PATHOLOGY - Wound Healing and Thrombosis Flashcards
What are the main steps involved in full thickness skin laceration healing? (4)
- Initial inflammatory response
- Epidermis epithelialisation
- cell migration stimualted by fibronectin
- cell proliferation (inhibited by chalones)
- cell differentiation - Vascularisation
- intact capillaries at wound edges release endothelial cells
- new vessels appear within first week - Wound Closure
- Macrophages migrate into wound and stimulate clot removal
- Fibroblasts migrate into wound and stimulate collagen and GAG production
- Myofibroblasts cause wound contraction
What are the main phases involved in full thickness corneal laceration healing?
- Immediate phase (Minutes)
- Descemet’s and stromal collagen retract causing anterior and posterior gaping
- Fibrin plug forms from aqueous firbinogen
- Stromal oedema occurs - Leukocytic phase (30 mins)
- Polymorphic leukocytes invade wound from conjunctival vessels and aqueous - Epithelial phase (Hours)
- Epithelial ingrowth - healthy endothelium prevents full thickness ingrowth by contact inhibition
- Epithelial downgrowth syndrome occurs with damaged endothelium which allows lens remnants and vitreous to enter wound - Fibroblastic phase (hours)
- Transformation of leukocytes and stromal keratocytes into fibroblasts
- Fibroblasts produce collagen and mucopoly-saccarides into the matrix
- The epithelium then retreats anteriorly and starts regeneration
- myofibroblasts close the wound. - Endothelial phase (after 24 hours)
- Endothelial sliding and mitotic/amitotic multiplication to cover posterior aspect of the wound - filling in gaps in descemet’s membrane and endothelium - Late phase (1 week)
- Cellular infiltrate diminishes
- Collagen fibres arranged uniformly
- Stroma and Bowman’s replaced by scar tissue
- normal corneal thickness returns at 4-6 weeks
What is the role of fibroblast growth factor in wound healing? (4).
- Monocyte chemotaxis
- Fibroblast migration and proliferation
- Angiogenesis
- Collagenase secretion
To overall remodel connective tissue and parenchymal constituents.
What is the process of scleral healing?
Does not actively heal - wounds are closed by granulation tissue derived from episclera and underlying uvea.
What is the process of iris healing?
Only heals if wound edges directly opposed - fibrinolysin in aqueous prevents fibrin clot formation across a wound.
PIs/iridectomies remain patent
What is the process of ciliary body / choroidal healing?
Heals with granulation tissue and replaced by scar tissue
What is the process of lens healing?
Responds to trauma with cataract formation
What is the process of retinal healing?
- Gliosis - replacement of nerve cells by glial cells by astrocytes/Muller cells
- RPE undergoes metaplasia and proliferation to form fibrous tissue
- Extensive gliosis/fibrosis leads to PVR (in retinal detachment)
What is the differences in mechanism between 5-FU and mitomycin C?
5-FU: competitively inhibits thymidylate synthetase in S phase so prevents DNA synthesis. This prevents fibroblast proliferation for 4-6 weeks when given during glaucoma filtration surgery. Can cause corneal epithelial toxicity.
Mitomycin-C: anti-proliferative at any stage of cell cycle but maximally in G and S phases. 100 times more potent than 5-FU on fibroblasts to permanantly inhibit their proliferation (but not migration). Does not cause corneal epithelial toxicity.
What type of agent is mitomycin-C? What is it derived from?
Antiproliferative alkylating agent derived from streptomyces caespitosus
What is the structure of a platelet?
- Peripheral zone: rich in glycoproteins and platelet factor 3 for adhesion and aggregation
- Structural zone: microtubules and microfilaments to maintain discoid shape
- Organelle zone: alpha granules and other granules containing clotting mediators
- Inner membrane zone: Dense tubular system for contractility and prostaglandin synthesis
What is the process of thrombosis (3).
- Endothelial exposure
Endothelial collagen and fibrin exposure leads to platelet adhesion to endothelium via glycocalyx signalling - Calcium release and coagulation cascade
Calcium released from platelets dense tubular system leading to their degranulation –> this releases factor V and fibronogen which form thrombin via the coagulation cascade - Platelet aggregation
Platelet aggregartion stimulated by ADP and thrombin so platelets form a clump.
Aggregation stimulated by thromboxane A2
Aggregation inhibited by prostaglandin I2 - Thrombus formation - these can break and form emboli or be lysed by plasmin
What are the inhibitory factors of thrombosis?
- Protein C - vitamin K dependent inhibitor of Factor 5a and Factor 3a. Factor 5 Leiden leads to resistance of factor 5 to activate protein C
- Protein S - phospholipid are co-factors in factor 5a and Factor 8a deactivation
- Antithrombin 3 inhibits many activated coagulation factors
What are the common components/material of retinal emboli? (4)
- Cholesterol - hollenhorst plaque
- Calcium - BRAO/CRAO
- Platelets - fibrin/platelet emboli cause TIAs
- Bacteria/vegetations - infective endocarditis
What is the process of atherosclerosis? (4)
- Endothelial damage
- Platelet response to injured endothelium
- platelet-derived growth factor release causing intimal smooth muscle proliferation
- Lipid accumulation as macrophages become foam cells and lipid accumulation within arterial wall.
