The main vascular reactions of acute inflammation are increased
blood flow secondary to vasodilation and increased vascular permeability,
both designed to bring blood cells and proteins to sites
of infection or injury. While the initial encounter of an injurious
stimulus, such as a microbe, is with macrophages and
other cells in the connective tissue, the vascular reactions
triggered by these interactions soon follow and dominate
the early phase of the response.
Changes in Vascular Caliber and Flow
Changes in blood vessels are initiated rapidly after infection
or injury but evolve at variable rates, depending on
the nature and severity of the original inflammatory
stimulus.
• After transient vasoconstriction (lasting only for
seconds), arteriolar vasodilation occurs, resulting in
locally increased blood flow and engorgement of the
down-stream capillary beds (Fig. 2–2). This vascular
expansion is the cause of the redness (erythema) and
warmth characteristic of acute inflammation, and mentioned
previously as two of the cardinal signs of
inflammation.
• The microvasculature becomes more permeable, and
protein-rich fluid moves into the extravascular tissues.
This causes the red cells in the flowing blood to become
more concentrated, thereby increasing blood viscosity
and slowing the circulation. These changes are reflected
microscopically by numerous dilated small vessels
packed with red blood cells, called stasis.
• As stasis develops, leukocytes (principally neutrophils)
begin to accumulate along the vascular endothelial
surface—a process called margination. This is the first
step in the journey of the leukocytes through the vascular
wall into the interstitial tissue (described later).
Increased Vascular Permeability
Increasing vascular permeability leads to the movement of
protein-rich fluid and even blood cells into the extravascular
tissues (Fig. 2–4). This in turn increases the osmotic
pressure of the interstitial fluid, leading to more outflow of water from the blood into the tissues. The resulting proteinrich
fluid accumulation is called an exudate. Exudates must
be distinguished from transudates, which are interstitial
fluid accumulations caused by increased hydrostatic pressure,
usually a consequence of reduced venous return.
Transudates typically contain low concentrations of protein
and few or no blood cells. Fluid accumulation in extravascular
spaces, whether from an exudate or a transudate,
produces tissue edema. Whereas exudates are typical of
inflammation, transudates accumulate in various noninflammatory
conditions, which are mentioned in Figure 2–4
and described in more detail in Chapter 3.
Several mechanisms may contribute to increased vascular
permeability in acute inflammatory reactions:
• Endothelial cell contraction leading to intercellular gaps in
postcapillary venules is the most common cause of
increased vascular permeability. Endothelial cell contraction
occurs rapidly after binding of histamine, bradykinin,
leukotrienes, and many other mediators to
specific receptors, and is usually short-lived (15 to 30
minutes). A slower and more prolonged retraction of
endothelial cells, resulting from changes in the cytoskeleton,
may be induced by cytokines such as tumor necrosis
factor (TNF) and interleukin-1 (IL-1). This reaction
may take 4 to 6 hours to develop after the initial trigger
and persist for 24 hours or more.
• Endothelial injury results in vascular leakage by causing
endothelial cell necrosis and detachment. Endothelial
cells are damaged after severe injury such as with burns
and some infections. In most cases, leakage begins
immediately after the injury and persists for several
hours (or days) until the damaged vessels are thrombosed
or repaired. Venules, capillaries, and arterioles
can all be affected, depending on the site of the injury.
Direct injury to endothelial cells may also induce a
delayed prolonged leakage that begins after a delay of
2 to 12 hours, lasts for several hours or even days, and
involves venules and capillaries. Examples are mild to
moderate thermal injury, certain bacterial toxins, and
x- or ultraviolet irradiation (i.e., the sunburn that has
spoiled many an evening after a day in the sun). Endothelial
cells may also be damaged as a consequence of
leukocyte accumulation along the vessel wall. Activated
leukocytes release many toxic mediators, discussed
later, that may cause endothelial injury or detachment.
• Increased transcytosis of proteins by way of an intracellular
vesicular pathway augments venular permeability,
especially after exposure to certain mediators such as
vascular endothelial growth factor (VEGF). Transcytosis
occurs through channels formed by fusion of intracellular
vesicles.
• Leakage from new blood vessels. As described later, tissue
repair involves new blood vessel formation (angiogenesis).
These vessel sprouts remain leaky until proliferating
endothelial cells mature sufficiently to form
intercellular junctions. New endothelial cells also have
increased expression of receptors for vasoactive mediators,
and some of the factors that stimulate angiogenesis
(e.g., VEGF) also directly induce increased vascular
permeability.
Although these mechanisms of vascular permeability are
separable, all of them may participate in the response to a particular stimulus. For example, in a thermal burn, leakage
results from chemically mediated endothelial contraction,
as well as from direct injury and leukocyte-mediated endothelial
damage.
Responses of Lymphatic Vessels
In addition to blood vessels, lymphatic vessels also participate
in the inflammatory response. In inflammation, lymph
flow is increased and helps drain edema fluid, leukocytes,
and cell debris from the extravascular space. In severe
inflammatory reactions, especially to microbes, the lymphatics
may transport the offending agent, contributing to
its dissemination. The lymphatics may become secondarily
inflamed (lymphangitis), as may the draining lymph nodes
(lymphadenitis). Inflamed lymph nodes are often enlarged
because of hyperplasia of the lymphoid follicles and
increased numbers of lymphocytes and phagocytic cells
lining the sinuses of the lymph nodes. This constellation of
pathologic changes is termed reactive, or inflammatory,
lymphadenitis (Chapter 11). 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 is diagnostic of lymphangitis; it
may be accompanied by painful enlargement of the draining
lymph nodes, indicating lymphadenitis.
Figure 2–4 Formation of transudates and exudates. A, Normal hydrostatic pressure (blue arrows) is approximately 32 mm Hg at the arterial end of
a capillary bed and 12 mm Hg at the venous end; the mean colloid osmotic pressure of tissues is approximately 25 mm Hg (green arrows), which is
nearly equal to the mean capillary pressure. Therefore, the net flow of fluid across the vascular bed is almost nil. B, A transudate is formed when fluid
leaks out because of increased hydrostatic pressure or decreased osmotic pressure. C, An exudate is formed in inflammation because vascular permeability
increases as a result of the increase in interendothelial spaces.
blood flow secondary to vasodilation and increased vascular permeability,
both designed to bring blood cells and proteins to sites
of infection or injury. While the initial encounter of an injurious
stimulus, such as a microbe, is with macrophages and
other cells in the connective tissue, the vascular reactions
triggered by these interactions soon follow and dominate
the early phase of the response.
Changes in Vascular Caliber and Flow
Changes in blood vessels are initiated rapidly after infection
or injury but evolve at variable rates, depending on
the nature and severity of the original inflammatory
stimulus.
• After transient vasoconstriction (lasting only for
seconds), arteriolar vasodilation occurs, resulting in
locally increased blood flow and engorgement of the
down-stream capillary beds (Fig. 2–2). This vascular
expansion is the cause of the redness (erythema) and
warmth characteristic of acute inflammation, and mentioned
previously as two of the cardinal signs of
inflammation.
• The microvasculature becomes more permeable, and
protein-rich fluid moves into the extravascular tissues.
This causes the red cells in the flowing blood to become
more concentrated, thereby increasing blood viscosity
and slowing the circulation. These changes are reflected
microscopically by numerous dilated small vessels
packed with red blood cells, called stasis.
• As stasis develops, leukocytes (principally neutrophils)
begin to accumulate along the vascular endothelial
surface—a process called margination. This is the first
step in the journey of the leukocytes through the vascular
wall into the interstitial tissue (described later).
Increased Vascular Permeability
Increasing vascular permeability leads to the movement of
protein-rich fluid and even blood cells into the extravascular
tissues (Fig. 2–4). This in turn increases the osmotic
pressure of the interstitial fluid, leading to more outflow of water from the blood into the tissues. The resulting proteinrich
fluid accumulation is called an exudate. Exudates must
be distinguished from transudates, which are interstitial
fluid accumulations caused by increased hydrostatic pressure,
usually a consequence of reduced venous return.
Transudates typically contain low concentrations of protein
and few or no blood cells. Fluid accumulation in extravascular
spaces, whether from an exudate or a transudate,
produces tissue edema. Whereas exudates are typical of
inflammation, transudates accumulate in various noninflammatory
conditions, which are mentioned in Figure 2–4
and described in more detail in Chapter 3.
Several mechanisms may contribute to increased vascular
permeability in acute inflammatory reactions:
• Endothelial cell contraction leading to intercellular gaps in
postcapillary venules is the most common cause of
increased vascular permeability. Endothelial cell contraction
occurs rapidly after binding of histamine, bradykinin,
leukotrienes, and many other mediators to
specific receptors, and is usually short-lived (15 to 30
minutes). A slower and more prolonged retraction of
endothelial cells, resulting from changes in the cytoskeleton,
may be induced by cytokines such as tumor necrosis
factor (TNF) and interleukin-1 (IL-1). This reaction
may take 4 to 6 hours to develop after the initial trigger
and persist for 24 hours or more.
• Endothelial injury results in vascular leakage by causing
endothelial cell necrosis and detachment. Endothelial
cells are damaged after severe injury such as with burns
and some infections. In most cases, leakage begins
immediately after the injury and persists for several
hours (or days) until the damaged vessels are thrombosed
or repaired. Venules, capillaries, and arterioles
can all be affected, depending on the site of the injury.
Direct injury to endothelial cells may also induce a
delayed prolonged leakage that begins after a delay of
2 to 12 hours, lasts for several hours or even days, and
involves venules and capillaries. Examples are mild to
moderate thermal injury, certain bacterial toxins, and
x- or ultraviolet irradiation (i.e., the sunburn that has
spoiled many an evening after a day in the sun). Endothelial
cells may also be damaged as a consequence of
leukocyte accumulation along the vessel wall. Activated
leukocytes release many toxic mediators, discussed
later, that may cause endothelial injury or detachment.
• Increased transcytosis of proteins by way of an intracellular
vesicular pathway augments venular permeability,
especially after exposure to certain mediators such as
vascular endothelial growth factor (VEGF). Transcytosis
occurs through channels formed by fusion of intracellular
vesicles.
• Leakage from new blood vessels. As described later, tissue
repair involves new blood vessel formation (angiogenesis).
These vessel sprouts remain leaky until proliferating
endothelial cells mature sufficiently to form
intercellular junctions. New endothelial cells also have
increased expression of receptors for vasoactive mediators,
and some of the factors that stimulate angiogenesis
(e.g., VEGF) also directly induce increased vascular
permeability.
Although these mechanisms of vascular permeability are
separable, all of them may participate in the response to a particular stimulus. For example, in a thermal burn, leakage
results from chemically mediated endothelial contraction,
as well as from direct injury and leukocyte-mediated endothelial
damage.
Responses of Lymphatic Vessels
In addition to blood vessels, lymphatic vessels also participate
in the inflammatory response. In inflammation, lymph
flow is increased and helps drain edema fluid, leukocytes,
and cell debris from the extravascular space. In severe
inflammatory reactions, especially to microbes, the lymphatics
may transport the offending agent, contributing to
its dissemination. The lymphatics may become secondarily
inflamed (lymphangitis), as may the draining lymph nodes
(lymphadenitis). Inflamed lymph nodes are often enlarged
because of hyperplasia of the lymphoid follicles and
increased numbers of lymphocytes and phagocytic cells
lining the sinuses of the lymph nodes. This constellation of
pathologic changes is termed reactive, or inflammatory,
lymphadenitis (Chapter 11). 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 is diagnostic of lymphangitis; it
may be accompanied by painful enlargement of the draining
lymph nodes, indicating lymphadenitis.
Figure 2–4 Formation of transudates and exudates. A, Normal hydrostatic pressure (blue arrows) is approximately 32 mm Hg at the arterial end of
a capillary bed and 12 mm Hg at the venous end; the mean colloid osmotic pressure of tissues is approximately 25 mm Hg (green arrows), which is
nearly equal to the mean capillary pressure. Therefore, the net flow of fluid across the vascular bed is almost nil. B, A transudate is formed when fluid
leaks out because of increased hydrostatic pressure or decreased osmotic pressure. C, An exudate is formed in inflammation because vascular permeability
increases as a result of the increase in interendothelial spaces.
