Fluid loss from the peritoneal cavity by back-filtration through the small pores of the three-pore model.

The partitioning of fluid flows among small and ultrasmall pores of the three-pore model in peritoneal dialysis has been traditionally assessed using 4-hour dwells with 3.86% glucose solutions. Under these conditions, however, back-filtration through small pores has been hard to demonstrate. As nicely shown by Asghar and Davies, however, the use of low-concentration (1.36%) glucose-based solutions allows accurate studies of the partitioning of fluid flows from the peritoneal cavity under conditions of fluid loss.

Glomerular sieving of three neutral polysaccharides, polyethylene oxide and bikunin in rat. Effects of molecular size and conformation.

AIM: Polysaccharides and many other non-protein polymers generally have a more open, flexible and asymmetrical structure compared with globular proteins. For a given molecular weight (MW), the Stokes-Einstein radius (a(e)) of the following polymers increases in the order: Ficoll < dextran

Effects of glomerular filtration rate on Ficoll sieving coefficients (theta) in rats.

The purpose of the present study was to assess the role of diffusion and convection during filtration of Ficoll across the glomerular filter by comparing glomerular sieving coefficients (theta) to neutral fluorescein isothiocyanate (FITC)-Ficoll 70/400 obtained at low (hydropenic) vs raised (normal) glomerular filtration rates (GFRs). The theta for FITC-Ficoll was determined in anesthetized Wistar rats (304 +/- 18 g) following laparotomy and cannulation of the ureters, used for urine sampling. After surgery, GFR was 1.2 +/- 0.16 ml/min (+/- s.e.), assessed using the plasma to urine clearance of FITC-inulin and (51)Cr-ethylenediaminetetraacetic acid. FITC-Ficoll 70/400 was infused intravenously (i.v.) following an initial bolus dose. To raise GFR, to an average of approximately 2 ml/min, 5 ml of serum together with glucagon (3 microg/min) was given i.v. FITC-inulin and FITC-Ficoll were determined in plasma and urine using size-exclusion high-performance liquid chromatography. The theta for Ficoll as a function of Stokes-Einstein radius was significantly reduced in the range of 13-43 A when GFR was raised. The maximal theta lowering effect, in relative terms, of raising GFR was obtained for a Ficoll a(e) of approximately 32 A. For Ficoll(36 A) (cf. albumin), theta was reduced from 0.111+/- 0.009 to 0.081+/- 0.012 (P < 0.05; n = 7) for the GFR increment imposed. The reduction in theta for Ficoll after raising GFR indicates the presence of a high diffusive component of glomerular Ficoll filtration in rats in vivo and contradicts the notion of a significant concentration polarization effect in the glomerular filter upon Ficoll molecules < 50 A in radius.

The peritoneal microcirculation in peritoneal dialysis.

This paper deals with the peritoneal microcirculation and with peritoneal exchange occurring in peritoneal dialysis (PD). The capillary wall is a major barrier to solute and water exchange across the peritoneal membrane. There is a bimodal size-selectivity of solute transport between blood and the peritoneal cavity, through pores of radius approximately 40-50 A as well as through a very low number of large pores of radius approximately 250 A. Furthermore, during glucose-induced osmosis during PD, nearly 40% of the total osmotic water flow occurs through molecular water channels, termed "aquaporin-1." This causes an inequality between 1 - sigma and the sieving coefficient for small solutes, which is a key feature of the "three-pore model" of peritoneal transport. The peritoneal interstitium, coupled in series with the capillary walls, markedly modifies small-solute transport and makes large-solute transport asymmetric. Thus, although severely restricted in the blood-to-peritoneal direction, the absorption of large solutes from the peritoneal cavity occurs at a high clearance rate ( approximately 1 mL/min), largely independent of molecular radius. True absorption of macromolecules to the blood via lymphatics, however, seems to be occurring at a rate of approximately 0.2 mL/min. Several controversial issues regarding transcapillary and transperitoneal exchange mechanisms are discussed in this paper.

Steady-state pleural fluid flow and pressure and the effects of lung buoyancy.

Both theoretical and experimental studies of pleural fluid dynamics and lung buoyancy during steady-state, apneic conditions are presented. The theory shows that steady-state, top-to-bottom pleural-liquid flow creates a pressure distribution that opposes lung buoyancy. These two forces may balance, permitting dynamic lung floating, but when they do not, pleural-pleural contact is required. The animal experiments examine pleural-liquid pressure distributions in response to simulated reduced gravity, achieved by lung inflation with perfluorocarbon liquid as compared to air. The resulting decrease in lung buoyancy modifies the force balance in the pleural fluid, which is reflected in its vertical pressure gradient. The data and model show that the decrease in buoyancy with perfluorocarbon inflation causes the vertical pressure gradient to approach hydrostatic. In the microgravity analogue, the pleural pressures would be toward a more uniform distribution, consistent with ventilation studies during space flight. The pleural liquid turnover predicted by the model is computed and found to be comparable to experimental values from the literature. The model provides the flow field, which can be used to develop a full transport theory for molecular and cellular constituents that are found in pleural fluid.

Transport asymmetry in peritoneal dialysis: application of a serial heteroporous peritoneal membrane model.

The transport of macromolecules during peritoneal dialysis is highly selective when they move from blood to dialysate but nearly completely unselective in the opposite direction. Aiming at describing this asymmetry, we modeled the peritoneal barrier as a series arrangement of two heteroporous membranes. First a three-pore membrane was considered, crossed by small [radius of the small pore (r(s)) approximately 45 A], large [radius of the large pore (r(L)) approximately 250 A], and transcellular pores accounting for 90, 8, and 2% to the hydraulic conductance, respectively, and with a corresponding pore area over diffusion distance (A(0)/Delta x) set to 50,000 cm. We calculated the second membrane parameters by fitting simultaneously the bidirectional clearance of molecules ranging from sucrose [molecular weight = 360, permeating solute radius (a(e)) approximately 5 A] to alpha(2)-macroglobulin (molecular weight = 820,000, a(e) approximately 90 A). The results describe a second two-pore membrane with very large pores (r(L) approximately 2,300 A) accounting for 95% of the hydraulic conductance, minor populations of small (r(s) approximately 67 A) and transcellular pores (3 and 2%, respectively), and an A(0)/Delta x approximately 65,000 cm. The estimated peritoneal lymph flow is approximately 0.3 ml/min. The two membranes can be identified as the capillary endothelium and an extracellular interstitium lumped with the peritoneal mesothelium.

Respiratory mechanics after 180 days space mission (EUROMIR'95).

The present study reports data on respiratory function of lung and chest wall following the 180 days long European - Russian EuroMir '95 space mission. Data reported refer to two subjects studied before the mission, on day 9 and 175 in flight and on days 1, 10, 12, 27 and 120 after return. In-flight vital capacity (VC) and expiratory reserve volume (ERV) were similar to those in supine posture, namely approximately 5% and approximately 30% less than in sitting posture. On day 1 after return, VC was reduced by approximately 30% in both postures. This reflected a decrease in ERV (approximately 0.5 L) and in IC (inspiratory capacity, approximately 1.7 L) that could be attributed to a marked weakening of the respiratory muscles. Regain of normal preflight values barely occurred 120 days after return. Post-flight pressure-volume curves of the lung, chest wall and total respiratory system are equal to preflight ones. The pressure-volume curve of the lung in supine posture is displaced to the right relative to sitting posture and shows a lower compliance. As far as the lung in-flight condition resembles that occurring in supine posture, this implies a lower compliance, a greater amount of blood in the pulmonary microvascular bed, a more homogeneous lung perfusion and therefore a greater microvascular filtration rate towards lung interstitium.

A semiautomatic procedure for edge detection of in vivo pulmonary microvessels and interstitial space.

OBJECTIVE: To develop an algorithm to detect the edges between lung tissue, perivascular interstitium, and microvessel using digital processing of in vivo microscopic images of lung surface. METHODS: A numerical technique was developed to identify three different regions (namely, pulmonary microvessel, perivascular interstitium, and lung tissue) based on their corresponding gray level distributions. We present a theoretical demonstration of the method and a semiautomatic procedure that, once the edges are detected, determines microvascular diameters and perivascular interstitium thickness. RESULTS: Microvessel diameters and perivascular interstitium thickness were calculated for precapillary arteriolar branching (40 to 140 microns) and saved in an ASCII file. CONCLUSIONS: We proved that the maximum value of the moving variance is useful to detect the edge between two adjacent regions whose gray level distributions satisfy the condition: magnitude of sigma Y2 - sigma X2 < or = (mu X - mu Y)2, where mu X, mu Y, sigma X2, sigma Y2 are the statistical moments of the two regions X and Y. Moreover, when the regions have similar means, the above conditions is not met, but the edge between them can be detected by the maximum of the moving variance error.

Estimation of in vivo pulmonary microvascular and interstitial geometry using digital image analysis.

OBJECTIVE: To determine microvascular diameter and perivascular interstitium thickness at the lung surface in the in situ, in vivo lung. METHODS: Microscopic images of the lung surface collected through a "pleural window" by a videocamera were digitized with a monochrome frame grabber (512 x 512 pixels, 8 bits per pixels) to be computer analyzed by image processing techniques. RESULTS: We found that the maxima in the distribution of the standard deviations of gray levels in adjacent neighbors 7 x 7 pixels wide identify the edges between the microvessel lumen and the surrounding perivascular interstitium. Furthermore, the maxima in the distribution of the standard deviation of the standard deviations of gray levels identify the edges between the perivascular interstitium and the lung tissue. CONCLUSIONS: This technique can be applied to microvessels ranging in diameter from 30 microns to 200 microns and perivascular interstitial thickness of the order of 10-150 microns. Our approach allows for the definition of microvascular geometry even for noisy images and represents an improvement compared to other edge detection methods. The proposed analytical procedure may provide a useful tool to study lung fluid balance and microvascular reactivity in the in situ lung in the normal state and in response to a variety of functional conditions.

Permeability of parietal pleura to liquid and proteins.

The permselectivity of the parietal pleura was determined in spontaneously breathing anesthetized rabbits and dogs. In rabbits, we injected intrapleurally 5 ml of 1-g/dl albumin solution containing 100 microCi of 131I-labeled albumin plus 100 microCi of either lactate dehydrogenase (LDH) or alpha 2-125I-macroglobulin. Dogs received 100 ml of 1-g/dl albumin solution containing 100 microCi of 131I-albumin plus 100 microCi of alpha 2-125I-macroglobulin. A transpleural pressure gradient was set, lowering the intracapsular pressure to -30 cmH2O. The solvent drag reflection coefficients (sigma f) were calculated as the ratio between tracer concentrations in capsular and pleural liquid collected at 60-180 min. In rabbits sigma f was 0.44 +/- 0.2 (SD) for albumin, 0.84 +/- 0.1 for LDH, and 0.93 +/- 0.05 for alpha 2-macroglobulin. In dogs sigma f was 0.30 +/- 0.19 for albumin and 0.53 +/- 0.15 for alpha 2-macroglobulin. The hydraulic conductivity of the parietal pleura was 2.18 +/- 1.54 microliters.h-1.cmH2O-1.cm-2 in rabbits and 1.22 +/- 1.13 microliters.h-1.cmH2O-1.cm-2 in dogs. The parietal pleura could be modeled by two pore populations with radii of 83-89 and 156-222 A. The permeability coefficient averaged 0.08-0.21 x 10(-6) cm/s for albumin, 0.06-0.09 x 10(-6) cm/s for LDH, and 0.01-0.03 x 10(-6) cm/s for alpha 2-macroglobulin.

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.

Fluid exchanges across the parietal peritoneal and pleural mesothelia.

In 31 anesthetized rabbits, after removal of superficial tissues, glass micropipettes filled with 0.5 M NaCl solution and connected to an electrohydraulic servo-null system were used to measure extraperitoneal interstitial fluid pressure (Pi,per) and peritoneal liquid pressure (Pliq,per) at various heights. Linear regressions relating pressure to recording height (H) were Pi,per = 1.07 - 0.27H and Pliq,per = 0.9 - 0.64H, respectively. Protein concentration (Cp;g/dl) and colloid osmotic pressure (II; cmH2O) of plasma and of peritoneal and pleural liquids were 5.48 +/- 0.38 and 24.61 +/- 3.23, 3.07 +/- 0.5 and 13.29 +/- 1.87, and 1.76 +/- 0.42 and 8.45 +/- 2, respectively. The equation relating II to Cp was II = 4.64Cp + 0.0027Cp2. Tissue fluid samples were collected with saline-soaked wicks implanted in vivo or dry wicks inserted postmortem in extraperitoneal and extrapleural interstitial spaces. After 60 and 15 min, respectively, wicks were withdrawn and centrifuged; wick fluid was analyzed in colloid osmometer for small samples. Average extraperitoneal and extrapleural II values were 14.2 +/- 2.49 and 11.94 +/- 1.52 cmH2O, corresponding to Cp of 3.07 and 2.57 g/dl, respectively. The average net pressure gradient, assuming reflection coefficient and hydraulic conductivity (Negrini et al. J. Appl. Physiol. 69: 625-630, 1990; 71: 2543-2547, 1991), was 1.18 and 0.98 cmH2O for parietal peritoneal and pleural mesothelia, respectively, favoring filtration from the extraserosal interstitia into the serosal cavities. Total parietal peritoneal filtration was 1.49 ml.kg-1.h-1, approximately 15-fold higher than that for pleural mesothelium.

Pulmonary interstitial pressure in intact in situ lung: transition to interstitial edema.

In anesthetized rabbits (n = 25) subject to slow intravenous saline loading (0.4 ml.min-1.kg-1) for 3 h, we measured pulmonary interstitial pressure (Pip) in intact in situ lungs with glass micropipettes inserted directly into the lung parenchyma via a "pleural window." Measurements were done in apneic animals at the end-expiratory volume with O2 delivered in the trachea. Pip was -10 +/- 1.5 (SD) cmH2O in control and increased to 0.6 +/- 3.8 and 5.7 +/- 3.3 cmH2O at 66 and 180 min, respectively. The wet-to-dry weight ratio (W/D) of the lung was 5.04 +/- 0.2 in the control group and 5.34 +/- 0.7 at 180 min (+6%); the corresponding W/D for intercostal muscles were 3.25 +/- 0.03 and 4.19 +/- 0.5 (+28%). Pulmonary interstitial compliance was 0.47 ml.mmHg-1.100 g wet wt-1. Pulmonary arterial and left atrial pressures were 18.4 +/- 2 and 3 +/- 1 cmH2O in control and increased to 19.5 +/- 2.9 and 4.6 +/- 1.7 cmH2O at 180 min, respectively. Aortic flow (cardiac output) increased from 103 +/- 35 to 131 +/- 26 ml/min; pulmonary resistance fell from 0.17 +/- 0.06 to 0.14 +/- 0.05 cmH2O.min.ml-1 (-18%), suggesting that the increase in Pip did not limit blood flow. The pulmonary capillary-to-interstitium filtration pressure gradient decreased sharply from a control value of 10 cmH2O to 0 cmH2O within 60 min because of the increase in Pip and remained unchanged for < or = 180 min. Data suggest that the pulmonary interstitial matrix can withstand fluid pressures above atmospheric, preventing the development of pulmonary alveolar flooding.

Intrapleural fluid movements described by a porous flow model.

We injected technetium-labeled albumin (at a concentration similar to that of the pleural fluid) in the costal region of anesthetized dogs (n = 13) either breathing spontaneously or apneic. The decay rate of labeled activity at the injection site was studied with a gamma camera placed either in the anteroposterior (AP) or laterolateral (LL) projection. In breathing animals (respiratory frequency approximately 10 cycles/min), 10 min after the injection the activity decreased by approximately 50% on AP and approximately 20% on LL imaging; in apneic animals the corresponding decrease in activity was reduced to approximately 15 and approximately 3%, respectively. We considered label translocation from AP and LL imaging as a result of bulk flows of liquid along the costomediastinal and gravity-dependent direction, respectively. We related intrapleural flows to the hydraulic pressure gradients existing along these two directions and to the geometry of the pleural space. The pleural space was considered as a porous medium partially occupied by the mesh of microvilli protruding from mesothelial cells. Solution of the Kozeny-Carman equation for the observed flow velocities and pressure gradients yielded a mean hydraulic radius of the pathways followed by the liquid ranging from 2 to 4 microns. The hydraulic resistivity of the pleural space was estimated at approximately 8.5 x 10(5) dyn.s.cm-4, five orders of magnitude lower than that of interstitial tissue.

In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma.

Reflectance spectrophotometry from 420 to 780 nm on 31 primary melanoma and 31 benign nevi has been performed by using an external integrating sphere coupled to a spectrophotometer. Measurements show that reflectance spectra of melanoma and nevi manifest dissimilar patterns. From these spectra four variables, whose physical and/or physiological meanings remain to be investigated, have been derived. All of them are significantly different when compared between melanoma and nevi. A discriminant function between the two groups of lesions has been determined by using a stepwise discriminant analysis, resulting in a test with a sensitivity of 90.3% and a specificity of 77.4%. This method of discrimination between melanoma and nevi seems to have a discriminating power almost equal to that of a clinical judgement from a specialized medical doctor, thus suggesting a new method for screening skin pigmented lesions.

In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions--I. Reflectance measurements.

Reflectance spectrophotometry from 400 to 800 nm on different cutaneous pigmented lesions, including primary and metastatic malignant melanoma, pigmented nevi, lentigo and seborrhoeic keratosis, has been performed by using an external integrating sphere coupled to a spectrophotometer. Measurements show that reflectance spectra of the different lesions manifest dissimilar patterns, particularly in the near IR region. Comparison of reflectance of nevi with that of malignant melanomas results in a highly significant difference (P less than 10(-6)) between the two samples. Though interpretation of the spectra remains difficult as a result of the complexity of the optical processes of scattering and absorption, our results suggest that a detailed analysis of the reflectance spectrum may give clinically useful information, and could be utilized as an aid in clinical diagnosis of cutaneous pigmented lesions, especially where malignant melanoma is concerned.