Transcript Inflammation

Inflammation
Jan Laco, MD, PhD
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
Terminology

Greek root + -itis
 metritis, not uteritis
 kolpitis, not vaginitis
 nephritis, not renitis

glossitis, not linguitis
 cheilitis, not labiitis
Mechanisms
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A) local - mild injury
B) systemic – severe injury
3 major changes
1. alteration – tissue change
2. exudation - inflammatory exudate
– liquid + proteins (exudate)
– cellular (infiltrate)
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3. proliferation
– formation of granulation and fibrous tissue
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usually - all 3 components - not the same intensity
Classification
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several points of view
 according to length
– acute × chronic (+ subacute, hyperacute)
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according to predominant component
– 1. alterative
– 2. exudative
– 3. proliferative
Classification
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according to histological features
– non-specific (not possible to trace etiology) - vast majority
– specific / granulomatous (e.g. TBC)
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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
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early response
 important role in inflammation has
microcirculation!
 supply of white blood cells, interleukins,
fibrin, etc.
Local symptomatology
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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
Systemic symptoms
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fever (irritation of thermoregulatory centre)
– TNF, IL-1
– IL-6 – high RBCs sedimentation rate (via fibrinogen)
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leukocytosis - increased WBCs number
– bacteria – neutrophils
– parasites – eosinophils
– viruses - lymphocytosis
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leukopenia - decreased WBCs number
– viral infections, salmonella infections, rickettsioses
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immunologic reactions – “acute phase reactants“
– C-reactive protein, complement, SAA, fibrinogen, ...
Vascular changes
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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
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3. endothelial injury – direct x leukocyte-dependent
– proteolysis – protein leakage
–  platelets adhesion  thrombosis
Cellular events
leukocytes margination  rolling  adhesion 
transmigration by diapedesis (in venules)
 transmigration
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– neutrophils (1-2 days)
– monocytes (2-3 days)
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chemotaxis (along chemical gradient)
– endogenous signaling molecules – ILs, LTs, C5a
– exogenous – toxins, bacterial proteins, ...
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phagocytosis (see below)
 passive migration of RBCs
– no active role in inflammation - hemorrhagic inflammation
Phagocytosis
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1. recognition and attachment
– facilitated by opsonins (IgG, C3b)
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2. engulfment
– pseudopods formation  phagocytic vacuole + lysosome 
phagolysosome
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3. killing and degradation
– oxidative burst – reactive oxygen metabolits – superoxide ion,
hydrogen peroxide, hypochlorous radicals
– lysosomal acid hydrolases
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in highly virulent microorganisms can die leukocyte and not
the microbe
in highly resistant microorganisms - persistence within
macrophage - activation after many years (TBC)
Outcomes of acute inflammation
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1. resolution - restoration to normal, in limited injury
–
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–
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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)
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3. progression into chronic inflammation
Chronic inflammation
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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)
Chronic inflammation
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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)
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Morphologic patterns
of inflammation
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1. alterative
– poliomyelitis anterior acuta, diphtherial myocarditis
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2. exudative
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2a. serous
2b. fibrinous
2c. suppurative
2d. necrotizing, gangrenous
2e. non-purulent
3. proliferative
– primary (rare) x secondary (cholecystitis)
Morphologic patterns
of inflammation
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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
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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
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2c. suppurative (purulent) - accumulation of
neutrophillic leukocytes - formation of pus
 pyogenic bacteria - Staphylococci
 interstitial
– phlegmone – diffuse
– abscess - localized collection
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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)
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complications of suppurative inflammation
 bacteremia
– no clinical symptoms!
– formation of secondary foci of inflamm. (endocarditis,
meningitis)
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sepsis = massive bacteremia
– septic fever, activation of spleen, septic shock
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thrombophlebitis
– secondary inflammation of vein wall followed by
thrombosis - embolization
– pyemia - hematogenous abscesses (infected infarctions)
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lymphangiitis, lymphadenitis
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2d. necrotizing
 inflammatory necrosis of the surface - ulcer (skin,
stomach)
 gangrenous - secondary modification by bacteria apendicitis, cholecystitis - risk of perforation –
peritonitis
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2e. non-purulent
– round cell inflammatory infiltrate
Granulomatous inflammation
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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
Granulomatous inflammation
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1. Bacteria
– TBC
– leprosy
– syphilis (3rd stage - gumma)
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2. Parasites + Fungi
 3. Inorganic metals or dust
– silicosis
– berylliosis
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4. Foreign body
– suture (Schloffer “tumor“), breast prosthesis, vascular graft
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5. Unknown
– – sarcoidosis, Wegener´s granulomatosis, Crohn disease
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)
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Leprosy
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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
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2. tuberculoid – sterile
– in peripheral nerves – tuberculoid granulomas -
anesthesia
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death – secondary infections + amyloidosis
Syphilis
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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
Syphilis
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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
Syphilis
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2. secondary syphilis - contagious
 after 2 months
 generalized lymphadenopathy + various
mucocutaneous lesions
 condylomata lata - anogenital region, inner
thighs, oral cavity
Syphilis
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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)
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2) neurosyphilis – tabes dorsalis + general paresis
– degeneration of posterior columns of spinal cord 
sensory + gait abnormality
– cortical atrophy  psychic deterioration
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3) gumma – ulcerative lesions of bone, skin,
mucosa – oral cavity
Congenital syphilis
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1) abortus
– hepatomegaly + pancreatitis + pneumonia alba
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2) infantile syphilis
– chronic rhinitis (snuffles) + mucocutaneous lesions
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3) late (tardive, congenital) syphilis
– > 2 years duration
– Hutchinson triad – notched central incisors + keratitis
(blindness) + deafness (injury of n. VIII)
– mulberry molars + saddle nose