Inflammation

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Inflammation

• Jan Laco, M.D., Ph.D.

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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

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Terminology

• Greek root -itis
• metritis, not uteritis
• kolpitis, not vaginitis
• nephritis, not renitis

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Mechanisms

• local - in cases of mild injury
• systemic
• 3 major
• 1. alteration
• 2. exsudation - inflammatory exsudate
• liquid (exsudate)
• cellular (infiltrate)
• 3. proliferation (formation of granulation and
  fibrous tissue)
• usualy - all 3 components - not the same intensity

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Classification

• several points of view
• length
• acute chronic ( subacute, hyperacute)
• according to predominant component
• 1. alterative (predominance of necrosis -
  diphtheria)
• 2. exsudative (pleuritis)
• 3. proliferative (cholecystitis - thickening of
  the wall by fibrous tissue)

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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

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Acute inflammation

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

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Local symptomatology

• classical 5 symptoms (Celsus 1st c. B.C., Virchow
  19th c. A.D.)
• 1. calor - heat
• 2. rubor - redness
• 3. tumor - swelling
• 4. dolor - pain
• 5. functio laesa - loss (or impairment) of
  function

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Systemic symptomatology

• fever (irritation of centre of thermoregulation)
• TNF, IL-1
• IL-6 high erythrocyte sedimentation rate
• leucocytosis - increased number of WBC
• bacteria neutrophils
• parasites eosinophils
• viruses - lymphocytosis
• leucopenia - decreased " "
  
• viral infections, salmonella infections,
  rickettsiosis
• immunologic reactions - increased level of some
  substances (C-reactive protein)

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Vascular changes

• vasodilation
• increased permeability of vessels due to widened
  intercell. junctions and contraction of
  endothelial cells (histamin, VEGF, bradykinin)
• protein poor transudate (edema)
• protein rich exsudate
• leukocyte-dependent endothelial injury
• proteolysis protein leakage
• ? platelet adhesion ? thrombosis

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Cellular events

• leukocytes margination ? rolling ? adhesion ?
  transmigration
• emigration of
• neutrophils (1-2 days)
• monocytes (2-3 days)
• chemotaxis
• endogenous signaling molecules - lymphokines
• exogenous - toxins
• phagocytosis - lysosomal enzymes, free radicals,
  oxidative burst
• passive emigration of RBC - no active role in
  inflamm. - hemorrhagic inflammation

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Phagocytosis

• adhesion 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

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Outcomes of acute inflammation

• 1. resolution - restoration to normal, limited
  injury
• chemical substances neutralization
• normalization of vasc. permeability
• apoptosis of inflammatory cells
• lymphatic drainage
• 2. healing by scar
• tissue destruction
• fibrinous inflammtion
• purulent infl. ? abscess formation (pus, pyogenic
  membrane, resorption - pseudoxanthoma cells -
  weeks to months)
• 3. progression into chronic inflammation

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Chronic inflammation

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

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Chronic inflammation

• chronic inflammatory cells ("round cell"
  infiltrate)
• lymphocytes
• plasma cells
• monocytes/macrophages activation of macrophages
  by various mediators - fight against invaders
• lymphocytes ? plasma cells, cytotoxic (NK) cells,
  coordination with other parts of immune system
• plasma cells - production of Ig
• monocytes-macrophages-specialized cells
  (siderophages, gitter cells, mucophages)

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Morphologic patterns of inflammation

• 1. alterative
• 2. exsudative
• 2a. serous
• 2b. fibrinous
• 2c. suppurative
• 2d. pseudomembranous
• 2e. necrotizing, gangrenous
• 3. proliferative
• primary (rare) x secondary (cholecystitis)

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Morphologic patterns of inflammation

• 2a. serous - excessive accumulation of fluid, few
  proteins - skin blister, serous membranes -
  initial phases of inflamm.
• modification - catarrhal - accumulation of mucus
• 2b. fibrinous - higher vascular permeability -
  exsudation of fibrinogen -gt fibrin - e.g.
  pericarditis (cor villosum, cor hirsutum -
  "hairy" heart
• fibrinolysis ? resolution organization ?
  fibrosis ? scar

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• 2c. suppurative (purulent) - accumulation of
  neutrophillic leucocytes - formation of pus
  (pyogenic bacteria)
• interstitial
• phlegmone diffuse soft tissue
• abscess - localized collection
• acute border surrounding tissue
• chronic border - pyogenic membrane
• Pseudoabscess pus in lumen of hollow organ
• formation of suppurative fistule
• accumulation of pus in preformed cavities -
  empyema (gallbladder, thoracic)

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• complications of suppurative inflamm.
• bacteremia (no clinical symptoms! danger of
  formation of secondary foci of inflamm.
  (endocarditis, meningitis)
• sepsis ( massive bacteremia) - 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

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• 2d. pseudomembranous - fibrinous pseudomembrane
  (diphtheria - Corynebacterium, dysentery -
  Shigella) - fibrin, necrotic mucosa, etiologic
  agens, leucocytes
• 2e. necrotizing - inflammatory necrosis of the
  surface - ulcer (skin, gastric)
• gangrenous - secondary modification by bacteria -
  wet gangrene - apendicitis, cholecystitis - risk
  of perforation - peritonitis

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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)
• NO agent elimination but walling off
• intracellulary agents (TBC)

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Granulomatous inflammation

• 1. Bacteria
• TBC
• leprosy
• syphilis (3rd stage)
• 2. Parasites Fungi
• 3. Inorganic metals or dust
• silicosis
• berylliosis
• 4. Foreign body
• suture (Schloffer tumor), breast prosthesis
• 5. Unknown - sarcoidosis

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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 exsudate sero-fibrinous exsudate
  (macrophages)

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Leprosy

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

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Syphilis

• Treponema pallidum (spichochete)
• STD transplacental fetus infection
• acquired (3 stages) x congenital
• basic microspical appearance
• 1. proliferative endarteritis (endothelial
  hypertrophy ? intimal fibrosis ? local ischemia)
  inflammation (plasma cells)
• 2. gumma central coagulative necrosis
  specific granulation tissue fibrous tissue

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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

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Syphilis

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

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Syphilis

• 3. tertiary syphilis
• after long time (5 years)
• 1) cardiovascular - syphilitic aortitis (proximal
  a.)
• endarteritis of vasa vasorum ? scaring of media ?
  dilation ? aneurysm
• 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

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Congenital syphilis

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