2. INFLAMMATION
DEFINITION : It is defined as the local response
of living mammalian tissues to injury from any
agent . it is body’s defense reaction .
4. SIGNS OF INFLAMMATION
FOUR CARDINAL SIGNS OF INFLAMMATION
• rubor (redness)
• tumor ( swelling)
• calor (heat)
• dolor (pain)
Fifth sign added by virchow
Functio laesa
5. TYPES OF INFLAMMATION
A. ACUTE INFLAMMATION- is of short duration ,
early body reaction , resolves quickly, followed by
healing . Features are:
1) Accumulation of fluid and plasma at the affected
site
2) Intravascular activation of platelates
3) Neutrophils as inflammatory cells
6. B) CHRONIC INFLAMMATION-It is of longer duration
and occurs after delay , char. Feature is presence of
lymphocytes , plasma cells , macrophages ,
granulation tissue formation , and in specific
situations as granulomatous inflammation
7. ACUTE INFLAMMATION
Rapid onset and short duration
Marked vascular changes
More abundant fluid exudate
Main inflammatory cells:
neutrophils and macrophages
Absent or mild fibrosis
CHRONIC INFLAMMATION
Gradual onset and long
duration
Mild vascular changes,
vascular thickening
Usually scanty fluid exudate
Main inflammatory cells:
macrophages, lymphocytes,
plasma cells and giant cells.
Marked fibrosis
8. Acute inflammatory response can be divided into
following two events:
vascular events : these alteration includes
Haemodynamic changes;
Changes in vascular permiability
cellular events :consists of two processes
exudation of leucocytes;
phagocytosis
9.
10. Changes in Vascular Flow and Caliber( Haemodynamic
changes)
begin early after injury and consist of the following.
• Vasodilation is one of the earliest manifestations of
acute inflammation; sometimes it follows a transient
constriction of arterioles, lasting a few seconds.. The result is
increased blood flow, which is the cause of heat and redness
(erythema) at the site of inflammation. Vasodilation is
induced by the action of several mediators, notably histamine
and nitric oxide (NO), on vascular smooth muscle.
• Vasodilation is quickly followed by increased permeability
of the microvasculature, with the outpouring of protein-rich
fluid into the extravascular tissues
11. • The loss of fluid and increased vessel diameter
lead to slower blood flow, concentration of red cells in
small vessels, and increased viscosity of the blood.
These changes result in dilation of small vessels that
are packed with slowly moving red cells, a condition
termed stasis
• As stasis develops, blood leukocytes, principally
neutrophils, accumulate along the vascular
endothelium(leukocyte margination) Leukocytes then
adhere to the endothelium, and soon afterward they
migrate through the vascular wall into the interstitial
tissue(emigration)
12. Increased Vascular Permeability (Vascular Leakage)
Several mechanisms are responsible for the increased
vascular permeability
1. Contraction of endothelial cells :
it is the most common mechanism of vascular leakage
and
is elicited by histamine, bradykinin, leukotrienes, the
neuropeptide substance P, and many other chemical
mediators
It is called the immediate transient response because it
occurs rapidly after exposure to the mediator and is
usually short-lived (15–30 minutes)
13. 2)contraction of endothelial cells or mild endothelial damage.
In some forms of mild injury (e.g. after burns, x-irradiation or
ultraviolet radiation, and exposure to certain bacterial toxins),
vascular leakage begins after a delay of 2 to 12 hours, and
lasts for several hours or even days; this delayed prolonged
leakage . Late-appearing sunburn is a good example of this
type of leakage.
3) Endothelial injury, resulting in endothelial cell necrosis and
detachment. Direct damage to the endothelium is
encountered in severe injuries, for example, in burns In most
instances leakage starts immediately after injury and is
sustained for several hours until the damaged vessels are
thrombosed or repaired.
14. 4)Leukocyte mediated endothelial injury :
Neutrophils that adhere to the endothelium during
inflammation may also injure the endothelial cells and thus
amplify the reaction
5) Transcytosis : VEGF , seem to promote vascular leakage in
part by increasing the number and perhaps the size of
vesiculovacuolar organelle(channels)
15.
16. CELLULAR EVENTS :
The processes involving leukocytes in inflammation
consist of:
• their recruitment from the blood into
extravascular tissues,
• recognition of microbes and necrotic tissues,
• removal of the offending agent.
17. Recruitment of Leukocytes to Sites of Infection
and Injury
The journey of leukocytes from the vessel lumen to
the interstitial tissue, called extravasation, can be
divided into the following steps:
1. In the lumen: margination, rolling, and
adhesion
2. Migration across the endothelium and vessel
wall
3. Migration in the tissues toward a chemotactic
stimulus
18.
19. Leukocyte Adhesion to Endothelium.
In normally flowing blood in venules,
red cells are confined to a central axial column, and the
leukocytes toward the wall of the vessel. Because of stasis a
white cells assume a peripheral position along the endothelial
surface. This process of leukocyte redistribution is called
margination.
Subsequently, individual and then rows of leukocytes adhere
transiently to the endothelium, detach and bind again, thus
rolling on the vessel wall.
The cells finally come to rest at some point where they
adhere firmly
20. Endothelial Molecule Leukocyte Molecule Major Role
P-selectin Sialyl-Lewis X–modified
proteins
Rolling (neutrophils,
monocytes, T lymphocytes)
E-selectin Sialyl-Lewis X–modified
proteins
Rolling and adhesion
(neutrophils, monocytes, T
lymphocytes)
GlyCam-1, CD34 L-selectin[*] Rolling (neutrophils,
monocytes)
ICAM-1 (immunoglobulin
family)
CD11/CD18 (β2) integrins (LFA-
1, Mac-1)
Adhesion, arrest,
transmigration (neutrophils,
monocytes, lymphocytes)
VCAM-1 (immunoglobulin
family)
VLA-4 (β1) integrin Adhesion (eosinophils,
monocytes, lymphocytes)
Endothelial-Leukocyte Adhesion Molecules
21. Leukocyte Migration through Endothelium.
The next step in the process of leukocyte recruitment is
migration of the leukocytes through the endothelium, called
transmigration or diapedesis.
occurs mainly in post-capillary venules.
Chemokines act on the adherent leukocytes and
stimulate the cells to migrate through interendothelial spaces
toward the site of injury or infection where the chemokines
are being produced.
leukocytes pierce the basement membrane, probably
by secreting collagenases, and enter the extravascular tissue.
The cells then migrate toward the chemotactic gradient
created by chemokines and accumulate in the extravascular
site.
22. Chemotaxis of Leukocytes
After exiting the circulation, leukocytes emigrate in
tissues toward the site of injury by a process called
chemotaxis, defined as locomotion oriented along a chemical
gradient.
Both exogenous and endogenous substances can act as
chemoattractants. Endogenous chemoattractants include
several chemical mediators (described later):
(1) cytokines, particularly those of the chemokine family
(e.g., IL-8);
(2) components of the complement system, particularly C5a;
and
(3) arachidonic acid (AA) metabolites, mainly leukotriene B4
(LTB4).
23. Recognition of Microbes and Dead Tissues
After recruitment at the site of cell death,leukocyte resopnd
by two sequential events:
(1) recognition of the offending agents
(2) leukocytes then ingest and destroy the offending agents
and amplify the inflammatory reaction.
24. Leukocytes express several receptors that recognize
external stimuli and deliver activating signals
•Receptors for microbial products: Toll-like receptors (TLRs)
recognize components of different types of microbes.
• G protein–coupled receptors found on neutrophils,
macrophages, and most other types of leukocytes recognize
short bacterial peptides containing N-formylmethionyl
residues.
25. • Receptors for opsonins : Leukocytes express receptors for
proteins that coat microbes. The process of coating a particle,
such as a microbe, to target it for ingestion (phagocytosis) is
called opsonization, and substances that do this are opsonins.
These substances include antibodies, complement proteins,
and lectins
•Receptors for cytokines: Leukocytes express receptors for
cytokines that are produced in response to microbes. One of
the most important of these cytokines is interferon-γ (IFN-γ),
26. Removal of the Offending Agents
Recognition of microbes or dead cells by the receptors
described above induces leukocyte activation. The
functional responses that are most important for
destruction of microbes and other offenders are
phagocytosis and intracellular killing.
27. Phagocytosis.
Phagocytosis involves three sequential steps :
(1) recognition and attachment of the particle to be
ingested by the leukocyte; Mannose receptors, scavenger
receptors, and receptors for various opsonins all function
to bind and ingest microbes.
(2) its engulfment, with subsequent formation of a
phagocytic vacuole; After a particle is bound to phagocyte
receptors, extensions of the cytoplasm (pseudopods) flow
around it, and the plasma membrane pinches off to form a
vesicle (phagosome) that encloses the particle
28. The phagosome then fuses with a lysosomal granule,
resulting in discharge of the granule's contents into the
phagolysosome (see Fig. 2-9 ). During this process the
phagocyte may also release granule contents into the
extracellular space.
(3) killing or degradation of the ingested material
Microbial killing is accomplished largely by reactive oxygen
species (ROS, also called reactive oxygen intermediates) and
reactive nitrogen species, mainly derived from NO. Microbial
killing can also occur through the action of other substances
in leukocyte granules.
29.
30. Patterns of acute inflammation
Serous
is derived from either the plasma or the secretions of
mesothelial cells lining the peritoneal, pleural, and
pericardial cavities (called effusion).
The skin blister resulting from a burn or viral infection
represents a large accumulation of serous fluid, either
within or immediately beneath the epidermis of the skin
31. Fibrinous
With more severe injuries and the resulting greater
vascular permeability, larger molecules such as fibrinogen
pass the vascular barrier, and fibrin is formed and
deposited in the extracellular space.
fibrinous exudate is characteristic of inflammation in the
lining of body cavities, such as the meninges, pericardium
and pleura
Either entirely removed or becomes fibrotic
32. Fibrinous pericarditis.
A- Deposits of fibrin on the pericardium.
B- A pink meshwork of fibrin exudate (F) overlies the
pericardial surface (P).
33. Suppurative
Suppurative or purulent inflammation is
characterized by the production of large amounts
of pus (pyogenic staph spp.) or purulent exudate
consisting of neutrophils, necrotic cells, and edema
fluid
34. Suppurative inflammation.
A- A subcutaneous bacterial abscess with collections of pus.
B- The abscess contains neutrophils, edema fluid, and cellular debris.
35. Ulceration
An ulcer is a local defect, or excavation, of the surface of an organ
or tissue that is produced by the sloughing (shedding) of
inflammatory necrotic tissue
It is most commonly encountered in:
inflammatory necrosis of the mucosa of the mouth,
stomach, intestines, or genitourinary tract; and
subcutaneous inflammation of the lower extremities
in older persons who have circulatory disturbances
that predispose to extensive necrosis.
Trauma, toxins, vascular insufficiency
36. A- A chronic duodenal ulcer.
B- Low-power cross-section of a duodenal ulcer crater
with an acute inflammatory exudate in the base.
37. Summary
Definition of inflammation
Types
Acute inflammation
Vascular events
-change in vessel caliber and
change in permiability
Cellular events
-Recruitment of Leukocytes to Sites of Infection and Injury,( Leukocyte Adhesion to
Endothelium, Leukocyte Migration through Endothelium, Chemotaxis of Leukocytes),
Recognition of Microbes , Removal of the Offending Agents, Phagocytosis,
