The chest radiographic findings of hydrostatic pulmonary edema are detailed in Box 100-1. These findings are all more reliably distinguishable on posteroanterior (PA) and lateral chest radiographs than on portable radiographs, but commonly patients with the greatest likelihood of hydrostatic pulmonary edema will be imaged using an anteroposterior technique (AP). AP techniques can make the diagnosis of hydrostatic pulmonary edema difficult because heart magnification, resulting from the considerably shorter focus-film distance as well as projectional magnification, can render determination of cardiac size unreliable, particularly in patients with low lung volumes. Additionally, pulmonary vascular congestion is difficult to determine accurately in nonerect patients because upper lobe vessels frequently normally appear larger than lower lobe vessels for patients imaged in a supine or semierect position. Furthermore, azygos vein dilation, often considered an indicator of elevated right atrial pressure, is a common and potentially normal finding on supine radiographs. Finally, pleural effusions often appear only as hazy attenuation projecting over lungs in patients imaged in a supine or semierect position. However, this appearance is not specific for pleural effusion and can be seen with extensive posterior atelectasis because anterior aerated lung superimposes on the increased opacity of the posteriorly located atelectatic lung. This pattern is often seen in severely ill patients and patients in the intensive care unit, which is the same patient population at risk for hydrostatic pulmonary edema.

The first chest radiographic signs of pulmonary venous hypertension include pulmonary vascular redistribution, appearing as equalization of the size of the upper and lower lobe vessels, which progresses to the upper lobe vessels becoming larger than those in the lower lobes (a reversal of the normal situation). In the acute setting, this phenomenon is seen with left atrial (wedge) pressures in the range of 12 to 19 mm Hg.² In chronically compensated patients, such as those with mitral stenosis, upper and lower lobe vascular equalization and reversal will occur with left atrial pressures between 15 to 25 mm Hg.² As the physiologic derangements worsen, pulmonary venous hypertension progresses to frank interstitial pulmonary edema, with the development of interlobular septal thickening, often referred to as Kerley A and B lines (Fig. 100-1A), perihilar indistinctness and vascular haze (see Fig. 100-1B), peribronchial cuffing (see Fig. 100-1C), and subpleural edema (see later).² Findings of interstitial edema usually are apparent on the chest radiograph, with left atrial pressures of 20 to 25 mm Hg in the acutely ill patient and 25 to 30 mm Hg in chronically compensated patients.² At higher left atrial pressures, frank alveolar edema occurs, with spillage of fluid into the air spaces. In these patients, the chest radiograph will show an air space consolidation pattern (see Fig. 100-1D) and acinar nodules,² often superimposed on findings of interstitial edema. The relationship between left atrial (pulmonary capillary wedge) pressure and radiographic findings is not precise, and the radiographic findings often lag behind the physiological changes. Furthermore, stepwise progression through these phases is not always seen, and some imaging findings of hydrostatic edema may be present in the absence of others.

FIGURE 100-1 Chest radiographic findings of interstitial (A-C) and alveolar (D) edema. A, Interlobular septal thickening. B, Perihilar “haze.” C, Peribronchial cuffing (arrow). D, Consolidation (alveolar edema).

CT

On thoracic CT, findings of hydrostatic pulmonary edema include those seen on chest radiographs, such as cardiomegaly, vascular engorgement, and pleural effusions. Findings of interstitial edema (see later), are also apparent and are more readily appreciable with thoracic CT, particularly high-resolution CT (HRCT), than with chest radiography. Bronchial wall thickening, smooth interlobular septal thickening (Fig. 100-2), and ground-glass opacity (often with hazy, poorly defined centrilobular nodules) are highly suggestive of hydrostatic pulmonary edema.

FIGURE 100-2 Interstitial pulmonary edema—interlobular septal thickening. This axial CT scan shows a pronounced linear pattern in the apices.

Classic Signs

Interstitial Edema

The findings of interstitial edema on chest radiography (see Box 100-1) are usually readily visible with CT scanning and, in addition to the findings noted, ground-glass opacity and centrilobular nodules are frequently present in patients with hydrostatic pulmonary edema.

Interlobular Septal Thickening (Kerley A and B lines)

Both Kerley A and B lines represent thickened interlobular septae. Kerley B lines are horizontal linear opacities, 1 to 2 cm in length, in contact with the pleural surface. Kerley B lines are most readily visible in the inferior and lateral aspects of the thorax, near the lateral costophrenic sulcus (see Fig. 100-1A). The regular appearance of Kerley B lines in the lung bases is the result of the regular organization of pulmonary lobules at the lung bases.

Kerley A lines also represent interlobular septal thickening but are relatively uncommon compared with Kerley B lines. Kerley A lines are obliquely oriented linear opacities several centimeters long, radiating outward from the central or perihilar lung. Kerley A lines have a somewhat different appearance from Kerley B lines because of the different organization of secondary lobules within the central lung.

The interlobular septal thickening resulting from hydrostatic pulmonary edema is readily visualized on thoracic CT, especially HRCT. Interlobular septal thickening in patients with hydrostatic pulmonary edema is smooth and often most readily visualized in the lung bases and in the pulmonary apices (Fig. 100-2). Poorly defined, ground-glass attenuation centrilobular nodules or lobular ground-glass opacity often coexists.

Vascular Indistinctness and Perihilar Haze

In patients with pulmonary venous hypertension and interstitial edema, fluid transudating from the vessels surrounds the vessels and blurs their margin on chest radiographs, rendering the vascular margins indistinct. Pulmonary vascular indistinctness is frequently most visible in the lower lobes and may be present before Kerley lines are apparent.

Perihilar haze is a term occasionally used to refer to poor definition of and slightly increased opacity surrounding the perihilar vessels; it manifests as perihilar vascular indistinctness with a hazy or ground-glass appearance (see Fig. 100-1B). Although not always easily recognizable, perihilar haze can be a useful finding that suggests hydrostatic pulmonary edema in patients with lower lobe atelectasis.

Peribronchial Cuffing

Peribronchial cuffing represents bronchial wall thickening, possibly accompanied by a variable amount of peribronchial interstitial fluid. Peribronchial cuffing is most readily recognizable in the central and perihilar regions of lung, when bronchi are seen in cross section (see Fig. 100-1C). Peribronchial cuffing may also be seen as a tram-track appearance when bronchi are visualized in longitudinal section. Peribronchial cuffing may also appear as nonspecific thickening of the interstitium radiating outward from the hilum. On thoracic CT, peribronchial thickening or cuffing usually appears as bronchial wall thickening. Peribronchial cuffing may represent a finding of interstitial edema in the proper clinical setting, but is not specific for that diagnosis; peribronchial inflammation or tumor may also produce this finding.

Distribution of Hydrostatic Edema

Hydrostatic edema may assume a number of different distributions, although a symmetric perihilar and basilar predominant distribution is most common. A distinct perihilar distribution of hydrostatic edema is often referred to as a bat wing or butterfly distribution, and is often seen when edema fluid accumulates rapidly. Uncommonly, hydrostatic edema will accumulate in a reverse bat wing distribution reminiscent of other causes of peripheral lung opacity. Other variations in the distribution of hydrostatic edema are frequently recognized (Box 100-2).²

PERMEABILITY EDEMA WITH DIFFUSE ALVEOLAR DAMAGE

Etiology and Pathophysiology

Permeability edema results from injury to the capillary endothelium from a wide variety of insults, and causes the alveolar-capillary membrane unit to become leaky. Such leaks allow protein and fluid to move from the vascular spaces into the alveoli. Unlike interstitial and alveolar hydrostatic pulmonary edema, which is low in protein content, permeability edema in the air spaces is high in protein, which prolongs retention of fluid transudated into the air spaces and is therefore comparatively slow to clear. Histopathologically, depending on the enticing insult, diffuse alveolar damage may coexist.

Manifestations of Disease

Clinical Presentation

Adult Respiratory Distress Syndrome

The adult respiratory distress syndrome (ARDS) is a form of diffuse pulmonary parenchymal lung injury associated with noncardiogenic pulmonary edema that results in hypoxemic respiratory failure.³ Histopathologically, ARDS is characterized by DAD. ARDS represents a constellation of clinical and physiologic findings that are thought to represent a single common process. The diagnostic criteria based on the American-European Consensus Conference for ARDS⁴ is as follows:

1 Multilobar, bilateral pulmonary opacities on chest radiography

2 Acute onset

3 Pulmonary capillary wedge pressure <18 mm Hg (or no clinical evidence for left atrial hypertension)

4 Arterial partial pressure of oxygen/fraction of inspired oxygen (Pao₂)/Fio₂) <200

When the Pao₂/Fio₂ ratio is <300, the term acute lung injury is often used. Acute lung injury is considered a milder version of diffuse lung injury, which may or may not progress to full ARDS.

Histopathologically, ARDS is characterized by DAD. The exact mechanism of injury that brings about DAD is not known, but undoubtedly free radicals and cellular infiltration with expression of proteolytic enzymes and cytokines play a prominent role in the resulting tissue damage. A wide variety of insults may result in ARDS (Box 100-3).

Histopathologic Abnormalities and Stages in Patients with Adult Respiratory Distress Syndrome

The histopathologic findings in patients with ARDS have been described in three overlapping stages (Box 100-4):

1 Acute exudative stage

2 Subacute proliferative stage

3 Chronic fibrotic stage

BOX 100-4

Stages of Adult Respiratory Distress Syndrome (ARDS)

ARDS: Diffuse pulmonary parenchymal lung injury associated with noncardiogenic pulmonary edema producing hypoxemic respiratory failure histopathologically characterized by diffuse alveolar damage (DAD)

Diagnostic criteria from the American-European Consensus Conference for ARDS

Multilobar, bilateral pulmonary opacities on chest radiography

Acute onset

Pulmonary capillary wedge pressure <18 mm Hg (or no clinical evidence for left atrial hypertension)

Arterial partial pressure of oxygen/fraction of inspired oxygen (Pao₂/Fio₂) <200

Stages and imaging findings

Acute exudative stage (days 1-8)

Patchy ground-glass opacity, air space consolidation, evolves rapidly; dependent atelectasis; minimal or no effusion

Subacute proliferative stage (starts as early as day 7, possibly even day 1 to day 30)

Air space consolidation regresses; linear and reticular opacities develop; ground-glass opacity may persist; traction bronchiectasis, architectural distortion

Chronic fibrotic stage (day 8 on)—most pulmonary opacities clear; anterior lung fibrosis may remain

The histopathologic findings in these stages are similar regardless of the cause of ARDS. In the exudative stage, the predominant histopathologic pattern is DAD, with hyaline membrane formation associated with high protein content. Neutrophilic infiltration, hemorrhage, epithelial cell injury, and macrophage accumulation are also seen. This phase lasts for approximately 5 to 7 days. The exudative stage is sometimes subdivided into an early phase, which occurs hours after the insult, and in which endothelial cell edema, capillary congestion, interstitial edema, and hemorrhage occur. In the late exudative phase, which occurs several days following the inciting insult, DAD with hyaline membrane formation is seen, associated with type I pneumocyte necrosis and protein-rich alveolar edema fluid.³

Imaging Techniques and Findings

Radiography

Imaging Findings During Exudative Phase of Adult Respiratory Distress Syndrome

Thoracic imaging studies early in the exudative phase may be normal, again reflecting a radiographic latent period, or lag phase. Later in the exudative phase, multifocal bilateral patchy opacities, usually ground-glass opacity and air space consolidation, will be seen. These opacities may be accompanied by air bronchogram formation (generally uncommon in patients with hydrostatic pulmonary edema). These opacities progress over the following days, and become increasingly confluent until the involved portions of all lobes bilaterally. Dependent atelectasis is commonly present. Radiographic opacities in patients with ARDS during the exudative phase may show a somewhat more peripheral predominance than in patients with hydrostatic pulmonary edema. Pleural effusions are uncommon and, when present, are smaller than in patients with hydrostatic pulmonary edema. Interlobular septal thickening is uncommon, and may be a useful feature for distinguishing patients with ARDS from those with hydrostatic edema. Similarly, patients with ARDS often have a normal heart size, whereas those with hydrostatic pulmonary edema will show cardiomegaly.

Because of severe hypoxemia, almost all patients with ARDS undergo mechanical ventilation. The positive pressure used during mechanical ventilation will increase lung volumes and create the appearance of improvement in the radiographic opacities, but usually this finding does not reflect true clearing of fluid from the alveoli. Because the alveoli are filled with protein-rich fluid, numerous inflammatory cells, and hyaline membranes, true radiographic clearing will be prolonged. Mechanical ventilation in patients with ARDS may result in complications, particularly because the lungs are very poorly compliant. Pneumomediastinum and pneumothorax are not uncommon.

The HRCT findings of the various stages of ARDS have been described. In the exudative phase, patchy areas of ground-glass opacity (Fig. 100-3) and air space consolidation are common. These opacities initially tend to predominate in the dependent lung regions. Patchy multifocal opacities may rapidly evolve to diffuse opacities later in the exudative phase and as the proliferative phase progresses. Pleural effusions, if present, are small. Mild interlobular septal thickening may occur, but is less pronounced than in patients with hydrostatic pulmonary edema.

FIGURE 100-3 Adult respiratory distress syndrome (ARDS), exudative stage. This axial thoracic CT scan shows patchy areas of ground-glass opacity and mild reticulation in a patient with developing ARDS. Hours later, the patient deteriorated and was intubated.

Although the various causes of ARDS are generally radiographically indistinguishable, the temporal sequence of films and presence of certain patterns can provide clues to the insults leading to ARDS. A sequence of films initially showing focal air space consolidation, perhaps suggesting community-acquired pneumonia, which subsequently shows development of multifocal bilateral opacities consistent with ARDS, suggests a primary lung insult causing ARDS. Furthermore, in patients with ARDS resulting from pulmonary disease, consolidation and ground-glass opacity are equally prevalent and pulmonary abnormalities are commonly asymmetric, reflecting the presence of the underlying causative pulmonary insult. In contrast, for patients with an extrapulmonary cause of ARDS, ground-glass opacity predominates and symmetric lung involvement is the rule.

The proliferative phase of ARDS occurs from 7 to 30 days following the onset of ARDS. During this phase, hyaline membranes become organized, pulmonary capillaries are obliterated, and collagen deposition begins. The amount of pulmonary edema fluid and inflammatory cell infiltration decreases. Recent studies have actually indicated that fibroproliferation may begin almost simultaneously with the onset of ARDS, rather than occurring sequentially in stages.

Imaging Findings During the Proliferative Phase of ARDS

After 1 week, air space consolidation begins to regress and linear and reticular opacities become more prominent (Fig. 100-4). Ground-glass opacity may persist. The imaging findings are not specific, but indicate development of a coarser, more organized appearance, which tends to reflect the underlying histopathologic changes. Traction bronchiectasis and bronchiolectasis and architectural distortion may appear. Patients with ARDS in the exudative or early proliferative phases who have more widespread findings of fibrosis, such as traction bronchiectasis, generally require prolonged ventilatory support, are at higher risk for ventilator-associated lung injury, and have higher mortality.

FIGURE 100-4 Adult respiratory distress syndrome, proliferative stage. This axial CT scan shows bilateral ground-glass opacity and consolidation, somewhat posteriorly dependent, with a background of mild reticulation.

The chronic fibrotic phase of ARDS may begin as early as 8 days following the initial insult, but is more commonly encountered in patients who survive 1 month or longer. In patients who survive ARDS more than 30 days, many of these histopathologic abnormalities resolve, and areas of fibrosis, architectural distortion (Fig. 100-5), and even honeycombing are seen on imaging studies. Ground-glass opacity may persist, but is often associated with coarse reticulation architectural distortion, and reflects the presence of fibrosis rather than edema, hyaline membrane formation, and inflammatory cell infiltration, as in the exudate and proliferative phases. The HRCT findings may show a striking anterior lung involvement (see Fig. 100-5), perhaps because of sparing of the posterior atelectatic lung from the adverse effects of mechanical ventilation, such as high ventilatory pressures and high oxygen tension. If this hypothesis is correct, the prevalence of anterior lung fibrosis in survivors of ARDS may be altered in the future with the use of prone ventilation for the treatment of ARDS patients.

FIGURE 100-5 Adult respiratory distress syndrome (ARDS), chronic stage. This axial CT scan in an ARDS survivor shows patchy ground-glass opacity and coarse reticulation with traction bronchiectasis, consistent with anterior lung fibrosis.

PERMEABILITY PULMONARY EDEMA WITHOUT DIFFUSE ALVEOLAR DAMAGE

Permeability pulmonary edema without DAD may be encountered in patients with reactions to various drugs (such as interleukin-2 treatment), transfusion reactions, infectious causes (e.g., hantavirus pulmonary syndrome), heroin overdose,¹ or other insults that may result in ARDS, such as air emboli or toxic shock syndrome.

Imaging Techniques and Findings

Radiography

Patients with pulmonary edema unaccompanied by DAD may present with chest radiographic and thoracic CT abnormalities resembling those of hydrostatic edema. Interlobular septal thickening is often a prominent feature, whereas air space consolidation is less conspicuous or absent altogether. Unlike ARDS, permeability edema without DAD may clear rapidly on chest radiographs.

MIXED EDEMA

A combination of hydrostatic pulmonary edema and permeability edema, termed mixed edema, may be seen in the presence of conditions producing increased intravascular pressure and capillary endothelial injury. This pattern of edema may be seen in patients with re-expansion pulmonary edema, high-altitude pulmonary edema, and neurogenic pulmonary edema, among other less commonly encountered situations (Box 100-5).

Imaging Techniques and Findings

Radiography

Chest radiography in patients with conditions producing mixed edema shows features typically associated with hydrostatic pulmonary edema as well as the multifocal or diffuse lung opacities typically encountered in permeability edema. It is therefore both nonspecific and difficult to interpret accurately.

NEUROGENIC PULMONARY EDEMA

Etiology and Pathophysiology

Neurogenic pulmonary edema occurs in patients with head trauma, intracranial hemorrhage, increased intracranial pressure, seizures, or other acute neurologic conditions producing intracranial hypertension.¹ Drug overdoses, particularly opiates, barbiturates, and alcohol, may also produce neurogenic pulmonary edema. The mechanism of neurogenic pulmonary edema formation includes sympathetic discharge caused by CNS injury, resulting in systemic vasoconstriction, elevated systemic blood pressure and, subsequently, elevated left ventricular pressure and dysfunction. Because the alveolar edema fluid is protein-rich and pulmonary capillary wedge pressures are often normal, some element of capillary leak is also present. Therefore, neurogenic pulmonary edema shows a histopathologic pattern of both hydrostatic and permeability pulmonary edema, representing a mixed edema pattern.

Manifestations of Disease

Clinical Presentation

The edema fluid may appear very quickly, within minutes to hours of the responsible episode.

Imaging Techniques and Findings

Radiography

Chest radiographs show multifocal, bilateral air space consolidation (Fig. 100-6), often predominating in the upper lobes,¹ with normal heart size or no pleural effusion. Radiographic opacities show clearing within 1 to 2 days.

FIGURE 100-6 Neurogenic pulmonary edema. This frontal chest radiograph in a patient with subarachnoid hemorrhage shows bilateral pulmonary opacity without widening of the vascular pedicle or features suggesting hydrostatic edema.

RE-EXPANSION PULMONARY EDEMA

Rapid re-expansion of lung after collapse for at least several days, usually caused by a large pleural effusion or pneumothorax, may produce edema in the re-expanded lung. This process is referred to as re-expansion pulmonary edema.

Etiology and Pathophysiology

The mechanism of re-expansion pulmonary edema includes a combination of several factors. First, diminished perfusion in the collapsed lung results in decreased surfactant production and decreased pulmonary compliance, requiring a more negative intrapleural pressure to achieve inflation of the collapsed lung. Additionally, pulmonary collapse increases vascular resistance. These factors favor the production of hydrostatic pulmonary edema when the pulmonary collapse is relieved. Additionally, the hypoxemia that accompanies the prolonged pulmonary collapse and hypoperfusion results in the release of free radicals that produce capillary endothelial injury, causing permeability edema that worsens from the increased perfusion that occurs with reperfusion. The production of free radicals that gain access to the blood stream may also explain the occasional occurrence of re-expansion pulmonary edema that develops in regions of lung that were not severely collapsed, and even pulmonary parenchyma on the contralateral side. Temporarily decreased pulmonary lymphatic or venous return may also play a role in re-expansion pulmonary edema.

Risk factors for the development of re-expansion pulmonary edema include prolonged pulmonary collapse (usually at least 72 hours), a large-volume pleural space-occupying process (>1500 mL fluid), and coexistent cardiovascular disease.

Manifestations of Disease

Clinical Presentation

Re-expansion pulmonary edema usually occurs within 2 to 4 hours of lung re-expansion, often after rapid removal of the space-occupying process within the pleural space, but may progress for 1 to 2 days.

Imaging Techniques and Findings

Radiography and CT

Thoracic imaging studies will show the abnormality producing the pulmonary collapse, usually a large pleural effusion (Fig. 100-7) or pneumothorax, that subsequently undergoes drainage. The history will usually suggest that a large volume of fluid or air was removed, and that the pleural process has usually been present for a number of days. Within hours of the drainage procedure, increased opacity, usually ground-glass opacity or air space consolidation, develops within the expanded lung (see Fig. 100-7B). HRCT will also show ground-glass opacity (see Fig. 100-7C) and air space consolidation within the affected lung. The pathologic and radiographic findings associated with re-expansion pulmonary edema usually resolve within a few days to a week.