INFLAMMATION

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Dr. Ali YaldrumB.D.S, M.Sc (London)

Faculty of Dentistry, SEGi University

Survival of all organisms requires they eliminate:

• foreign invaders (infectious pathogens: viruses, bacteria, fungi)

• damaged tissues

• Achieved via a complex mechanism called “inflammation”

Inflammation is a protective response intended to eliminate the initial cause of cell injury as well as the necrotic cells and tissues resulting from the original insult

Diluting Destroying/ Neutralising

Heal & Repair

Restoration of Function

A double edge sword?

Although inflammation helps clear infections and other noxious stimuli and initiates repair, the inflammatory reaction and the subsequent repair process can cause considerable harm.

Signs of Inflammation

Cardinal signs are

• Heat (calor)

• Redness (rubor)

• Swelling (tumor)

2 additional signs seen in acute inflammation

• Pain (dolor)

• Loss of function (function laesa)

Steps of Inflammation

5R’s

1. Recognition of injurious agent 2. Recruitment of leukocytes 3. Removal of agent 4. Regulation of the response 5. Resolution

Types of Inflammation

• Acute

• Chronic

Acute Inflammation

Acute Inflammation

rapid response to injury or microbes and other foreign substances that is designed to deliver leukocytes and plasma proteins to sites of injury

Stimuli

can be triggered by a variety of stimuli

• Infections

• Trauma

• Physical & chemical agents

• Foreign bodies

• Immune reactions

Acute inflammat ion has two ma jo r components

• Vascular changes

• Cellular events

Vascular

• Changes in Vascular Caliber and Flow

• Increased Vascular Permeability

Changes in Vascular Caliber and Flow

• Changes in blood vessels begin rapidly after infection or injury but may develop at variable rates, depending on the nature and severity of the original inflammatory stimulus.

transient vasoconstriction

arteriolar vasodilation

increased viscosity & slowing of circulation

stasis

migration

lasting few seconds

• Endothelial cell contraction leads to intercellular gaps in post capillary venules

• Histamine, bradykinin, leukotrines

• immediate

• short lived 15 to 30 mins

• called as immediate transient response

• IL1 and TNF

• prolonged changes in cytoskeleton of endothelial cells

• take 4-6 hours to develop

• lasts for up to 24 hours

Cellular Events

• an important function of the inflammatory response is to deliver leukocytes to the site of injury and to activate them

Leukocyte recruitment

Sequence consists of: 1. margination, adhesion to endothelium &

rolling along the vessel wall 2. firm adhesion to endothelium

3. transmigration between endothelial cells; 4. migration in interstitial tissues toward a

chemotactic stimulus

Leukocyte activation

• Once leukocytes have been recruited to the site of infection or tissue necrosis, they must be activated to perform their functions

• Stimuli for activation include microbes, products of necrotic cells, and several mediators

Phagocytosis

Consists of 3 distinct but interrelated steps

1. recognition and attachment of the particle to the ingesting leukocyte

2. engulfment, with subsequent formation of a phagocytic vacuole

3. killing and degradation of the ingested material.

Patterns of acute inflammation

Patterns of acute inflammation

• vascular and cellular reactions that characterize acute inflammation are reflected in the morphologic appearance of the reaction

• serous inflammation

• fibrinous inflammation

• suppurative inflammation

serous

characterized by:

• the outpouring of a watery

• re lat ive ly prote in-poor flu id that , depending on the site of injury

fibrinous

• occurs as a consequence of more severe injuries,

• resulting in greater vascular permeability that allows large molecules (such as fibrinogen) to pass the endothelial barrier

suppurative

• manifested by the presence of large amounts of purulent exudate (pus) consisting of neutrophils, necrotic cells, and edema fluid

• Abscesses are focal collections of pus that may be caused by seeding of pyogenic organisms into a tissue or by secondary infections of necrotic foci.

Chemical mediators of inflammation

Chemical mediators of inflammation

• Mediators may be produced locally by cells at the site of inflammation,

• or may be circulating in the plasma as inactive precursors that are activated at the site of inflammation

Chronic Inflammation

Chronic Inflammation

• is inflammation of prolonged duration (weeks to months to years) in which active inflammation, tissue injury, and healing proceed simultaneously.

Characterized by:

• infiltration with mononuclear cells

• plasma cells tissue destruction

• repair

• angiogenesis

• fibrosis

When acute inflammation converts to chronic?

Chronic inflammation arises in the following settings: 1. T l ymphocy te -med ia ted immune

r e s p o n s e c a l l e d d e l a y e d - t y p e hypersensitivity

2. Immune-mediated inflammatory diseases 3. autoimmune diseases

Chronic Inflammatory Cells and Mediators

• fundamen ta l f ea tu re o f ch ron i c inflammation is its persistence

• results from complex interactions between the cells that are recruited to the site of inflammation and are activated at this site

Macrophages

• dominant cell of chronic inflammation

• derived from circulating blood monocytes

• act as filters for particulate matter, microbes, and senescent cells, as well as acting as sentinels

• scattered in most connective tissues,

• also found in organs such as the liver

• spleen and lymph nodes

• central nervous system

• lungs

• Together these cells comprise the so-called mononuclear phagocyte system, also known by the older name of reticulo-endothelial system

Lymphocytes

• mobilized to the setting of any specific immune stimulus

• as wel l as non-immune-mediated inflammation

Eosinophils

• characteristically found in inflammatory sites around parasitic infections

• or as part of immune reactions mediated by IgE, typically associated with allergies.

Mast cells

• sentinel cells widely distributed in connective tissues throughout the body,

• participate in both acute and chronic inflammatory responses

• "armed" with IgE antibody specific for certain environmental antigens

• Neutrophils are the classic hallmarks of acute inflammation, many forms of chronic inflammation may nevertheless continue to show extensive neutrophilic infiltrates

References

• Robins, Basic Pathology, 8th Edition.