532
DIAGNOSTIC ASPECTS OF PLEURAL E F F U S IO N * L. FRED AYVAZIAN, M.D. Chief, Pulmonary Disease Section Veterans Administration Hospital East Orange, N.J. Professor of Medicine College of Medicine and Dentistry of New Jersey Newark, N.J.
N ORMAL pleural membranes are permeable to liquid and gas. Normally, at least 3 ml. of fluid lubricate each hemithorax. Following strenuous exercise, 15 to 30 ml. have been aspirated from athletes. The vascular supply of the parietal pleura derives from intercostal and phrenic arteries which empty into the azygos and internal mammary veins and which produce a driving pressure of 9 to 30 cm. H20 from the parietal surfaces into the pleural spaces. The visceral pleura are supplied by branches of the pulmonary artery and, to a far lesser degree, the bronchial arteries. This finer, more extensive capillary bed has lower net pressures (5 to 10 cm. H20) and favors absorption from the pleural space. The filtration coefficient between the pleural surfaces (filtration/ reabsorption) is a function of: 1) Mechanical, hydrostatic, osmotic, and oncotic changes 2) Total functional pleural surface areas 3) Integrity (permeability) of the pleural membranes 4) Competence of lymphatic drainage This, however, does not apply to protein content. Once protein is filtered into pleural fluid it is reabsorbed solely through lymphatic channels. The filtration/reabsorption ratio increases during pleural inflammation. The pleural lymphatic system is rich in the immediate subserosal area. Both the parietal and visceral membranes ultimately drain into the mediastinal and thoracic duct complex. Particulate matter (such as cells, graphite, and asbestos) is removed only by the parietal pleura at the lowest gravita*Presented as part of a Symposium on Selected Aspects of Pulmonary Disease held by the Section on Medicine of the New York Academy of Medicine March 3, 1976.
Bull. N. Y. Acad. Med.
PLEURAL EFFUSION
533 533
tional areas. Thus, for example, diaphragmatic calcification is a late consequence of exposure to asbestos. Diaphragmatic pleural lymphatics are more extensive on the right side than the left, and they appear to have potential channels (or stomata) for the flow of fluid or gas from the peritoneum to the pleural space. The opposite transition is unreported. Normally sealed, these channels open or become permeable during inflammation or abdominal pressure produced by ascites or subphrenic abscess; pneumoperitoneum may cause, by leakage, pleural effusion, empyema, or pneumothorax. Such flow is more rapid through the right diaphragmatic surface than through the left. This rate of flow increases during sleep. After instillation of India ink into abdominal fluid the particles are found in pleural fluid within 12 hours. Transudates and exudates have the following characteristics:
Protein Specific gravity Lactic dehydrogenase Cells
Transudates Less than 3 gm.% Less than 1.014 Less than 200 units "Round cells"
Exudates More than 3 gm.% More than 1.016 More than 200 units Predominately white and red blood cells
Pleural fluid containing 10,000 red blood cells per cu. mm. is pink; it is visibly but not deeply bloody at 100,000. Right-sided effusions are commonest in heart failure, ascites, tuberculosis, subphrenic abscess, and peritoneal dialysis; if bilateral effusions are present they are usually greater on the right side. Both sides are assaulted equally by cancer, whether primary or metastatic, and by pulmonary infarction. Left-sided pleural effusion may be consequent to splenic injury, perinephric abscess, or inflammation of the tail of the pancreas. Significant effusions are rare in mycoplasma infections, viral pneumonia, and sarcoidosis. Reports list "minimal blunting" or "pleural lines" in lateral-decubitus films. Such effusions are rarely large enough for successful thoracentesis. Few controls study normal individuals with films taken under similar circumstance. Pleural effusions are uncommon in fungal diseases other than histoplasmosis; indeed, this finding should arouse doubt and a renewed search for mycobacterial infection, parapneumonia, or malignant disease. Thin, "parapneumonia" effusions are unusual in anaerobic infection. Vol. 53, No. 6, July-August 1977
534
534
L. F. AYVAZIAN
L.
F.
AYVAZIAN
When present, they tend to be associated with necrotizing pneumonia, aspiration abscess, and mixed infections. The fluid may be loculated, thick, and not free-flowing. Different types of fluid may occur in separate loculations. The mortality is high, and bronchopleural fistula is frequent. Drainage or resection is commonly required, but is rarely performed at an early optimal time. The pH of the pleural fluid may be of diagnostic importance; the usual range is 6.8 to 7.6. When an unusualpH is found in the pleural fluid, that of the arterial blood should be determined. The pH in congestive heart failure is high unless systemic acidosis is present. Malignant effusions show a pH above 7.4, but this is more characteristic of acute than chronic situations. The pH of tuberculosis effusions usually falls to 7.3 or lower. Parapneumonic effusions range from 7.2 to 6.9. Where the value falls below 7.2 empyema is more common, and intubation and surgical drainage may be necessary. With a low pH in pleural fluid the pCO2 and bicarbonate also fall. ThepH of transudates is close to that of arterial blood. A pH of 5.0 or less in pleural material suggests esophageal fistula or rupture. A sugar content of less than 30 mg.% in the pleural fluid is characteristic of thoracic disease complicating rheumatoid arthritis. Significant levels of amylase in pleural fluid may result from carcinoma, pancreatitis (the tail of the pancreas touches the lower surface of the left leaflet of the diaphragm), or esophageal rupture. In the last instance, fractionation shows the amylase to be of salivary, not of pancreatic type. Postoperative empyema as a complication appears to favor survival after resection of lung cancer. This may derive from a nonspecific mechanism involving residual tumor cells and enhancement of the host's immunity. Postoperative intrapleural injections of Bacillus Calmette-Guerin are now being tried. Eosinophilia of the pleural fluid, the detection of which requires stained differential cell counts, may occur in allergy, hypersensitivity syndromes, parasitic disease, systemic lupus erythematosus, polyarthritis, fungal infections, Hodgkin's disease, mesothelioma (bloody fluid), pulmonary infarction, trauma (including spontaneous or therapeutic pneumothorax), or simply the presence of red blood cells. It is rarely due to uncomplicated heart failure without infarction or with tuberculosis. Effusions in mesothelioma may be recurrent, bloody, eosinophilic, and high in hyaluronic acid. Fibrinous tuberculosis is common. Pleuritic pain, however, is less common. An audible friction rub is not often heard as judged against nonmycobacterial infectious (nonviral) pleuritis. Pleural infection is the Bull. N. Y. Acad. Med.
PLEURAL EFFUSION
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EFFUSION
535
most common form of extrapulmonary tuberculosis. In this condition the tuberculin skin test may remain negative for periods of three weeks to three months. These effusions are seen characteristically within the first three months of "primary" tuberculosis. Later effusions may result from ulceration of subpleural foci of "dormant" caseation residual from postprimary seeding. Erythrocytes and eosinophils are rare in tuberculous effusions. The total white blood cell count may be low and a study of differential morphology is essential. In tuberculosis with pleural effusion more than 80% of the white cells are lymphocytes after the third week of presenting illness. Pleural biopsy, an essential part of all diagnostic thoracenteses, may yield microscopic and cultural data diagnostic of tuberculosis. Culture of pleural biopsy material occasionally leads to the important differentiation from sarcoidosis or fungal disease, especially histoplasmosis, which may show true caseation at the core of its early granuloma. Culture of concentrates of large amounts of fluid (more than 500 ml.) before chemotherapy is initiated may be positive and may yield valuable information. In cases of infection the glucose level in the pleural fluid is usually low, the protein level is usually high, and the electrolyte content is unhelpful. The complications of empyema and bronchopleural fistula now are rare in tuberculosis which is diagnosed and treated early. The syndrome of primary lymphedema associated with yellow nails and pleural effusion is accompanied by: 1) Edema of the legs, hands, and face. 2) Discolored and dystrophic cuticula. 3) Pleural effusions, recurrent to a given level after each thoracentesis. These all may be congenital or familial. They are considered a result of hypoplastic lymphatic insufficiency. Associated conditions include underactive thyroid disease, sinusitis, bronchiectasis, and such neoplasms as lymphoma and sarcoma. Chylothorax results mainly from trauma, endoscopy, and surgery. The thoracic duct is situated to the right of the midline, alongside the azygos vein. Some instances of chylothorax are due to malignant disease, mainly lymphoma. Unusually, idiopathic and reversible chylothorax is encountered. In all cases the primary condition should be treated. Drainage of the thoracic duct by catheter leads to severe nutritional deprivation. Ligations are often followed by fistulization. The success of radiotherapy is debatable. True chyle always shows a positive Sudan III stain. Milky effusions may be due to concentrated cholesterol in chronic and neglected or locuVol. 53, No. 6, July-August 1977
536
L. F. AYVAZIAN AVZA
53l.F
lated effusions of decades' duration, such as those that occur after abandoned therapeutic pneumothorax. Effusion ex vacuo surrounding unexpandable lung represents the physiologic abhorrence of a vacuum and the organization-from fluid to solid-of an anatomic space left unhealthily rigid and idle. Chorioembryonic antigen (CEA) content in pleural fluid may be of more prognostic usefulness in following the therapy of cancer than in its diagnosis. A recent report indicates the superiority of ultrasonic techniques over radiologic ones in detecting pleural effusion, differentiating from pleural thickening, and accurately localizing (for successful thoracentesis) even small (3 to 5 ml.) areas of loculation, thus making it useful in both diagnosis and treatment.
Bull. N. Y. Acad. Med.
DIAGNOSTIC ASPECTS OF PLEURAL E F F U S IO N * L. FRED AYVAZIAN, M.D. Chief, Pulmonary Disease Section Veterans Administration Hospital East Orange, N.J. Professor of Medicine College of Medicine and Dentistry of New Jersey Newark, N.J.
N ORMAL pleural membranes are permeable to liquid and gas. Normally, at least 3 ml. of fluid lubricate each hemithorax. Following strenuous exercise, 15 to 30 ml. have been aspirated from athletes. The vascular supply of the parietal pleura derives from intercostal and phrenic arteries which empty into the azygos and internal mammary veins and which produce a driving pressure of 9 to 30 cm. H20 from the parietal surfaces into the pleural spaces. The visceral pleura are supplied by branches of the pulmonary artery and, to a far lesser degree, the bronchial arteries. This finer, more extensive capillary bed has lower net pressures (5 to 10 cm. H20) and favors absorption from the pleural space. The filtration coefficient between the pleural surfaces (filtration/ reabsorption) is a function of: 1) Mechanical, hydrostatic, osmotic, and oncotic changes 2) Total functional pleural surface areas 3) Integrity (permeability) of the pleural membranes 4) Competence of lymphatic drainage This, however, does not apply to protein content. Once protein is filtered into pleural fluid it is reabsorbed solely through lymphatic channels. The filtration/reabsorption ratio increases during pleural inflammation. The pleural lymphatic system is rich in the immediate subserosal area. Both the parietal and visceral membranes ultimately drain into the mediastinal and thoracic duct complex. Particulate matter (such as cells, graphite, and asbestos) is removed only by the parietal pleura at the lowest gravita*Presented as part of a Symposium on Selected Aspects of Pulmonary Disease held by the Section on Medicine of the New York Academy of Medicine March 3, 1976.
Bull. N. Y. Acad. Med.
PLEURAL EFFUSION
533 533
tional areas. Thus, for example, diaphragmatic calcification is a late consequence of exposure to asbestos. Diaphragmatic pleural lymphatics are more extensive on the right side than the left, and they appear to have potential channels (or stomata) for the flow of fluid or gas from the peritoneum to the pleural space. The opposite transition is unreported. Normally sealed, these channels open or become permeable during inflammation or abdominal pressure produced by ascites or subphrenic abscess; pneumoperitoneum may cause, by leakage, pleural effusion, empyema, or pneumothorax. Such flow is more rapid through the right diaphragmatic surface than through the left. This rate of flow increases during sleep. After instillation of India ink into abdominal fluid the particles are found in pleural fluid within 12 hours. Transudates and exudates have the following characteristics:
Protein Specific gravity Lactic dehydrogenase Cells
Transudates Less than 3 gm.% Less than 1.014 Less than 200 units "Round cells"
Exudates More than 3 gm.% More than 1.016 More than 200 units Predominately white and red blood cells
Pleural fluid containing 10,000 red blood cells per cu. mm. is pink; it is visibly but not deeply bloody at 100,000. Right-sided effusions are commonest in heart failure, ascites, tuberculosis, subphrenic abscess, and peritoneal dialysis; if bilateral effusions are present they are usually greater on the right side. Both sides are assaulted equally by cancer, whether primary or metastatic, and by pulmonary infarction. Left-sided pleural effusion may be consequent to splenic injury, perinephric abscess, or inflammation of the tail of the pancreas. Significant effusions are rare in mycoplasma infections, viral pneumonia, and sarcoidosis. Reports list "minimal blunting" or "pleural lines" in lateral-decubitus films. Such effusions are rarely large enough for successful thoracentesis. Few controls study normal individuals with films taken under similar circumstance. Pleural effusions are uncommon in fungal diseases other than histoplasmosis; indeed, this finding should arouse doubt and a renewed search for mycobacterial infection, parapneumonia, or malignant disease. Thin, "parapneumonia" effusions are unusual in anaerobic infection. Vol. 53, No. 6, July-August 1977
534
534
L. F. AYVAZIAN
L.
F.
AYVAZIAN
When present, they tend to be associated with necrotizing pneumonia, aspiration abscess, and mixed infections. The fluid may be loculated, thick, and not free-flowing. Different types of fluid may occur in separate loculations. The mortality is high, and bronchopleural fistula is frequent. Drainage or resection is commonly required, but is rarely performed at an early optimal time. The pH of the pleural fluid may be of diagnostic importance; the usual range is 6.8 to 7.6. When an unusualpH is found in the pleural fluid, that of the arterial blood should be determined. The pH in congestive heart failure is high unless systemic acidosis is present. Malignant effusions show a pH above 7.4, but this is more characteristic of acute than chronic situations. The pH of tuberculosis effusions usually falls to 7.3 or lower. Parapneumonic effusions range from 7.2 to 6.9. Where the value falls below 7.2 empyema is more common, and intubation and surgical drainage may be necessary. With a low pH in pleural fluid the pCO2 and bicarbonate also fall. ThepH of transudates is close to that of arterial blood. A pH of 5.0 or less in pleural material suggests esophageal fistula or rupture. A sugar content of less than 30 mg.% in the pleural fluid is characteristic of thoracic disease complicating rheumatoid arthritis. Significant levels of amylase in pleural fluid may result from carcinoma, pancreatitis (the tail of the pancreas touches the lower surface of the left leaflet of the diaphragm), or esophageal rupture. In the last instance, fractionation shows the amylase to be of salivary, not of pancreatic type. Postoperative empyema as a complication appears to favor survival after resection of lung cancer. This may derive from a nonspecific mechanism involving residual tumor cells and enhancement of the host's immunity. Postoperative intrapleural injections of Bacillus Calmette-Guerin are now being tried. Eosinophilia of the pleural fluid, the detection of which requires stained differential cell counts, may occur in allergy, hypersensitivity syndromes, parasitic disease, systemic lupus erythematosus, polyarthritis, fungal infections, Hodgkin's disease, mesothelioma (bloody fluid), pulmonary infarction, trauma (including spontaneous or therapeutic pneumothorax), or simply the presence of red blood cells. It is rarely due to uncomplicated heart failure without infarction or with tuberculosis. Effusions in mesothelioma may be recurrent, bloody, eosinophilic, and high in hyaluronic acid. Fibrinous tuberculosis is common. Pleuritic pain, however, is less common. An audible friction rub is not often heard as judged against nonmycobacterial infectious (nonviral) pleuritis. Pleural infection is the Bull. N. Y. Acad. Med.
PLEURAL EFFUSION
PLEURAL
EFFUSION
535
most common form of extrapulmonary tuberculosis. In this condition the tuberculin skin test may remain negative for periods of three weeks to three months. These effusions are seen characteristically within the first three months of "primary" tuberculosis. Later effusions may result from ulceration of subpleural foci of "dormant" caseation residual from postprimary seeding. Erythrocytes and eosinophils are rare in tuberculous effusions. The total white blood cell count may be low and a study of differential morphology is essential. In tuberculosis with pleural effusion more than 80% of the white cells are lymphocytes after the third week of presenting illness. Pleural biopsy, an essential part of all diagnostic thoracenteses, may yield microscopic and cultural data diagnostic of tuberculosis. Culture of pleural biopsy material occasionally leads to the important differentiation from sarcoidosis or fungal disease, especially histoplasmosis, which may show true caseation at the core of its early granuloma. Culture of concentrates of large amounts of fluid (more than 500 ml.) before chemotherapy is initiated may be positive and may yield valuable information. In cases of infection the glucose level in the pleural fluid is usually low, the protein level is usually high, and the electrolyte content is unhelpful. The complications of empyema and bronchopleural fistula now are rare in tuberculosis which is diagnosed and treated early. The syndrome of primary lymphedema associated with yellow nails and pleural effusion is accompanied by: 1) Edema of the legs, hands, and face. 2) Discolored and dystrophic cuticula. 3) Pleural effusions, recurrent to a given level after each thoracentesis. These all may be congenital or familial. They are considered a result of hypoplastic lymphatic insufficiency. Associated conditions include underactive thyroid disease, sinusitis, bronchiectasis, and such neoplasms as lymphoma and sarcoma. Chylothorax results mainly from trauma, endoscopy, and surgery. The thoracic duct is situated to the right of the midline, alongside the azygos vein. Some instances of chylothorax are due to malignant disease, mainly lymphoma. Unusually, idiopathic and reversible chylothorax is encountered. In all cases the primary condition should be treated. Drainage of the thoracic duct by catheter leads to severe nutritional deprivation. Ligations are often followed by fistulization. The success of radiotherapy is debatable. True chyle always shows a positive Sudan III stain. Milky effusions may be due to concentrated cholesterol in chronic and neglected or locuVol. 53, No. 6, July-August 1977
536
L. F. AYVAZIAN AVZA
53l.F
lated effusions of decades' duration, such as those that occur after abandoned therapeutic pneumothorax. Effusion ex vacuo surrounding unexpandable lung represents the physiologic abhorrence of a vacuum and the organization-from fluid to solid-of an anatomic space left unhealthily rigid and idle. Chorioembryonic antigen (CEA) content in pleural fluid may be of more prognostic usefulness in following the therapy of cancer than in its diagnosis. A recent report indicates the superiority of ultrasonic techniques over radiologic ones in detecting pleural effusion, differentiating from pleural thickening, and accurately localizing (for successful thoracentesis) even small (3 to 5 ml.) areas of loculation, thus making it useful in both diagnosis and treatment.
Bull. N. Y. Acad. Med.
