Wound healing Flashcards by Liz Mahon

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

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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

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phases of corneal laceration

immediate phase
leukocytic phase (30mins)
epithelial phase (1hr)
fibroblastic phase
endothelial phase (24hrs)
late phase (after 1 week)

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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

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leukocytic phase in corneal laceration

Leukocytic phase (within 30 minutes):
 PMLs invade wound from conjunctival vessels and aqueous

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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

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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

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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

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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

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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

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slcearal healing

scares formed by proliferation of episclearal fibroblasts
Does not heal by itself
Acellular and avascular
Granulation tissue derived from choroid and episclera

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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

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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

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lens healing

doesn’t heal
just turns into cataract

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retina healing

damaged nerve cells are replaced by glial cells

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choroid healing

melanocytes don’t proliferate, scar tissue in the choroid is derived from sclearal fibroblasts

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optic nerve healing

axonal loss and demyelination

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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