Quantitative interrelationship between Gibbs-Donnan equilibrium, osmolality of body fluid compartments, and plasma water sodium concentration.

The presence of negatively charged, impermeant proteins in the plasma space alters the distribution of diffusible ions in the plasma and interstitial fluid (ISF) compartments to preserve electroneutrality. We have derived a new mathematical model to define the quantitative interrelationship between the Gibbs-Donnan equilibrium, the osmolality of body fluid compartments, and the plasma water Na+ concentration ([Na+]pw) and validated the model using empirical data from the literature. The new model can account for the alterations in all ionic concentrations (Na+ and non-Na+ ions) between the plasma and ISF due to Gibbs-Donnan equilibrium. In addition to the effect of Gibbs-Donnan equilibrium on Na+ distribution between plasma and ISF, our model predicts that the altered distribution of osmotically active non-Na+ ions will also have a modulating effect on the [Na+]pw by affecting the distribution of H2O between the plasma and ISF. The new physiological insights provided by this model can for the first time provide a basis for understanding quantitatively how changes in the plasma protein concentration modulate the [Na+]pw. Moreover, this model defines all known physiological factors that may modulate the [Na+]pw and is especially helpful in conceptually understanding the pathophysiological basis of the dysnatremias.     

Chemical composition of seminal and ovarian fluids of chinook salmon (Oncorhynchus tshawytscha) and their effects on sperm motility traits

The relationships between the compositions of ovarian, seminal fluids and sperm function are not well known in teleostean fish species. The objective of the present study was to determine the concentration of the major inorganic ions (Na(+), K(+), Ca(2+), Mg, Cl(-)), osmolality, and pH of ovarian and seminal fluid of sexually mature chinook salmon (Oncorhynchus tshawytscha), and to determine if the composition of these fluids influences sperm motility traits (swimming speed, duration of forward mobility, swimming path trajectory, and percent motility). Cation concentrations and osmolality were significantly different in the two fluids. The ionic composition of ovarian fluid differed among individual females, and also among samples collected at different times through the spawning season. Carbonate and bicarbonate were the principal buffer ions in ovarian fluid, and its viscosity was considerably greater than that of water and was shear-dependent. The duration of forward motility (longevity) of spermatozoa, swimming speed, percent motility, and path trajectory were measured using milt from 10 males activated in the ovarian fluid from 7 females whose ion concentrations were known. No significant correlations were observed between the composition of the seminal fluid and sperm traits. However, in ovarian fluid, sperm longevity was negatively correlated with variation in [Ca(2+)] and [Mg(2+)], while percent motility increased with increasing [Mg(2+)]. These observations provide a possible chemical basis for cryptic female mate choice whereby female ovarian fluid differentially influences the behaviour of sperm from different males, and thus their fertilization success.     

Effect of extracellular space on kallikrein excretion in the rat

Urinary kallikrein excretion was positively correlated with urine flow and negatively with urinary osmolality, it was also positively correlated with inulin space and its both components, plasma volume and interstitial space. We postulate that increased extracellular fluid increases kallikrein excretion and kallikrein avoids water reabsorption leading to a decrease in the extracellular fluid.     

Rectal water absorption in seawater-adapted Japanese eel Anguilla japonica

Marine teleosts drink large amounts of seawater to compensate for continuous osmotic water loss. We investigated a possible significant role of the rectum in water absorption in seawater-adapted eel. In rectal sacs filled with balanced salt solution (BSS) and incubated in isotonic BSS, water absorption was greater in seawater-adapted eel than in freshwater eel. Since rectal fluid osmolality was slightly lower than plasma osmolality in seawater-adapted eel, effects of rectal fluid osmolality on water absorption were examined in rectal sacs filled with artificial rectal fluid with different osmolality. Rectal water absorption was greater at lower rectal fluid osmolality, suggesting that an osmotic gradient between the blood and rectal fluid drives the water movement. Ouabain, a specific inhibitor of Na⁺/K⁺-ATPase, inhibited water absorption in rectal sacs, indicating that an osmotic gradient favorable to rectal water absorption was created by ion uptake driven by Na⁺/K⁺-ATPase. Expression levels of aquaporin 1 (AQP1), a water-selective channel, were significantly higher in the rectum than in the anterior and posterior intestines. Immunoreaction for Na⁺/K⁺-ATPase was detected in the mucosal epithelial cells in the rectum with more intense staining in the basal half than in the apical half, whereas AQP1 was located in the apical membrane of Na⁺/K⁺-ATPase-immunoreactive epithelial cells. The rectum is spatially separated from the posterior intestine by a valve structure and from the anus by a sphincter. Such structures allow the rectum to swell as intestinal fluid flows into it, and a concomitant increase in hydrostatic pressure may provide an additional force for rectal water absorption. Our findings indicate that the rectum contributes greatly to high efficiency of intestinal water absorption by simultaneous absorption of ions and water.     

Distribution of body fluid and change of blood viscosity in broilers (Gallus domesticus) under high temperature exposure

This study was to observe the distribution of body fluid by measuring blood volume, extracellular and intracellular fluid volumes and total body water under heat exposure, in order to clarify the mechanism of decrease in whole blood viscosity of the heat-exposed broilers. Whole blood viscosity, haematocrit, plasma protein concentration, plasma osmolality and extracellular fluid volume decreased during high temperature exposure, while plasma and blood volumes increased. No significant changes were found in both intracellular fluid volume and total body water between thermoneutral and high temperature exposure. These results indicate the decreased whole blood viscosity is induced by a plasma volume expansion, in which water may come from the interstitial space and alimentary tract, under heat exposure.     

Modeling a hydropic recipient twin in twin-twin transfusion syndrome

We developed a mathematical model of twin-twin transfusion syndrome (TTTS) that includes a hydropic recipient twin, adding interstitial and intracellular fluid compartments, fetal congestive cardiac failure, and the dynamics of renin-angiotensin system (RAS) mediators to our previous TTTS model. Ten differential equations for each twin, coupled by the net fetofetal transfusion of blood and blood components, i.e., colloids, osmoles, and RAS mediators, describe the development of fetal arterial and venous blood volumes, blood osmolality and colloid osmotic pressure (COP), interstitial fluid volume and COP, intracellular fluid volume, amniotic fluid volume and osmolality, and RAS mediator concentration. We included varying placental anastomoses, placental sharing, and amnionicity. The 20 differential equations were solved numerically from 0 to 40 wk with a 0.6-s time step. Consistent with clinical experience, model predictions are as follows. Unidirectional arteriovenous anastomoses and arteriovenous anastomoses inadequately compensated by oppositely directed anastomoses cause severe TTTS that includes a hydropic recipient. Adequately compensated arteriovenous anastomoses simulated TTTS without hydrops. The probability that oppositely directed anastomoses prevent onset of a hydropic recipient after TTTS onset, i.e., the largest interval between onset of TTTS and onset of hydrops in the recipient, was best for a venovenous anastomosis, closely followed by an arterioarterial and finally an oppositely directed arteriovenous anastomosis. Hydropic recipients have decreased amniotic fluid volume. Unequal placental sharing and amnionicity modify hydrops onset. In conclusion, our model simulates a sequence of events that results in a hydropic recipient twin in severe TTTS. The model may allow an assessment of the efficacy of current therapeutic interventions for TTTS cases that include a hydropic recipient twin.     

Environmental hypoxia affects osmotic and ionic regulation in freshwater midge-larvae

The effect of anaerobic metabolism on the osmotic and ionic regulation of the extracellular fluid was examined. Larvae of three species, characterized by different hypoxia tolerance, were studied: Chaoborus crystallinus, Culex pipiens and Chironomus gr. plumosus. The use of the capillary electrophoresis technique made it possible to determine approximately 15 different ions from individual hemolymph samples. The hemolymph concentration of both inorganic and organic anions and cations as well as the osmolality were measured. A correlation between the hypoxia tolerance and the capability to avoid net changes in the ion concentration or in the osmolality of the three species studied here is proposed: Culex larvae, which have the lowest hypoxia tolerance, show a very large and very rapid lactate accumulation in their hemolymph under experimental hypoxia. This lactate accumulation is not compensated for by a change in the concentration of any other ion. Chaoborus larvae, with a medium hypoxia tolerance, utilize their very large hemolymph malate pool as a source of anaerobic energy. It is converted into succinate, thus inducing little net changes in the sum of the anions. There is a marked increase of the hemolymph osmolality, though. Chironomus larvae have the highest hypoxia tolerance and there are remarkably little changes in their hemolymph under hypoxia. Although these larvae are described as relying mainly on ethanol fermentation under environmental anaerobiosis, we demonstrated a marked lactate fermentation in severe hypoxia. The lactate accumulation observed in our study was compensated by a concomittant decrease of the hemolymph chloride concentration.     

Changes in osmolality and blood serum ion concentrations in pregnancy

Changes in osmolality and the concentration of cations (Na, K, Ca, Mg) were studied in blood serum of pregnant women from two weeks after conception, throughout the whole pregnancy, and within the first week after delivery. Altogether 239 women from 18 to 40 years of age were studied. Blood serum osmolality decreased from 287±0.8 to 278±1.6 mOsm/kg H₂O from the fifth week of pregnancy and remained virtually at this level until the end of pregnancy. Hyponatremia was found during the three trimesters of pregnancy, in trimesters II and III hypokalemia was not observed, whereas hypocalcemia and hypomagnemia were found. On the first day after delivery, the blood serum osmolality and concentrations of magnesium ions returned to their levels in nonpregnant women, whereas concentrations of sodium and calcium ions remained decreased. No correlation was found between hypoosmia and changes in blood serum concentrations of ions under study during the three trimesters of pregnancy. Thus, in normal pregnancy, hypoosmia develops from the fifth week after conception and persists until delivery. The concentrations of sodium, potassium, calcium, and magnesium ions are regulated by independent mechanisms to provide retention of these parameters within certain periods of pregnancy at the level of nonpregnant women on the background of hypoosmia.     

Elevated levels of colloid osmotic pressure in cecal contents of germfree animals.

Determinations of colloid osmotic pressure in the supernatant of germfree rat cecal contents indicated substantially elevated values in comparison to those of rat blood plasma or of conventional rat cecal supernatant. The germfree cecal supernatant, under conditions of similar total osmolality, was able to draw water at a sizable rate from a polyvinylpyrollidone solution whose colloid osmotic pressure was taken to be equivalent to that of interstitial fluid. It is suggested that the water absorption inhibition which was observed in the lower bowel of germfree rodents, is in part caused by the colloid osmotic pressure gradient which exists in these animals between the luminal contents and the tissue component.     

Interstitial Fluid Colloid Osmotic Pressure in Healthy Children

Objective

The colloid osmotic pressure (COP) of plasma and interstitial fluid play important roles in transvascular fluid exchange. COP values for monitoring fluid balance in healthy and sick children have not been established. This study set out to determine reference values of COP in healthy children.

Materials and Methods

COP in plasma and interstitial fluid harvested from nylon wicks was measured in 99 healthy children from 2 to 10 years of age. Nylon wicks were implanted subcutaneously in arm and leg while patients were sedated and intubated during a minor surgical procedure. COP was analyzed in a colloid osmometer designed for small fluid samples.

Results

The mean plasma COP in all children was 25.6 ± 3.3 mmHg. Arbitrary division of children in four different age groups, showed no significant difference in plasma or interstitial fluid COP values for patients less than 8 years, whereas patients of 8-10 years had significant higher COP both in plasma and interstitial fluid. There were no gender difference or correlation between COP in interstitial fluid sampled from arm and leg and no significant effect on interstitial COP of gravity. Prolonged implantation time did not affect interstitial COP.

Conclusion

Plasma and interstitial COP in healthy children are comparable to adults and COP seems to increase with age in children. Knowledge of the interaction between colloid osmotic forces can be helpful in diseases associated with fluid imbalance and may be crucial in deciding different fluid treatment options.

Trial Registration

ClinicalTrials.gov NCT01044641     

Rapid evolution of body fluid regulation following independent invasions into freshwater habitats

Colonizations from marine to freshwater environments constitute among the most dramatic evolutionary transitions in the history of life. Colonizing dilute environments poses great challenges for acquiring essential ions against steep concentration gradients. This study explored the evolution of body fluid regulation following freshwater invasions by the copepod Eurytemora affinis. The goals of this study were to determine (1) whether invasions from saline to freshwater habitats were accompanied by evolutionary shifts in body fluid regulation (hemolymph osmolality) and (2) whether parallel shifts occurred during independent invasions. We measured hemolymph osmolality for ancestral saline and freshwater invading populations reared across a range of common-garden salinities (0.2-25 PSU). Our results revealed the evolution of increased hemolymph osmolality (by 16-31%) at lower salinities in freshwater populations of E. affinis relative to their saline ancestors. Moreover, we observed the same evolutionary shifts across two independent freshwater invasions. Such increases in hemolymph osmolality are consistent with evidence of increased ion uptake in freshwater populations at low salinity, found in a previous study, and are likely to entail increased energetic costs upon invading freshwater habitats. Our findings are consistent with the evolution of increased physiological regulation accompanying transitions into stressful environments.     

The theory of urine formation in water diuresis with implications for antidiuresis

We investigate a model of the renal medulla in which active NaCl transport is restricted to the thick ascending limb of Henle's loop. The model contains a vas rectum, a loop of Henle, salt, and water. The model generates interstitial osmolality curves consonant with the known functioning of the kidney in water diuresis. Using data from the white rat and the curves generated by the model, one can predict the permeability of the thin limb of Henle's loop to NaCl and the percentage of total renal blood flow entering the inner medulla. In this model interstitial osmolality at the papilla can be about twice plasma osmolality, so that NaCl transport restricted to the outer medulla can contribute significantly to the work required in producing a hypertonic urine. However, the interstitial osmolality monotonically decreases proceeding from the junction of the outer and inner medulla to the papilla, and the maximum interstitial osmolality in the outer medulla is greater than the maximum interstitial osmolality in the inner medulla. Thus we infer that a source of active transport located in the inner medulla is needed to explain the high osmolalities observed in hydropenia. A sketch of an alternative model, a “lineal multiplication mechanism”, for the renal concentrating process is presented in which active transport in the inner medulla is restricted to active salt transport by the collecting duct. The lineal multiplication mechanism makes no use of counter-current multipliers in the inner medulla. The research of this author was supported in part by NIH Grant AM06864-03 and a Career Scientist Award from the Health Research Council of New York City, Contr. No. 1391. The research of this author was supported in part by the Office of Naval Research, U.S. Navy under Contr. N(onr) 595(17). The research of this author was supported in part by Grant NSF GP-2067 from the National Science Foundation and was performed at the University of Maryland.     

A mathematical model of the urine concentrating mechanism in the rat renal medulla. I. Formulation and base-case results

A new, region-based mathematical model of the urine concentrating mechanism of the rat renal medulla was used to investigate the significance of transport and structural properties revealed in anatomic studies. The model simulates preferential interactions among tubules and vessels by representing concentric regions that are centered on a vascular bundle in the outer medulla (OM) and on a collecting duct cluster in the inner medulla (IM). Particularly noteworthy features of this model include highly urea-permeable and water-impermeable segments of the long descending limbs and highly urea-permeable ascending thin limbs. Indeed, this is the first detailed mathematical model of the rat urine concentrating mechanism that represents high long-loop urea permeabilities and that produces a substantial axial osmolality gradient in the IM. That axial osmolality gradient is attributable to the increasing urea concentration gradient. The model equations, which are based on conservation of solutes and water and on standard expressions for transmural transport, were solved to steady state. Model simulations predict that the interstitial NaCl and urea concentrations in adjoining regions differ substantially in the OM but not in the IM. In the OM, active NaCl transport from thick ascending limbs, at rates inferred from the physiological literature, resulted in a concentrating effect such that the intratubular fluid osmolality of the collecting duct increases ~2.5 times along the OM. As a result of the separation of urea from NaCl and the subsequent mixing of that urea and NaCl in the interstitium and vasculature of the IM, collecting duct fluid osmolality further increases by a factor of ~1.55 along the IM.     

A synthesis of interstitial fluid regulation and lymph formation.

The interstitial fluid spaces are filled with a mat of collagen fibers, and the interstices of this mat contain a mucopolysaccharide gel ground substance. Both the collagen fibers and the gel are elastic structures that can be expanded or compacted. In the expanded state the collagen fibers are pushed far apart and pockets of free fluid develop witin the gel. In the compacted state the elastic recoil of the compressed collagen fibers and gel reticular fibrillae seems to cause suction on the fluid within the tissue spaces, thus creating a subatmospheric pressure. Measurements of interstitial fluid pressure using a perforated capsule method indicate that this is normally slightly negative (subatmospheric) in most soft tissues. However, even very slight extra filtration of fluid into the tissue spaces increases the interstitial fluid pressure toward more positive values, which in turn increases lymph flow. The increased lymph flow then decreases the interstitial fluid volume and pressure back toward normal because of two mechanism, 1) direct removal of fluid from the tissue spaces in the lymph, and 2) removal of protein from the interstitial fluid in the lymph, thus decreasing the interstitial fluid colloid osmotic pressure and allowing more effective osmosis of fluid directly from the interstitial spaces back into the capillaries.     

Fluid trapping of erythrocytes under hypoosmolar conditions

125I albumin was used to assess the amount of trapped fluid after microhematocrit centrifugation of erythrocytes suspended in buffers of different osmolality. Surprisingly the total amount of trapped fluid per volume unit of packed erythrocytes decreased with decreasing osmolality of the suspending buffer despite erythrocyte swelling. However, if the contribution of the individual erythrocyte to the trapped fluid was calculated, the trapped fluid per erythrocyte did not change between 311 mosm/kg and 256 mosm/kg. For osmolalities below 256 mosm/kg a significant increase of trapped fluid was obtained. It is concluded that the packing ability of erythrocytes is not impaired in suspending fluid of moderate to severe infraphysiological tonicity. The daily clinical experience that considerable degrees of plasma hypoosmolality are tolerated in vivo without hemolysis or impairment of oxygen transport by erythrocytes may be explained by the excellent ability of shape adaptation of erythrocytes to each other and to other surfaces such as vascular endothelia. The method of trapped fluid determination might be of potential value as a complementary method in the evaluation of erythrocyte rheology if the amount of trapped fluid is related to the individual erythrocyte.     

Effect of cryptorchidism on steroidogenic and mitogenic activities in rat testicular interstitial fluid

There was a significant (P less than 0.05) and consistent increase in the potency of steroidogenic stimulatory activity (testosterone production by purified Leydig cells in vitro) in testicular interstitial fluid of the cryptorchid compared to the scrotal testis from 1 to 4 weeks after the induction of unilateral cryptorchidism. In contrast, the level of mitogenic activity [( 3H]thymidine incorporation into 3T3 cells) was not significantly different between interstitial fluid from cryptorchid and scrotal testes for up to 4 weeks after surgery. These results indicate that the steroidogenic activity and the mitogenic activity are due to different, as yet unidentified, factors in testicular interstitial fluid.     

Hypotonicity-induced increases in duodenal mucosal permeability facilitates adjustment of luminal osmolality

The integrated response to hypotonic NaCl solutions (100, 50, 25, and 0 mM NaCl) in proximal duodenum of anesthetized rats was examined. Luminal alkalinization, fluid flux, duodenal contractions, blood-to-lumen clearance of 51Cr-labeled EDTA (mucosal permeability), and perfusate osmolality were studied in the absence and presence of the cyclooxygenase inhibitor indomethacin. In response to hypotonic solutions net fluid absorption, increases in permeability and perfusate osmolality were markedly higher in indomethacin-treated animals than in controls, and these effects were diminished by the nicotinic-receptor antagonist hexamethonium. Infusion of iloprost, a stable PGI2 analog, to indomethacin-treated animals markedly reduced the hypotonicity-induced increase in mucosal permeability and diminished the rise in perfusate osmolality. Lowering the NaCl concentration in the perfusion solution but maintaining isotonicity with mannitol had no effect on mucosal permeability. Very good linear correlations were obtained between the degree of luminal hypotonicity and the increase in permeability and between increases in permeability and perfusate osmolality. It is concluded that luminal hypotonicity increases duodenal mucosal permeability. The hypotonicity-induced increase in permeability modulated by prostaglandins and nicotinic receptors fulfills the function of increasing blood-to-lumen transport of Na+ facilitating adjustment of luminal osmolality.     

Osmotic Regulation of Toad Bladder Responsiveness to Neurohypophyseal Hormones

The effect of dilution of the interstitial fluids on the responsiveness of the toad urinary bladder to antidiuretic hormones has been examined in vivo and in vitro. Toads were given periodic injections with vasopressin while in water so that their plasma osmolality fell below 190 mosmoles/kg H₂O. The hydraulic conductivity of bladders which had been removed from the animal and fixed with 1% glutaraldehyde was 10-fold less in overhydrated toads than in normally hydrated controls. A similar inhibitory phenomenon was observed in in vitro studies, when the tonicity of Ringer's fluid in which the bladders were suspended was lowered from its isotonic value. Mannitol, but not urea, could be effectively substituted for one-half of the NaCl content of Ringer's fluid. In other experiments it has been shown that the responsiveness of the bladder to vasotocin is depressed during bulk water movement across the tissue. This "flux inhibition" was found to depend upon the velocity and the duration of water flow from mucosa to the serosa. It is suggested that the responsiveness of the toad bladder to antidiuretic hormones diminishes as the effective osmotic pressure of the interstitial fluids declines.     

Effect of chronic maternal hyperkalaemia on plasma, cerebrospinal fluid and brain interstitial fluid potassium in developing rats

Plasma hyperkalaemia was induced in pregnant and lactating rats using a high potassium diet. Fetuses of high-K-diet mothers showed no increase in the potassium concentration [( K+]) of plasma, cerebrospinal fluid (CSF) and brain interstitial fluid, presumably due to placental control. Neonates from high-K-diet rats did show an increase in plasma [K+] but this increase was very small and there was no increase in CSF or interstitial fluid [K+]. Maternal milk [K+] was not affected by plasma hyperkalaemia. Weanling rats fed the high-K diet directly showed marked plasma hyperkalaemia but no increase in CSF or interstitial fluid [K+]. Thus, prior to weaning, a relatively stable plasma [K+] is maintained by maternal influence reducing the need for direct brain fluid K+ regulation.     

In vivo muscle amino acid transport involves two distinct processes

We have tested the hypothesis that transit through the interstitial fluid, rather than across cell membranes, is rate limiting for amino acid uptake from blood into muscle in human subjects. To quantify muscle transmembrane transport of naturally occurring amino acids, we developed a novel 4-pool model that distinguishes between the interstitial and intracellular fluid compartments. Transport kinetics of phenylalanine, leucine, lysine, and alanine were quantified using tracers labeled with stable isotopes. The results indicate that interstitial fluid is a functional compartment insofar as amino acid kinetics are concerned. In the case of leucine and alanine, transit between blood and interstitial fluid was potentially rate limiting for muscle amino acid uptake and release in the postabsorptive state. For example, in the case of leucine, the rate of transport between blood and interstitial fluid compared with the corresponding rate between interstitial fluid and muscle was 247 +/- 36 vs. 610 +/- 95 nmol.min(-1).100 ml leg(-1), respectively (P < 0.05). Our results are consistent with the process of diffusion governing transit from blood to interstitial fluid without selectivity, and of specific amino acid transport systems with varying degrees of efficiency governing transit from interstitial fluid to muscle. These results imply that changes in factors that affect the transit of amino acids from blood through interstitial fluid, such as muscle blood flow or edema, could play a major role in controlling the rate of muscle amino acid uptake.