Pleural Liquid Volume Research Articles

Pleural liquid and kinetic friction coefficient of mesothelium after mechanical ventilation

Volume and protein concentration of pleural liquid in anesthetized rabbits after 1 or 3h of mechanical ventilation, with alveolar pressure equal to atmospheric at end expiration, were compared to those occurring after spontaneous breathing. Moreover, coefficient of kinetic friction between samples of visceral and parietal pleura, obtained after spontaneous or mechanical ventilation, sliding in vitro at physiological velocity under physiological load, was determined. Volume of pleural liquid after mechanical ventilation was similar to that previously found during spontaneous ventilation. This finding is contrary to expectation of Moriondo et al. (2005), based on measurement of lymphatic and interstitial pressure. Protein concentration of pleural liquid after mechanical ventilation was also similar to that occurring after spontaneous ventilation. Coefficient of kinetic friction after mechanical ventilation was 0.023±0.001, similar to that obtained after spontaneous breathing.

Pleural function and lymphatics

The pleural space plays an important role in respiratory function as the negative intrapleural pressure regimen ensures lung expansion and in the mean time maintains the tight mechanical coupling between the lung and the chest wall. The efficiency of the lung-chest wall coupling depends upon pleural liquid volume, which in turn reflects the balance between the filtration of fluid into and its egress out of the cavity. While filtration occurs through a single mechanism passively driving fluid from the interstitium of the parietal pleura into the cavity, several mechanisms may co-operate to remove pleural fluid. Among these, the pleural lymphatic system emerges as the most important one in quantitative terms and the only one able to cope with variable pleural fluid volume and drainage requirements. In this review, we present a detailed account of the actual knowledge on: (a) the complex morphology of the pleural lymphatic system, (b) the mechanism supporting pleural lymph formation and propulsion, (c) the dependence of pleural lymphatic function upon local tissue mechanics and (d) the effect of lymphatic inefficiency in the development of clinically severe pleural and, more in general, respiratory pathologies.

Complications of permanent dual‑chamber pacing such as late purulent pacemaker pocket infection with broken and looped atrial lead, complicated by pulmonary embolism after transvenous lead removal: a case report

We present a complication of the infected pacing system extraction by lobular pneumonia in a 73-year-old female patient. The pacing system involved DDD pacemaker, atrial and ventricular endocardial leads implanted 12 year beforehand. The defect of the atrial lead emerged during the pacemaker replacement 4 years ago. The diagnosis of the injury cause and its reparation were not undertaken at that time. An interruption of the atrial lead which resulted in the formation of a loop inside the cardiac chamber was found when purulant pacemaker pocket infection had been diagnosed. The patient was referred for the pacing system extraction after preoperative specific antibiotic treatment. After a long-lasting, difficult, two-step leads extraction procedure, pneumonia developed. An echocardiogram revealed enlargement of the right atrium and ventricle, with elevated pulmonary artery pressure up to 40 mmHg. An atypical chest X-ray with the presence of a large pleural liquid volume led to the work-up of hemorrhagic complications and postponed the antithrombotic therapy. With the delay of 1.5 month the pulmonary scintigraphy showed features of pulmonary embolism. The embolism was most likely caused by a vegetation mobilized from the endocardial lead and/or endocardium during the extraction maneuvers. Before the surgery, the vegetations attached to the leads or to the endocardium had not been visualized. Anticoagulant therapy with antivitamins K was successful, which resulted in the pulmonary pressure normalization. The patient has remained in a good condition for the next 3 months of follow-up.

Pleural liquid and its exchanges

After an account on morphological features of visceral and parietal pleura, mechanical coupling between lung and chest wall is outlined. Volume of pleural liquid is considered along with its thickness in various regions, and its composition. Pleural liquid pressure (P(liq)) and pressure exerted by lung recoil in various species and postures are then compared, and the vertical gradient of P(liq) considered. Implications of lower P(liq) in the lung zone than in the costo-phrenic sinus at iso-height are pointed out. Mesothelial permeability to H(2)O, Cl(-), Na(+), mannitol, sucrose, inulin, albumin, and various size dextrans is provided, along with paracellular "pore" radius of mesothelium. Pleural liquid is produced by filtration from parietal pleura capillaries according to Starling forces. It is removed by absorption in visceral pleura capillaries according to Starling forces (at least in some species), lymphatic drainage through stomata of parietal mesothelium (essential to remove cells, particles, and large macromolecules), solute-coupled liquid absorption, and transcytosis through mesothelium.

Pleural liquid during hemorrhagic hypotension

The effect of approximately 25% or 35% blood loss (b.l.) on volume, pressure, and protein concentration of pleural liquid has been determined in anesthetized rabbits in lateral or supine posture. Volume and pressure of pleural liquid did not change with 25% b.l. 30 and 60 min after beginning of hemorrhage, and with 35% b.l. at 30 min (bleeding time approximately 10 and 12 min, respectively). With 35% b.l. protein concentration of pleural liquid was 85% greater (P<0.01) than control; moreover, percent albumin was smaller (P<0.05), and percent globulin greater (P<0.05) than control. Decrease in arterial plasma protein concentration, hematocrit, and pH after hemorrhage fit literature data. Ventilation at 15 and 30 min increased (P<0.01) by 16% and 23%, respectively, with 25% b.l., but it did not change with 35% b.l., a condition borderline to survival in anesthetized rabbits without ad hoc treatment. Pleural liquid seems protected against derangements from hemorrhage up to 25% b.l. for periods shorter than 1 h.

Pleural mechanics and fluid exchange.

The pleural space separating the lung and chest wall of mammals contains a small amount of liquid that lubricates the pleural surfaces during breathing. Recent studies have pointed to a conceptual understanding of the pleural space that is different from the one advocated some 30 years ago in this journal. The fundamental concept is that pleural surface pressure, the result of the opposing recoils of the lung and chest wall, is the major determinant of the pressure in the pleural liquid. Pleural liquid is not in hydrostatic equilibrium because the vertical gradient in pleural liquid pressure, determined by the vertical gradient in pleural surface pressure, does not equal the hydrostatic gradient. As a result, a viscous flow of pleural liquid occurs in the pleural space. Ventilatory and cardiogenic motions serve to redistribute pleural liquid and minimize contact between the pleural surfaces. Pleural liquid is a microvascular filtrate from parietal pleural capillaries in the chest wall. Homeostasis in pleural liquid volume is achieved by an adjustment of the pleural liquid thickness to the filtration rate that is matched by an outflow via lymphatic stomata.

Physiology and pathophysiology of pleural fluid turnover.

Tight control of the volume and composition of the pleural liquid is necessary to ensure an efficient mechanical coupling between lung and chest wall. Liquid enters the pleural space through the parietal pleura down a net filtering pressure gradient. Liquid removal is provided by an absorptive pressure gradient through the visceral pleura, by lymphatic drainage through the stomas of the parietal pleura, and by cellular mechanisms. Indeed, contrary to what was believed in the past, pleural mesothelial cells are metabolically active, and possess the cellular features for active transport of solutes, including vesicular transport of protein. Furthermore, the mesothelium was shown, on the basis of recent experimental evidence, both in vivo and in vitro, to be a less permeable barrier than previously believed, being provided with permeability characteristics similar to those of the microvascular endothelium. Direct assessment of the relative contribution of the different mechanisms of pleural fluid removal is difficult, due to the difficulty in measuring the relevant parameters in the appropriate areas, and to the fragility of the mesothelium. The role of the visceral pleura in pleural fluid removal under physiological conditions is supported by a number of findings and considerations. Further evidence indicates that direct lymphatic drainage through the stomas of the parietal pleura is crucial in removing particles and cells, and important in removing protein from the pleural space, but should not be the main effector of fluid removal. Its importance, however, increases markedly in the presence of increased intrapleural liquid loads. Removal of protein and liquid by transcytosis, although likely on the basis of morphological findings and suggested by recent indirect experimental evidence, still needs to be directly proven to occur in the pleura. When pleural liquid volume increases, an imbalance occurs in the forces involved in turnover, which favours fluid removal. In case of a primary abnormality of one ore more of the mechanisms of pleural liquid turnover, a pleural effusion ensues. The factors responsible for pleural effusion may be subdivided into three main categories: those changing transpleural pressure balance, those impairing lymphatic drainage, and those producing increases in mesothelial and capillary endothelial permeability. Except in the first case, pleural fluid protein concentration increases above normal: this feature underlies the classification of pleural effusions into transudative and exudative.

Albumin transcytosis from the pleural space.

Occurrence of transcytosis in pleural mesothelium was verified by measuring removal of labeled macromolecules from pleural liquid in experiments without and with nocodazole. To this end, we injected 0.3 ml of Ringer-albumin with 750 microg of albumin-Texas red or with 600 microg of dextran 70-Texas red in the right pleural space of anesthetized rabbits, and after 3 h we measured pleural liquid volume, labeled macromolecule concentration, and, hence, labeled macromolecule quantity in the liquid of this space. Labeled albumin left was 318 +/- 28 microg in control and 419 +/- 17 microg in nocodazole experiments (means +/- SE); hence, whereas ventilation was similar its removal was greater (P < 0.01) in control experiments. Labeled dextran left was 283 +/- 10 microg in control and 381 +/- 21 microg in nocodazole experiments; hence, whereas ventilation was similar its removal was greater (P < 0.01) in control experiments. These findings indicate occurrence of transcytosis from the pleural space. Liquid removed by transcytosis was 0.05 ml/h. This amount times unlabeled albumin concentration under physiological conditions (10 mg/ml) times lumen-vesicle partition coefficient for albumin (0.78) provides fluid-phase albumin transcytosis: approximately 203 microg. h(-1) kg(-2/3). Transcytosis might contribute a relevant part of protein and liquid removal from the pleural space.

Cytokines in pleural liquid for diagnosis of tuberculous pleurisy

An elevated level of adenosine deaminase (ADA) in pleural liquid has been considered as a supplemental diagnostic marker for tuberculous pleurisy. However, this is complicated by false-positives and -negatives. Recently, it has been revealed that various cytokines are intimately involved in the pathognomonic physiology of tuberculosis. In this study, interleukin-8 (IL-8), tumour necrosis factor α (TNF α) and interferon γ (IFN γ ) were compared with ADA in pleural liquid of patients with inflammatory (21 cases), malignant (28 cases) and tuberculous (21 cases) disease. The pleural ADA, IL-8, TNF α and IFN γ levels in the tuberculous group were higher than in the other three groups. Analysis of receiver operating characteristic (ROC) curves, to evaluate the utility of the various parameters, demonstrates values for the area under the curve (AUC) of 0·770, 0·875, 0·892 and 0·987, respectively for IL-8, TNF α, ADA and IFN γ,. No false-positives were encountered with IFN γ and only one case with a small volume of pleural liquid was a false-negative. This indicates that IFN γ is a very reliable marker of tuberculous pleurisy.

Pleural Tissue Hyaluronan Produced by Postmortem Ventilation in Rabbits

We developed a method that used Alcian blue bound to hyaluronan to measure pleural hyaluronan in rabbits postmortem. Rabbits were killed, then ventilated with 21% O2--5% CO2--74% N2 for 3 h. The pleural liquid was removed by suction and 5 ml Alcian blue stock solution (0.33 mg/ml, 3.3 pH) was injected into each chest cavity. After 10 min, the Alcian blue solution was removed and the unbound Alcian blue solution (supernatant) separated by centrifugation and filtration. The supernatant transmissibility (T) was measured spectrophotometrically at 613 nm. Supernatant Alcian blue concentration (Cab) was obtained from a calibration curve of T versus dilutions of stock solution Cab. Alcian blue bound to pleural tissue hyaluronan was obtained by subtracting supernatant Cab from stock solution Cab. Pleural tissue hyaluronan was obtained from a calibration curve of hyaluronan versus Alcian blue bound to hyaluronan. Compared with control rabbits, pleural tissue hyaluronan (0.21 +/- 0.04 mg/kg) increased twofold, whereas pleural liquid volume decreased by 30% after 3 h of ventilation. Pleural effusions present 3 h postmortem without ventilation did not change pleural tissue hyaluronan from control values. Thus ventilation-induced pleural liquid shear stress, not increased filtration, was the stimulus for the increased hyaluronan produced from pleural mesothelial cells.

Physiology and pathophysiology of pleural fluid turnover.

The pleural space contains a tiny amount (approximately 0.3 mL.kg-1) of hypooncotic fluid (approximately 1 g.dL-1 protein). Pleural fluid turnover is estimated to be approximately 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 approximately 700 mL.day-1 (approximately 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.

Model of pleural fluid turnover

A model of pleural fluid turnover, based on mass conservation law, was developed from experimental evidence that 1) pleural fluid filters through the parietal pleura and is drained by parietal lymphatics and 2) lymph flow increases after an increase in pleural liquid volume, attaining a maximum value 10 times greater than control. From the differential equation describing the time evolution of pleural liquid pressure, we obtained the equation for the steady-state condition ("set point") of pleural liquid pressure: Pss = (KfPi*+KlPzf)/Kf+Kl), where Kf is parietal pleura filtration coefficient, Kl is initial lymphatic conductance, Pzf is lymphatic potential absorption pressure, and Pi* is a factor accounting for the protein reflection coefficient of parietal mesothelium and hydraulic and colloid osmotic pressure of parietal interstitium and pleural liquid. Lymphatics act as a passive negative-feedback control tending to offset increases in pleural liquid volume. Some features of this control are summarized here: 1) lymphatics exert a tight control on pleural liquid volume or pressure so that the set point is maintained close to the potential absorption pressure of lymphatics; 2) a 10-fold increase in Kf would cause only a 2- and 5-fold increase in pleural liquid volume with normal (1.8 g/dl) and increased (3.4 g/dl) protein concentration of the pleural fluid, respectively; and 3) the reduction in maximum lymph flow greatly reduces the range of operation of the control with increased filtration and/or protein concentration of pleural fluid.

Liquid and protein dynamics using a new minimally invasive pleural catheter in rabbits.

To obtain continuous access to the pleural space without causing injury, we tested a new transdiaphragmatic pleural catheter for its ability 1) to drain the pleural space without injury and 2) to drain liquid at a rate equal to normal pleural liquid production. In 13 anesthetized rabbits, we opened the abdomen and dissected through the diaphragm to insert a flared-tip catheter into the ventral pleural space on one side and then turned the rabbit prone. In 10 of the rabbits (8 for 6 h, 2 for 24 h), we continuously collected draining pleural liquid, and in 3 rabbits (6 h), we did not open the catheter. We injected radiolabeled albumin intravenously as a protein marker. Terminally, we collected pleural liquid from both pleural spaces and lavaged for total radioactivity. In 14 awake control rabbits without catheters, we measured normal pleural liquid production by the rate of equilibration of radiolabeled albumin from plasma to pleural liquid. We found that, although the percentage of neutrophils was increased on the side with the catheter (54 vs. 1% in control rabbits), the pleural liquid volume, protein concentration, specific activity of albumin, and total radioactivity in the pleural space were the same on the side with the catheter as on the opposite side and in the control rabbits. The liquid flow rate through the catheter over 6 h was 53 +/- 23 microliters/h [0.017 +/- 0.008 (SD) ml.kg-1.h-1], which was not significantly different from the computed rate of normal pleural liquid production in the control rabbits, 49 +/- 14 microliters/h (0.016 +/- 0.004 ml.kg-1.h-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Starling forces and lymphatic drainage in pleural liquid and protein exchanges

Pleural liquid volume and protein concentration (C) were determined in rabbits 60 min after a 2 ml hydrothorax with various albumin concentrations in Ringer, homologous serum or plasma. The absorption rate of the hydrothorax decreased with the increase in colloid osmotic pressure of the pleural liquid ( π), being 0.56 ± 0.03, 0.32 ± 0.02 and 0.17 ± 0.05 ml/h with Ringer, 1.1 and 3% albumin, respectively, and nil with 5% albumin, serum or plasma. C increased with Ringer and 1.1% albumin, did not change with 3% albumin, and decreased with 5% albumin, serum or plasma. The protein content in the pleural liquid increased with Ringer, did not change with 1.1% albumin, and decreased with the other hydrothoraces. These findings indicate that with hydrothoraces of this size: (1) the Starling forces plus the solute-coupled liquid absorption [Agostoni and Zocchi (1990) Respir. Physiol. 81: 19–28] provide most of the pleural liquid absorption when π is ≤ physiological ; (2) the lymphatic drainage increases with π, providing most of the liquid outflow when π is similar to that of plasma. This increase in lymphatic drainage, however, does not compensate for the effects of the changes in Starling forces produced by the increased π.

Pleural Lymphatics as Regulators of Pleural Fluid Dynamics

Pleural fluid is filtered across the parietal mesothelium in the top of the pleural cavity and removed by lymphatic stomatas in the more dependent mediastinal and diaphragmatic regions. The pleural lymphatics act as a feedback system that regulates pleural liquid volume and its protein composition around a low volume set point.

Clearance of lung edema into the pleural space of volume-loaded anesthetized sheep

To determine whether lung edema leaks into the pleural space, we measured flow rates of visceral pleural liquid from exposed sheep lungs during volume loading and then compared the protein concentration of visceral pleural liquid and lung interstitial liquids (lymph and peribronchovascular cuff liquid). For 4 h, we volume loaded 24 anesthetized ventilated sheep with one side, both sides, or neither side of the chest open. During the experiment, we collected visceral pleural liquid from a bag surrounding the exposed lung and lung lymph; after the experiment, we collected peribronchovascular cuff liquid. We found that during volume loading visceral pleural liquid flow increased significantly by 2 h, and its protein concentration over the final hour was the same as that of lung interstitial liquids. The volume of visceral pleural liquid correlated with excess lung water and wedge pressure elevation. By our estimates, clearance of edema from the lung into the pleural space constituted 23-29% of all edema liquid collected, similar to measured lymph edema clearance. We conclude that edema liquid leaks directly from edematous sheep lungs into the pleural space and that this leakage provides an important additional route of edema clearance.

Intrapleural liquid flow down a gravity-dependent hydraulic pressure gradient.

We studied the vertical movement of 2 mg technetium-labeled albumin injected intrapleurally in 0.5 ml saline (15% of pleural liquid volume) in eight spontaneously breathing anesthetized dogs subject to a sudden change in posture (prone to supine or vice versa). The albumin movements were evaluated through a large field gamma camera placed laterally to the animal and detecting total (AT) and regional activities from two superimposed equal areas (At and Ab, top and bottom, respectively). The At/Ab ratio decreased from 2.1 to 1.3 in four animals up to 20 min from the change in posture and from 0.9 to 0.5 in four more animals studied from 50 to 90 min from turning maneuver. The rate of change in At and Ab was similar in the two groups of animals and unaffected by the acquisition posture. AT decreased by 7.7 and 3.5% for the two groups, respectively, reflecting albumin clearance from the pleural space. The opposite time course of regional activities and the independence of their rate of change of the At/Ab ratio and of the animal posture suggest a top-to-bottom albumin transfer occurring through a bulk flow of liquid estimated at 0.006 ml.kg-1.h-1. The data are consistent with a measured vertical pleural liquid pressure gradient that does not reflect a hydrostatic condition.

Removal of pleural liquid and protein by lymphatics in awake sheep.

The contribution of the parietal pleural lymphatics to pleural liquid and protein removal is unclear. We asked two questions. What is the rate of removal of sterile, artificial hydrothoraxes in awake sheep? What percentage is removed through parietal pleural lymphatics? Three days after the placement of a rib capsule in 18 sheep, we instilled a 10 ml/kg 1.0 g/dl autologous protein solution with labeled albumin and erythrocytes through the capsule into the pleural space. Erythrocytes were used as a marker for lymphatic flow. We measured terminal pleural liquid volume and radioactivity at periods from 2 to 48 h. In three sheep, we obtained a third volume measurement at 6 h by the volume of dilution technique. We found that hydrothorax removal could be described by a linear function with a constant rate: 0.28 +/- 0.01 ml.kg-1.h-1 (mean +/- SE) for the grouped data, and 0.20, 0.28, and 0.31 ml.kg-1.h-1 for the individual sheep. At 24 h, erythrocyte clearance was 89 +/- 16% (mean +/- SD) that of liquid and albumin clearance. We conclude that in awake sheep with large hydrothoraxes, pleural liquid and protein are removed at a rate of 0.28 +/- 0.01 ml.kg-1.h-1 (mean +/- SE) and lymphatics are responsible for at least 89% of this removal.

Contribution of Starling and lymphatic flows to pleural liquid exchanges in anesthetized rabbits.

We studied the time course of volume and protein reabsorption of a 2-ml hydrothorax using whole (WP) or diluted (DP) homologous plasma injected into the right pleural cavity in anesthetized spontaneously breathing supine rabbits. Animals were killed at 5 (WP, n = 4; DP, n = 3), 36 (WP, n = 3; DP, n = 4), 55 (WP, n = 4), 90 (WP, n = 8; DP, n = 4), and 150 (WP, n = 4; DP, n = 5) min after the injection. The volume and protein content of the pleural liquid in control conditions (n = 12) amounted to 0.35 +/- 0.015 (SE) ml/kg and 1.8 +/- 0.27 g/100 ml, respectively, which are not significantly different at 90 min (n = 7). Pleural liquid volume decreased at a similar rate during WP or DP reabsorption according to the equation V = 0.84 +/- 0.05 X e-0.02t, with net reabsorptive flow expressed as dV/dt. The globulin quantity (Q) of the pleural liquid for WP and DP, respectively, decreased according to the equations Qwp = 1 + 1.5 X e-0.04t and Qdp = 0.7 + 0.6 X e-0.03t. Assuming a major lymphatic globulin clearance and no filtration into the cavity, we obtained lymph flow using the equation VL = dQ/dt X l/C where dQ/dt is calculated from the equations for Qwp and Qdp and C represents globulin concentration. The Starling flow (Vs) was then calculated by the equation Vs = dV/dt-VL. With increasing time, lymph flow was found to decrease progressively and was not significantly different from net flow with DP, which implied a Starling flow value of zero. During WP reabsorption, lymph flow initially exceeded the net flow, with the difference disappearing at approximately 60 min; accordingly, Starling filtration flow decreased progressively, becoming zero at the same time.

The effect of changing the contact surface area between pleural liquid and pleura on the turnover of pleural liquid.

To study the dynamics of pleural liquid, 250 ml of saline labeled with markers were injected into the pleural cavity of anesthetized dogs. For 3 h, liquid volume and concentration of these markers were measured. In a control group of dogs, the turnover rate of pleural liquid was 19.6 +/- 5.6 ml/min and lymphatic flow was 0.58 +/- 0.07 ml/min. In a group of pneumonectomized dogs, the turnover rate and lymphatic flow fell to about one fourth of those in the control group. When the left pulmonary artery was occluded, the turnover rate was halved, but lymphatic flow was not significantly different from that in the control group. These results suggest that the turnover rate of pleural liquid is dependent on the area of contact between pleural liquid and pleura and on the blood flow of the pleura. In addition, it appears that changes in pleural liquid volume are dependent on lymphatic flow.