Acute

Inflammation

NEFPanuelos, PTRP
Basic Pathology
 INFLAMMATION
• Response of vascularized
tissues to infections and
damaged tissues that
brings cells and
molecules of host
defense from the
circulation to the sites
where they are needed,
in order to eliminate the
offending agents.
 Sequence of Events
• The offending agent, which is located in extravascular
tissues, is recognized by host cells and molecules.
• Leukocytes and plasma proteins are recruited from the
circulation to the site where the offending agent is located.
• The leukocytes and proteins are activated and work together
to destroy and eliminate the offending substance.
• The reaction is controlled and terminated.
• The damaged tissue is repaired.
 FUNDAMENTAL PROPERTIES
• Components of the
inflammatory response
• Harmful consequences of
inflammation
• Local vs Systemic
Inflammation
• Mediators of Inflammation
 FUNDAMENTAL PROPERTIES

• Acute vs Chronic Inflammation

• Termination of inflammation and
initiation of tissue repair.
 CAUSES of INFLAMMATION
• Infections
• Determined largely by the type of pathogen
• Tissue necrosis
• Ischemia, Trauma, Physical Injury
• Foreign bodies
• Immune responses (Hypersensitivity)
• Auto-immune Dse, Allergy
 RECOGNITION OF MICROBES AND
DAMAGED CELLS
• Cellular receptors for microbes.
• Toll-like receptors (TLRs)
• Sensors of cell damage.
• Inflammasome
• Other cellular receptors involved in inflammation.
• Circulating proteins.
• complement system
 ACUTE
INFLAMMATION:
Components
• Dilation of small vessels
leading to an increase in
blood flow
• Increased permeability of the
microvasculature
• Emigration of the leukocytes
from the microcirculation
 REACTION OF BLOOD VESSELS

• Escape of fluid, proteins,

and blood cells from the
vascular system into the
interstitial tissue or body
cavities
• Exudate
• Transudate
• Edema
• Pus
 CHANGES IN VASCULAR FLOW AND
CALIBER
• Vasodilation is induced by the action of several mediators, notably
histamine, on vascular smooth muscle.
• One of the earliest manifestations of acute inflammation
• Increased permeability of the microvasculature,
• Stasis
• Blood leukocytes, principally neutrophils, accumulate along the
vascular endothelium.
 INCREASED VASCULAR
PERMEABILITY
(VASCULAR LEAKAGE)

• Contraction of endothelial cells

• most common mechanism of
vascular leakage.
• Endothelial injury, resulting in
endothelial cell necrosis and
detachment.
• Increased transport of fluids and
proteins,
 LEUKOCYTE RECRUITMENT TO THE SITE OF
INFLAMMATION
• Endothelium is activated and can bind leukocytes as a prelude
to their exit from the blood vessels.
• Migration across the endothelium and vessel wall
• Migration in the tissues toward a chemotactic stimulus
• Attachment of leukocytes to Selectins
• Margination
• Transmigration and Diapedesis via the PECAM
 CHEMOTAXIS

• Locomotion along a chemical gradient.

• In most forms of acute inflammation neutrophils predominate in the
inflammatory infiltrate during the first 6 to 24 hours and are replaced by
monocytes in 24 to 48 hours
 PHAGOCYTOSIS: STEPS

• Recognition and
attachment of the
particle to be
ingested by the
leukocyte
• Engulfment, with
subsequent
formation of a
phagocytic vacuole
• Killing or
degradation of the
ingested material.
 MEDIATORS OF INFLAMMATION

• Cell-derived mediators are normally sequestered in intracellular granules and

can be rapidly secreted by granule exocytosis.
• Plasma-derived mediators (e.g., complement proteins) are produced mainly
in the liver and are present in the circulation
 HISTAMINE AND SEROTONINS
• First mediators to be released during inflammation
• Present in the connective tissue adjacent to blood
vessels.
• Activated by:
• physical injury binding of antibodies to mast cells
• products of complement called anaphylatoxins
• Histamine causes dilation of arterioles and increases the
permeability of venules.
 ARACHIDONIC ACID METABOLITES
• Prostaglandins and leukotrienes are produced from arachidonic acid (AA)
present in membrane phospholipids, and stimulate vascular and cellular
reactions in acute inflammation.
End of Part 1