferation - PDGF, FGF, TGFα, c5a from macrophages, platelets and endothelial cells Migration - stimulated by fibronectin Chemoattraction by macrophages Secretion of collagen and fibronectin: TGFβ
41
Complicated for a reason?
``` Essential process Multiple cells types Multiple control points Control is key *diagram on slides ```
42
Dysregulated healing = cancer?
``` Wound healing and cancer both: •keratinocyte proliferation & migration •fibroblast ‘activation’ •angiogenesis •proteases upregulated •integrin expression altered BUT -Wound healing: reversible changes -Cancer: irreversible changes ```
43
Scarring
Good healing scarring decreased/ non-healing
44
Scar definition
``` Macroscopic disturbance of normal structure & function of skin architecture resulting from end product of healed wound ```
45
Problems
``` Burns Hypertrophic scars Contractures Keloids Neuroma Loss of function Restricted growth Cosmetic (Collagen, fibroblasts) ```
46
Hypertrophic scars
> incidence of hypertrophic scars/ keloid in those with darker skin Used as decoration/ tribal identity Facial scars attractive to opposite sex
47
Contractures
Muscle/ tendon shortening
48
Keloid scar histology
Thick bundles of collagen, with high levels of type III Abnormal cross-linkage and high turnover Altered cytokine levels
49
Keloid scar - prevention and treatment
Avoid “cosmetic” procedures in “at risk” individuals Treat with dressings, cryosurgery, pressure, corticosteroids etc Excision often results in recurrence New therapy – intralesional interferon
50
Problems: neuroma
Thickening of nerve tissue that may develop -term also used to refer to any swelling of a nerve, even in the absence of abnormal cell growth. In particular, traumatic neuroma results from trauma to a nerve, often during a surgical procedure
51
Girls dig scars?
Females found scarred faces more attractive in the short-term
52
Foetal wounds
``` ‘Scarless’ < inflammation, < neutrophils Fibroblast phenotype (ECM synthesis, cytokine production, RTK signalling) Prompt disappearance of PDGF VEGF increased (angiogenesis) & FGF Homeobox genes (transciption factors) ```
53
Keloid scars
People with darker skin more prone with these | Sticks out of wound
54
Wound healing -->
Scarless e.g. foetal skin, oral mucosa Scarring e.g. adult skin Non-healing e.g. chronic wounds
55
Oral vs skin
``` Environment: Saliva Fibroblast are heterogeneous Oral have > ability to contract More ‘foetal’ like ‘Younger’ phenotype (telomerase) > secretion of growth factors (KGF, HGF, VEGF) > keratinocyte proliferation ```
56
Oral vs skin
``` Environment: Saliva Fibroblast are heterogeneous Oral have > ability to contract More ‘foetal’ like ‘Younger’ phenotype (telomerase) > secretion of growth factors (KGF, HGF, VEGF) > keratinocyte proliferation ```
57
Aids to wound healing
``` Basic wound care Assisted wound care -dressings -hyperbaric oxygen maggots and Leeches negative pressure/ vacuum therapy Recombinant growth factors: EGF, KGF-2, PDGF Matrix materials – collagen, hyaluronin Experimental – cell therapy ```
58
Cystic / pulmonary/ fibrosis/ scarring of the heart
Cystic fibrosis: inherited condition that causes sticky mucus to build up in the lungs and digestive system -causes lung infections & problems digesting food
59
Maggot therapy
Results quite similar to surgical debridement | Eat necrotic and dead material
60
Leech therapy
Contain Nitrogen oxygen in saliva - helps circulation | Keeps wound healthy e.g. on flaps after surgery
61
Negative pressure/ vacuum therapy
Works quite well for chronic wounds - vacuum dressing used to enhance & promote wound healing in acute, chronic and burn wound - therapy involves using sealed wound dressing attached to pump to create negative pressure environment in wound
62
Hilotherapy
Wearing mask/ bandage which circulates warm water around wound -reduces swelling, healing time
63
Research - TGFβ
TGFβ1 and TGFβ2 low in embryonic and high in adult TGFβ3 high in embryonic (keratinocytes and fibroblasts) and low in adult Alter ratio of TGFβ isoforms Neutralising antibodies to TGFβ1 and TGFβ2 Enhance TGFβ3 Clinical trials
64
Problems: chronic wounds
``` 'Stuck' in inflammatory phase Increased proteases (destroy ECM) Reduced growth factors (PDGS, EGF, FGF) Fibrin 'cuffs' Underlying disease (venous insufficiency, diabetes) Infection Necrosis ```