1. Inflammation
Jan Laco, MD, PhD

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
glossitis, not linguitis
cheilitis, not labiitis

4. Mechanisms A) local - mild injury B) systemic – severe injury
3 major changes
1. alteration – tissue change
2. exudation - inflammatory exudate
liquid + proteins (exudate)
cellular (infiltrate)
3. proliferation
formation of granulation and fibrous tissue
usually - all 3 components - not the same intensity

5. Classification several points of view according to length
acute × chronic (+ subacute, hyperacute)
according to predominant component
1. alterative
2. exudative
3. proliferative

6. Classification according to histological features
non-specific (not possible to trace etiology) - vast majority
specific / granulomatous (e.g. TBC)
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 early response
important role in inflammation has microcirculation!
supply of white blood cells, interleukins, fibrin, etc.

8. Local symptomatology classical 5 symptoms (Celsus, 1st c. BC)
1. calor – heat, warmth
2. rubor – redness, erythema
3. tumor – swelling, edema
4. dolor - pain
5. functio laesa – function loss/impairment

9. Systemic symptoms fever (irritation of thermoregulatory centre)
TNF, IL-1
IL-6 – high RBCs sedimentation rate (via fibrinogen)
leukocytosis - increased WBCs number
bacteria – neutrophils
parasites – eosinophils
viruses - lymphocytosis
leukopenia - decreased WBCs number
viral infections, salmonella infections, rickettsioses
immunologic reactions – “acute phase reactants“
C-reactive protein, complement, SAA, fibrinogen, ...

10. Vascular changes 1. arteriolar vasodilation (redness + warmth)
2. increased permeability of vessels
widened intercellular junctions
retraction of endothelial cells (histamin, VEGF, bradykinin)
protein-poor transudate (edema)
protein-rich exudate
3. endothelial injury – direct x leukocyte-dependent
proteolysis – protein leakage
 platelets adhesion  thrombosis

11. Cellular events
leukocytes margination  rolling  adhesion  transmigration by diapedesis (in venules)
transmigration
neutrophils (1-2 days)
monocytes (2-3 days)
chemotaxis (along chemical gradient)
endogenous signaling molecules – ILs, LTs, C5a
exogenous – toxins, bacterial proteins, ...
phagocytosis (see below)
passive migration of RBCs
no active role in inflammation - hemorrhagic inflammation

12. Phagocytosis 1. recognition and attachment 2. engulfment
facilitated by opsonins (IgG, C3b)
2. engulfment
pseudopods formation  phagocytic vacuole + lysosome  phagolysosome
3. killing and degradation
oxidative burst – reactive oxygen metabolits – superoxide ion, hydrogen peroxide, hypochlorous radicals
lysosomal acid hydrolases
in highly virulent microorganisms can die leukocyte and not the microbe
in highly resistant microorganisms - persistence within macrophage - activation after many years (TBC)

13. Outcomes of acute inflammation
1. resolution - restoration to normal, in limited injury
chemical substances neutralization
normalization of vascular permeability
apoptosis of inflammatory cells
increased lymphatic drainage
2. healing by granulation tissue / fibrous scar
tissue destruction
fibrinous inflammation  adhesions, fibrosis
purulent inflammation  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 inflammations (otitis, rhinitis)
primary chronic inflammation - low virulence, sterile inflammations (silicosis)
autoimmune reactions (rheumatoid arthritis, glomerulonephritides, multiple sclerosis)

15. Chronic inflammation
chronic inflammatory cells ("round cell" infiltrate)
lymphocytes (T and B), plasma cells
eosinophils – parasites, allergies
monocytes / macrophages activation by various mediators - fight against invaders
B lymphocytes  plasma cells, Ig production
NK cells
monocytes-macrophages specialized cells (siderophages, gitter cells, mucophages)

16. Morphologic patterns of inflammation
1. alterative
poliomyelitis anterior acuta, diphtherial myocarditis
2. exudative
2a. serous
2b. fibrinous
2c. suppurative
2d. necrotizing, gangrenous
2e. non-purulent
3. proliferative
primary (rare) x secondary (cholecystitis)

17. Morphologic patterns of inflammation
2a. serous
excessive accumulation of fluid, few proteins
e.g. skin blister, serous membranes - initial phases of inflammation, effusions
modification - catarrhal - accumulation of mucus on mucosas - larynx
2b. fibrinous
higher vascular permeability - exudation of fibrinogen -> fibrin
formation of pseudomembranes - fibrin, necrotic mucosa, etiologic agens, leukocytes
e.g. diphtheria - Corynebacterium, dysentery – Shigella spp., Cl. difficile
e.g. pericarditis (cor villosum, cor hirsutum - "hairy" heart)
e.g. lobar pneumonia – Str. pneumoniae
fibrinolysis  resolution
organization  fibrosis  scar, adhesions

18. pyogenic bacteria - Staphylococci interstitial
2c. suppurative (purulent) - accumulation of neutrophillic leukocytes - formation of pus
pyogenic bacteria - Staphylococci
interstitial
phlegmone – diffuse
abscess - localized collection
acute – border – surrounding tissue
chronic – border - pyogenic membrane
pseudoabscess – pus in lumen of hollow organ (epithelium)
formation of suppurative fistule
accumulation of pus in preformed cavities - empyema (gallbladder, thoracic cavity)

19. complications of suppurative inflammation bacteremia
no clinical symptoms!
formation of secondary foci of inflamm. (endocarditis, meningitis)
sepsis = massive bacteremia
septic fever, activation of spleen, septic shock
thrombophlebitis
secondary inflammation of vein wall followed by thrombosis - embolization
pyemia - hematogenous abscesses (infected infarctions)
lymphangiitis, lymphadenitis

20. inflammatory necrosis of the surface - ulcer (skin, stomach)
2d. necrotizing
inflammatory necrosis of the surface - ulcer (skin, stomach)
gangrenous - secondary modification by bacteria - apendicitis, cholecystitis - risk of perforation – peritonitis
2e. non-purulent
round cell inflammatory infiltrate

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)
lymphocytic rim
NO agent elimination but walling off
intracellulary agents (TBC) x inert foreign bodies

22. Granulomatous inflammation
1. Bacteria
TBC
leprosy
syphilis (3rd stage - gumma)
2. Parasites + Fungi
3. Inorganic metals or dust
silicosis
berylliosis
4. Foreign body
suture (Schloffer “tumor“), breast prosthesis, vascular graft
5. Unknown
– sarcoidosis, Wegener´s granulomatosis, Crohn disease

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 exudate – sero-fibrinous exudate (macrophages)

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

25. Syphilis Treponema pallidum (spirochete)
STD + transplacental fetus infection
acquired (3 stages) x congenital
basic microscopic 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 (thoracic aorta)
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 2) infantile syphilis
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