Extracellular Fluid Volume Status Research Articles

Disorders of Potassium Homeostasis: An Approach Based on Pathophysiology

Disorders of potassium (K+) homeostasis are frequently encountered in clinical medicine and may have serious sequelae, particularly cardiac arrhythmias. Since long-term K+ balance depends on regulation of renal excretion of K+, the focus of this paper is to provide a novel way to analyze the K+ excretory process at the bedside in a noninvasive fashion. A fundamental aim was to incorporate recent new advances in K+ physiology to the clinical analysis of K+ disorders. In so doing, we have tried to replace eponyms and largely descriptive terms with more specific, but hypothetical pathophysiologic diagnoses. The approach we used focuses on an assessment of the components of K+ excretion in vivo. If the rate of excretion of K+ differs from the “expected” value for the stimulus of hypokalemia or hyperkalemia, one should determine whether the fault is with the flow rate and/or the [K+] in the terminal cortical collecting duct. The former is influenced primarily by the rate of excretion of osmoles when antidiuretic hormone acts, whereas the [K+] in the cortical collecting duct is determined by factors that modulate rate of electrogenic reabsorption of Na+ in that segment and its conductance for K+. By examining the extracellular fluid (ECF) volume status, the plasma renin activity, and the renal response to the induction of ECF volume contraction, we attempted to deduce whether the change in electrogenic reabsorption of Na+ was due to an altered Na+ transport or apparent permeability to chloride in the cortical collecting duct. We believe that an approach which draws heavily on pathophysiology can be of practical use at the bedside and, in addition, indicate areas in which more research could be fruitful. To illustrate these points, two clinical cases with hypokalemia and two with hyperkalemia were analyzed. Nevertheless, it is important to emphasize that the approach provided is speculative.

Changes in Brain Natriuretic Peptide and Atrial Natriuretic Peptide Plasma Concentrations During Hemodialysis in Patients with Chronic Renal Failure

The present study aimed to investigate whether brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), cortisol and thyroid hormone concentrations change during hemodialysis in patients with chronic renal failure. Blood samples were withdrawn in 30 patients with chronic renal failure before hemodialysis, 2 hours after the beginning and at the end of hemodialysis. ANP and BNP concentrations were determined by radioimmunoassay after Sep Pak C18 extraction. Cortisol, T3, T4, FT4 and TSH serum concentrations were measured by enzyme immunoassay. BNP and ANP plasma levels were strongly elevated in patients with renal failure (BNP 22.4 fold, ANP 4.7 fold versus controls [n = 20]) and decreased significantly (p < 0.001) during hemodialysis (BNP [pg/ml]: 192.1 +/- 24.9, 178.6 +/- 23.0, 167.2 +/- 21.8; ANP [pg/ml]: 240.2 +/- 28.7, 166.7 +/- 21.3, 133.0 +/- 15.5). BNP plasma concentrations showed a stronger elevation than ANP plasma levels and a less pronounced decrease during hemodialysis (BNP: 13.5 +/- 1.8%, ANP: 40.2 +/- 3.5%, p < 0.001) which might in part be due to the longer half-life of BNP. Cortisol and TSH levels did not change significantly whereas T3, T4 and FT4 levels increased significantly (p < 0.001) during hemodialysis. Since corticosteroids and thyroid hormones stimulate natriuretic peptide release, these data suggest that the dialysis-induced decrease of ANP and BNP plasma concentrations is not augmented by a loss of cortisol or thyroid hormones during hemodialysis. The present data provide support that BNP and ANP plasma concentrations are sensitive indicators of the extracellular fluid volume status.(ABSTRACT TRUNCATED AT 250 WORDS)

Disorders of water and sodium balance.

The serum sodium concentration reflects a patient's relative water balance and thus determines if the patient needs more or less water than normal maintenance needs would dictate. The serum sodium concentration has no bearing on whether a patient requires sodium restriction or saline administration. Rather, the sodium/saline balance is determined by clinical assessment of the patient's extracellular fluid volume. Physicians must clearly understand the principles involved when assessing a patient's water and sodium needs. After maintenance water needs and any foreseeable ongoing losses have been factored in, an intelligent plan of fluid management can be initiated. Frequent reassessments, with serial weight measurements, clinical evaluations of extracellular fluid volume status, and determinations of serum sodium concentration, are essential to determine if the desired therapeutic goals are being reached.

The Electrolytes in Hyponatremia

It is commonly taught that retention of free water is the dominant factor reducing the serum sodium concentration in hyponatremia. To determine whether the concentrations of other electrolytes are similarly diluted, we identified 51 patients with hyponatremia (Na = 121 +/- 1 mmol/L [mEq/L]) and compared electrolyte and laboratory values at the time of hyponatremia with values at a time when serum sodium was in the normal range (138 +/- 1 mmol/L). The medium interval between these measurements was 12 days. At the time of hyponatremia, serum sodium and chloride were substantially and significantly reduced by 12% to 15%. Although many hyponatremic patients had overtly increased or decreased concentrations of the other measured electrolytes, there were no significant changes in the mean concentration for any of these at the time of hyponatremia. Unchanged mean values were found for the plasma concentration of bicarbonate (26.1 +/- 0.6 normal v 25.2 +/- 0.8 mmol/L at the time of hyponatremia), potassium (4.31 +/- 0.10 v 4.33 +/- 0.15 mmol/L), albumin, phosphate, and creatinine. The stability of these laboratory values was observed both in patients with clinically normal extracellular fluid (ECF) volume and in those with true or effective ECF depletion. The urinary sodium (UNa) concentration was found to be a reliable predictor of the ECF volume status, whereas the fractional sodium excretion (FENa) was not. Electrolyte derangements are common in patients with hyponatremia, but are usually confined to patients on diuretics or who have an abnormal ECF volume. In the absence of these complicating situations, the plasma electrolytes are typically normal and are not reduced by dilution to the same extent as Na and CI. Based on a review of both the classic and recent knowledge concerning electrolyte regulation in hyponatremia, we propose that two factors explain these observations. First, the degree of dilution is overestimated because of Na losses in urine and perhaps Na shift into cells. Second, both renal and extrarenal adaptive mechanisms are activated by hyponatremia that stabilizes the concentration of other ions. One of these mechanisms is cell swelling, which triggers a volume-regulatory response leading to the release of ions and water into the ECF. Other adaptive mechanisms are mediated by antidiuretic hormone (ADH) per se, and by atrial natriuretic peptide (ANP).

Salt Sensitive Human Hypertension

Heterogeneity exists among humans in the responses of blood pressure to alterations in sodium and extracellular fluid volume status. A variety of approaches have been utilized to characterize sodium responsivity of blood pressure including rapid volume expansion and contraction and dietary sodium manipulation. Studies conducted in our laboratories over the past 15 years have enabled us to examine salt sensitivity of blood pressure in different ways and to characterize this phenomenon as well as to define neurohumoral, demographic and genetic factors associated with it in normotensive and hypertensive humans.

Digitalislike Immunoreactive Substances and Extracellular Fluid Volume Status in Chronic Hemodialysis Patients

Circulating digitalislike immunoreactive substances (DLIS) may represent a class of volume-sensitive natriuretic factors. Chronic renal failure patients are known to have elevated levels of circulating natriuretic activity and also to have detectable DLIS. Using digoxin radioimmunoassay, DLIS levels were measured in desalted, deproteinized plasma from 15 stable hemodialysis patients. Predialysis DLIS was 109.3 +/- 6.3 pg/mL (digoxin equivalents) and decreased to 97.5 +/- 5.9 pg/mL following dialysis (P less than 0.001). Predialysis DLIS correlated with weight gain from the prior dialysis (P less than 0.01). The degree of extracellular fluid volume expansion predialysis also correlated with predialysis DLIS (P less than 0.01). Postdialysis DLIS also correlated with postdialysis extracellular fluid volume status (P less than 0.01). DLIS levels in dialysis patients were higher than in 50 normal subjects (30.0 +/- 1.2 pg/mL; P less than 0.001). Also, the changes in DLIS with dialysis were paralleled by similar changes in simultaneously measured human alpha-atrial natriuretic peptide (ANP) levels. These results demonstrate that (1) DLIS levels are higher in hemodialysis patients than in normal individuals; (2) with dialysis, DLIS levels increase and decrease in association with extracellular fluid volume expansion and removal, respectively; (3) DLIS levels correlate with the degree of extracellular fluid volume expansion in dialysis patients; and (4) DLIS levels change in parallel with levels of another class of natriuretic factor ANP. These characteristics are consistent with the hypothesis that DLIS represents a volume-sensitive factor.

Clinical assessment of extracellular fluid volume in hyponatremia

Assessment of the status of extracellular fluid volume is important in evaluating the cause and selecting appropriate therapy for hyponatremic disorders. Since the sensitivity and specificity of clinical assessment of extracellular fluid volume status in hyponatremic states remain unknown, 58 non-edematous patients with serum sodium less than 130 meq/liter were prospectively evaluated. Patients were judged to be either normovolemic (no response of serum sodium to saline infusion) or hypovolemic (saline infusion significantly corrected hyponatremia). Hypovolemic patients had significantly higher plasma renin activity (5.0 ± 1.5 versus 2.5 ± 0.5 ng/ml per three hours, p <0.05) and norepinephrine (1,054 ± 252 versus 519 ± 55 pg/ml, p <0.05) concentrations than did normovolemic patients. Clinical assessment correctly identified only 47 percent of hypovolemic patients and 48 percent of normovolemic patients. Thus, clinical assessment was of limited sensitivity and specificity in identifying extracellular fluid volume status in these hyponatremic patients. However, the concentration of sodium in a spot urine sample clearly separated hypovolemic (mean U Na = 18.4 ± 3.1 meq/liter) from normovolemic (mean U Na = 72 ± 3.7 meq/liter, p <0.001) hyponatremic patients.

Abnormal antidiuretic hormone secretion in patients with systemic lupus erythematosus.

There have been anecdotal reports describing patients with systemic lupus erythematosus (SLE) and inappropriately elevated secretion of antidiuretic hormone (ADH), but no systematic studies of ADH and its metabolism in SLE have been performed. We measured plasma ADH levels in 36 stable SLE patients with normal renal function and examined the relationship of the circulating ADH concentration to clinical disease activity and effective extracellular fluid volume as reflected by peripheral plasma renin activity (PRA) and plasma aldosterone concentration. The mean ADH level was elevated, 11.4 +/- 1.0 microU/ml (normal 0.4-1.4 microU/ml), while mean PRA and aldosterone were 5.4 +/- 0.6 ng/ml/h and 10.6 +/- 1.6 ng/100 ml, respectively. When patients were divided into two groups according to disease duration, those with SLE for 2 years or more had significantly higher plasma ADH levels (13.9 +/- 1.4 vs. 7.7 +/- 0.9 microU/ml; p less than 0.001 and urinary osmolality (697 +/- 63 vs. 445 +/- 49 mosm/kg; p less than 0.02) compared to those with SLE of less than 2 years duration. No differences in serum Na+, K+, PRA, plasma aldosterone concentration, C3, or 24-hour urinary protein excretion were noted between these two groups. Six patients with SLE for less than 2 years underwent a standard water load (20 ml/kg); in 3/6 there was a paradoxical increase in the plasma ADH concentration. These findings indicate that SLE is associated with elevated plasma ADH levels that increase with prolonged disease duration. This abnormality is unrelated to the usual serologic indices of SLE activity, effective extracellular fluid volume status, or any apparent renal unresponsiveness to ADH.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of extracellular fluid volume and plasma bicarbonate concentration on proximal acidification in the rat.

The effects of systemic bicarbonate concentration and extracellular fluid volume status on proximal tubular bicarbonate absorption, independent of changes in luminal composition and flow rate, were examined with in vivo luminal microperfusion of rat superficial proximal convoluted tubules. Net bicarbonate absorption and bicarbonate permeability were measured using microcalorimetry. From these data, net bicarbonate absorption was divided into two parallel components: proton secretion and passive bicarbonate diffusion. The rate of net bicarbonate absorption was similar in hydropenic and volume-expanded rats when tubules were perfused with 24 mM bicarbonate, but was inhibited in volume-expanded rats when tubules were perfused with 5 mM bicarbonate. Volume expansion caused a 50% increase in bicarbonate permeability, which totally accounted for the above inhibition. The rate of proton secretion was unaffected by volume expansion in both studies. The rate of net bicarbonate absorption was markedly inhibited in alkalotic expansion as compared with isohydric expansion. Bicarbonate permeabilities were not different in these two conditions, and the calculated rates of proton secretion were decreased by greater than 50% in alkalosis. Net bicarbonate absorption was stimulated in acidotic rats compared to hydropenic rats. This stimulation was attributable to a 25% increase in the rate of proton secretion. We conclude that (a) proton secretion is stimulated in acidosis, inhibited in alkalosis, and is not altered by volume status; (b) bicarbonate permeability is increased by volume expansion but is not altered by increases in plasma bicarbonate concentration; (c) when luminal bicarbonate concentrations are similar to those of plasma, net bicarbonate absorption is dominated by proton secretion and is thus sensitive to peritubular bicarbonate concentrations, and insensitive to extracellular fluid volume; (d) when luminal bicarbonate concentrations are low and proton secretion is slowed, bicarbonate permeability and thus extracellular fluid volume have a greater influence on net bicarbonate absorption.

Renal fluoride excretion: experimental evaluation of the role of extracellular volume status during intact and impaired kidney function.

The renal disease of inorganic fluoride was studied in 5/6-nephrectomized and kidney-intact rats in order to evaluate the influence of the extracellular fluid volume status on net tubular fluoride reabsorption. Loss of renal functional mass impaired the ability of the hydropenic uremic rat to excrete fluoride, although tubular reabsorption of fluoride was depressed. Fractional fluoride excretion was closely correlated to urinary flow rate in hydropenic rats; no influence of urinary pH from 5.80 to 6.18 could be demonstrated. Acute, moderate expansion of the extracellular fluid volume by isotonic saline was followed by a significant rise in fractional fluoride excretion in uremic as well as in control rats, indicating that extracellular fluid volume is an important physiological determinant of passive tubular fluoride reabsorption.

Renal effects of prostaglandin E1 in hypertensive patients.

The effects of prostaglandin E1 on fluid and sodium excretion, creatinine clearance and renin release were examined in 26 hypertensive patients including 9 cases of essential hypertension, 10 of renovascular hypertension and 7 of primary aldosteronism. When prostaglandin was infused intravenously in a total dose of 120 mug in 60 min, urine volume was increased in 70% of cases, and sodium excretion in 61%, but little changes were observed in creatinine clearance. The most prominent diuresis and natriuresis were obtained in primary aldosteronism (mean increase was 319% in urinary volume, and 222% in sodium output). The average increases in urinary volume were 61% in patients with essential hypertension and 97% in renovascular hypertension. And urinary output of sodium was increased by 63% in the former and 56% in the latter. The remarkable renal effects of prostaglandin E1 in primary aldosteronism were completely abolished after the administration of spironolactone. Significant elevation of plasma renin activity resulted from prostaglandin E1 infusion in essential hypertension, while no constant effect was obtained in renovascular hypertension and primary aldosteronism. The present experiments indicate that prostaglandin E1 has different effects on the kidney according to the types of hypertension and the effects correlate closely with patient's status of extracellular fluid volume or sodium balance.

Effect of changes in extracellular fluid volume upon the volumes of distribution of ferrocyanide and inulin.

ArticleEffect of Changes in Extracellular Fluid Volume Upon the Volumes of Distribution of Ferrocyanide and InulinF. H. Epstein, C. R. Kleeman, M. E. Rubini, and E. LamdinF. H. EpsteinFrom the Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, C. R. KleemanFrom the Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, M. E. RubiniFrom the Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, and E. LamdinFrom the Department of Internal Medicine, Yale University School of Medicine, New Haven, ConnecticutPublished Online:01 Sep 1955https://doi.org/10.1152/ajplegacy.1955.182.3.553MoreSectionsPDF (603 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByEfficacy and safety of sugammadex in the reversal of deep neuromuscular blockade induced by rocuronium in patients with end-stage renal diseaseEuropean Journal of Anaesthesiology, Vol. 32, No. 10Assessment of Extracellular Fluid Volume and Fluid Status in Hemodialysis Patients: Current Status and Technical Advances11 June 2012 | Seminars in Dialysis, Vol. 25, No. 4Determination of extracellular fluid volume in the dog with ferrocyanidePfl�gers Archiv European Journal of Physiology, Vol. 357, No. 3-4Indirect determination of mean whole body and intracellular CO2 and buffer capacityRespiration Physiology, Vol. 11, No. 2Elektrolythaushalt und parenterale Flüssigkeitstherapie beim Hund13 May 2010 | Zentralblatt für Veterinärmedizin Reihe A, Vol. 14, No. 8The apparent expansion of the inulin space in the nephrectomized dogExperientia, Vol. 12, No. 11 More from this issue > Volume 182Issue 3September 1955Pages 553-556 Copyright & PermissionsCopyright © 1955 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1955.182.3.553PubMed13258853History Received 13 February 1955 Published online 1 September 1955 Published in print 1 September 1955 Metrics