Etiology

A pleural effusion develops when the rate of fluid formation in the pleural space is greater than that of fluid removal.[1]

An effusion can be exudative or transudative. An exudative effusion occurs when local factors are altered, such as inflammation of the lung or the pleura leading to capillary leakage of fluid into the pleural space. Common causes include malignancy, pleural infection, pulmonary embolism, and autoimmune pleuritis. A number of medications have been reported to also cause exudative effusions, with tyrosine kinase inhibitors being the most commonly implicated.[7]​ Other medications which have been known to cause pleural effusion and idiosyncratic reactions are nitrofurantoin and dantrolene. The mechanisms are multiple and generally poorly understood. A transudative effusion, by contrast, is mediated by systemic factors. These include an elevated portal pressure from cirrhosis, elevated visceral pulmonary capillary pressure from left-sided heart failure, elevated parietal pleural capillary pressure from right-sided heart failure, low oncotic pressure due to hypoalbuminemia (with or without fluid overload).[7]

Pleural effusion is relatively common after thoracic surgery,[8] with a number of factors implicated, including topical cardiac cooling, surgical interruption of mediastinal lymphatic drainage, pleuritis, and possible underlying pericarditis.

Gonadotrophin-induced ovarian hyperstimulation syndrome (OHSS) is an uncommon cause of pleural effusion.[9] OHSS is characterized by an increase in capillary permeability resulting in shifts of intravascular fluid to third space compartments, particularly the abdominal cavity. Pleural effusions usually occur in conjunction with ascites, but isolated pleural effusions have been reported.[10] Large pleural effusions are unlikely to be due to pulmonary emboli, where local tissue hypoxia and the consequent release of inflammatory, vasoactive cytokines may result in pleuritis and increased pleural fluid production.[11]

Pathophysiology

The primary cause of a pleural effusion is simply an imbalance between the fluid production and fluid removal in the pleural space.[1] The pleural space must, under normal circumstances, have a small amount of lubricating fluid present to allow the lung surface to glide within the thorax during the respiratory cycle. Normally approximately 15 mL/day of fluid enters this potential space, primarily from the capillaries of the parietal pleura. This fluid is removed by the lymphatics in the parietal pleura. At any one time there is about 20 mL of fluid in each hemithorax and the layer of fluid is 2 to 10 micrometers thick.[2]

This regulated fluid balance is disrupted when local or systemic derangements occur. When local factors are altered, the fluid is protein- and lactate dehydrogenase (LDH)-rich and is called an exudate. Local factors include leaky capillaries from inflammation secondary to infection, infarction, or tumor. When systemic factors are altered, producing a pleural effusion, the fluid tends to have low protein and LDH levels and is called a transudate. This can be caused by an elevated pulmonary capillary pressure with heart failure, excess ascites with cirrhosis, or low oncotic pressure due to hypoalbuminemia (e.g., with nephrotic syndrome). In clinical practice, transudates are often multifactorial, with renal failure plus cardiac failure plus poor nutritional status being a common cause.[2]

Classification

Light criteria for transudate/exudate differentiation[2]

Light criteria are used to differentiate between a transudative and exudative effusion. An exudate is defined as the presence of any of the following:

  • Pleural protein to serum protein ratio >0.5

  • Pleural lactate dehydrogenase (LDH) to serum LDH ratio >0.6

  • Pleural LDH greater than two-thirds of upper limit of normal for serum.

However, 7.8% to 15% of effusions may be misclassified as exudates using this criteria.[3]

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