inflammation jan laco, md, phd. inflammation complex protective reaction caused by various endo- and...
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InflammationInflammation
Jan Laco, MD, PhD
InflammationInflammation
complex protective reactioncaused by various endo- and exogenous
stimuliinjurious agents are destroyed, diluted or
walled-offwithout inflammation and mechanism of
healing could organism not survivecan be potentially harmfull
TerminologyTerminology
Greek root + -itismetritis, not uteritiskolpitis, not vaginitisnephritis, not renitis
glossitis, not linguitischeilitis, not labiitis
MechanismsMechanisms
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
ClassificationClassification
several points of viewaccording to length
– acute × chronic (+ subacute, hyperacute)
according to predominant component– 1. alterative – 2. exudative – 3. proliferative
ClassificationClassification 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
Acute inflammationAcute inflammation
early responseimportant role in inflammation has
microcirculation!supply of white blood cells, interleukins,
fibrin, etc.
Local symptomatologyLocal symptomatology
classical 5 symptoms (Celsus, 1st c. BC)1. calor – heat, warmth2. rubor – redness, erythema3. tumor – swelling, edema4. dolor - pain5. functio laesa – function loss/impairment
Systemic symptomsSystemic 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, ...
Vascular changesVascular 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
Cellular eventsCellular 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
PhagocytosisPhagocytosis
1. recognition and attachment– 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)
Outcomes of acute Outcomes of acute inflammationinflammation
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
Chronic inflammationChronic 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)
Chronic inflammationChronic 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)
Morphologic patterns Morphologic patterns of inflammationof 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)
Morphologic patterns Morphologic patterns of inflammationof 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
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)
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
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
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)
lymphocytic rim NO agent elimination but walling off intracellulary agents (TBC) x inert foreign bodies
Granulomatous inflammationGranulomatous 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
Tuberculosis Tuberculosis – general pathology– 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)
LeprosyLeprosy
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
SyphilisSyphilis
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
SyphilisSyphilis
1. primary syphilis - contagiouschancre (ulcus durum, hard chancre)M: penis x F: vagina, cervixpainless, firm ulceration + regional painless
lymphadenopathyspontaneous resolve (weeks) scar
SyphilisSyphilis
2. secondary syphilis - contagiousafter 2 monthsgeneralized lymphadenopathy + various
mucocutaneous lesionscondylomata lata - anogenital region, inner
thighs, oral cavity
SyphilisSyphilis
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
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