Pleural Fluid Interpretation

This guide provides a structured approach to the interpretation of pleural fluid results for specific diseases. Reference ranges vary between labs, so always consult your local medical school or hospital guidelines.

A pleural effusion is usually diagnosed on the basis of a chest X-ray. At least 300mL of fluid must be present before chest X-rays can detect a pleural effusion.

Once the accumulated fluid is more than 300 mL, clinical signs such as decreased chest-wall movement, dullness to percussion and diminished breath sounds on the affected side of the chest become evident. If there is a large effusion then tracheal deviation may occur away from the effusion. CT thorax is more accurate for diagnosis and is better at characterising the size and location of a pleural effusion.

Normal pleural fluid

Typical findings of normal pleural fluid are as follows:

• Appearance: clear
• pH: 7.60-7.64
• Protein: < 2% (1-2 g/dL)
• White blood cells (WBC): < 1000/mm³
• Glucose: similar to that of plasma
• LDH: <50% plasma concentration
• Amylase: 30-110 U/L
• Triglycerides: <2 mmol/l
• Cholesterol: 3.5–6.5 mmol/l

Transudate vs exudate

Transudate

Transudative pleural effusions are defined as effusions that are caused by factors that alter hydrostatic pressure, pleural permeability, and oncotic pressure.

Conditions associated with transudative pleural effusions include:

• Congestive heart failure
• Liver cirrhosis
• Severe hypoalbuminemia
• Nephrotic syndrome

Exudate

Exudative pleural effusions are caused by changes to the local factors that influence the formation and absorption of pleural fluid.

Conditions associated with exudative pleural effusions include:

• Malignancy
• Infection (e.g. empyema due to bacterial pneumonia)
• Trauma
• Pulmonary infarction
• Pulmonary embolism

Light’s criteria

Light’s criteria are more accurate for the diagnosis of exudative effusions.

The fluid is considered an exudate if any of the following are present:

• The ratio of pleural fluid to serum protein is greater than 0.5
• The ratio of pleural fluid to serum LDH is greater than 0.6
• The pleural fluid LDH value is greater than two-thirds of the upper limit of the normal serum value

If a patient is thought to have a transudative pleural effusion but the Light’s Criteria suggest an exudate, the serum–pleural fluid protein gradient should be examined.

Colour

Frankly purulent fluid indicates an empyema (an anaerobic empyema is likely if the fluid has a putrid odour).

A milky fluid suggests chylothorax or pseudochylothorax. This is most often caused by lymphatic obstruction secondary to malignancy, chronic inflammation or thoracic duct injury by trauma or a surgical procedure.

Grossly bloody fluid is usually associated with trauma. Less common causes include tuberculosis (TB), aortic dissection, ruptured aortic aneurysm and malignancy.

Straw-coloured fluid with the distinctive smell of ammonia is indicative of urinothorax.

The presence of food particles suggests oesophageal rupture.

Black pleural fluid is extremely rare, indicative of only a few diseases, including:

• Aspergillus niger infection
• Malignant melanoma (black colour caused by cells containing melanin pigment)
• Haemorrhage and haemolysis associated with non-small cell lung cancer

Pleural fluid LDH

Levels greater than 1000 IU/L are suggestive of empyema, malignancy or rheumatoid effusion.

Glucose

A low pleural fluid glucose level (<3.4 mmol/l) may be found in empyema, rheumatoid pleuritis and pleural effusions associated with TB, malignancy and oesophageal rupture.

A very low pleural glucose concentration (<1.6 mmol/l) is indicative of empyema and rheumatoid disease.

Pleural pH

A pleural fluid pH of less than 7.3 is associated with the same pathologies that cause low pleural fluid glucose levels.

In malignant effusions, a pleural fluid pH of less than 7.3 has been associated with more extensive pleural involvement and shorter life expectancies.

Amylase

Pleural fluid amylase levels greater than 110U/L are indicative of pancreatitis, malignancy or a ruptured oesophagus.

White blood cells (WBC)

Results generally are not diagnostic, but most transudates have WBC counts less than 1000 cells/µL, whereas exudates generally have WBC counts greater than 50,000 cells/µL.

Pleural fluid lymphocytosis suggests TB, sarcoidosis or malignancy.

Neutrophil dominant effusions are associated with empyema or pulmonary embolism.

Pleural fluid eosinophilia (PFE) is usually caused by the presence of air or blood in the pleural space.

Blood in the pleural space may be the result of pulmonary embolism or benign asbestosis. The presence of PFE does not exclude malignancy.

Cholesterol and triglycerides

Pleural fluid triglyceride levels greater than 1.24 mmol/l with a cholesterol level of less than 5.18 mmol/l is diagnostic of chylothorax.

A triglyceride level of less than 0.56 mmol/l with a cholesterol level of greater than 5.18 mmol/l is associated with pseudochylothorax.

Worked examples

Case 1

A 52-year-old male presents with a cough, shortness of breath and fever. CXR shows a right-sided pleural effusion. A thoracentesis is performed and the results of the pleural fluid analysis are as follows:

• Colour: purulent
• Pleural/serum total protein ratio: >0.5
• pH: 7.1
• WBC count: 67,000 cells/µL
• Glucose: 1.5 mmol/l
• LDH: 1430 IU/L

Case 2

A 56 -year-old, previously well woman was admitted with a 4-week history of a cough, night sweats and 1-week history of progressive breathlessness. She had never smoked and has no history of heart disease or rheumatological disease. Pleural fluid results are as follows:

• Colour: milky-white, odourless
• Triglyceride: 0.5 mmol/l
• Cholesterol: 12.4 mmol/l

References

1. Light RW, Macgregor MI, Luchsinger PC, Ball WC Jr. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med1972;77:507-13.
2. Pettersson T, Riska H. Diagnostic value of total and differential leukocyte counts in pleural effusions. Acta Med Scand 1981;210:129–35. (3)
3. Saraya T; Light RW; Takizawa H; Goto H, Black pleural effusion. Am J Med.  2013; 126(7):641.e1-6 (ISSN: 1555-7162)
4. Sahn S. Pleural fluid analysis: narrowing the differential diagnosis. Semin Respir Med 1987;9:22–9. (4).
5. Good JT Jr., Taryle DA, Maulitz RM, et al. The diagnostic value of pleural fluid pH. Chest 1980;78:55–9.(3)
6. Light RW, Ball WC. Glucose and amylase in pleural effusions. JAMA 1973;225:257–60. (3).
7. Villena V, Lopez-Encuentra A, Garcia-Lujan R, et al. Clinical implications of the appearance of pleural fluid at thoracentesis. Chest 2004;125:156–9. (3).

Editor

Fiona Kirkham