Transcript 08. hemodynamics 09 MEDICAL & dental2010-10

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 hemosiderin-laden macrophages
(heart failure cells).
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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
hemosiderin-laden macrophages. Longstanding 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
 Prolonged bed rest or immobilization
 Myocardial infarction,Atrial fibrillation
 Tissue damage (surgery, fracture, burns)
 Cancer
 Prosthetic cardiac valves
 Disseminated intravascular coagulation
 Heparin-induced thrombocytopenia
 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 XII-dependent 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
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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.
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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
gram-negative 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 so-called 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.