Inflammation ppt kml

Kamal Ch. Upreti

Pharmaceutical marketing

INFLAMMATION

INFLAMMATION

GOOD SIDE BAD SIDE

INFLAMMATION

“A dynamic response of vascularised tissue to injury.”

Host ImmunityHost Immunity

INFLAMMATION

Causes of inflammation

Physical

Chemical

Mechanical

Thermal

Biological

TYPES OF INFLAMMATION

ACUTE

INFLAMMATION

CHRONIC

INFLAMMATION

Rapid Development & Short life

Slow Development & Last will long

ACUTE INFLAMMATION

Non-specific response to any cell injury

Involves blood vessels, chemical mediators, and white blood cells

Purposes

Destroy an organism

Limit damage to a certain area

Prevent reproduction of an organism Virus, bacterium

Clear debris and lay groundwork for healing

Heat Redness Swelling Pain Loss Of Func.

The 5 Cardinal Signs of ACUTE INFLAMMATION

Inflammation is characterized by five cardinal signs:-

Rubor (redness),

Calor (increased heat),

Tumor (swelling),

Dolor (pain), and

Functio laesa (loss of function).

Cardinal Signs (primary or major clinical sign)

Vascular component Cellular component

Two components

ACUTE INFLAMMATION

Arteriolodilation Microcirculation

EXUDATION

Inflammation - Mechanism

1. Vasodilatation

2. Exudation - Edema

3.4. Emigration of cells

5. Chemotaxis

Vascular component

Cellular component

Vascular Events

Initial vasoconstriction near site of injury

Vasodilation of arterioles and capillaries

Increased blood flow to the area

Increased hydrostatic pressure

Vascular Events

HISTAMINPROSTAGLANDINS

NITRIC OXIDEBRADIKININ

PARANCHYMAL CELL

NORMAL BLOOD FLOW

Hydrostatic PressureOsmotic Pressure

Vascular Events

DURING INJURY

PLASMA PROTEIN LEAKOUT

Hydrostatic PressureOsmotic Pressure

Vascular Events

HISTAMINPROSTAGLANDINS

NITRIC OXIDE

ENDOTHELIAL CELL

Vascular Events

Vascular Events

Increased capillary permeability

Secondary to tight junction disruption in endothelial layer of blood vessels

Plasma moves out of the blood vessels (exudate)

Exudate = large amount of protein

Transudate = relatively little protein

ENDOTHELIAL CELL

HISTAMINPROSTAGLANDINS

NITRIC OXIDE

TNFCYTOKINES

THROUGH GENOMIC PROGRAMME OF PR-CEL

CONTRECTIONShort Time

RETRECTIONLong Time

NORMAL CELL

Vascular Events

Fluid environment surrounding inflammation is thick with cells and debris

Cells and debris will become purulent over time

Vascular Events

Rubor, Calor, Tumor

Vascular Events

Kinin cascade

Group of plasma proteins that stimulate the vascular component of inflammation

Bradykinin is most important kinin

Kinins and prostaglandin E cause pain at site

Chemical Mediator

Histamine Stimulates vascular component of inflammation

Nitrous oxide -Promotes vasodilation , Blocks platelet clumping and clot formation , Cytotoxic.

Aracodonic acid metabolites from cell membrane phospholipids

Leukotrienes (C-4, D-4, E-4) maintain inflammation in cellular and vascular inflammation

Prostaglandins prolong inflammatory process

PGD2, E2, F2 - Vasodilation and increased capillary permeability

PGI2 – vasodilation, inhibits platelet clumping

Chemical Mediator

Vascular component Cellular component

Two components

Microcirculation

EXUDATION

Arteriolodilation

WBCs

Chemotaxis

Emigration of cells

Cellular component

How WBC pass through Vascular component to Interstitial component ?

Cellular Components of Inflammation

Primary circulating WBC's are granulocytes

1.) Neutrophils

2.) Eosinophils

3.) Basophils

Other components:

platelets, monocytes (precursors of macrophages), and lymphocyte-like natural killer cells (NK cells)

Neutrophils and monocytes (phagocytes)

move to the inflammatory site

Margination

Phagocytes adhere to the blood vessel walls

Emigration (diapedesis)

Phagocytes slip out of the blood vessels through endothelial junctions

Neutrophils arrive the earliest – 6-24 hours

Monocytes arrive approx. 24-48 hours after injury

Phagocytosis

WBC recognizes and attaches to the organism or antigen

The organism is engulfed

Degranulation (release of lysosomes) leads to death of the organism

Platelet clumping at the site of injury

Cellular Events

Emigration of Leukocytes from Vascular components to cellular components

Chemotaxis

Leukocyte movement towards the source of Inflammation

How the WBC pass the vascular compartment to Interstitial Components ?

Emigration of Leukocytes

Mar

gina

tion

Rolling

Tight Adhesion

ImigrationDiapediasis

Normal Blood Flow

Vascular Events

Hydrostatic Pressure Hydrostatic Pressure

Protein Rich Fluid -ExudationProtein Rich Fluid -Exudation

More Viscus Blood More Viscus Blood

Less blood velocityLess blood velocity

Coming blood increaseComing blood increase

Normal Blood Flow- DisturbedNormal Blood Flow- Disturbed

RBC start sticking to each other

Protein rich fluid - Exudation Increase Blood viscosity

1- Margination

WBC now hit the endothelial cell

Chemical Mediator act on the endothelial cell— Activation

The sticky molecule of WBC –SIALATED SUGAR (oligisaccharide)

Adhesion of WBC with Endothelial cell

But the conjugation is not longer

2- ROLLING

Sticky WBC rolling with Endothelial cell

3- Tight Adhesion

Chemokines released from inflammatory area, attached with Endothelial cell surface- IL8- Induced

Activated INTEGRINE (peptide)

Non activated INTEGRINE

Chemomkines

ICAM- Inter Cellular Adhesion Molecule

VCAM- Vascluar Cellular Adhesion Molecule

Chemokine stimulate the INTEGRINE and this INTEGRINE bind with ICAM, VCAMStrong Bonding of WBC with Endothelial cell -Tight adhesion

4- DIAPEDIASIS (Imigration, Extravassation, Migration )

PECAM- Platelet Cell Adhesion Molecule

Homophilic Interaction

Collegenase -Make a hole on endothelial lining

Gprotein C-Receptor - IP3-ER-Activation – Proteinkinase-C - Polymer

Chemoattractant

Chemotaxis

Systemic effects of inflammation

● Fever● Effects of pyrogen from neutrophils and macrophages

● Effects of interleukin-1 on hypothalamus●Increased temp is harmful to some organisms (good)●Some organisms release endotoxins when killed(bad)

Leukocytosis● Stimulated by complement (C3a)● Large release of stored neutrophils● Production of leukocytes by bone marrow

Loss of appetite

Increased deep sleep

Weight loss

Weakness

Systemic effects of inflammation

Benefits of Inflammation

1.) CONTROLS TISSUE DAMAGE

●The clotting systems and WBC's (i.e. eosinophils)

2.) PREVENTS INFECTION

The plasma protein systems that help destroy

and contain bacteria (i.e. complement &

clotting systems) and the influx of WBC's

Benefits of Inflammation

3.) INITIATES THE ADAPTIVE IMMUNE

RESPONSE

4.)INITIATES HEALING THRU REMOVAL OF

DEAD CELLS

Benefits of Inflammation

Return to normal vascular permeability

Removal of edema and plasma proteins by lymphatics and macrophages

Phagocytosis by macrophages

Cellular debris and dead neutrophils removed

Resolution of inflammation

THANK YOU