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objectives
 Overview
 Historical aspect
 classification
 Acute inflammation
 Mediators of inflammation
 MorphologicP...

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INFLAMMATI
ON
Protective
Mechanism
Tissue damage
Necrotic
tissue
Foreign
Invader
Plasma
protein
leukocyte phagocytes
Types...

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Classification of inflammation
 1- According to principle
constituent of exudates:-
SEROUS
FIBRINOUS
HAEMORRAGIC
PURULENT...

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Inflammation and necrosis
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Inflamation

  1. 1. objectives  Overview  Historical aspect  classification  Acute inflammation  Mediators of inflammation  MorphologicPatterns of Inflammation  Outcomes of AcuteInflammation  Systemic effects on inflammation
  2. 2. INFLAMMATI ON Protective Mechanism Tissue damage Necrotic tissue Foreign Invader Plasma protein leukocyte phagocytes Types Acute chronic B U T adly ncontrolled riggered Inflammatory Response TISSUE INJURY
  3. 3. Classification of inflammation  1- According to principle constituent of exudates:- SEROUS FIBRINOUS HAEMORRAGIC PURULENT ACUTE INFLAMMATION
  4. 4. II-According to duration  Per-acute inflammation  Acute inflammation  Sub-acute inflammation  Chronic inflammation
  5. 5. III-According to fate of inflammation:-  Hyperplastic inflammation  Hypertrophic inflammation  Atrophic inflammation  Fibrous inflammation  Adhessive inflammation:
  6. 6. IV- According to the cause:  Mechanical inflammation  Physical inflammation  Chemical Inflammation  Biological inflammation
  7. 7. Agents causing inflammation Infective agents Immunologi cal agents Physical agents Chemical agents Inert materials Bacteria Viruses and their toxins, fungi, parasites Cell mediated Antigen antibody reactions Heat Cold Radiation Mechanical trauma Organic Inorganic poisons Foreign bodies
  8. 8. characteristic  RapidHostResponse  Alterationsinvascularcalibre  Increasebloodflow  Structuralchangesinmicrovasculature  Plasmaprotein&Leukocyteleave circulation  Emigration  Leukocyte  Toaccumulateininjuriousfoci normal inflamed
  9. 9. Acute inflammation VASCULAR EVENTS CELLULAR EVENTS HAEMODYNAMIC CHANGES  Transient vasoconstriction  Persistent progressive vasodilatation  Local hydrostatic pressure  Slowing or stasis of blood ALTERED VASCULAR PERMEABILITY  Contraction of endothelial cells  Retraction of endothelial cells  Direct injury to endothelial cells  Endothelial injury mediated by leucocytes  Neovascularisation EXUDATION OF LEUCOCYTES  Changes in formed elements of blood  Rolling and Adhesion  Emigration  Chemotaxis PHAGOCYTOSIS  Recognition and attachment  Engulfment  Killing and degradation
  10. 10. Haemodynamic changes  Transient vasoconstriction  Persistant progressive vasodilatation  Slowing or stasis of blood  Margination  Pavementing  Emigration
  11. 11. TRANSIENT VASONSTRICTION  Irrespective of the type of injury , immediate vascular response is of transient vasoconstriction of arterioles.  With mild form of injury, the blood flow may be reestablished in 3-5 seconds while with more severe injury the vasoconstriction may last for about 5 minutes
  12. 12. Persistant progressive vasodilatation  Involves mainly the arterioles but to lesser extent other components of the microcirculation like venules and capillaries  This change is obvious within half an hour of injury  Vasodilatation results in increased blood volume in microvascular bed of the area,which is responsible for redness and warmth at the site of acute inflammation
  13. 13. Local hydrostatic pressure  Progressive vasodilatation may elevate local hydrostatic pressure resulting in the transudation of fluid into the extracellular space  This is responsible for swelling at the local site of acute inflammation
  14. 14. Slowing or stasis of blood  Slowing or stasis of microcirculation follows which causes increased concentration of red cells and thus increased viscocity
  15. 15. margination  Stasis or slowing is followed by leucocyte margination  Peripheral orientation of leucocytes along the vascular endothelium  Leucocytes rolls over the surface of endothelial cells and is called pavementing
  16. 16. emigration  The leucocytes stick to the vascular endothelium briefly and then move and migrate through the gaps between the endothelial cells into the extravascular space. This process is called emigration
  17. 17.  SIR THOMAS LEWIS : established the concept that chemical substances, locally induced by injury, mediate the vascular changes of inflammation.(1924)  The reaction so elicited is known as TRIPLE RESPONSE or REDLINE RESPONSE consisting of following:  Redline: appears within a few seconds following stroking & results from local vasodilation of capillaries & venules.  Flare: is the bright reddish appearance or flush surrounding the redline & results from vasodilation of adjacent arterioles.  Wheal: is the swelling or edema of the surrounding skin occurring due to transudation of fluid into the extravascular spaces.
  18. 18. Alteredvascular permeability  The appearance of inflammatory oedema due to increased vascular permeability of microvascular bed is explained on the basis of starlings hypothesis  In normal circumstances the fluid balance is maintained by two opposing sets of forces
  19. 19. OSMOTIC PRESSURE OF INTERSTITIAL FLUID TISSUE HYDROSTATIC PRESSURE INTRAVASCULAR HYROSTATIC PRESSUE OSMOTIC PRESSURE OF PLASMA PROTEINS OUTWARD MOVEMENT OF FLUID INWARD MOVEMENT OF FLUID STARLING’S HYPOTHESIS
  20. 20. Forces that cause outward movement of fluid from microvasculation are intravascular hydrostatic pressure and colloid osmotic pressure of interstitial fluid Forces that cause inward movement of interstitial fluid into circulation are intravascular colloid osmotic pressure and hydrostatic pressure of interstitial fluid
  21. 21. Transudate Exudate Filtrate of blood plasma without changes in endothelial permeability Non inflammatory edema Ph more than 7.3 Few cells ,mainly mesothelial and cellular debris Oedema of inflamed tissue associated with increased vascular permeability Inflammatory edema Ph less than 7.3 Many cells, inflammatory as well as parenchymal Rivalta’s test:: is a very simple, inexpensive method that does not require special laboratory equipment and can be easily performed in private practice. This test was originally developed by the Italian researcher Rivalta around 1900 and was used to differentiate transudates and exudates in human patients. A test tube is filled with distilled water and acetic acid is added. To this mixture one drop of the effusion to be tested is added. If the drop dissipates, the test is negative, indicating a transudate. If the drop precipitates, the test is positive, indicating an exudate
  22. 22. • Hallmark of acute inflammation • 3 types: • Immediate transient response: • Immediate sustained response: • Delayed prolonged leakage:
  23. 23. Mechanisms of increased vascular permeability Contraction of endothelial cells Retraction of endothelial cells Direct injury to endothelial cells Endothelial injury mediated by leucocytes Leakiness in neovascularisation
  24. 24. Contraction of endothelial cells This is the most common mechanism of increased leakiness that affects venules exclusively while capillaries and arterioles remains unaffected The endothelial cells develop temporary gaps between them due to their contraction resulting in vascular leakiness It is mediated by the release of histamine, bradykinin and other chemical mediators The response begins immediately after injury, is usually reversible and is for short duration(15-30 minutes)
  25. 25. Retraction of endothelial cells  In this mechanism, there is structural re-organisation of the cytoskeleton of endothelial cells that causes reversible retraction at the intercellular juctions  This change too affects venules and is mediated by cytokines such as interleukin 1 and tumor necrosis factor(TNFα).  The onset of response takes 4-6 hours after injury and lasts for 2-4 hrs or more
  26. 26. Direct injury to endothelial cells  Direct injury to the endothelium causes cell necrosis and appearance of physical gaps at the sites of detached endothelial cells  Process of thrombosis is initiated at the site of damaged endothelial cells  The increased permeability may either appear immediately after injury and last for several hours or days ,or may occur after a delay of 2-12 hours and lasts for hours or days
  27. 27. Endothelial injury mediated by leucocytes  Adherence of leucocytes to the endothelium at the site of inflammation may result in activation of leucocytes  The activated leucocytes release release proteolytic enzymes and toxic oxygen species which may cause endothelial injury and increased vascular leakiness  This form of increased vascular leakiness affects mostly venules and is a late response
  28. 28. Leakiness in neovascularisation  The newly formed capillaries under the influence of vasculr endothelial growth factor(VEGF) during the process of repair and in tumours are excessively in leaky
  29. 29. Cellular events  Exudation of leucocytes  Phagocytosis
  30. 30. EXUDATION OF LEUCOCYTES  Changes in the formed elements of blood  Rolling and adhesion  Emigration  Chemotaxis
  31. 31. CHEMOTAXIS  After exiting the circulation leukocyte emigrate in tissues towards the site of injury by a process called chemotaxis.  Exogenous and endogenous substance can act as chemoattractants.  Exogenous – bacterial products.  Endogenous- 1) cytokines- IL-8 2) Leukotriene- B4 3) components of complement system. 4) soluble bacterial products
  32. 32. PHAGOCYTOSIS RECOGNITION & ATTACHMENT KILLING OR DEGRADATION ENGULFMENT The process of engulfment of solid particulate material by the cell. 2 types: a) Microphages b) macrophages
  33. 33. PHAGOCYTO SIS RECOGNITION AND ATTACHMENT Opsonins - C3b, IgG, lectins ENGULFMENT STAGE Cytoskeletal mechanisms Degranulation KILLING / DEGRADATION O2-Dependent - H2O2 HOCl O2-Independent - lysozyme, cationic proteins, defensins, lactoferrin NO -Dependent
  34. 34.  Lymph flow is increased  Drains edema fluid that accumulate at extra vascular space  Lymph channels proliferate to control the edema  Painfull enlargement of draining lymph node – LYMPHADENITIS  Secondarily infected lymphatics – LYMPHANGITIS  TELLTALE sign  red streak near wound  indicative of infection  involvement of lymphatics
  35. 35. Release of soluble mediators Vasodilation Increased blood flow Extravasation of fluid (permeability) Cellular influx (chemotaxis) Elevated cellular metabolism Heat (calor) Redness (rubor) Swelling (tumor) Pain (dolor) Physiological Symptoms Responses
  36. 36. INFLAMMATORY CELLS
  37. 37. Polymorphonuclear Leukocytes Along with basophils and eosiniphils these are known as granulocytes- due to presence of granules in cytoplasm. DIAMETER: 10-15 μm, active motile 40-75% of circulating leukocytes Arise in the bone marrow from stem cell. No. increased in blood and tissues in acute inflammation. Function: initial phagocytosis, engulfment, harmful effects.
  38. 38. Eosinophils 1-6%of WBCs Similarities like PMNs- Production in bone marrow, locomotion, phagocytosis, lobuled nuclues, granules in cytoplasm containing variety of enzymes. Granules richer in myeloperoxidase prominent in allergic reactions, parasitic infections, skin disease, malignant lymphomas. live longer than PMNs, are present in chronic inflammation
  39. 39. Basophils 1% of WBCs Contain coarse basophilic granules in the cytoplasm & polymorphonuclear nucleus. Granules laden with heparin & histamine. most prominent in allergic reactions regulated by immunoglobulin E rich in vasoactive substances histamine precursors of mast cells
  40. 40. Macrophages Blood monocytes 4-8% of wbc. appear 3-4 days after infection or tissue destruction long life span, present in chronic inflammation capable of phagocytosis rich in lytic enzymes secrete cytokines locally and systemically recruit lymphocytes to site of inflammation
  41. 41. Lymphocytes main means of providing the body with immunity 20-45% of the WBCs Present in blood, spleen, thymus, lymphnode, MALT. Scanty cytoplasm & consists almost entirely of nucleus. In tissues: dominant cells in chronic inflammation & in late stage of acute inflammation. In blood: no. increased in lymphocytosis.
  42. 42. Plasma cells Eccentric nucleus, abundant cytoplasm Nucleus has cart-wheel pattern of chromatin Develop from B-lymphocytes, & rich in RNA. MOST ACTIVE IN ANTIBODY SYNTHESIS. Increased in prolonged infection with immunological response- syphilis, rheumatoid arthritis, hypersensitivity states, Multiple myeloma.
  43. 43. Chemical mediators
  44. 44. Mediators of inflammation Mediators Principal sources Actions CELL DERIVED Histamine Mast cell, basophil, platelet Vasodilation , increased vascular permeability, pain, endothelial activation Serotonin Chromaffin cells of GIT, spleen & platelet Vasodilation , increased permeability Prostaglandin Mast cell, leukocyte Vasodilation, pain, fever Leukotrienes Mast cell, leukocyte Increase permeability, Chemotaxis, leukocyte adhesion & activation Platelet- activating factor Leukocyte, mast cell Increase permeability, bronchoconstriction, chemotaxis Reactive Oxygen Species Leukocyte Microbicidal, Tissue damage Nitric Oxide Endothelium, Macrophages Vascular smooth muscle relaxation Cytokine ( TNF, IL-1) Chemokines Macrophage, mast cell leukocyte Local endothelial activation Chemotaxis, leukocyte activation
  45. 45. Mediator Principal source Functions PLASMA PROTEIN DERIVED Complement Products (C5a, C3a, C4a) Plasma (produced in liver) Leukocyte chemotaxis and activation, vasodialation Increased permeability, smooth muscle contraction Vasodilation, pain. Endothelial activation, leukocyte recruitment Kinins Plasma (produced in liver) Protease activated during coagulation Plasma (produced in liver)
  46. 46. Lysosomal components  Inflammatory cells- neutrophils and monocytes, contain lysosomal granules which on release elaborate a variety of mediators of inflammation.  1) granules of neutrophils- a) primary or azurophilic- myeloperoxidase, acid hydrolase, acid phosphatase. b)secondary or specific- lectoferrin, gelatinase, collagenase c)tertiary granules- gelatinase, acid hydrolase.  2) granules of monocytes and tissue macrophages- plasminogen activator, protease, elastase.
  47. 47. Platelet Activating Factor  Released from IgE- sensitised basophils and mast cells, other leucocytes, endothelium and platelets.  ACTIONS: 1) Increased vascular permeability 2) bronchoconstriction 3) adhesion of leukocytes to endothelium 4) chemotaxis 5) vasodilation- in low conc.
  48. 48. CYTOKINES  Cytokines are polypeptide substances produced by activated lymphocytes and activated monocytes.  Major cytokines are: IL-1, TNF- alpha and beta, IFN- gamma, chemokines (IL-8 , PF-4)
  49. 49. OXYGEN DERIVES METABOLITES: released from activated neutrophils and monocytes include O’2, H2O2, OH’ and toxic NO products. Actions: 1) endothelial cell damage 2) activation of protease 3)damage to other cells. NITRIC OXIDE: vascular relaxation factor produced by endothelial cells. Action: 1)vasodilation, 2)anti-platelet activating agent, 3)possibly microbicidal action
  50. 50. THE COMPLEMENT SYSTEM  The activation of this complement system can occur either: 1) By classic pathway through antigen- antibody complex or, 2) by alternate pathway via non-immunologic agents such as bacterial toxins, cobra venoms and IgA. ACTIONS: 1) C3a, C5a, C4a activate mast cells and basophils to release of histamine, cause increased vascular permeability causing oedema in tissues 2) C3b is an opsonin 3) C5a is chemotactic for leukocytes 4) C5b-C9 are lipid dissolving agent
  51. 51. Systemic effects of acute inflammation  Fever  Leucocytosis (15-20,000) Bacterial infection- Neutrophilia Viral infection -Lymphocytosis Parasitic infection- Eosinophilia  Hypotension  Increased ESR and C-reactive protein
  52. 52. FATE OF ACUTE INFLAMMATION
  53. 53. refferences  Basics of Pathology, Robins & Cotrans  Essential pathology for dental students, 4th edition, Harsh Mohan.  Inflammation- a review of the process, 5th edition. Henry o. trowbridge.
  54. 54. DIFFUSE SUPPURATIVE GRANULOMATOUS FIBRINOID CHRONIC INFLAMMATION
  55. 55.  Is the persistence of inflammation with attempts of repair resulting from persistence of the injurious agent.
  56. 56.  Persisting infection or prolonged exposure to irritants (intracellular surviving of agents -TB)  Repeated acute inflammations (otitis, rhinitis)  Primary chronic inflammation -low virulence, sterile inflammations (silicosis)  Autoimmune reactions (rheumatoid arthritis, glomerulonephritis, multiple sclerosis)
  57. 57. Mechanism......  Defective acute inflammatory response  Poor blood supply  Poor general nutrition  Abnormal neutrophil function  Anti-inflammatory drugs, especially corticosteroids  Agent is resistant to phagocytosis and/or intracellular destruction  Intracellular infectious agents, e.g. tuberculosis, salmonellosis, brucellosis, viral infections  Foreign-body reactions  The provoking agent is a body constituent as in:  Auto-immune diseases, e.g. diffuse lymphocytic thyroiditis (Hashimoto’s disease), auto-immune atrophic gastritis, adrenal atrophy, etc.  Reactions to altered self-antigens, e.g. contact dermatitis to rubber, nickel, etc
  58. 58.  Continuing some features of acute inflammation  Polymorph infiltration  Fibrinous exudation  Increased vascularity  Features of healing-repair and/or regeneration  Infiltration by chronic inflammatory cells  Lymphocytes  Plasma cells  Macrophages  Eosinophils
  59. 59. Granulomatous inflammation  A distinct pattern of chronic inflammation characterized by formation of granulation tissue.  It is a protective response to chronic infection or foreign material, preventing dissemination and restricting inflammation.  Some autoimmune diseases such as rheumatoid arthritis and Crohn’s disease are also associated with granulomas
  60. 60. ? Granuloma.......  A granuloma is a localized mass of granulation tissue with aggregations of chronic inflammatory cells  The granuloma consists of a kernel of infected macrophages surrounded by foamy macrophages and a ring of lymphocytes and a fibrous cuff.
  61. 61. Causes of granuloma......  Bacteria:  Tuberculosis, Leprosy, Syphilis, Actinomycosis  Parasites:  Schistosomiasis  Fungi:  Histoplasmosis, Blastomycosis  Foreign bodyGranulomas  Endogenous  keratin, necrotic bone or adipose tissue uric acid crystals  Exogenous  wood, silica, asbestos, silicone  Unknown cause such as sarcoidosis
  62. 62.  Inflammatory reaction is greater in diabetic status  Conversely local inflammation causes intensification of diabetes  According to Russel in 1966  Cellular dehydration  Loss of alkali reserve  Vessels lumen get obliterated  Thickening of capillaries - Role in inflammation acts as a barrier to leukocytic emigration into site (Brayton et al 1970)
  63. 63. NSAIDs: Drug Effects  Analgesic (mild to moderate)  Anti-gout  Anti-inflammatory  Antipyretic  Relief of vascular headaches  Platelet inhibition (ASA)
  64. 64. Role in inflammation
  65. 65. Chemical Make-Up  Hydrocortisone or cortisol is the primary agent  Glucocorticoid, which is naturally secreted by body is derivative  Currently, many AI steroids are available more powerful than cortisol, but have the same chemical structure as glucocorticoid  Long term use will inhibit body’s glucocorticoid activity and the body’s ability to produce this substance naturally
  66. 66. How it Works
  67. 67. Adverse effect of corticosteroids  Receive long-term, high-dose steroid  Hypertension, heart failure  Osteoporosis, DM, impaired wound healing, metal depression and psychosis  Peptic ulcer, Cataract, glaucoma, growth suppression, hypocalcemia, PTH increased  Cushing syndrome  Secondary adrenal insufficiency
  68. 68. conclusion  Humans owe to inflammation & repair their ability to contain injuries & heal defects. Without inflammation, infections would go unnoticed, would never heal, & injured organs might remain permanent festering sores. However inflammation & repair may be potentially harmful

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