MOD3 - A Deeper Look Into Inflammation KIN273 Click to edit...

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Click to edit Master subtitle style A Deeper Look Into:   KIN273 FEB 25, 2010 SPX075
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Review n Inflammation n provoked response to tissue injury n trauma  n invasion of pathogens, microbes, etc. n chemical agents, cold, heat, etc. n serves to  destroy, dilute or isolate the injurious agent n protective response n induces repair n potentially   harmful   
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Acute Inflammation n Series  of reactions of  vascularized tissue  to injury
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Acute Inflammation n Series of events  n Neurologic events n Hemodynamic events n Cellular events n Overlapping, inter-related n Predictable sequence n Magnitude of events depends on: n severity of injury
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Acute Inflammation – Neurologic events n Initial Vasoconstriction (~30 sec) n n Gradual Vasodilation n Relaxation of reflexive spasm n Causes “bleeding” to start n Accounts for warmth and redness n Increased intravascular pressure causes an early 
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Acute Inflammation – Hemodynamic events n Vasodilation n n Slowing of bloodflow n Relationship of flow to diameter n Margination of Leukocytes n Hemostasis n Permeability Changes
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Acute Inflammation – Hemodynamic events n Permeability Changes n Mostly from inflammatory chemicals n n Junctions between epithelial cells loosen n Fluid leaks (transudate       exudate) n Leads to hemoconcentration n Makes margination easier
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Vascular Permeability n Five mechanisms known to cause  vascular leakiness n Histamines, bradykinins, leukotrienes   cause an early, brief (15 – 30 min.)  immediate transient response  n Endothelial cell contraction  n widens intercellular gaps of venules
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Vascular Permeability n Cytokine mediators (TNF, IL-1)  induce  endothelial cell junction retraction through  cytoskeleton reorganization  n Typically at 4-6 hrs post-injury, lasting >24 hrs n Severe injuries may cause immediate  direct endothelial cell damage  (necrosis,  detachment) making them leaky until they  are repaired or may cause delayed 
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Vascular Permeability n Marginating and endothelial cell-adherent  leukocytes may pile-up and damage the  endothelium through activation and release  of  toxic oxygen radicals and proteolytic  enzymes  (i.e., leukocyte-dependent  endothelial cell injury) making the vessel  leaky
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Vascular Permeability n Certain mediators (VEGF)  may cause  increased transcytosis via intracellular   vesicles which travel from the luminal to  basement membrane surface of the  endothelial cell n Permeability changes may occur from  one or more of these
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n Mast Cells n Already present in connective tissue n Damage to connective tissue leads to 
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MOD3 - A Deeper Look Into Inflammation KIN273 Click to edit...

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