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Inflammation
Inflammation
DefinitionInflammation is biochemical, structural and
cellular non-specific protective process occurring locally in vascularized tissues aimed to destroy impairing factors, or to remove they and to restart reparation of tissue, to separate the impairing agents and to limit their effect to the whole body and to induce specific immune response.
Hallmarks of inflammation
Hallmarks of inflammation
Rubor (redness) Calor (heat) Dolor (pain) Tumor (swelling) Functio laesa (loss of function)
Classification
Type (course) acute 6 – 14 days subacute 3 – 6 weeks chronic several months
Pathology alterative exudative proliferative garanulomatous
Classification
Etiology
Exogenous biological (viruses, bacteria, parasites) physical (trauma, radiation, heat) chemical (acids, poisons, toxins)
Endogenous dead cells immunological defects metabolic diseases
Stages of inflammation
1. Alteration
primary direct effect of pathogenic factor
secondary enzymes and other chemicals released from
impaired cells reactive oxygen species
Stages of inflammation
2. Microvascular reactions
vasodilatation - hyperemia higher permeability – oedema
3. Acute cellular respose
granulocytes (Neu, Ba, Eo)
Stages of inflammation
4. Chronic cellular respose
monocytes, macrophages, lymphocytes
5. Reparation
Mediators of inflammation
1. Histamine (mastocytes, basophiles) vasodilatation permeability
2. Serotonine (trombocytes) vasodilatation permeability
Mediators of inflammation
3. Bradykinin (plasma kinine system) vasodilatation permeability pain chemotaxis for Neu
Mediators of inflammation
4. Lipid mediators
membrane phospholipids PLA 2
arachidonic acid
cyclooxygenase 5-lipoxygenase
prostaglandins leukotrienesprostacyclins lipoxinstromboxans
Mediators of inflammation
4. Lipid mediators
PGE (endothelial cells, macrophages)– vasodilatation– permeability– pain– antiagregation effect on platelets– histamine release– chemotaxis
Mediators of inflammation
4. Lipid mediators
PGI (endothelial cells)– vasodilatation– antiagregation effect on platelets
TXA (platelets)– vasoconstriction– agregation of platelets
Mediators of inflammation
5. NO (EDRF)– vasodilatation
Mediators of inflammation
6. CytokinesProinflammatory cytokins alarm cytokines - IL-1, TNF acute phase reaction– IL-1, IL-6, IL-11, TNF pyrogens - IL-1, IL-6, TNF chemokins - IL-8, NAP-2, MIP-1, MCP-1... colony stimulation – G-CSF, GM-CSF
Antiinflammatory cytokins IL-4, IL-10
Mediators of inflammation
7. Plasma protein systems Complement
– lysis of bacteria C5b678(9)n
– opsonisation C3b, C4b– mastocytes degranulation C3a, C4a, C5a permability C3a, C4a, C5a– chemotactic factors C5b
Mediators of inflammation
7. Plasma protein systems Clotting system
– stops bleeding– prevents from spreading infection– keeps foreign bodies in the site of maximum
fagocytosis Fibrinolytic system Kinin system
– bradykinin
Cellular components of inflammation
1. Neutrophiles– acute inflammation– phagocytosis
2. Monocytes, macrophages– chronic inflammation– phagocytosis– production of PGE, PGI
3. Eosinophiles– allergy– parasites
4. Mastocytes, basofiles– production of histamin
Cellular components of inflammation
5. Lymphocytes– chronic inflammation– production of mediators– production of antibodies
6. Endothelial cells– production of PGI, NO, lipid mediators– production of adhesive molecules
Cellular components of inflammation
7. Trombocytes– coagulation– serotonin
8. Dendritic cells– antigen-presenting cells– T cell stimulation– cytokine production
Cellular components of inflammation
Phagocytosis
Chemotaxis
Rolling, margination, diapedesis
margination diapedesis
Rolling, margination, diapedesis
Adhesion molecules
•Immunoglobulin superfamily – ICAM-1, VCAM-1, PECAM
•Integrins – CD34, GLYCAM-1
•Cadherins - E-cadherins (epithelial), P-cadherins (placental), and N-cadherins (neural)
•Selectins – E-selectin (endothelial), L-selectin ( leucocyte), P-selectin (platelet)
Opsonization
Respiratory burst
Acute vs. chronic inflammation
Acute Chronic
Causative agent pathogents, injured tissue persistent acute inflammation,
Cells neutrophils monocytes, macrophages, lymphocytes
Mediators vasoactive amines, eicosanoides
cytokines
Duration few days up to many months or years
Outcomes resolution, chronic inflammation
tissue destruction, fibrosis
Acute phase reaction
Positive" acute-phase proteins:
C-reactive-protein – opsonin of microbes
Serum amyloid P component - opsonin
Serum amyloid A – chemotaxis
Complement factors – opsonisation, lysis, chemotaxis
Fibrinogen and other coag. factors - trapping invading microbes in blood clots, some cause chemotaxis
Plasminogen - degradation of blood clots
Ferritin - binding iron, inhibiting microbe iron uptake
Ceruloplasmin - oxidizes iron, facilitating for ferritin, inhibiting microbe iron uptake
Acute phase reaction
"Negative" acute-phase proteins:
Antithrombin - increase coagulation
Albumin
Transcortin - icrease free cortisol in blood, restoring homeostasis after stress
Transferrin – bind iron
Transthyretin – bind thyroxine and retinol
Retinol-binding protein – bind retinol
Wound healing
1.phase – Hemostasis
vasoconstriction platelets adhesion coagulation growth factors – PDGF → activation of fibroblasts → collagen fibril
construction
2.phase – Inflammation
vasodilatation from 6-8 up to 24-48 hours - polymorphonucler leucocytes –
phagocytosis – „cleaning“ of the wound, clearing it from debris later – monocytes, macrophages - phagocytosis
Wound healing
3.phase – Granulation
angiogenesis – neovascularization - growth factors (EGF) – migration of endothelial cells - new vessels
collagen deposition - migration of fibroblasts into wound – lay down collagen III
glycosaminoglycans and proteogycans contribute to matrix deposition
formation of granulation tissue contraction of wound – myofibroblasts (fibroblasts/smooth muscle
cells) – reduction of wound size (40 - 80 %) epithelialization – epithelial cells – barrier between wound end
environment
Wound healing
4.phase – Remodeling
collagen production and degradation equilibrium collagen III is replaced by collagen I scar
Wound healing
Orofacial inflammatory lessions
granulomas – irritation – infectionforeign bodies
- containing multinuclear giant cells
1.Nonspecific granulomas2.Foreign body granulomas – dental cement, dental abrasives
food – pulsesoil granuloma
3.Specific granulomas - Mycobacterium tuberculosisHistoplasmosisCoccidioidomycosis....
Orofacial granulomatosis
Cheilitis granulomatosa
- multiple nodules
Orofacial granulomatosis
Melkersson-Rosenthal syndrome
- fissured tongue- nodular lip swelling- unilateral facial palsy
Orofacial granulomatosis
Sarcoidosis
- mainly lungs- oral and facial nodules
Crohn disease
- inflammatory bowel disease – regional enteritis- inflammatory lesions – anywhere
along the GIT – oral lesions
Orofacial granulomatosis
Wegener granulomatosis
- vasculitis- mainly lungs and kidneys- gingiva, nasal mucosa, eyes