Download HEMODYNAMIC DISORDERS

60% of lean body weight is water; two thirds of
this water is intracellular, remainder is in the
extracellular space, mostly interstitial fluid.
EDEMA signifies increased fluid in the
interstitial tissue spaces. Depending on the site,
fluid collections are variously designated
hydrothorax, hydropericardium, and
hydroperitoneum (ascites).
Anasarca: severe, generalized edema with
profound subcutaneous tissue swelling.
Pathophysiologic Categories of Edema
Increased Hydrostatic Pressure
Impaired venous return
Congestive heart failure
Constrictive pericarditis
Ascites (liver cirrhosis)
Venous obstruction or compression
Thrombosis
External pressure (e.g., mass)
Lower extremity inactivity with prolonged
dependency
Arteriolar dilation
Heat
Neurohumoral dysregulation
Reduced Plasma Osmotic Pressure
(Hypoproteinemia)
Protein-losing glomerulopathies (nephrotic syndrome)
Liver cirrhosis (ascites)
Malnutrition
Protein-losing gastroenteropathy
Lymphatic Obstruction
Inflammatory
Neoplastic
Postsurgical
Postirradiation
Sodium Retention
Excessive salt intake with renal insufficiency
Increased tubular reabsorption of sodium
Renal hypoperfusion
Increased renin-angiotensin-aldosterone
secretion
Inflammation
Acute inflammation
Chronic inflammation
Angiogenesis
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Transdate: protein poor (<3 gm/dl) fluid with
specific gravity of <1.012 due to imbalances in
normal hemodynamic forces e.g. congestive
heart failure, liver and renal disease etc.
Exudate - protein rich (>3 gm/dl) fluid with a
specific gravity of >1.020 results from
endothelial damage and alteration of vasular
permeability e.g. inflammatory and
immunologic pathology.
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Hyperemia is an active
process resulting from
tissue inflow because of
arteriolar dilation, e.g.
skeletal muscle during
exercise or at sites of
inflammation. The
affected tissue is redder
because of the
engorgement of vessels
with oxygenated blood.
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Congestion is a passive
process resulting from
impaired outflow from
a tissue. It may be
systemic e.g. cardiac
failure, or local e.g. an
isolated venous
obstruction. The tissue
has a blue-red color
(cyanosis), due to
accumulation of
deoxygenated
hemoglobin in the
affected tissues.
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The cut surfaces are hemorrhagic and wet.
LUNGS: Microscopically, acute pulmonary
congestion is characterized by alveolar
capillaries engorged with blood,alveolar septal
edema and/or focal intra-alveolar hemorrhage.
In chronic pulmonary congestion, the septa
are thickened and fibrotic, and the alveolar
spaces may contain numerous hemosiderinladen macrophages (heart failure cells).
In acute hepatic congestion: central vein and
sinusoids are distended with blood with or
without central hepatocyte degeneration.
 In chronic passive congestion of the liver: on
cut surface central regions of the hepatic
lobules are red-brown and surrounded by
zones of uncongested tan liver (nutmeg liver).
Microscopically: centrilobular necrosis with loss
of hepatocytes, hemorrhage and hemosiderinladen macrophages. Long-standing cases (most
commonly associated with heart failure),
hepatic fibrosis (cardiac cirrhosis) may
develope.
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Hemorrhage generally indicates extravasation
of blood due to vessel rupture
Hematoma: accumulation of blood within
tissue.
Petechiae: Minute 1- to 2-mm hemorrhages into
skin, mucous membranes, or serosal surfaces.
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Purpura: Slightly larger (≥3 mm)
hemorrhages.
Ecchymoses: Larger (>1 to 2 cm)
subcutaneous hematomas (i.e., bruises).
Large accumulations of blood in one or
another of the body cavities are called
hemothorax, hemopericardium, hemoperitoneum,
or hemarthrosis (in joints).
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It represents hemostasis in the intact vascular
system.
It is a process by which a thrombus is formed.
A thrombus is a solid mass of blood
constituents which developes in artery or vein.
Is intravascular coagulation of blood often
causing sinificant interuption to blood flow.
Three primary influences predispose to
thrombus formation, the so-called Virchow
triad:
(1) endothelial injury
(2) stasis or turbulence of blood flow
(3) blood hypercoagulability
In other words it results from interaction platelets,
damaged endothelial cells and the coagulation
cascade.
Figure 4-13 Virchow triad in thrombosis. Endothelial integrity is the single most important factor. Note that injury to endothelial cells can affect local blood flow and/or
coagulability; abnormal blood flow (stasis or turbulence) can, in turn, cause endothelial injury. The elements of the triad may act independently or may combine to cause
thrombus formation.
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Mutation in factor V gene (factor V Leiden)
Mutation in prothrombin gene
Mutation in methyltetrahydrofolate
gene
)
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
Fibrinolysis defects
High risk for thrombosis
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Prolonged bed rest or immobilization
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Myocardial infarction,Atrial fibrillation
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Tissue damage (surgery, fracture, burns)
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Cancer
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Prosthetic cardiac valves
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Disseminated intravascular coagulation
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Heparin-induced thrombocytopenia
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Antiphospholipid antibody syndrome (lupus anticoagulant
syndrome)
Lower risk for thrombosis
Cardiomyopathy,Nephrotic syndrome,Hyperestrogenic states
(pregnancy),Oral contraceptive use,Sickle cell anemia,Smoking.
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- maintain the integrity of the vascular
endothelium.
-participate in endothelial repair through the
contirbution of PDGF
-form platelet plugs
-promote the coagulation cascade through the
platelet phospholipid complex.
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- are resistant to the thrombogenic influence of
platelets and coagulation proteins. Intact
endothelial cells act to modulate several
aspects of hemostasis and oppose coagulation
after injury by thromboresistance.
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The coagulation cascade constitutes the third
component of the hemostatic process and is a
major contributor to thrombosis.
The coagulation cascade is essentially a series
of enzymatic conversions, turning inactive
proenzymes into activated enzymes and
culminating in the formation of thrombin.
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Thrombin then converts the soluble plasma
protein fibrinogen precursor into the insoluble
fibrous protein fibrin.
-intrinsic pathway
-extrinsic pathway
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Besides inducing coagulation, activation of the
clotting cascade also sets into motion a
fibrinolytic cascade that limits the size of the final
clot. This is primarily accomplished by the
generation of plasmin. Plasmin is derived from
enzymatic breakdown of its inactive circulating
precursor plasminogen, either by a factor XIIdependent pathway or by two distinct types of
plasminogen activators
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Runs concurrently with thrombogenesis.
Restores blood flow in vessels occluded by a
thrombus and facilitates healing after
inflammation and injury.
The proenzyme plasminogen is converted by
proteolysis to plasmin, the most important
fibrinolytic protease.
Plasmin split fibrin.
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- can be anti-thrombotic (hemorrhagic), leading
to pathologic bleeding states such as
hemophilia, Christmas disease and von
Willebrand disease.
- can also be prothrombotic, leading to
hypercoagulability with pathologic thrombosis.
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Is a prothrombotic familial syndrome.
Charecterized by recurrent venous thrombosis
and thromboembolism
Can be caused by deficiency of antithrombotic
proteins including antithrombin 3, protein C,
and protien S.
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Is a prothrombotic disorder charecterized by
autoantibodies directed against a number of
protein antigens complexed to phospholipids
Is further charecterized by recurrent venous
and arterial thromboembolism, fetal loss,
thrombocytopenia and a variety of
neurological manifestations.
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It is most often diagnosed because of an
incidental finding of prolonged PTT.
It is sometimes associated Systemic Lupus
Erythematosus and so this antibody is also
known as lupus anticoagulant.
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Is both prothrombotic and antithrombotic
disorder characterized by widespread
thrombosis and hemorrhage resulting from the
consumption of platelets and coagulation
factors.
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Thrombi may develop anywhere in the
cardiovascular system, the cardiac chambers,
valve cusps, arteries, veins, or capillaries. They
vary in size and shape, depending on the site of
origin.
Arterial or cardiac thrombi usually begin at a
site of endothelial injury (e.g., atherosclerotic
plaque) or turbulence (vessel bifurcation)
Venous thrombi characteristically occur in sites
of stasis.
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Arterial thrombi grow in a retrograde direction
from the point of attachment
Venous thrombi extend in the direction of
blood flow (i.e., toward the heart).
The propagating tail of either thrombi may
not be well attached (particularly in veins) is
prone to fragmentation, creating an embolus.
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When formed in the heart or aorta, thrombi
may have grossly (and microscopically)
apparent laminations, called lines of Zahn;
these are produced by alternating pale layers of
platelets admixed with some fibrin and darker
layers containing more red cells.
When arterial thrombi arise in heart chambers
or in the aortic lumen, they usually adhere to
the wall of the underlying structure and are
termed mural thrombi.
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are usually occlusive
most common sites in descending order, are
coronary, cerebral, and femoral arteries.
It is usually superimposed on an
atherosclerotic plaque and are firmly adherent
to the injured arterial wall and are gray-white
and friable, composed of a tangled mesh of
platelets, fibrin, erythrocytes, and degenerating
leukocytes.
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Also called phlebothrombosis, is almost
invariably occlusive
the thrombus often takes the shape of the vein.
Because these thrombi form in a relatively
static environment, they contain more
enmeshed erythrocytes and are therefore
known as red, or stasis thrombi.
Phlebothrombosis most commonly affects the
veins of the lower extremities (90% of cases).
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At autopsy, postmortem clots may be confused
for venous thrombi.
Postmortem clots are gelatinous with a dark
red dependent portion where red cells have
settled by gravity and a yellow chicken fat
supernatant resembling melted and clotted
chicken fat. They are not attached to the
underlying wall.
Red thrombi are firmer, almost always have a
point of attachment, and on transection reveal
vague strands of pale gray fibrin.
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Bacterial or fungal blood-borne infections may result in
the development of large thrombotic masses on heart
valves, called as vegetations (infective endocarditis).
Sterile vegetations can also develop on noninfected
valves in patients with hypercoagulable states, socalled nonbacterial thrombotic endocarditis.
Less commonly, noninfective, verrucous (LibmanSacks) endocarditis attributable to elevated levels of
circulating immune complexes may occur in patients
with systemic lupus erythematosus
Figure 4-15 Potential outcomes of venous thrombosis.
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An embolus is a detached intravascular solid, liquid,
or gaseous mass that is carried by the blood to a site
distant from its point of origin.
Almost all emboli represent some part of a
dislodged thrombus, hence the commonly used
term thromboembolism.
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The emboli ultimately lodge in vessels too
small to permit further passage, resulting in
partial or complete vascular occlusion leading
to ischemic necrosis of distal tissue, (infarction).
Depending on the site of origin, emboli may
lodge in the pulmonary or systemic
circulations.
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Depending on size of embolus, it may occlude
main pulmonary artery, or impact across the
bifurcation (saddle embolus), or pass out into the
smaller, branching arterioles
Rarely, embolus may pass through an
interatrial or interventricular defect to gain
access to the systemic circulation (paradoxical
embolism).
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Most pulmonary emboli (60% to 80%) are
clinically silent because they are small. Sudden
death, right heart failure (cor pulmonale), or CVS
occurs when 60% or more of the pulmonary
circulation is obstructed with emboli.
Embolic obstruction of small end-arteriolar
pulmonary branches may result in infarction.
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refers to emboli traveling within the arterial
circulation.
Most (80%) arise from intracardiac mural thrombi.
The major sites for arteriolar embolization are the
lower extremities (75%) and the brain (10%).
The consequences of systemic emboli depend on the
extent of collateral vascular supply in the affected
tissue, the tissue's vulnerability to ischemia, and the
caliber of the vessel occluded; in general, arterial
emboli cause infarction of tissues supplied by the
artery
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Microscopic fat globules may be found in the
circulation after fractures of long bones (which
have fatty marrow) or, rarely, in soft tissue
trauma and burns.
Fat is released by marrow or adipose tissue
injury and enters the circulation through
rupture of the blood vessels.
Less than 10% of patients with fat embolism
have any clinical findings.
Fat embolism syndrome is characterized by
pulmonary insufficiency, neurologic symptoms,
anemia, and thrombocytopenia.
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Gas bubbles within the circulation can obstruct
vascular flow (and cause distal ischemic injury)
acting as thrombotic masses. Bubbles may
coalesce to form frothy masses sufficiently
large to occlude major vessels.
Air may enter the circulation during obstetric
procedures or as a consequence of chest wall
injury.
An excess of 100 cc is required to have a clinical
effect.
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Occurs when individuals are exposed to sudden
changes in atmospheric pressure.
Scuba and deep sea divers, underwater
construction workers, and individuals in
unpressurized aircraft in rapid ascent are all at
risk.
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When air is breathed at high pressure (e.g.,
during a deep sea dive), increased amounts of
gas (particularly nitrogen) become dissolved in
the blood and tissues. If the diver then ascends
(depressurizes) too rapidly, the nitrogen
expands in the tissues and bubbles out of
solution in the blood to form gas emboli.
‘Bends’ and ‘chokes’.
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Treatment: placing the individual in a
compression chamber where the barometric
pressure may be raised, thus forcing the gas
bubbles back into solution followed by
subsequent slow decompression.
A more chronic form of decompression
sickness is called caisson disease in which,
persistence of gas emboli in the skeletal system
leads to multiple foci of ischemic necrosis; the
more common sites are the heads of the
femurs, tibia, and humeri.
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A grave and uncommon complication of labor
and the immediate postpartum period,
characterized by sudden severe dyspnea,
cyanosis, and hypotensive shock, followed by
seizures and coma.
If the patient survives the initial crisis,
pulmonary edema develops, along with DIC,
owing to release of thrombogenic substances
from amniotic.
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Caused by infusion of amniotic fluid or fetal
tissue into the maternal circulation via a tear in
the placental membranes or rupture of uterine
veins.
Microscopy: presence in the pulmonary
microcirculation of squamous cells shed from
fetal skin, lanugo hair, fat from vernix caseosa,
and mucin derived from the fetal respiratory or
gastrointestinal tract. Marked pulmonary
edema and diffuse alveolar damage are also
present. Systemic fibrin thrombi indicative of
DIC can also be seen.
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An infarct is an area of ischemic necrosis caused by
occlusion of either the arterial supply or the venous
drainage in a particular tissue e.g. myocardial,
cerebral, pulmonary and bowel infarction.
Most infarcts result from thrombotic or embolic
events, and almost all result from arterial
occlusion. Although venous thrombosis may
cause infarction, it more often merely induces
venous obstruction and congestion.
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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 (hemorrhagic) infarcts occur
 with venous occlusions (such as in ovarian
torsion)
 in loose tissues (such as lung), and in tissues
with dual circulations (e.g., lung and small
intestine), permitting flow of blood from the
unobstructed vessel into the affected zone
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White (anemic) infarcts occur with arterial
occlusions in solid organs with end-arterial
circulation (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.
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Gross: Most infarcts are wedge-shaped, with
the occluded vessel at the apex and the
periphery of the organ forming the base.
Micro: An inflammatory response begins along
the margins of infarcts within a few hours and
is usually well defined within 1 or 2 days,
followed by gradual degradation of the dead
tissue with phagocytosis of the cellular debris
by neutrophils and macrophages. Most infarcts
are ultimately replaced by scar tissue.
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Septic infarctions may develop when
embolization occurs by fragmentation of a
bacterial vegetation from a heart valve or when
microbes seed an area of necrotic tissue. The
septic infarct is converted into an abscess, with
a correspondingly greater inflammatory
response
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The consequences of a vascular occlusion can
range from no or minimal effect, all the way up
to death of a tissue or even the individual. The
major determinants include: (1) the nature of the
vascular supply; (2) the rate of development of the
occlusion; (3) the vulnerability of a given tissue to
hypoxia; and (4) the blood oxygen content.
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Shock, or cardiovascular collapse, is the final
common pathway for a number of potentially
lethal clinical events, including severe
hemorrhage, extensive trauma or burns, large
myocardial infarction, massive pulmonary
embolism, and microbial sepsis.
In shock there is
 systemic hypoperfusion caused by reduction
either in cardiac output or in the effective
circulating blood volume.
 The end results are hypotension, followed by
impaired tissue perfusion and cellular hypoxia.
 Initially the cellular injury is reversible,
persistence of shock eventually causes
irreversible tissue injury.
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Cardiogenic shock results from myocardial pump
failure e.g intrinsic myocardial infarction,
ventricular arrhythmias.
Hypovolemic shock results from loss of blood or
plasma volume e.g. hemorrhage, fluid loss
from severe burns, or trauma.
Septic shock is caused by systemic microbial
infection. Most commonly due to gramnegative infections (endotoxic shock), but it can
also occur with gram-positive and fungal
infections.
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Neurogenic shock: anesthetic accident or spinal
cord injury can lead to loss of vascular tone and
peripheral pooling of blood.
Anaphylactic shock: initiated by a generalized
IgE-mediated hypersensitivity response, is
associated with systemic vasodilation and
increased vascular permeability.
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Septic shock results from spread and expansion
of an initially localized infection (e.g., abscess,
peritonitis, pneumonia) into the bloodstream.
Most cases of septic shock (approximately 70%)
are caused by endotoxin-producing gramnegative bacilli. Endotoxins are bacterial wall
lipopolysaccharides (LPSs) that are released
when the cell walls are degraded (e.g., in an
inflammatory response).
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If uncorrected, leads to death. Unless insult is massive
and lethal (e.g. a massive hemorrhage), shock tends to
evolve through three general phases.
A nonprogressive phase: reflex compensatory
mechanisms are activated and perfusion of vital organs
is maintained
A progressive stage: tissue hypoperfusion and onset of
worsening circulatory and metabolic imbalances,
including acidosis
An irreversible stage: sets in after body has incurred
cellular and tissue injury so severe that even if the
hemodynamic defects are corrected, survival is not
possible.
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The cellular and tissue changes induced by
shock are essentially those of hypoxic injury,
since shock is characterized by failure of
multiple organ systems, the cellular changes
may appear in any tissue.
They are particularly evident in brain, heart,
lungs, kidneys, adrenals, and gastrointestinal
tract.
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brain - ischemic encephalopathy
heart - coagulation necrosis, may exhibit
subendocardial hemorrhage and/or contraction band
necrosis.
kidneys - tubular ischemic injury (acute tubular
necrosis, therefore oliguria, anuria, and electrolyte
disturbances constitute major clinical problems.
lungs are seldom affected in pure hypovolemic shock
because they are resistant to hypoxic injury. When
shock is caused by bacterial sepsis or trauma, however,
changes of diffuse alveolar damage may appear, the socalled shock lung
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In hypovolemic and cardiogenic shock, the
patient presents with hypotension; a weak,
rapid pulse; tachypnea; and cool, clammy,
cyanotic skin. In septic shock, the skin may
initially be warm and flushed because of
peripheral vasodilation.
As shock progresses, electrolyte disturbances
and metabolic acidosis (lactic acidosis)
complicate the situation followed by
progressive fall in urine output.
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The prognosis varies with the origin of shock
and its duration. 80% to 90% of young,
otherwise healthy patients with hypovolemic
shock survive with appropriate management,
whereas cardiogenic shock associated with
extensive myocardial infarction and gramnegative shock carry mortality rates of up to
75%, even with the best care currently
available.