Interstitial Fluid Space Research Articles

Distensibility of the Papaverine-induced Passive Vascular Bed in Dermis of Generalized Scleroderma

Passive distensibility of of the vascular bed in cutaneous tissue of the hand was examined in 7 normal persons and 15 patients suffering from generalized scleroderma of the acrosclerosis type. Paralysis of vascular smooth muscle cells was obtained by locally injected papaverine. Increase in vascular transmural pressure was induced by lowering the limb. Blood flow was estimated by the local Xenon wash-out technique. There was no significant difference between the patients and the normals in relative blood flow during lowering, when injection volumes of 0.005 and 0.02 ml were used, indicating that distensibility of the vascular bed in cutaneous tissue in generalized scleroderma is not diminished. However, in generalized scleroderma an injection volume of 0.1 ml caused a significant decrease in relative blood flow during lowering. This phenomenon observed in the patients probably reflects changes in total tissue pressure opposing distension of the vascular bed. This suggests an altered pressure-volume relationship of the interstitial fluid spaces in cutaneous tissue of generalized scleroderma.

Whole body transvascular filtration coefficient and interstitial space capacitance.

Infusion experiments with Ringer's solution were performed on 5 splenectomized dogs with continuous monitoring of blood volume and hematocrit. The plasma volume was calculated from these data and followed during the infusion and also during the recovery period. Applying electrical equivalent simulation analysis to the result of the plasma volume, the capacitance of the interstitial fluid space and the transvascular filtration coefficient of water in the whole body were determined simultaneously. The mean values of the capacitance and the coefficient were 5.91 ml/kg-mmHg and 0.314 ml/min-kg-mmHg, respectively. From this simulation study, a transfer function which predicts the fluid shift between the vascular system and the interstitial fluid space was also derived. Using the transfer function, predictions of the changes in plasma volume are possible from any given rate of infusion.

Effect of vascular, pleural, and alveolar pressures on filtration in isolated, perfused lobes of dogs

The vascular pressure ( Pvas), pleural pressure ( Pl), and alveolar pressure ( Palv), play an important role in determining the state of the lung. In this paper, we vary these pressures systematically to measure their effect on the rate of weight gain of the isolated perfused lung. As the lung's lymphatic system was ligated, this rate is taken as the rate of transvascular filtration, J f. Designating the change in J f when Pvas alone is lowered by 8 cmH 2O as 100%, we found the change in J f when all pressures are increased by 8 cmH 2O is 0 ± 2% and that when Palv is raised from 8 to 14 cmH 2O is −2 ± 5%. These results, together with the linear dependence of J f on Pvas and Pl, yield this empirical equation: J f = K( Pvas − Pl − A) where K and A are constants. The correlation of this equation with the Starling equation on transvascular filtration and the comparison of the mechanical equilibrium of the membrane surrounding fluid cuffs in the interstitia of the lung and that of the pleural membrane identify K as the filtration coefficient. and the interstitial fluid pressure in the lung closely approximates the pleural pressure for lungs undergoing moderate edema. The transmission of the pleural pressure to the interstitial fluid space is due to the action of the lung tissue and the surface tension. A similar dependence of J f on Pvas, Pl, and the tracheal pressure is found for alveolar edema.

THE RENAL FACTOR IN THE POST-TRAUMATIC “FLUID OVERLOAD” SYNDROME

Hypervolemia with hypertension often occurs 36-72 hours following massive blood and fluid replacement for hypovolemic shock. This syndrome of "fluid overload" has been attributed to the rapid intravascular flux of previously sequestered fluid in patients with impaired diuresis. This hypothesis was tested in 35 injured patients who received a mean of 9.3 L of blood and 17.4 L of salt during resucitation. The renal parameters measured soon after resuscitation included: 1) renal clearance of inulin (GFR), para-amino hippurate (ERPF), milliosmoles, sodium, and free water; 2) inulin space, renal vascular resistance (RVR), O2 consumption, renin, renal blood flow (RBF), and response to furosemide. Eighteen patients developed hypertension, hypervolemia, and respiratory insufficiency. When compared to the 17 normovolemic, non-hypertensive patients, the 18 hypervolemic patients had significantly increased RVR, with a significant decrease in RBF despite an increase in plasma volume and cardiac output. Furosemide produced less diuresis and natriuresis in the hypertensive patients. The balance between hypovolemia and "fluid overload" seemed percarious in the hypertensive patients. Peripheral renin and catecholamine levels were normal in both groups. Patients with post-traumatic "fluid overload" appear to have a combination of hypervolemia, respiratory insufficiency, hypertension, increased cardiac output, decreased extracellular fluid space, and decreased renal perfusion. These findings suggest that decreased interstitial fluid space compliance rather than "fluid overload" is the underlying factor leading to respiratory insufficiency. The therapeutic aspects of these findings are discussed.

Is capillary micropinocytosis of any significance for the transcapillary transfer of plasma proteins?

It has been repeatedly suggested that micropinocytosis plays a decisive role in the transfer of macromolecules across capillary walls. The evidence for this hypothesis is, however, only indirect. Thus physiological data (e.g. Carter et al. 1974, Renkin et al. 1974) cannot exclude that macromolecular transfer takes place by way of diffusion and/or filtration through e.g.“large pores” (cf. Landis and Pappenheimer 1963, Crone 1974). Ultramicroscopic pictures (e.g. Simionescu et al. 1973, 1975, Jennings and Florey 1967) no doubt illustrate uptake of macromolecular tracers within endothelial micropinocytotic vesicles, and their rapid appearance in the interstitial fluid space. It should be stressed, however, that such pictures cannot alone be taken as proof of any directed transendothelial vesicle passage and here opinions, also among experts on ultrastructure, seem to differ somewhat. The tracer appearance in the interstitial fluid may, for example, be the result of diffusion and/or filtration through nearby pores which, because they make out such a minor fraction of capillary walls, are very difficult to visualize. In fact, the ultrastructural pictures might rather illustrate e.g. an endothelial “phagocytotic activity”, of great importance in its own right but without relevance for “active”transcapillary passage.

Mechanisms for localization of radiopharmaceuticals in neoplasms

Localization of a radiopharmaceutical agent in a "tumor" is best conceptualized in terms of the altered regional physiology attendant to the presence of the "tumor". Such localization should be expected to occur in association with other disease states characterized by similar altered regional physiology. Neoplasms, areas of inflammation, and certain phases of infarct development are characterized by increased permeability of their capillary beds to macromolecules. This is largely due to neovascularization and the large intercapillary pores associated with new growth of capillary beds in these circumstances. Often, total perfusion to such lesions is increased in comparison to surrounding normal tissue. Thus, in all three clinical conditions, the entry of macro-molecules into the interstitial fluid space from the intravascular space is increased above that seen in normal tissue. Moreover, with neoplasms and inflammatory processes, there may be a delay in new lymphatic vessel growth adding to the residence time of the macromolecules in the interstitial fluid space. In all three conditions, the increased macrophage activity associated with tissue necrosis may result in ingestion of the labeled macromolecule by the macrophage. Pinocytosis may result in ingestion of the labeled macromolecule by other cells in the lesion, or there may be specific receptor sites on the cell membrane for the macromolecule, which may lead to fixation of the labeled macromolecule on the cell surface and possible intracellular translocation of the label itself. Radiolabeled macromolecules such as albumin, fibrinogen, or gamma globulins, and radionuclides that bind to macromolecules such as radiogallium, radioindium, and other radioelements, exhibit localizing behavior in tumors, inflammatory lesions, and during certain stages of infarcts. In the case of radiogallium and radioindium, the binding macromolecule is transferrin, and it is known that some cells have specific receptor sites for transferrin-bound iron on the cell membrane. It is possible that certain cells within these lesions have cell membrane receptor sites for radiogallium- and radioindium-labeled transferrin, and the cell erroneously accepts these radioelements from the transferrin in lieu of iron in attempting to engage in heme enzyme synthesis. Another mechanism that may be operative in the localization of agents in neoplasms, infarcts, and inflammatory lesions may be the altered cell permeability found in many cells of such lesions. It is known that many agents, such as supravital dyes, are excluded from entering normal cells by the selective permeability of normal cell membranes. When cell membrane permeability is altered, such as can be seen in traumatized, dying, or dead cells, the normally excluded agent may penetrate the abnormal cell membrane and bind, and consequently accumulate in intracellular constituents.

Age-related changes in ouabain pharmacology. Ouabain exhibits a different volume of distribution in adult and young dogs.

To better understand why one must administer much higher doeses of digitalis glycosides to immature than to mature humans and animals, we studied ouabain pharmacokinetics in adult and young dogs. Consistent with reported observations that ouabain-binding, metabolism, and excretion do not change with age, we found no significant differences in the transfer coefficients in a linear two-compartment open model for ouabain pharmacokinetics following a bolus of 0.05 mg/kg. We did find, however, that young dogs had nearly twice the ouabain volumes of distribution per kilogram of body weight as adults (155.4 +/- 1.2 (SE) ml/kg vs. 80 +/- 0.6, P less than 0.0005) and that one could account for this difference with the fact that young dogs had nearly twice the plasma volume 108 +/- 9.8, vs. 68 +/- 7.3, P = 0.001) and interstitial fluid space (318 +/- 35 vs. 190 +/- 6.5, P = 0.006) as the adults. For the same dose per kilogram, left and right ventricular ouabain concentrations were inversely related to the volume of distribution, with the adults having significantly higher tissue levels and incidence of arrhythmias. One must give more ouabain to a young dog to get the same plasma concentration as in an adult because the mass of ouabain in rapid equilibrium with the plasma is diluted in a larger volume of distribution.

Metabolism of 14C-histamine in amphibians (Bufo bufo) and reptiles (Pseudemys scripta and Testudo hermanni).

AbstractPressure‐volume characteristics of the interstitial fluid space in cat skeletal muscle were determined by plethysmographic recordings of the tissue volume changes following net capillary filtration or absorption. The concomitant changes in interstitial fluid pressure (Pif) were assessed by estimating the isovolumetric capillray pressure (Pci). In resting muscle Pci averaged 13.7 mni Hg during perfusion with blood, having an average colloid osmotic pressure of 18.3 mm Hg. As there is no net fluid exchange, these findings indicate a balancing filtration iorce of 4.6 mm Hg which is exerted chiefly by the colloid osmotic pressure of the tissue fluid (πif), with the possible contribution of a slightly subatmospheric Pif.A reduction of tissue fluid volume of 30 % led to a reduction of Pci of approximately 4 mm Hg, while doubling the volume raised Pci by 3–4 mm Hg. Since these Pci changes must be partly ascribed to alterations in πif, the actual changes in Pif were even smaller. The compliance of the interstitial fluid space in skeletal muscle is therefore high (above 1.4 ml/100 g tissue × mm Hg) within the normal range of Pif. The large extravascular fluid dept in skeletal muscle is thus easily mobilized to replenish the circulatory system when capillary pressure falls. as after a blood loss.

Regulation of interstitial fluid volume and pressure.

Recently the structure of the interstitial fluid spaces has been greatly clarified, and with the clarification has also come, we believe, a clear understanding of the mechanisms by which both interstitiel fluid volume and pressure are regulated.

Acceleration of renal hypertension accompanied by increase in plasma volume as a result of prior thoracic sympathectomy.

The renal pressor system exerts a dramatic effect on body fluid volumes when the thoracic sympathetic chains are removed in dogs. This effect was demonstrated in experiments designed originally to determine the influence of cardiac sympathectomy on the increase in cardiac output that precedes development of renal hypertension. While removal of the cardiac sympathetic nerve supply did not prevent the increase in cardiac output after wrapping one kidney in cellophane, a modest rise in blood pressure was accompanied by a remarkable 46 ± 8 (S.E.) % (p < 0.005) increase in plasma volume at the expense of interstitial fluid space. Removal of the contralateral kidney caused the appearance of malignant hypertension within 6 to 56 days while the plasma volume decreased somewhat though it remained well above control values. Unwrapping the kidney restored the blood pressure and fluid volumes to normal. Infusion of small dosage of angiotensin for 5 days into two other dogs after removal of the thoracic sympathetic chains had a similar effect on plasma volume; infusions were without effect prior to sympathectomy. The findings uncover an as yet unexplained interaction between the renal pressor and sympathetic nervous systems.

Tubular systems of Limulus myocardial cells investigated by use of electron-opaque tracers and hypertonicity

The transverse (T) tubules and sarcoplasmic reticulum (SR) of Limulus myocardium have been examined by infusing hearts with materials which either produce electron-opaque reaction products (horseradish peroxidase, cytochrome c) or which are inherently electron opaque (colloidal thorium dioxide and lanthanum hydroxide). The thick basal lamina of the heart cells is a barrier to the penetration of peroxidase and thorium dioxide. Cytochrome c infiltrates the heart poorly, its farthest penetration being evidenced by reactive sites in the walls of the T tubules. However, lanthanum hydroxide readily fills both intercellular spaces and transverse tubules. There is very close apposition of the SR with the sarcolemma and T tubules. However, there is no penetration of exogenous material into the lumina of the SR; that is, the SR is not continuous with the interstitial fluid space. Therefore, the tubular systems of this invertebrate myocardium are similar in this respect to those of mammalian ventricular muscle. In confirmation of this, whereas many of the T tubules swell, in hypertonic solution the SR shrinks from an average luminal diameter of 460 A to 320 A. An estimate of the fractional SR volume is 11%, which is considerably greater than values given for mammalian myocardial cells.

Implanted tissue cages—A study in rabbits

Summary Tissue cages of various designs have been implanted subcutaneously in 50 rabbits. The pressure within the cages was always found to be sub-atmospheric at 1 month after implantation and as late as 1 year afterwards. The pressure within the cage could be altered by local external pressure and by general plasmophoresis. The protein content of the cage fluid was found to be less than half that of serum while the chloride was higher and the potassium lower. Sodium, urea, bicarbonate and pH were identical in the two fluids. When labelled albumin a larger molecule and antibiotics were injected intravenously they could be recovered from cage fluid, indicating that such fluid was in continuity with the general interstitial fluid space. Microscopically, cages were lined with an open weave of collagen containing tissue spaces and blood vessels, in contrast to the dense avascular tissue around a solid implant. The above findings suggest strongly that the fluid within a cage is interstitial fluid and representative of the general body interstitial fluid.

Interstitial fluid pressure. 3. Its effect on resistance to tissue fluid mobility.

The resistance to fluid mobility in the interstitial fluid spaces has been measured between perforated catheters inserted into the subcutaneous abdominal tissues of the dog and between perforated capsules implanted in the tissues 1 month previously. When the pressures in the catheters or perforated capsules were less than atmospheric pressure, the resistance to fluid movement was almost infinite, but when the pressures were increased almost to or above atmospheric pressure the resistance usually decreased more than 100,000-fold, indicating a suddenly increased size of the tissue spaces. The shape of the pressure-volume curve relating (a) interstitial fluid pressure to (b) volume of mobile interstitial fluid was calculated from pressure-conductance curves recorded in these experiments. On comparing this pressure-volume curve with a previously measured pressure-volume curve of the entire interstitial fluid compartment, two important points were observed: first, both curves exhibit a sudden increase in volume when the interstitial fluid pressure rises above atmospheric pressure. Second, the mobile interstitial fluid volume approaches zero when the interstitial fluid pressure falls below atmospheric pressure while the measured volume is still very great. It is postulated that this difference is caused by entrapment of large amounts of water in a relatively immobile state in the gelatinous matrix of the ground substance filling the interstitial spaces.

Fine structure of the surface of mouse hepatic cells.

AbstractMouse hepatic cells appear in thin sections as polygons with six or more sides. The plasma membrane covering these sides may contact either bile canaliculi, the narrow intercellular space, the space of Disse or extensions of the space of Disse between adjacent cells. The plasma membrane covering microvilli in bile canaliculi and the space of Disse is thicker than that in contact with the narrow intercellular space. Bile canaliculi, which contact about 6% of the perimeter of each cell, are each separated by tight junctions from the narrow intercellular space. This space contacts more than one‐half the perimeter of each cell and is about 220 Å in width. It is continuous around the occasional studlike junctions which occur, but is interrupted at frequent intervals by circumscribed tight junctions, and occasionally by desmosomes. The narrow intercellular space is in free communication through the space of Disse with the plasma space. An interstitial fluid space, separate from the plasma space, does not occur in the liver lobule. Protein molecules from plasma enter hepatic cells in both coated and pinocytotic vesicles. These vesicles are derived from invaginations of the plasma membrane that borders the narrow intercellular space and the spaces between microvilli in the space of Disse. Pinocytotic vesicles may also incorporate fat droplets into hepatic cells.

A mathematical and physiological model for early distribution of radioiodide in man

A model is proposed for the early distribution of radioiodide in man. This model is formalized as a set of eight simultaneous differential equations, each predicting the rate of change of radioiodide in a compartment. These equations have been fitted by numerical integration on a digital computer to plasma curves from sessions with and without aspiration of gastric contents, curves of the aspirated radioiodide, and thyroidal and renal plasma clearance rates. In this model, plasma radioiodide is distributed reversibly to the erythrocytes, interstitial fluid (space E) and a “slowly diffusible space” (space C). Distribution to the thyroid and kidney is irreversible. Radioiodide distributed to the salivary glands and gastric mucosa must pass through a gastrointestinal cycle before eventual reabsorption from the intestine. Successive compartments of this cycle are the “inaccessible gastric space” (space M), free gastric juice (space S) and the intestine (space D). All of the modes of distribution mentioned are governed by rate constants except for transfer from space S to space D, which occurs as a complete transfer at a fixed interval tau. gastrointestinal iodide cycle; pooling of radioiodide in gastrointestinal tract; plasma radioiodide curve; multicompartment model; iterative solution of mathematical model Submitted on September 28, 1964

INTERSTITIAL FLUID PRESURE. II. PRESSURE-VOLUME CURVES OF INTERSTITIAL SPACE .

Pressure-volume curves of the interstitial fluid spaces were estimated using four different methods. Interstitial fluid pressure was measured from implanted perforated capsules while interstitial fluid volume was varied (a) by perfusing the isolated hind limb of the dog with several types of fluid and at different perfusion pressures, (b) by elevating the venous pressure so that fluid would transude into the interstitial compartment, (c) by infusing large quantities of Tyrode's solution into the whole animal, and (d) by intravenous infusion of concentrated dextran solution. In all these studies, the compliance of the interstitial fluid system was found to be very low when the interstitial fluid pressure was negative but very high when the pressure rose slightly above atmospheric pressure. A physical model of the interstitial spaces was also constructed. Pressure-volume curves recorded from this model demonstrated a pattern of compliance changes similar to that shown by the interstitial pressure-volume curves recorded from dogs. These experiments give further support to the concept that the interstitial fluid pressure is normally negative but becomes positive as edema fluid accumulates.

Changes in the volume of the plasma, interstitial and intracellular fluid spaces during hydration and dehydration in normal and edematous subjects

Changes in the volume of the plasma, interstitial and intracellular fluid spaces during hydration and dehydration in normal and edematous subjects