Congestive heart failure is among the most common causes of transudative effusions. Left-sided heart failure increases the pulmonary capillary pressure (see Chapter 32), which forces excess fluid into the interstitium. Right ventricular failure contributes by raising central venous pressure, which elevates the hydrostatic force in the capillaries of the parietal pleura and diminishes fluid reabsorption. Most effusions associated with congestive failure are bilateral, but at times, an isolated right-sided effusion is seen. Isolated left-sided effusions resulting from congestive failure are rare. The reason for the right-sided preference is unknown. Symptoms and signs of congestive failure (see Chapter 32) are usually evident. In more than 85% of effusions resulting from heart failure, the protein concentration is less than 3.0 g/100 mL. The concentration may be greater if the effusion is chronic or the patient has recently been undergoing a brisk diuresis. The pleural fluid is usually clear, but it may be bloody with red cell counts in excess of 5,000/mL.

Pulmonary embolism is accompanied by pleural effusion in approximately 40% of cases. The effusions are usually small, and about 20% of them are transudates, which can occur in the absence of pulmonary infarction. Cell count, differential, and protein concentration vary considerably. The transudative effusion associated with a pulmonary embolus may result from localized interstitial edema. Bilateral effusions can be seen when emboli affect both lungs. A small effusion on chest x-ray films in a patient with pleuritic chest pain can be an important clue (see Chapter 20). The effusions that result from infarction are more likely to be exudates and more likely to be bloody, as discussed later.

In the nephrotic syndrome, a similar but more generalized interstitial edema may ensue and lead to effusion. Overexpanded extracellular volume as a consequence of severe hypoalbuminemia or salt retention can produce a transudative effusion, but edematous fluid first collects in parts of the body where hydrostatic pressures are greatest (e.g., lower extremities) before fluid appears in the pleural space. Cardiomegaly may be in evidence, but overt signs of congestive failure are usually absent. Generalized edema is rare before the serum albumin level falls below 2.0 to 2.5 g/100 mL.

Intraabdominal diseases are occasionally responsible for transudative effusions. A right-sided pleural effusion develops in between 5% and 10% of patients with ascites resulting from cirrhosis; the composition of the effusion resembles that of the ascitic fluid. In cases of pancreatitis or a subphrenic abscess, a sympathetic effusion with the characteristics of a transudate sometimes forms; it soon changes into an exudate.

Pleural effusions are common after coronary bypass graft surgery and do not imply serious pathology. The same holds for the postpartum patient. Transudates may form in the setting of pericardial disease, myxedema, and sarcoidosis; the mechanisms are unknown.

Malignant tumors are often responsible for the development of effusions. Most pleural fluid accumulations caused by malignancies have the characteristics of exudates, although at times the protein concentration is less than 3.0 g/100 mL. Mechanisms of exudate formation include pleural metastasis with increased permeability and obstruction of lymphatic outflow. The formation of a malignant effusion is often a poor prognostic sign, particularly if the pH of the fluid is less than 7.3 and the glucose level is less than 60 mg/dL, which indicates extensive pleural involvement with tumor.

Bronchogenic carcinoma is the tumor most frequently associated with a pleural effusion. Fluid collects in most instances as a direct result of pleural invasion; unilateral effusions are the rule. Patients report dyspnea when the effusion is large and occasionally complain of pleuritic chest pain. The pleural fluid is usually clear and straw colored, but it may be bloody, and the glucose level may be very low. The white cell count is typically around 2,500/mL, with most cells being lymphocytes. Malignant cells are found in about 60% of instances. Unfortunately, the disease and its effusions are progressive; thoracentesis is followed by rapid reaccumulation.

Pleural effusions caused by metastatic carcinoma are more likely to be bilateral than are those associated with bronchogenic carcinoma because they occur as a consequence of lymphatic obstruction or diffuse seeding of the pleura. When effusions are caused by seeding, results of cytologic examination of the pleural fluid are positive in up to 90% of cases. Carcinoma of the breast is the leading metastatic tumor producing pleural effusions, accounting for 25% of all malignant effusions. The characteristics of the pleural fluid are similar to those of effusions caused by bronchogenic carcinoma. Lymphoma is another major cause of malignant bilateral pleural effusions, responsible for up to 20% of cases. The formation of a large effusion is a sign of advanced disease; evidence of pleural, parenchymal, and lymph node involvement is often present by the time a significant effusion appears. The pleural fluid may be a transudate or an exudate; most of the cells are lymphocytes. Cough and dyspnea accompany parenchymal involvement, but pleuritic pain is rare.

Mesotheliomas have become an increasingly important source of effusion as the incidence of disease associated with asbestos exposure has increased. Only malignant mesotheliomas produce important pleural fluid accumulations. The latent period for mesothelioma formation ranges from 20 to 40 years after asbestos exposure; the degree of exposure may appear inconsequential (see Chapter 39). Chest pain, cough, and shortness of breath
result from extensive pleural disease and large effusions. The fluid may be bloody and often contains malignant cells, but they are sometimes hard to identify cytologically, so chromosomal analysis is necessary. The fluid may be high in hyaluronic acid. Because the tumor is only locally invasive, no signs of extrathoracic disease are present.

Impressive effusions can form as a consequence of benign ovarian neoplasms (Meigs syndrome). The tumor produces ascites, and fluid tracks across the diaphragm and into the thorax. The effusion is typically on the right but may be left sided or even bilateral; it is exudative in quality, free of malignant cells, and similar in composition to the ascitic fluid from which it derives. Removal of the ovarian tumor results in prompt resolution of the effusion.

Pulmonary infections are an important source of exudative pleural effusions, but effusions are uncommonly associated with the acute bacterial pneumonias encountered in ambulatory patients. For example, an effusion develops in only about 5% of patients with pneumococcal pneumonia, and it is usually small and transient. Such effusions are termed parapneumonic to imply that bacteria need not have entered the pleural space to cause the effusion. The term empyema is reserved for cases in which organisms are recovered from the pleural fluid, either by Gram stain or culture. Empyema is a rare but worrisome event, seen in less than 1% of the cases of pneumococcal pneumonia that present in the outpatient setting; most cases occur when proper antibiotic therapy is delayed. Cough, sputum production, fever, chills, and pleuritic pain may be prominent. Early, the pleural fluid appears serous and may be sterile, but it quickly turns purulent and positive for organisms when empyema develops. In some instances, the pleural fluid offers the only opportunity for recovery of the causative organism. Characteristics of the pleural empyema fluid include a white cell count in excess of 5,000 to 10,000/mL, with neutrophils predominating. The concentration of glucose is typically less than 20 mg/100 mL. Pleural scarring may be substantial if the empyema fluid is allowed to remain.

Viral pneumonitis and mycoplasmal pneumonia are sometimes associated with pleural effusions in the course of illness, but the effusions are small, transient, and of little consequence (see Chapter 52).

The effusion caused by postprimary tuberculosis (TB) represents a delayed hypersensitivity reaction to spillage of organisms into the pleural space during early bacteremia or subclinical parenchymal disease (see Chapter 49). The effusion is almost always unilateral. The patient may be relatively free of symptoms or exhibit lethargy, fever, and weight loss; at times, the clinical picture is dominated by acute onset of pleuritic pain and fever. Cough and sputum are conspicuously absent. The chest radiograph may show little more than an isolated effusion, but the result of an intermediate-strength tuberculin skin test is usually positive. The pleural fluid has the qualities of an exudate; the glucose concentration may be low. The white cell count averages 1,000 to 2,000/mL; lymphocytes predominate; mesothelial cells are scarce (<2%). Neutrophils may be seen early in the course of the illness. Organisms are rarely found on acid-fast stain of the fluid and can be cultured from the fluid in only 25% of cases. Most of these effusions resolve spontaneously within a few months and leave little or no residual; however, symptomatic pulmonary parenchymal involvement eventually develops in more than half of such patients (see Chapter 47).

Connective tissue disease, particularly systemic lupus erythematosus, can produce transient pleuropericardial inflammation during its course, usually after other signs and symptoms have appeared. There may be a brief period of pleuritic pain. On occasion, pleural involvement may be the initial clinical presentation of the disease. In most instances, the pleural fluid has the characteristics of an exudate and may demonstrate low glucose and serum complement levels.

Rheumatoid arthritis is much less likely to produce a pleural effusion than is lupus, but the fluid often persists. Fewer than 5% of patients experience pleuropericardial involvement; these patients usually have a history of extraarticular manifestations and joint symptoms.

Occasionally, the effusion is the first manifestation of rheumatoid disease. The effusion is an exudate, with a predominance of lymphocytes and a very low (<20 mg/100 mL) glucose concentration. Although the fluid may contain rheumatoid factor, its presence is not unique to this disease.

As noted earlier, pleural effusions are found in approximately 40% of pulmonary embolism cases. Of these, about 80% are exudates. In these cases, the fluid is likely to be bloody. Effusions due to embolism have no specific distinguishing features. A high index of clinical suspicion is essential.

Infection and other intraabdominal pathology can lead to the production of an exudative pleural effusion, particularly when recent abdominal surgery, intestinal perforation, or hepatobiliary disease is complicated by development of a subdiaphragmatic abscess. In addition to gastrointestinal symptoms, pleuritic pain, fever, weight loss, and malaise may be present. Often, the symptoms are nonspecific, so that patients put off the decision to seek medical help. The diaphragm on the involved side (which is the right in two thirds of the cases) is elevated and moves poorly on fluoroscopy. A pathognomonic subdiaphragmatic air-fluid level may be present on chest film. The pleural fluid is usually sterile, although it may have a high leukocyte count. If the diaphragm has been perforated, an empyema can form. The pleural effusion associated with pancreatitis may begin as a transudate but usually becomes exudative. The effusions are most often on the left, but may be bilateral or right sided. The fluid characteristically has a high amylase concentration and is blood tinged in one third of cases.