Inflammation
Inflammation:
is a response of vascularized tissues to infections and tissue damage that brings
cells and molecules of host defense from the circulation to the sites where they are needed, to
eliminate the offending agents.
Inflammation suggests a harmful reaction, it is actually a protective response that is essential for
survival. It serves to rid the host of both the initial cause of cell injury (e.g., microbes, toxins)
and the consequences of such injury (e.g., necrotic cells and tissues).
The typical inflammatory reaction develops through a series of sequential steps:
1- The offending agent, which is located in extravascular tissues, is recognized by host cells
and molecules.
2- Leukocytes and plasma proteins are recruited from the circulation to the site where the
offending agent is located.
3- The leukocytes and proteins are activated and work together to destroy and eliminate the
offending substance.
4- The reaction is controlled and terminated.
5- The damaged tissue is repaired.
Inflammation may be of two types
acute
and
chronic
acute inflammation:
is a rapid response to infections and
tissue damage, it typically
develops within minutes or hours and is of short duration, lasting for several hours or a few
days. Its main characteristics are the exudation of fluid and plasma proteins (edema) and the
emigration of leukocytes, predominantly neutrophils (also called polymorphonuclear
leukocytes), when acute inflammation achieves its desired goal of eliminating the offenders, the
reaction subsides and residual injury is repaired.
Inflammation is induced by chemical mediators that are produced by host cells in response to
injurious stimuli, When a microbe enters a tissue or the tissue is injured, the presence of the
infection or damage is sensed by resident cells, including macrophages, dendritic cells,
mast cells, and other cell types. These cells secrete molecules (cytokines and other mediators)
that induce and regulate the subsequent inflammatory response.
The external manifestations of inflammation:
Often called its cardinal signs are
1- heat
2- redness.
3- swelling (tumor).
4- Pain .
5- and loss of function .
CAUSES OF INFLAMMATION
Inflammatory reactions may be triggered by a variety of stimuli:
1- Infections
(bacterial, viral, fungal, parasitic) and microbial toxins are among the most
common and medically important causes of inflammation. Different infectious pathogens
elicit distinct inflammatory responses, from mild acute inflammation that causes little or
no lasting damage and successfully eradicates the infection, to severe systemic reactions
that can be fatal, to prolonged chronic reactions that cause extensive tissue injury.
2- Tissue necrosis
elicits inflammation regardless of the cause of cell death, which may
include ischemia (reduced blood flow, the cause of myocardial infarction), trauma, and
physical and chemical injury (e.g., thermal injury, as in burns or frostbite; irradiation;
exposure to some environmental chemicals). Several molecules released from necrotic
cells are known to trigger inflammation .
3- Foreign bodies (splinters, dirt, sutures)
may elicit inflammation by themselves or because
they cause traumatic tissue injury or carry microbes. Even some endogenous substances
stimulate potentially harmful inflammation if large amounts are deposited in tissues; such
substances include urate crystals (in the disease gout), and cholesterol crystals (in
atherosclerosis).
4- Immune reactions
(also called hypersensitivity) are reactions in which the normally
protective immune system damages the individual’s own tissues. The injurious immune
responses may be directed against self-antigens, causing autoimmune diseases, or may be
inappropriate reactions against environmental substances, as in allergies, or against
microbes. Inflammation is a major cause of tissue injury in these diseases . Because the
stimuli for the inflammatory responses in autoimmune and allergic diseases (self and
environmental antigens) cannot be eliminated, these reactions tend to be persistent and
difficult to cure, are often associated with chronic inflammation, and are important causes
of morbidity and mortality.
ACUTE INFLAMMATION
Acute inflammation has three major components:
(1)
dilation of small vessels, leading to an increase in blood flow.
(2)
increased permeability of the microvasculature, enabling plasma proteins and leukocytes to
leave the circulation.
(3)
emigration of the leukocytes from the microcirculation, their accumulation in the focus of
injury, and their activation to eliminate the offending agent ,when an injurious agent, such as an
infectious microbe or dead cells, is encountered, phagocytes that reside in all tissues try to
eliminate these agents. At the same time, phagocytes and other sentinel cells in the tissues
recognize the presence of the foreign or abnormal substance and react by liberating soluble
molecules that mediate inflammation. Some of these mediators act on small blood vessels in the
vicinity and promote the efflux of plasma and the recruitment of circulating leukocytes to the
site where the offending agent is located.
Reactions of Blood Vessels in Acute Inflammation
The vascular reactions of acute inflammation consist of changes in the flow of blood and the
permeability of vessels, both designed to maximize the movement of plasma proteins and
leukocytes out of the circulation and into the site of infection or injury. The escape of fluid,
proteins, and blood cells from the vascular system into interstitial tissues or body cavities is
known as exudation. An exudate is an extravascular fluid that has a high protein concentration
and contains cellular debris. Its presence implies that there is an increase in the permeability of
small blood vessels, typically during an inflammatory reaction. In contrast, a transudate is a
fluid with low protein content, little or no cellular material, and low specific gravity, the
inflammatory exudate rich in leukocytes (mostly neutrophils), the debris of dead cells, and, in
many cases, microbes.
Changes in Vascular Flow and Caliber
Changes in vascular flow and caliber begin early after injury and consist of the following:
1-
Vasodilation
is induced by the action of several mediators, notably histamine, on vascular
smooth muscle. It is one of the earliest manifestations of acute inflammation, and may be
preceded by transient vasoconstriction. Vasodilation first involves the arterioles and then
leads to the opening of new capillary beds in the area. The result is increased blood flow,
which is the cause of heat and redness (erythema) at the site of inflammation.
2- Vasodilation is quickly followed by increased permeability of the microvasculature, with
the outpouring of protein-rich fluid (an exudate) into the extravascular tissues.
3- 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
stasis of blood flow, engorgement of small vessels jammed with slowly moving red cells,
seen histologically as vascular congestion and externally as localized redness (erythema)
of the involved tissue.
4- As stasis develops, blood leukocytes, principally neutrophils, accumulate along the
vascular endothelium. At the same time endothelial cells are activated by mediators
produced at sites of infection and tissue damage, and express increased levels of adhesion
molecules. Leukocytes then adhere to the endothelium, and soon afterward they migrate
through the vascular wall into the interstitial tissue .
Increased Vascular Permeability (Vascular Leakage)
Several mechanisms are responsible for increased vascular permeability in acute inflammation
which include:
1-
Retraction of endothelial cells
resulting in opening of inter-endothelial spaces is the most
common mechanism of vascular leakage, it is elicited by histamine, bradykinin,
leukotrienes, and other chemical mediators. It occurs rapidly after exposure to the
mediator (within 15 to 30 minutes) and is usually short-lived; hence, it is referred to as
the immediate transient response, to distinguish it from the delayed prolonged response
that follows endothelial injury, the main sites for this rapid increase in vascular
permeability are postcapillary venules.
2-
Endothelial injury,
resulting in endothelial cell necrosis and detachment. Direct damage
to the endothelium is encountered in severe injuries, for example, in burns, or is induced
by the actions of microbes and microbial toxins that target endothelial cells. Neutrophils
that adhere to the endothelium during inflammation may also injure the endothelial cells
and thus amplify the reaction. In most instances leakage starts immediately after injury
and is sustained for several hours until the damaged vessels are thrombosed or repaired.
Responses of Lymphatic Vessels and Lymph Nodes
In addition to blood vessels, lymphatic vessels also participate in acute inflammation. The
system of lymphatics and lymph nodes filters and polices the extravascular fluids. Lymphatics
drain the small amount of extravascular fluid that seeps out of capillaries under normal
circumstances. In inflammation, lymph flow is increased to help drain edema fluid that
accumulates because of increased vascular permeability. In addition to fluid, leukocytes and cell
debris, as well as microbes, may find their way into lymph. Lymphatic vessels, like blood
vessels, proliferate during inflammatory reactions to handle the increased load. The lymphatics
may become secondarily inflamed (lymphangitis), as may the draining lymph nodes
(lymphadenitis). Inflamed lymph nodes are often enlarged because of increased cellularity. This
constellation of pathologic changes is termed reactive, or inflammatory, lymphadenitis. For
clinicians the presence of red streaks near a skin wound is a telltale sign of an infection in the
wound. This streaking follows the course of the lymphatic channels and indicates the presence
of lymphangitis; it may be accompanied by painful enlargement of the draining lymph nodes,
indicating lymphadenitis.