60
U N I T 1
Cell and Tissue Function
proliferation. However, at higher levels these mediators
can produce endothelial cell damage, with a resultant
increase in vascular permeability; inactivate antiprote-
ases, such as
α
1
-antitrypsin, which protect against lung
damage in smokers; and produce injury to other cell
types, including red blood cells.
2
Thus, the influence of
ROS in any inflammatory process depends on a bal-
ance between the generation and inactivation of these
metabolites.
Local Manifestations
The local manifestations of acute inflammation, which
are determined by severity of the reaction, its specific
cause, and the site of involvement, can range from mild
swelling and redness to abscess formation or ulceration.
As part of the normal defense reaction, inflammation
can also injure adjacent tissues.
2
In some infections,
such as tuberculosis and certain viral infections, the host
response can cause more damage than the microbe itself.
As a normal attempt to clear damaged and dead tissues
(e.g., after a myocardial infarction), the inflammatory
response may prolong and exacerbate the injurious con-
sequences of the infarction.
Characteristically, the acute inflammatory response
involves the production of exudates. These exudates
vary in terms of fluid type, plasma protein content, and
presence or absence of cells. They can be serous, hemor-
rhagic, fibrinous, membranous, or purulent. Often the
exudate is composed of a combination of these types.
Serous exudates
are watery fluids low in protein con-
tent that result from plasma entering the inflammatory
site.
Hemorrhagic exudates
occur when there is severe
tissue injury that causes damage to blood vessels or
when there is significant leakage of red cells from the
capillaries.
Fibrinous exudates
contain large amounts of
fibrinogen and form a thick and sticky meshwork, much
like the fibers of a blood clot.
Membranous
or
pseudo-
membranous exudates
develop on mucous membrane
surfaces and are composed of necrotic cells enmeshed in
a fibropurulent exudate.
A
purulent
or
suppurative exudate
contains pus,
which is composed of degraded white blood cells, pro-
teins, and tissue debris. The term
pyogenic
refers to
“pus forming.” Certain pyogenic microorganisms, such
as
Staphylococcus
, are more likely to induce localized
suppurative inflammation than others. An
abscess
is a
localized area of inflammation containing a purulent
exudate. Abscesses typically have a central necrotic core
containing purulent exudates surrounded by a layer of
neutrophils.
2
Fibroblasts may eventually enter the area
and wall off the abscess. Because antimicrobial agents
cannot penetrate the abscess wall, surgical incision and
drainage may be required as a cure.
An
ulceration
refers to a site of inflammation where
an epithelial surface (e.g., skin or gastrointestinal epithe-
lium) has become necrotic and eroded, often with asso-
ciated subepithelial inflammation. Ulceration may occur
as the result of traumatic injury to the epithelial surface
(e.g., peptic ulcer) or because of vascular compromise
(e.g., foot ulcers associated with diabetes). In chronic
lesions where there is repeated insult, the area surrounding
the ulcer develops fibroblastic proliferation, scarring,
and accumulation of chronic inflammatory cells.
2
Resolution
Although the manifestations of acute inflammation are
largely determined by the nature and intensity of injury,
the tissue affected, and the person’s ability to mount a
response, the outcome generally results in one of three pro-
cesses: resolution, progression to chronic inflammation,
or substantial scarring and fibrosis.
2
Resolution involves
the replacement of any irreversibly injured cells and return
of tissues to their normal structure and function.
21,22
It is
seen with short-lived and minimal injuries and involves
neutralization or degradation of inflammatory mediators,
normalization of vascular permeability, and cessation of
leukocyte infiltration. Progression to chronic inflamma-
tion may follow acute inflammation if the offending agent
is not removed. Depending on the extent of injury, as well
as the ability of the affected tissues to regenerate, chronic
inflammation may be followed by restoration of normal
structure and function. Scarring and fibrosis occurs when
there is substantial tissue injury or when inflammation
occurs in tissues that do not regenerate.
Although the mechanisms involved in the resolution
of acute inflammation have remained somewhat elusive,
emerging evidence suggests that an active, coordinated
program of resolution begins in the first hours after an
inflammatory response begins.
2,21
Studies suggest that
after entering the site of acute inflammation, neutrophils
trigger a switch from the previously described proinflam-
matory eicosanoids (e.g., prostaglandins and leukotri-
enes) to other anti-inflammatory classes of eicosanoids,
also generated from arachidonic acid. These eicosanoids
initiate the termination sequence during which neutro-
phil recruitment ceases and programmed cell death by
apoptosis commences. The apoptotic neutrophils then
undergo phagocytosis by macrophages, leading to their
clearance and release of anti-inflammatory and repara-
tive cytokines. Although much new information regard-
ing the resolution of inflammation has been obtained
over the past few years, many issues require further clar-
ification. New therapeutic targets are currently being
investigated and potential proresolution properties of
existing drugs studied. These discoveries may bring
profound advances in therapies aimed at reducing the
adverse effects of persistent inflammation.
SUMMARY CONCEPTS
■■
The classic signs of an acute inflammatory
response are redness, swelling, local heat, pain,
and loss of function.These manifestations can
be attributed to the immediate vascular changes
that occur (vasodilation and increased capillary
