Wound healing Flashcards
Full thickness skin laceration healing
Initial inflammatory response
Epidermis epithelialisation:
Cell migration stimulated by fibronectin
Cell proliferation (inhibited by chalones)
Cell differentiation
Vascularisation
Intact capillaries at wound edges send out buds of endothelial cells
New vessels appear within first week
skin wound closure
Macrophages and fibroblasts migrate into wound
Macrophages: clot removal
Fibroblasts: collagen and GAG production
Myofibroblasts can cause wound contraction
Scarring may affect function of the structure
Matrix metalloproteinases are essential for collagen degradation and act on
fibronectin, laminin and other extracellular components
phases of corneal laceration
immediate phase
leukocytic phase (30mins)
epithelial phase (1hr)
fibroblastic phase
endothelial phase (24hrs)
late phase (after 1 week)
immediate phase in corneal laceration
Descemet’s membrane and stromal collagen retract causing anterior and
posterior gaping
Fibrin plug forms from aqueous fibrinogen
Stromal oedema
leukocytic phase in corneal laceration
Leukocytic phase (within 30 minutes):
PMLs invade wound from conjunctival vessels and aqueous
epithelial phase in corneal laceration
Epithelial phase (1 hour): epithelial ingrowth. Contact inhibition by healthy
endothelium prevents full thickness ingrowth. Epithelial downgrowth syndrome:
Damaged endothelium
Lens remnants in wound
Vitreous in wound
fibroblastic phase in corneal laceration
Fibroblasts are derived from invading leukocytes and stromal keratocytes in
central wounds
Produce collagen and mucopolysaccharides into matrix
As this occurs, the epithelium retreats anteriorly
endothelial phase in corneal laceration
(after 24 hours):
Endothelial sliding and mitotic/amitotic multiplication to cover the posterior
aspect of the wound: filling in gaps in DM and endothelium
late phase in corneal laceration
Cellular infiltrate diminishes
Collagen fibres arrange uniformly
Stroma and Bowman’s are replaced by scar tissue (cannot regenerate)
Descemet’s membrane cannot regenerate either but during endothelial sliding,
cells deposit secondary layers in DM
fibroblast growth factor
Crucial role in wound healing
Remodels connective tissue and parenchymal constituents
Collagenisation and acquisition of wound strength
Monocyte chemotaxis, fibroblast migration and proliferation, angiogenesis,
collagenase secretion
slcearal healing
scares formed by proliferation of episclearal fibroblasts
Does not heal by itself
Acellular and avascular
Granulation tissue derived from choroid and episclera
corneal healing
healing usually leads to corneal opacity (because of loss of the alignment of collagen)
corneal epithelium regenerates from the limbus
bowman’s layer and decements do not regenerate
stromal keratocytes transform into fibroblasts and myofibroblasts to heal stromal wounds
iris wound healing
doesn’t heal
presence of fibrinolysins in the aqueous inhibits fibrin clost formation so scar tissue doesn’t form
May get iris pigment proliferation 2nd to trauma
lens healing
doesn’t heal
just turns into cataract
retina healing
damaged nerve cells are replaced by glial cells
choroid healing
melanocytes don’t proliferate, scar tissue in the choroid is derived from sclearal fibroblasts
optic nerve healing
axonal loss and demyelination
5-fu
converted intracellularly to active form (FdUMP)
Competitively inhibits thymidylate synthetase in S phase cells so impedes DNA
synthesis
Metabolites are also incorporated into DNA to render it unstable and interfere
with RNA processing
adverse effect of 5-fu
corneal epithelial toxicity
how long does 5-fu last
Inhibits fibroblast proliferation for 4-6 weeks when given during glaucoma
filtration surgery
mitomycin-c
alkylating agent with antibiotic and antineoplastic properties
derived from Streptomyces caespitosus
Antiproliferative on cells at any stage of the cell cycle but maximal in G and S
phases
100 times more potent than 5FU on fibroblasts and permanently inhibits their
proliferation (but does not inhibit their migration)
Not usually associated with epithelial toxicity
stages of atheroscleorsis
- vascular endothelial damage
- platelet adhesion to endothelium (mainly stimulated by platelets), smooth muscle proliferation
- Endothlial cell barrier breaks down leading to intra and extra-cellular lipid accumulation
- fomation of fibrolipid or atheroscleortic plaque
platelet zones
peripheral zone
sol-gel zone
organelle zone
inner membrane zone
platelet zones -peripheral zone
Rich in glycoproteins and platelet factor 3 for adhesion and aggregation
platelet zones - sol-gel zon
Microtubules and microfilaments to maintain discoid shape
platelet zones - organelle zone
Alpha granules and other granules containing mediators of clotting (factor VIII
related antigen, factor V, fibrinogen, fibronectin, platelet-derived growth factor,
chemotactics)
platelet zones - inner membrane zone
Dense tubular system for contractility and prostaglandin synthesis
thrombosis
Endothelial collagen and fibrin exposure leads to platelet adhesion to endothelium
via glycocalyx signalling
Calcium is released from platelets dense tubular system leading to their
degranulation (releasing factor V and fibrinogen which form thrombin via the
coagulation cascade)
Aggregation is then stimulated by ADP and thrombin: platelets form a clump
inhibition of thrombosis
Protein C: vitamin-K dependent inhibitor of factors Va and VIIIa. Protein C
deficiency is autosomal dominant trait
o Factor V Leiden leads to resistance of factor V to activated protein C (may
contribute to 12% of patients with CRVO)
Protein S and phospholipid are cofactors in factor Va and VIIIa deactivation.
Protein S deficiency is also autosomal dominant
Antithrombin III inhibits numerous activated coagulation factors
thrombi may
- break and form emboli
- be lysed by plasmin
- persist and become orgainsed (flow my be re-established by collateralisation / recanalisation)
retinal emboli
Most commonly originate from an atheromatous plaque at the carotid bifurcation
Cholesterol (Hollenhorst plaque)
Calcium: tend to cause more extensive pathology: BRAO, CRAOs
Platelets: fibrin-platelet emboli cause TIAs
Bacteria/vegetations: infective endocarditis
stem cells
Initially arise during the embryonic period and then produce daughter cells
Multipotent: may give rise to many different types
Unipotent: limbal stem cells can only give rise to corneal epithelial cells
Stem cells are found in specific sites within tissues
epidermal growth factor
Epidermal growth factor: autocrine control of corneal epithelial turnover
Stimulates corneal epithelial migration and proliferation
transforming growth factor beta
three isoforms and many roles
Inhibits epithelial proliferation
Transdifferentiation of conjunctival to corneal epithelium
Proliferation of stromal fibroblasts
Increased collagen synthesis
platelet derived growth factor
limbal stem cell proliferation
fibroblast growth factor
epithelial and fibroblast proliferation
extra-cellular matrix - laminin
Located in basal lamina
Re-synthesised within 48 hours of corneal trauma under migrating cells
extra-cellular matrix - fibronectin
Found on the stromal side of Descemet’s membrane
Promotes adhesion between cells via integrins
Stimulated by EGF and TGF
Deposited on bare stromal surface within moments of epithelial injury to act as
a temporary scaffold
extra-cellular matrix - intergrins
Transmembrane glycoproteins present in almost all cells
Mediate cell-ECM and cell-cell attachments
Can also convey biochemical signals
Disruption of normal integrin-ECM interactions prevents normal eye
development
giant cells
three types: langhan’s, FB giant cell, touton’s cell
langhan’s cells
: horseshoe ring of nuclei. Seen in GCA, sarcoidosis, sometimes
TB
FB giant cells
central nuclei that overlap
touton’s cells
proliferation of non-Langhans histiocytes. Ring of nuclei
enclosing central eosinophilic cytoplasm from peripheral clear cytoplasm.
Formed by fusion of epithelioid cells. Seen rarely in xanthogranuloma
