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Definition of Pleural Effusion

x-ray successful management of refractory pleural effusion

Image: Successful management of refractory pleural effusion due to systemic immunoglobulin light chain amyloidosis by vincristine adriamycin dexamethasone chemotherapy. By J Med Case Rep (2010). License: CC BY 2.0.

Pleural effusion as an accumulation of fluid in the pleural cavity

Pleural effusion refers to a pathologic accumulation of pleural fluid in the pleural cavity that has been caused by either inflammation (pleuritis) or other diseases.

Pleural fluid is physiologically produced at the capillary bed of the parietal pleura and is absorbed by the parietal pleural lymphatics and visceral pleura.

Pathology of Pleural Effusion

Pleural effusion: transudate and exudate

Depending on the overall protein concentration of the pleural effusion, a distinction is made between transudate (< 30 g/L) and exudate (> 30 g/L).

Transudate is a clear fluid containing few cells. It can emerge as a consequence of stasis due to increased hydrostatic pressure, which causes the fluid efflux from the capillaries to increase. Another cause occurs when the colloid osmotic pressure in the vessels decreases (e.g., in the event of hypoalbuminemia), causing more fluid to leak.

Exudate, on the other hand, is rich in cells and is mostly a consequence of inflammation or tumor diseases. Here, the permeability of the capillary walls for tumor cells, plasma proteins, and other blood components increases (barrier dysfunction). These particles will then form part of the pleural effusion, which is why exudate has such a high content of cells and proteins.

In both cases, an increase in lymph production can also be observed. This increased production then exceeds the maximum reabsorption capacity of the pleura and, thus, also contributes to the increased fluid accumulation.

At a glance: study aid for the differentiating criteria of both forms of pleural effusion

Overall protein concentration Quotient:  protein effusion/ protein serum LDH Quotient:  LDH effusion/ LDH serum
Transudate < 30 g/L < 0.5 < 200 U/L < 0.6
Exudate > 30 g/L > 0.5 > 200 U/L > 0.6

The most telling parameters are the protein and lactate dehydrogenase (LDH) quotients. Therefore, if one of these parameters is elevated (> 0.5 or > 0.6), the fluid is considered exudate.

Special forms of pleural effusion

Chylothorax and hemothorax are special forms of pleural effusion. A chylothorax consists primarily of lymphatic fluid, causing the pleural effusion to be milky and cloudy with a markedly elevated triglyceride content (> 110 mg/dL). A hemothorax is basically an accumulation of blood.

Note: A bloody pleural effusion must be considered suspicious for a tumor until proven otherwise.

Etiology of Pleural Effusion

Causes of pleural effusions

The three most frequent causes of transudate are:

  • Lung embolism
  • Decompensated left cardiac insufficiency
  • Liver cirrhosis

In the case of exudate, pneumonia, malignas, and lung embolisms should be considered. A lung embolism can cause both transudate and exudate. Additional causes are an increased rate of formation, a decreased rate of absorption, and direct extension from the peritoneum. Tuberculosis is the most frequent cause of pleural effusion in patients under 40 years of age.

Study aid: the most important causes of pleural effusion

Causes
Transudate Increased hydrostatic pressure: decompensated cardiac insufficiency, lung embolism, and venous congestion
Decreased colloid osmotic pressure: liver cirrhosis, hypoalbuminemia, nephrotic syndrome, uremia, and exudative enteropathy
Exudate Malignant: bronchial carcinoma (40%), metastases (breast carcinoma, 25%; gastrointestinal, 5%; and ovarian carcinoma, 5%), malignant lymphomas (10%), and pleural mesotheliomas
Infectious: pneumonia and tuberculosis
Rheumatic: lupus erythematosus and rheumatoid arthritis
Others: lung embolism, pancreatitis, pericarditis, and endometriosis
Chylothorax Shifting or lesions of the thoracic duct by tumors/metastases, trauma, or iatrogenic causes
Hemothorax Trauma, iatrogenic (after biopsies or punctures) causes, aortic aneurysm rupture, and pleural malignas

Symptoms of Pleural Effusion

Dyspnea is the cardinal symptom of pleural effusion

Aside from symptoms that are due to accompanying or underlying diseases, dyspnea is the only direct symptom. A patient’s shortness of breath can be more or less pronounced, depending on the severity of the effusion.

Diagnostics of Pleural Effusion

Anamnesis and clinical examination of pleural effusions

Anamnesis is always the first step in the diagnostic process for pleural effusion. In addition, a healthcare provider must consider different possible etiologies (tumor in medical history, risk factors for lung embolism, etc.).

The clinical examination can reveal an asymmetric chest expansion, with delayed expansion on the side of the effusion. Auscultation presents as decreased or inaudible breath sounds over the effusion. Sometimes, bronchial breath sounds can be heard over the lung parts directly above the effusion because the lung is consolidated, i.e. compressed, in this area.

Also, bronchophony can be absent over the pleural effusion because the vibration is being reflected at the line between lung tissue and pleural effusion (two matters of different density) and is, thus, not conducted to the hand of the examiner. In the case of an effusion > 300 mL, chest examination will also be notable for dullness to percussion. The upper border of this dullness follows a laterally ascending curve (Ellis-Damoiseau line). Palpation of larger effusions is notable for a reduced fremitus over the affected side for the same reasons that bronchophony is absent.

Imaging of pleural effusion

If the torso is erect, the effusion follows gravity and accumulates on the costophrenic angles of the pleural spaces (costodiaphragmatic recess). The most sensitive and gentle way to confirm a pleural effusion diagnosis is through the use of sonography while the patient is sitting down. This way, effusions with a volume of 20 mL or more will be depicted as an anechoic (= dark) area. Sonographic imaging also allows for the assessment of the pleura (fibrosis? tumor?) and the organization of the effusion, as well as for identifying a suitable puncture site.

bedside lung ultrasound

Image: Bedside lung ultrasound in a critically ill patient with pulmonary pathology. By Crit Ultrasound J (2012). License: CC BY 2.0.

Chest X-rays for diagnosing pleural effusions can be made in different positions and planes:

Position and plane Limit of detection
Example
Lateral decubitus (with the affected side facing down) 100 mL Chest X-ray in lateral decubitus position with evidence of pleural effusion

Pleural_effusion

Pleural effusion

Erect (lateral projection) 150 mL Recesses easily visible because they reach down furthest on the dorsal side
Erect posterior-anterior (PA) projection 200 mL Pleural effusion left and right with bilateral shadowed costophrenic angles

Medical_X-Ray

Image: Medical X-rays. By © Nevit Dilmen. License: CC BY 2.0.

In X-ray images, the effusion is depicted as a homogenous shadow, which sometimes ascends laterally (crescent sign). When the patient is standing, this shadow is usually seen in the lowest costodiaphragmatic recesses. Furthermore, the diaphragm is usually difficult to identify because an extensive decrease in transparency of the entire lung is possible along with a mediastinal shift to the opposing side. In rare cases, atypical localizations of the effusion may be found: for example, encapsulated and intralobular (DD: round lesion) or encapsulated in the area of pleural adhesions.

Left pleural effusion with mediastinal shift to the opposing side:

pleural effusion with mediastinal shifting

Image: Mediastinal shift to the right in the case of a very large pleural effusion on the left. By Hellerhoff. License: CC BY-SA 3.0

When the etiology is unclear, thoracic computed tomography (CT) scans will typically be performed as part of advanced diagnostic procedures. CT scans will detect even the smallest amounts of effusion, which will be notable as sickle-shaped consolidations between the lung and thoracic wall.

Thoracic CT scan with distinct pleural effusion, right

Pleural_effusion_CT_axial

Image: Pleural effusion in computer tomography axial soft tissue window right pleural cavity. By Hellerhoff. License: CC BY-SA 3.0.

Pleural puncture: diagnostics and treatment

For the purposes of differential diagnosis, an important step is to obtain testing material through a puncture of the pleural effusion. This procedure applies, in particular, to any case of a first or etiologically unclear pleural effusion.

For this procedure, the patient is sitting down, a local anesthetic is applied, and the puncture needle is inserted dorsally into the area of the effusion. However, the needle must not be inserted below the ninth rib (to avoid sub-diaphragmatic injuries). It is crucial to insert the needle at the upper edge of the rib to prevent any injuries to the nerves and vessels at the inferior edge of the rib. In cases of encapsulated effusions or atypical localizations, the finding of the puncture site should be assisted sonographically.

The material obtained from the puncture should be stored in four tubes:

  1. The first tube is for microbiology. From this material, a bacterial culture is made in order to perform a gram stain and, in cases of suspected tuberculosis, a Ziehl-Neelsen stain. This tube must be kept sterile at all times.
  2. The second tube is for clinical chemistry. With this material, various parameters will be determined such as cell count (e.g., lymphocytosis for cases of tuberculosis and sarcoidosis), pH level, glucose (diminished glucose levels and an acidic pH suggest an inflammatory or malignant genesis), triglyceride (elevated in cases of a chylothorax), amylase and lipase (elevated in cases of a pancreatic effusion caused by pancreatitis, pancreas carcinoma, or others), and specific tumor markers in cases of a suspected tumor disease.
  3. The third tube is for pathology. Here, a cytologic smear is prepared for the evaluation of malignancy. Indications for malignancy would include inter alia, a shift in the nucleus-plasma relation, many mitoses, and multinucleated cells.
  4. A fourth tube is kept for other, not yet foreseeable, examinations.

Macroscopically, a first assessment of the punctured effusion can be made:

Serous Bright, clear, ‘amber’ fluid: mostly transudate with few cells
Hemorrhagic  Reddish: bloody transudate or exudate—trauma or malignancy?
Chylous Milky and cloudy: chylothorax
Purulent Yellowish and dull: exudate in cases of pleural empyema, tuberculosis, or abscesses

The puncture furthermore provides relief for the patient and can thus be considered as part of symptomatic treatment, especially in cases of severe dyspnea due to lung compression and cardiopulmonary strains due to a mediastinal shift (i.e. in very severe cases of pleural effusions).

Note: Every pleural puncture should be followed by a chest X-ray to exclude iatrogenic pneumothorax.

Treatment of Pleural Effusion

Pleural draining and pleurodesis

Treating the underlying disease should be the focus of any treatment approach. When this treatment is followed through, transudates will most likely resolve completely.

As explained in the section on diagnostics, larger effusions with severe dyspnea are therapeutically punctured in order to relieve the patient’s shortness of breath. However, never extract more than 1.5 L in a single session because there is the risk of re-expansion edema or great losses of protein. Therefore, for larger effusions, treatment consists of suction drainage over the course of several days.

If the pleural effusion is recurrent (especially in cases of malignant genesis) and/or cannot be controlled with medication, chemical pleurodesis can be performed. After the puncture of the effusion, a fibrosing substance (e.g., talcum) is introduced into the pleural cavity through the chest drain. The substance triggers an inflammatory reaction that causes the two pleural layers to adhere to each other and, thus, prevents any further accumulation of fluids in the pleural cavity.

For a well-aimed biopsy and the isolation of histologic tissue samples in cases of malignant effusions, and also for additional bacteriologic diagnostics of non-controllable parapneumonic effusions and pleural empyema, an additional video-assisted thoracoscopy may be performed as well.

Complications of Pleural Effusion

Pleural fibrosis and pleural empyema

Sometimes, the formation of pleural fibrosis follows a pleural effusion, which manifests as cicatricial altered, mostly thickened, adhesions of the pleurae.

If the pleural effusion is the result of pneumonia, it is called a parapneumonic effusion. These effusions, in particular, tend to become infected and are then further classified, by using various parameters, as uncomplicated (= not infected), complicated (= infected), or pleural empyema (= infected).

Puncture specimen Detection of bacteria Leukocytes pH
Uncomplicated Clear Sterile + > 7.3
Complicated Cloudy (+) ++ 7.1–7.2
Pleural empyema Purulent + +++ < 7.1
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One thought on “Pleural Effusion: Diagnoses, Treatment, Transudate, and Exudate

  • Mohamed Alhazaa

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