Inflammation Jan Laco M D Ph D Inflammation

Inflammation Jan Laco, M. D. , Ph. D.

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

Terminology l Greek root + -itis l metritis, not uteritis l kolpitis, not vaginitis l nephritis, not renitis

Mechanisms l l 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) l usualy - all 3 components - not the same intensity l

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

Classification l according to histological features – nonspecific (not possible to trace the etiology) - vast majority – specific (e. g. TB) l 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 l important role in inflammation has microcirculation! l supply of white blood cells, interleukins, fibrin, etc.

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

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

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

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

Phagocytosis l adhesion and invagination into cytoplasm l engulfment l lysosomes - destruction l in highly virulent microorganisms can die leucocyte and not the microbe l in highly resistant microorganisms persistence within macrophage - activation after many years

Outcomes of acute inflammation l 1. resolution - restoration to normal, limited injury – – l 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) l 3. progression into chronic inflammation

Chronic inflammation l 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)

Chronic inflammation l 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 l plasma cells - production of Ig l monocytes-macrophages-specialized cells (siderophages, gitter cells, mucophages) l

Morphologic patterns of inflammation 1. alterative l 2. exsudative l – – – l 2 a. serous 2 b. fibrinous 2 c. suppurative 2 d. pseudomembranous 2 e. necrotizing, gangrenous 3. proliferative – primary (rare) x secondary (cholecystitis)

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

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

l l l 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

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

Granulomatous inflammation l distinctive chronic inflammation type l cell mediated immune reaction (delayed) l aggregates of activated macrophages epithelioid cell multinucleated giant cells (of Langhans type x of foreign body type) l NO agent elimination but walling off l intracellulary agents (TBC)

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

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

Leprosy l l l 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 l 2. tuberculoid – steril – in peripheral nerves – tuberculoid granulomas - anesthesia l death – secondary infections + amyloidosis

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

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

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

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

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