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PubMed1990

Regulation of the amiloride-blockable sodium channel from epithelial tissue.

The first step in net active transepithelial transport of sodium in tight epithelia is mediated by the amiloride-blockable sodium channel in the apical membrane. This sodium channel is the primary site for discretionary control of total body sodium and, therefore, investigating its regulatory mechanisms is important to our understanding of the physiology of fluid and electrolyte balance. Because essentially all of the regulatory sites on the channel are on the intracellular surface, patch clamp methods have proven extremely useful in the electrophysiological characterization of the sodium channel by isolating it from other channel proteins in the epithelial membrane and by allowing access to the intracellular surface of the protein. We have examined three different regulatory mechanisms. (1) Inhibition of channel activity by activation of protein kinase C; (2) activation of the channel by agents which activate G-proteins; and (3) modulation of channel kinetics and channel number by mineralocorticoids. Activation of protein kinase C by phorbol esters or synthetic diacylglycerols reduces the open probability of sodium channels. Protein kinase C can be activated in a physiological context by enhancing apical sodium entry. Actions which reduce sodium entry (low luminal sodium concentrations or the apical application of amiloride) increase channel open probability. The link between sodium entry and activation of protein kinase C appears to be mediated by intracellular calcium activity linked to sodium via a sodium/calcium exchange system. Thus, the intracellular sodium concentration is coupled to sodium entry in a negative feedback loop which promotes constant total entry of sodium. Activation of G-proteins by pertussis toxin greatly increases the open probability of sodium channels. Since channels can also be activated by pertussis toxin or GTP gamma S in excised patches, the G-protein appears to be closely linked in the apical membrane to the sodium channel protein itself. The mechanism for activation of this apical G-protein, when most hormonal and transmitter receptors are physically located on the basolateral membrane, is unclear. Mineralocorticoids such as aldosterone have at least two distinct effects. First, as expected, increasing levels of aldosterone increase the density of functional channels detectable in the apical membrane. Second, contrary to expectations, application of aldosterone increases the open probability of sodium channels. Thus aldosterone promotes the functional appearance of new sodium channels and promotes increased sodium entry through both new and pre-existant channels.

Aldosterone↗
PubMed1984

Potassium homeostasis and clinical implications.

The clinical estimation of potassium balance generally depends on the level of serum potassium. Since the extracellular fluid contains only 2 percent of the total body potassium, it must be recognized that potassium deficits are usually large before significant hypokalemia occurs, whereas smaller surfeits of potassium will cause hyperkalemia. The total body potassium is regulated by the kidney in which distal nephron secretion of potassium into the urine is enhanced by aldosterone, alkalosis, adaptation to a high potassium diet, and delivery of increased sodium and tubular fluid to the distal tubule. However, the distribution of potassium between the intracellular and extracellular fluids can markedly affect the serum potassium level without a change in total body potassium. Cellular uptake of potassium is regulated by insulin, acid-base status, aldosterone, and adrenergic activity. Hypokalemia, therefore, may be caused by redistribution of potassium into cells due to factors that increase cellular potassium uptake, in addition to total body depletion of potassium due to renal, gastrointestinal, or sweat losses. Similarly hyperkalemia may be caused by redistribution of potassium from the intracellular to the extracellular fluid due to factors that impair cellular uptake of potassium, in addition to retention of potassium due to decreased renal excretion. An understanding of the drugs that affect potassium homeostasis, either by altering the renal excretion of potassium or by modifying its distribution, is essential to the proper assessment of many clinical potassium abnormalities. Both hypokalemia and hyperkalemia may cause asymptomatic electrocardiographic changes, serious arrhythmias, muscle weakness, and death. Hypokalemia has also been associated with several other consequences, including postural hypotension, potentiation of digitalis toxicity, confusional states, glucose intolerance, polyuria, metabolic alkalosis, sodium retention, rhabdomyolysis, intestinal ileus, and decreased gastric motility and acid secretion.

Acid-Base Equilibrium↗
PubMed1998

Cellular orientation of atrial natriuretic peptide in the human brain.

Many peptide hormones and neurotransmitters have been detected in human neuronal tissue. The localisation of atrial natriuretic peptide (ANP) in the human brain was considered to be both interesting and relevant to the understanding of neurochemistry and brain water-electrolyte homeostasis. This vasoactive peptide hormone has been localised in rat and frog neuronal tissue. In the present study, we report the immunohistochemical localisation of ANP in autopsy samples of human brain tissue employing the avidin-biotin-peroxidase complex technique, using an antibody against a 28 amino acid fragment of human ANP. The most intense staining of immunoreactive ANP was detected in the neurones of preoptic, supraoptic and paraventricular nuclei of the hypothalamus, epithelial cells of the choroid plexus and ventricular ependymal lining cells. Immunoreactive neurones were also observed in the median eminence, lamina terminalis, infundibular and ventromedial nuclei of the hypothalamus, and in neurones of the brain stem, thalamic neurones and some neurones of the caudate nucleus. The network of ANP cells in numerous hypothalamic centres may regulate the salt and water balance in the body through a hypothalamic neuro-endocrine control system. ANP in the brain may also modulate cerebral fluid homeostasis by autocrine and paracrine mechanisms.

Adult↗
PubMed2000

Dynamic leg volume changes when sitting in a locked and free floating tilt office chair.

It is well established that prolonged sitting may lead to swelling of the lower extremities. However, activation of the vein pump system by repeated walking breaks or dynamic tiltable foot-rests have been shown to reduce foot and leg oedema. Some office chairs incorporate tilt mechanisms facilitating movements of the body from the feet up. The present study was undertaken to establish whether a beneficial effect on the transcapillary fluid balance of the legs by enabling such mechanisms could be documented. An office chair where the tilt mechanism could be locked or open was used for the study. The seat position and seat activity level was recorded by a transducer system developed for the study. Calf volume and calf muscle pump activity was detected by mercury strain gauge plethysmography. In the locked position there was a steady increase in volume of mean = 1.2% (range = 0.8-1.8%) for all participants in the 30-min study period. On the other hand, for all participants there was a decrease in calf volume (mean = 0.7%, range = 0.1-1.2%, p = 0.008) when the tilt mechanism was open (30-min period), irrespective of what study period came first. The study showed that upward seat deflection was not associated with concomitant venous obstruction, since such obstruction was detected in less than 2% of the time period with more than 50% of maximal upward deflection. A locked seat mechanism does not prevent activation of the vein pump mechanism, but the study indicates that office chairs that permit variation in seat angle per se stimulate movements of the leg. This, in turn, activates vein pumps and counteracts local oedema formation in seated working postures.

Adult↗
PubMed2003

Transvascular and intravascular fluid transport in the rainbow trout: revisiting Starling's forces, the secondary circulation and interstitial compliance.

The kinetics of transvascular fluid transport across fish capillaries and redistribution of fluids between intravascular compartments in intact fish are unknown. Cannulae were placed in the dorsal aorta (DA) and caudal vein (CV) of rainbow trout Oncorhynchus mykiss (mass 0.45-0.85 kg) and the fish spleenectomized. The following day a peristaltic pump was fitted to complete the extracorporeal arterio-venous circulation. Hematocrit (Hct) was monitored in unanesthetized fish either manually, by collecting blood from the extracorporeal loop at 5 min intervals for a period of 1 h (groups 1 and 2), or continuously (instantaneously) with an impedance flow-cell inserted in the aortic cannula (group 3). Fish in group 1 were volume expanded by injecting a volume of saline (0.9 g% NaCl; SI) or trout plasma (PI) equivalent to 40% of the plasma volume. In group 2, 20% or 35% of the blood volume was removed, and in group 3, 35% of the blood volume was removed. Plasma volume (Vp) was calculated from an assumed blood volume of 35 ml kg(-1) and the Hct. Vp declined mono-exponentially after SI with a half-time of 6.8 min and Vp reached a new steady state at 28.1 ml kg(-1); 30% of the injected volume remained in the vasculature. Volume recovery after PI was also mono-exponential, but slower (half-time=15.4 min) than SI, whereas the steady-state Vp (27.3 ml kg(-1)) was similar and 30% of the injected volume remained in the vasculature. Thus the presence of plasma proteins delayed fluid efflux from the vasculature, but did not affect the volume lost. Transvascular fluid filtration coefficients calculated from this data were 5.5 (SI) and 4.5 ml mmHg(-1) kg(-1) min(-1) (PI), and interstitial compliance was 11.8 (SI) and 9.7 ml mmHg(-1) kg(-1) (PI). The rate of volume recovery after 20% or 35% hemorrhage was independent of the hemorrhage volume (half-time=13.3 and 15.1 min, respectively) and similar to the half-time of PI, indicating that protein-rich interstitial fluid is returned to the vasculature. There is a nearly instantaneous change in Hct that occurs during the hemorrhage period; it is dependent on hemorrhage duration and volume and not associated with the subsequent mono-exponential recovery. This initial response is best explained by a rapid fluid shift from a large-volume (approximately 40% of total blood volume), low-hematocrit (less than half of systemic Hct) microcirculation into the higher-hematocrit macrocirculation. These studies are consistent with transcapillary fluid flux across a barrier that is highly permeable to protein, and cannot be explained by fluid shift between primary and secondary circulations, or by transcapilllary flux across a capillary bed that is impermeable to plasma proteins. The results support the hypothesis that whole-body reflection coefficients in trout are very low and that plasma oncotic pressure is not a determinant of transcapillary fluid balance. They also show that both transvascular and intravascular fluid movements are important effectors of central volume homeostasis.

Animals↗
PubMed1998

Mechanisms of tubular sodium chloride transport.

Extracellular fluid volume is determined by sodium and its accompanying anions. There are control mechanisms which regulate sodium balance in the body. These include high and low pressure baroreceptors, intrarenal baroreceptors, renal autoregulation, tubuloglomerular feedback, aldosterone, and numerous other physical and hormonal factors. Sodium transport by the nephron involves active and passive processes which occur in several different nephron segments. Mechanisms of cotransport, Na(+)-H+ exchange, antiporters and ion-specific channels are all utilized by the nephron to maintain sodium balance. These regulatory factors and transport mechanisms for sodium in the kidney will he discussed in detail.

Biological Transport, Active↗
PubMed1989

[Nutrition in continuous ambulatory peritoneal dialysis].

Adequate nutrition is of major importance in CAPD patients. This is particularly due to the considerable protein and amino acid loss. Peritoneal glucose absorption, in particular during the use of hypertonic dialysate, though providing considerable quantities of calories, may interfere with appropriate protein intake. Therefore, periodic assessment of the nutritional status is recommended. In general, protein intake of 1,2 g/kd body weight will yield positive nitrogen balance or nitrogen equilibrium. The generous use of hypertonic dialysate is discourage. Rather mild fluid restriction is recommended in order to allow fluid equilibrium.

Humans↗
PubMed1999

Volume kinetics of Ringer solution after surgery for hip fracture.

PURPOSE: To study the time course of volume changes during and after infusion of Ringer's solution in elderly patients after a standardised trauma. METHODS: The kinetics of 12.5 ml.kg-1 Ringer's solution infused over 30 min were studied in ten patients one day after surgery for hip fracture (mean age, 70 yr) and in an age- and sex-matched control group. Hemodilution, as measured every five minutes for 90 min, was used to calculate the size of the fluid space expanded by the fluid (V) and the elimination rate constant (kr). The baseline fluid balance status in the patients and the controls was compared by bioelectrical impedance analysis. RESULTS: The size of V was 4.1 +/- 0.51 (mean +/- SEM) in the patients and 3.4 +/- 0.21 in the controls (P:NS) while the corresponding results for kr were 85 +/- 12 and 166 +/- 27 ml.min-1, respectively (P < 0.04). Bioelectrical impedance analysis showed that the extracellular fluid space and the total body water volumes did not differ between the two groups. Computer simulations based on the data obtained for V and kr indicate that trauma increases the dilution of the plasma volume and the retention of fluid in response to slow and moderate infusion rates, while these indices of short-term changes in fluid balance remain the same in the two groups during very rapid infusion of Ringer's solution. CONCLUSION: A slower elimination rate increased dilution of plasma and retention of fluid when Ringer's solution was infused in elderly trauma patients.

Aged↗
PubMed1986

Validation of doubly labeled water for measuring energy expenditure during parenteral nutrition.

The doubly labeled water method was compared with intake-balance for measuring energy expenditure in five patients receiving total parenteral nutrition (TPN). Because parenteral solutions were isotopically different from local water, patients had to be placed on TPN at least 10 days before the metabolic period. Approximately 0.1 g 2H2O and 0.25 g H2(18)O per kg total body water were given orally. We collected saliva before, 3 h, and 4 h after the dose for measurement of total body water and urine before, 1 day, and 14 days after the dose for measurement of isotope eliminations. On day 14, total body weight was remeasured and change in body energy stores was calculated, assuming constant hydration. Intake was assessed from weights of TPN fluids plus dietary record for any oral intake. Energy expenditure from doubly labeled water (+/- SD) averaged 3 +/- 6% greater than intake-balance. Doubly labeled water method is a noninvasive, nonrestrictive method for measuring energy expenditure in patients receiving TPN.

Adult↗
PubMed1978

Changes in the body composition of monkeys during long-term exposure to high acceleration fields.

Adult, 10-14 kg, male pig-tailed monkeys (Macaca nemestrina) were subjected to continuous centrifugation for 7 months in acceleration fields up to 2.5 g. Several major parameters of body composition, body-fluid distribution, and hematology were evaluated at various levels of high g by in vivo analytical techniques. Statistically significant decreases in total body mass, lean body mass, total body water, extracellular water content and interstitial water content proportional to the level of high g were also demonstrated. Body cell mass, total body fat, dry body mass, lean body solids, and red cell volume did not change significantly. Significant decreases in red cell count, blood hemoglobin level and venous hematocrit value accorded with the plasma volume and red cell volume findings. Total plasma protein concentration did not change significantly. The results indicate a substantial loss of total body mass in the form of body water. The loss apparently occurred from the interstitial spaces of the body in the face of a sizeable increase in plasma volume. Physiological significance of the body composition and fluid distribution changes at high g is discussed and compared to the changes described for astronauts at low g. Current theory of fluid-balance physiology favors the concept that interstitial volume and blood volume are tightly coupled and change in the same direction. However, it appears that the changes which occur where the ambient acceleration field is varied may represent an exception to the general hypothesis for the regulation of the extracellular fluid volume.

Acceleration↗
PubMed2001

Role of diuretics in the preservation of residual renal function in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Patients on continuous ambulatory peritoneal dialysis (CAPD) are dependent on residual renal function for solute and water clearances, and this declines with time on dialysis. Loop diuretics have been postulated to slow this decline. METHODS: Sixty-one patients new to dialysis were randomly assigned to either furosemide 250 mg every day or no furosemide at the time of CAPD training and were followed prospectively. Urine volume (UV), urea clearance (C(Urea)), and creatinine clearance on cimetidine (C(Cr)) were measured at randomization at six months and at one year. Patients underwent a standard four-hour peritoneum equilibrium test, and total body water was measured by bioelectrical impedance. Results were expressed on an intention-to-treat basis. RESULTS: UV, C(Cr), and C(Urea) were similar at randomization (1020 +/- 104 vs. 1040 +/- 130 mL/24 hours, 4.95 +/- 0.51 vs. 4.07 +/- 0.40 mL/min/1.73 m2, 0.91 +/- 0.09 vs. 0.84 +/- 0.08, diuretic vs. control). UV in the diuretic-treated group increased, whereas in the control group, it declined (+176 vs. -200 mL/24 hours at 6 months and +48.8 vs. -305 mL/24 hours at 1 year, P < 0.05). C(Cr) and C(Urea) declined at a constant rate and were unaffected by diuretic administration (0.12 +/- 0.05 vs. 0.071 +/- 0.04 mL/min/1.73 m2/month, 0.020 +/- 0.01 vs. 0.019 +/- 0.01 per month). Urinary sodium excretion increased in the diuretic group and declined in the control group (+0.72 +/- 0.85 vs. -2.56 +/- 1.31 mmol/24 hours/month, P = 0.04). Body weight rose in both groups (4.3 vs. 3.0 kg), but the percentage of total body weight rose in the control group and remained constant in the diuretic group (52 +/- 2.4 vs. 64 +/- 6.6%, P = 0.10). CONCLUSIONS: Long-term furosemide produces a significant increase in UV over 12 months when on CAPD and may result in clinically significant improvement in fluid balance. However, furosemide has no effect on preserving residual renal function.

Adult↗
PubMed1996

Endocrine, renal, and circulatory influences on fluid and electrolyte homeostasis during weightlessness: a joint Russian-U.S. project.

Microgravity is known to have a substantial effect on fluid homeostasis. The research described here was planned as part of the first joint Russian-U.S. science program carried out during a Shuttle flight. The aim of the program was to study the nature of the changes in fluid homeostasis induced by microgravity, as well as to determine the possible mechanisms underlying the regulation of fluid balance under conditions of spaceflight. To determine the effects of spaceflight on the homeostasis of fluid and electrolytes, measurements were taken of total body water, extracellular fluid plasma volumes, levels of regulatory hormones, and nutrient consumption before, during, and after a nine-day flight. Changes in renal function were studied before and after the flight. In these 2 subjects, weightlessness was not associated with a decreased extracellular fluid volume. However, there were the characteristic decreases in plasma atrial natriuretic peptide concentrations, and increases in plasma and urinary cortisol. Results indicated decreased urine volume, even through the first 48 hours of flight. Fluid volumes and glomerular filtration rate were increased after landing, probably related to the saline-loading countermeasure used by Shuttle crewmembers. The information obtained as a result of this research will facilitate the development of future research programs, as well as preventive measures for future long-duration spaceflights.

Body Water↗
PubMedDate not supplied

Postoperative hypocaloric parenteral nutrition. A study in patients without neoplasm.

Hypocaloric peripheral parenteral nutrition during the postoperative period aims to reduce or minimize protein loss and avoid use of central venous catheters. The efficacy of such nutrition in regard to postoperative outcome and nitrogen balance was evaluated in comparison with standard fluid therapy. The study was performed on 49 well-nourished patients who underwent major surgery for non-neoplastic conditions. Group I received 1 g amino acids + 1 g xylitol and 1 g sorbitol/kg body weight, while standard fluid therapy was given in group II. No significant intergroup difference was found in serum levels of albumin, total protein, prealbumin, transferrin or retinol-binding protein. The blood urea, nitrogen excretion and nitrogen balance were significantly higher in group I. The postoperative outcome was similar in both groups, as were the observed complications. Thus although the nitrogen balance was superior in group I, no intergroup difference was clinically evident.

Abdomen↗
PubMed1999

Changes in weight, fluid balance and serum albumin in patients referred for nutritional support.

BACKGROUND AND AIMS: Starvation and injury impair the excretion of an excess sodium and water load, resulting in oedema and hypoalbuminaemia, which may have adverse effects on gastrointestinal physiology. We have retrospectively assessed clinical signs and fluid balance in 44 adult patients referred for nutritional support for >== 10 days. METHODS: Clinical evidence of oedema was noted. Oedematous patients were managed with a low sodium (0-50 mmol/day), low volume (2 l/day) feed. Some also received albumin and a diuretic. Body weight was recorded daily and serum albumin three times weekly. The lowest recorded weight during nutritional support and the weight at the time of discharge were correlated with serum albumin concentration. RESULTS: The 21 patients with oedema had acute surgical conditions and complications such as sepsis while the 23 non-oedematous patients had chronic conditions with gradual nutritional depletion. During nutritional support the mean (SEM) weight in kg of the oedematous patients fell from 79.3 (2.9) to 69.2 (3.2) (P>> 0.00001) and subsequently rose to 70.1 (3.2) (P= 0.005). Corresponding values for the non-oedematous patients were 61.4 (4.0), 60.2 (3.9) (P>> 0.05) and 61.2 (3.7) (P= 0.002) respectively. Weight reduction reflected negative salt and water balance and correlated with a rise in serum albumin (r = -0.61 for oedematous and r = -0.65 for non-oedematous patients) largely reflecting reversal of previous dilution. CONCLUSION: These findings have important implications for the salt and water content of perioperative fluid and nutritional prescriptions. They also emphasize the dilutional component of hypoalbuminaemia in these patients.

Albumins↗