meaning literally "blood
movement" is the study of blood flow or the
It explains the physical laws that govern the
flow of blood in the blood vessels.
health of cells and tissues depends not
only on an intact circulation to deliver
oxygen and remove wastes but also on
normal fluid homeostasis.
fluid homeostasis requires vessel
wall integrity as well as maintenance of
intravascular pressure and osmolarity within
certain physiologic ranges.
Increases in vascular volume or pressure, decreases in
plasma protein content, or alterations in endothelial function can
result in a net outward movement of water across the vascular
Such water extravasation into interstitial spaces is called
edema; depending on its location, edema may have minimal or
Thus, in the lower extremities edema fluid causes primarily
swelling; however, in the lungs, edema fluid will fill alveoli and
can result in life-threatening breathing difficulties.
Normal fluid homeostasis also means maintaining blood as a liquid until such
time as injury necessitates formation of a clot.
Absence of clotting after vascular injury results in hemorrhage; local bleeding
can compromise regional tissue perfusion, while more extensive hemorrhage
can result in hypotension (shock) and death.
Conversely, inappropriate clotting (thrombosis) or migration of clots
(embolism) can obstruct tissue blood supplies and cause cell death
Abnormal fluid homeostasis (i.e., hemorrhage or thrombosis) underlies three
of the most important causes of morbidity and mortality in Western society:
myocardial infarction, pulmonary embolism, and cerebrovascular accident
Approximately 60% of lean body weight is water, two-thirds
of which is intracellular and the remainder is in extracellular
compartments, mostly as interstitial fluid; only 5% of total
body water is in blood plasma.
The term edema signifies increased fluid in the interstitial
Fluid collections in different body cavities are variously
designated hydrothorax, hydropericardium, or
Anasarca is a severe and generalized edema
with profound subcutaneous tissue swelling.
The mechanism of inflammatory edema mostly
involves increased vascular permeability.
Causes of Edema
Two types :
- Increased hydrostatic pressure
- Decreased plasma osmotic pressure
- Lymphatic obstruction.
- During the process of inflammation.
The effects of edema may range from merely
annoying to rapidly fatal.
Subcutaneous edema in cardiac or renal failure
is important primarily because it indicates underlying
In contrast, pulmonary edema can cause death by
interfering with normal ventilatory function and also
creates a favorable environment for bacterial
Brain edema is serious and can be rapidly
If severe, brain edema can cause Herniation
(extrusion of the brain) through the foramen
The brainstem vascular supply can also be
compressed by edema causing increased
HYPEREMIA AND CONGESTION
Both indicate a local increased volume of blood in
a particular tissue.
Hyperemia is an active process resulting from
augmented blood flow due to arteriolar dilation
(e.g., at sites of inflammation or in skeletal muscle
The affected tissue is redder than normal because
of engorgement with oxygenated blood.
Congestion is a passive process resulting from
impaired venous return out of a tissue.
It may occur systemically, as in cardiac failure,
or it may be local, resulting from an isolated
The tissue has a blue-red color (cyanosis),
especially as worsening congestion leads to
accumulation of deoxygenated hemoglobin
in the affected tissues
Congestion of capillary beds is closely related to the
development of edema, so that congestion and edema
commonly occur together.
In long-standing congestion, called chronic passive
congestion, the stasis of poorly oxygenated blood causes
chronic hypoxia, which in turn can result in degeneration
or death of parenchymal cells and subsequent tissue
Capillary rupture at such sites of chronic congestion can
also cause small foci of hemorrhage; phagocytosis and
catabolism of the erythrocyte debris can result in
accumulations of hemosiderin-laden macrophages.
Cut surfaces of hyperemic or congested tissues are
hemorrhagic and wet.
Microscopically, acute pulmonary congestion is
characterized by alveolar capillaries engorged with blood;
there may also be associated alveolar septal edema
and/or focal minute intra-alveolar hemorrhage.
In chronic pulmonary congestion the septa become
thickened and fibrotic, and the alveolar spaces may
contain numerous hemosiderin-laden macrophages .
In acute hepatic congestion the central vein and
sinusoids are distended with blood.
There may even be central hepatocyte degeneration.
The periportal hepatocytes, better oxygenated because of
their proximity to hepatic arterioles, undergo less severe
hypoxia and may develop only fatty change.
chronic passive congestion of the liver
the central regions of the hepatic lobules are
grossly red-brown and slightly depressed
(because of a loss of cells) "nutmeg liver.
Liver with chronic passive congestion & hemorrhagic necrosis
A, Central areas are red
and slightly depressed
compared with the
surrounding tan viable
parenchyma, forming a
"nutmeg liver" pattern (so
called because it
resembles the alternating
pattern of light and dark
seen when a whole
nutmeg is cut).
B, Centrilobular necrosis
Hemorrhage is extravasation of blood from vessels into
the extravascular space.
Capillary bleeding can occur under conditions of chronic
congestion; an increased tendency to hemorrhage (usually
with insignificant injury) occurs in a wide variety of clinical
disorders collectively called hemorrhagic diseases.
Rupture of a large artery or vein results in severe
hemorrhage, and is almost always due to vascular injury,
including trauma, atherosclerosis, or inflammatory or
neoplastic erosion of the vessel wall.
can be external or can be confined
within a tissue; any accumulation is referred to as
can be relatively insignificant (e.g., a
bruise) or can involve so much bleeding as to
cause death (e.g. a massive subarachnoid
hematoma resulting death.)
Types of Hemorrhage
Minute (1- to 2-mm) hemorrhages into skin, mucous
membranes, or serosal surfaces are called petechiae
and are typically associated with locally increased
intravascular pressure, low platelet counts
(thrombocytopenia), defective platelet function, or
clotting factor deficiencies
Slightly larger (3- to 5-mm) hemorrhages are called
purpura and can be associated with many of the same
disorders that cause petechiae; in addition, purpura can
occur with trauma, vascular inflammation (vasculitis)
Larger (1- to 2-cm) subcutaneous hematomas (bruises) are called
Large accumulations of blood in one or another of the body cavities
are called hemothorax, hemopericardium, hemoperitoneum, or
hemarthrosis (in joints).
Patients with extensive hemorrhages occasionally develop jaundice
from the massive breakdown of red blood cells and systemic
increases in bilirubin.
Depends on the volume and rate of blood loss.
Rapid removal of around 20% of blood volume or slow losses of even
larger amounts may have little impact in healthy adults;
Greater losses, however, can cause hypovolemic shock.
The site of hemorrhage is also important; bleeding that would be trivial in
the subcutaneous tissues may cause death if located in the brain.
Finally, chronic or recurrent external blood loss (e.g., a peptic ulcer or
menstrual bleeding) causes a net loss of iron, leading to iron deficiency
In contrast, when red cells are retained (e.g., with hemorrhage into body
cavities or tissues), the iron can be reutilized for hemoglobin synthesis.
A, Punctate petechial hemorrhages of the colonic mucosa, a
consequence of thrombocytopenia.
B, Fatal intracerebral hemorrhage.
HEMOSTASIS AND THROMBOSIS
Normal hemostasis is a consequence of tightly regulated
processes that maintain blood in a fluid, clot-free state in
normal vessels while inducing the rapid formation of a
localized hemostatic plug at the site of vascular injury.
The pathologic form of hemostasis is thrombosis; it
involves blood clot (thrombus) formation in uninjured CVS
or thrombotic occlusion of a vessel after relatively minor
Both hemostasis and thrombosis involve three
components: the vascular wall, platelets, and the
There are three
primary influences on
(1) endothelial injury,
(Alteration in wall)
(2) stasis or turbulence
of blood flow (Alteration
This is a dominant influence, since endothelial loss by
itself can lead to thrombosis.
It is particularly important for thrombus formation
occurring in the heart or in the arterial circulation,
where the normally high flow rates might otherwise
hamper clotting by preventing platelet adhesion or
diluting coagulation factors.
Thus, thrombus formation within the cardiac
chambers (e.g., after endocardial injury due to
myocardial infarction), over ulcerated plaques in
atherosclerotic arteries, or at sites of traumatic or
inflammatory vascular injury (vasculitis) is largely a
function of endothelial injury.
Clearly, physical loss of endothelium leads to exposure of
subendothelial ECM, adhesion of platelets, release of
tissue factor, and local depletion of PGI2 and
However, endothelium need not be denuded or physically
disrupted for thrombosis; any imbalance between
prothrombotic and antithrombotic activities of endothelium
can influence local clotting events
Significant endothelial dysfunction (in the
absence of endothelial cell loss) may occur
with hypertension, turbulent flow over
scarred valves, or by the action of bacterial
Even relatively subtle influences, such as
hypercholesterolemia, radiation, or products
absorbed from cigarette smoke, may be
sources of endothelial dysfunction
Alterations in Normal Blood Flow
Turbulence contributes to arterial and cardiac
thrombosis by causing endothelial injury or
dysfunction, as well as by forming countercurrents
and local pockets of stasis; stasis is a major
contributor to the development of venous thrombi.
Normal blood flow is laminar, such that platelets flow
centrally in the vessel lumen, separated from the
endothelium by a slower moving clear zone of plasma.
Stasis and turbulence therefore:
Disrupt laminar flow and bring platelets into contact
with the endothelium
Retard the inflow of clotting factor inhibitors and
permit the buildup of thrombi
Promote endothelial cell activation, resulting in local
thrombosis, leukocyte adhesion, etc.
Generally contributes less frequently to thrombotic .
It is loosely defined as any alteration of the coagulation
pathways that predisposes to thrombosis, and it can be
divided into primary (genetic) and secondary (acquired)
Of the inherited causes mutations in the factor V gene
and the prothrombin gene are the most common:
Acquired thrombotic diatheses: multifactorial and
In some situations (e.g., cardiac failure or trauma), stasis or vascular
injury may be most important.
Hypercoagulability due to use of oral contraceptive use and
hyperestrogenic state of pregnancy, related to increased hepatic
synthesis of coagulation factors and reduced synthesis of
In disseminated cancers, release of procoagulant
tumor products predisposes to thrombosis.
Hypercoagulability in advancing age has been
attributed to increasing platelet aggregation and
reduced endothelial PGI2 release.
Smoking and obesity promote hypercoagulability by
Thrombi can develop anywhere in the cardiovascular system (in
cardiac chambers, on valves, in arteries, veins, capillaries).
The size and shape of a thrombus depend on the site of origin and
Arterial or cardiac thrombi begin at sites of endothelial injury or
turbulence; venous thrombi occur at sites of stasis.
Thrombi are focally attached to the underlying vascular surface.
Arterial thrombi tend to grow in a retrograde
direction from the point of attachment,
Venous thrombi extend in the direction of
blood flow (thus both tend to propagate
toward the heart).
The propagating portion of a thrombus is
poorly attached and therefore prone to
fragmentation, generating an embolus.
Thrombi can have grossly (and microscopically) apparent
laminations called lines of Zahn; these represent pale platelet and
fibrin layers alternating with darker erythrocyte-rich layers.
Such lines are significant only in that they represent thrombosis in
the setting of flowing blood; their presence can therefore potentially
distinguish antemortem thrombosis from the bland nonlaminated
Thrombi occurring in heart chambers or in the aortic lumen are
designated mural thrombi.
Arterial thrombi are frequently occlusive and are
produced by platelet and coagulation activation; they
are typically a friable meshwork of platelets, fibrin,
erythrocytes, and degenerating leukocytes.
Venous thrombosis (phlebothrombosis) is almost
invariably occlusive, venous thrombosis is largely the
result of activation of the coagulation cascade, and
platelets play a secondary role.
Because these thrombi form in the sluggish venous
circulation, they also tend to contain more enmeshed
erythrocytes and are therefore called red, or stasis,
Specific types of Thrombi
Thrombi on heart valves are called vegetations.
Bacterial or fungal blood-borne infections can cause valve
damage, subsequently leading to large thrombotic
masses (infective endocarditis,).
Sterile vegetations can also develop on noninfected
valves in hypercoagulable states, so-called nonbacterial
Fate of the Thrombus
Propagation: accumulation of additional platelets and
fibrin, eventually causing vessel obstruction.
Embolization: Thrombi dislodge or fragment and are
transported elsewhere in the vasculature.
Dissolution: Thrombi are removed by fibrinolytic activity.
Organization and recanalization.
Thrombi induce inflammation and fibrosis (organization). These
can eventually recanalize (re-establishing some degree of flow),
or they can be incorporated into a thickened vessel wall
Low-power view of an artery with an old thrombus.
A, H&E-stained section.
B, Stain for elastic tissue.
The original lumen is delineated by the internal elastic lamina
(arrows) and is totally filled with organized thrombus, now punctuated
by a number of recanalized channels (white spaces).
An embolus is a intravascular solid, liquid, or gaseous
mass that is carried by the blood to a site distant from its
point of origin (Formation or entry).
Virtually 99% of all emboli represent some part of a
dislodged thrombus, hence the term
Rare forms of emboli include fat droplets, bubbles of
air , atherosclerotic debris (cholesterol emboli), tumor
fragments, bits of bone marrow, or foreign bodies
such as bullets.
However, unless otherwise specified, an embolism
should be considered to be thrombotic in origin.
Inevitably, emboli lodge in vessels too small to permit
further passage, resulting in partial or complete
The consequences of thromboembolism include
ischemic necrosis (infarction) of downstream tissue.
Depending on the site of origin, emboli may lodge
anywhere in the vascular tree; the clinical outcomes are
best understood from the standpoint of whether emboli
lodge in the pulmonary or systemic circulations
Embolus derived from a lower extremity deep venous thrombosis
and now impacted in a pulmonary artery branch
They are carried through progressively larger channels and pass
through the right side of the heart before entering the pulmonary
Depending on the size of the embolus, it may occlude the main
pulmonary artery, impact across bifurcation (saddle embolus), or
pass out into the smaller, branching arterioles.
Frequently, there are multiple emboli, perhaps sequentially, or as a
shower of smaller emboli from a single large thrombus; in general, the
patient who has had one pulmonary embolus is at high risk of having
Rarely, an embolus can pass through an interatrial or interventricular
defect, thereby entering the systemic circulation (paradoxical
Sudden death, right ventricular failure (cor pulmonale),
or cardiovascular collapse occurs when 60% or more of
the pulmonary circulation is obstructed with emboli.
Embolic obstruction of medium-sized arteries can cause
pulmonary hemorrhage but usually not pulmonary
infarction because the lung has a dual blood supply and
the intact bronchial arterial circulation continues to supply
blood to the area
Many emboli occurring over a period of time may
cause pulmonary hypertension with right ventricular
Systemic thromboembolism refers to emboli in the arterial circulation.
Most (80%) arise from intracardiac mural thrombi, two-thirds of which
are associated with left ventricular wall infarcts and another quarter
with dilated left atria (e.g., secondary to mitral valve disease).
The remainder originate from aortic aneurysms, thrombi on ulcerated
atherosclerotic plaques, or fragmentation of valvular vegetations
Arterial emboli can travel to a wide variety of sites; the site of arrest
depends on the point of origin of the thromboembolus and the relative
blood flow through the downstream tissues.
The major sites for arteriolar embolization are the lower extremities
(75%) and the brain (10%), with the intestines, kidneys, and spleen
affected to a lesser extent
An infarct is an area of ischemic necrosis caused by
occlusion of either the arterial supply or the venous
drainage in a particular tissue.
Tissue infarction is a common and extremely important cause of
More than half of all deaths in the United States are caused by
cardiovascular disease, and most of these are attributable to
myocardial or cerebral infarction.
Pulmonary infarction is a common complication in several
clinical settings, bowel infarction is frequently fatal, and
ischemic necrosis of the extremities (gangrene) is a serious
problem in the diabetic population.
Nearly 99% from thrombotic or embolic events, and from arterial occlusion.
Infarction may also be caused by other mechanisms:s local vasospasm,
expansion of an atheroma secondary to intraplaque hemorrhage, or extrinsic
compression of a vessel (e.g., by tumor).
Uncommon causes include vessel twisting (e.g., in testicular torsion or bowel
volvulus), vascular compression by edema or entrapment in a hernia sac, or
traumatic vessel rupture.
Although venous thrombosis can cause infarction, it more often merely induces
venous obstruction and congestion.
Usually, bypass channels open rapidly after the occlusion forms, providing
some outflow from the area that, in turn, improves the arterial inflow.
Infarcts caused by venous thrombosis are more likely in organs with a single
venous outflow channel (e.g., testis and ovary).
Infarcts are classified on the basis of their color (reflecting the amount of
hemorrhage) and the presence or absence of microbial infection.
Therefore, infarcts may be either red (hemorrhagic) or white (anemic) and
may be either septic or bland.
Red infarcts occur;
(1) with venous occlusions (such as in ovarian torsion);
(2) in loose tissues (lung) that allow blood to collect in the infarcted zone;
(3) in tissues with dual circulations e.g. lung and small intestine, permitting flow of blood
from an unobstructed parallel supply into a necrotic area
(4) in tissues that were previously congested because of sluggish venous outflow;
(5) when flow is re-established to a site of previous arterial occlusion and necrosis (e.g.,
fragmentation of an occlusive embolus or angioplasty of a thrombotic lesion).
White infarcts occur with:
1. Arterial occlusions or in solid organs (such as heart, spleen,
and kidney), where the solidity of the tissue limits the amount of
hemorrhage that can seep into the area of ischemic necrosis
from adjoining capillary beds
All infarcts tend to be wedge shaped, with the occluded vessel at
the apex and the periphery of the organ forming the base; when
the base is a serosal surface there can be an overlying fibrinous
At the outset, all infarcts are poorly defined and slightly
hemorrhagic. The margins of both types of infarcts tend to
become better defined with time by a narrow rim of congestion
attributable to inflammation at the edge of the lesion
The dominant histologic characteristic of infarction is ischemic coagulative
An inflammatory response at the margins of infarcts within a few hours and is
usually well defined within 1 to 2 days.
Inflammatory response is followed by a reparative response beginning in the
In stable or labile tissues, parenchymal regeneration can occur at the
periphery, where underlying stromal architecture is spared.
However, most infarcts are ultimately replaced by scar.
The brain is an exception to these generalizations; ischemic tissue injury
in the central nervous system results in liquefactive necrosis .
Septic infarctions occur when bacterial vegetations
from a heart valve embolize or when microbes seed
an area of necrotic tissue.
In these cases the infarct is converted into an
abscess, with a correspondingly greater
The eventual sequence of organization, however,
follows the pattern previously described.
Factors That Influence Development of
Vascular occlusion can have no or minimal effect,
or can cause death of a tissue or even the
The major determinants of the eventual outcome
nature of the vascular supply,
the rate of development of the occlusion,
vulnerability to hypoxia,
and the oxygen content of blood.
Red and white infarcts. A, Hemorrhagic, roughly wedge-shaped pulmonary infarct
(red infarct). B, Sharply demarcated pale infarct in the spleen (white infarct).
Kidney infarct, now replaced by a large