PubMed Health⌕ Search

Biomedical subjects

M F Flessner

Publications and source records attributed to M F Flessner.

51 records · Page 3Linked to original sources

Net acid transport by isolated perfused inner medullary collecting ducts.

The isolated perfused tubule technique was used to study net acid transport in rat terminal inner medullary collecting duct (IMCD) segments. The stop-flow luminal pH [measured fluorometrically with the acidic form of the pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein in the lumen] fell 0.35 units below the bath pH in tubules from control rats and 0.53 units below the bath in tubules from deoxycorticosterone-treated rats. Tubules from control rats absorbed bicarbonate and secreted ammonium against concentration gradients, although at low rates. In control rats, 10(-8) M vasopressin added to the bath increased bicarbonate absorption almost threefold. Treatment of rats in vivo with deoxycorticosterone significantly increased the rate of bicarbonate absorption in vitro. In vivo NH4Cl loading also significantly increased bicarbonate absorption. Staining microdissected tubules with acridine orange confirmed that the perfused segments lacked intercalated cells. We conclude that the terminal IMCD spontaneously acidifies the lumen despite an absence of intercalated cells. Bicarbonate absorption appears to be regulated by the same factors that affect net acidification in other collecting duct segments.

Absorption↗

Ammonium transport in collecting ducts.

In vivo studies have shown that ammonium is secreted into the lumen of each of the major collecting duct segments. This secretion occurs by passive diffusion of NH3 in parallel with active H+ secretion. In vitro measurements in each segment have established that the NH3 permeability is relatively high (10(-3) to 10(-2) cm/s) while the NH4+ permeability is essentially zero. Interstitium to lumen NH3 concentration gradients have been observed in vivo in the inner medulla and are presumed to exist in other segments. The active H+ secretion causes a pH disequilibrium in segments which lack carbonic anhydrase and enhances the NH3 gradient driving NH3 secretion by decreasing the luminal NH3 concentration. The low NH4+ permeability prevents NH4+ backflux.

Ammonia↗

Exchange of macromolecules between peritoneal cavity and plasma.

The exchange of fluorescein isothiocyanate-labeled dextrans ranging in weight-averaged molecular weight from 19,400 to 160,000 and 125I-bovine serum albumin (BSA) between dialysis fluid (5% BSA in Krebs-Ringer solution) in the peritoneal cavity and the plasma was studied in anesthetized female Sprague-Dawley rats. Plasma and peritoneal samples were collected for 3-4 h after either 1) an intraperitoneal injection of dialysis fluid with tracer or 2) an intravenous injection of tracer material simultaneously with an intraperitoneal injection of dialysis solution without tracer. Analysis of the data by means of a mathematical model of the transport process suggests a functional asymmetry in transport of large molecules across the blood capillary wall. Substances injected intravenously have a net transport from the blood capillaries to the peritoneal cavity. Substances of molecular weight greater than or equal to 39,000 transport from the cavity to the plasma via peritoneal lymphatics; 19,400 molecular-weight dextran transports from the cavity to the plasma primarily via lymphatics with some blood capillary uptake. Tissue diffusivities and capillary mass transport coefficients are derived for the substances tested.

Animals↗

Peritoneal absorption of macromolecules studied by quantitative autoradiography.

Transport experiments of 125I-human serum albumin from the peritoneal cavity to the plasma were conducted in 200-g female rats. Blood and peritoneal samples were collected at intervals over 2-3 h. After death and rapid freezing of the animal, transverse sections were cut in a cryomicrotome from several tissues surrounding the peritoneal cavity, and the distribution of the labeled albumin was measured by computerized quantitative macroautoradiography. Tissue concentrations (counts/min per wet tissue wt) in parietal tissues (anterior abdominal wall and the diaphragm) were relatively constant versus distance from the peritoneum and represented a large fraction (0.5-1.0) of the concentration in the peritoneal cavity. Fractional concentrations in visceral tissues (liver, stomach, intestine) decreased from 0.20-0.35 at the peritoneal surface to 0.03-0.06 at a distance of 900 micron from the peritoneum. Uterine tissue concentrations lay between those of the parietal tissues and those of the viscera. The data are related to mechanisms of interstitial and lymphatic transport in these tissues.

Abdominal Muscles↗

A distributed model of peritoneal-plasma transport: analysis of experimental data in the rat.

Transport of uncharged, water-soluble substances (ranging in molecular weight from 180 to 5,000) between the fluid in the peritoneal cavity and plasma was studied in anesthetized female Sprague-Dawley rats. In certain experiments the effect of fluid shifts on the transport was observed by manipulating the effective osmotic pressure or the hydrostatic pressure of the dialysis fluid. Parameters for the distributed model outlined in previous work were obtained from the experimental data for the substances tested. Capillary membrane transport was modeled by pore theory. A single pore radius of 40 A and a pore density of 600 cm-2 were satisfactory. Tissue diffusivities for these substances were found to correspond closely to those in the literature. Additional simulations were performed with a three-compartment model and the results were compared with those of the distributed model.

Animals↗

A distributed model of peritoneal-plasma transport: tissue concentration gradients.

Peritoneal dialysis transport studies were carried out in anesthetized rats. Injections of [14C]EDTA were made by intravenous bolus or intraperitoneal dialysis solution, and blood and peritoneal fluid samples were collected for 1 h. After death and rapid freezing of the animal, transverse sections through the abdominal cavity were cut for quantitative macroautoradiography. The plasma-to-peritoneal transport experiments with a clinical dialysis solution resulted in essentially horizontal concentration profiles versus distance in all tissues except large intestine. Estimates of the extracellular tissue fraction were: small intestine, 0.34; large intestine, 0.28; stomach, 0.30; uterus, 0.66; liver 0.35; diaphragm, 0.16; and anterior abdominal wall, 0.15. Similar experiments with an isotonic salt solution resulted in larger (13-300%) extracellular fractions in all tissues. In contrast, peritoneal-to-plasma transport studies demonstrated decreasing concentration profiles in all visceral tissues, with the first 90% of the gradient contained in the initial 400 micron of tissue from the peritoneum. Parietal tissue gradients were less steep and had higher concentration levels deep within the tissue than visceral tissues. Computer simulations using a distributed model approach compared favorably with the experimental measurements and established the validity of this approach.

Animals↗

A distributed model of peritoneal-plasma transport: theoretical considerations.

Transport of water-soluble substances between the peritoneal cavity and the plasma was modeled with a distributed approach. The model includes diffusion and convection through tissue as well as membrane transport across blood capillaries, which are assumed to be distributed uniformly in the tissue. Lymphatic uptake via the diaphragm is also included. Transport in the remainder of the body is modeled by a system of compartments. The resulting system of mass balances and rate equations is solved numerically to provide predictions of peritoneal volume and concentrations in plasma, peritoneal fluid, and tissue surrounding the cavity. The model sensitivity is explored by varying key parameters to determine whether the changes would have a significant effect on model output. Key parameters include peritoneal surface area, tissue diffusivity, capillary permeability, tissue void fraction, and hydrostatic and osmotic pressures in the capillaries and interstitium.

Absorption↗

Peritoneal lymphatic uptake of fibrinogen and erythrocytes in the rat.

Intact and thoracic duct-cannulated rats were dialyzed at various intraperitoneal pressures with 5% bovine serum albumin solutions containing 125I-fibrinogen or 51Cr-erythrocytes. Lymphatic transport rates were calculated from the mass of tracer passing into the plasma space as function of tracer concentration in the peritoneal fluid during dialysis periods ranging between 143 and 360 min. Peritoneal protein concentrations were constant over the duration of the experiments. The calculated lymph flow rate was independent of intraperitoneal pressure and in intact rats averaged 2.85 +/- 1.22 microliters/min for uptake of 125I-fibrinogen and 2.60 +/- 1.17 for uptake of 51Cr-erythrocytes. However, the observed fluid loss rates from the peritoneal cavity were sensitive to the intraperitoneal pressure and were 5 to 20 times the calculated lymph flow rate. Mass balance experiments in two rats dialyzed with 125I-fibrinogen indicated that a significant proportion (28%) of tracer leaving the peritoneal cavity is absorbed by the anterior muscle wall of the abdomen and is probably trapped there because of its large molecular weight. Results from 125I-fibrinogen and 51Cr-erythrocyte uptake experiments both indicated that only approximately 30% of the total lymphatic drainage of the peritoneal cavity passes through the thoracic duct in rats.

Animals↗

Concentration-dependent disappearance of fluorouracil from peritoneal fluid in the rat: experimental observations and distributed modeling.

The rate of disappearance of fluorouracil from peritoneal fluid has been experimentally measured and mathematically modeled. The experimental data were obtained following the instillation of 50 ml of dialysis fluid which contained an initial fluorouracil concentration ranging from 24 microM to 12 mM. The rate of disappearance was strongly dependent upon concentration. A distributed model has been formulated which incorporates concepts of diffusion with saturable metabolism and nonsaturable capillary uptake in the tissue surrounding the peritoneal fluid. This model successfully describes the experimental observations and also suggests that the effective penetration depth into tissue is highly dependent upon concentration.

Animals↗

Computerized kinetic modeling: a new tool in the quest for adequacy in peritoneal dialysis.

Until recently, kinetic modeling of peritoneal dialysis (PD) was performed by engineers, scientists, or nephrologists at major teaching institutions. Now there are several "user-friendly" computer programs which permit the practicing nephrologist and dialysis staff to monitor adequacy of the individual PD patient and to optimize the dialysis prescription. In this brief article, the capabilities, methods, and data requirements of three programs are reviewed, and specific recommendations for the selection of a particular program are discussed.

Computer Simulation↗