Introduction
Background
Pleural effusion is defined as an abnormal accumulation of fluid in the pleural space. Excess fluid results from the disruption of the equilibrium that exists across pleural membranes.
In terms of anatomy, the pleural space is bordered by parietal and visceral pleura. Parietal pleurae cover the inner surface of the thoracic cavity, including the mediastinum, diaphragm, and ribs. Visceral pleurae envelop all surfaces of the lungs, including the interlobar fissures. This lining is absent at the hilus, where pulmonary vessels, bronchi, and nerves enter the lung tissue. The mediastinum completely separates the right and left pleural spaces.
Both parietal and visceral membranes are smooth, glistening, and semitransparent. Despite these similarities, the two membranes have unique differences in anatomic architecture, innervation, pain fibers, blood supply, lymphatic drainage, and function. For example, the visceral pleurae contain no pain fibers and have a dual blood supply (bronchial and pulmonary).
Pathophysiology
Pleural effusion is an indicator of a pathologic process that may be of primary pulmonary origin or of an origin related to another organ system or to systemic disease. It may occur in the setting of acute or chronic disease and is not a diagnosis in itself.
Normal pleural fluid has the following characteristics: clear ultrafiltrate of plasma, pH 7.60-7.64, protein content less than 2% (1-2 g/dL), fewer than 1000 WBCs per cubic millimeter, glucose content similar to that of plasma, lactate dehydrogenase (LDH) level less than 50% of plasma and sodium, and potassium and calcium concentration similar to that of the interstitial fluid.
The principal function of pleural fluid is to provide a frictionless surface between the two pleurae in response to changes in lung volume with respiration. The following mechanisms play a role in the formation of pleural effusion:
- Altered permeability of the pleural membranes (eg, inflammatory process, neoplastic disease, pulmonary embolus)
- Reduction in intravascular oncotic pressure (eg, hypoalbuminemia, hepatic cirrhosis)
- Increased capillary permeability or vascular disruption (eg, trauma, neoplastic disease, inflammatory process, infection, pulmonary infarction, drug hypersensitivity, uremia, pancreatitis)
- Increased capillary hydrostatic pressure in the systemic and/or pulmonary circulation (eg, congestive heart failure, superior vena caval syndrome)
- Reduction of pressure in pleural space; lung unable to expand (eg, extensive atelectasis, mesothelioma)
- Inability of the lung to expand (eg, extensive atelectasis, mesothelioma)
- Decreased lymphatic drainage or complete blockage, including thoracic duct obstruction or rupture (eg, malignancy, trauma)
- Increased fluid in peritoneal cavity, with migration across the diaphragm via the lymphatics (eg, hepatic cirrhosis, peritoneal dialysis)
- Movement of fluid from pulmonary edema across the visceral pleura
- Persistent increase in pleural fluid oncotic pressure from an existing pleural effusion, causing accumulation of further fluid
- Iatrogenic causes (eg, central line misplacement)
Frequency
United States
Pleural effusion affects 1.3 million individuals each year. Approximate annual incidences of pleural effusions are based on major underlying disease processes, as follows: congestive heart failure, 500,000; bacterial pneumonia, 300,000 (uncomplicated, 270,000; complicated, 30,000); malignancy, 200,000; pulmonary embolus, 150,000; cirrhosis with ascites, 50,000; pancreatitis, 20,000; collagen vascular disease, 6,000; and tuberculosis, 2,500.
International
The relative annual incidence of pleural effusion is estimated to be 320 per 100,000 people in industrialized countries. When extrapolating these figures to apply to other countries, the distribution and incidence of pleural effusion causes are dependent on the population studied. For instance, in areas where tuberculosis (TB) is prevalent, a higher percentage of pleural effusions from TB is possible. Congestive heart failure, pneumonia, malignancy, and pulmonary emboli account for most pleural effusions.
Mortality/Morbidity
Morbidity and mortality of pleural effusions are directly related to cause, stage of disease at the time of presentation, and biochemical findings in the pleural fluid.
- Morbidity and mortality rates of patients with pneumonia and pleural effusions are higher than those of patients with pneumonia alone.
- Development of a malignant pleural effusion is associated with a poor prognosis. The average life expectancy of a patient after a diagnosis of malignant pleural effusion is 3-6 months. Patients with pleural effusions associated with carcinoma of the lung and GI tract tend to have the shortest mean survival time. Other indicators of poor prognosis in malignant pleural effusions can be determined from the cellular and biochemical findings in the fluid. For example, malignant pleural fluid with a glucose level less than 60 mg/dL and/or a pH less than 7.2 has a poor prognosis. Similarly, persistently negative cytologic findings in patients with known cancer and exudative effusions are associated with a decreased survival time.
- With malignant mesothelioma, the prognosis depends on the pathologic stage of the disease at time of presentation, microscopic characterization of tumor (eg, epithelial mesothelioma has a longer median survival rate compared with mesenchymal or sarcomatous type), sex (ie, better prognosis in women than men), and age (inverse relationship). In general, malignant mesothelioma has a poor prognosis, and median survival is approximately 7-10 months.
Sex
In general, the incidence is equal between the sexes; however, certain causes have a sex predilection. About two-thirds of malignant pleural effusions occur in women. Malignant pleural effusions are significantly associated with breast and gynecologic malignancies.
- Yellow nail syndrome (triad of deformed yellow nails, lymphedema, and pleural effusion of unknown cause) is more predominant in females, as is pleural effusion associated with systemic lupus erythematosus.
- In the United States, the incidence of malignant mesothelioma is more prevalent in males, probably because of their higher occupational exposure to asbestos.
- Pleural effusions associated with chronic pancreatitis are more predominant in males, the majority of whom have alcoholism as the etiologic factor for pancreatic disease.
- Rheumatoid effusions occur more commonly in males (80%).
- Prevalence of fetal pleural effusion, with estimated incidence of 1 in 10,000-15,000 deliveries, is twice as common in males than in females.
Age
Pleural effusions usually occur in adults.
Clinical
History
The clinical manifestations of pleural effusion are variable and often are related to the underlying disease process. The most commonly associated symptoms are progressive dyspnea, cough (typically nonproductive), and pleuritic chest pain.
- Dyspnea
- Dyspnea is the most common clinical symptom at presentation.
- It indicates a large effusion (usually not <500 mL).
- It is reported to occur in 50% of patients with malignant pleural effusions.
- However, other factors (eg, underlying lung disease, cardiac dysfunction, anemia) also may contribute to the development of dyspnea.
- Chest pain
- Chest pain may be mild or severe; it typically is described as sharp or stabbing, is exacerbated with deep inspiration, and is pleuritic.
- Pain may be localized to the chest wall or referred to the ipsilateral shoulder or upper abdomen (frequently seen with malignant mesothelioma), usually because of diaphragmatic involvement.
- It often diminishes in intensity as the pleural effusion increases in size.
- Chest pain signifies pleural irritation, which can aid in the diagnosis of the cause of the effusion, since most transudative effusions do not cause direct pleural irritation.
- Other signs and symptoms occurring with pleural effusions are associated more closely with the underlying disease process.
- Increasing lower extremity edema, orthopnea, and paroxysmal nocturnal dyspnea all may occur with congestive heart failure.
- Night sweats, fever, hemoptysis, and weight loss may occur with TB.
- An acute febrile episode, purulent sputum production, and pleuritic chest pain may occur in patients with an effusion associated with aerobic bacterial pneumonia.
Physical
Physical findings are variable and depend on the volume of the pleural effusion. Generally, findings are undetectable for effusions smaller than 300 mL. With an effusion larger than 300 mL, physical findings often may include the following:
- Dullness or decreased resonance to percussion
- Diminished or inaudible breath sounds
- Decreased tactile fremitus
- Egophony ("e" to "a" changes) at the most superior aspect of the pleural effusion (This finding signifies atelectasis and consolidation caused by compression of lung parenchyma with subsequent decrease in gas content per unit volume.)
- Pleural friction rub
- Present throughout respiratory cycle and loudest at end inspiration and early expiration
- Seldom present, but when present, best heard over the area of pleural inflammation, over posterior inferior aspect of thoracic cage, or over inferior lateral anterior surface of thoracic cage
- Described as a rubbing or grating (eg, leather rubbing on leather), harsh, dry, and scratchy sound that disappears with breath holding
- Asymmetric expansion of thoracic cage, with lagging expansion on the affected side (ie, Hoover sign)
- Mediastinal shift
- Seen only with massive effusions (usually >1000 mL)
- Noted on chest radiographs as displacement of the trachea and mediastinum to the contralateral side of the pleural effusion (In contrast with complete atelectasis of the ipsilateral lung, the trachea deviates toward the side of the effusion and is most commonly seen with complete obstruction of ipsilateral mainstem bronchus caused by bronchogenic carcinoma.)
- Other important findings that provide clues to the cause of the pleural effusion
- Anasarca
- Cutaneous changes of chronic liver disease
- Distended neck veins
- S3 gallop rhythm
- Clubbing of the fingers
- Breast nodule or intraabdominal mass
Causes
Four main types of fluids in the pleural space are serous fluid (hydrothorax), blood (hemothorax), lipid (chylothorax), and pus (pyothorax or empyema). Classification of pleural effusion is based on the mechanism of fluid formation and pleural fluid chemistry. Generally, pleural effusions are categorized into transudative or exudative effusions; however, with some causes, the pleural fluid may have either transudative or exudative characteristics. The etiologic spectrum of pleural effusion is extensive; however, pleural effusions are caused by congestive heart failure, pneumonia, malignancy, or pulmonary emboli.
- With transudative pleural effusions, systemic factors that govern formation of fluid include increased systemic and/or pulmonary capillary hydrostatic pressure (elevated pulmonary capillary wedge pressure of 10 cm H2 O or higher), decreased colloid osmotic pressure in the systemic circulation, or both. Pleural membranes are intact and not involved in pathogenesis of the fluid formation. The permeability of pleural capillaries to proteins is normal.
- With exudative pleural effusions, local factors governing formation of fluid include altered permeability of pleural membranes, increased capillary wall permeability or vascular disruption, and decreased or complete obstruction of lymphatic drainage of pleural space. Pleural membranes are involved in pathogenesis of the fluid formation. Permeability of pleural capillaries to proteins is high, resulting in an elevated protein content.
- Hemothorax is present when the pleural fluid hematocrit level is 50% greater than that of peripheral blood. A late complication of moderate or large hemothoraces is fibrothorax, which is characterized by gradual deposition of a thick layer of fibrous tissue on the visceral pleura.
- Chyliform or pseudochylous pleural effusion grossly resembles chylothorax. However, this effusion contains no chylomicrons, and pathogenesis does not involve the thoracic duct. High lipid levels (cholesterol crystals or lecithin-globulin complexes) are present and cause a milky white appearance. Pseudochylous pleural effusions commonly occur with long-standing (mean, 5 y) pleural effusions associated with rheumatoid pleuritis, tuberculosis, and paragonimiasis worm infection.
- Neoplastic disease causes 13-40% of all pleural effusions. Pleural effusion develops in nearly one half of all patients with metastatic cancer. The most common tumors that cause malignant pleural effusions are adenocarcinoma and other carcinomas of the lung, breast cancer, lymphoma, and leukemia. These malignancies, combined, account for approximately 75% of all malignant pleural effusions. Other relatively common malignancies associated with pleural effusion are ovarian carcinoma, stomach cancer, and sarcomas (including melanoma).
- Pleural effusion develops in 30-40% of patients with bacterial pneumonia. Those with bacterial pneumonia, especially that caused by Streptococcus pneumoniae, have a high predilection for complications. These complications can include bacteremia, multilobar involvement, and pleural effusion. Pleural effusions are relatively uncommon in patients with acquired immunodeficiency syndrome; however, Kaposi sarcoma, bacterial pneumonia, and TB are among the most common causes of pleural effusion in this population.
- A well-known risk factor for benign inflammatory exudative pleural effusion is asbestos exposure. Asbestos also is implicated in the pathogenesis of diffuse malignant mesothelioma. Other pleural reactions associated with asbestos exposure include pleural plaques, pleural calcifications, diffuse pleural fibrosis and/or thickening, and rounded atelectasis (subpleural focus of airless lung).
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Further Reading
Keywords
pleural fluid, transudative effusion, exudative effusion, thoracentesis, congestive heart failure, bacterial pneumonia, pulmonary embolus, cirrhosis, chronic pancreatitis, collagen vascular disease, tuberculosis, yellow nail syndrome, malignant mesothelioma, rheumatoid effusions, pleural friction rub, hydrothorax, hemothorax, chylothorax, pyothorax, empyema
