inflammation. definition inflammation is biochemical, structural and cellular non-specific...

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