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Inflammation / dental courses

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The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
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Inflammation / dental courses

  1. 1. INFLAMMATION Enflammare Set a fire INDIAN DENTAL ACADEMY Leader in continuing Dental Education www.indiandentalacademy.com
  2. 2. 1. INTRODUCTION 2. HISTORY 3. CAUSES 4. CARDINAL SIGNS 5. TYPES OF INFLAMMATION 6. ACUTE INFLAMMATION VASCULAR EVENTS CELLULAR EVENTS www.indiandentalacademy.com
  3. 3. 7. CHEMICAL MEDIATORS 8. MORPHOLOGICAL PATTERNS OF ACUTE INFLAMMATION 9. CHRONIC INFLAMMATION 10. SYSTEMIC EFFECTS OF INFLAMMATION 11.REGULATORS OF INFLAMMATION 12. FACTORS DETERMINIG VARIATIONS IN RESPONSE www.indiandentalacademy.com
  4. 4. Introduction Defined as “Local response of living tissues to injury due to any agent”  Fundamentally protective response  Ultimate goal is to get rid of intial cause cell injury(microbes, toxins)  Consequence of such injury(necrosis, tissues)  without inflammation wounds go unchecked, never heal www.indiandentalacademy.com
  5. 5. HISTORICAL HIGHLIGHTS 3000B.C Egyptians first described 1st century Celsus described cardinal signs 1793 John hunter inflammation not disease, non specific response that has salutary effect on host 1839 Conheihm used microscope to observe changes in vessels www.indiandentalacademy.com
  6. 6. 1880 Metchinkoff discovered phagocytosis Paul ehrlich proposed humoral theory of immunity 1908 Both got nobel prize 1924 Lewis explained role of chemical mediators in inflammation www.indiandentalacademy.com
  7. 7. Pioneers of inflammation www.indiandentalacademy.com
  8. 8. EVOLUTION OF INFLAMMATION Sponges , coelenterates body cavity is filled with coelum, cells are called coelomocytes Mollusca , urochordates body cavity is filled With hemocele, cells are hemocytes Amebocytes are seen in urochordates www.indiandentalacademy.com
  9. 9. Invertebrates respond to local injury by Phagocytosis Encapsulation(similar to granuloma formation) Neutralization of noxious stimuli by hypertrophy of cells Chemical mediators are also seen in some invertebrates A F Rowley The evolution of inflammation ; journal of inflammation vol-5 1996 www.indiandentalacademy.com
  10. 10. CAUSES OF INFLAMMATION LIVING Bacteria Viruses Mycoplasma Fungi Protozoa Parasites www.indiandentalacademy.com
  11. 11. Non living Trauma - osteomyelitis Heat – burns Ionizing radiation Uv light, infared Chemicals , acids, alkalies Foreign body Idiopathic www.indiandentalacademy.com
  12. 12. GENETIC VARIATIONS Variations in inherited genes can place them at risk/ predispose them to inflammatory Disease. These usually don’t cause disease by themselves Unless they are challenged by particular trigger www.indiandentalacademy.com
  13. 13. CARDINAL SIGNS OF INFLAMMATION Celsus (1St century) 1. RUBOR - redness 2. TUMOR - swelling 3. CALOR - heat 4. DOLOR - pain www.indiandentalacademy.com
  14. 14. FUNCTIO LAESA – loss of function (later added by galen and virchow in 3rd century) www.indiandentalacademy.com
  15. 15. Rubor Redness is due to VASODILATION (DUE TO RELEASE OF MEDIATORS) INCREASED BLOOD SUPPLY TRIPLE RESPONSE OF LEWIS(1924) www.indiandentalacademy.com
  16. 16. RED LINE APPEARS IN A FEW SECONDS DUE TO VASODILATION OF CAPILLARIE AND VENULE FLARE FLUSH AROUND RED LINE APPEARS SLOWLY DUE TO AXON REFLEX CAUSING DILATION OF ADJACENT ARTERIOLES WHEAL SWELLING OEDEMA APPEARS IN MINUTES DUE TO TRANSUDATION OF FLUID INTO EXTRA VASCULAR SPACE www.indiandentalacademy.com
  17. 17. CALOR Due to increase in blood supply Due to increase in metabolic activity in that area Appreciation of heat is possible in superficial areas with heat receptors… e.g : skin subcutaneous tissues In deeper organs although associated with heat in the area , it is not associated with perception of increased heat www.indiandentalacademy.com
  18. 18. Due to release of mediators which stimulate nerve endings Occurs only when appropriate sensory N. endings exists in inflamed area Type of pain depends on extent of stimulus rather than type of causative agent www.indiandentalacademy.com
  19. 19. REFERRED PAIN:  Due to spread of pain stimuli along the nerves to relevant spinal segment and relay of pain sensation to other areas served by same segmental distribution  E.g Pain of myocardial ischemia referred to left shoulder www.indiandentalacademy.com
  20. 20. PAIN CAUSED BY INFLAMMATION OF CHARACTER SKIN BURNING , ITCHING DENSE TISSUES LIKE PERITONIUM BONE , ENCAPSULATED ORGANS DULL , BORING , ACHING PROGRESSED TO SUPPURATION THROBBING PUS REACHES TO SURFACE SHARP , DARTING ,LANCINATING NERVE TRUNK BORING , TINGLING www.indiandentalacademy.com
  21. 21. TUMOR/SWELLING Due to increased vascularity Accumulation of fluid and cells in damaged part EDEMA- Excess fluid in interstitial / serous cavities it may be exudate / transudate in nature PUS: Purulent exudate rich in leukocytes(mostly neutrophils), debris of dead cells and in many cases microbes www.indiandentalacademy.com
  22. 22. EXUDATE TRANSUDATE Edema of inflammed tissues due to alteration in normal permeability of small bvs Ultrafiltrate of blood plasma that results from osmotic/hydrostatic imbalance across the vessel wall Inflammatory edema Non inflammatory edema High protein(2.5-3.5g/dl) readily coagulates due to high fibrinogen Low protein (>1g/dl)mainly albumin low fibrinogen, no tendency to coagulate Specific gravity >1.018 ph <7.3 Specific gravity low<1.015 ph>7.3 Glucose is low(<60mg/dl) same as plasma LDH is high LDH is low Many cells, inflammatory , parenchymal cells Few cells mainly mesothelial cells and cellular debris e.g: purulent exudate such as pus Edema in congestive cardiac failurewww.indiandentalacademy.com
  23. 23. TYPES OF INFLAMMATION Acute inflammation Rapid response to an injurious agent that serves to deliver mediators of host defense , leukocytes and plasma proteins to the site of injury Chronic inflammation Inflammation of prolonged duration in which active inflammation, tissue destruction, and attempts at repair are proceeding simultaneously www.indiandentalacademy.com
  24. 24. ACUTE CHRONIC ONSET IMMEDIATE DELAYED DURATION FEW DAYS UPTO MONTHS, YEARS CAUSATIVE AGENTS BACTERIA INJURED TISSUES PERSISTENT ACUTE , FOREIGN BODY , VIRAL AUTOIMMUNE MAJOR CELLS NEUTROPHILS ,BASOPHILS MONOCYTESMACROPHAGES MONONUCLEAR CELLS MONO,LYMHPHOCYTES PLASMA CELLS FIBROBLASTS PRIMARY MEDIATORS VASOACTIVE AMINES EICOSANOIDS OUTCOMES RESOLUTION ABSCESS FORMATION CHRONIC INFLAMMATION TISSUE DESTRUCTION FIBROSIS NECROSISwww.indiandentalacademy.com
  25. 25. ACUTE INFLAMMATION VASCULAR HEMODYNAMIC CHANGES ALTERED VASCULAR PERMEABILITY CELLULAR EXUDATION PHAGOCYTOSIS www.indiandentalacademy.com
  26. 26. INJURY TRANSIENT VAOCONSTRICTI ON MILD 3-5SECONDS SEVERE 5MINUTES HEMO DYNAMIC CHANGES PERSISTENT PROGRESIVE VASODILATION INCREASED BLOOD VOLUME LOCAL ELEVATION OF HYDROSTATIC PRESSURE red heat edema www.indiandentalacademy.com
  27. 27. Five mechanisms of increased vascular permeability Venules,vasoactiv mediators Imm transient Venules IL-1, TNF DELAYED Persists till intercellular junction forms Toxins Chemicals Imm, sustained www.indiandentalacademy.com
  28. 28. 1.Mediators bind to endothelium  Activates intracellular signaling pathways  Lead to phosphorylation of contractile proteins like myosin  Imm…….15 to 30 minutes……..so transient 2.Cytokines cause structural reorganisation of cytoskeleton causing retraction 3. Direct injury……….sustained…….till vessel wall repaired 4. Neutrophils while migrating secrete proteases, ros www.indiandentalacademy.com
  29. 29.  In places like bbb tight junctions exisist between endothelial cells  Cell cytoplasm communicates with exterior through a process called transcytosis  Vesicles are formed from cytoplasm  Called vesiculovacular organelle  In infl……inc VDGF..............inc in no these channels…..leadin to inc vas.perm www.indiandentalacademy.com
  30. 30. INCREASED VASCULAR PERMEABILITY ESCAPE OF PROTEINS FLUID DECREASE INTRAVAS CULAR OSMOTIC PRESSURE INCREASED OSMOTIC PRESSURE OF INTERSTITIAL FLUID OUT FLOW OF FLUID INCREASED CONCENTRATION OF BLOOD CELLS RAISED VISCOSITY SLOWING STASIS www.indiandentalacademy.com
  31. 31. CELLULAR EVENTS EXUDATION The escape of fluid, protein, and blood cells from vascular system into interstitial tissue/body cavities Changes leading to migration are Changes in formed elements of blood Rolling and Adhesion ,Emigration Chemotaxis www.indiandentalacademy.com
  32. 32. NORMAL AXIAL FLOW • RBC , WBC in the centre • Peripheral zone of plasma INFLAMMATION • Leakage of plasma-narrowing of peripheral zone • Redistribution of leukocytes to periphery- MARGINATION EMIGRATION • Endothelium is virtually lined by leukocytes –pavementing • Tumble slowly , adhere transiently –ROLLING ADHESION • After firm adhesion leukocytes insert pseudopods into intercellular junctions and escape into extra vascular space www.indiandentalacademy.com
  33. 33. www.indiandentalacademy.com
  34. 34. ADHESION MOLECULES INVOLVED IN INFLAMMATION SELECTINS 3 closely related proteins( P, E , L) function in adhesion They differ in their cellular distribution L-SELECTIN/CD62L Expressed in lymphocytes/other leukocytes Founds on tips of microvillus projection of leukocytes Facilitating it interaction with ligands on endothelium www.indiandentalacademy.com
  35. 35. E-SELECTIN Previously know as endothelial leukocyte adhesion molecule Expressed on cytokine activated endothelial cells P-SELECTIN Present on secretory granules of platelets also found in granules of endothelial cells www.indiandentalacademy.com
  36. 36. INTEGRINS 30 structurally homologus proteins promote cell-cell/cell-matrix interactions IMMUNOGLOBULIN SUPER FAMILY ADHESION MOLECULES ICAM VCAM Leukocytes express CHOligands for selectins, integrins These are low affinity reactions Fast off rate…easily disrupt by flowing blood As a result bound WBC detach and bind again roll along endothelial surface www.indiandentalacademy.com
  37. 37. ENDOTHELIAL MOLECULE LEUKOCYTE RECEPTOR ROLE P-SELECTIN SIALYL-LEWIS X ROLLING E-SELECTIN SIALYL –LEWIS X ROLLING ,ADHESION ICAM-1 CD 11/CD18 INTEGRINS ADHESION, TRANSMIGRATION VCAM-1 ALPHA 4, BETA 1 ADHESION www.indiandentalacademy.com
  38. 38. www.indiandentalacademy.com
  39. 39. CHEMOTAXIS Locomotion oriented along a chemical gradient Chemokines acts chemoattractants for specific leukocytes C-X-C Chemokine / alpha chemokine NEUTROPHILS C-C Chemokine/beta chemokine Acts On Eosinophils, Basophils, Monocytes, Lymphocytes e.g: MCP, EOTAXIN C-Chemokine/gamma LYMPHOCYTES www.indiandentalacademy.com
  40. 40. Chemokines mediate their activities by binding to seven transmembrane coupled receptor Receptors are CXCR, CCR, CR (CXCR-4, CCR-5 act as co receptor for viral envelope glycoprotein of HIV and thus are involved in entry and binding of virus) chemokines stimulate leukocyte recruitment and control normal migration of cells through various tissues www.indiandentalacademy.com
  41. 41. Leukocyte activation Once recruited to site of injury, they must be activated Stimuli are  Microbes, Necrotic cells  Ag-Ab complex  cytokines Leukocytes express a number of receptors on their surface  Toll like receptors – recognize LPS  Cytokine receptor www.indiandentalacademy.com
  42. 42. leukocyte activation www.indiandentalacademy.com
  43. 43. PHAGOCYTOSIS DEFINED AS Process of engulfment of solid particulate material by cells Steps involved are Recognition and attachment stage Engulfment stage Digestion/degradation stage www.indiandentalacademy.com
  44. 44. RECOGNITION AND ATTACHMENT The process of coating a particle , such as microbe to target it for phagocytosis is called OPSONISATION substances are called opsonins Main opsonin present in serum are IGg opsonin(Fc) PMN possess receptor C3b opsonin www.indiandentalacademy.com
  45. 45. • Tuftsin is a phagocyte enhancing material in serum • Acts directly on cell to stimulate phagocytosis • 2 types of disorders 1. congenital an abnormal peptide competitively inhibit 2.deficiency seen in splenectomy • Due to lack of tuftesin releasing enzyme from spleen. www.indiandentalacademy.com
  46. 46. Engulfment This is accomplished by formation of pseudopod around particle due to actin filament beneath cellwall Eventually complete closure of particle with in a phagosome created by plasma membrane Limiting membrane of phagocytic vacuole fuses with Lysosome - phagolysosome www.indiandentalacademy.com
  47. 47. www.indiandentalacademy.com
  48. 48. www.indiandentalacademy.com
  49. 49. Oxygen dependent Reactive metabolites Oxygen independent granules of phagocytic cell Killing degrading Nitric oxide www.indiandentalacademy.com
  50. 50. Oxygen dependent By production of reactive oxygen metabolites HOCl , HOI , HOBR , HYDROGEN PEROXIDE, HYDROXYL NADPH OXIDASE present in cell membrane of phagosome reduces it to superoxide anion www.indiandentalacademy.com
  51. 51. MPO dependent killing  MPO acts on hydrogen peroxide in presence of halides to form hypohalous acid  This is more potent antibacterial agent www.indiandentalacademy.com
  52. 52. MPO independent killing  Mature macrophages lack MPO  They carry out bactericidal actions by forming hydroxyl ions www.indiandentalacademy.com
  53. 53. Oxygen independent  Agents released from phagocytic cells donot require oxygen  These include Lysosomal hydrolases Permeability increasing factors Defensins Cationic proteins www.indiandentalacademy.com
  54. 54. Chemical mediators of inflammation www.indiandentalacademy.com
  55. 55. Chemical Mediator Of Inflammation • Also called permeability factors • Induce their action by binding to specific receptors on target cells • Stimulate target cell to release secondary effector molecules Two types: 1. Cell derived 2. Plasma derived www.indiandentalacademy.com
  56. 56. VASOACTIVE AMINES ARACHIDONIC ACID METABOLITES LYSOSOMAL COMPONENTS PAF CYTOKINES NITRIC OXIDE CELL DERIVED MEDIATORS Platelets Neutrophils Monocytes Endothelium Fibroblast Smooth muscle www.indiandentalacademy.com
  57. 57. Histamine  First autacoid to be discovered  Formed from histidine by decarboxylation  Synthesized in all tissues  More in skin , lungs , GIT  Stored in high concentration in mast cells and basophils  Involved in inflammation and anaphylactic reactions www.indiandentalacademy.com
  58. 58. HISTAMINE RECEPTORS RECEPTOR TYPE LOCATION BIOLOGICAL EFFECTS H1 SMOOTH MUSCLE ENDOTHELIAL CELLS VD, BRONCHOCONSTRICTION, ACUTE ALLERGIC RESPONSE H2 GASTRIC PARIETAL CELLS VD , SECRETION OF GASTRIC ACID H3 CNS NEUROTRANSMISSION MODULATE WAKEFULLNESS COGNITIVE ABILITY FOOD CONSUMPTION H4 MAST CELLS EOSINOPHILS T-CELLS DENDRITIC CELLS REGULATE IMMUNE RESPONSE ROLE IN CHEMOTAXIS www.indiandentalacademy.com
  59. 59. Exocrine glands salivary , sweat lacrimal , bronchial secretion pancreas , gastric Arterioles , capillaries , venules Vasodilation , systemic hypotension Increased permeability(edema) smooth muscle Bronchus , uterus, contraction GIT www.indiandentalacademy.com
  60. 60. Screen clipping taken: 1/5/2013, 7:29 PM Screen clipping taken: 1/5/2013, 7:16 PM Screen clipping taken: 1/5/2013, 7:12 PM Screen clipping taken: 1/5/2013, 5:40 PM www.indiandentalacademy.com
  61. 61. HISTAMINE ANTAGONISTS/ ANTI HISTAMINES Bovet got nobel prize in 1944 Inhibit action of histamine by blocking receptor Inhibit enzyme histidine decarboxylase (atypical antihistamines) H1 ANTAGONISTS: USED TO TREAT ALLERGY First generation second generation Chlorpheneramine Fexofenadine Diphenhydramine Loratidine Promethazine, hydroxyzine Levo Cetrizine www.indiandentalacademy.com
  62. 62. serotonin  Also called 5-hydroxytryptamine(5HT)  Formed from L-Tryptophan  Present in platelets and enterochromaffin cells  Actions are similar to histamine  Vaso constrictor www.indiandentalacademy.com
  63. 63. ARACHIDONIC ACID METABOLITES  20 CARBON PUFA  Derived from dietary source  Conversion of linoleic acid  Does not occur freely in cell but esterified in membrane phospholipids www.indiandentalacademy.com
  64. 64. Phospholipase A2 www.indiandentalacademy.com
  65. 65. Cell membrane phospholipids Arachidonic acid PGD2,PGE2,PGF2 PROSTACYCLIN PGI2 THROMBOXANE TXA2 PGG2 PGH2+FREE RADICALS PHOSPHO LIPASE A2 Calcium Various kinases Cycloo oxygenase Vd Inhibit platelet aggregation Vasoconstriction Promotes aggregation Vasodilation Potentiates edema Cyclooxygenase pathway www.indiandentalacademy.com
  66. 66. ARACHIDONIC ACID 5-HYDROPEROXYEICOSATETRAENOIC ACID 5-HPETE LEUKOTRIENE A4 LEUKOTRIENE C4,D4,E4 LEUKOTRIENE B4 LIPOXIN A4 LIPOXIN B4 12 LIPO OXYGENASE 55 LIPO OXYGEN ASE CHEMOTAXIS 5-HETE VASO, BRONCHO CONSTRICTION INC PERMEABILITY CHEMOTAXIS CELL ADHESION VD Inhibits CHEMOTAXIS LIPOOXYGENASE PATHWAY www.indiandentalacademy.com
  67. 67. MYELOPEROXIDASE ACID HYDROLASE NEUTRAL PROTEASE ELASTASE PROTEINASE CATHEPSIN NON SP COLLAGENASE LYSOZYME LACTOFERRIN COLLAGENASE GELATINASE HISTAMINASE PLASMINOGEN ACTIVATOR ALKALINE PHOSPHATASE SMALLER SPECIFIC SECONDARY LARGER AZUROPHILIC PRIMARY LYSOSOMAL COMPONENTS www.indiandentalacademy.com
  68. 68.  Neutral proteases are capable of degrading various extracellular component  Collagen, Basement membrane,  Fibrin, Elastin, Cartilage  Also cleave C3 and C5 directly releasing anaphylotoxins  This results in tissue destruction Because of its destructive effects ,if initial leukocyte infiltration if left unchecked results in tissue damage www.indiandentalacademy.com
  69. 69. PLATELET ACTIVATING FACTOR www.indiandentalacademy.com
  70. 70. www.indiandentalacademy.com
  71. 71. IL-1 TNF ENDOTHELIAL INCREASED LEUKOCYTE ADHERENCE PGI SYNTHESIS PROCOAGULANT ACTIVITY LEUKOCYTE EFFECTS INCREASED CYTOKINE SECRETION IL-1 AND 6 FEVER INCREASED SLEEP,ACUTEPHASE PROTEINS DECREASED APETITE NEUTROPHILIA FIBROBLASTS INCREASED PROLIFERATION, COLLAGEN,PROTEASE PGE SYNTHESIS www.indiandentalacademy.com
  72. 72. NITRIC OXIDE METABOLITES  Factor released from ENDOTHELIAL CELLS  Also called ENDOTHELIAL DERIVED RELAXING FACTOR  Also from MACROPHAGES and NEURONS in brain  Synthesized from L-ARGININE by enzyme nitric oxide synthetase(NOS) 3 types eNOS endothelial produced at low levels nNOS neuronal calcium influx cause rapid production iNOS inducible (cytokines) www.indiandentalacademy.com
  73. 73. ROLE IN INFLAMMATION  Potent vasodilator  Reduces platelet aggregation  Reduce leukocyte adhesion  Inhibit several features of mast cell induced inflammation  Endogenous regulator for leukocyte recruitment  No and its derivatives are microbicidal NO is an endogenous compensatory mechanism that reduces inflammatory response www.indiandentalacademy.com
  74. 74. www.indiandentalacademy.com
  75. 75. kinin clotting Fibrino lytic comple ment PLASMA DERIVED www.indiandentalacademy.com
  76. 76. COMPLEMENT SYSTEM  Consists of 20 component proteins and their cleavage products  Found in plasma  Function in both innate and adaptive immunity  In process of complement activation a number of components are elaborated that cause - Increased vascular permeability - Chemotaxis - Opsonisation www.indiandentalacademy.com
  77. 77. www.indiandentalacademy.com
  78. 78. www.indiandentalacademy.com
  79. 79. C3a and C5a  Stimulate histamine release  Anaphylotoxins  They have effects similar to mast cell mediators C5a  Activates LOX pathway  Powerful chemotactic agent  Role in leukocyte adhesion C3b  Acts as opsonin www.indiandentalacademy.com
  80. 80. REGULATION OF COMPLEMENT ACTIVATION The activation of complement is controlled by cell associated and circulatory regulatory proteins Regulation of C3 and C5convertase  Regulators function by enhancing dissociation of convertase complex  E.g: decay accelerating factor  Proteolytic cleaving of C3b www.indiandentalacademy.com
  81. 81. Binding of active complement components by specific proteins in plasma  C1 binding to immune complex is blocked by C1 INHIBITOR(C1INH)  Deficiency of C1INH is associated with HERIDITARY ANGIONEUROTIC EDEMA Episodic edema in skin, extremities, laryngeal and intestinal mucosa provoked by stress/trauma www.indiandentalacademy.com
  82. 82. KININ SYSTEM Hageman factor [XII] Activated Hageman Factor [XIIa] prekallikrein activator (fragment of XIIa) Plasmakallikrein Kallikrein HMW Kininogen Bradykinin Contact with -ve charged Collagen,Basement membrane cofactor for Activation of XII chemotaxis C5 to C5a www.indiandentalacademy.com
  83. 83. BRADYKININ  Potent vasodilator  Increases vascular permeability( lower BP)  Causes constriction of smooth muscles  Pain  But the actions are short lived  As it is quickly inactivated by kininase  Any remaining kinin is inactivated by passage of plasma through lung (degraded by ACE) SO ACE INHIBITORS PREVENTS DEGRADATION THERE BY FURTHER LOWERING BP www.indiandentalacademy.com
  84. 84. Ca PL www.indiandentalacademy.com
  85. 85. FACTOR XIIa PRE KALLIKREIN KALLIKREIN PLASMINOGEN PLASMIN FIBRIN FIBRINOGEN THROMBIN C3 C3a KININ SYSTEM COMPLEMENT CLOTTING SYSTEM FIBRINOLYTIC SYSTEM www.indiandentalacademy.com
  86. 86. FACTOR 1 FIBRINOGEN FACTOR 2 PROTHROMBIN FACTOR 3 TISSUE FACTOR/ thromboplastin FACTOR 4 CALCIUM FACTOR 5 PROACCELERIN HMW KININOGEN FITZ GERALD FACTOR FACTOR 7 PRO CONVERTIN /STABLE FACTOR SERUM PROTHROMBIN CONVERSION ACCELERATOR FACTOR 8 ANTI HEMOPHILIC FACTOR/AHFA FACTOR 9 PLAS.THROMBOPLASTIN COMP CHRISTMAS FACTOR / AHB FACTOR 10 STUART / PROWER FACTOR 11 PLASMA THROMBOPLASTIN ANTECEDENT FACTOR 12 HAGEMAN FACTOR FACTOR 13 FIBRIN STABILISING FACTOR PRE KALLIKREIN FLETCHER FACTORwww.indiandentalacademy.com
  87. 87. Morphological patterns of acute inflammation Serous inflammation  Marked by outpouring of thin fluid  Derived either from plasma  Or secretions of mesothelial cells lining peritoneal, pleural, pericardial cavities  E.g: skin blister resulting from burn viral infection causing fluid accumulation either within or immediately beneath epidermis www.indiandentalacademy.com
  88. 88. Fibrinous inflammation  Due increased permeability, severe injury large molecules such as fibrinogen pass vascular barrier  Fibrin is formed and deposited in extracellular space  Fibrinous exudates are removed by fibrinolysis, clearing of debris by macrophages  If it is not removed it may stimulate ingrowth of fibroblasts, blood vessels leading to scarring www.indiandentalacademy.com
  89. 89. Suppurative/purulent inflammation  Characterised by formation of pus  An accumulation of pus in enclosed tissue spaces - ABSCESS  Certain bacteria like staphylococci produce this localised suppuration  E.G: Brain abscess Pyelo nephritis www.indiandentalacademy.com
  90. 90. ULCER  Is A Break In Continuity Of Epithelium Due To Necrosis Or Pathologic Death Of Tissues Extending Into Submucosa  Common sites are mucosa of mouth, stomach  In acute stage infiltration with polymorphs is seen  In chronic ulcers infiltration by plasma cells, lymphocytes, macrophages associated with fibroblastic proliferation www.indiandentalacademy.com
  91. 91. Microbes Toxins trauma ACUTE INFLAMMATION RESOLUTION Clearance of injurious stimuli , mediators Replacement of injured cells Normal function PROGRESS HEALING HEALING FIBROSIS Loss of function LOCALISATION abscess HEALING Chronic inflammation Angiogenesis Mononuclear cell infiltrate Viral infections Persistent injury Autoimmune diseases outcomes www.indiandentalacademy.com
  92. 92. CHRONIC INFLAMMATION Chronic inflammation is of prolonged duration(weeks/ months) in which active inflammation, tissue destruction, and attempts to repair are proceeding simultaneously…. www.indiandentalacademy.com
  93. 93. CAUSES 1.Persistent infections  By tubercle bacilli, certain virus, fungi  These organisms are of low toxicity  Evoke an immune reaction called delayed type of hypersensitivity  Leading to formation of a granuloma www.indiandentalacademy.com
  94. 94. Macrophages Dendritic cells critical for induction of t-h cells IL- 12 IF IF-Y ACTIVATES MACROPHAGES CAUSE RELEASE OF PDGF FIBROSIS MECHANISM OF TYPE IV HYPERSENSITIVITY IN FORMATION OF GRANULOMA www.indiandentalacademy.com
  95. 95. • Antigen binding to mannose receptor(mhc) on surface of macrophage • This act as antigen presenting cell • Ag bearing macrophage(icam-1) interacts with receptor on t-cells(cd11a cd2) • Helper t cells - MHC CLASS II • Cytotoxic t cells – MHC CLASS I www.indiandentalacademy.com
  96. 96. 2. Prolonged exposure to potentially toxic agents Either Exogenous/ Endogenous  Exogenous : Silica when inhaled for prolonged periods, results in inflammatory lung disease SILICOSIS  Endogenous : Toxic plasma lipid components lead to inflammatory process of arterial wall ATHEROSCLEROSIS www.indiandentalacademy.com
  97. 97. 3. AUTO IMMUNITY  Immune reactions develop against individuals own tissues  Autoantigens evoke a self perpetuating immune reaction that results in chronic tissue damage and inflammation  E.g: Rheumatoid arthritis Systemic lupus erythematosus www.indiandentalacademy.com
  98. 98. ROLE OF INFLAMMATION IN AUTOIMMUNITY www.indiandentalacademy.com
  99. 99. Chronic inflammation is characterised by 1. Infiltration with mononuclear cells which include macrophages, lymphocytes, plasma cells 2. Tissue destruction induced by persistent offending agent or by inflammatory cells 3. Attempts at healing by connective tissue replacement of damaged tissue accomplished by proliferation of blood vessels (angiogenesis), fibrosis www.indiandentalacademy.com
  100. 100. Mononuclear cell infiltration  Macrophage is dominant cell in chronic inflammation  It is component of mononuclear phagocyte system(MPS)  Previously called reticuloendothelial system  Comprises blood monocytes, tissue macrophages  Half life of blood monocyte is about 1day  Tissue macrophage is several months to years www.indiandentalacademy.com
  101. 101. Connective tissue(histiocytes) Spleen(sinusoidal lining cells) Serous cavity(peritoneal pleural) Skin(langerhans cells) Synovia(A cells) INFLAMMATION Exudate macrophages Epitheloid cells Multi nucleated giant cells www.indiandentalacademy.com
  102. 102. MECHANISM OF MACROPHAGE ACCUMULATION IN TISSUES ,CONTINUOUS RECRUITMENT FROM MICROCIRCULATION STIMULI ARE CHEMOKINES BY ACTIVATED MACROPHAGES LYMPHOCYTE MCP-1 C5a PDGF TGF-ALPHA FRAGMENTS FROM BROKEN COLLAGEN FIBRONECTIN CYTOKINES OXIDISED LIPIDS www.indiandentalacademy.com
  103. 103. www.indiandentalacademy.com
  104. 104. Other cells in chronic inflammation are  Lymphocytes, plasma cells, eosinophils and mast cells  LYMPHOCYTES are involved in both types of immune reactions(humoral , cell mediated)  Lymphocytes(B, T) use various adhesion molecules and chemokines to migrate in to inflammatory sites  Lymphocytes , macrophages interact in a bidirectional way www.indiandentalacademy.com
  105. 105. www.indiandentalacademy.com
  106. 106.  Microbial ag should be recognised as non self  This require immunological memory and specificity  This property resides in lymphocytes www.indiandentalacademy.com
  107. 107. www.indiandentalacademy.com
  108. 108. EOSINOPHILS  Abundant in immune reactions mediated by IgE  And in parasitic infections Granules contain major basic protein  A highly cationic protein toxic to parasites  Also causes lysis of mammalian epithelial cells www.indiandentalacademy.com
  109. 109. MAST CELLS  Basophils in tissues  Participate in both acute and chronic  Express on their surface receptors which bind to Fc portion of IgE  Degranulation cause release of mediators such as histamine, PAF, eicosanoids, neutral proteases www.indiandentalacademy.com
  110. 110. TYPES OF CHRONIC INFLAMMATION  When injurious agent causes a characteristic histological tissue response – SPECIFIC  E.g: TB , Leprosy  Histologically characterized by granuloma formation  when irritant produces a non specific inflammatory reaction with formation of granulation tissue and healing by fibrosis – NON SPECIFIC  E.g: chronic osteomyelitis , ulcer  Histologically Non specific cell infiltration www.indiandentalacademy.com
  111. 111. GRANULOMATOUS INFLAMMATION GRANULOMA IS A FOCUS OF CHRONIC INFLAMMATION CONSISTING OF MICROSCOPIC AGGREGATION OF MACROPHAGES THAT ARE TRANSFORMED INTO EPITHELIUM LIKE CELLS SURROUNDED BY A COLLAR OF MONONUCLEAR LEUKOCYTES , PRINCIPALLY LYMPHOCYTES , OCCASIONAL PLASMA CELLS www.indiandentalacademy.com
  112. 112. www.indiandentalacademy.com
  113. 113. BACTERIAL TB LEPROSY SYPHILITIC GUMMA FUNGAL HISTOPLASMOSIS BLASTOMYCOSIS CRYPTOCOCCUS PARASITIC SCHISTOSOMIASIS FOREIGN BODY SUTURE , ANY PROSTHESIS , VASCULAR GRAFT INORGANIC METALS,DUSTS SILICOSIS BERYLLOSIS UN KNOWN SARCOIDOSIS www.indiandentalacademy.com
  114. 114. Epitheloid cells They are modified macrophages/ histiocytes which are somewhat elongated, having pale staining abundant cytoplasm, vesicular, lightly stained slipper shaped nucleus  Cell membrane of adjacent epitheloid cell is closely apposed due to hazy outline  They are weakly phagocytic www.indiandentalacademy.com
  115. 115. GIANT CELLS  Formed by fusion of epitheloid cells  May have 20/more nuclei  Nuclei present centrally- FOREIGN BODY TYPE  Nuclei at periphery like horse shoe/ ring/clustered at two poles- LANGHANS TYPE  They are also weakly phagocytic  Produce secretory products which helps to remove invading agents www.indiandentalacademy.com
  116. 116. NECROSIS  It is feature of some granulomatous conditions  E.g: caseation necrosis in TB FIBROSIS  Due to proliferation of fibroblasts at periphery of granuloma www.indiandentalacademy.com
  117. 117. Factors favouring formation of granuloma 1. Presence of poorly digestible irritant 2. Presence of cell mediated immunity to irritant implying role of hypersensitivity in granulomatous inflammation Types of granuloma 1. FOREIGN BODY GRANULOMA : Material can be seen in center when viewed with polarised light 2. IMMUNE GRANULOMA : Due to microbes capable of activating cell mediated immunity www.indiandentalacademy.com
  118. 118. SYSTEMIC EFFECTS OF INFLAMMATION www.indiandentalacademy.com
  119. 119. LPS EXOGENOUS PYROGENS TNF,IL-1 ENDOGENOUS PYROGENS INCREASE CYCLOOXYGENASE PGE2 STIMULATE RELEASE OF CYCLIC AMP RESET TEMPERATURE SET POINT AT HIGHER LEVEL FEVER www.indiandentalacademy.com
  120. 120. • Temperature > 40C • Triggers cold receptors Severe Inflammation • Pallor • A feeling of coldness of skin surface Reflex Vasoconstriction Of Vessels RIGOR Shaking Exaggerated shivering which occurs with a high fever www.indiandentalacademy.com
  121. 121. Changes in pulse rate  Increase in temperature accompany increase in pulse  For every 1 degree F rise in temp pulse increase by 10beats/minute  Conversely bradycardia occurs in typhoid fever www.indiandentalacademy.com
  122. 122. Acute phase proteins  Mostly synthesized in liver  Clinical concentration increase 100fold in inflammation  E.g: CRP, serum amyloid A protein(SAA), Fibrinogen  Cytokines upregulate their synthesis by stimulating hepatocytes  CRP, SAA acts as opsonins and fix complement www.indiandentalacademy.com
  123. 123. They have beneficial effects in acute inflammation but in chronic prolonged production leads to secondary amyloidosis CRP  Levels increased in infection , inflammation  Tissue necrosis , malignancy , auto immune diseases  It binds to phosphocholine on dead / dying cells and activate complement  Enhances phagocytosis by microbes  Marked increase indicates risk for CVD , hypertension diabetes www.indiandentalacademy.com
  124. 124. LEUKOCYTOSIS  Common feature of especially for bacterial infections  Count increase by 15,000 to 20,000cells/cumm  If it increase up to 1lakh – LEUKEMOID REACTION (but splenomegaly, lymphadenopathy, hemorrhages are absent) MYELOID LEUKEMOID TB, MENINGITIS ENDOCARDITIS BURNS MERCURY POISONING LYMPHOID LEUKEMOID INFECTIOUS MONONUCLEOSIS TB, PERTUSIS CHICKEN POX MEASLES www.indiandentalacademy.com
  125. 125. INITIAL INCREASE ACCELERATED RELEASE OF CELLS DUE TO TNF, IL-1 INCREASE IMMATURE NEUTROPHILS IN BLOOD PROLONGED INFECTION INCREASED COLONY STIMULATING FACTORS INCREASED CELLS FOR COMPENSATION OF CELL LOSS LEUKOCYTOSIS www.indiandentalacademy.com
  126. 126. NEUTROPHILIC LEUKOCYTOSIS BACTERIAL INFECTIONS, MI, BURNS EOSINOPHILIC LEUKOCYTOSIS PARASITIC INFESTATIONS, ASTHMA, ALLERGIES BASOPHILIC LEUKOCYTOSIS (RARE) INDICATIVE OF MYELOPROLIFERATIVE DISEASE (CML) MONOCYTOSIS (COMMON IN CHRONIC) TB, ENDOCARDITIS, COLLAGEN VASCULAR DISEASE(SLE), INFLAMMATORY BOWEL DISEASE(ULCERATIVE COLITIS) LYMPHOCYTOSIS TB, VIRAL(HEP-A, CMV, EBV)www.indiandentalacademy.com
  127. 127. LPS (TNF, IL-1) TISSUE FACTOR EXPRESSION BY ENDOTHELI AL CELLS INTIATES COAGULATI ON DIC CYTOKINES LIVER INJURY FAILURE TO MAINTAIN NORMAL GLUCOSE SHOCK www.indiandentalacademy.com
  128. 128. OVER PRODUCTION OF NO BY CYTOKINE ACTIVATED CARDIAC MYOCYTES HEART FAILURE DIC HEART FAILURE HYPOGLYCEMIA SEPTIC SHOCK www.indiandentalacademy.com
  129. 129. LYMPHANGITIS- LYMPHADENITIS  Lymphatics and lymphnodes that drain the inflammed tissue show reactive inflammatory changes  This is a non specific reaction to mediators released from inflammed tissues  LYMPHANGITIS Inflammation Of Lymphatic Vessels And Channels  LYMPHADENITIS Inflammation of lymph node www.indiandentalacademy.com
  130. 130. REGULATION OF INFLAMMATION 1. ACUTE PHASE PROTEINS Alpha 1 anti trypsin:  It Is a Protease Inhibitor  Protects Tissues From Enzymes Of Inflammatory Cells  Especially Neutrophil Elastase  In Absence Degradation Of Elastin  If This Occur In Lungs , This Leads To Respiratory Problems www.indiandentalacademy.com
  131. 131.  Protease inhibitor  Hapatglobin  It Scavangers Hb Released Into Circulation  Potent Antioxidant  Resist Cell Oxidative Stress  Inhibits COX , LOX www.indiandentalacademy.com
  132. 132. 2. CORTICOSTEROIDS  Endogenous glucocorticoids act as anti inflammatory agents  Their levels are increased in infection , trauma by self regulating mechanism 3. Supressor T cells / regulator T cells  Modulate immune system  Maintain tolerance to self antigens www.indiandentalacademy.com
  133. 133. 4. Anti inflammatory chemical mediators propree RESOLVINS RvS OMEGA 3 www.indiandentalacademy.com
  134. 134. FACTORS DETERMINING VARIATIONS IN INFLAMMATORY RESPONSE www.indiandentalacademy.com
  135. 135. FACTORS INVOLVING THE ORGANISM Type of injury and infection  Lung reacts to pneumococci by occurrence of pneumonia  While it responds to tubercle bacilli by granulomatous inflammation Dose  Concentration of organism in small dose form local lesions  Large dose cause severe spreading infections www.indiandentalacademy.com
  136. 136. Portal Of Entry  Vibrio cholera is not pathogenic if injected sub cutaneously but cause cholera if swallowed Product Of Organisms  Certain products cause spread of infection  e.g : streptokinase by streptococci coagulase by staphylococci www.indiandentalacademy.com
  137. 137. FACTORS INVOLVING THE HOST 1. AGE : very young, very old are less able to combat infection because of lack of inflammatory response Many elderly patients respond with a chronic inflammatory response which in young patients have provoked acute response 2. DAMAGE TO BONE MARROW AND RETICULO ENDOTHELIAL SYSTEM www.indiandentalacademy.com
  138. 138. 3. ANTIBIOTIC THERAPY  Antibiotics decrease inflammation because clearing infection removes reason for inflammation  Inflammatory response is modified depending on how the agent respond to therapy www.indiandentalacademy.com
  139. 139. 4. Diet  when you eat your body forms PG’s from nutrients in diet  This can be inflammatory / anti inflammatory  Imbalance in diet leads to formation of inflammatory PG  On other hand omega-3 fatty acids , antoxidants , phyto nutrients can produce anti inflammatory PG www.indiandentalacademy.com
  140. 140. FOODS HIGH SATURATED FAT MEAT EGGS DAIRY PRODUCTS COFFEE CONTAINS CRP PROCESSED MEATS COOKING FOODS AT HIGH TEMP CAUSE RELEASE OF TOXINS TRANS FAT INTAKE OF PROCESSED FRIED FOODS HIGH GLYCEMIC INDEX CHO INSULIN CAUSE METABOLISM OF AA PRO INFLAMMATORY FOODS www.indiandentalacademy.com
  141. 141. ANTI INFLAMMATORY FOODS www.indiandentalacademy.com
  142. 142. CONCLUSSION WAR AND INFLAMMATION  Both are stereotyped responses to outside threats  There are specialised troops(immune cells)  Supply routes(vessels)  Communication and intelligence(mediators)  Huge array of lethal weapons(enzymes) IN WAR AS IN INFLAMMATION THERE IS DAMAGE TO BOTH ENEMY AND FRIENDLY FORCES AND SEVERE DAMAGE TO BATTLE FIELD ITSELF www.indiandentalacademy.com
  143. 143. PROBABLY YOUR OWN DEATH WILL BE CAUSED BY YOUR LAST INFLAMMATORY RESPONSE www.indiandentalacademy.com
  144. 144. References 1. Robbins and Cotran Pathologic Basis of Disease 7th edition 2. Guyton and Hall Text Book of Medical Physiology 11th edition 3. Harsh Mohan Text Book of Pathology 5th edition PRESENTED BY ANUSHA.V PG-1ST YEARwww.indiandentalacademy.com
  145. 145. www.indiandentalacademy.com

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