1 inflammation

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1 inflammation

  1. 1. Inflammation Jan Laco, M.D., Ph.D.
  2. 2. Inflammation <ul><li>complex protective reaction </li></ul><ul><li>caused by various endo- and exogenous stimuli </li></ul><ul><li>injurious agents are destroyed, diluted or walled-off </li></ul><ul><li>without inflammation and mechanism of healing could organism not survive </li></ul><ul><li>can be potentially harmfull </li></ul>
  3. 3. Terminology <ul><li>Greek root + -itis </li></ul><ul><li>metritis, not uteritis </li></ul><ul><li>kolpitis, not vaginitis </li></ul><ul><li>nephritis, not renitis </li></ul>
  4. 4. Mechanisms <ul><li>local - in cases of mild injury </li></ul><ul><li>systemic </li></ul><ul><li>3 major: </li></ul><ul><li>1. alteration </li></ul><ul><li>2. exsudation - inflammatory exsudate </li></ul><ul><ul><li>liquid (exsudate) </li></ul></ul><ul><ul><li>cellular (infiltrate) </li></ul></ul><ul><li>3. proliferation (formation of granulation and fibrous tissue) </li></ul><ul><li>usualy - all 3 components - not the same intensity </li></ul>
  5. 5. Classification <ul><li>several points of view </li></ul><ul><li>length: </li></ul><ul><ul><li>acute × chronic (+ subacute, hyperacute) </li></ul></ul><ul><li>according to predominant component </li></ul><ul><ul><li>1. alterative (predominance of necrosis - diphtheria) </li></ul></ul><ul><ul><li>2. exsudative (pleuritis) </li></ul></ul><ul><ul><li>3. proliferative (cholecystitis - thickening of the wall by fibrous tissue) </li></ul></ul>
  6. 6. Classification <ul><li>according to histological features </li></ul><ul><ul><li>nonspecific (not possible to trace the etiology) - vast majority </li></ul></ul><ul><ul><li>specific (e.g. TB) </li></ul></ul><ul><li>according to causative agent </li></ul><ul><ul><li>aseptic (sterile) - chemical substances, congelation, radiation - inflammation has a reparative character </li></ul></ul><ul><ul><li>septic (caused by living organisms) - inflammation has a protective character </li></ul></ul>
  7. 7. Acute inflammation <ul><li>important role in inflammation has microcirculation! </li></ul><ul><li>supply of white blood cells, interleukins, fibrin, etc. </li></ul>
  8. 8. Local symptomatology <ul><li>classical 5 symptoms (Celsus 1st c. B.C., Virchow 19th c. A.D.) </li></ul><ul><li>1. calor - heat </li></ul><ul><li>2. rubor - redness </li></ul><ul><li>3. tumor - swelling </li></ul><ul><li>4. dolor - pain </li></ul><ul><li>5. functio laesa - loss (or impairment) of function </li></ul>
  9. 9. Systemic symptomatology <ul><li>fever (irritation of centre of thermoregulation) </li></ul><ul><ul><li>TNF, IL-1 </li></ul></ul><ul><ul><li>IL-6 – high erythrocyte sedimentation rate </li></ul></ul><ul><li>leucocytosis - increased number of WBC </li></ul><ul><ul><li>bacteria – neutrophils </li></ul></ul><ul><ul><li>parasites – eosinophils </li></ul></ul><ul><ul><li>viruses - lymphocytosis </li></ul></ul><ul><li>leucopenia - decreased &quot; &quot; </li></ul><ul><ul><li>viral infections, salmonella infections, rickettsiosis </li></ul></ul><ul><li>immunologic reactions - increased level of some substances (C-reactive protein) </li></ul>
  10. 10. Vascular changes <ul><li>vasodilation </li></ul><ul><ul><li>increased permeability of vessels due to widened intercell. junctions and contraction of endothelial cells (histamin, VEGF, bradykinin) </li></ul></ul><ul><li>protein poor transudate (edema) </li></ul><ul><li>protein rich exsudate </li></ul><ul><li>leukocyte-dependent endothelial injury </li></ul><ul><ul><li>proteolysis – protein leakage </li></ul></ul><ul><li> platelet adhesion  thrombosis </li></ul>
  11. 11. Cellular events <ul><li>leukocytes margination  rolling  adhesion  transmigration </li></ul><ul><li>emigration of: </li></ul><ul><ul><li>neutrophils (1-2 days) </li></ul></ul><ul><ul><li>monocytes (2-3 days) </li></ul></ul><ul><li>chemotaxis </li></ul><ul><ul><li>endogenous signaling molecules - lymphokines </li></ul></ul><ul><ul><li>exogenous - toxins </li></ul></ul><ul><li>phagocytosis - lysosomal enzymes, free radicals, oxidative burst </li></ul><ul><li>passive emigration of RBC - no active role in inflamm. - hemorrhagic inflammation </li></ul>
  12. 12. Phagocytosis <ul><li>adhesion and invagination into cytoplasm </li></ul><ul><li>engulfment </li></ul><ul><li>lysosomes - destruction </li></ul><ul><li>in highly virulent microorganisms can die leucocyte and not the microbe </li></ul><ul><li>in highly resistant microorganisms - persistence within macrophage - activation after many years </li></ul>
  13. 13. Outcomes of acute inflammation <ul><li>1. resolution - restoration to normal, limited injury </li></ul><ul><ul><li>chemical substances neutralization </li></ul></ul><ul><ul><li>normalization of vasc. permeability </li></ul></ul><ul><ul><li>apoptosis of inflammatory cells </li></ul></ul><ul><ul><li>lymphatic drainage </li></ul></ul><ul><li>2. healing by scar </li></ul><ul><ul><li>tissue destruction </li></ul></ul><ul><ul><li>fibrinous inflammtion </li></ul></ul><ul><ul><li>purulent infl.  abscess formation (pus, pyogenic membrane, resorption - pseudoxanthoma cells - weeks to months) </li></ul></ul><ul><li>3. progression into chronic inflammation </li></ul>
  14. 14. Chronic inflammation <ul><li>reasons: </li></ul><ul><ul><li>persisting infection or prolonged exposure to irritants (intracell. surviving of agents - TBC) </li></ul></ul><ul><ul><li>repeated acute inflamations (otitis, rhinitis) </li></ul></ul><ul><ul><li>primary chronic inflammation - low virulence, sterile inflammations (silicosis) </li></ul></ul><ul><ul><li>autoimmune reactions (rheumatoid arthritis, glomerulonephritis, multiple sclerosis) </li></ul></ul>
  15. 15. Chronic inflammation <ul><li>chronic inflammatory cells (&quot;round cell&quot; infiltrate) </li></ul><ul><ul><li>lymphocytes </li></ul></ul><ul><ul><li>plasma cells </li></ul></ul><ul><ul><li>monocytes/macrophages activation of macrophages by various mediators - fight against invaders </li></ul></ul><ul><li>lymphocytes  plasma cells, cytotoxic (NK) cells, coordination with other parts of immune system </li></ul><ul><li>plasma cells - production of Ig </li></ul><ul><li>monocytes-macrophages-specialized cells (siderophages, gitter cells, mucophages) </li></ul>
  16. 16. Morphologic patterns of inflammation <ul><li>1. alterative </li></ul><ul><li>2. exsudative </li></ul><ul><ul><li>2a. serous </li></ul></ul><ul><ul><li>2b. fibrinous </li></ul></ul><ul><ul><li>2c. suppurative </li></ul></ul><ul><ul><li>2d. pseudomembranous </li></ul></ul><ul><ul><li>2e. necrotizing, gangrenous </li></ul></ul><ul><li>3. proliferative </li></ul><ul><ul><li>primary (rare) x secondary (cholecystitis) </li></ul></ul>
  17. 17. Morphologic patterns of inflammation <ul><li>2a. serous - excessive accumulation of fluid, few proteins - skin blister, serous membranes - initial phases of inflamm. </li></ul><ul><li>modification - catarrhal - accumulation of mucus </li></ul><ul><li>2b. fibrinous - higher vascular permeability - exsudation of fibrinogen -> fibrin - e.g. pericarditis (cor villosum, cor hirsutum - &quot;hairy&quot; heart </li></ul><ul><li>fibrinolysis  resolution; organization  fibrosis  scar </li></ul>
  18. 18. <ul><li>2c. suppurative (purulent) - accumulation of neutrophillic leucocytes - formation of pus (pyogenic bacteria) </li></ul><ul><li>interstitial </li></ul><ul><ul><li>phlegmone – diffuse soft tissue </li></ul></ul><ul><ul><li>abscess - localized collection </li></ul></ul><ul><ul><ul><li>acute – border – surrounding tissue </li></ul></ul></ul><ul><ul><ul><li>chronic – border - pyogenic membrane </li></ul></ul></ul><ul><ul><ul><li>Pseudoabscess – pus in lumen of hollow organ </li></ul></ul></ul><ul><li>formation of suppurative fistule </li></ul><ul><li>accumulation of pus in preformed cavities - empyema (gallbladder, thoracic) </li></ul>
  19. 19. <ul><li>complications of suppurative inflamm.: </li></ul><ul><li>bacteremia (no clinical symptoms!; danger of formation of secondary foci of inflamm. (endocarditis, meningitis) </li></ul><ul><li>sepsis (= massive bacteremia) - septic fever, activation of spleen, septic shock </li></ul><ul><li>thrombophlebitis - secondary inflammation of wall of the vein with subsequent thrombosis - embolization - pyemia - hematogenous abscesses (infected infarctions) </li></ul><ul><li>lymphangiitis, lymphadenitis </li></ul>
  20. 20. <ul><li>2d. pseudomembranous - fibrinous pseudomembrane (diphtheria - Corynebacterium, dysentery - Shigella) - fibrin, necrotic mucosa, etiologic agens, leucocytes </li></ul><ul><li>2e. necrotizing - inflammatory necrosis of the surface - ulcer (skin, gastric) </li></ul><ul><ul><li>gangrenous - secondary modification by bacteria - wet gangrene - apendicitis, cholecystitis - risk of perforation - peritonitis </li></ul></ul>
  21. 21. Granulomatous inflammation <ul><li>distinctive chronic inflammation type </li></ul><ul><li>cell mediated immune reaction (delayed) </li></ul><ul><li>aggregates of activated macrophages  epithelioid cell  multinucleated giant cells (of Langhans type x of foreign body type) </li></ul><ul><li>NO agent elimination but walling off </li></ul><ul><li>intracellulary agents (TBC) </li></ul>
  22. 22. Granulomatous inflammation <ul><li>1. Bacteria </li></ul><ul><ul><li>TBC </li></ul></ul><ul><ul><li>leprosy </li></ul></ul><ul><ul><li>syphilis (3rd stage) </li></ul></ul><ul><li>2. Parasites + Fungi </li></ul><ul><li>3. Inorganic metals or dust </li></ul><ul><ul><li>silicosis </li></ul></ul><ul><ul><li>berylliosis </li></ul></ul><ul><li>4. Foreign body </li></ul><ul><ul><li>suture (Schloffer „tumor“), breast prosthesis </li></ul></ul><ul><li>5. Unknown - sarcoidosis </li></ul>
  23. 23. Tuberculosis – general pathology <ul><li>1. TBC nodule – proliferative </li></ul><ul><li>Gross: grayish, firm, 1-2 mm (milium)  central soft yellow necrosis (cheese-like – caseous)  calcification </li></ul><ul><li>Mi: central caseous necrosis (amorphous homogenous + karyorrhectic powder) + macrophages  epithelioid cells  multinucleated giant cells of Langhans type + lymphocytic rim </li></ul><ul><li>2. TBC exsudate – sero-fibrinous exsudate (macrophages) </li></ul>
  24. 24. Leprosy <ul><li>M. leprae, Asia, Africa </li></ul><ul><li>in dermal macrophages and Schwann cells </li></ul><ul><li>air droplets + long contact </li></ul><ul><li>rhinitis, eyelid destruction, facies leontina </li></ul><ul><li>1. lepromatous – infectious </li></ul><ul><ul><li>skin lesion – foamy macrophages (Virchow cells) + viscera </li></ul></ul><ul><li>2. tuberculoid – steril </li></ul><ul><ul><li>in peripheral nerves – tuberculoid granulomas - anesthesia </li></ul></ul><ul><li>death – secondary infections + amyloidosis </li></ul>
  25. 25. Syphilis <ul><li>Treponema pallidum (spichochete) </li></ul><ul><li>STD + transplacental fetus infection </li></ul><ul><li>acquired (3 stages) x congenital </li></ul><ul><li>basic microspical appearance: </li></ul><ul><ul><li>1. proliferative endarteritis (endothelial hypertrophy  intimal fibrosis  local ischemia) + inflammation (plasma cells) </li></ul></ul><ul><ul><li>2. gumma – central coagulative necrosis + specific granulation tissue + fibrous tissue </li></ul></ul>
  26. 26. Syphilis <ul><li>1. primary syphilis - contagious </li></ul><ul><li>chancre (ulcus durum, hard chancre) </li></ul><ul><li>M: penis x F: vagina, cervix </li></ul><ul><li>painless, firm ulceration + regional painless lymphadenopathy </li></ul><ul><li>spontaneous resolve (weeks)  scar </li></ul>
  27. 27. Syphilis <ul><li>2. secondary syphilis - contagious </li></ul><ul><li>after 2 months </li></ul><ul><li>generalized lymphadenopathy + various mucocutaneous lesions </li></ul><ul><li>condylomata lata - anogenital region, inner thighs, oral cavity </li></ul>
  28. 28. Syphilis <ul><li>3. tertiary syphilis </li></ul><ul><li>after long time (5 years) </li></ul><ul><li>1) cardiovascular - syphilitic aortitis (proximal a.) </li></ul><ul><ul><li>endarteritis of vasa vasorum  scaring of media  dilation  aneurysm </li></ul></ul><ul><li>2) neurosyphilis – tabes dorsalis + general paresis </li></ul><ul><ul><li>degeneration of posterior columns of spinal cord  sensory + gait abnormality </li></ul></ul><ul><ul><li>cortical atrophy  psychic deterioration </li></ul></ul><ul><li>3) gumma – ulcerative lesions of bone, skin, mucosa – oral cavity </li></ul>
  29. 29. Congenital syphilis <ul><li>1) abortus </li></ul><ul><ul><li>hepatomegaly + pancreatitis + pneumonia alba </li></ul></ul><ul><li>2) infantile syphilis </li></ul><ul><ul><li>chronic rhinitis (snuffles) + mucocutaneous lesions </li></ul></ul><ul><li>3) late (tardive, congenital) syphilis </li></ul><ul><ul><li>> 2 years duration </li></ul></ul><ul><ul><li>Hutchinson triad – notched central incisors + keratitis (blindness) + deafness (injury of n. VIII) </li></ul></ul><ul><ul><li>mulberry molars + saddle nose </li></ul></ul>

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