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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
