ACUTE INFLAMMATION

Dr.mounika

Fist year MDS

CONTENTS:

Definition

Acute inflammation.

Inflammatory exudate

Outcome of acute inflammation

Chemical mediators and regulators of inflammation

DEFINITION

Inflammation is a protective response involving host

cells, blood vessels, and proteins and other

mediators that is intended to eliminate the initial

cause of cell injury, as well as the necrotic cells and

tissues resulting from the original insult, and to

initiate the process of repair.

Inflammare (Latin) : To set on fire

TYPES OF INFLAMMATION

Acute: rapid onset and short duration.

Chronic: Slowest onset and prolonged duration.

EXTERNAL MANIFESTATIONS OR

CARDINAL SIGNS

Calor-heat

Rubor-redness

Tumor-swelling

Dolor-pain

Functio laesa- loss of function

STEPS OF INFLAMMATORY RESPONSE

1)recognition of injurious agent

2)recruitment of leukocytes

3)removal of the agent

4)regulation of response

5)resolution

ACUTE INFLAMMATION

-Immediate and early response .

-rapidly deliver leukocytes and plasma proteins .

It has two major events:

Vascular events

Cellular events

STIMULI

Infections

Trauma

Physical and chemical agents

Foreign bodies

Immune reactions

VASCULAR CHANGES

Altered blood vessel caliber and flow

Vasodilation slowing of flow stasis of blood cells

leukocyte margination

Increased vascular permeability (leakage)

Escape of protein-rich fluid into interstitium altered

osmotic pressure gradient further outflow of fluid

INCREASED VASCULAR PERMEABILITY

INFLAMMATORY EXUDATE

Increased vascular permeability: results protein rich fluid accumulation called exudate.

Mechanisms: 1)endothelial cell contraction leading to intercellular gaps in post capillary venules.

2)endothelial injury causing endothelial cell necrosis and detachment.

3)leukocyte mediated vascular injury.

4)leakage from new blood vessels.

FUNCTION OF INFLAMMATORY EXUDATES

1-Dilution

2-Bring antibodies .

3-Bring leukocytes .

4-Bring fibrinogen .

RESPONSES OF LYMPHATIC VESSELS:

Lymph flow is increased and helps drain edema

fluid, leukocytes and cell debris from extravascular

space.

Lymphatics and draining lymph nodes may become

secondarily inflamed termed inflammatory

lymphadenitis.

CELLULAR EVENTS

Emigration of leucocytes ,accumulation .

Activation of leucocytes, enabling them to eliminate

the offending agent

Principal leucocytes are polymorpho nuclear

leucocytes

CELLULAR EVENTS

LEUKOCYTE RECRUITMENT:

Sequence of events:

1)margination and rolling: as blood flows, circulating

cells are swept by laminar flow against the vessel

wall.

larger LEUCOCYTES are pushed out of central

axial column and thus interact with lining

endothelial cells. = margination.

If endothelial cells are activated by cytokines and

mediators--express adhesion molecules to which

leukocytes attach loosely.

these cells bind and detach and thus begin to

tumble on endothelial surface, a process called

rolling.

Mediated by selectin family of adhesion molecules.

three members are-

E-SELECTIN-on endothelial cells.

P-SELECTIN-on platelets and endothelium

L-SELECTIN-on surface of most leucocytes

They are induced after stimulation.

2)ADHESION:

Rolling leucocytes sense changes .

initiate firm adhesion.

mediated by integrins - leukocyte cell surfaces +

ligands - endothelial cells.

Cytokine stimulated increased integrin affinity and

increased expression of integrin ligands provides

stable attachment of leucocytes to endothelial cells

at sites of inflammation.

3)TRANSMIGRATION:

By squeezing between cells at intercellular

junctions called diapedesis.

mainly in venules of systematic vasculature.

Leucocytes secrete collagenases - pass through

the vascular basement membrane.

Driven by chemokines produced in extravascular

tissues toward their chemical gradient

4)CHEMOTAXIS

After extravasating from blood, leucocytes move

toward sites of infection or injury along a chemical

gradient by a process called chemotaxis.

Chemotactic substances:

Soluble bacterial products.

Cytokines

Components of complement system,C5

Products of lipooxygenase pathway of arachidonic

acid metabolism, leukotriene B4.

They bind to specific receptors, triggers cytoskeletal

contractile elements for movement.

LEUCOCYTE LOCOMOTION

Leucocytes move by extending pseudopods that anchor to ECM and then pull the cell in direction of extension.

Neutrophils predominate in inflammatory infiltrate during first 6 to24 hours and are replaced by monocytes in 24 to 48 hours.

LEUCOCYTE ACTIVATION: cellular receptors - responses in leukocytes -

defensive function =leukocyte activation.

Functions:

Phagocytosis of particles

Intracellular destruction of phagocytosed microbes

and dead cells.

Liberation of substances that destroy extracellular

microbes and dead tissues

Production of mediators.

PHAGOCYTOSIS

Steps :

1) recognition and

attachment-

opsonization

2) engulfment, with

subsequent formation

of a phagocytic vacuole

3)killing and

degradation of ingested

material.

RECOGNITION OF MICROBES , NECROTIC

CELLS ,AND FOREIGN SUBSTANCES

Toll like receptors: there are 10 mammalian TlRs

which recognize products of bacteria and other

pathogens located in plasma membranes and

endosomes , so they are able to detect extracellular

and ingested microbes.

provide defense against essentially all classes of

infectious pathogens

Recognition stimulates production of mediators of

inflammation, antiviral cytokines and proteins that

promote lymphocyte activation and even more

potent immune response.

INFLAMMASOME: multi-protein cytoplasmic

complex that recognizes products of dead cells

such as uric acid and extracellular ATP ,crystals

and some microbial products.

activates enzyme called caspase-1 which cleaves

inflammatory cytokine interleukin-1B into

biologically active form. It recruits leukocyte and

they phagocytose and destroy dead cells.

FACTORS INVOLVED IN TERMINATION OF

ACUTE INFLAMMATION

- Short half-life of inflammatory mediators.

- Lipoxins

Anti-inflammatory mediators.

Derived from arachidonic acid metabolites.

Inhibit transmigration and chemotaxis.

-Resolvins

Synthesized from omega-3 fatty acids.

Inhibit production and recruitment of

inflammatory cells to the site of inflammation.

-Clearance of neutrophils by apoptosis

OUT COMES OF ACUTE INFLAMMATION

CHEMICAL MEDIATORS OF

INFLAMMATION

- Mediators may be circulating in the plasma or they

may be produced locally by cells at the site of

inflammation.

- Most mediators induce their effects by binding to

specific receptors on target cells.

- Mediators may stimulate target cells to release

secondary effector molecules.

- Mediators may act on only one or a very few

targets or they may have widespread activity.

PREFORMED MEDIATORS

Vaso active amines:

Histamine

serotonin

ARACHADONIC ACID METABOLITES

LYSOSOMAL CONSTITUENTS

- Acid proteases - degrade bacteria and debris

within phagolysosome

- Neutral proteases – capable of degrading

various extra cellular components such as

collagen, basement membrane

PLATELET ACTIVATING FACTOR

. Released by IgE sensitised platelets, mast cells,

basophils, macrophages, endothelial cells.

Functions:

platelet aggregation

low doses – vasodilatation, otherwise

vasoconstriction

increased leukocyte adhesion

chemotaxis

PLASMA PROTEIN DERIVATED

MEDIATORS

Plasma proteases

- Kinnins

- Clotting system

- Fibrinolytic system

- Complement cascade

IN DENTISTRY

ACUTE NECROTISING ULCERATIVE

GINGIVITIS:

A painful, erythematous gingivitis with necrosis of

interdental papillae Most likely caused by both a fusiform bacillus and a

spirochete (Borrelia vincentii)

ACUTE PERICORONITIS

Inflammation around the crown of a partially

erupted, impacted tooth Most commonly a lower third molar

Trauma from an opposing molar and impacted food

under the soft tissue flap (operculum) may precipitate.

ACUTE OSTEOMYELITIS

Acute inflammation of the bone and bone marrow Most commonly the result of a periapical abscess

May follow fracture of a bone

May result from a bacteremia

ACUTE PULPITIS, ACUTE PERIAPICAL

ABSCESS, ACUTE APICAL PERIODONTITIS

Inflammation of dental pulp due to dental caries,

trauma or dental procedures

Surgical removal of impacted 3rd molars.