1. What is inflammation
    response to injury by vascularized living tissue
  2. What can elicit inflammation
    • microbial infection
    • physical agents, chemicals, necrotic tissue, immune reaction
  3. Role of inflammation
    • contain and isolate injury
    • destroy microorganisms
    • inactivate toxins
    • prepare tissue for healing and repair
  4. Characteristics of inflammation
    • two main; vascular wall response and inflammatory cell response
    • termination when invader is eliminated
  5. General acute inflammation
    • early onset
    • short duration
    • fluid exudation, edema
    • nutrophil migration
  6. General chronic inflammation
    • later onset, days
    • longer duration, weeks to years
    • involves lymphocytes and macrophages
    • new blodd vessels
    • scaring
  7. four signs of inflammation
    • heat
    • redness
    • edema
    • pain
  8. Exudate
    • extravascular fluid of a high protein concentration
    • SG above 1.02
  9. Purulent
  10. Transudate
    • extravascular fluid with little protein
    • SG below 1.012
  11. Vascular change with acute edema
    • Dilation; causes increased flow and increased hydrostatic pressure
    • increased vascular permeability; causes exudation
    • Net fluid outflow
    • stasis can occur with a large fluid lose increasing viscosity and slowing blood flow; allows white cells to accumulate and begin to migrate
  12. Pathways to increased vascular permeability
    • venule gaps; endothelial cells contract ( histamine immediate, IL1 and TNF in 4-6 hours)
    • Direct endothelial injury; burns, affects arterials capillaries and venues
    • delayed prolonged leakage; 2-12 hour delay, ;sat for days, sunburn and X-rays, venules and capillaries
    • Leukocyte mediated endothelial injury; release of oxygen species
    • increased transendothelial channels; VEGF
    • leakage from new vessels; angiogenesis results in leaky vessels until the vessel matures
  13. Three steps of extravasation
    • margination
    • transmigration; diapedesis
    • migration; chemotaxis
  14. Selectins bind to
    • sailyl lewis X, GP
    • P selectin glicoprotein ligand, PSGL-1
    • LFA-1 and MAC-1 / VLA4
    • intigrens
    • ICAM leukocytes
    • VCAM eosinophils, monocytes, lymphosytes
  16. PECAM
    • CD32
    • leukocyte migration through endothelium
  17. Affects of chemokines and cytokines
    • redistribution of preformed adhesion molecules to cell surface
    • induction of adhesion molecules on endothelium, IL1 and TNF increase endothelial expression of selections and intigrins
    • Increased avidity to binding; most imoirtant fo intigrens
  18. Steps of neutrophil transmigration
    • endothelial activation; increase selection expression, IL1 and TNF
    • rolling; helped by blood stasis,
    • integrin activation and stable binding, cytokines increase integrin avidity
    • transmigration, PECAM platelet endothelial cell adhesion molecule
  19. What cell emigrates to site of inflammation acute/chronic
    • neutrophile / macrophage
    • 6-24h / 24-48h
  20. Chemotaxic cell receptors
    • G protein coupled
    • activates phospholipase c, increase in DAG and IP3, increased calcium, increased GTPase activity, activates movement by pseudopods
  21. Toll like receptors
    involved in leukocyte activation and response to microbes
  22. Two major benefits of neutrophils and macrophages at inflammation site
    phagosytosis and enzyme release
  23. Two major opsonins
    C3b, Fc fragment
  24. Three steps of phagocytosis
    • recognition
    • engulfment
    • killing
  25. Two components of the oxygen burst
    • H2O2, NADPH oxidase
    • HOCl, myloperoxidase
  26. Lysosomal enzymes may be released outside the cell
    • frustrated phagocytosis
    • premature fusion of forming phagosome with lysosome
    • damage by ingested material, urate crystals
  27. LAD-1
    • leukocyte adhesion deficiency
    • defective synthesis of LFA-1 and MAC-1 (Beta1 intigrens)
  28. LAD-2
    • loss of silly lewis X
    • selectin ligand
  29. Chediak-Higashi syndrome
    Defective lysosome enzyme delivery to phagosome
  30. Chronic granuloma disease
    inherent defect in NADPH oxidase
  31. Termination of acute response
    • Mediators are only produced in quick bursts and have short half lives
    • anti-inflammatory cytokines TGF-B
  32. Vasoactive Amines
    • histomine, seritonin
    • Increased vascular permeability
    • mast cells, basophils and plts
    • Mest cell release by IgE, C3a, C5a, IL1 and IL8
    • platelet release by ADP, collogen, thrombin, PAF
  33. Most important step in compliment
    • activation of C3
    • C3 convertase
    • Classical pathway, C1 fixation to antigen
    • Alternative pathway, microbial surface endotoxin
    • Lectin pathway, C1 is activated by mannose binding
  34. Membrane attack complex
    C3b cleaves C5 to C5 a and b, C5b binds to 6-9 forming MAC
  35. Two biologic functions of compliment
    • MAC induced cell lysis
    • Compliment incduced canges in vascular permability, chemotaxis, opsinization
  36. C3a and C5a
    • anaphalatoxins
    • stimulate histamine release from mast cells
    • increase vascular permeability and vasodilation
  37. Two regulators of compliment
    • DAF, decay regulating factor
    • C1 inhibitor
  38. Paroxysmal nocturmal hemoglobinuria
    • Defercts in DAF
    • recurrent compliment mediated red cell lysis and anemia
  39. Hereditary angioneurotic edema
    • C1 inhibitor defect
    • life threatening edema
  40. Kinin system
    • kininogens are cleaved by kallikreins to generate bradykinin
    • causes vasodilation, increased vascular permeability, and pain
    • Initiated by factor XIIa
    • Also activates factor XII
  41. Clotting system is linked to inflammation
    thrombin causes leukocyte adhesion to endothelium
  42. How does plasmin contribute to inflammation
    • cleaves C3
    • forms fibrin split products, increased vascular permeability
    • activates XII
  43. Products of cyclooxygenase
    prostaglandins and thromboxanes
  44. Lipoxygenase products
    leukotrienes and lipoxins
  45. Leukotrien B4
  46. Leukotriene C,D,E
    • vasoconstrict
    • broincospasm
    • increase permeability
  47. Lipoxin
    • vaso dilate
    • inhibits neutrophil chemotaxis
    • stimulates monocyte adhesion
    • regulate leukotriene action
  48. Prostaglandin E2
    increase sensitivity to pain and metiate fever
  49. Platelet activating factor
    • from mast cells and other leukocytes
    • pltelet aggregation
    • bronchospasm
    • vasodilation
    • increased vascular permeability
    • increased leukocyte adhesion and chemotaxis
    • All cardinal features of inflammation
  50. Two major inflammation mediators
    IL1 and TNF, induce enothelial activation
  51. Cachexia
    • pathogenic state of weight lose and anorexia
    • mediated by TNF and IL1
  52. Chemokines
    • CXC; recruit neutrophiles
    • CC; monocytes, eosonophiles, bsophiles, lymohocytes
    • C; lymphocytes
    • G protein receptors
  53. NO
    • synthesized in macrophages and endothelium
    • IF1
    • major pathogenesis of septic shock
  54. ROS protection
    • catalase
    • superoxide dismutase
    • glutathione peroxidase
  55. Supstance P
    • Neuropeptide
    • mediator of vascular permeability
    • transmites pain
  56. Hypoxia induced factor 1
  57. Vasodilation
    • prostoglandin
    • NO
    • Histamine
  58. Increased vascular permeability
    • Vasoactive amines
    • C3a, C5a
    • bradykinin
    • leukotriene C, D, E
    • PAF
    • Substance P
  59. Chemotaxis
    • Leukotriene B
    • chemokines
    • IL1, TNF
    • Endotoxin
  60. Fever
    • IL1,
    • TNF
    • Prostoglandins
  61. Pain
    • Prostglandins
    • bradykinin
  62. Tissue damage
    • neutrophil and macrophage
    • lysosomal enzymes
    • oxygen metabolites
    • NO
  63. Three outcomes of acute inflammation
    • resolve
    • healing by scar tissue, fibrosis, when healing occurs in non regenerating tissues
    • progression to chronic
  64. Serous inflamation
    • reflected by tissue fluid accumulation
    • modest increase in vascular permeability
    • burn blisters
  65. Fibrous inflammation
    • more marked increase in vascular permeability
    • exudate containing large amounts of fibrinogen
  66. Suppurative or Purulent inflammation
    pus consisting of leukocytes and necrotic cells
  67. Abscess
    localization of purulent inflammation accompanied by liquefaction necrosis (staphylococcal abscess)
  68. Ulcers
    Local erosions of epithelial surfaces
  69. Chronic inflammation
    When active inflammation, tissue distraction, and healing are all going on at the same time
  70. Typical chronic inffammation
    • Infiltration with mononuclear inflammatory cells; macrophages, lymphocytes, plasma cells
    • tissue distruction
    • Healing, connective tissue replacement and angiogenesis
  71. Dominant cell type of chronic inflammation
  72. Two factors that activate macrophages
    endotoxins, IF
  73. Macrophage products that damage host tissue
    • NO,
    • reactive oxygen
    • proteases
  74. What produces INF
  75. eotoxin
    • cc chemokin
    • recroutes eosonphiles
  76. What leads to mast cell degranulation
    binding IgE
  77. Granulomatous inflammation
    • focal accumulation of macrophages; become enlarged and flattened and called epotheliod macrophages
    • macrophages are surrounded by lymphocytes secreting IFN
    • may form giant cells
    • Can form around inert objects
    • In tuberculosis the granuloma has caseous necrosis
  78. Lymphagitis
    inflammed lymphatics
  79. Lymphadenitis
    inflammed lymph node
  80. Systemic inflammatory response syndrome
    • fever; IL1/TNF stimulate cyclooxygenase to produce prostaglandin's, prostoglandins induce cAMP in the hypothalamus that resets the temp
    • Acute phase proteins; c reactive protein, fibrinogen, amyloid a. bind to microbial wall and act as opsonins
    • Leukocytosis; increase white cell count,
  81. Defective inflammation
    • increased susceptibility to infection and delayed healing
    • Inflammation is essential for clearing damaged tissue
  82. Inheritence patern of NADPH oxidase disease
    X linked
  83. excessive inflammation
    • allergies
    • autoimmune
    • fibrosis
Card Set
Robbins chapter 2