Dist of Circulation, Inflammation, Healing/Repair, Shock

  1. Platelet contents
    • Integrin membrane receptors, p-selectin
    • arachidonic acid (Thromboxane A2)
    • alpha granules
    • electron dense bodies
  2. Alpha granules in platelets (7)
    • fibrinogen
    • fibronectin
    • factor V
    • factor VIII
    • thrombospondin
    • PDGF
    • TGF-B
  3. Electron dense bodies in platelets (5)
    • ADP
    • Ca2+
    • Histamine
    • serotonin
    • epinephrine
  4. Platelet Aggregators (6)
    • ADP and Thromboxane A2
    • Thrombin
    • Collagen
    • Epinephrine
    • Immune complexes
    • platelet activating factor
  5. Platelet adhesion steps
    • von Willebrand's factor binds subendothelial collagen
    • platelets bind von Willebrand's factor via gpIb surface integrins
  6. Promote platelet aggregation producing primary hemostatic plug
    ADP and Thromboxane A2
  7. Promotes further platelet aggregation and polymerizes fibrin
    Thrombin
  8. This links platelets with adjacent platelets during aggregation
    Fibrinogen binding
  9. Endothelial pro-coagulant factors (5)
    • von Willebrand's factor - synthesize it
    • Tissue factor - express in response to cytokines and endotoxin
    • binding sites for activated clotting factors
    • platelet activating factor
    • tissue type plasminogen activating factor - inhibits fibrinolysis
  10. Endothelial cell anti-coagulant factors
    • cover thrombogenic subendothelial collagen
    • NO & PGI2 - inhibit platelet aggregation
    • Antithrombins
    • plasminogen inhibitors (and activators)
  11. Blood anticoagulant factors
    • Antithrombins
    • Proteins C & S
  12. Processes of thrombosis inhibition (3)
    • Heparin-like surface molecules activate antithrombin - thrombin inactivated
    • Thrombomodulin binds thrombin and activates proteins C & S - cleave factors V & VIII
    • NO & PFI2 inhibit platelet aggregation
  13. Where is plasminogen located?
    Plasma and platelet membranes
  14. Steps of plasminogen-plasmin system (3)
    • Plasminogen binds fibrin
    • cleaved by plasminogen activators to form plasmin
    • plasmin digests polymerized fibrin
  15. Plasminogen activators (2)
    • tissue type plasminogen activator (endothelial cells)
    • urokinase like plasminogen activator (plasma)
  16. Released during arteriolar constriction
    epinephrine
  17. causes vasodilation of venules
    histamine
  18. Relaxes vascular smooth muscle
    • bradykinin
    • prostaglandins
  19. Chemical mediators of vascular permeability (6)
    • vasoactive amines (5-HT, serotonin, histamine)
    • kinins
    • complement
    • arachidonic acid mediators (prostaglandins)
    • cytokines
    • platelet activating factor
  20. Inflammatory exudate that is thin and watery
    serous
  21. inflammatory exudate containing mucus
    catarrhal
  22. exudate containing abundant fibrin
    fibrinous
  23. Sequence of WBC Emigration
    • Neutrophils within 1 hr
    • Macrophages after 12 - 48 hrs
    • Lymphocytes - slow to enter
  24. Suppurative inflammation is dominated by
    neutrophils
  25. purulent inflammation of connective tissues
    cellulitis
  26. fluctuant pocket of pus in subcutis
    phlegmon
  27. purulent inflammation of fascia
    fasciitis
  28. local collection of pus
    abscess
  29. accumulation of pus in body cavity
    empyema
  30. How long do neutrophils last in the circulation?
    8 hrs
  31. First line of defense
    neutrophils
  32. Neutrophils have what kind of metabolism
    glycolytic (anaerobic)
  33. Neutrophils release (3)
    • enzymes
    • antimicrobial molecules
    • pro-inflammatory mediators
  34. Neutrophil granule contents (among others) (13)
    • cd18/11b - integrin adhesion molecule
    • complement receptor 1
    • CD14 (endotoxin receptor)
    • Gelatinase
    • cytochrome B
    • lysozyme
    • collagenase
    • elastase
    • lactoferrin
    • myeloperoxidase
    • defensins
    • acid hydrolases
    • cathepsins
  35. 4 main types of proteases
    • Serine
    • Metallo-
    • Cysteine
    • Aspartic
  36. Protease important in wound healing and cancer metastasis
    Metallo
  37. Inhibits all 4 protease classes
    Alpha 2 macroglobulin
  38. Inhibit serine proteases
    serpins
  39. antiplasmin, plasminogen activator inhibitor, antithrombin III are examples of
    serpins
  40. TIMPs stands for
    Tissue inhibitors of matrix metalloproteinases
  41. Avian, reptile and rabbit equivalent of the neutrophil
    heterophils
  42. Eosinophilic inflammation occurs when?
    • allergic/hypersensitivity reactions
    • fungal infections
    • parasitic infections
  43. Eosinophil granules do what?
    inactivate mast cell derived mediators
  44. Eosinophil granules contain (3)
    • major basic protein
    • arylsulfatase
    • enzymes
  45. Mast cell granules stain metachromatically with
    toluidine blue
  46. Mast cell granules contain
    • histamine
    • proteolytic enzymes
    • anticoagulants (heparin & chondroitin sulfate)
    • chemotactic factors for EOS & Neutrophils
  47. These are the circulating counterpart of mast cells (only in blood)
    basophils
  48. Types of mature monocytes (6)
    • alveolar
    • pulmonary intravascular
    • microglia
    • kuppfer
    • epithelioid
    • multinucleate giant cell
  49. Macrophage metabolism
    oxidative respiration (cannot function in dead tissue)
  50. Monocytes/Macrophages produce (6)
    • Lysosomal proteases & hydrolases
    • reactive oxygen species
    • complement components
    • arachidonic acid mediators
    • cytokines
    • growth factors
  51. Chronic inflammatory process with immune component
    lymphocytic inflammation
  52. These mediate vascular changes in inflammation
    platelets
  53. Platelets secrete (5)
    • histamine
    • thromboxane A2
    • p-selectin
    • growth factors
    • enzymes
  54. Endothelial cells & fibroblasts secrete
    • cytokines
    • growth factors
    • proteases
  55. Fibroblasts secrete
    ECM components
  56. What cells regulate clotting?
    endothelial cells
  57. Major players in inflammation
    • Platelets
    • endothelial cells
    • fibroblasts
    • neutrophils, monocytes/macrophages, mast cells, etc.
  58. Sequence of events in leukocyte efflux from vasculature (5)
    • Margination - slow blood flow
    • Rolling - selectins
    • Adhesion & Pavementing
    • Transmigration - integrins
    • Migration in tissue - integrins/chemotaxins
  59. These are involved in recirculation of lymphocytes to lymphnodes
    Addressins
  60. Chemotactic molecules (5)
    • c5a
    • bacterial products
    • leukotrienes
    • fibrin degredation products
    • WBC products (IL-8)
  61. Phagocytic events (4)
    • opsonization
    • attachment
    • ingestion
    • killing & degradation
  62. These coat particles to be opsonized (4)
    • C3b
    • Immunoglobulin (antibodies)
    • lysozyme
    • fibronectin
  63. hernia in non-natural opening
    eventration
  64. Steps in Killing/Digestion during phagocytosis
    • phagosome & lysosome fuse - degranulation
    • phagolysosome becomes acidified
    • respiratory burst
  65. components of oxygen-independent killing of a microbe within a phagolysosome (6)
    • Acidic phagolysosomal environment
    • BPI - phospholipase activated membrane degradation Bactericidal permeability increasing molecule
    • Defensins - cationic cytotoxic peptides
    • Lysozyme - hydrolyzes bacterial coat
    • Lactoferrin - sequesters iron
    • Nramp-1 – Pumps Fe out of the phagosome
  66. The first step in Oxygen-dependent killing of a microbe in a phagolysosome
    NADPH oxidase reduces oxygen to superoxide
  67. After the superoxide is formed within the phagolysosome, subsequent reactions form these oxygen based radicals (4)
    • hydrogen peroxide
    • hydroxyl radical
    • singlet oxygen
    • secondary reactive nitrogen oxides
  68. Myeloperoxidase-halide system forms
    hypohalous acids
  69. Myeloperoxidase-independent systems rely on
    oxygen based radicals
  70. Neutrophil-mediated tissue damage is caused by (3)
    • lysosomal suicide
    • frustrated phagocytosis
    • regurgitation while feeding
  71. Example of frustrated phagocytosis of neutrophils
    degranulation against immune complex deposited in glomerular basement membrane
  72. Regurgitation while feeding is a result of what
    asynchronous phagolysosome fusion
  73. Hallmark of chronic inflammation is
    neovascularization & fibrosis with macrophages
  74. Macrophage accumulation during chronic inflammation is due to
    • continued recruitment
    • local proliferation (mitosis in tissues)
    • immobilization at site
  75. Macrophages are continually recruited during chronic inflammation by (4)
    • C5a
    • chemokines
    • growth factors
    • fibrin degradation products
  76. Immobilization of macrophages is done by what factor?
    Migration Inhibition Factor
  77. A granuloma consists of
    • epithelioid macrophages
    • lymphoid cells
    • peripheral fibrosis
  78. Two types of granulomas
    • foreign body
    • immune granuloma
  79. Two mechanisms of healing and repair
    • parenchymal regeneration
    • replacement by fibrous tissue
  80. Fibrosis occurs when (3)
    • stromal framework destroyed
    • permanent cell population destroyed
    • exudate cannot be reabsorbed
  81. Two factors affecting healing
    • stromal integrity
    • regenerative capacity of tissue
  82. Populations of cells that are constantly being replaced are called
    labile
  83. Populations of cells that undergo mitosis are called
    stable
  84. Growth factors involved in wound healing (6)
    • epidermal
    • Platelet derived
    • transforming
    • fibroblast
    • macrophage-derived -wound contraction
    • Vascular endothelial GF - angiogenic
  85. Three phases of granulation tissue formation
    • Inflammatory phase
    • Proliferative phase 
    • remodeling phase
  86. Cells of granulation tissue (3)
    • macrophages
    • fibroblasts
    • endothelial cells
  87. What do macrophages do in granulation tissue?
    • remove exudate
    • secrete fibrogenic & angiogenic factors
  88. Zones of granulation tissue (4) and features of each
    • Zone of necrotic debris - fibrin, neutrophils, blood clots
    • Zone of capillary sprouts + arches - macrophages
    • Zone of capillary proliferation - proliferating towards surface, fibroblasts
    • Zone of Mature connective tissue - fibroblasts
  89. Phases of wound healing (6)
    • 1. Inflammation
    • 2. Cell migration
    • 3. Matrix deposition
    • 4. Vascular proliferation
    • 5. Collagen synthesis
    • 6. Remodeling
  90. Adverse outcomes of healing (5)
    • Adhesion
    • Ankylosis
    • Stricture
    • contracture
    • critical tissue replaced by scar tissue
  91. Reduction of lumen size during healing is called
    stricture
  92. Fixation of a joint during healing
    ankylosis
  93. A fibrous adhesion is composed of
    • collagen
    • fibroblasts
    • blood vessels
  94. These adhesions can be broken
    fibrinous adhesions
  95. Plasma derived mediators of inflammation (3)
    • Hageman Factor - clotting factor
    • Complement components
    • Kininogens - become kinins and increase vascular permeability
  96. Activated in first step of intrinsic coagulation cascade by negatively charged surfaces
    Hageman factor
  97. Hageman factor initiates generation of these 4 processes
    • Clotting
    • fibrinolysis
    • kinin generation
    • complement cascade
  98. Actions of kinins
    • vasodilation
    • increased vascular permeability
    • pain
  99. Cell-derived mediators of inflammation
    • Histamine & serotonin (preformed)
    • Arachidonic acid derivatives (newly synthesized)
  100. Histamine and Serotonin are stored in granules of these cells (3)
    • mast cells
    • basophils
    • platelets
  101. Arachidonic acid is formed by
    phospholipases acting on cell membranes
  102. Arachidonic acid can be converted into (2)
    • Cyclooxygenase
    • Lipoxygenase
  103. This form of cyclooxygenase is constitutively expressed
    Cox 1
  104. Steroids inhibit
    phospholipase
  105. What does Prostacyclin do?
    • vasodilation
    • inhibits platelet aggregation
  106. What does Thromboxane A2 do?
    • causes vasoconstriction
    • promotes platelet aggregation
  107. Cyclooxygenase products (3)
    • Prostacyclin
    • Thromboxane A2
    • Prostaglandins (vasodilation)
  108. Lipoxin formation requires
    contact between pmn & platelet in presence of a clot
  109. Lipoxins resolve injury and promote healing by (2)
    • decreasing pmn adhesion & chemotaxis
    • promote monocyte adhesion
  110. lipid, derived from most inflammatory cells, produces all cardinal signs of inflammation
    Platelet Activating Factor
  111. Reactive Oxygen Species is produced by
    activated phagocytes
  112. What does ROS do? (3)
    • Damage
    • activates neutrophils
    • increases vascular permeablility
  113. Cytokine classes (5)
    • regulate lymphocytes
    • natural immunity
    • activate inflammatory cells
    • stimulate hematopoiesis
    • chemokines
  114. Chemokine really important for recruiting neutrophils
    IL-8
  115. Causal classifications of Shock
    • Hypovolemic
    • Neurogenic
    • Cardiogenic
    • septic
  116. Phases of shock
    • 1. Nonprogressive
    • 2. Reversible
    • 3. Irreversible
  117. What happens during the nonprogressive stage of shock
    • baroreceptor reflexes
    • catecholamine release
    • RAAS
    • ADH release
    • Resulting in: tachycardia, peripheral vasoconstriction, decreased urine output
  118. What happens in the reversible stage of shock
    • Hypoxemia leads to acidosis which blunts vasomotor responses
    • Arterioles dilate, blood pools in microcirculation resulting in worsened hypotension
    • widespread cell injury and DIC
    • Organs begin to fail, myocardial contractility decreases
    • Confusion
  119. Cytokine storms beginning with LPS binding
    • LPS binds TLR
    • TNF release
    • IL-1 release
    • Il-6/8 release
    • NO, PAF release
Author
kenleyc
ID
317797
Card Set
Dist of Circulation, Inflammation, Healing/Repair, Shock
Description
BOD exam 2
Updated