Inflammation

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Inflammation

  1. 1. INFLAMMATIONINFLAMMATIONDr Sapna MDr Sapna MDept pathologyDept pathologySNIMS,KERALASNIMS,KERALA
  2. 2. INFLAMMATIONINFLAMMATION
  3. 3. INFLAMMATIONINFLAMMATION• Protective response intendedto eliminate initial cause of cellinjury , necrotic cells andtissues resulting from originalinsult
  4. 4. Introduction:Introduction:• “Inflame” – to set fire• Inflammation is “dynamicresponse of vascularisedtissue to injury.”
  5. 5. -itis-itisAppendicitisAppendicitisCellulitisCellulitisMeningitisMeningitisPneumonitisPneumonitisNephritisNephritisMyocarditisMyocarditis
  6. 6. TYPES OF INFLAMMATIONTYPES OF INFLAMMATION• ACUTE• CHRONIC
  7. 7. Acute Inflammation-FeaturesAcute Inflammation-Features• Rapid onset• Short duration( mts. to few days)• Fluid , plasma protein exudation• Neutrophil accumulation
  8. 8. ChronicChronic Inflammation-FeaturesInflammation-Features• Onset- insidious• Longer duration (days to years)• Lymphocytes ,macrophages ,plasmacells• Vascular proliferation & fibrosis(scarring)
  9. 9. HEAT REDNESS SWELLING PAIN LOSS OF5 Cardinal Signs of Inflammation5 Cardinal Signs of Inflammation
  10. 10. 4 cardinal clinical signs of inflammation4 cardinal clinical signs of inflammationdescribed by Celsus, 1 A.D.:described by Celsus, 1 A.D.:• Rubor - redness• Tumor - swelling• Calor - heat• Dolor - pain• Virchow added a fifth--loss offunction(functio laesa)
  11. 11. Steps Of Inflammatory ResponseSteps Of Inflammatory Response• Remembered as five Rs:• (1) Recognition of injurious agent• (2) Recruitment of leukocytes• (3) Removal of agent• (4) Regulation of response• (5) Resolution (repair).
  12. 12. •ACUTE INFLAMMATION
  13. 13. Stimuli for Acute InflammationStimuli for Acute Inflammation• Infections (b, v, f, p)• Trauma• Physical & chemical agents• Tissue necrosis (MI)• Foreign bodies• Immune reactions
  14. 14. Acute Inflammation-componentsAcute Inflammation-components
  15. 15. Acute Inflammation-componentsAcute Inflammation-components
  16. 16. ACUTE INFLAMMATIONACUTE INFLAMMATIONVascular changes Cellular events•VasodilationIncreased vascular permeability.
  17. 17. Acute Inflammation-componentsAcute Inflammation-components• 1.Vascular changes:• Vasodilation• ↑ vascular perm.• 2.Cellular events• Cellular recruitment & activation
  18. 18. VASCULAR CHANGESVASCULAR CHANGES• 1.Changes In Vascular Caliber And Flow• Transient vasoconstriction (sec.)• Arteriolar vasodilation( rednesswarmth)
  19. 19. • ↑ bld flow & engorgement capillary beds↓protein-rich fluid moves into EVtissues↓RBCs conc., ↑ blood viscosity↓Stasis↓margination of neutrophils
  20. 20. ACUTE INFLAMMATIONACUTE INFLAMMATION• 2. ↑ Vascular Perm.{ mechanisms }• 1.Endothelial cell contraction–immediate transient response:reversible process, by histamine,bradykinin, leukotrienes ,15-30 min.2 .Retraction of EC: TNF and IL-1, 24 hours or more
  21. 21. ↑↑ Vascular Permeability{ mechanisms }Vascular Permeability{ mechanisms }• 3.Endothelial injury-immediate sustained response , delayedprolonged leakage• 4.Leukocyte-mediated endothelial injury• 5.Increased transcytosis• 6.Leakage from new blood vessels.
  22. 22. EXUDATE : INFLAMMATIONEXUDATE : INFLAMMATION
  23. 23. • 1.Vascular changes:• Vasodilation• Increased vascular permeability.
  24. 24. Cellular Events: LeukocyteCellular Events: LeukocyteRecruitment and ActivationRecruitment and Activation
  25. 25. Leukocyte RecruitmentLeukocyte Recruitment• 4 steps1. Margination, rolling, andadhesion2. Diapedesis (transmigrationacross endothelium)3. Migration toward chemotacticstimulus - Chemotaxis4. Phagocytosis
  26. 26. Neutrophil MarginationNeutrophil Margination
  27. 27. ROLLINGROLLING::Leukocytes tumble on endothelialsurface, transiently sticking alongthe way• Mediated by SELECTIN family ofadhesion molecules• 3 members of this family
  28. 28. SELECTINSSELECTINS• E-selectin (CD62E) on EC• P-selectin (CD62P) EC & platelets• L-selectin (CD62L) leukocytes• Selectins bind sialylatedoligosaccharides ( sialyl-Lewis Xon leukocytes)
  29. 29. ROLLINGROLLING
  30. 30. ADHESION & TRANSMIGRATIONADHESION & TRANSMIGRATION• Adhesion mediated by integrins• Activated by chemokines• TNF and IL-1 activate EC to ↑expression of ligands for integrins
  31. 31. ADHESIONADHESION
  32. 32. Ligands For IntegrinsLigands For Integrins• ICAM-1(intercellular adhesion molecule1)- binds integrins LFA-1 (CD11a/CD18)and Mac-1 (CD11b/CD18),• VCAM-1 (vascular cell adhesionmolecule1)- bind integrin VLA-4
  33. 33. DIAPEDESISDIAPEDESIS
  34. 34. DIAPEDESISDIAPEDESIS
  35. 35. DIAPEDESISDIAPEDESIS• Leukocytes migrate thr’u vessel wall bysqueezing between cells at IC junctions• Mediated by PECAM-1 (plateletendothelial cell adhesion molecule 1(CD31) on leukocytes & EC
  36. 36. CHEMOTAXISCHEMOTAXIS• Leukocytes migrate toward sites ofinfection or injury along a chemicalgradient• Chemotactic substances(1) bacterial products (2) cytokines(3) C5a (4) LTB4.
  37. 37. 6 to 24 hours 24 to 48 hours
  38. 38. LEUKOCYTE ACTIVATIONLEUKOCYTE ACTIVATION
  39. 39. LEUKOCYTE ACTIVATIONLEUKOCYTE ACTIVATION• Leukocytes receptors sensing p/omicrobes:–Toll-like receptors (TLRs) - LPS–Seven-transmembrane G-protein-coupled receptors - bacterialpeptides and mediators
  40. 40. PHAGOCYTOSISPHAGOCYTOSIS• 3 steps• (1) recognition and attachment ofparticle to ingesting leukocyte• (2) engulfment & formation ofphagocytic vacuole• (3) killing and degradation of ingestedmaterial.
  41. 41. (1)(1) Recognition & attachment ofRecognition & attachment ofparticle to ingesting leukocyteparticle to ingesting leukocyte• Opsonins : host proteins that coatmicrobes and target them forphagocytosis (opsonization).• Leukocytes express receptors foropsonins
  42. 42. OPSONISATION RECEPTORS
  43. 43. OPSONINS RECEPTORS FOROPSONINSIgG FcγRIBreakdownproducts of C3CR1 and 3Collectins C1q
  44. 44. 2.ENGULFMENT2.ENGULFMENT & FORMATION& FORMATIONOF PHAGOCYTIC VACUOLEOF PHAGOCYTIC VACUOLE
  45. 45. 3.Killing and Degradation of Microbes3.Killing and Degradation of Microbes• Important microbicidal substances :reactive oxygen species (ROS) andlysosomal enzymes• ROS• HOCl• (hypochlorous radical)•Superoxide radicals(superoxide,H2O2, and OH•).• Reactive nitrogen species( NO)
  46. 46. Lysosomal enzymesLysosomal enzymes• Lysosomal acid hydrolases-degradedead microorganisms• Elastase - kill bacteria
  47. 47. Defects in Leukocyte FunctionDefects in Leukocyte Function• Common causes• BM suppression ( tumors CT,RT)- ↓leukocyte no.• Diabetes - abnormal leukocytefunction
  48. 48. Defects in leukocyte function:Defects in leukocyte function:• Margination and adhesion–Etoh, steroids, AR leukocyte adhesiondeficiency• Emigration toward a chemotactic stimulus–drugs–chemotaxis inhibitors• Phagocytosis–Chronic granulomatous disease(CGD) :phagocyte oxidase generating ROS
  49. 49. Defects in leukocyte function:Defects in leukocyte function:• Myeloperoxidase (MPO) deficiency:Absent MPO-H2O2 system• Chédiak-Higashi syndrome :impairfusion of lysosomes with phagosomes
  50. 50. ACUTE INFLAMMATION - THREEACUTE INFLAMMATION - THREEOUTCOMESOUTCOMES• Resolution• Progression to chronic inflammation• Abscess• Scarring or fibrosis
  51. 51. Acute inflammationChronic inflammationRepairResolutionAbscessInjury
  52. 52. MORPHOLOGIC PATTERNS OFMORPHOLOGIC PATTERNS OFACUTE INFLAMMATIONACUTE INFLAMMATION• SEROUS INFLAMMATION• Watery, protein-poor fluid .Serum/secretions of mesothelial cells• Skin blister• Fluid in a serous cavity - effusion.
  53. 53. SEROUS INFLAMMATIONSEROUS INFLAMMATION
  54. 54. FIBRINOUS INFLAMMATIONFIBRINOUS INFLAMMATION• Severe injuries, ↑ vascular perm. &fibrinogen pass• Histology: eosinophilic meshworkof threads or amorphous coagulum• Site : Lining of body cavities• Resolution• Organization & scarring
  55. 55. SUPPURATIVE (PURULENT)SUPPURATIVE (PURULENT)INFLAMMATIONINFLAMMATION• Purulent exudate (pus) -neutrophils, necrotic cells, andedema fluid• Staphylococci – pyogenic• Completely walled off ,replaced byconnective tissue.
  56. 56. ABSCESSESABSCESSES• Focal collections of pus• Central, large necrotic regionrimmed by neutrophils(surrounded by vessels andfibroblastic proliferation )
  57. 57. ABSCESSESABSCESSES
  58. 58. ABSCESSESABSCESSES
  59. 59. ULCERULCER• Local defect / excavation, surface of anorgan/ tissue prod. by necrosis of cells& sloughing of inflammatory necrotictissue• Sites (1)mucosa of GIT( Peptic ulcer),GUT• (2) Lower extremities, older personswith circulatory distur.
  60. 60. CHEMICAL MEDIATORS OFCHEMICAL MEDIATORS OFINFLAMMATIONINFLAMMATIONCELL DERIVED
  61. 61. CHEMICAL MEDIATORS OFCHEMICAL MEDIATORS OFINFLAMMATIONINFLAMMATIONPLASMA PROTEIN DERIVED
  62. 62. CHEMICAL MEDIATORS OFCHEMICAL MEDIATORS OFINFLAMMATIONINFLAMMATION• CELL-DERIVED MEDIATORS• VASOACTIVE AMINES• 1.HISTAMINE released by• (1) physical injury• (2) immune reactions• (3) Anaphylatoxins:C3a and C5a• (4) leukocyte-derived histamine-releasingproteins• (5) neuropeptides• (6) IL-1 and IL-8
  63. 63. HISTAMINEHISTAMINE• Action: arteriolar dilation , ↑ vascularperm.• Inactivated by histaminase• SEROTONIN (5-hydroxytryptamine)effects similar to histamine
  64. 64. CELL DERIVED –NEWLYCELL DERIVED –NEWLYSYNTHESISEDSYNTHESISED
  65. 65. Arachidonic Acid Metabolites:Arachidonic Acid Metabolites:((eicosanoidseicosanoids))• Sources: Leukocytes, mast cells, EC,platelets• 2 major enzymatic pathways:• Cyclooxygenase• Lipoxygenase• Cyclooxygenase : prostaglandins andthromboxanes• Lipoxygenase: leukotrienes and lipoxins
  66. 66. Arachidonic Acid (AA) MetabolitesArachidonic Acid (AA) Metabolites• CYCLOOXYGENASE PATHWAY• Products :PGE2, PGD2, PGF2α,PGI2 (prostacyclin), TXA2• TXA2: Platelets - thromboxanesynthase ,platelet-aggregatingagent and vasoconstrictor
  67. 67. CYCLOOXYGENASE PATHWAYCYCLOOXYGENASE PATHWAY• PGI2 : EC - prostacyclin synthase ,vasodilator and inhibitor of plateletaggregation• PGD2: mast cells; + PGE2 & PGF2αcauses vasodilation & edema• PGE2 : pain sensitivity, fever.
  68. 68. LIPOXYGENASE PATHWAYLIPOXYGENASE PATHWAY• 5-Lipoxygenase :AA-metabolizingenzyme in neutrophils• 5-HPETE (5-hydroperoxyeicosatetraenoic acid)• Reduced to 5-HETE (5-hydroxyeicosatetraenoic acid) - chemotactic forneutrophils• or converted into leukotrienes
  69. 69. Lipoxygenase Pathway- LeukotrieneLipoxygenase Pathway- Leukotriene• LTA4 gives rise to LTB4 or LTC4• LTB4: chemotactic agent forneutrophils• LTC4 , LTD4 & LTE4: mast cells ,cause vasoconstriction,bronchospasm, ↑ vascular perm.
  70. 70. LIPOXINSLIPOXINS• Inhibitors of inflammation• Endogenous antagonists ofleukotrienes.
  71. 71. Principal Inflammatory Actions ofPrincipal Inflammatory Actions ofAA MetabolitesAA Metabolites• Vasodilation:PGI2 (prostacyclin),PGE1, PGE2, PGD2• Vasoconstriction:Thromboxane A2,leukotrienes C4, D4, E4• ↑ vascular perm. :Leukotrienes C4,D4, E4 & PGE2, PGD2• Chemotaxis, leukocyte adhesion:Leukotriene B4, 5-HETE
  72. 72. Cyclooxygenase enzyme -COXCyclooxygenase enzyme -COX• Two forms : COX-1 and COX-2• COX-1 : gastric mucosa, PGsprotective against acid-induceddamage.• COX inhibitors :Aspirin ,NSAIDs: treatpain and fever
  73. 73. Platelet-Activating FactorPlatelet-Activating Factor• Stimulate platelets• Vasoconstriction & bronchoconstriction• Vasodilation & ↑vascular perm.• Leukocyte adhesion, chemotaxis,degranulation, oxidative burst• Synthesis of mediators , (eicosanoids).
  74. 74. CytokinesCytokines• Polypeptide products .Mediators ofinflammation and immune responses• Molecularly characterized cytokines -interleukins• A/c inflam : TNF, IL-1, chemokines• C/C inflam: IFN-γ , IL-12.
  75. 75. CHEMOKINESCHEMOKINES• 2 functions : leukocyte recruitment ininflam. & N anatomic organization of cellsin lymphoid and other tissues• Four groups• Two major groups• CXC :IL-8• CC chemokines:MCP-1 , MIP-1α,RANTES (regulated on activation normalT expressed and secreted) and eotaxin .
  76. 76. Reactive Oxygen Species (ROSReactive Oxygen Species (ROS• Synthesized via NADPH oxidase(phagocyte oxidase) pathway• Action (1) endothelial damage, withthrombosis & ↑ perm.• (2) protease activation andantiprotease inactivation• (3) direct injury to other cells• Catalase, SOD, glutathione -↓ toxicity
  77. 77. NONO• Synthesized from l-arginine, molecularO2, NADPH by enzyme NOS.• 3 isoforms of NOS• Type I (nNOS)• Type II (iNOS) present in macrophages& EC induced by IL-1, TNF,IFN-γ,bacterial endotoxin• Type III (eNOS)
  78. 78. Nitric OxideNitric Oxide
  79. 79. NO -NO -FunctionsFunctions• (1) vasodilation (endothelium-derivedrelaxation factor)• (2) antagonism all stages of plateletactivation(a,a,d)• (3) reduction of leukocyte recruitmentat inflammatory sites• (4)Microbicidal agent
  80. 80. Lysosomal Enzymes of LeukocytesLysosomal Enzymes of Leukocytes• Acid proteases:acidic pH optima ,active within phagolysosomes• Neutral proteases: elastase,collagenase , cathepsin, active inECM• Cleave C3 & C5 to C3a & C5a• Generate bradykinin-like peptidesfrom kininogen.
  81. 81. AntiproteasesAntiproteases• α1-antitrypsin-major inhibitor ofneutrophil elastase• α2-macroglobulin• α1-antitrypsin deficiency - lung ,panacinar emphysema
  82. 82. NeuropeptidesNeuropeptides• Small proteins, such as substance P• Transmit pain signals• Regulate vessel tone• Modulate vascular permeability• Lung and GIT- Nerve fibers secrete NP
  83. 83. PLASMA PROTEIN-DERIVEDPLASMA PROTEIN-DERIVEDMEDIATORSMEDIATORS• 3 systems– Complement– Kinin– Coagulation
  84. 84. ComplementComplementImmunity and inflammation• Opsonize particles: phagocytosis anddestruction• ↑ vascular perm. & vasodilatation• Leuko. chemotaxis• Generates MAC (C5b-9)
  85. 85. ComplementComplement
  86. 86. Critical steps : activation of C3Critical steps : activation of C3• (1) Classical pathway : fixation of C1to antig-antib complexes• (2) Alternative pathway: bacterialpolysaccharides / microbial cell-wallcomponents, involve properdin andfactors B , D• (3) Lectin pathway: plasma lectinbinds mannose residues on microbes, activates early component of CP
  87. 87. ComplementComplement• 3 pathways form C3 convertase :cleavesC3 to C3a and C3b• C3b deposits on cell or microbial surface• Binds to C3 convertase complex to formC5 convertase• C5 convertase cleaves C5 → C5a & C5b• Initiate final stages of assembly of C6 toC9• Thrombin : cleave C5
  88. 88. ComplementComplement• 1.Anaphylatoxins: C3a and C5a↑vascular perm. and vasodilation ,inducemast cells to release histamine.• 2.C5a: activates lipoxygenase pathway• 3.Leukocyte activation, adhesion, andchemotaxis. C5a• 4.Phagocytosis: C3b & iC3b act asopsonins• 5.Lysis of microbes - MAC
  89. 89. Coagulation and Kinin SystemsCoagulation and Kinin Systems• 4 systems activated by Hagemanfactor (factor XIIa)• (1) Kinin system• (2) Clotting system• (3) Fibrinolytic system• 4) Complement system.
  90. 90. Coagulation and Kinin SystemsCoagulation and Kinin Systems
  91. 91. Clotting SystemClotting System• Factor Xa: ↑ vascular perm. and leuk.Emigration• Thrombin : leuk. Adhesion• Fibrinopeptides :↑ vascular perm. andchemotactic for leuk.
  92. 92. FIBRINOLYTIC SYSTEMFIBRINOLYTIC SYSTEM• FDP : ↑ vascular perm.• Plasmin :cleaves C3 to C3a causingvasodilation and ↑ vascular perm.
  93. 93. KININ SYSTEMKININ SYSTEM• Bradykinin :↑ vascular perm, arteriolardilation, bronchial smooth musclecontraction, pain• Kallikrein: chemotactic activity
  94. 94. Role of Mediators in DifferentRole of Mediators in DifferentReactions of InflammationReactions of Inflammation• 1.Vasodilation:Prostaglandins, Nitric oxide Histamine• 2.↑ vascular perm:Histamine and serotoninC3a and C5aBradykininLeukotrienes C4, D4, E4PAFSubstance P
  95. 95. Mediators in InflammationMediators in Inflammation• 3. Leukocyte recruitment andactivationTNF, IL-1ChemokinesC3a, C5aLeukotriene B4Bacterial products, e.g., N-formylmethyl peptides
  96. 96. Mediators in InflammationMediators in Inflammation• 4. FeverIL-1, TNF, PG• 5. PainPG, Bradykinin, Neuropeptides• 6. Tissue damageLysosomal enzymes , ROS,Nitric oxide
  97. 97. CHRONIC INFLAMMATIONCHRONIC INFLAMMATION• Prolonged duration .Activeinflammation, tissue injury & healingsimultaneously• Characterized by• Infiltration with mononuclear cells• Tissue destruction• Repair : angiogenesis and fibrosis
  98. 98. Chronic InflammationChronic Inflammation• Time course:–> 48 hours (weeks, months, years)• Cell type–Mononuclear cells (Macrophages,Lymphocytes, Plasma cells)
  99. 99. Chronic InflammationChronic Inflammation• Histology :– L,M,P– Fibroblasts & small BV– ↑ CT– Tissue destruction
  100. 100. MACROPHAGESMACROPHAGES• Derived from circulatingblood monocytes• SITES:• Connective tissues• Liver (Kupffer cells)• Spleen & LN (sinushistiocytes)• CNS( microglial cells)• Lungs (alveolarmacrophages)•Mononuclearphagocytesystem(RES)
  101. 101. MACROPHAGESMACROPHAGESFUNCTION–Filters: particulate matter,microbes,senescent cells–Alert T and B lymphocytes toinjurious stimuli• Lymphocytes, Plasma Cells,Eosinophils, and Mast Cells
  102. 102. Settings For Chronic InflammationSettings For Chronic Inflammation• 1.Microbes difficult to eradicateMycobacteria, Treponema pallidum ,viruses and fungi• 2.Immune-mediated inflammatorydiseases : RA ,IBD, Asthma• 3.Toxic agents :Silica, atherosclerosis
  103. 103. GRANULOMATOUS INFLAMMATIONGRANULOMATOUS INFLAMMATION• Distinctive pattern of chronicinflammation• Characterized by aggregates ofactivated macrophages that assumean epithelioid appearance
  104. 104. Diseases with GranulomatousDiseases with GranulomatousInflammationInflammation• Tuberculosis :M. tuberculosis• Noncaseating tubercle : a focus ofepithelioid cells, rimmed by fibroblasts,lymphocytes, histiocytes, occasionalgiant cells• Caseating tubercle: central amorphousgranular debris, loss of all cellular detail;acid-fast bacilli
  105. 105. LANGHANS GIANT CELLS - HORSE SHOE SHAPE
  106. 106. LANGHANS GIANT CELL
  107. 107. Granulomatous InflammationGranulomatous Inflammation• Leprosy• Mycobacterium leprae• Acid-fast bacilli in macrophages;noncaseating granulomas• Syphilis:Treponema pallidum,Gumma
  108. 108. Granulomatous InflammationGranulomatous Inflammation• Cat-scratch disease :Gram-negativebacillus , Rounded or stellategranuloma• Sarcoidosis : Unknown etiologyNoncaseating granulomas• Crohn disease :Immune reactionagainst intestinal bacterial, self-antigens noncaseating granulomas
  109. 109. Foreign body granulomas.Foreign body granulomas.
  110. 110. EPITHELIOID CELLSEPITHELIOID CELLS• Elongated, finely granular, paleeosinophilic cytoplasm• Nucleus:central, oval orelongate,small nucleoli ,slippershaped• Indistinct shape , merge to formaggregates.
  111. 111. • Lymphocytes secrete cytokines →macrophage activation• Multinucleated giant cells• Hypoxia and free-radical injury leads tocaseous necrosis• Healing of granulomas accompaniedby fibrosis
  112. 112. SYSTEMIC EFFECTS OFSYSTEMIC EFFECTS OFINFLAMMATIONINFLAMMATION• ACUTE-PHASE REACTION/ SYSTEMICINFLAMMATORY RESPONSESYNDROME.• TNF, IL-1, and IL- 6
  113. 113. Clinical And Pathologic ChangesClinical And Pathologic Changes-APR-APR• 1.Fever- pyrogens –stimulate PGsynthesis in hypothalamus
  114. 114. LPS(EX .P)LUECOCYTES(IL-1 &TNF)ENDO.PAAPG(PGE2)STIMULATE NEUROTRANSMITTERSRESET TEMP.↑ CYCLOOXYGENASE
  115. 115. 2.Acute-phase proteins2.Acute-phase proteins• 2.Synthesized in liver• Up-regulated by IL-6• I) CRP II) Fibrinogen III)Serum amyloid A(SAA) protein.• Fibrinogen cause rouleaux- ↑ ESR• CRP: ↑ risk of MI or stroke in pts. withatherosclerotic vascular disease
  116. 116. 3. Leukocytosis• TNF & IL-1-release cells from BM .Shift to left• CSFs - ↑ output of leukocytes from BM• Neutrophilia , lymphocytosis ,eosinophilia , leukopenia
  117. 117. Other manifestationsOther manifestations• ↑ heart rate and BP• ↓ sweating• Rigors (shivering)• Chills• Anorexia, somnolence & malaise:cytokines on brain cells• Chronic inflammation: wasting syndromecalled cachexia, TNF- mediated appetitesuppression & mobilization of fat stores
  118. 118. SEPTIC SHOCKSEPTIC SHOCK• High levels of TNF cause DIC,hypoglycemia, and hypotensiveshock.
  119. 119. 1.A 65-year-old woman had fever the past day.On physical examination her temperature is 39 Cand blood pressure 90/50 mm Hg with heart rateof 106/minute. A blood culture is positive forEscherichia coli. Her central line pressure fallsmarkedly. She goes into hypovolemic shock as aresult of the widespread inappropriate release of achemical mediator derived from macrophages.Which of the following mediators is most likely toproduce these findings?A Nitric oxideB BradykininC HistamineD ProstacyclinE Complement C3a
  120. 120. 2.The major difference between atransudate and an exudate is(A) transudate has proteins whereasexudate is essentially devoid of proteins(B) both these are only seen during acuteinflammatory processes(C) both are associated with a Suppurativeor Purulent inflammatory process(D) transudate is associated with serousinflammation whereas exudate isassociated with fibrinous inflammation
  121. 121. 3.Granulomatous Inflammation isassociated with which of the followinga. distinct acute inflammatoryprocessb. distinct chronic inflammatoryprocessc. persistent B-cell response tocertain microbesd. IgM mediated response
  122. 122. 4.Which of the following is/are consideredan anaphylatoxins(s)(A) lipoxins(B) leukotrines(C) C3a(D) IL-1 and TNF
  123. 123. 5.What is the most common form ofincreased vascular permeabilityassociated with acute inflammation(A) direct endothelial injury(B) endothelial cell retraction(C) endothelial cell contraction(D) leukocyte-dependent endothelialdamage
  124. 124. 6.Endothelial cell contraction &retraction occur ina) Postcapillary venulesb) Capillariesc) Arteriolesd) All of the above

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