Pathology of wound healing Flashcards
What are the 2 categories of wound healing?
regeneration
repair
What is required for tissue regeneration to occur?
tissue requires ongoing mitotic activity
What is repair aspect of wound healing?
replaces damaged cells with fibrous connective tissue
leaves permanent scar
occurs in non-mitotic tissue and with more severe injuries
What type of repair occurs if the injury is extreme?
fibrous repair
What 2 structural components are tissues and organs divided into?
parenchymal tissue
stromal regions
What are parenchymal cells of tissues and organs?
functional cells of the organ
highly specialised
What are the stromal regions of tissues and organs
support tissue
connective tissue, ECM, blood vessles, nerves
What are examples of parenchymal tissues?
hepatocytes, kidney, tubular cells
What is regeneration?
injured cells replaced by identical new cells
What is repair?
damaged cells replaced by stromal/fibrous scar tissue
What are the 3 categories of tissue according to cell types?
- labile cells
- stable cells
- fixed cells
What can dictate if regeneration or repair will occur?
mitotic activity of teh cell/tissue
What are labile cells?
continuous division
continuously divide
Where would you find labile cells?
surface epithelium (skin, oral cavity, GI tract, uterus)
When does division of stable cells stop?
when growth is complete
still gave potential for division
What are examples f stable cells?
hepatocytes
kidney tubular cells
smooth muscle
Are mitotic cells capable of mitotic diivision?
no
What are damaged fixed cells replaced by?
fibrous scar tissue
Are wound healings by regeneration and fibrous tissue repair controlled by similar regulatory mechanisms?
yes
What does would healing by regeneration And repair involve?
inflammatory mediators
growth factors
ECM
What WBC release inflammatory mediators?
monocytes
macrophages
What are examples of inflammatory mediators?
TNF-a
interleukins
interferons
arachnoid acid
leukotrienes
prostaglandins
What isthe effect of inflammatory mediators?
blood clotting (initial vasodilation)
immune cell infiltration (delayed vasodilation)
phagocytosis of debris and bacteria
new cell growth/fibroblast infiltration
angiogenesis
What cells release growthfactors?
fibroblasts and macrophaes and endothelial cells
neutrophils
What are examples of growth factors?
FGF
EGF
TGF
What is the effect of growth factors?
inflammatory response (cross-talk)
chemotaxis
proliferation and differentiation
generation of ECM
angiogenesis
What is the overall goal of growth factors?
moves process onwards to regeneration/repair damaged region
mature scar
What do endothelial cells, immune cells, fibroblasts secrete?
ECM
What are the different types of ECM?
collagen and elastin
proteoglycans and hyaluronic acid
fibronectin and laminin
What are the fibrous/structural proteins (ECM)?
COLLAGEN AND ELASTON
What is the role of collagen and elastin ECM?
Scaffolding of ECM, provides framework and tensile strength
What is the water-hydrated gels (ECM)
proteoglycans and hyaluronic acid
What is the role of proteoglycans and hyaluronic acid in the ECM?
provides lubrication, resilience and flexibility
What are the adhesive glycoproteins (ECM)?
Fibronectin and laminin
What is the role of fibronectin and laminin in the ECM?
Provide cohesion between matrix components and cells
What are the 2 forms of ECM?
BASEMENT membrane
Interstitial matrix
What is the most common type pf ECM?
interstitial matrix
What is the basement membrane?
ECM ‘sheet’ that epithelial, endothelial and smooth muscle cells lie on
physical/chemical barrier, structural support, strength
Where is the interstitial tissue found?
found between cells within a tissue
Where is the interstitial matrix sparse?
nerves
Where is the interstitial matrix dense/abundant?
bone/cartilage
What is the role of the interstitial matrix?
provides adherence, structure - ‘glue’ holding cells together
protects against tissue compression
What does the ECM help regulate?
proliferation, differentiation, movement
What is the primary objective of wound healing?
fill the area of destroyed tissue
Is regeneration limited?
yes, can often form scar tissue
What are the 3 phases of wound healing?
inflammatory phase
proliferative
remodelling
What stage of wound healing is platelet activation occur?
first stage - inflammatory phase
clot
How log does the inflammatory phase last?
0-48hr
What WBC clear oput wound?
phagocytes and neutrophils
ingest debris and fibrin
What else do macrophages do in inflammatory phase?
stimulate angiogenesis
secrete growth factors that attract other cells
When does the proliferative phase occur?
48-3 weeks
What stage of wound healing do fibroblasts playa role?
proliferative phase (phase 2)
what recruits fibroblasts?
macrophages
What is the effect of fibroblasts secreting GF at wound?
angiogenesis
further fibroblast recruitment/ECM production
What is the pre-cursor to scar tissue?
granulation tissue
What phase of wound healing does granulation tissue form?
phase 2
proliferation phase
Describe granulation tissue?
moist, red connective tissue
What 2 processes are in involved in granulation tissue formation?
angiogenesis
fibrogenesis
What phase is inflammation no longer apparent?
late proliferative phase
phase 2
(few macrophages, no oedema)
When does late proliferative phase occur?
3 weeks
What cells persist at late proliferative phase?
fibroblasts
What are fibroblasts secreting in LPP?
collagen
strengthens ECM
What happens to granulation tissue in late proliferative phase?
migrates upward, leaving fibrous scar behind
less angiogenesis, vasculature degenerates, scar largely avascular
What is epithelialization?
upper epithelial layer proliferates
uses granulation tissue as matrix
seals wound with new epithelium
when does remodelling phase occur?
3-6 weeks
in remodelling phase, what do the fibroblasts secrete?
collagenase
what is the role of collagenase secreted by the fibroblasts?
break down collagen fibres
but not collapse the scaffold
remodel scar and shrink scar
in the remodelling phase, how does the scar shrink inwards?
myofibroblasts
contractile fibroblasts
helps remodelling
shrinks visible area
does the mature scar tissue have more of less collagen?
more
How long can the remodelling phase last?
up to 6 months
What has more ECM, repair or regeneration?
repair has more
What does regeneration have a higher emphasis on?
division of regenerating cells
What factors are required for wound healing?
nutrition
O2 and blood flow
immune and inflammatory function
What are factor which disrupt wound healing?
infection
separation (large loss of ECM)
foreign bodies
What are the 2 types of injury
primary and secondary intention
What controls proliferative phase?
growth factors
What is remodelling phase controlled by?
ECM
