Download Inflammation

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
• greek root + -itis
• metritis, not uteritis
• nephritis, not renitis
Mechanisms
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local - in cases of mild injury
systemic
3 major
alteration
exsudation (inflammatory exsudate - 2 components
- luquid (exsudate) and cellular (infiltrate))
• poliferation (formation of granulation and fibrous
tissue)
• usualy - all 3 components - not the same intensity
Classification
• several points of view
• length
• acute × chronic (+ subacute, hyperacute)
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according to predominant component
alterative (predominance of necrosis - diphtheria)
exsudative (pleuritis)
proliferative (cholecystitis - thickening of the wall
by fibrous tissue)
Classification
• according to histological features
• nonspecific (not possible to trace the etiology) - vast
majority
• specific (e.g. TB)
• 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
Acute inflammation
• important role in inflammation has
microcirculation!
• (supply of white blood cells, interleukins,
fibrin, etc.)
Local symptomatology
• classical 5 symptoms (Celsus 1st c. B.C.,
Virchow 19th c. A.D.)
• calor - heat
• rubor - redness
• tumor - swelling
• dolor - pain
• functio laesa - loss (or impairment) of
function
Systemic symptomatology
• fever (irritation of centre of thermoregulation)
• leucocytosis - increased number of WBC
(neutrophils)
• leucopenia - decreased "
"
- viral
infections, salmonella infections, rickets
• immunologic reactions - increased level of some
substances (C-reactive protein)
Vascular changes
• vasodilatation, increased permeability of vessels due
to widened intercell. junctions and contraction of
endothelial cells (histamin, VEGF, bradykinin)
• protein poor transudate (edema)
• protein rich exudate
• leukocyte-dependent endothelial injury
• aggregation, adhesion, proteolysis) - leakage
Cellular events
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margination and adhesion of leukocytes
emigration of:
neutrophils (1-2 days)
monocytes (2-3 days)
chemotaxis (endogenous signaling moleculeslymphokines, exogenous-toxins)
• phagocytosis - lysosomal enzymes, free radicals, NO
- bacteriotoxicity, cytotoxicity
• passive emigration of RBC - no active role in
inflamm. - hemorrhagic inflammation
Outcomes of acute inflammation
• resolution - restoration to normal
• healing by scar (in case of tissue destruction)
• abscess formation (pus, pyogenic membrane,
resorption - pseudoxanthoma cells - weeks
to months)
• progression into chronic inflammation
Phagocytosis
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aghesion and invagination into cytoplasm
engulfment
lysosomes - destruction
in highly virulent microorganisms can die
leucocyte and not the microbe
• in highly resistant microorganisms persistence within macrophage - activation
after many years
Chronic inflammation
• reasons: persisting infection or prolonged
exposure to irritants
• repeated acute inflamations (otitis, rhinitis)
• primary chronic inflammation - low
virulence, sterile inflammations (silicosis)
• autoimmune reactions (rheumatic arthritis,
glomerulonephritis)
Chronic inflammation
• chronic inflammatory cells: lymphocytes, plasma
cells, monocytes/macrophages ("round cell"
infiltrate)
• activation of macrophages by various mediators fight against invaders
• lymphocytes - differentiation into plasma cells,
cytotoxic (NK), coordination with other parts of
immune system
• plasma cells - production of Ig
• monocytes-macrophages-specialized cells
(siderophages, gitter cells, mucophages)
Morphologic patterns of
inflammation
• serous - excessive accumulation of fluid, few
proteins - skin blister, serous membranes - initial
phases of inflamm.
• (modification - catarrhal - accumulation of mucus)
• fibrinous - higher vascular permeability - exsudation
of fibrinogen -> fibrin - e.g. pericarditis (cor
villosum, cor hirsutum - "hairy" heart
• fibrinolysis-resolution; organization-fibrosis-scar
• suppurative (purulent) - accumulation of
neutrophillic leucocytes - formation of pus
(pyogenic bacteria)
• interstitial-phlegmone - soft tissue
• localized collection-abscess (pyogenic membrane) e.g. folliculitis - furuncle - carbuncle
• formation of suppurative fistule
• accumulation of pus in preformed cavities empyema (gallbladder, thoracic)
• complications of suppurative inflamm.:
• bacteriemia (no clinical symptoms!; danger of
formation of secondary foci of inflamm.
(endocarditis, meningitis)
• sepsis (= massive bacteriemia) - septic fever,
activation of spleen, septic shock
• thrombophlebitis - secondary inflammation of wall
of the vein with subsequent thrombosis embolization - pyemia - hematogenous abscesses
(infected infarctions)
• lymphangiitis, lymphadenitis
• • pseudomembranous - fibrinous pseudomembrane
(diphtheria - Corynebacterium, dysenteria - Shigella)
- fibrin, necrotic mucosa, etiologic agens, leucocytes
• necrotizing - inflamatory necrosis of the surface ulcer (skin, gastric)
• gangrenous - secondary modification by bacteria wet gangrene - apendicitis, cholecystitis - risk of
perforation - peritonitis
• proliferative - primary × secondary; cholecystitis
• granulomatous - foreign body granuloma
(engulfment of foreign material - e.g. stitches) giant cells (multinucleated)
• specific inflammation - epithelioid granulomas
(epithelioid histiocytes, giant cells of Langhans type)
- TB, sarcoidosis, leprosy, syphilis, cat-scratch
disease, brucelosis, tularemia, beryliosis, infectious
rhinoscleroma
• cell mediated immune reaction