inflammation terminology, mechanism,.ppt

Related to MBBS field

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