Arsi University

College of Health Science

InflammatioN
By: Birhanu Fiseha
(General Doctor of Medicine &
Lecturer)

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 Inflammation
 The survival of all organisms requires that they eliminate foreign
invaders, such as infectious pathogens, and damaged tissues.

 These functions are mediated by a complex host response

called inflammation.

 It is a protective response … eliminates the initial cause of cell

injury and the necrotic cells and tissues arising from the injury

 It accomplishes its protective mission by diluting, destroying, or

otherwise neutralizing harmful agents (e.g., microbes and
toxins)
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 …

Without inflammation, infections would go

unchecked and wounds would never heal.

Serves to bring defense & healing mechanisms to the

site of injury.

Can sometimes be harmful. How ?

Nomenclature:

• Appendicitis, Cellulitis, Meningitis, Pneumonitis, 3

 …
Inflammation is terminated when the offending
agent is eliminated.

The reaction resolves rapidly, because:

 The mediators are broken down and dissipated and

 The leukocytes have short life spans in tissues.

 Anti-inflammatory mechanisms are activated

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 Historical Highlights of inflammation
 Celsus first listed the four cardinal signs of inflammation:
rubor (redness), tumor (swelling), calor (heat), and dolor
(pain).
more prominent in acute inflammation than in chronic
inflammation.

 A fifth clinical sign, loss of function (functio laesa), was

added by Rudolf Virchow in the 19th century.

 “Inflammation is not a disease but a nonspecific response

that has a salutary effect on its host.” Scottish surgeon John
Hunter In 1793. 5
 Etiologies
• Microbial infections--pneumonia, skin infections, etc.
• Physical agents: burns, trauma--like cuts, radiation
• Chemicals: toxins and caustic substances like battery
acid
• Others: immunologic reactions-- rheumatoid arthritis
• Five cardinal clinical signs of inflammation(external
manifestations):
 rubor - - redness
 tumor - - swelling
 calor - - heat
 dolor- - pain
 functio laesa - - loss of function 6
 Mechanisms of the external signs of inflammation
 Redness and heat - due to increased blood flow to the
inflamed area.
 Swelling - due to accumulation of fluid.
 Pain - due to release of chemicals that stimulate specialized
nerve endings.
 Loss of function - due to a combination of factors.

• These signs are manifested when acute inflammation

occurs on the surface of the body, but not all of them will
be apparent in acute inflammation of internal organs.

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Erysipelas of the face due to group A streptococcus

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 Mediators of Inflammation
 Shared properties and general principles of
mediators of Inflammation.
 Mediators are generated either from cells or from
plasma proteins.

 Active mediators are produced in response to

various stimuli.

 One mediator can stimulate the release of other

mediators. 9
 Mediators…
 Mediators vary in their range of cellular targets.
 can act on one or a few target cell types

 can have diverse targets

 may even have differing effects on different types of cells.

 Once activated and released from the cell, most of

these mediators are short-lived.

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 The Actions of the Principal Mediators of Inflammation
Mediator Principal Sources Actions
Serotonin Platelets Vasodilation, increased vascular
permeability
Prostaglandins Mast cells, leukocytes Vasodilation, pain, fever

Leukotrienes Mast cells, leukocytes Increased vascular permeability,

chemotaxis, leukocyte adhesion
and activation

Platelet-activating factor Leukocytes, mast cells Vasodilation, increased vascular

permeability, leukocyte adhesion,
chemotaxis, degranulation, oxidative
burst

Reactive oxygen species Leukocytes Killing of microbes, tissue damage

Nitric oxide Endothelium, macrophages Vascular smooth muscle relaxation,
killing of microbes
Cytokines (TNF, IL-1) Macrophages, endothelial cells, Local endothelial activation
mast cells (expression of adhesion molecules),
fever/pain/anorexia/hypotension,
decreased vascular resistance
(shock)
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Chemokines Leukocytes, activated macrophages Chemotaxis, leukocyte activation
Chemical mediators of inflammation

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 I. Cell-Derived Mediators
• Histamine and Serotonin

• Are among the first mediators to be released in

acute inflammatory reactions.

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 Vasoactive amines
 Histamine
– Found in mast cells, basophils and platelets

– Preformed histamine is released from mast cell granules

in response to a variety of stimuli:
physical injury such as trauma or heat

immune reactions involving binding of IgE antibodies to

Fc receptors on mast cells

Etc…
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 Vasoactive…

– Promotes arteriolar dilation and venular

endothelial contraction

 Serotonin
– Vasoactive effects similar to histamine
– Found in platelets
– Released when platelets aggregate

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 II. Cell membrane phospholipid derivative
mediators
A. Arachidonic Acid (AA ):
• Is a component of cell membrane phospholipids

• Is released from the cell membrane by

phospholipases

• Arachidonic Acid (AA) Metabolites: Prostaglandins,

Leukotrienes, and Lipoxins.

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 …
• AA metabolism occurs via two major pathways
named for the enzymes that initiate the reactions:

lipoxygenase pathway and

Cyclooxygenase pathway

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AA metabolites (eicosanoids)
Cyclooxygenases synthesize
Prostaglandins
Thromboxanes
Lipoxygenases synthesize
Leukotrienes
Lipoxins

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 Cell membrane…
B. Platelet-Activating Factor (PAF)
• Another phospholipid-derived mediator released by
phospholipases

• Induces aggregation of platelets

• 100 to 1,000 times more potent than histamine in

inducing vasodilation and vascular permeability.

• Enhances leukocyte adhesion, chemotaxis,

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 Classification of inflammation
Inflammation is classified into two: acute and
chronic depending on:

 The nature of the stimulus and

 The effectiveness of the initial reaction in

eliminating the stimulus or the damaged tissues.

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 Acute inflammation
• Rapid in onset (typically minutes) and is of short
duration, lasting for hours or a few days.

• Main characteristics are:

– the exudation of fluid and plasma proteins (edema) and

– the emigration of leukocytes, predominantly neutrophils (also called

polymorphonuclear leukocytes).

• It is nonspecific and may be evoked by any injury short

of one that is immediately lethal.

• It is the first line of defense against injury. 22

 Acute…
• When acute inflammation is successful in eliminating the
offenders the reaction subsides, but if the response fails to
clear the invaders it can progress to a chronic phase.

• Has three major components:

(1) Alterations in vascular caliber that lead to an increase in
blood flow,
(2) Structural changes in the microvasculature that permit
plasma proteins and leukocytes to leave the circulation,
and
(3) Emigration of the leukocytes from the microcirculation,
their accumulation in the focus of injury, and their
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activation to eliminate the offending agent
 TERMINATION OF THE ACUTE INFLAMMATORY
RESPONSE
 In part, inflammation declines simply because:

 The mediators of inflammation have short half-lives.

 Neutrophils have short half-lives in tissues and die by apoptosis

within a few hours after leaving the blood.

 As inflammation develops the process also triggers a variety of stop

signals

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 Outcomes of Acute Inflammation
All acute inflammatory reactions may have one of three
outcomes:
 Complete resolution

 Is the usual outcome.

 Occurs:
When the injury is limited or short-lived
 when there has been little tissue destruction and
When the damaged parenchymal cells can regenerate.

 Resolution involves removal of cellular debris and microbes by

macrophages, and resorption of edema fluid by lymphatics. 25
 …

 Healing by connective tissue replacement

(fibrosis).
 Occurs after substantial tissue destruction.

 Occurs when the inflammatory injury involves tissues that

are incapable of regeneration

 Progression of the response to chronic

inflammation
 May follow acute inflammation, or the response may be
chronic from the onset.
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Outcome of acute inflammation

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Morphologic Patterns of Acute Inflammation
The morphologic hallmarks of all acute
inflammatory reactions are:
 dilation of small blood vessels

 slowing of blood flow

 accumulation of leukocytes and fluid in the

extravascular tissue.

The morphologic hallmarks often provide valuable

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 Morphologic patterns…

A. SEROUS INFLAMMATION
 Is marked by the outpouring of a thin fluid

 The skin blister resulting from a burn or viral infection.

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…

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 Morphologic patterns…
B. FIBRINOUS INFLAMMATION
Fibrin is formed and deposited in the extracellular
space.

A fibrinous exudate develops when the vascular

leaks are large or there is a local procoagulant
stimulus (e.g., cancer cells).

A fibrinous exudate is characteristic of inflammation

in the lining of body cavities, such as the meninges,
pericardium and pleura. 32
Fibrinous inflammation

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 Morphologic patterns…
C. SUPPURATIVE OR PURULENT INFLAMMATION;
ABSCESS
Is characterized by the production of large amounts
of pus.

Certain bacteria (e.g., staphylococci) ---pyogenic

(pus-producing) bacteria.

A common example of an acute suppurative

inflammation is acute appendicitis.
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 Morphologic patterns…
D. ULCERS
 An ulcer is a local defect, or excavation, of the surface of an
organ or tissue

 t is most commonly encountered in:

(1) the mucosa of the mouth, stomach, intestines, or
genitourinary tract

(2) the skin and subcutaneous tissue of the lower extremities

in older persons who have circulatory disturbances that
predispose to extensive ischemic necrosis.
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Ulcer

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 Morphologic patterns…

E. Pseudomembranous inflammation
• Bacterial toxin-induced damage of the mucosal
lining, producing a shaggy membrane composed of
necrotic tissue
• Example-
– Pseudomembranes associated with Clostridium difficile
in pseudomembranous colitis.

– Corynebacterium diphtheriae produces a toxin causing

pseudomembrane formation in the pharynx and trachea.
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Pseudomembranous colitis

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 Chronic inflammation
• Inflammation of prolonged duration (weeks or months) in
which active inflammation, tissue destruction, and attempts at
repair are proceeding simultaneously.

• May follow acute inflammation or be insidious in onset.

- Insidious in onset e.g., rheumatoid arthritis, atherosclerosis,
tuberculosis, and pulmonary fibrosis.

• It is of longer duration and is associated with the presence of

lymphocytes and macrophages, the proliferation of blood
vessels, fibrosis, and tissue destruction.

• Influx of lymphocytes and macrophages 39

 CAUSES OF CHRONIC INFLAMMATION
Chronic inflammation arises in the following settings:
Persistent infections by microorganisms that are
difficult to eradicate.
 E.g. mycobacteria, and certain viruses, fungi, and
parasites.

 These organisms often evoke an immune reaction

called delayed-type hypersensitivity.

 The inflammatory response sometimes takes a

specific pattern called a granulomatous reaction. 40
 CAUSES OF CHRONIC…
Immune-mediated inflammatory diseases.

Prolonged exposure to potentially toxic agents, either

exogenous or endogenous.
 Exogenous agent …silica----silicosis.

 Atherosclerosis is thought to be a chronic inflammatory

process of the arterial wall induced, at least in part, by
endogenous toxic plasma lipid components.

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 CELLS IN CHRONIC INFLAMMATION
 Lymphocytes :

 Plasma cells :

 Eosinophils :

 Mast cells :

 Macrophages :
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 Systemic Effects of Inflammation
 The systemic changes associated with acute
inflammation are collectively called the acute-phase
response, or the systemic inflammatory response
syndrome (SIRS).

 The acute-phase response consists of several clinical

and pathologic changes:

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 …
A. Fever
o Characterized by an elevation of body temperature, usually
by 1° to 4°C.

o Fever is produced in response to substances called

pyrogens that act by stimulating prostaglandin synthesis in
the vascular and perivascular cells of the hypothalamus.

o Bacterial products, such as LPS (called exogenous

pyrogens), stimulate leukocytes to release cytokines such
as IL-1 and TNF (called endogenous pyrogens)

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 …

B. Increased acute-phase proteins

 Are plasma proteins, mostly synthesized in the liver.

 Three of the best-known of these proteins are C-reactive

protein (CRP), fibrinogen, and serum amyloid A (SAA)
protein.

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 …
C. Leukocytosis
 Is a common feature of inflammatory reactions, especially
those induced by bacterial infections.

 15,000 to 20,000 cells/μL, but sometimes it may reach

extraordinarily high levels of 40,000 to 100,000 cells/μL.

 These extreme elevations are referred to as leukemoid

reactions, because they are similar to the white cell counts
observed in leukemia and have to be distinguished from
leukemia.

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 …
D. Increased pulse and blood pressure

E. In severe bacterial infections (sepsis)---septic shock

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Thank you!

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