Wound Healing :)

Wound Healing :)

1. 1. Vasospasm

   • Reflex induced by the pain receptors
   • Slows blood flow BUT arterial pressure maintained
     • 2. Vasoconstriction
       • Vasodilators inhibited
         • Nitrous Oxide
         • Prostacyclin
       • Increase in Endothelin
         • Vasoconstrictor
           • helps prevent blood loss
             • Need more stabilization
               • 3. Platelet Plug
                 • Requires platelets
                   • Myeloid Stem Cells
                     • Megakaryocytes
                       • 1000x Thrombocytes
                         • Produced in Red Bone Marrow
                           • Stimulated by thrombopoietin
                             • Liver and Kidneys produce thrombopoietin
                         • Have no nuclei
                         • Lightest and smallest in the blood
                         • are granulocytes
                 • temporary blood clot via 3 steps
                   • 1a. Adhesion
                     • Integrins bind to Collagen
                       • Integrins: on platelet surface
                       • Epithelium breaks
                         • Tunica Intima becomes exposed
                           • Collagen becomes exposed
                           • Von Willebrand Factor leaks in
                             • Von Willebrand Factor = glue of the platelet plug
                               • vWF from blood/plasma
                               • Binds to collagen and microfibrils
                                 • Binds to glycoprotein 1-B
                                   • on platelets surface
                                     • hence vWF captures platelets
                                       • 1b) Platelet activation
                                         • GP1-B conformational change
                                           • Degranulation
                                             • Alpha Granule
                                             • Dense Granule
                                             • Release
                                               • ADP
                                                 • Increased Platelet Aggregation
                                               • Calcium Ions
                                               • Serotonin
                                                 • Increased Vascular Spasm
                                               • Thromboxane (TXA2)
                                               • Platelet Derived Growth Factor (PDGF)
                                                 • 1c) Causes Platelet Aggregation
                                                   • Activated platelets latch onto other platelets and bring them together
                                                     • Further activation of platelets
                                                       • Temporary Clot formed
                                                         • Clot needs further stabilization
                                                           • 4. Coagulation Cascade
                                                             • 12
                                                               • 12a
                                                                 • 11
                                                                   • 11a
                                                                     • 9
                                                                       • 9a
                                                                         • 10
                                                                           • 10a
                                                                             • Prothrombin
                                                                               • Thrombin (2)
                                                                                 • Fibrinogen
                                                                                   • Loose Fibrin
                                                                                     • Tight Fibrin
                                                                                       • CLOT
                                                                                         • 5. Clot Stabilization
                                                                                           • Clot Contraction
                                                                                             • Clot Retraction
                                                                                               • Leads to serum being squeezed out of the clot
                                                                                               • Platelet Derived Growth Factor causes fibroblasts to form temporary connective tissue patch
                                                                                                 • Smooth muscle cells restore musculature
                                                                                                 • VEGF: Vascular Endothelial Growth Factor
                                                                                                   • Endothelial lining restored
                                                                                               • Need to remove Clot
                                                                                                 • 6. Anticoagulation Systems
                                                                                                   • Heparin
                                                                                                     • Produced by Mast cells in peripheral connective tissues
                                                                                                     • on endothelial cells
                                                                                                     • on basophils
                                                                                                     • Enhances Antithrombin III
                                                                                                       • Binds to thrombin
                                                                                                         • Inactivates Thrombin
                                                                                                           • Prevents further formation of fibrin
                                                                                                   • Tissue Plasminogen Activator
                                                                                                     • Thrombin activates
                                                                                                     • Factor 12 activates
                                                                                                     • Plasminogen
                                                                                                       • Plasmin
                                                                                                         • main fibrinolytic enzyme
                                                                                                           • directly degrades thrombus (clot)
                                                                                                         • Removes deoxygenated blood within clot
                                                                                                           • 7. Bruising
                                                                                                             • • Due to deoxygenated blood clot within skin/tissue
                                                                                                             • 7a. Breakdown of Hemoglobin
                                                                                                               • Red-Blue color
                                                                                                                 • 7b. Biliverdin
                                                                                                                   • Green color
                                                                                                                     • 7c. Bilirubin
                                                                                                                       • Yellow
                                                                                                                         • 7d. Hemosiderin
                                                                                                                           • Brown/Golden
                                                                                                                             • 8. Immune Response
                                                                                                                               • Mast cell degranulation
                                                                                                                                 • Release Histamine
                                                                                                                                   • Vasodilation
                                                                                                                                     • White blood cells arrive, etc. etc.
                                                                                                                                       • Platelets affect neutrophils: bring over to site of interest
                                                                                                                                       • Macrophages cause fibroblast proliferation/maturation
                                                                                                                                         • Fibroblasts lay down collagen
                                                                                                                                           • Lay down new tissue
                                                                                                                                             • Tissue Repair
                                                                                                                                               • 9. Proliferation Phase
                                                                                                                                                 • Form granulation tissue
                                                                                                                                                   • Pink Tissue
                                                                                                                                                     • Highly resistant to infection
                                                                                                                                                       • Organizational Stage
                                                                                                                                                         • Very basic capillaries
                                                                                                                                                           • 10. Angiogenesis
                                                                                                                                                             • need blood to heal
                                                                                                                                                               • New vessels branch off of pre-existing capillaries
                                                                                                                                                                 • 11. Epithelialization
                                                                                                                                                                   • Macrophage stimulation of fibroblasts
                                                                                                                                                                     • Release of FGF7 (fibroblast growth factor 7)
                                                                                                                                                                       • Stimulates keratinocyte proliferation
                                                                                                                                                                         • Keratinocyte migration upwards to build back tissue
                                                                                                                                                                           • 12. Tissue Maturation
                                                                                                                                                                             • 12a. Provisional Matrix
                                                                                                                                                                               • moves a lot
                                                                                                                                                                               • Original Collagen III
                                                                                                                                                                               • Fibrin
                                                                                                                                                                               • Plasmafibrinectin
                                                                                                                                                                               • 12b. remodels into Matrix
                                                                                                                                                                                 • sturdier
                                                                                                                                                                                 • Collagen I
                                                                                                                                                                                 • tougher skin
                                                                                                                                                                                   • 13. Scarring may occur
                                                                                                                                                                                     • SCAR
                                                                                                                                                                                       • usually via Deep Injury
                                                                                                                                                                                       • usually lies underneath skin
                                                                                                                                                                                       • severe--> "tight white line" appearance
                                                                                                                                                                                         • HOW: myofibroblasts lining edge of the wound contract
                                                                                                                                                                                           • THE END!!!
                                                                                                                                                             • VEGF (Vascular Endothelial Growth Factor) promotes
                                                                                                                                                             • Endostatin (anti-VEG) inhibits
                                                                                                                                       • Macrophages release 1L-6
                                                                                                                                         • Proinflammation
                                                                                                                                 • Release Bradykinin
                                                                                                                                   • Increased vascular permeability
                                                                                                           • Phagocytic cells also remove
                                                                                                   • Thrombomodulin
                                                                                                     • binds to thrombin
                                                                                                       • Converts thrombin so that it doesn’t make fibrin anymore
                                                                                                   • Fibrin
                                                                                                     • Down regulates thrombin's positive feedback loop
                                                                                                   • Protein C
                                                                                                     • cleaves factor 5
                                                                                                   • Protein S
                                                                                                     • cleaves factor 8
                                                                                 • Factor 13
                                                                                 • Cleaves fibrinogen into fibrin
                                                                             • 5
                                                                               • Calcium
                                                                                 • Platelet Factor 3 (PF3)
                                                                           • 3
                                                                             • Tissue Thromboplastin
                                                                               • released when tissue damaged
                                                                           • 7
                                                                             • Calcium
                                                                           • Limiting Factor
                                                                         • 8
                                                                           • Calcium
                                                                             • Platelet Factor 3 (PF3)
                                                                     • 4
                                                                       • Calcium
                                                             • "Hemostasis"
                                                             • Minerals and Calcium needed to make factors
                                                               • factors are in blood
                                                                 • Liver makes most factors
                                                   • Aggregation also attracts white blood cells to the site