Pleural Fluid, Transudate and Exudate

Pleural effusion is a common clinical problem. In the normal state, the pleural cavity is bathed in a small volume of physiologic pleural fluid containing mainly macrophages and lymphocytes. The volume of the pleural fluid can increase dramatically with most pathologic conditions affecting the pleura. The pleural effusion will alter the respiratory mechanics, commonly resulting in dyspnea. It is useful to differentiate the pleural effusion into transudates and exudates. Traditionally, such differentiation is made using Light’s criteria, based on the protein and lactate dehydrogenase levels in pleural fluid and serum. Transudates occur as a result of altered hydrostatic and/or oncotic pressures and are usually secondary to congestive cardiac failure or hepatic cirrhosis. Exudates develop as a result of plasma extravasation, which is at least in part due to pleural or pulmonary inflammation. Evidence suggests that cytokines, such as vascular endothelial growth factor, play a role in exudative effusion formation. Parapneumonic effusion, malignant effusion, and tuberculous pleuritis are the most common causes of exudative effusions worldwide. Pleural Fluid Formation in the Normal State In the healthy state, the pleural cavity – which is extremely thin (10 mm) but has a large surface area (1–2m) – contains a small amount of fluid that serves as a lubricant to facilitate the gliding of the visceral pleura over the parietal pleural membrane. This fluid is a transudate and contains mainly macrophages. Most of the knowledge on the volume, composition, and dynamics of normal pleural fluid has been obtained in animal studies, and very few human studies are available. Pleural fluid volume assessment in normal circumstances can be performed using direct measurements (e.g., gentle aspiration after pleural puncture, pleural catheterization, or even thoracotomy) or using indirect techniques (e.g., pleural lavage). The normal physiologic pleural fluid is formed by filtration from systemic vessels and occurs predominantly at the less dependent region of the pleural cavity, where the blood vessels are closest to the mesothelial surface. The systemic blood supply from the intercostal arterial circulation of parietal pleura is believed to be the principal source of this fluid. In humans, the bronchial circulation of the visceral pleura is not likely to contribute significantly because the human visceral pleura is thick and the microvascular pressure for fluid filtration in the bronchial circulation is low (relative to that of the parietal intercostal circulation). Water filters into the pleural space according to the net hydrostatic–oncotic pressure gradient. Water and small molecules (p4nm) pass freely between the mesothelial cells. Larger molecules can be actively transported through the mesothelial cells via a transcytoplasmatic pinocytic mechanism. This mechanism probably also contributes to liquid and protein exchange in the pleural space, although its overall contribution is unclear. Direct measurements of normal pleural fluid volume in various animal models (e.g., rabbits, dogs, and sheep) consistently show volumes between 0.04 and 0.12ml kg 1 per pleural space. Differences in measurement results are caused by the various methodologies used and by the fact that the fluid volume adherent to the lung surface has not always been included. In humans, one direct measurement study by Yamada (puncture of the pleural space in the 9th or 10th intercostal space at the posterior axillary line) yielded some fluid in one-third of normal individuals. Interestingly, after exercise, up to two-thirds of individuals had detectable pleural fluid. Most often, only some foam was retrieved, but in some individuals up to 20ml of fluid was collected. In another study, a pleural lavage procedure was performed in normal subjects undergoing thoracoscopy for treatment of sympathetic disorders. Estimation of the volume of the original pleural fluid present was performed using the urea dilution method, based on the principles of dilution and mass conservation. The volume of the original fluid present in each hemithorax was 0.1370.06ml kg 1 body mass. The biochemical composition of normal pleural fluid resembles that of other interstitial fluids. The 358 PLEURAL EFFUSIONS /Pleural Fluid, Transudate and Exudate