Inflammation

Dr. Raid Jastania

Insult

Results

Stress

Overload

Injury

Cell
Death

Response

Adaptation

Inflammation

Causes of Inflammation
Injury and cell
Death
Physical
Chemical
Infections
Ischemia
Immune
Metabolic

Inflammation

Types of Inflammation
Injury and cell
Death
Physical
Chemical
Infections
Ischemia
Immune
Metabolic

Acute
Inflammation

Chronic
Granuloma

Immune Reaction
Injury and cell
Death
Physical
Chemical
Infections
Ischemia
Immune
Metabolic

Acute
Inflammation

Chronic
Granuloma

Immune

Chronic Inflammatory Diseases

Injury and cell
Death
Physical
Chemical
Infections
Ischemia
Immune
Metabolic

Acute
Inflammation

Chronic
Granuloma

Immune
Chronic
Inflammatory
Diseases

Acute Inflammation
Chronic Inflammation
Chemical Mediators of
Inflammation

 Intended Learning Outcomes:

1. Students should be able to define inflammation and
understand clinical features of inflammation and its
systemic effect.
2. Students should know the vascular and cellular events
in acute inflammation and understand its morphology.
3. Students should know the cellular events in chronic
inflammation.
4. Students should be able to define granulomatous
inflammation and know its causes.
5. Students should be able to apply the rules of acute
and chronic inflammation to predict the features of
inflammation in the different organs of the body.

Inflammation
Inflammation is a protective response of
connective tissue to injury.
Aim: to eliminate the injury and start the process
of repair.
Inflammation starts with activation of endothelial
cells and white blood cells.
Changes in vessels
Cellular events.
Chemical mediators

Inflammation
Inflammation is divided into acute and
chronic type.
Acute inflammation is the immediate
response to injury, and neutrophils are the
main cell type.
Chronic inflammation is mediated by
mononuclear cells (macrophages,
lymphocytes, plasma cell)

Clinical Features:
Exercise:
During a foot ball game, a player was
injured and had twist in ankle joint.
What are the signs/symptoms that he
would have?

Clinical Features:
Exercise:
19 year old boy has inflammation of the
appendix, Appendicitis.
What are the signs/symptoms that he
would have?

Clinical Features:
Localized or systemic.
The localized features are: Redness,
Swelling, Heat, Pain and Loss of
function.
The systemic features include: Fever,
elevated WBC, malaise, anorexia, and
hypotension, Acute phase reaction

Acute Inflammation

Acute Inflammation:
It is the immediate early response to injury.
It is characterized by neutorphil infiltrate
and fluid exudates.
The changes in acute inflammation may be
divided to: vascular changes and cellular
events.

Vascular changes:
1. Change in the vascular caliber and flow
initial transient vasoconstriction of the arterioles
followed by vasodilatation. The end result is
blood stasis.
2. Increase in vascular permeability
increase in the hydrostatic pressure and leakage of
fluid to the extravascualr space (Transudate).
increase in the osmotic pressure of the interstitium
leading to leakage of protein-rich fluid (Exudate).
The end result is Edema.

Mechanisms of increased
vascular permeability:
1. Endothelial contraction: histamine, PG,
Immediate transient response
2. Endothelial retraction: 4-6 hours after
injury
3. Direct endothelial damage: Immediate
sustained Response
4. Delayed prolonged leakage:

Mechanisms of increased
vascular permeability:
5. Leukocyte-dependent endothelial injury
6. Increased Transcytosis: Through
intracellular vesicular pathway, and occurs
after exposure to VEGF.
7. Leakage from new blood vessels
(angiogenesis)

Cellular Events

Cellular Events:
1. Margination and Rolling:
WBC slow down and are pushed to the
side of the vessel near endothelial cells.
This process is Margination
WBCs transiently stick to endothelial
cells. This process is Rolling
The adhesion is facilitated by the action of
adhesion molecules called Selectins.

Cellular Events:
1. Margination and Rolling:
Selections are present on WBC, endothelial cells
and platelets.
E-Selectin: on endothelial cell
P-Selectin: on Platelets and endothelial cells
L-Selectin: on WBCs
Selectins are up regulated by IL-1, and TNF.
Selectins bind to sugar molecules. Example:
Sialyl-Lewis X

Cellular Events:
2. Adhesion and Transmigration:
Firm adhesion of WBCs to endothelial cells.
Integrins on WBCs and Immunoglobulins on
endothelial cells.
Example of immunoglobulins: ICAM
(intercellular adhesion molecule), VCAM
(vascular adhesion molecule)
ICAM binds to LFA-1 (integrin)
VCAM binds to VLA-4 (integrin)

Cellular Events:
2. Adhesion and Transmigration:
IL-1 and TNF induce the expression of ICAM
and VCAM
Integrins bind only when WBCs are activated.
Transmigration occurs as the WBCs pass through
intercellular junction. This process is facilitated
by PECAM (platelet endothelial cell adhesion
molecule, CD31).

Cellular Events:
3. Migration in interstitium: Chemotaxis
Migration of WBCs is facilitated by
chemotactic agents. These are molecules
that attract WBCs. They include:
a.
b.
c.
d.

Bacterial products
Complement system, C5a
Leukotriene B4 (LTB4)
Cytokines (IL-8)

Leukocyte Activation:
by G-protein activation
WBC activation is characterized by:
a. Degranulation of WBC granules and formation
of oxidative burst
b.Secretion of arachidonic acid metabolites
(Leukotrienes and prostaglandins)
c. Expression of adhesion molecules.

Phagocytosis
1. Recognition and attachment:
opsonins:
immunoglobulins IgG
C3b molecule of the complement system
Collectins
WBCs have specific receptors to these
opsonins.

Phagocytosis
2. Engulfment in phagocytic vacuole:
phagosome.
3. Killing and degradation:
Phagosome fuses to lysosome to form
phagolysosome.
Killing is facilitated by:
a.
Oxygen free radicals (oxidative burst)
b. Lysosomal enzymes (myeloperoxidase)

Outcome of Acute
Inflammation:
1. Resolution
2. Acute persists with complications:
Abscess
3. Progression to chronic inflammation
4. Scarring and Fibrosis
organization and fibrosis

Inflammation-Induced
Tissue Injury