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

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

4. 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

5. 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)

6. 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

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

8. 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

9. 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)

10. 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

11. 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

12. 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

13. 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

14. 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)

15. 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)

16. 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)

17. 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 -> fibrin - e.g.
pericarditis (cor villosum, cor hirsutum - "hairy"
heart
 fibrinolysis  resolution; organization  fibrosis
 scar

18.  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)

19.  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

20.  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

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

22. 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

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 exsudate – sero-fibrinous exsudate
(macrophages)

24. 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

25. 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

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
 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