Acromegaly 19.07.08
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Acromegaly 19.07.08

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    Acromegaly 19.07.08 Acromegaly 19.07.08 Presentation Transcript

    • Wound Healing The Basic Principles
    •  
    • Wound healing Day 21 - 2yrs Remodelling Contracture Day 4 - 21 Proliferation Granulation Day 1 - 4 Inflammation Immediate Haemostasis Days post injury Phase of healing
    • Haemostasis
      • Sealing of damaged blood vessels
      • Vasoconstriction
      • Platelet –utility worker
      • Under the influence of the ADP, platelets aggregate and adhere to the exposed collagen. Intrinsic clotting cascade -> thrombin -> fibrinogen ->fibrin -> platelet aggregate into a stable haemostatic plug
    • Inflammatory phase
      • Characterised by “ rubor et tumor cum calore et dolore” – 4 days.
      • Polymorphonuclear leukocytes - non skilled laborers – phagocytize debri and microorganisms, aided by local mast cells.
      • Macrophages – contractor – phagocytize bacteria –second line of defence and secrete IMs and growth factors like FGF,EGF,TGF beta, IL-1 which appears to direct the next stage.
    • Proliferative phase (4 – 21 days)
      • Involves proliferation, granulation and contraction
      • Framers build the framework of the new house – “framer” cells – fibroblasts secrete collagen network – specialised fibroblasts -> wound contraction
      • The “plumber” cells , pericytes and endothelial cells -> angiogenesis
      • The “roofer” and “sider”cells - keratinocytes -> epithelisation
    • Remodelling or Maturation phase
      • Interior finishing Ξ Remodeling or Maturation -> ↑Tensile strength
      • The cell -> fibroblast
      • Results in scar – active dynamic tissue
      • Stage I (upto 4 wks) – soft, fine&weak
      • Stage II (4 – 12 wks)–red, hard & strong
      • Stage III (12wks to 2 yrs) – soft, white& supple scar
    •  
    • Platelets
      • Vessel damage
        • Platelet aggregation
        • Activation of coagulation cascade
        • Clot
        • Degranulation Inflammatory mediators
    • Neutrophils
      • Adhesion
      • Diapedesis
      • Migration by chaemotaxis
      • Phagocytose bacteria
      • Scavenge necrotic debris and foreign material
    • Monocytes
      • Monocyte MACROPHAGE
      • Phagocytose bacteria
      • Release of cytokines
      • Degradation of connective tissue
      • Stimulate angiogenesis
      • Inflammatory phase Reparative phase
    • Lymphocytes
      • Helper T cells
      • Produce chaemotactic factors like
        • IFN –r, IL – 2, CSF
      • Involved in chronic wound healing
    • Fibroblast
      • Synthesize
        • Collagen
        • Fibronectin
        • Protein
      • Fibroblast Myofibroblast Contraction
      Extracellular matrix
    • Angiocytes
        • Proliferation of endothelial cells
        • Formation of capillary buds
        • Angiogenesis
    • Keratinocytes
      • Migration Resurface the wound
      • Phagocytosis
      • Cytokine release
      • Reconstitution of basement membrane
      • Collagen secretion Anchoring fibrils
    • Healing responses Haemostsis Inflammation Proliferation Immediate Day 1 - 4 Day 4 - 21 Platelets Neutrophils Macrophages Lymphocyte Fibroblast Framers Contracture Angiocyte Plumber Keratinocytes Roofers & siders Utility worker Unskilled workers Contractor Asst. Contractor Remodeling Day 21–2 yrs Fibrocytes Remodelers
    •  
    • Matrix
      • Formation of fibrin plug marks the first stage of tissue repair
      • It serves as a provisional matrix
      • Provisional matrix replaced by mature matrix during proliferative phase
    • Matrix contd.
      • Matrix is composed of
        • Fibrous protein
        • Polysaccharide gel
          • Proteoglycans
          • Function
            • Permits difussion of nutrients to the cells
    • Matrix contd.
      • Fibrous protein has two parts
        • Structural part formed by collagen & elastin
        • Adhesive part formed by fibronectin and laminin
    • Fibronectin
      • Linear glycoproteins with modular cell/matrix binding structure
      • This structure encourages cell to cell & cell to substrate interaction
      • Fibronectin and its degradation products are chemo attractant
    • Collagen
      • They are the most abundant proteins in mammals
      • They are secreted by fibroblast
      • At least 13 types have been described
      • Type 1- 4 are most common
      • Rich in glycine and proline
    • Collagen contd.
      • During fibroblastic phase PDGF,TGF & EGF stimulate fibroblast
      • Initially type 3 is secreted in higher conc: (as in embryo)
      • Collagen degradation by collagenase occurs concurrently with collagen synthesis
    • Matrix metalloproteases
      • Comprise the core wound enzyme
      • Brings about wound remodelling by matrix degradation
      • Produced by fibroblast
      • Regulated by cytokines
      • Increased level is seen in chronic wounds
    • Factors affecting wound healing
      • Local factors
      • Infection
      • Blood supply
      • Foreign body
      • Tissue characteristics
      • Epithelium heals well
      • Nerve cells, cardiac muscle once
      • injured,do not heal
    • Factors affecting wound healing
      • Systemic factors:
      • Age
      • Nutrition
      • Haematologic disturbance
      • Diabetes
      • Renal failure
      • Jaundice
      • Malignancy
    • Systemic factors
      • Steroids
      • Immune deficiency
      • Cytotoxic drugs
      • Whole body irradiation
    • Nutrition & wound healing
      • Glucose
      • ATP, source of cellular energy
      • Diabetes impairs wound healing
      • Inhibits
        • Fibroblast
        • Endothelial cells
        • Leucocyte chaemotaxis
      • Components of phospholipid and prostaglandins
      • Phospholipid Cell membrane synthesis
      • Prostaglandins Important in inflammation
      • Deficiency of free fatty acids causes impaired wound healing
      Fats
    • Proteins
      • Deficiency causes
        • Impaired collagen deposition
        • Decreased wound breaking strength
        • Increased wound infection rates
        • Decreased angiogenesis
        • Decreased cellular replication
      • Glutamine
        • Most abundant amino acid
        • Essential for lymphocyte proliferation
        • Stimulates immune response
        • Precursor for synthesis of nucleotides in fibroblasts & macrophages
      Amino acids
    • Arginine
      • Enhances collagen deposition
      • Enhances wound breaking strength
      • Substrate for nitric oxide synthesis
      • NO important in wound healing
    • Vitamins
      • Vitamin A
        • Influence inflammatory response in wounds
        • Increase macrophage influx
        • Stimulates collagen synthesis, cross linking
        • Stimulates epithelialisation
    • Vitamins
      • Vitamin C deficiency
        • Impaired collagen synthesis & cross linking
        • Decreased angiogenesis
        • Haemorrhage
        • Susceptibility to infection
    • Vitamins
      • Vitamin E
        • Decreases excess scar formation
        • As an antioxidant
    • Micronutrients
      • Magnesium
        • Co-factor for protein synthesis
        • Provide structural stability to ATP & collagen synthesis
      • Zinc
        • Important in immune function
        • Deficiency causes wound infection
    • Iron
      • For hydroxylation of Proline & Lysine
      • Part of Oxygen transport system
      • Deficiency
        • Impaired collagen production
    • Diabetes Mellitus
      • Fibroblast & endothelial cells adversely affected
      • Collagen deposition reduced
      • Wound Remodelling reduced
      • Chaemotaxis & phagocytosis reduced
      • Renal failure-> adverse effect
    • Tissue ischemia
      • Tissue oxygen pr < 40mm hg
        • Delayed wound repair
      • Reduced collagen formation
      • Reduced cross linking
    • Tissue ischemia
      • Tissue O 2 pressure < 30 mm hg
      • Reduced killing of bacteria by phagocytosis
      • Inhibition of angiogenesis
      • Inhibition of epithelialisation
    • Wound debridement
      • Reduces effects of ischaemia on wound healing
      • Removes tissue laden with bacteria
    • Types of wound healing
      • Primary
      • Delayed primay
      • Secondary intention
    • Ideal wound dressing
      • Mechanical & bacterial protection
      • Moist environment
      • Facilitate epithelialisation
      • Allow gas & fluid exchange
      • Remain non adherent
    • Ideal wound dressing – contd.
      • Non toxic & non allergenic
      • Highly absorbable & sterile
      • Easy to use
      • Suitable forms & sizes should be available
      • Aesthetically attractive
      • Cost effective
    • Occlusive wound dressing
      • Non resorbable
      • Sterile or non sterile device
      • Covers the wound
      • Moist environment
      • Allow gas & fluid exchange
    • Advantages of occlusive dressings
      • ↓ dehydration and cell death
      • ↑ angiogenesis
      • Enhanced autolytic debridement
      • ↑ re – epithelisation
      • Bacterial barrier and ↓infection rates
      • ↓ Pain
      • ↓ Costs
    • Non biologic occlusive dressing
      • Films & foams
      • Hydrocolloids
      • Alginates
      • Hydrogels
      • Silicon gel coats
      • Octylcyano acrylate
    • Biologic Occlusive Dressing
      • Allograft
      • Xenograft
      • Amnion
      • Skin substitutes