Hoofdstuk 3
Hyperemia and congestion both refer to an increase in blood volume within a tissue
but they have different underlying mechanisms. Hyperemia is an active process
resulting from arteriolar dilation and increased blood inflow, as occurs at sites of
inflammation or in exercising skeletal muscle. Congestion is a passive process
resulting from impaired outflow of venous blood from a tissue. Congested tissues
have an abnormal blue-red color (cyanosis) that stems from the accumulation of
deoxygenated hemoglobin in the affected area. Edema is an accumulation of
interstitial fluid within tissues. Edema is the result of the movement of fluid from the
vasculature into the interstitial spaces; the fluid may be protein-poor (transudate) or
protein-rich (exudate). Extravascular fluid can also collect in body cavities such as
the pleural cavity (hydrothorax), the pericardial cavity (hydropericardium), or the
peritoneal cavity (hydroperitoneum, or ascites). Anasarca is severe, generalized
edema marked by profound swelling of subcutaneous tissues and accumulation of
fluid in body cavities. Fluid movement between the vascular and interstitial spaces is
governed mainly by two opposing forces—the vascular hydrostatic pressure and the
colloid osmotic pressure produced by plasma proteins. The edema fluid that
accumulates owing to increased hydrostatic pressure or reduced intravascular
colloid typically is a protein-poor transudate. Generalized increases in venous
pressure, with resultant systemic edema, occur most commonly in congestive heart
failure. The reduced cardiac output leads to hypoperfusion of the kidneys, triggering
the renin-angiotensin-aldosterone axis and inducing sodium and water retention
(secondary hyperaldosteronism). In nephrotic syndrome, damaged glomerular
capillaries become leaky, leading to the loss of albumin (and other plasma proteins)
in the urine and the development of generalized edema. Reduced albumin synthesis
occurs in the setting of severe liver disease (e.g., cirrhosis). Regardless of cause, low
albumin levels lead in a stepwise fashion to edema, reduced intravascular volume,
renal hypoperfusion, and secondary hyperaldosteronism. Impaired lymphatic
drainage and consequent lymphedema usually result from a localized obstruction
caused by an inflammatory or neoplastic condition. Excessive retention of salt (and
its obligate associated water) can lead to edema by increasing hydrostatic pressure
(due to expansion of the intravascular volume) and reducing plasma osmotic
pressure.
Edema may be caused by: increased hydrostatic pressure (e.g., heart failure),
increased vascular permeability (e.g., inflammation), decreased colloid osmotic
pressure, due to reduced plasma albumin decreased synthesis (e.g., liver disease,
, protein malnutrition) or increased loss (e.g., nephrotic syndrome), lymphatic
obstruction (e.g., inflammation or neoplasia), sodium retention (e.g., renal failure).
Hemorrhage, defined as the extravasation of blood from vessels, occurs in a
variety of settings. Different appearances: Hemorrhage may be external or
accumulate within a tissue as a hematoma, Petechiae are minute (1 to 2 mm in
diameter) hemorrhages into skin, mucous membranes, or serosal surfaces, Purpura
are slightly larger (3 to 5 mm) hemorrhages, Ecchymoses are larger (1 to 2 cm)
subcutaneous hematomas (colloquially called bruises). The pathologic counterpart
of hemostasis is thrombosis, the formation of blood clot (thrombus) within intact
vessels.
Both hemostasis and thrombosis involve three elements: the vascular wall, platelets,
and the coagulation cascade. Normal hemostasis steps: (1) Vascular injury causes
transient arteriolar vasoconstriction through reflex neurogenic mechanisms,
augmented by local secretion of endothelin. (2) Endothelial injury exposes highly
thrombogenic subendothelial extracellular matrix (ECM), facilitating platelet
adherence, activation, and aggregation. The formation of the initial platelet plug is
called primary hemostasis. (3) Exposed tissue factor, acting in conjunction with
factor VII, is the major in vivo trigger of the coagulation cascade and its activation
eventually culminates in the activation of thrombin, which has several roles in
regulating coagulation. (4) Activated thrombin promotes the formation of an
insoluble fibrin clot by cleaving fibrinogen; thrombin also is a potent activator of
additional platelets, which serve to reinforce the hemostatic plug. secondary
hemostasis. (5) As bleeding is controlled, counter regulatory mechanisms (e.g.,
factors that produce fibrinolysis, such as tissue-type plasminogen activator) are set
into motion to ensure that clot formation is limited to the site of injury. Endothelial
cells are central regulators of hemostasis; Normal endothelial cells express a variety
of anticoagulant factors that inhibit platelet aggregation and coagulation and
promote fibrinolysis.
Inhibitory effect on platelets: Endothelium, prostacyclin, NO inhibit platelet
aggregation.
Inhibitory Effects on Coagulation Factors: The heparin-like molecules act
indirectly: They are cofactors that greatly enhance the inactivation of thrombin (and
other coagulation factors) by the plasma protein antithrombin III. Thrombomodulin
also acts indirectly: It binds to thrombin, thereby modifying the substrate specificity
of thrombin, so that instead of cleaving fibrinogen, it instead cleaves and activates
protein C, an anticoagulant. Fibrinolysis: Endothelial cells synthesize tissue-type
plasminogen activator, a protease that cleaves plasminogen to plasmin; plasmin, in
turn, cleaves fibrin to degrade thrombi.
Activation of Platelets Endothelial injury brings platelets into contact with the
subendothelial ECM, which includes among its constituents von Willebrand factor
(vWF). Activation of Clotting Factors In response to cytokines or certain
Hyperemia and congestion both refer to an increase in blood volume within a tissue
but they have different underlying mechanisms. Hyperemia is an active process
resulting from arteriolar dilation and increased blood inflow, as occurs at sites of
inflammation or in exercising skeletal muscle. Congestion is a passive process
resulting from impaired outflow of venous blood from a tissue. Congested tissues
have an abnormal blue-red color (cyanosis) that stems from the accumulation of
deoxygenated hemoglobin in the affected area. Edema is an accumulation of
interstitial fluid within tissues. Edema is the result of the movement of fluid from the
vasculature into the interstitial spaces; the fluid may be protein-poor (transudate) or
protein-rich (exudate). Extravascular fluid can also collect in body cavities such as
the pleural cavity (hydrothorax), the pericardial cavity (hydropericardium), or the
peritoneal cavity (hydroperitoneum, or ascites). Anasarca is severe, generalized
edema marked by profound swelling of subcutaneous tissues and accumulation of
fluid in body cavities. Fluid movement between the vascular and interstitial spaces is
governed mainly by two opposing forces—the vascular hydrostatic pressure and the
colloid osmotic pressure produced by plasma proteins. The edema fluid that
accumulates owing to increased hydrostatic pressure or reduced intravascular
colloid typically is a protein-poor transudate. Generalized increases in venous
pressure, with resultant systemic edema, occur most commonly in congestive heart
failure. The reduced cardiac output leads to hypoperfusion of the kidneys, triggering
the renin-angiotensin-aldosterone axis and inducing sodium and water retention
(secondary hyperaldosteronism). In nephrotic syndrome, damaged glomerular
capillaries become leaky, leading to the loss of albumin (and other plasma proteins)
in the urine and the development of generalized edema. Reduced albumin synthesis
occurs in the setting of severe liver disease (e.g., cirrhosis). Regardless of cause, low
albumin levels lead in a stepwise fashion to edema, reduced intravascular volume,
renal hypoperfusion, and secondary hyperaldosteronism. Impaired lymphatic
drainage and consequent lymphedema usually result from a localized obstruction
caused by an inflammatory or neoplastic condition. Excessive retention of salt (and
its obligate associated water) can lead to edema by increasing hydrostatic pressure
(due to expansion of the intravascular volume) and reducing plasma osmotic
pressure.
Edema may be caused by: increased hydrostatic pressure (e.g., heart failure),
increased vascular permeability (e.g., inflammation), decreased colloid osmotic
pressure, due to reduced plasma albumin decreased synthesis (e.g., liver disease,
, protein malnutrition) or increased loss (e.g., nephrotic syndrome), lymphatic
obstruction (e.g., inflammation or neoplasia), sodium retention (e.g., renal failure).
Hemorrhage, defined as the extravasation of blood from vessels, occurs in a
variety of settings. Different appearances: Hemorrhage may be external or
accumulate within a tissue as a hematoma, Petechiae are minute (1 to 2 mm in
diameter) hemorrhages into skin, mucous membranes, or serosal surfaces, Purpura
are slightly larger (3 to 5 mm) hemorrhages, Ecchymoses are larger (1 to 2 cm)
subcutaneous hematomas (colloquially called bruises). The pathologic counterpart
of hemostasis is thrombosis, the formation of blood clot (thrombus) within intact
vessels.
Both hemostasis and thrombosis involve three elements: the vascular wall, platelets,
and the coagulation cascade. Normal hemostasis steps: (1) Vascular injury causes
transient arteriolar vasoconstriction through reflex neurogenic mechanisms,
augmented by local secretion of endothelin. (2) Endothelial injury exposes highly
thrombogenic subendothelial extracellular matrix (ECM), facilitating platelet
adherence, activation, and aggregation. The formation of the initial platelet plug is
called primary hemostasis. (3) Exposed tissue factor, acting in conjunction with
factor VII, is the major in vivo trigger of the coagulation cascade and its activation
eventually culminates in the activation of thrombin, which has several roles in
regulating coagulation. (4) Activated thrombin promotes the formation of an
insoluble fibrin clot by cleaving fibrinogen; thrombin also is a potent activator of
additional platelets, which serve to reinforce the hemostatic plug. secondary
hemostasis. (5) As bleeding is controlled, counter regulatory mechanisms (e.g.,
factors that produce fibrinolysis, such as tissue-type plasminogen activator) are set
into motion to ensure that clot formation is limited to the site of injury. Endothelial
cells are central regulators of hemostasis; Normal endothelial cells express a variety
of anticoagulant factors that inhibit platelet aggregation and coagulation and
promote fibrinolysis.
Inhibitory effect on platelets: Endothelium, prostacyclin, NO inhibit platelet
aggregation.
Inhibitory Effects on Coagulation Factors: The heparin-like molecules act
indirectly: They are cofactors that greatly enhance the inactivation of thrombin (and
other coagulation factors) by the plasma protein antithrombin III. Thrombomodulin
also acts indirectly: It binds to thrombin, thereby modifying the substrate specificity
of thrombin, so that instead of cleaving fibrinogen, it instead cleaves and activates
protein C, an anticoagulant. Fibrinolysis: Endothelial cells synthesize tissue-type
plasminogen activator, a protease that cleaves plasminogen to plasmin; plasmin, in
turn, cleaves fibrin to degrade thrombi.
Activation of Platelets Endothelial injury brings platelets into contact with the
subendothelial ECM, which includes among its constituents von Willebrand factor
(vWF). Activation of Clotting Factors In response to cytokines or certain
