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Notes about inflammation

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  2. 2. OBJECTIVES Causes of inflammation Inflammation classifications – Acute Inflammation – Chronic Inflammation Systemic effects of inflammation
  3. 3. INFLAMMATION Latin word, inflammare = to burn Bodys response to injury DEFINITION: − Local defence mechanism initiated by tissue injury
  4. 4. INFLAMMATION Physiological response to tissue damage & accompanied by a characteristic series of local changes – Inflammatory reaction takes place in the surviving adjacent vascular & connective tissues
  5. 5. INFLAMMATION Purpose: Protection ⇨to localize & isolate toxic substances ⇨remove/destroy the injurious stimuli (pathogens) and damaged tissue ⇨initiate the healing and repair process – remove the cellular debris from the area
  6. 6. NOMENCLATURE Inflammatory lesion are usually indicated by the suffix ~itis Example: ⇨Appendicitis = inflammation of the appendix ⇨Meningitis = inflammation of the meninges Some exceptions, example: pneumonia, typhoid fever
  7. 7. CAUSES Physical agents →Mechanical injuries, alteration of temperature & pressure, radiation injuries, ultraviolet Chemical agents →Organic – microbial toxins & organic poisons (weedkillers) →Inorganic – acids, alkaline, drugs Biological agents/microbes →Infectious = bacteria, viruses, fungi, protozoa
  8. 8. CAUSES Immunologic disorders →Hypersensitivity reactions, autoimmunity, immunodificiency states Genetic/metabolic disorders → Gout, diabetes mellitus Antigens that stimulate immunological response
  10. 10. CLASSIFICATION Based on duration of the lesion and histologic appearances 2 classifications ⇨Acute inflammation ⇨Chronic inflammation
  12. 12. ACUTE INFLAMMATION Immediate & early response to an injurious agent = protective response! →Early vascular response and late cell response Relatively non-specific response →eliminate dead tissue, protect against local infection & allows immune system to response = beneficial
  13. 13. ACUTE INFLAMMATION Relatively short duration → lasting for minutes, several hours of a few days → may range from normal to severe
  14. 14. ACUTE INFLAMMATION 5 cardinal signs 1)Rubor 2)Calor 3)Tumor 4)Dolor 5)Functio laesa - latin words
  15. 15. ACUTE iNFLAMMATION1) Rubor  Redness  Due to dilation of small blood vessels within damaged tissue as it occurs in cellulitis by the action of mediators*cellulitis: inflammation spread to the connective tissue
  16. 16. ACUTE iNFLAMMATION2) Calor  Heat  Results from increased blood flow (hyperemia) due to:  regional vascular dilation  cellular metabolism
  17. 17. ACUTE iNFLAMMATION3) Tumor  Swelling  Due to accumulation of fluid in the extravascular space = increased vascular permeability
  18. 18. ACUTE iNFLAMMATION4) Dolor  Pain  Partly results from the stretching & destruction of tissues due to inflammatory edema & part from pus under pressure in as abcess cavity  Some chemicals of acute inflammation are also known to induce pain  Bradykinins, prostaglandin & serotonin
  19. 19. ACUTE iNFLAMMATION5) Functio leasa  Loss of function  Inflamed area is inhibited by pain while severe swelling may also physically immobilize the tissue
  20. 20. Steps ofAcute Inflammation
  21. 21. Steps of acute inflammation1) Increased blood flow = hyperemia2) Exudation of fluids & plasma proteins  Exudate: discharge of fluid or substances from cells or blood vessels onto the skin or organ surface3) Emigration of leucocytes
  22. 22. Capillaries become engorged & dilated with blood (congestion) Leakage of fluids and protein into the tissues = infiltration of leukocytes into the area of injuryLeukocytes engulf and digest the pathogens and help remove it from the area (phagocytosis)
  23. 23. 1) Hyperemia(a) Injured tissues by any agents(b) Following injury, both the arterioles supplying the damaged area and local capillaries dilate – increasing blood flow to the site • this causes redness (rubor) & increased heat (calor) in the affected region
  24. 24. 1) HyperemiaCaused mainly by local released of a number of chemical mediators from damaged cellsMast cells release histamine in response to tissue injury or infection
  25. 25. INJURY Damaged Cells Nervous Direct reactioneffect on (axon vessels CHEMICAL reflex) MEDIATORS VASCULAR DILATATION
  26. 26. 2) Exudation of Fluids* Exudation: increased passage of protein-rich fluid through the vessel wall into the interstitial tissue Fluid leaving local blood vessels & entering interstitial space = swelling / oedemaCaused by → Increased permeability of small blood vessels wall → Increased hydrostatic pressure
  27. 27. 2) Exudation of FluidsINCREASED PERMEABILITY Caused by → inflammatory mediators released by injured cells– prostaglandin, histamine & serotonin → cells that formed the single-layered venules pull apart from one another
  28. 28. 2) Exudation of FluidsINCREASED PERMEABILITY The opening of channels that allow the movement of → Excess fluid = leaves blood & enters tissues → Plasma proteins =albumin, globulin etc – normally retained in bloodstream  reduced osmotic pressure of blood
  29. 29. 2) Exudation of FluidsINCREASED HYDROSTATIC PRESSURE Increased blood flow into the capillary bed forces fluid out of the vessels & into the tissues Some interstitial fluid returns to capillaries but most of the inflammatory exudates, phagocytes & cell debris removed in lymph vessels → pores of the lymph vessels larger & pressure inside it is lower than blood capillaries
  30. 30. 3) Emigration of LeukocytesLoss of fluid → thicken the blood → reduced the flow → allowing leukocytes make contact & adhere to the vessel wall = selectin & integrins
  31. 31. 3) Emigration of LeukocytesMost important leukocyte = neutrophil → Adhere to the blood vessels lining → Squeeze between endothelial cells → Enters tissue and went to the inflamed area by chemotaxis → Main function: phagocytosis of antigen
  32. 32. 3) Emigration of LeukocytesMacrophages → larger and longer lived than neutrophils → phagocytose dead/dying tissue, microbes & other antigenic material and dead/dying neutrophils → predominently in inflamed tissue after 24hours → persist in the tissue if the situation is not resolved = chronic inflammation
  33. 33. CHEMOTAXISMovement of a motile cell/organism in a directioncorresponding to a gradient of increasing or decreasingconcentration of the particular chemotactic agent – Chemical attraction of leukocytes to an area of inflammation
  34. 34. PHAGOCYTOSIS eating CellMacrophages & neutrophils attracted to theinflammatory & infectious site by chemotaxisChemo-attractans released by injured cells & invadingmicrobesPhagocytes trap particles either by engulfing them withtheir body mass or by extending long psedopodia towardsthemNon-selective = bind, engulf and digest foreign cells orparticles
  35. 35. CHEMICAL MEDIATORSVarious chemical mediators have roles ininflammatory processThey may be circulating in plasma and requireactivation or may be secreted by inflammatory cells  Mast cells = histamine  Platelets = serotoninMany of these mediators have overlapping actions
  36. 36. Chemical mediators of InflammationVasodilating Histamine, serotonin,chemicals bradykinins, prostaglandinChemotactic Fibrin, collagen, mast cell,factors bacterial peptidesSubstances with Complement fragments ofboth vasodilating C5a and C3a, interferons,& chemotactic interleukines and plateleteffects secretion
  37. 37. Morphology ofAcute Inflammation
  38. 38. MORPHOLOGY Involves production of exudates (edema fluid with high protein concentration, frquently contain inflammatory cells)*Transudate? Non-inflammatory edema Caused by cardiac, renal, undernutritional and other disorders
  39. 39. MORPHOLOGY Different morphologic types of accute inflammation i. Serous inflammation - watery ii. Fibrinous inflammation - haemorrhagic iii.Suppurative (purulent) inflammation - pus iv.Catharral inflammation – mucous membrane v. Pseudomembranous inflammation
  40. 40. BLISTER, “Watery”, i.e., SEROUS
  41. 41. i. Serous Inflammation Characterized by an outpouring of a thin fluid that is derived from either the blood serum or secretion of mesothelial cells lining the peritoneal, pleural, and pericardial cavities It resolves without reactions
  42. 42. FIBRINOUS
  43. 43. ii. Fibrinous Inflammation More severe injuries Result in greater vascular permeability that ultimately leads to exudation of larger molecules such as fibrinogens through the vascular barrier Fibrinous exudate is characteristic of inflammation in serous body cavities such as the pericardium (butter and bread appearance) and pleura
  44. 44. ii. Fibrinous Inflammation Course of fibrous inflammation include: – Resolution by fibrinolysis – Scar formation between perietal and visceral surfaces i.e. the exudates get organized – Fibrous strand formation that bridges the pericardial space
  46. 46. iii. Suppurative Inflammation Characterized by the production of a large amount of pus – Pus is a thick creamy liquid, yellowish or blood stained in colour and composed of • A large number of living or dead leukocytes (pus cells) • Necrotic tissue debris • Living and dead bacteria • Edema fluid
  47. 47. iii. Suppurative Inflammation 2 types:A) Abscess formation: – abscess = a circumscribed accumulation of pus in a living tissue – encapsulated by a so-called pyogenic membrane, which consists of layers of fibrin, inflammatory cells and granulation tissue
  48. 48. iii. Suppurative Inflammation 2 types:B) Acute diffuse (phlegmonous) inflammation – characterized by diffuse spread of the exudate through tissue spaces – caused by virulent bacteria (eg. streptococci) without either localization or marked pus formation – example: Cellulitis (in palmar spaces)
  49. 49. iv. Catharral Inflammation Mild and superficial inflammation of the mucous membrane Commonly seen in the upper respiratory tract following viral infections where mucous secreting glands are present in large numbers example: Rhinitis.
  50. 50. v. Pseudomembranous Inflammation Basic elements – extensive confluent necrosis of the surface epithelium of an inflamed mucosa – severe acute inflammation of the underlying tissues The fibrinogens in the inflamed tissue coagulate within the necrotic epithelium
  51. 51. v. Pseudomembranous Inflammation Fibrinogen, necrotic epithelium, neutrophilic polymorphs, red blood cells, bacteria and tissue debris form a false (pseudo) membrane = forms a white or colored layer over the surface of inflamed mucosa Example: – Dipthetric infection of the pharynx or larynx – Clostridium difficille infection in the large bowel following certain antibiotic use
  52. 52. Effects ofAcute Inflammation
  53. 53. EFFECTS2 types of effects(a) Beneficial effects(b) Harmful effects
  54. 54. BENEFICIAL EFFECTSa) Dilution of toxins: ►concentration of chemical and bacterial toxins at the site of inflammation reduced by dilution in the exudate ►removal from the site by the flow of exudates from the venules through the tissue to the lymphatic
  55. 55. BENEFICIAL EFFECTSb) Protective antibodies: ►Formation of tissue exudation allows protective proteins including antibodies at the site of inflammation ►Thus, antibodies promote microbial destruction by phagocytosis or complement- mediated cell lysis = neutralise their toxins
  56. 56. BENEFICIAL EFFECTS(c)Fibrin formation: – Tissue damage is repaired and scars can form if fibroblasts are involved.
  57. 57. BENEFICIAL EFFECTSd) Promotion of phagocytosis ►Neutrophils & macrophages actively recruited to the inflamed areas = engulf biological & non-biological origin ►Phagocyte activity promoted by increasing temperature (local & systemic) ►Phagocytes may die at the inflamed area if the material they ingest resist digestion or excessive = disintegrate & released material that cause further damage
  58. 58. BENEFICIAL EFFECTSe) Cell nutrition: ►The flow of inflammatory exudates brings with it glucose, oxygen and other nutrients to meet the metabolic requirements of the greatly increased number of cells ►It also removes their solute waste products via lymphatic channels
  59. 59. BENEFICIAL EFFECTSf) Promotion of immunity: ►Micro-organisms and their toxins are carried by the exudates, either free or in phagocytes, along the lymphatics to local lymph nodes • they stimulate an immune response with the generation of antibodies and cellular immune mechanisms of defence
  60. 60. HARMFUL EFFECTS Tissue swelling ⇨Result of the increased blood flow & exudation ⇨Often accompanies by loss of function ⇨Effects can be harmful = depending on the site • Joint = limitation of movement • Larynx = interference with breathing
  61. 61. HARMFUL EFFECTS Pain ⇨Occurs when local swelling compress sensory nerve endings ⇨Exacerbated by chemical mediators of the inflammatory process that potentiate the sensitivity of the sensory nerve endings • Bradykinin • Prostaglandin
  62. 62. Course ofAcute Inflammation
  63. 63. COURSE OF ACUTE INFLAMMATIONpossible outcomes depend on removalof inflammatory exudate and replacementby either regenerated cells or scar tissue4 possible outcomes (1) Resolution (2) Healing by fibrosis (3) Abscess formation (4) Chronic inflammation
  64. 64. COURSE OF ACUTE INFLAMMATIONFactors affecting outcome of acuteinflammation (1) severity of tissue damage (2) capacity of stem cells to divide (3) type of agent causing damage
  65. 65. (1)Resolution involves complete restitution of normalarchitecture and function 3 main features which potentiate thissequel are → Minimal cell death & tissue damage → Rapid elimination of the causal agent → Local conditions favouring of fluid & debris
  66. 66. (1)Resolution Inflammatory process is reversed and → damaged cells are phagocytosed → fibrin strands are broken down by fibrinolytic enzymes → waste material is removed in lymph and blood vessels → repair is complete leaving only a small car
  67. 67. (1)Resolution Arises from damage to parenchyma inlabile/stable tissues  cells replaced by regeneration  normal function restoredCan only occur if the connective tissueframework of the tissue is intact & the tissueinvolved has the capacity to replace anyspecialised cells that have been lost
  68. 68. (2)Healing by Fibrosis Occurs when  connective tissue framework damage  tissue lacks the ability to regenerate specialised cells 1St: dead tissues & acute inflammatoryexudate removed by macrophages Defect filled by ingrowth of a specialisedvascular connective tissue called granulationtissue
  69. 69. (2)Healing by Fibrosisgranulation tissue - gradually producescollagen = form a fibrous (collagenous) scar =repairloss of some specialised cells & somearchitectural distortion by fibrous scar =structural integrity is re-established any impairment of function = dependent on theextent of loss of specialised cells
  70. 70. (2)Healing by Fibrosis Modified forms of repair occur in ► bone after a fracture when new bone is created ► brain with the formation of an astrocytic scar
  71. 71. (3)Abscess Formation Takes place when  acute inflammatory reaction fails to destroy/remove the cause of tissue damage  continues with a component of chronic inflammation Most common: infection by pyogenic bacteria As the acute inflammation progresses, there isliquefaction of the tissue to form pusPeripherally, a chronic inflammatory component& fibrous tissue surrounds the area = localising puss
  72. 72. (3)Abscess Formation If abscess left untreated, it can lead to  sinus formation  fistula formation
  73. 73. (3)Abscess FormationSinus  tract lined by granulation tissue  leading from a chronically inflamed cavity to a surface  cause the continuing presence of foreign or necrotic material  Example: sinus associated with osteomyelitis & pilonidal sinus
  74. 74. A pilonidal dimple is a small pit or sinus in the sacral areajust at the top of the crease between the buttocks - deeptract, rather than a shallow depression, leading to a sinusthat may contain hair.During adolescence the pilonidal dimple or tract maybecome infected forming a cyst-like structure called apilonidal cyst = may require surgical drainage or totalexcision to prevent reinfection
  75. 75. (3)Abscess FormationFistula  tract open at both ends  Abnormal communication b etween two surfaces is established  2 main types  congenital = development abnormality  acquired = trauma, inflammation or necrosis
  76. 76. (4)Chronic Inflammation May result following acute inflammationwhen an injurious agent persists over aprolonged period Causing concomitant tissue destruction,inflammation, organisation and repair Some injurious agents induced a chronicinflammatory type of response from theoutset
  78. 78. CHRONIC INFLAMMATION prolonged inflammatory process (weeks or months) where an active inflammation, tissue destruction and attempts at repair are proceeding simultaneously
  79. 79. Causes Persistent infections →Certain microorganisms associated with intracellular infection = tuberculosis, leprosy, certain fungi characterictically cause chronic inflammation →These organisms have low tosicity and evoke delayed hypersensitivity reactions
  80. 80. Causes Prolonged exposure to nondegradable but partially toxic substances →endogenous lipid components which result in atherosclerosis →exogenous substances such as silica, asbestos
  81. 81. Causes Progression from acute inflammation →acute inflammation almost always progresses to chronic inflammation following persistent suppuration as a result of • uncollapsed abscess cavities • foreign body materials (dirt, cloth, wool, etc) • sequesterum in osteomylitis • sinus/fistula from chronic abscesses
  82. 82. Causes Autoimmunity →autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosis are chronic inflammations from the outset
  83. 83. Morphology Cells of chronic inflammation – Monocytes & macrophages = main cells – T-lymphocytes – B-lymphocytes & plasma
  84. 84. Classification Classified into 2 types based on histologic features 1. Non-specific chronic inflammation 2. Specific inflammation (granulomatous inflammation)
  85. 85. Classification1. Non-specific chronic inflammation – involves a diffuse accumulation of macrophages and lymphocytes at site of injury that is usually productive with new fibrous tissue formations – example: Chronic cholecystitis.
  86. 86. Classification2. Specific inflammation – Granulomatous inflammation – characterized by the presence of granuloma • granuloma is a microscopic aggregate of epithelioid cells (modified macrophages)
  87. 87. Classification2. Specific inflammation – Epithelioid cell • is an activated macrophage, with a modified epithelial cell-like appearance (hence the name epithelioid) • can fuse with each other & form multinucleated giant cells – foreign body- type giant cells & Langhans giant cells
  88. 88. Classification2. Specific inflammation – granuloma is basically a collection of epithelioid cells, it also usually contains multinucleated giant cell & is usually surrounded by a cuff of lymphocytes and occasional plasma cells
  89. 89. Pathogenesis 2 types of granuloma 1. Foreign body granuloma 2. Immune granuloma
  90. 90. Pathogenesis1.Foreign body granuloma – initiated by inert foreign bodies such as talc, sutures (nonabsorbable), fibers, etc… – these foreign bodies are large enough to preclude phagocytosis by a single macrophage and do not incite an immune response
  91. 91. Pathogenesis2.Immune granulomas – antigen presenting cells (macrophages) engulf a poorly soluble inciting agent – then, the macrophage processes and presents part of the antigen and activated lymphocytes – the activated lymphocytes produce cytokines that activate another lymphocytes = transform macrophages into epitheloid & multinucleated giant cells & maintain the granuloma – Macrophage inhibitory factor helps to localize activated macrophages & epitheloid cells
  92. 92. Causes Major causes of granulomatious inflammation: – Bacterial: Tuberculosis, Leprosy, Syphilis, Cat scratch disease, Yersiniosis – Fungal: Histoplasmosis, Cryptococcosis, Coccidioidomycosis, Blastomycosis – Helminthic: Schistosomiasis – Protozoal: Leishmaniasis, Toxoplasmosis – Chlamydia: Lymphogranuloma venerum – Inorganic material: Berrylliosis – Idiopathic: Acidosis, Cohn’s disease, Primary biliary cirrhosis
  94. 94. Systemic effects of Inflammation Include 1. Fever 2. Endocrine & metabolic responses 3. Autonomic responses 4. Behavioural responses 5. Leukocytosis 6. Leukopenia 7. Weight loss
  95. 95. 1.Fever most important systemic manifestation of inflammation. It is coordinated by the hypothalamus & by cytokines released from macrophages and other cells2. Endocrine & metabolic responses the liver secrets acute phase proteins such as C- reactive proteins, Serum Amyloid A, complement and coagulation proteins Glucocorticoids (increased) Vasopressin (decreased)
  96. 96. 3. Autonomic responses redirection of blood flow from the cutaneous to the deep vascular bed pulse rate and blood pressure (increased) sweating (decreased)4. Behavioural responses Rigor, chills, anoroxia, somnolence and malaise
  97. 97. 5. Leukocytosis also a common feature of inflammation, especially in bacterial infections its usual count is 15,000 to 20,000 cells/mm3 most bacterial infections induce neutrophilia some viral infections such as infectious mononucleosis, & mumps cause lymphocytosis parasitic infestations & allergic reactions such as bronchial ashma & hay fever induce eosinophilia
  98. 98. 6. Leukopenia Also a feature of thyphoid fever and some parasitic infections7. Weight loss Catabolism of skeletal muscle, adipose tissue and the liver with resultant negative nitrogen balance