Physiology and pathophysiology of pleural fluid turnover

A review on pleural space is certainly most welcome, for the simple reason that on opening a textbook of physiology the concepts concerning pleural fluid turnover date back to 1927 [1]. The same comment, in fact, applies in general to microvascular water and solute exchange. This appears particularly misleading, considering the major advances achieved in the field over the last 70 yrs. Around the turn of the 19th century, STARLING and TUBBY [2] interpreted microvascular fluid and solute exchange as resulting from the balance between hydraulic and colloidosmotic pressures. This concept is still valid today, but the complete formulation of transmicrovascular exchange has become much more complex because water crosses biological membranes more easily than large solutes (namely, plasma proteins) do [3]. In fact, different equations describe water and solute fluxes [4]. As a result, the general model of transcapillary fluid exchange still taught to students, based on fluid filtration at the arteriolar end of the capillary bed and reabsorption at the venular end, appears rather simplistic. Due to the different permeability to water and solutes, one could predict on a mathematical basis that such a model would lead to a progressive increase in interstitial protein concentration over time [3, 4], a condition that cannot be confirmed experimentally. Similarly, the old hypothesis claiming that pleural fluid filters at parietal level and is reabsorbed through the visceral pleura [1] would imply that pleural liquid protein concentration would keep increasing with age, but again there are no indications that this occurs. The existence of partial restriction to the movement of large solutes, compared to that of water molecules, posed scientists the major problem of explaining how interstitial volume and protein concentration are kept fairly steady. Ideologically, this led to re-evaluation of lymphatics as the major route for interstitial fluid drainage. In fact, since lymphatics do not sieve proteins, they leave the interstitial protein concentration unaltered the latter depending only upon the sieving properties of the filtering membrane. Accordingly, the description of interstitial fluid homeostasis under steady state conditions is now being explained as a balance between capillary filtration and lymphatic absorption. Major validation of this model has come from the accumulating experimental data over the past 30 yrs concerning interstitial tissues [4] and serous spaces [5]. Interestingly, since the pioneering, work of STARLING and TUBBY [2] the pleural space has been used as a useful experimental model to study the interaction between microvascular filtration and lymphatic drainage. This article presents an integrated view of pleural fluid turnover, based on data gathered from experimental studies on animals over the last 15 yrs. The situation in man is, unfortunately, still poorly defined; yet, where possible, Physiology and pathophysiology of pleural fluid turnover. G. Miserocchi. ©ERS Journals Ltd 1997. ABSTRACT: The pleural space contains a tiny amount (≈0.3 mL·kg-1) of hypooncotic fluid (≈1 g·dL-1 protein). Pleural fluid turnover is estimated to be ≈0.15 mL·kg-1·h-1. Pleural fluid is produced at parietal pleural level, mainly in the less dependent regions of the cavity. Reabsorption is accomplished by parietal pleural lymphatics in the most dependent part of the cavity, on the diaphragmatic surface and in the mediastinal regions. The flow rate in pleural lymphatics can increase in response to an increase in pleural fluid filtration, acting as a negative feedback mechanism to control pleural liquid volume. Such control is very efficient, as a 10 fold increase in filtration rate would only result in a 15% increase in pleural liquid volume. When filtration exceeds maximum pleural lymphatic flow, pleural effusion occurs: as an estimate, in man, maximum pleural lymph flow could attain 30 mL·h-1, equivalent to ≈700 mL·day-1 (≈40% of overall lymph flow). Under physiological conditions, the lung interstitium and the pleural space behave as functionally independent compartments, due to the low water and solute permeability of the visceral pleura. Pleural fluid circulates in the pleural cavity and intrapleural fluid dynamics may be represented by a porous flow model. Lubrication between lung and chest wall is assured by oligolamellar surfactant molecules stratified on mesothelial cells of the opposing pleurae. These molecules carry a charge of similar sign and, therefore, repulse each other, assuring a graphite-like lubrication. Eur Respir J., 1997; 10: 219–225. Istituto di Fisiologia Umana, Università degli Studi, Milano, Italy