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Extracellular fluid expansion during parenteral refeeding.

Life emerged on our planet from a fluid environment which probably contained a similar concentration of sodium and other electrolytes to that of the extracellular fluid of mammals (1). The maintenance of the volume and composition (homeostasis) of this internal fluid surrounding all the body cells is essential for survival. Malnutrition and illness are associated with alterations in the distribution and in the renal handling of water and sodium within the body (2). Thus, an understanding of water and salt physiology is essential for the proper practice of nutritional support.

Journal Article↗

Role of arginine vasopressin in the regulation of extracellular fluid volume.

The Henry-Gauer hypothesis postulates that changes in left atrial pressure induce changes in the release of arginine vasopressin (AVP), which subsequently modulates the renal output of fluid. Results of the past decades indicate that this hypothesis is too simplistic in explaining the complexity of extracellular fluid volume (ECFV) regulation in humans. Factors controlling renal sodium excretion are the primary modulators of ECFV. AVP is probably important in the related adjustments of renal water excretion whereby changes in plasma sodium concentration induce changes in plasma osmolality and, subsequently, in release of AVP. Evidence has accrued that changes in arterial variables, e.g., arterial pulse pressure, induce changes in the release of AVP during acute changes in central blood volume. Thus, arterial baroreflex regulation of AVP release might constitute one of several pathways of ECFV regulation. Recent results from the D2-Spacelab mission on ECFV regulation are surprising. Following an isotonic saline infusion, renal sodium and fluid output were lower than expected from results of simulation experiments, and venous plasma NE and renin higher. Since plasma AVP was low, high levels of this variable cannot constitute an explanation for the attenuated renal output of fluid during flight. Thus, the currently used models (in particular head-down bed rest) for simulating microgravity should be critically reevaluated. In addition, the relationship between central cardiovascular variables, endocrine mediators, and renal function during microgravity should be a focus of future research.

Animals↗

The extrarenal effects of aldosterone on the distribution of extracellular fluid in conscious adrenalectomized-nephrectomized rats.

In order to examine the extrarenal roles of aldosterone in cardiovascular homeostasis, the present study compared blood pressure, extracellular fluid volume (ECFV) and plasma volume (PV) in the three following groups: 10 nephrectomized (NX) rats, 10 nephrectomized-adrenalectomized (NX-AX) rats, and 10 NX-AX and aldosterone-treated (NX-AX-A) rats. Two-hundred and fifty micrograms of aldosterone, mixed with sesame oil, was given subcutaneously in the NX-AX-A rats. Mean arterial pressure (MAP) was recorded through previously implanted carotid catheters. ECFV and PV were measured using 35S-Na2SO4 and 131I-RISA, respectively, 24 h after the operation. These measurements were performed in an unanesthetized and unrestricted condition. MAP gradually increased in the NX group, while a gradual decrease was observed in the other groups. However, MAP was significantly higher in the NX-AX-A group than in the NX-AX group 6 h after the operation and thereafter. Changes in body weight were comparable in the three groups 24 h after the operation. ECFV and PV were both reduced in the NX-AX and the NX-AX-A groups as compared to the NX group (P less than 0.001 NX-AX vs NX, and P less than 0.05 and P less than 0.025 NX-AX-A vs NX, respectively). Although ECFV was comparable in the NX-AX and the NX-AX-A groups, PV was significantly greater in the NX-AX-A group than in the NX-AX group (P less than 0.05). There was a significant positive correlation between MAP and PV in the rats as a whole (r = 0.68, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Extracellular fluid restoration in dehydration: a critique of rapid versus slow.

We compared current recommendations for treatment of severe dehydration by World Health Organization physicians and by the American Academy of Pediatrics Committee on Pediatric Gastroenterology with those in general textbooks of pediatrics, written mostly by pediatric nephrologists. The former recommend rapid (1- to 2-h) and generous intravenous restoration of extracellular fluid (ECF) volume followed by oral rehydration therapy (ORT) to replace potassium, current maintenance, and diarrheal losses--the rapid rehydration regimen. Oral feedings usually are resumed in 8-24 h. General textbooks of pediatrics usually recommend giving 20 ml/kg saline "to restore circulation," followed by the deficit therapy regimen to correct serum electrolyte abnormalities and replace remaining deficits of water, sodium, chloride, and potassium over 1-2 days. Mortality for hospitalized patients with dehydration treated with rapid rehydration was <3 per 1,000; no recent results are reported for patients treated by deficit therapy. The rapid rehydration regimen improves patient well being and restores perfusion, so that oral feedings are readily tolerated and renal function corrects serum electrolyte abnormalities in 6 h. Amounts of saline given correspond to amounts given for treating various forms of shock. Deficit therapy regimens provide less ECF restoration and are slower at restoring perfusion; tolerance for oral feedings is delayed. Two hundred pediatric nephrologists were surveyed, asking how they would treat a patient with severe dehydration and a patient with 40% burns. Only 30 of 200 responded; 29 used a deficit therapy regimen, with 20-40 ml/kg ECF replacement, while a majority rapidly and generously restored ECF volume in burn shock. We recommend that fluid therapy chapters should stop teaching deficit therapy for treating severe dehydration and instead teach the rapid rehydration regimen.

Child↗

Estimation of extracellular fluid volume from plasma clearance on technetium-99m DTPA by a single-injection, two-sample method.

A simple method is presented for estimating extracellular fluid volume from the plasma clearance of [99mTc])DTPA or [169Yb]DTPA. Two plasma samples are required, at 1 and 3 hr, following a single intravenous injection. (The same plasma samples can be used for measurement of glomerular filtration rate.) Using the complete plasma clearance curve as a reference (eight samples at 10 to 240 min), the error of the two-sample method in 40 patients was 1.5 I for [99mTc]DTPA, 2.1 I for [169Yb]DTPA (residual standard deviation).

Extracellular Space↗

[Kidney reaction to an increase in the volume of extracellular fluid in rabbits with ischemic cerebral hypertension].

The excretion of water, electrolytes and osmotically active substances and the blood plasma natriuretic activity were studied following isotonic dilation of the extracellular space in experiments on rabbits with ischemic cerebral hypertension. Rabbits with hypertension were marked by the phenomenon of exaggerated natriuresis and increased excretion of water and osmotically active substances after volumetric stimulation, which was due to a greater inhibition of processes of tubular reabsorption than in intact animals. The increase in the content of the natriuretic factor in the blood plasma of rabbits with ischemic cerebral hypertension after an increase in the volume of extracellular fluid could not be identified as one of the possible causes of inhibition of sodium reabsorption.

Animals↗

Correction of metabolic alkalosis by the kidney after isomertric expansion of extracellular fluid.

Metabolic alkalosis was induced in dogs by administering ethacrynic acid and sustained by feeding a chloride-deficient diet. At the height of the alkalosis extracellular fluid was expanded "isometrically," i.e., with an infusion that duplicated plasma sodium, chloride, and bicarbonate concentrations. Correction of metabolic alkalosis promptly followed such expansion and was attributed to the selective retention by the kidneys of chloride from the administered solution. Since plasma chloride concentration was not increased as an immediate consequence of the infusion, it is concluded that the change in renal tubular function that led to the selective retention of chloride must have been mediated by factors independent of filtrate chloride concentration.A decrease in circulating mineralocorticoid level, as a consequence of volume expansion, does not seem to account for this change in tubular function since identical studies in dogs receiving excessive amounts of 11-deoxycorticosterone acetate during the day of infusion yielded similar findings. Moreover, no other consequence of volume expansion appears to be sufficient to cause this change in tubular function in the absence of metabolic alkalosis; when the alkalosis was corrected with hydrochloric acid before infusion, isometric expansion of extracellular volume did not induce selective chloride retention. We suggest that isometric expansion during metabolic alkalosis causes a decrease in proximal sodium reabsorption that relinquishes filtrate to a more distal site in the nephron and that this site may retain chloride preferentially when hypochloremia or chloride deficiency is present.

Acid-Base Equilibrium↗

Interstitial-lymphatic mechanisms in the control of extracellular fluid volume.

While the study of the physiochemical composition and structure of the interstitium on a molecular level is a large and important field in itself, the present review centered mainly on the functional consequences for the control of extracellular fluid volume. As pointed out in section I, a biological monitoring system for the total extracellular volume seems very unlikely because a major part of that volume is made up of multiple, separate, and functionally heterogeneous interstitial compartments. Even less likely is a selective volume control of each of these compartments by the nervous system. Instead, as shown by many studies cited in this review, a local autoregulation of interstitial volume is provided by automatic adjustment of the transcapillary Starling forces and lymph flow. Local vascular control of capillary pressure and surface area, of special importance in orthostasis, has been discussed in several recent reviews and was mentioned only briefly in this article. The gel-like consistency of the interstitium is attributed to glycosaminoglycans, in soft connective tissues mainly hyaluronan. However, the concept of a gel phase and a free fluid phase now seems to be replaced by the quantitatively more well-defined distribution spaces for glycosaminoglycans and plasma protein, apparently in osmotic equilibrium with each other. The protein-excluded space, determined mainly by the content of glycosaminoglycans and collagen, has been measured in vivo in many tissues, and the effect of exclusion on the oncotic buffering has been clarified. The effect of protein charge on its excluded volume and on interstitial hydraulic conductivity has been studied only in lungs and is only partly clarified. Of unknown functional importance is also the recent finding of a free interstitial hyaluronan pool with relatively rapid removal by lymph. The postulated preferential channels from capillaries to lymphatics have received little direct support. Thus the variation of plasma-to-lymph passage times for proteins may probably be ascribed to heterogeneity with respect to path length, linear velocity, and distribution volumes. Techniques for measuring interstitial fluid pressure have been refined and reevaluated, approaching some concensus on slightly negative control pressures in soft connective tissues (0 to -4 mmHg), zero, or slightly positive pressure in other tissues. Interstitial pressure-volume curves have been recorded in several tissues, and progress has been made in clarifying the dependency of interstitial compliance on glycosaminoglycan-osmotic pressure, collagen, and microfibrils.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Transthoracic electrical impedance as an index of extracellular fluid volume in man.

Findings in 76 subjects without cardiac failure were analyzed to detect relationships between observed changes in transthoracic electrical impedance (TEI) and total body extracellular fluid volume (ECFV) during various manoeuvres and between absolute TEI and ECFV values. TEI was normalized to electrode distance (Z0/delta el) and ECFV to lean body mass (ECFV/LBM). A distinct relation was found between percent changes of TEI and ECFV (r = -0.76, p less than 0.0001) and between absolute Z0/delta el and ECFV/LBM values (r = -0.66, p less than 0.0001 for men; r = -0.61, p less than 0.0001 for women). It is concluded that in the same subject a change in TEI is possibly a sensitive index for a change in ECFV and that a single measurement of TEI, normalized to electrode distance, gives information about the state of hydration (ECFV) of patients without cardiac failure.

Adult↗

Effect of expansion of extracellular fluid volume on the maximal reabsorptive capacity for inorganic phosphate in parathyroidectomized and intact rats.

Clearance studies were performed in order to examine the effect of expansion of extracellular fluid volume (ECFV) on the maximal reabsorptive capacity for inorganic phosphate (TmPi) in acutely parathyroidectomized (PTX) and intact rats. TmPi values were obtained in both control and volume expansion. In PTX rats, the TmPi values in control and expansion were 8.25 +/- 1.52 and 6.14 +/- 1.02 micronmol/min (mean values +/- S.D.), respectively; the TmPi/GFR values were 2.96 +/- 0.31 and 2.09 +/- 0.30 micronmol/ml, respectively. In intact rats, the TmPi values in control and expansion were 3.56 +/- 0.94 and 2.98 +/- 0.94 micronmol/min, respectively, and the TmPi/GFR values were 1.34 +/- 0.23 and 1.05 +/- 0.23 micronmol/ml, respectively. From these results it is concluded that expansion of ECFV decreases the TmPi values both in the absence and presence of parathyroid hormone.

Absorption↗

The depressant influence of extracellular fluid hyperoxia on liver slice oxygen uptake.

The effect of oxygen tension (Po2) on oxygen consumption (Vo2) of rabbit liver slices was investigated to determine the relationship between extracellular fluid Po2 and liver slice Vo2. Seventy rabbits, 5 kg each, were sacrificed with air embolism. Liver slices (0.3 gm) in Krebs-Ringer's-phosphate (KRP) dextrose were placed in a constantly agitated, 37 degrees C, closed cuvette, and Po2 was continuously monitored down to 10 torr. The system was reoxygenated and closed, and observations were repeated. Hemoglobin concentration was measured on the liver slice homogenate, and a P50 was measured on autologous blood. The presence of small amounts of hemoglobin in the supernatant was confirmed by electrophoretic, spectrophotometric, and morphologic studies. The pH decreased from mean 7.47 to mean 7.37 during each run. The resultant increase in P50 was recalculated and included in the determination of each deltaO2 content/min (Vo2). Vo2 at Po2 30 torr was greater than Vo2 at Po2 90 torr (p less than 0.0001 in each case). Vo2 at Po2 30 torr was not significantly different in the first vs. the second run (p greater than 0.85). The critical oxygen tension for hepatocyte respiration appears to be 30 torr.

Animals↗

Relative expansion of extracellular fluid in obese vs. nonobese women.

There is a conflict in previous studies with regard to the relation between adipose tissue mass and total body fluid distribution. This study tested the hypothesis that obesity is accompanied by an increase in the extracellular-to-intracellular fluid ratio above that observed in nonobese subjects. Extracellular fluid was evaluated in obese (n = 39) and nonobese (n = 26) healthy women, using two different dilution volumes, 35SO4 [extracellular water (ECW)] and 24NaCl [exchangeable sodium (Nae)]. Intracellular water (ICW = 3H2O dilution volume-ECW) and total body potassium (TBK; 40K whole body counting) were assumed to represent intracellular fluid. Two independent markers of relative fluid distribution were formulated as ECW/ICW and Nae/TBK. Obese and nonobese women were of similar age and height but differed in body weight and TBW by 67.7 kg and 12.9 liters, respectively. The obese women had significantly larger absolute ECW, Nae, ICW, and TBK compared with the nonobese women (all P less than 0.001). The ratios ECW/ICW and Nae/TBK were significantly higher in obese vs. nonobese women and were highly correlated with each other (r = 0.54, P less than 0.001) in the pooled group of subjects. Fluid volumes are thus increased in obese women, and the expansion is relatively greater for the extracellular compartment. These results have implications in the study of human body composition and may also account in part for the fluid-overload states that often accompany severe obesity.

Adult↗

Effects of hypertonic saline (7.5%) on extracellular fluid volumes compared with normal saline (0.9%) and 6% hydroxyethyl starch after aortocoronary bypass graft surgery.

OBJECTIVE: To compare the effects of hypertonic (7.5%) saline (HS), normal (0.9%) saline (NS), and 6% hydroxyethyl starch (HES) on extracellular fluid volumes in the early postoperative period after cardiopulmonary bypass. DESIGN: A prospective, randomized, double-blind study. SETTING: University teaching hospital. PARTICIPANTS: Forty-eight patients scheduled for elective coronary artery bypass graft surgery. INTERVENTIONS: Patients were randomly allocated to receive 4 mL/kg of HS, NS, or HES during 30 minutes when volume loading was needed during the postoperative rewarming period in the intensive care unit. Plasma volume was measured using a dilution of iodine-125-labeled human serum albumin. Extracellular water and cardiac output were measured by whole-body impedance cardiography. MEASUREMENTS AND MAIN RESULTS: Plasma volume had increased by 19 +/- 7% in the HS group and by 10 +/- 3% in the NS group (p = 0.001) at the end of the study fluid infusion. After 1-hour follow-up time, the plasma volume increase was greatest (23 +/- 8%) in the group receiving HES (p < 0.001). The increase of extracellular water was greater than the infused volume in the HS and HES groups at the end of the infusion. One-hour diuresis after the study infusion was greater in the HS group (536 +/- 280 mL) than in the NS (267 +/- 154 mL, p = 0.006) and HES groups (311 +/- 238 mL, p = 0.025). CONCLUSION: The effect of HS on plasma volume was short-lasting, but it stimulated excretion of excess body fluid accumulated during cardiopulmonary bypass and cardiac surgery. HS may be used in situations in which excess free water administration is to be avoided but the intravascular volume needs correction.

Aged↗

Pharmacokinetics and clinical utility of sodium bromide (NaBr) as an estimator of extracellular fluid volume in horses.

The purpose of this study was to describe the pharmacokinetics of bromide in horses and to evaluate the corrected bromide space as an indicator of extracellular fluid volume (ECFV) in horses after the administration of a single dose of bromide by intravenous infusion. Sodium bromide (30 mg/kg of body weight, IV) was administered to 6 clinically healthy mares over a period of 3 minutes. Blood samples were collected before infusion and at intervals between 0.5 hours and 53 days after infusion. Mean elimination half-life (harmonic mean) was 126 hours (5.2 days), clearance was 1.4 +/- 0.09 mL/(kg x h), area under the curve was 17,520 +/- 1,100 microg x h/mL. and volume of distribution (steady state) was 0.255 +/- 0.015 L/kg. The mean corrected bromide space was determined from the volume of distribution (steady state) and the serum concentrations of bromide at equilibration. Corrected bromide space, an estimate of ECFV, was 0.218 +/- 0.01 L/kg. The conclusion was made that ECFV of horses can be estimated by measuring bromide concentrations in a preinfusion serum sample and a sample obtained 5 hours after the administration of bromide.

Animals↗

Measurement of extracellular fluid after acute myocardial infarction.

The volume of distribution of [60Co]EDTA in normal dog myocardium is slightly less than that calculated from tissue contents of H2O, Cl, K, and their extracellular fluid (ECF) concentrations subsuming a steady state across cell membranes. The volume of distribution of [3H-]sorbitol was substantially higher than the measured CoEDTA space. [60Co]EDTA can be measured in ischemic myocardium that remains perfused. Extraction of [60Co]EDTA and [3H-]sorbitol is incomplete from dried biopsies.

Animals↗

Normalization of glomerular filtration rate in children: body surface area, body weight or extracellular fluid volume?

UNLABELLED: Glomerular filtration rate (GFR) is usually expressed in relation to body surface area (BSA) for standardization and comparison between individuals of different sizes, although relating it to extracellular fluid volume (ECV) is technically much simpler because the ratio GFR/ECV is almost equal to the rate constant of the second exponential of the 51Cr-EDTA plasma clearance curve. The aim of this study was to investigate the physiological validity of expressing GFR in relation to ECV by comparing it with GFR normalized for BSA and body weight. METHODS: GFR was measured from a five-sample 51Cr-EDTA plasma clearance curve. After appropriate scaling, the rate constant of the terminal exponential is equal to GFR/ECV. RESULTS: GFR normalized by any of the three variables increased between 0-6 mo, but was less in the case of GFR/weight compared with the other two. From 6 to 24 mo, GFR/BSA continued to increase, whereas GFR/ECV and, in particular, GFR/weight remained relatively constant. It appears that as the child grows to age 6 mo, weight outstrips BSA and ECV but is followed by GFR. From 6 to 24 mo, weight, ECV and GFR increase at a faster rate than BSA. By applying regression analysis to the curves of GFR and its normalization variables versus age, expected (e) and relative (r, i.e., observed/expected) values were obtained for each patient. In the age group 6-24 mo, but not 0-6 mo, r[GFR/ECV] was significantly closer to e[GFR/ECV] than the corresponding comparisons with r and e[GFR/BSA] (p < 0.001) and r and e[GFR/weight] (p < 0.002), supporting the hypothesis that as ECV deviates from the expected value for the patient's age, it tends to be followed by GFR. CONCLUSION: Our data show that ECV is the optimal normalization variable in children, particularly those over the age of 6 mo.

Aging↗

Changes in plasma and extracellular fluid volume during long-term treatment with alpha-methyldopa in 11 thiazide-treated patients with essential hypertension.

In eleven patients with essential hypertension, plasma volume (T-1824) (PV), extracellular fluid volume (82Br-distribution space) (ECFV), blood pressure (BP) and the ratio plasma to interstitial fluid volume (PV/IF) have been determined three times before treatment, after more than two months of thiazide treatment and after three and six months of combined thiazide-alpha-methyldopa (AMD) therapy. During combined treatment, PV/IF showed a significant increase, whereas PV and ECFV did not change significantly. Compared to values during thiazide therapy, PV and PV/IF increased, whereas ECFV was unchanged. BP was reduced significantly after thiazide treatment and showed a further significant fall when AMD was added. Based on the results and a review of the literature, it is concluded that AMD acts by interfering with the normal sympathetic activity, thereby producing a reduced venomotor tone and increased venous capacity. The concomitant reduced venous return of blood to the heart is suggested to contribute to the antihypertensive effect of AMD by means of a decreased cardiac output.

Aged↗

Removal of extracellular fluid from muscle: assessment of a method.

Controlled compression of mouse biceps brachii muscle caused only partial extrusion of an extracellular protein (125I-albumin) from the muscle. Concentrations of sodium and potassium in the expressed fluid at any stage of compression did not correspond with concentrations expected for extracellular fluid. This procedure, therefore, does not selectively remove extracellular fluid from muscle.

Albumins↗