Introduction

Pleural fluid serves a physiologic function in respiration, while also being a useful measure to diagnose and assess disease, trauma, and other abnormalities. A brief review of the anatomy and physiology of normal pleural fluid gives a point of reference for assessing the causes of abnormal pleural fluid collections and pleural effusions.  [1][2][3]

The Light criteria is a useful way to differentiate between transudate and exudate, which can then be further evaluated with lab tests and in the context of the clinical presentation of the patient. Evaluation of pleural fluid can be used to determine the cause of pleural effusion and help guide the treatment of the underlying cause.

Issues of Concern

Many conditions can cause problems within the pleural cavity and in the pleural fluid. [4][5][6][7] The following are some of the most common:

• Pleurisy - pleura inflammation, causing sharp pain with breathing; most commonly caused by a viral infection
• Pleural effusion - excess fluid in the pleural space; commonly from congestive heart failure or malignancy. 
• Pneumothorax - a buildup of air or gas in the pleural space; commonly from acute lung injury, trauma, or chronic diseases such as a chronic obstructive pulmonary disease or tuberculosis
• Hemothorax - a buildup of blood in the pleural space; commonly from injury or trauma to the chest

In adults, congestive heart failure and liver cirrhosis are the most common causes of transudative pleural effusions. Pneumonia, malignant pleural disease, pulmonary embolism, and gastrointestinal disease account for almost all exudative pleural effusions. In children, congenital heart disease, pneumonia, and malignancy are the most common causes of pleural effusions.

Cellular Level

The composition of normal pleural fluid consists of total white blood cell count of 1.716 x 10(3) cells mL(-1). Differential cell counts: 75% macrophages, 23% lymphocytes, and marginally present mesothelial cells (1% to 2%), neutrophils (1%), and eosinophils (0%). Of note, there is a slight increase in the percent of neutrophils found in smokers over nonsmokers.

Development

Pleural fluid is continuously produced by the parietal circulation in the way of bulk flow, while it is also continuously reabsorbed by the lymphatic system via the stomata in the parietal pleura. In a healthy human, the pleural space contains a small amount of fluid (about 10 to 20 mL), with a low protein concentration (less than 1.5 g/dL).

Pleural fluid is filtered at the parietal pleural level from systemic microvessels to the extrapleural interstitium and into the pleural space down a pressure gradient. The lymphatics open as stomata directly onto the surface of the parietal pleura and provide most (about 75%) of the drainage of the pleural cavity, while absorption through the visceral pleura is negligible. The visceral pleura does not account for any significant pleural fluid drainage under normal conditions.   

The rate of reabsorption can increase as a physiological response to accumulating pleural fluid or other fluid in the pleural space. The rate of absorption can increase roughly 40 times the reference rate before excess fluid begins to accumulate in the pleural space. Significant fluid accumulation in the pleural cavity usually indicates excess production of pleural fluid, lymphatic blockage, or some other source of fluid such as bleeding.

Organ Systems Involved

The pleural fluid is contained in the pleural cavity, which is the space between the internal thoracic wall and the lungs. The pleural cavity is lined by a fibrous mesothelial membrane that is made up of a parietal and visceral layer. The parietal layer is the lining of the internal thoracic cavity, and the visceral layer covers the outside of the lungs. These layers are continuous and meet to form a double layer at the hilum of each lung, with no communication between the right and left pleural cavities.  

The innervation of the pleural cavity can be divided between the two pleural layers. The visceral pleura is innervated by autonomic fibers and is generally insensitive to irritation and inflammation; however, the parietal layer is innervated by somatic fibers and highly sensitive. The parietal innervation can be divided into four sections that have distinct and clinically significant presentations in the setting of physiologic insult: (1) cervical, (2) costal, (3) mediastinal, and (4) peripheral pleural zones. The cervical pleura is innervated by the first thoracic spinal nerve and when irritated may refer pain to the inner aspect of the upper limb. The costal pleura is innervated by the overlying thoracic nerves and may refer pain to the overlying thorax. The mediastinal pleura is innervated by the phrenic nerve, which runs down the fibrous pericardium and may refer pain to the ipsilateral shoulder in the distribution of the C4 dermatome. The peripheral diagrammatic pleura are innervated by the lower six thoracic nerves and may refer pain to the anterior abdominal wall.

The intercostal, internal thoracic and musculophrenic arteries provide the blood supply to the parietal pleura. The intercostal veins provide the venous drainage of the parietal pleura. The lymphatics of the parietal pleura drain into the intercostal, parasternal, diaphragmatic, and posterior mediastinal group of nodes. The blood supply and venous drainage of the visceral pleura come from the bronchial vessels, with the lymphatic drainage going through the hilar lymph nodes.

The anatomical protection of the pleural cavities is the bony thorax, which leaves three areas of vulnerability that may be clinically relevant in the setting of trauma to the lungs and pleura: (1) above the medial end of the first ribs, (2) below the costal-xiphisternal angle on the right side, and (3) below the costovertebral angles.

Pleural fluid enters the pleural space through the systemic capillaries in the parietal pleurae and exits via parietal pleural stomata and lymphatics.

Function

The fluid functions as a lubricant to allow the two layers of the pleura to glide smoothly past each other during respiration. The pressure of the pleural fluid is subatmospheric and maintains the negative pressure between the lungs and thoracic cavity, which is necessary for inhalation while also preventing the lungs from collapsing.

Related Testing

Physical examination can detect abnormal pleural fluid accumulation, and chest x-ray, followed by an evaluation by thoracentesis and pleural fluid analysis can determine the cause of the effusion. A thoracentesis typically is indicated if a clinically significant pleural effusion is present that is radiographically at least 10 mm thick. Pleural fluid accumulations can be further evaluated by gross appearance, clinical microscopy, cytopathologic findings, microbiology, pH, tumor markers, and other chemical studies.  

The Light Criteria

The Light criteria are used to determine if an effusion is exudative or transudative.  [8][9]

• Pleural fluid protein/Serum protein greater than 0.5
• Pleural fluid LDH/Serum LDH greater than 0.6
• Pleural fluid LDH greater than 2/3 *Serum LDH upper limit of the reference range

Pathophysiology

Pleural effusions develop when changes in fluid and solute homeostasis occur, and the mechanism causing these changes determines whether it will be an exudative (high protein content) or transudative (low protein content) effusion. Exudate is fluid that leaks around the cells of the capillaries and is caused by inflammation, while transudate is fluid pushed through the capillary due to high pressure within the capillary. An imbalance between the hydrostatic and oncotic pressure within the capillaries causes a transudate effusion. An alteration of the local inflammatory factors that precipitate a pleural fluid accumulation represents an exudative effusion.[10]

The accumulation of fluid in the pleural space is due to the rate of pleural fluid production exceeding the rate of reabsorption. Effusion of exudative type occurs when filtration rate exceeds maximum lymph flow, resulting in an effusion with higher than usual protein content. Exudate forms when protein permeability of the systemic capillaries is increased, causing an increase in pleural liquid protein concentration. Exudative pleural effusions generally are caused by infections such as pneumonia, malignancy, granulomatous diseases such as tuberculosis or coccidioidomycosis, collagen vascular diseases, and other inflammatory states.  

An increase of both capillary and mesothelial water permeability leads to hypooncotic fluid (lower protein content), and if filtration exceeds the maximum lymph reabsorption through the parietal stomata, transudate forms. Transudative pleural effusions occur in congestive heart failure, cirrhosis, nephrotic syndrome and malnutrition. The last three conditions reflect a decrease in colloid oncotic pressure due to hypoalbuminemia.

Localized pleural fluid effusion seen from a pulmonary embolism may result from increased capillary permeability due to cytokine and inflammatory mediator release from the platelet-rich thrombi.

Clinical Significance

Diagnosis of the etiology is essential, as the treatments for exudative and transudative etiologies differ significantly. Exudative effusions almost always require a further investigative workup, which may include cytopathology studies, biopsy, or even an emergent thoracotomy. Attempts should be made to determine the etiology of a patient with an exudative effusion. Conversely, transudative effusions usually do not require treatment, and therapy should be directed toward the underlying heart failure or cirrhosis. Malignant pleural effusion is common and denotes a poor prognosis. Dyspnea and a unilateral, large pleural effusion are the typical presentations of malignant pleural effusion. CT and ultrasound can help differentiate between benign and malignant pleural effusion.

Management of pleural effusion should be as follows:

• Diagnostic or therapeutic thoracentesis or chest tube drainage
• Obtain pleural fluid and serum studies of protein and LDH
• If indicated consider additional pleural fluid studies such as cell count, differential, cultures, or triglycerides
• Evaluate fluid using the Light criteria to determine if it is exudative
• Narrow differential diagnosis based on whether transudative or exudative