This document discusses inflammation and its various aspects. It defines inflammation as a complex protective reaction caused by endo- and exogenous stimuli. It then describes the different mechanisms, classifications, symptomatology, cellular events, and outcomes of acute and chronic inflammation. It also summarizes specific inflammatory diseases like tuberculosis, leprosy, syphilis, and their histopathological characteristics.

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

2. InflammationInflammation
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. TerminologyTerminology
Greek root + -itis
metritis, not uteritis
kolpitis, not vaginitis
nephritis, not renitis

4. MechanismsMechanisms
 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. ClassificationClassification
 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. ClassificationClassification
 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 inflammationAcute inflammation
important role in inflammation has
microcirculation!
supply of white blood cells, interleukins,
fibrin, etc.

8. Local symptomatologyLocal 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 symptomatologySystemic 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 changesVascular 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 eventsCellular 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. PhagocytosisPhagocytosis
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 inflammationOutcomes 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 inflammationChronic 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 inflammationChronic 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 ofMorphologic patterns of
inflammationinflammation
 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 ofMorphologic patterns of
inflammationinflammation
 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 inflammationGranulomatous 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 inflammationGranulomatous 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 – generalTuberculosis – general
pathologypathology
 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. LeprosyLeprosy
 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. SyphilisSyphilis
 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. SyphilisSyphilis
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. SyphilisSyphilis
2. secondary syphilis - contagious
after 2 months
generalized lymphadenopathy + various
mucocutaneous lesions
condylomata lata - anogenital region, inner
thighs, oral cavity

28. SyphilisSyphilis
 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 syphilisCongenital 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