Pleural Fluid Analysis

Pleural fluid analysis is used to help diagnose the cause of inflammation of the pleura (pleuritis) and/​or accumulation of fluid in the pleural space (pleural effusion). There are two main reasons for fluid accumulation, and an initial set of tests (albumin, cell count and appearance of the fluid) is used to differentiate between the two types of fluid that may be produced:

• An imbalance between the pressure within blood vessels (which drives fluid out of the blood vessel) and the amount of protein in blood (which keeps fluid in the blood vessel) can result in accumulation of fluid (called a transudate). Transudates are most often caused by cirrhosis of the liver or congestive heart failure. If the fluid is determined to be a transudate, then usually no more tests on the fluid are necessary.
• Injury or inflammation of the pleurae may cause abnormal collection of fluid (called an exudate). Exudates are associated with a variety of conditions and diseases and several tests, in addition to the initial ones performed, may be used to help diagnose the specific condition including:
  • Infectious diseases – caused by viruses, bacteria, or fungi. Infections may originate in the pleurae or spread there from other places in the body. For example, pleuritis and pleural effusion may occur along with or following pneumonia.
  • Bleeding – bleeding disorders, pulmonary embolism, or trauma can lead to blood in the pleural fluid.
  • Inflammatory conditions – such as lung diseases, chronic lung inflammation due to prolonged exposure to large amounts of asbestos (asbestosis), sarcoidosis, or autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus.
  • Cancer – such as lymphoma, mesothelioma or metastatic cancer
  • Other conditions –unknown cause (idiopathic), cardiac bypass surgery, heart or lung transplantation, or pancreatitis.
  • Drug induced – certain medications such as hydralazine (as part of a lupus syndrome), nitrofurantoin, sulphonamides and methotrexate

Pleural fluid analysis may be requested when a doctor suspects that a patient has a condition or disease that is causing pleuritis and/​or pleural effusion. It may be requested when a patient has some combination of the following signs and symptoms:

• Chest pain that worsens with deep breathing
• Coughing
• Difficulty breathing, shortness of breath
• Fever, chills
• Fatigue
• Pleural effusion may not cause any symptoms

An initial set of tests performed on a sample of pleural fluid helps determine whether the fluid is a transudate or exudate.

Transudate:

• Physical characteristics—fluid appears clear
• Protein or albumin concentration—decreased
• Cell count—few cells are counted

Transudates usually require no further testing. They are most often caused by either cirrhosis or congestive heart failure.

Exudate:

• Physical characteristics—fluid may appear cloudy
• Protein or albumin concentration—higher than normal
• Cell count—increased

Exudates can be caused by a variety of conditions and diseases and usually require further testing to aid diagnosis. Exudates may be caused by, for example, infections, trauma, various cancers, or pancreatitis. The following is a list of additional tests that the doctor may request depending on the suspected cause:

Physical characteristics – the normal appearance of a sample of pleural fluid is usually light yellow and clear. Abnormal results may give clues to the conditions or diseases present:

• Milky appearance may point to lymphatic system involvement
• Reddish pleural fluid may indicate the presence of blood
• Cloudy thick pleural fluid may indicate the presence of microorganisms and/​or white blood cells

Additional tests –tests that may be performed in addition to protein or albumin may include:

• Lactate dehydrogenase (LDH) – may be required for the purpose of differentiation of exudate from transudate according to Light’s criteria
• Glucose—typically about the same as blood glucose levels. May be lower with infection and rheumatoid arthritis.
• Lactate levels can increase with infectious pleuritis, either bacterial or tuberculosis.
• Amylase levels may increase with pancreatitis, oesophageal rupture, or malignancy.
• Triglyceride and cholesterol levels may be increased with lymphatic system involvement.

Microscopic examination – Normal pleural fluid has small numbers of white blood cells (WBCs) but no red blood cells (RBCs) or microorganisms. Laboratories may examine the pleural fluid and/​or use a special centrifuge (cytocentrifuge) to concentrate the fluid’s cells on a slide. The slide is treated with a special stain and evaluated for the different kinds of cells that may be present.

• Total cell counts—the WBCs and RBCs in the sample are counted. Increased WBCs may be seen with infections and other causes of pleuritis. Increased RBCs may suggest trauma, malignancy, or pulmonary infarction.
• WBC differential—determination of percentages of different types of WBCs. An increased number of neutrophils may be seen with bacterial infections. An increased number of lympocytes may be seen with cancers and tuberculosis.
• Cytology – a cytocentrifuged sample is treated with a special stain and examined under a microscope for abnormal cells. This is often done when a mesothelioma or metastatic cancer is suspected. The presence of certain abnormal cells, such as tumour cells or immature blood cells, can indicate what type of cancer is involved.

Infectious disease tests – these tests may be performed to look for microorganisms if infection is suspected:

• Gram stain – for direct observation of bacteria or fungi under a microscope. There should be no organisms present in pleural fluid.
• Bacterial culture and susceptibility testing is used to detect any microorganisms that may be present in the pleural fluid. If bacteria are present, susceptibility testing can be performed to guide antimicrobial therapy. If there are no microorganisms present, it does not rule out an infection; they may be present in small numbers or their growth may be inhibited because of prior antibiotic therapy.
• Adenosine Deaminase – rarely, this test may be used to help detect tuberculosis. Markedly elevated level in pleural fluid in a person with symptoms suggestive of tuberculosis means likely that person has Mycobacterium tuberculosis infection. Sensitivity of this tests in only about 80%.

Other tests for infectious diseases that are less commonly used may include tests for viruses, mycobacteria (AFB smear and culture), and parasites.

A blood glucose, protein, or albumin result may be used to compare concentrations with those in the pleural fluid. In order to differentiate exudate from transudate the total protein and LDH are measured in both blood and pleural fluid.

Thoracentesis is the removal of pleural fluid from the pleural cavity with a needle and syringe. The person is positioned sitting upright with arms raised and supported. A local anaesthetic is applied and then the doctor inserts the needle into the pleural cavity and the sample is removed.

Yes. Sometimes it will be performed to drain excess pleural fluid – to relieve pressure on the lungs. A catheter tube may be used to drain larger amounts of fluid and to drain recurrent fluid accumulations.