Background

Cardiogenic pulmonary edema (CPE) is defined as pulmonary edema due to

increased capillary hydrostatic pressure secondary to elevated pulmonary
venous pressure. CPE reflects the accumulation of fluid with a low-protein
content in the lung interstitium and alveoli as a result of cardiac dysfunction
(see the image below). (See Etiology.)

Radiograph shows acute

pulmonary edema in a patient who was admitted with acute anterior
myocardial infarction. Findings are vascular redistribution, indistinct hila, and
alveolar infiltrates.
View Media Gallery
Pulmonary edema can be caused by the following major pathophysiologic
mechanisms:
 Imbalance of Starling forces - Ie, increased pulmonary capillary pressure,
decreased plasma oncotic pressure, increased negative interstitial
pressure
 Damage to the alveolar-capillary barrier
 Lymphatic obstruction
 Idiopathic (unknown) mechanism
Increased hydrostatic pressure leading to pulmonary edema may result from
many causes, including excessive intravascular volume administration,
pulmonary venous outflow obstruction (eg, mitral stenosis or left atrial [LA]
myxoma), and LV failure secondary to systolic or diastolic dysfunction of the
left ventricle. CPE leads to progressive deterioration of alveolar gas exchange
and respiratory failure. Without prompt recognition and treatment, a patient's
condition can deteriorate rapidly.
(See Etiology, Prognosis, Presentation, Workup, Treatment, and Medication.)
Complications
The major complications associated with CPE are respiratory fatigue and
failure. Prompt diagnosis and treatment usually prevent these complications,
but the physician must be prepared to provide assisted ventilation if the
patient begins to show signs of respiratory fatigue (eg, lethargy, fatigue,
diaphoresis, worsening anxiety). (See Prognosis and Treatment.)
Sudden cardiac death secondary to cardiac arrhythmia is another concern,
and continuous monitoring of heart rhythm is helpful in prompt diagnosis of
dangerous arrhythmias.
Patient education
To help prevent recurrence of CPE, counsel and educate patients in whom
pulmonary edema is due to dietary causes or medication noncompliance.
Etiology
CPE is caused by elevated pulmonary capillary hydrostatic pressure leading
to transudation of fluid into the pulmonary interstitium and alveoli. Increased
LA pressure increases pulmonary venous pressure and pressure in the lung
microvasculature, resulting in pulmonary edema.
Mechanism of CPE
Pulmonary capillary blood and alveolar gas are separated by the alveolar-
capillary membrane, which consists of 3 anatomically different layers: (1) the
capillary endothelium; (2) the interstitial space, which may contain connective
tissue, fibroblasts, and macrophages; and (3) the alveolar epithelium.
Exchange of fluid normally occurs between the vascular bed and the
interstitium. Pulmonary edema occurs when the net flux of fluid from the
vasculature into the interstitial space is increased. The Starling relationship
determines the fluid balance between the alveoli and the vascular bed. Net
flow of fluid across a membrane is determined by applying the following
equation:
Q = K(Pcap - Pis) - l(Pcap - Pis),
where Q is net fluid filtration; K is a constant called the filtration coefficient;
Pcap is capillary hydrostatic pressure, which tends to force fluid out of the
capillary; Pis is hydrostatic pressure in the interstitial fluid, which tends to force
fluid into the capillary; l is the reflection coefficient, which indicates the
effectiveness of the capillary wall in preventing protein filtration; the second
Pcap is the colloid osmotic pressure of plasma, which tends to pull fluid into the
capillary; and the second Pis is the colloid osmotic pressure in the interstitial
fluid, which pulls fluid out of the capillary.
The net filtration of fluid may increase with changes in different parameters of
the Starling equation. CPE predominantly occurs secondary to LA outflow
impairment or LV dysfunction. For pulmonary edema to develop secondary to
increased pulmonary capillary pressure, the pulmonary capillary pressure
must rise to a level higher than the plasma colloid osmotic pressure.
Pulmonary capillary pressure is normally 8-12 mm Hg, and colloid osmotic
pressure is 28 mm Hg. High pulmonary capillary wedge pressure (PCWP)
may not always be evident in established CPE, because the capillary pressure
may have returned to normal when the measurement is performed.
Lymphatics
The lymphatics play an important role in maintaining an adequate fluid
balance in the lungs by removing solutes, colloid, and liquid from the
interstitial space at a rate of approximately 10-20 mL/h. An acute rise in
pulmonary arterial capillary pressure (ie, to >18 mm Hg) may increase
filtration of fluid into the lung interstitium, but the lymphatic removal does not
increase correspondingly. In contrast, in the presence of chronically elevated
LA pressure, the rate of lymphatic removal can be as high as 200 mL/h, which
protects the lungs from pulmonary edema.
Stages
The progression of fluid accumulation in CPE can be identified as 3 distinct
physiologic stages.
Stage 1
In stage 1, elevated LA pressure causes distention and opening of small
pulmonary vessels. At this stage, blood gas exchange does not deteriorate, or
it may even be slightly improved.
Stage 2
In stage 2, fluid and colloid shift into the lung interstitium from the pulmonary
capillaries, but an initial increase in lymphatic outflow efficiently removes the
fluid. The continuing filtration of liquid and solutes may overpower the
drainage capacity of the lymphatics. In this case, the fluid initially collects in
the relatively compliant interstitial compartment, which is generally the
perivascular tissue of the large vessels, especially in the dependent zones.
The accumulation of liquid in the interstitium may compromise the small
airways, leading to mild hypoxemia. Hypoxemia at this stage is rarely of
sufficient magnitude to stimulate tachypnea. Tachypnea at this stage is mainly
the result of the stimulation of juxtapulmonary capillary (J-type) receptors,
which are nonmyelinated nerve endings located near the alveoli. J-type
receptors are involved in reflexes modulating respiration and heart rates.
Stage 3
In stage 3, as fluid filtration continues to increase and the filling of loose
interstitial space occurs, fluid accumulates in the relatively noncompliant
interstitial space. The interstitial space can contain up to 500mL of fluid. With
further accumulations, the fluid crosses the alveolar epithelium in to the
alveoli, leading to alveolar flooding. At this stage, abnormalities in gas
exchange are noticeable, vital capacity and other respiratory volumes are
substantially reduced, and hypoxemia becomes more severe.
Cardiac disorders manifesting as CPE
Atrial outflow obstruction
This can be due to mitral stenosis or, in rare cases, atrial myxoma, thrombosis
of a prosthetic valve, or a congenital membrane in the left atrium (eg, cor
triatriatum). Mitral stenosis is usually a result of rheumatic fever, after which it
may gradually cause pulmonary edema. Other causes of CPE often
accompany mitral stenosis in acute CPE; an example is decreased LV filling
because of tachycardia in arrhythmia (eg, atrial fibrillation) or fever.
LV systolic dysfunction
Systolic dysfunction, a common cause of CPE, is defined as decreased
myocardial contractility that reduces cardiac output. The fall in cardiac output
stimulates sympathetic activity and blood volume expansion by activating the
renin-angiotensin-aldosterone system, which causes deterioration by
decreasing LV filling time and increasing capillary hydrostatic pressure.
Chronic LV failure is usually the result of congestive heart failure (CHF) or
cardiomyopathy. Causes of acute exacerbations include the following:
 Acute myocardial infarction (MI) or ischemia
 Patient noncompliance with dietary restrictions (eg, dietary salt
restrictions)
 Patient noncompliance with medications (eg, diuretics)
 Severe anemia
 Sepsis
 Thyrotoxicosis
 Myocarditis
 Myocardial toxins (eg, alcohol, cocaine, chemotherapeutic agents such
as doxorubicin [Adriamycin], trastuzumab [Herceptin])
 Chronic valvular disease, aortic stenosis, aortic regurgitation, and mitral
regurgitation
LV diastolic dysfunction
Ischemia and infarction may cause LV diastolic dysfunction in addition to
systolic dysfunction. With a similar mechanism, myocardial contusion induces
systolic or diastolic dysfunction.
Diastolic dysfunction signals a decrease in LV diastolic distensibility
(compliance). Because of this decreased compliance, a heightened diastolic
pressure is required to achieve a similar stroke volume. Despite normal LV
contractility, the reduced cardiac output, in conjunction with excessive end-
diastolic pressure, generates hydrostatic pulmonary edema. Diastolic
abnormalities can also be caused by constrictive pericarditis and tamponade.
Dysrhythmias
New-onset rapid atrial fibrillation and ventricular tachycardia can be
responsible for CPE.