inflammation jan laco, md, phd. inflammation complex protective reaction caused by various endo- and...

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