PLEURAL FLUID: FUNCTIONS, WHERE IT IS PRODUCED, CULTURE, ANALYSIS - BIOLOGY - 2025

The pleural fluid is a plasma ultrafiltrate which acts as a biological lubricant from the pleural cavity, helping the movement of the lungs during breathing (inhalation and exhalation).

The amount of pleural fluid is very small, approximately each hemithorax houses 5 to 15 ml. It is located inside the pleural cavity, which comprises the space between the outside of the lungs and the thoracic cavity. The membrane that delimits this area is called the pleura.

X-ray showing pleural effusion in the left hemithorax and sample of pleural fluid. Sources: Clinical_Cases: I made the photo myself, licensed under Creative Commons license. / The original uploader was Bk0 at English Wikipedia.

In different pathologies, an increase in pleural fluid can occur and an effusion may occur. This increase can occur due to the production of transudates or exudates.

Establishing the difference between exudate and transudate is essential to reach the diagnosis. Cytochemical analysis determines whether the accumulated fluid is a transudate or exudate. For this, Light's criteria are followed, determined mainly by the pH value, total proteins, LDH and glucose.

However, today other analytes have been added that help to differentiate the transudate from the exudate, increasing the precision.

The most frequent pathologies that cause transudation are: congestive heart failure, neoplasms, decompensated liver cirrhosis, chronic kidney failure or pulmonary embolism, among others.

It can also occur in other less common causes, such as: constrictive pericarditis, Dressler syndrome, nephrotic syndrome, hypothyroidism, peritoneal dialysis, Meigs syndrome, among other causes. Meanwhile, infectious, neoplastic, inflammatory pathologies, among others, can cause the formation of exudates.

The cytochemical, smear, Gram and culture are laboratory tests that guide towards the origin of the pleural effusion.

Features

Pleural fluid is necessary for the proper functioning and homeostasis of the respiratory system. It keeps the pleura lubricated, and thus the lungs can easily expand and retract, without friction between the parietal and visceral pleura.

Where is it produced?

The pleura is a membrane that has two leaves, the parietal (attached to the thoracic cavity) and the visceral (attached to the lungs).

Both are irrigated by vessels of the systemic circulation, however, the venous return is different, since in the case of the parietal sheet, the capillaries drain through the vena cava, while the visceral sheet returns through the pulmonary veins.

Pleural fluid is an ultrafiltrate of the blood, which flows through the capillaries at a rate of 0.5 ml / hour into the pleural space. The parietal sheet is crucial in the absorption of the pleural filtrate and the cells found within the pleural cavity.

If an imbalance occurs in the circulation (increased production or incorrect reabsorption), the liquid accumulates and can generate a spill. Among the causes that can cause a pleural effusion are:

- The formation of transudates (hydrothorax) is formed from the pulmonary capillaries: by an increase in hydrostatic pressure and capillary permeability, by a decrease in oncotic pressure and by an increase in the negative pressure of the pleural space.

- Also due to altered lymphatic flow or invasion of ascites fluid into the pleural cavity.

What is it studied for?

Radiographic studies may reveal the existence of a pleural effusion. In minimal effusions, other studies are sometimes necessary, such as chest CT scan or chest ultrasound.

The extraction of pleural fluid for analysis is indicated in patients who have suffered a pleural fluid effusion. The cytochemical and culture of the pleural fluid can help determine the cause.

Thoracentesis procedure: sampling of pleural fluid. Source: National Heart, Lung and Blood Institute

Pleural effusion is a very dangerous clinical complication, the main symptoms being dyspnea, pleuritic pain or dry cough.

Pleural effusion can be primary or secondary. Primary when there is a pathology of the pleura and secondary when it occurs due to extrapleural involvement.

Pleural fluid is removed through a procedure called thoracentesis. This must be done by a doctor. The liquid is collected in different tubes according to the analyzes.

Determining the cause of the pleural effusion is crucial to establishing effective treatment.

Cytochemical analysis

For the cytochemical analysis, the sample must be collected in sterile tubes with heparin anticoagulant for the biochemical study and with EDTA for the cell count. Anticoagulants should be used because this fluid tends to clot.

The cytochemical study includes: physical study, biochemical study and cytological or cellular study.

Physical study

Determination of pH, density, color, appearance.

Biochemical study

Glucose, total proteins, lactate dehydrogenase enzyme (LDH).

At times, the doctor may request additional tests, especially when specific pathologies are suspected: Examples:

- Pleural effusions due to tuberculosis: determination of adenosine deaminase (ADA), lysozyme and gamma interferon.

-Chylothorax: the triglyceride value is very useful, in general the pleural fluid is milky, although there are exceptions.

-Pseudochylothorax: determination of cholesterol.

-Pancreatitis and pancreatic pseudocyst: determination of amylase.

-Urinothorax: determination of creatinine.

-Lupus pleuritis: antinuclear antibodies (ANA).

-Pleural effusion due to rheumatoid arthritis: Complement (C4), rheumatoid factor.

-Mesotheliomas: Pleural mesothelin.

Cell study

Red blood cell and leukocyte count, leukocyte formula.

Microbiological analysis

Sampling

Pleural fluid for microbiological analysis should be collected in a sterile tube.

Gram del

To perform the Gram, the pleural fluid is centrifuged and a smear is performed with the fluid sediment. It is stained with the Gram stain and observed under a microscope.

Pleural fluid is naturally sterile, therefore any organisms observed are of clinical importance. It must be accompanied by a culture.

Smear microscopy

With the sediment of the liquid, a smear is made for the BK (Ziehl Neelsen stain to search for the Koch bacillus, Mycobacterium tuberculosis). However, this study has low sensitivity.

Culture

The pleural fluid pellet is seeded in nutritious culture media: blood agar and chocolate agar. A Sabouraud agar can also be included for the study of fungi and by means of Löwenstein-Jensen in case of suspecting Mycobacterium tuberculosis. The latter usually requires a previous step of decontamination of the sample with 4% NaOH.

However, if bacteria are not observed on the Gram, it is not necessary to decontaminate the sample. In this case, the sediment is seeded directly on the Löwenstein-Jensen medium.

Study of anaerobic bacteria may also be included, especially in pleural fluids that present a foul odor.

Biopsy

Biopsy

Biopsy is necessary in certain neoplasms. It can be analyzed through pap smear of pleural fluid.

Thoracoscopy

Sometimes thoracoscopy is required. This moderately invasive procedure is relevant when other non-neoplastic etiologies have been ruled out. It is contraindicated when there is a risk of bleeding. It consists of the induction of an artificial pneumothorax for curative or diagnostic purposes.

Bronchoscopy

A procedure used to explore the airways, using a bronchoscope.

Normal values

There may be pleural effusions that have normal values, that is, there is an accumulation of fluid, but there are no major changes in its composition and appearance. This type of liquid corresponds to a transudate. They are usually more benign.

Physical study

pH: similar to plasma pH (7.60–7.66). It must be measured in a blood gas equipment.

Density: <1,015.

Appearance: Transparent.

Color: Light yellow (watery).

Odor: odorless.

Biochemical study

Total proteins (PT): 1 - 2.4 g / dl.

LDH: <50% of the plasma value.

Glucose: similar to plasma.

Cell study

Cells: count <5000 cells / mm ³

Formula: predominance of lymphocytes, macrophages and mesothelial cells.

Red blood cells: they must not exist or they are very scarce.

Mesothelial cells: their count has no clinical importance.

Neoplastic cells: Absent.

Other analysis

ADA: <45 U / L.

Pleural fluid lysozyme / plasma lysozyme ratio: <1.2.

Gamma interferon: <3.7 IU / ml.

Microbiologic analysis

Culture: negative.

Gram: No microorganisms observed.

BK: Acid-fast bacilli are not observed.

Pathological values

Other types of pleural effusions not only present with an exacerbation of the fluid, but there are also important physical, biochemical and cytological changes. These correspond to the exudates.

- Physical study

pH

Trasudados: 7.45-7.55.

Exudates: 7.30-7.45.

It can reach lower figures (<7.0-7.20) in effusions of parapneumonic, tuberculous, neoplastic origin, among other causes.

Density

> 1.015.

Appearance

Purulent and thick (empyema).

Milky and watery (chylothorax and pseudochylothorax).

Color

Yellowish (serous).

Orange when it contains moderate red blood cells (serohematic).

Reddish or bloody when it contains abundant red blood cells (hemothorax).

Milky whitish (chylothorax).

Odor

In urinothorax, the pleural fluid has a characteristic urine odor. While it may have a foul or putrid odor in infections caused by anaerobic microorganisms.

- Biochemical study

Total proteins: ratio PT of the pleural fluid / PT of plasma> 0.5 or total proteins of the pleural fluid> 3 g / dl.

LDH: > 2/3 of the upper limit normal value of plasma (> 200 IU / ml) or ratio pleural fluid LDH / plasma LDH> 0.6

LDH values> 1000 IU / ml are indicative of pleural effusion due to tuberculosis or neoplasms.

Glucose: decreased values ​​with respect to plasma. It can reach values ​​close to zero in case of empyemas, tuberculosis, etc.

- Cell study

Count:> 5000 cells / mm ³ (although some authors consider it pathological above 1000 cells / mm ³). Values> 10,000 mm ³ suggest parapneumonic pleural effusion.

Red blood cells : Presence of moderate to abundant red blood cells. In hemothorax, the count can reach 100,000 cells / mm ³, (hematocrit> 50% of blood).

Leukocyte formula: cellular predominance can aid differential diagnosis, especially in exudates.

Neutrophil-predominant pleural effusions: increased in inflammatory pleural effusions. Example in pneumonia, acute tuberculosis, pancreatitis, pulmonary embolism and some neoplasms.

Pleural effusions with a predominance of lymphocytes: it generally increases in the case of pleural effusions due to chronic tuberculosis, or due to malignancy (exudates), although there are usually other causes (chylothorax, lung transplant rejection, pulmonary embolism, sarcoidosis, among others). The lymphocyte count has no diagnostic value in the case of transudates.

Pleural effusions with eosinophilia (> 10%): Fluids with a high number of eosinophils rule out a malignant or neoplastic etiology. It is frequent in parasitic or fungal infections, in pleural effusions due to trauma, in spontaneous pneumothorax, cirrhosis, sarcoidosis, among others.

- Other analyzes

According to the clinical suspicion, the doctor may request additional studies or analytes, including:

ADA: > 45 U / L (tuberculosis).

Pleural fluid lysozyme / plasma lysozyme ratio: > 1.2 (tuberculosis).

Gamma interferon: > 3.7 IU / ml in tuberculosis

Cholesterol: transudates <60 mg / dl, exudates> 60 mg / dl (pseudochylothorax).

Triglycerides: > 110 mg / dl or above the plasma level, (chylothorax).

Amylase: > than the plasma value, (pancreatitis, pancreatic pseudocysts, esophageal rupture.

Pleural fluid creatinine / plasma creatinine ratio: > 1 (urinothorax).

Creatinine: <serum level (chronic kidney failure).

ANA: titers> 1: 160 or above the plasma value, (lupus pleurisy).

Rheumatoid factor: titers above 1: 320 or higher than the plasma value (rheumatoid pleurisy).

C-Reactive Protein (CRP): CRP ratio of pleural fluid / CRP of serum> 0.41. If the CRP value exceeds 100 mg / L, the effusion is considered to have a complicated prognosis.

Pleural mesothelin: > 20 nM (Mesotheliomas).

Natriuretic peptides: present (heart failure).

Complement C3 and C4: in exudates are low, especially in pleural effusion due to tuberculosis or malignant. While C4 figures <0.04 g / dl suggest rheumatoid arthritis effusion.

Ferritin: values> 805 µ / L exudate but> 3000 µ / L (indicates malignant pleural effusion).

Pleural fluid ferritin / serum ferritin ratio: > 1.5-2.0 (exudate).

- Microbiologic analysis

In case of infectious pleural effusions:

Culture: positive. The most commonly isolated microorganisms are: Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Escherichia coli and Pseudomonas aeruginosa.

Gram: Gram positive or Gram negative cocci, bacilli or coccobacilli can be observed.

BK: acid-fast bacilli (tuberculosis) may be seen.

- Biopsy

Neoplastic cells: it is studied through pleural fluid cytology. However, sometimes it is necessary to perform analysis by immunohistochemical techniques and flow cytometry. These techniques make it possible to distinguish cases of metastatic adenocarcinoma, mesotheliomas, and lymphomas.

References

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3. "Pleuric version." Wikipedia, L'enccyclopedia releases. 25 Giu 2019, 22:10 UTC. 25 lug 2019, 16:12.wikipedia.org
4. Quesada R, Pozo S, Martínez J. Transudated and exudated pleural effusions: classification. Rev Cuba Reumatol. 2018; 20 (3): e38. Available at: scielo.sld
5. Clavero J. Pleuroscopy module Pleural pathology: Thoracoscopy and videothoracoscopy. Rev. chil. sick breathe. 2008; 24 (1): 27-34. Available at: scielo.org