Pleural Fluid Analysis, Normal Values and Abnormalities

Pleural fluid analysis involves taking out the fluid out from the pleural cavity [ by a procedure called thoracocentesis, where a needle is placed through the skin on the chest into the pleural space.

Pleural fluid is the fluid that is found between the layers of the pleura. Pleura is the  membrane lining the lungs. There are two layers of pleural membranes, outer parietal and inner visceral. The space between these two is known as  the pleural cavity or pleural space. Normal pleural fluid consists of a small amount of a thin (serous) fluid that functions as a lubricant during breathing.

Pleural fluid fills this cavity.

Pleural fluid functions to lubricate the space between the pleura, allowing the pleura to glide smoothly during inspiration and expiration.

Several conditions may cause the pleural fluid in the pleural cavity to increase. Pleural effusion is the term used for increased fluid in pleural  the pleural cavity.

Pleural effusion may be caused by many conditions like congestive heart failure, pulmonary embolism, malignancies etc.

When fluid builds up in the pleural space it can compress the underlying lung. This, in turn, can cause symptoms of shortness of breath and chest pain.

Pleural Fluid Analysis

Pleural fluid analysis involves taking out the fluid out from the pleural cavity [ by a procedure called thoracocentesis, where a needle is placed through the skin on the chest into the pleural space. Sometimes, if a chest tube is put to relieve the increased fluid built up, sample for analysis may be taken from there as well.

After fluid is taken, it is subjected to gross, microscopic, biochemical and cytological examination. If needed, the fluid may be subjected to culture and sensitivity.

Characteristics of Normal Pleural Fluid

Normal pleural fluid analysis has the following characteristics:

• Clear ultrafiltrate of plasma that originates from the parietal pleura
• A pH of 7.60-7.64
• Protein< 2% (1-2 g/dL)
• <1000 WBC  per cubic millimeter
• Glucose content similar to that of plasma
• Lactate dehydrogenase (LDH) less than 50% of plasma

Abonormalities of Pleural Fluid Analysis

First thing is to determine if the fluid is exudates or transudate.

Exudate is the extravascular fluid with high protein content, usually because of inflammatory response [as in infection]

Transudate is the extravascular fluid with low protein content due to increased hydrostatic pressure (as in congestive heart failure) or decrease osmotic pressure (decreased protein synthesis in case of liver failure)

Laboratory tests help to distinguish pleural fluid transudates from exudates.

Physical Examination of the Pleural Fluid

However, certain types of exudative pleural effusions might be suspected simply by observing the gross characteristics of the fluid obtained during thoracentesis.

Distinguishing Between Transudates and Exudates

Light’s Criteria

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

• Ratio of pleural fluid to serum protein greater than 0.5
• Ratio of pleural fluid to serum LDH greater than 0.6
• Pleural fluid LDH greater than two thirds of the upper limits of normal serum value

The fluid is considered a transudate if all of the above are absent.

Another equally effective criteria is

• Pleural fluid LDH value greater than 0.45 of the upper limit of normal serum values
• Pleural fluid cholesterol level greater than 45 mg/dL
• Pleural fluid protein level greater than 2.9 g/dL

Light’s criteria and other alternative criteria misclassify approximately 20-25% of transudates as exudates, usually in patients on long-term diuretic therapy for congestive heart failure (because of the concentrating effect of diuresis on protein and LDH levels within the pleural space).

For these patients following may be used

• Serum protein minus pleural protein < 3.1 g/dL – exudates
• Serum albumin to pleural fluid albumin ratio < 1.2 g/dL – Exudate
• High pleural levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), >1300-4000 ng/L  – Confirm heart failure

Lab Studies

Pleural fluid Lactate Dehydrogenase

• Levels greater than 1000 IU/L
  • Empyema
  • Malignant effusion,
  • Rheumatoid effusion
  • Pleural paragonimiasis

Pleural fluid LDH levels are also increased in effusions from Pneumocystis jiroveci (previously called, P carinii) pneumonia. Pleural fluid/serum LDH > 1 and  pleural fluid/serum protein > 0.5 suggests the diagnosis.

Pleural fluid Glucose

Low pleural glucose concentration (30-50 mg/dL)

• Malignant effusion
• Tuberculous pleuritis
• Esophageal rupture
• Llupus pleuritis

Very low pleural glucose concentration (ie, < 30 mg/dL)

• Rheumatoid pleurisy
• Empyema

Pleural fluid pH

Pleural fluid pH is highly correlated with pleural fluid glucose levels. A pleural fluid pH of less than 7.30 with a normal arterial blood pH level is caused by the same diagnoses as listed above for low pleural fluid glucose.

In case of effusions due to pneumonic lesion, a pleural fluid pH of less than 7.1-7.2 indicates the need for urgent drainage of the effusion, while a pleural fluid pH of more than 7.3 suggests that the effusion may be managed with systemic antibiotics alone.

Additional Tests on Exudative Pleural Fluid

If an exudate is suspected clinically or is confirmed by lab results consider the following studies on pleural fluid

• Total and differential cell counts
• Gram stain
• Culture

Cell Count

Leucocytosis

Acute leucocytosis suggests bacterial infection

Lymphocytosis

• 85% of the total nucleated cells
  • Tuberculosis
  • Lymphoma
  • Sarcoidosis
  • Chronic rheumatoid pleurisy
  • Yellow nail syndrome
• Lymphocytes 50-70% of the nucleated cells

Pleural fluid eosinophilia

• > 10% of nucleated cells
  • Pneumothorax
  • Hemothorax
  • Parasitic disease (especially paragonimiasis)
  • Fungal infection
    • Coccidioidomycosis
    • Cryptococcosis
    • Histoplasmosis

Gram stain

For direct observation of bacteria or fungi under a microscope. There should be no organisms present in pleural fluid.

Pleural Fluid Culture

Cultures of infected pleural fluids yield positive results in approximately 60% of cases. This occurs even less often for anaerobic organisms.

Cytology

Direct tumor involvement of the pleura is diagnosed most easily by performing pleural fluid cytology.

The reported diagnostic yields in cytology vary from 60-90%.

Cytology findings are positive in 58% of effusions related to mesothelioma.

Adenosine deaminase (ADA) activity

> 43 U/mL in pleural fluid supports the diagnosis of tuberculous pleuritis. However, the test has a sensitivity of only 78%.

Interferon gamma Levels

Interferon-gamma levels of greater than 140 pg/mL in pleural fluid also support the diagnosis of tuberculous pleuritis. Unfortunately, this test is not routinely available.

Risks Associated with Thoracocentesis/Pleural Fluid Analysis

• Pneumothorax, which is a partial or complete collapse of your lung
• Bleeding at puncture site
• an infection at the puncture site
• Injury to internal viscera – rare

References

• Noppen M. Normal volume and cellular contents of pleural fluid. Curr Opin Pulm Med. 2001 Jul. 7(4):180-2.
• Khaleeq G, Musani AI. Emerging paradigms in the management of malignant pleural effusions. Respir Med. 2008 Jul. 102(7):939-48
• Froudarakis ME. Diagnostic work-up of pleural effusions. Respiration. 2008. 75(1):4-13.
• Kolditz M, Halank M, Schiemanck CS, Schmeisser A, Hoffken G. High diagnostic accuracy of NT-proBNP for cardiac origin of pleural effusions. Eur Respir J. 2006 Jul. 28(1):144-50.
• Sakuraba M, Masuda K, Hebisawa A, Sagara Y, Komatsu H. Pleural effusion adenosine deaminase (ADA) level and occult tuberculous pleurisy. Ann Thorac Cardiovasc Surg. 2009 Oct. 15(5):294-6.