1 / 29

Inflammation

Inflammation. Jan Laco, MD, PhD. Inflammation. complex protective reaction caused by various endo- and exogenous stimuli injurious agents are destroyed, diluted or walled-off without inflammation and mechanism of healing could organism not survive can be potentially harmfull. Terminology.

dominguezm
Télécharger la présentation

Inflammation

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Inflammation Jan Laco, MD, PhD

  2. Inflammation • complex protective reaction • caused by various endo- and exogenous stimuli • injurious agents are destroyed, diluted or walled-off • without inflammation and mechanism of healing could organism not survive • can be potentially harmfull

  3. Terminology • Greek root + -itis • metritis, not uteritis • kolpitis, not vaginitis • nephritis, not renitis • glossitis, not linguitis • cheilitis, not labiitis

  4. Mechanisms • A) local - mild injury • B) systemic – severe injury • 3 major changes • 1. alteration – tissue change • 2. exudation - inflammatory exudate • liquid + proteins (exudate) • cellular (infiltrate) • 3. proliferation • formation of granulation and fibrous tissue • usually - all 3 components - not the same intensity

  5. Classification • several points of view • according to length • acute × chronic (+ subacute, hyperacute) • according to predominant component • 1. alterative • 2. exudative • 3. proliferative

  6. Classification • according to histological features • non-specific (not possible to trace etiology) - vast majority • specific / granulomatous (e.g. TBC) • according to causative agent • aseptic (sterile) - chemical substances, congelation, radiation - inflammation has a reparative character • septic (caused by living organisms) - inflammation has a protective character

  7. Acute inflammation • early response • important role in inflammation has microcirculation! • supply of white blood cells, interleukins, fibrin, etc.

  8. Local symptomatology • classical 5 symptoms (Celsus, 1st c. BC) • 1. calor – heat, warmth • 2. rubor – redness, erythema • 3. tumor – swelling, edema • 4. dolor - pain • 5. functio laesa – function loss/impairment

  9. Systemic symptoms • fever (irritation of thermoregulatory centre) • TNF, IL-1 • IL-6 – high RBCs sedimentation rate (via fibrinogen) • leukocytosis - increased WBCs number • bacteria – neutrophils • parasites – eosinophils • viruses - lymphocytosis • leukopenia - decreased WBCs number • viral infections, salmonella infections, rickettsioses • immunologic reactions – “acute phase reactants“ • C-reactive protein, complement, SAA, fibrinogen, ...

  10. Vascular changes • 1. arteriolar vasodilation (redness + warmth) • 2. increased permeability of vessels • widened intercellular junctions • retraction of endothelial cells (histamin, VEGF, bradykinin) • protein-poor transudate (edema) • protein-rich exudate • 3. endothelial injury – direct x leukocyte-dependent • proteolysis – protein leakage •  platelets adhesion  thrombosis

  11. Cellular events • leukocytes margination  rolling  adhesion  transmigration by diapedesis (in venules) • transmigration • neutrophils (1-2 days) • monocytes (2-3 days) • chemotaxis (along chemical gradient) • endogenous signaling molecules – ILs, LTs, C5a • exogenous – toxins, bacterial proteins, ... • phagocytosis (see below) • passive migration of RBCs • no active role in inflammation - hemorrhagic inflammation

  12. Phagocytosis • 1. recognition and attachment • facilitated by opsonins (IgG, C3b) • 2. engulfment • pseudopods formation  phagocytic vacuole + lysosome  phagolysosome • 3. killing and degradation • oxidative burst – reactive oxygen metabolits – superoxide ion, hydrogen peroxide, hypochlorous radicals • lysosomal acid hydrolases • in highly virulent microorganisms can die leukocyte and not the microbe • in highly resistant microorganisms - persistence within macrophage - activation after many years (TBC)

  13. Outcomes of acute inflammation • 1. resolution - restoration to normal, in limited injury • chemical substances neutralization • normalization of vascular permeability • apoptosis of inflammatory cells • increased lymphatic drainage • 2. healing by granulation tissue / fibrous scar • tissue destruction • fibrinous inflammation  adhesions, fibrosis • purulent inflammation  abscess formation (pus, pyogenic membrane, resorption - pseudoxanthoma cells - weeks to months) • 3. progression into chronic inflammation

  14. Chronic inflammation • reasons: • persisting infection or prolonged exposure to irritants (intracell. surviving of agents - TBC) • repeated acute inflammations (otitis, rhinitis) • primary chronic inflammation - low virulence, sterile inflammations (silicosis) • autoimmune reactions (rheumatoid arthritis, glomerulonephritides, multiple sclerosis)

  15. Chronic inflammation • chronic inflammatory cells ("round cell" infiltrate) • lymphocytes (T and B), plasma cells • eosinophils – parasites, allergies • monocytes / macrophages activation by various mediators - fight against invaders • B lymphocytes  plasma cells, Ig production • NK cells • monocytes-macrophages specialized cells (siderophages, gitter cells, mucophages)

  16. Morphologic patterns of inflammation • 1. alterative • poliomyelitis anterior acuta, diphtherial myocarditis • 2. exudative • 2a. serous • 2b. fibrinous • 2c. suppurative • 2d. necrotizing, gangrenous • 2e. non-purulent • 3. proliferative • primary (rare) x secondary (cholecystitis)

  17. Morphologic patterns of inflammation • 2a. serous • excessive accumulation of fluid, few proteins • e.g. skin blister, serous membranes - initial phases of inflammation, effusions • modification - catarrhal - accumulation of mucus on mucosas - larynx • 2b. fibrinous • higher vascular permeability - exudation of fibrinogen -> fibrin • formation of pseudomembranes - fibrin, necrotic mucosa, etiologic agens, leukocytes • e.g. diphtheria - Corynebacterium, dysentery – Shigella spp., Cl. difficile • e.g. pericarditis (cor villosum, cor hirsutum - "hairy" heart) • e.g. lobar pneumonia – Str. pneumoniae • fibrinolysis  resolution • organization  fibrosis  scar, adhesions

  18. 2c. suppurative (purulent) - accumulation of neutrophillic leukocytes - formation of pus • pyogenic bacteria - Staphylococci • interstitial • phlegmone – diffuse • abscess - localized collection • acute – border – surrounding tissue • chronic – border - pyogenic membrane • pseudoabscess – pus in lumen of hollow organ (epithelium) • formation of suppurative fistule • accumulation of pus in preformed cavities - empyema (gallbladder, thoracic cavity)

  19. complications of suppurative inflammation • bacteremia • no clinical symptoms! • formation of secondary foci of inflamm. (endocarditis, meningitis) • sepsis = massive bacteremia • septic fever, activation of spleen, septic shock • thrombophlebitis • secondary inflammation of vein wall followed by thrombosis - embolization • pyemia - hematogenous abscesses (infected infarctions) • lymphangiitis, lymphadenitis

  20. 2d. necrotizing • inflammatory necrosis of the surface - ulcer (skin, stomach) • gangrenous - secondary modification by bacteria - apendicitis, cholecystitis - risk of perforation – peritonitis • 2e. non-purulent • round cell inflammatory infiltrate

  21. Granulomatous inflammation • distinctive chronic inflammation type • cell mediated immune reaction (delayed) • aggregates of activated macrophages  epithelioid cell  multinucleated giant cells (of Langhans type x of foreign body type) • lymphocytic rim • NO agent elimination but walling off • intracellulary agents (TBC) x inert foreign bodies

  22. Granulomatous inflammation • 1. Bacteria • TBC • leprosy • syphilis (3rd stage - gumma) • 2. Parasites + Fungi • 3. Inorganic metals or dust • silicosis • berylliosis • 4. Foreign body • suture (Schloffer “tumor“), breast prosthesis, vascular graft • 5. Unknown • – sarcoidosis, Wegener´s granulomatosis, Crohn disease

  23. Tuberculosis – general pathology • 1. TBC nodule – proliferative • Gross: grayish, firm, 1-2 mm (milium)  central soft yellow necrosis (cheese-like – caseous)  calcification • Mi: central caseous necrosis (amorphous homogenous + karyorrhectic powder) + macrophages  epithelioid cells  multinucleated giant cells of Langhans type + lymphocytic rim • 2. TBC exudate – sero-fibrinous exudate (macrophages)

  24. Leprosy • M. leprae, Asia, Africa • in dermal macrophages and Schwann cells • air droplets + long contact • rhinitis, eyelid destruction, facies leontina • 1. lepromatous – contagious • skin lesion – foamy macrophages (Virchow cells) + viscera • 2. tuberculoid – sterile • in peripheral nerves – tuberculoid granulomas - anesthesia • death – secondary infections + amyloidosis

  25. Syphilis • Treponema pallidum (spirochete) • STD + transplacental fetus infection • acquired (3 stages) x congenital • basic microscopic appearance: • 1. proliferative endarteritis (endothelial hypertrophy  intimal fibrosis  local ischemia) + inflammation (plasma cells) • 2. gumma – central coagulative necrosis + specific granulation tissue + fibrous tissue

  26. Syphilis • 1. primary syphilis - contagious • chancre (ulcus durum, hard chancre) • M: penis x F: vagina, cervix • painless, firm ulceration + regional painless lymphadenopathy • spontaneous resolve (weeks)  scar

  27. Syphilis • 2. secondary syphilis - contagious • after 2 months • generalized lymphadenopathy + various mucocutaneous lesions • condylomata lata - anogenital region, inner thighs, oral cavity

  28. Syphilis • 3. tertiary syphilis • after long time (5 years) • 1) cardiovascular - syphilitic aortitis (proximal a.) • endarteritis of vasa vasorum  scaring of media  dilation  aneurysm (thoracic aorta) • 2) neurosyphilis – tabes dorsalis + general paresis • degeneration of posterior columns of spinal cord  sensory + gait abnormality • cortical atrophy  psychic deterioration • 3) gumma – ulcerative lesions of bone, skin, mucosa – oral cavity

  29. Congenital syphilis • 1) abortus • hepatomegaly + pancreatitis + pneumonia alba • 2) infantile syphilis • chronic rhinitis (snuffles) + mucocutaneous lesions • 3) late (tardive, congenital) syphilis • > 2 years duration • Hutchinson triad – notched central incisors + keratitis (blindness) + deafness (injury of n. VIII) • mulberry molars + saddle nose

More Related