Total Extracellular Fluid Volume Research Articles

Pathophysiology of vasopressin in edematous disorders.

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome and pregnancy. In recent years the use of a sensitive radioimmunoassay for plasma vasopressin has implicated the role of nonosmotic vasopressin release in the water retention of these edematous disorders. In experimental studies and studies in humans it has been found that the nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin (carotid and aortic baroreceptors) and activation of the renin-angiotensin system (renal beta-adrenergic receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. In this context neither total extracellular fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by either a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g. high-output cardiac failure, cirrhosis, pregnancy, sepsis, arteriovenous fistulae and pharmacologic vasodilators). With a decrease in effective arterial blood volume (EABV), initiated by either a fall in cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation, limits the distal tubular delivery of sodium and water thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated glomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium and water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation.

EXTRACELLULAR BODY FLUID VOLUMES IN CHRONICALLY HYPOXEMIC LAMBS

The extent to which body fluid volumes change as a consequence of chronic hypoxemia is not exactly known. Therefore we measured extracellular and plasma volumes in 5 chronically hypoxemic lambs. Before the 10th day of life we placed an inflatable balloon around the pulmonary artery, performed an atrial septostomy and inserted catheters. On days 3-4 after surgery the balloon was gradually inflated. In another 7 lambs only catheters were placed. At 5 weeks of age the lambs were studied. We used single injections of ferrocyanide and Evans blue to measure extracellular and plasma volumes, respectively.The hypoxemic lambs had a lower aortic oxygen saturation (69±9 (SD) vs 92±2%, p<0.01), and a higher hemoglobin concentration (142±17 vs 97±10 g.1−1, p<0.001) and hematocrit (43±5 vs 29±6%, p<0.01). Total extracellular fluid volume (320±31 vs 273±17 ml·kg−1 p<0.01) and blood volume (134±33 vs 80±12 ml·kg−1, p<0.05) were increased in hypoxemic lambs. This was also true for plasma volume (81±22 vs 58±5 ml·kg−1) and interstitial fluid volume (238±29 vs 215±18 ml·kg−1), although these differences did not reach statistical significance.These results show that total extracellular fluid volume and blood volume are both increased in hypoxic lambs, and that total hemoglobin mass is even more increased than the hemoglobin concentration would lead us to expect.

The second Sir George Pickering memorial lecture. What regulates whole body autoregulation? Clinical observations.

The autoregulation theory of essential hypertension states that the characteristic haemodynamic derangement of this disease, i.e. increased vascular resistance, is a homeostatic response to abnormal sodium retention by the kidneys. The postulated relationship between arterial pressure and urinary sodium excretion is disturbed in such a way that a higher than normal pressure is required for sodium excretion to keep up with intake. This will initially expand plasma volume and raise cardiac output. However, hyperperfusion of the tissues will ultimately induce vasoconstriction, presumably by greater than normal wash-out of vasodilator metabolic products. Thus, cardiac output will be restored. Some elements of this theory are not supported by current evidence, but the key element, i.e. the assumption that increased vascular resistance is somehow dependent on abnormal renal sodium handling, is consistent with the following clinical observations: Arterial pressure and urinary sodium excretion are directly correlated over a wide range of pressures in patients with autonomic failure, both acutely during titling and chronically with changes in posture during a 24-h period. The failure to demonstrate pressure-natriuresis in normal subjects may therefore be related to the amplifying effect of the sympathetic nervous system on this mechanism, so that small changes in pressure are capable of inducing large changes in sodium excretion. The pressure-natriuresis curve in patients with autonomic failure is shifted to higher pressures by administration of aldosterone, which is consistent with an important role of renal sodium retention in mineralocorticoid hypertension. Measurements of total extracellular fluid volume, plasma volume/interstitial fluid volume ratio, transcapillary escape rate of serum albumin, cardiac output and arterial pressure at timed intervals during the development of hypertension, in patients exposed to mineralocorticoid excess, or during the reversal of hypertension in nephrectomized patients treated with ultrafiltration haemodialysis, revealed an association of increased total peripheral resistance with a reduced plasma volume/interstitial fluid volume ratio and an increased transcapillary escape rate of serum albumin. This association has also been observed in cross-sectional studies of patients with essential hypertension and suggests that part of the increase in resistance is located at a post-capillary level. It may be related to compression of collapsible venules and veins due to abnormally increased interstitial fluid pressure, not only in sodium-dependent secondary forms of hypertension but also in essential hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Changes in total body water and extracellular fluid volume in infants receiving total parenteral nutrition

The nature of weight gain seen in infants receiving total parenteral nutrition continues to be controversial. The debate centers around whether or not the weight gain represents an increase in body mass or water retention. The following study was carried out to answer this question. Eighteen infants receiving peripheral or central intravenous nutrition following major surgery were studied for periods ranging from 1 to 17 weeks. The following studies were carried out after receiving informed consent from the parents and in accordance with the standards established by the Human Use Committee. Total body water was measured using the nonradioactive isotope, deuterium oxide; extracellular fluid volume was assayed using the nonradioactive isotope, sodium bromide. Both body fluid compartments were calculated using the Fick principle of dye dilution. Following double vacuum distillation, serum deuterium oxide was assayed using the falling drop technique. Serum bromide was measured by a technique developed in our laboratory that involves the complexing of bromide with gold chloride and the measurement of this chemical complex colorimetrically. Weight gain was observed in all patients. Total body water percent body weight was 82% +/- 15% prior to the initiation of intravenous nutrition; it decreased within the first week to 71% +/- 12% and then stabilized for the remainder of the study period at 75% +/- 7%. The extracellular fluid volume percent body weight was 56% +/- 15% prior to the start of intravenous nutrition; it fell to 47% +/- 10% during the first week of parenteral nutrition, and then stabilized at 40% +/- 9%.(ABSTRACT TRUNCATED AT 250 WORDS)

Testicular interstitial fluid as a monitor for changes in the intratesticular environment in the rat.

The use of testicular interstitial fluid (IF) collected from the rat testis has been validated as (1) an index of the total extracellular extratubular fluid volume of the testis (which reflects the permeability of testicular capillaries) and (2) as a means of measuring changes in the interstitial hormonal environment. The former was tested by comparing the albumin 'space' with the volume of recovered IF in the same testes from control and bilaterally cryptorchid rats sampled at 0-40 h after injection of hCG. Although the volume of IF recovered was on average only 50% of the albumin 'space', both measures increased in parallel after hCG injection and were always closely correlated (P less than 0.001) over a 4- to 5-fold range. The volume of recovered IF increased with age in parallel with increase in testicular weight, and the testosterone concentration in IF paralleled changes in peripheral serum, increasing from 45 to 80 days of age and then declining. After injection of 25 micrograms bovine LH, testosterone levels in IF, spermatic venous (SV) and peripheral venous (PV) blood increased up to 10-fold by 1 h and returned to control levels over the next 11 h. Testosterone levels in IF were always considerably higher than those in SV blood, but this difference was not constant. Subcutaneous injection of rats with an LH-RH agonist resulted in parallel increases in the serum levels of LH and in the IF and PV levels of testosterone. However, at 6 h there was an 'LH-independent' secondary increase in testosterone levels which was associated with an increase in IF volume, reflecting an increase in capillary wall permeability and hence increased transport of LH into the testis.

Changes in body fluid compartments following live Escherichia Coli septic shock in puppies

The basis for the fluid resuscitation of patients suffering from shock is the experimental and clinical data indicating a decrease in extracellular fluid following the hypotensive insult. This study was undertaken to investigate the changes in total body water and extracellular fluid volume in puppies subjected to live Escherichia coli shock. Total body water was measured using the nonradioactive stable isotope deuterium oxide and extracellular fluid volume was assayed with the nonradioactive isotope sodium bromide. Twelve, 6-week-old puppies were divided into three groups of four each. Septic shock was produced in all 12 animals by the rapid intravenous infusion of ten 9 live E coli organisms per kilogram body weight. In all animals the cardiac output and mean arterial pressure rapidly decreased below the control value within 15 minutes after the infusion. The first group of animals acted as the controls and received no treatment during the course of the study. The second group was treated with gentamicin immediately after the E coli infusion and with methylprednisolone (30 mg/kg) 15 minutes after the bacterial infusion. The third group of animals was treated with the same antibiotic and steroid protocol and in addition received a solution of Ringer's lactate plus 5% albumin at 35% of the estimated blood volume, ten minutes after the onset of shock. The animals were studied for three hours after shock was produced. The first two groups of animals (controls and antibiotic and steroid-treated animals) showed no changes in total body water or extracellular fluid volume during the entire period of study. The third group of puppies showed a transient rise in extracellular fluid volume shortly after the intravenous infusion; however, this rise returned to a base-line level two hours after the onset of shock. In this third group of animals, there was a concomitant gradual increase in total body water over the period of study which was not statistically significant. These data refute some of the older concepts of major extracellular fluid loss in animals subjected to various types of shock.

Effects of isotonic fluid load on plasma water and extracellular fluid volumes in the rat.

An isotonic fluid load was given to rats by infusing 12 ml saline i.v. in 60 min. The plasma water and extracellular fluid volumes of the whole animal and selected tissues were subsequently studied with 125I human serum albumin and 51Cr EDTA. The fluid infused was equivalent to 130% of the plasma water volume. The total extracellular fluid volume increased by 17%, while the total plasma water measured with RIHSA remained unchanged. The regional extracellular fluid volumes increased in the lung (14%), the gastric fundus (15%), large intestine (21%) and skin (28%). The results illustrate the selective distribution of an isotonic fluid overload, those tissues being effected having high compliances.

Pregnancy-associated hypertension: interrelationships of volume and blood pressure changes.

In normal human pregnancy there is considerable expansion of both plasma volume and total extracellular fluid volume, together with marked diminution of vascular reactivity in response to intravenous infusion of vasopressor agents. Pregnancy-associated hypertension (pre-eclampsia) is characterised by increased vascular reactivity, vasoconstriction and a fall in plasma volume associated with a shift of fluid from intravascular to interstitial fluid space. Direct expansion of plasma volume in patients with pregnancy-associated hypertension leads to partial correction of the abnormalities of volume homeostasis together with a significant fall in blood pressure. Certain forms of antihypertensive therapy also lead to reversal of volume contraction and improvement in cardiac function. This is associated with lowered vascular resistance and improved placental function, leading to improved pregnancy outcome. Although these observations do not elucidate the ultimate cause/causes of pregnancy-associated hypertension, they help to unravel the pathologic mechanisms by which the syndrome causes its effects and to suggest rational paths by which therapeutic endeavours may be expected to benefit mother and fetus.

The precision of a modern method for body compartment measurements using multiple isotopes

Using readily available beta and gamma detectors, combined measurements of exchangeable sodium, exchangeable potassium, total body water and extracellular fluid volume using the isotopes 24Na, 43K, 3H and 35S were made in ten normal subjects. These measurements were repeated 1–6 weeks later so that an index of precision for each isotope study could be calculated. For such measurements the precision was 55 mmol for exchangeable sodium, 149 mmol for exchangeable potassium, 1.26 litres for total body water and 1.11 litres for extracellular fluid volume. The precision of our method is the best so far reported using readily available apparatus. These results may encourage further studies on different pathological conditions in man to be undertaken in peripheral laboratories.

Pathophysiologic evidence of gentamicin nephrotoxicity in neonatal puppies.

Newborn puppies were paired (n = 21 pairs) at birth, given gentamicin (5 mg/kg/day for 7 days and the 7.5 mg/kg/day) or saline intramuscularly (IM) and studied at 10, 20, or 30 days of age. Peak gentamicin concentrations correlated neither with total body water nor extracellular fluid volume. The ratio of outer/inner cortical gentamicin concentrations increased with therapy (n = 0.579; P < 0.01). Pathologic changes in proximal tubular cells of superficial and juxtamedullary cortices corresponded to tissue accumulation of gentamicin. Inulin clearance was lower but not statistically different in gentamicin puppies at 20 and 30 days, but tubular reabsorption of phosphate was lower at 30 days (P < 0.02). Plasma creatinine decreased during the first month of life in both control and gentamicin puppies (n = -0.370; P < 0.02) and was not different between puppies even at 20 and 30 days when tubular damage was marked. No differences in urine sediment, osmolarity, glucose, and protein concentrations were noted between paired animals. Mean values of gentamicin half-life in gentamicin (control) puppies decreased from 80.3 (84.0) min at 10 days to 45.3 (50.3) min at 20 days, but increased to 61.0 (40.0; P < 0.05) min at 30 days. Similar studies in older puppies and adult animals given gentamicin resulted in an increase in plasma creatinine and gentamicin half-life within 10 days. Results of these studies confirmed that gentamicin nephrotoxicity occurred within 10 days in puppies treated from birth. The relative tolerance of the neonatal puppy to the toxic effects of gentamicin was attributed to the distribution of renal blood flow predominantly to juxtamedullar nephrons at birth which spared superficial nephrons from gentamicin accumulation and toxicity until renal blood flow was redistributed to the outer cortex and filtration in superficial nephrons began after the first wk of life.

Nutritional assessment: Whole body impedance and body fluid compartments

Abstract Measures of total body water and extracellular fluid volume would provide valuable information for the assessment of nutritional status in patients. Time and cost factors make the use of tracer dilution techniques impractical in routine nutritional assessment batteries. Some studies suggest that measurements of the electrical impedance properties of the body can be used to estimate total body water and extracellular fluid volume. The observed and predicted relationships between whole body impedance and body fluid compartment volumes are discussed, and problems which may limit the accuracy of prediction of body fluid compartment volume from whole body impedance measures are discussed. With further improvements, whole body impedance measurement could provide a practical bedside method for measurement of body fluid compartment volumes.

Sodium, extracellular fluid volume, and cardiac output changes in the genesis of mineralocorticoid hypertension in the intact dog.

SUMMARY Twenty-four trained, conscious dogs with chronically implanted iliac catheters were used to assess the relative roles of sodium (Na) and volume in the development of mineralocorticoid hypertension. All were maintained on restricted Na diets; supplemental Na was given as slow I.V. infusions of 0.9% NaCl solution. The effect of gradual replenishment of total body sodium on arterial blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR) and extracellular fluid volume (ECFV) was assessed at four separate levels of cumulative Na intake (70,140,420 and 840 mEq). The sequence of changes in 12 metyrapone-treated dogs was compared with 12 untreated controls submitted to the same protocol. Changes in fluid volumes and CO were virtually identical in the two groups; however, only dogs previously treated with metyrapone became significantly hypertensive (AMAP » 16 and 28 mm Hg,p 140 TPR and BP rose in the face of increases in output and ECFV that were not greater than those found at 140 mEq cumulative Na intake. These findings suggest that this steroid-induced hypertension in the dog is resistance-m ediated from its earliest stages, and that restoration of sodium stores rather than volume expansion played the more important role in the initiation of this hypertension. (Hypertension 1: 331-336, 1979)

Fluoride concentration in tooth germs of permanent teeth of the domestic pig

Unerupted teeth and the overlying enamel organs and associated fibrous tooth follicles, collectively referred to as ‘supra-coronal tissue’ (SCT), were removed from mandibles of 3 pigs aged 7 months. Fluoride was determined in the SCT, dental papilla, surface enamel and bulk enamel. F concentrations averaged about 2.3 μg F/g wet wt SCT and 0.2 μg F/g dental papilla. There were statistically-significant positive correlations between F concentration in SCT and (a) the degree of mineralization (density) of enamel and (b) the F concentration in surface enamel. Ca and P were determined in the ash of SCT and dental papillae. Total water and extracellular fluid volume were also measured. The percentage of F extracted in water and 10 per cent EDTA, pH 6.5, was estimated. On the basis of these preliminary results, it is suggested that fluoride which accumulates in the tissue overlying the crown is loosely bound and that some is associated with calcium.

Extravascular Contrast Material: The Major Component of Contrast Enhancement

The distribution volume of 125l-diatrizoate in rat tissues was studied 5 seconds to 5 minutes after intravenous injection and 5 seconds to 2 minutes after intra-arterial injection. Immediately after injection, diatrizoate was distributed into a larger volume than plasma. Marked temporal changes in the distribution volume of individual tissues occurred during the first 2 minutes. At 5 minutes, the diatrizoate space approached the total extracellular fluid volume, with more than 80% of the contrast agent remaining outside the blood vessels. Thus the relative magnitude of contrast enhancement of a tissue appears to be related to the volume of the rapidly equilibrating extracellular space. Intra-arterial administration can significantly overload muscle with contrast material for about 2 minutes. This and other temporal changes in contrast distribution may prove useful in contrast-enhanced computed tomography using short scanning times.

Blood volume of the ascidian Pyura praeputialis

Blood dilution curves have been obtained by injecting 125I labelled albumin and 125I labelled gamma‐globulin into the blood of Pyura praeputialis. After mixing is complete the dilution curve shows a two‐stepped pattern.There is some question as to how the two steps of the curve should be interpreted. The first step has been extrapolated to give blood volume s.s., i.e. volume of the vessels, sinuses and lacunae of the vascular system. Values for this range from 30% to 45 % of body weight, with a mean value of 35%.The second step has been extrapolated to give total extracellular fluid volume, i.e. blood volume plus interstitial fluid volume. Values for this range from 21 % to 52 % of body weight, the average being 38 %.The interstitial space ranges from 15 % to 32 % of the weight of the visceral mass, the average being 23 %.The rationale for the above interpretation of the dilution curve is stated and discussed. Most reliable is extracellular fluid volume which probably corresponds to the blood volume of other invertebrates with open systems.An attempt was made to assess the relative importance of (a) the visceral circuit and (b) the tunic circuit, by comparing the specific activities of the visceral mass and the tunic. The specific activities indicate little or no blood in the tunic circuit: this result is suspect.

An approach to the measurement of body fluid compartment volumes in non-steady conditions in the rat.

A method has been developed by which body fluid volume changes can be assessed frequently after only one initial injection of the appropriate radioactive tracers. This method is based on the assumptions that, 1. following their intravenous injection, the temporal behaviour of tritiated water or radio-sodium can be adequately modelled by the kinetic behaviour of an open, interconnected two-compartment system; 2. known amounts of tracer are added to or irreversibly removed from the system only via the first compartment. In the measurement of body fluid volume changes in rats after isotonic blood volume expansion, the rapid urinary tracer excretion was treated as a series of negative tracer "injections" made instantaneously into the first tracer compartment at the mid point of each short urine collection period. The effect of these "injections" on the first compartment was regarded as diminishing with time in accordance with the steady state rate constants. The vaolues for non steady state changes in total body water volume and functional extracellular fluid volume obtained by such a mathematical treatment, agreed closely with directly measured changes where such direct comparisons could be made.

Water and electrolyte alterations during the life course of the BIO 14.6 Syrian golden hamster. A disease model of a hereditary cardiomyopathy

In a hereditary cardiomyopathy of the Syrian hamster, changes in water and electrolyte metabolism were investigated. Four age groups were differentiated histopathologically. Body weight of cardiomyopathic animals was initially decreased but later exceeded that of controls. The total extracellular fluid volume was larger than in controls, with a decreased haematocrit; these changes were especially pronounced in the oldest hamsters. The myocardial extracellular space and water content underwent similar changes to those in total extracellular volume. Besides a tendency to hyponatraemia there were no alterations of the serum potassium and sodium levels in the youngest three groups. However, in animals with congestive heart failure, serum potassium was decreased and serum sodium increased. Initially serum calcium was increased and the magnesium value was normal. In prenecrotic tissue myocardial magnesium was markedly decreased but calcium only slightly increased. In the necrotizing myocardium, however, calcium was greatly elevated; in the later stages, calcium tended to decrease. Surprisingly, magnesium was unchanged in necrotizing tissue, and decreased later. Myocardial sodium and potassium did not exhibit changes during the prenecrotic but in the following stages, when potassium was lowered and sodium was elevated. A distinct rise of the extracellular sodium concentration was observed in animals with obvious congestive heart failure. Disturbed myocardial calcium and magnesium metabolism is restricted to cardiomyopathic cells and is thought to play an essential role in the necrotic process. Succeeding changes, especially in sodium and potassium, are thought to occur in myocardial cells developmentally normal but subjected to a sustained volume overload. Secondary aldosteronism is believed to be the cause for the terminal fluid and electrolyte changes in serum and myocardium.

Studies on the New Zealand strain of genetically hypertensive rats.

1. The New Zealand strain of rats with genetic hypertension (GH rats), the Japanese strain with spontaneous hypertension and the salt-sensitive strain of Dahl are now well established as three genetically pure lines for use in hypertensive research. Other pure lines not consciously selected for high blood pressure have also recently been shown to exhibit hypertension. 2. In the GH rats the inheritance of the blood pressure appears to be polygenic; thus a simple causation of the hypertension appears unlikely. The inheritance is also complex in the other pure lines of hypertensive rats. 3. In the GH rats variation in intake of sodium from 0.05% to 1% of the solid diet does not affect the development of the hypertension. 4. The renin-angiotensin-aldosterone system does not appear to play a primary role in the initiation of the hypertension in the GH rats. Compared with normotensive rats of the parent colony, plasma and renal renin are decreased, total exchangeable and carcass sodium are decreased, as are also the plasma volume and total extracellular fluid volume. Plasma sodium is normal and plasma potassium increased. 5. There is no evidence of a primary abnormality of catecholamine storage or turnover. Prevention of the development of the sympathetic nervous system from birth does not entirely abolish the difference in blood pressure between GH rats and comparably treated normotensive rats. 6. The increased peripheral resistance in blood-perfused hind limbs and tails of GH rats is due both to increased neurogenic and myogenic components and to a structural element. Increased vascular reactivity to a variety of constrictor agents is readily demonstrated in saline-perfused preparations. 7. The different strains of hypertensive rats may in their diversity mirror the differences between the various forms of human essential hypertension.

The relationship between body fluid compartment volumes, renin activity and blood pressure in chronic renal failure.

1. The relationship between various body fluid compartment volumes, plasma renin activity and mean arterial blood pressure was studied in twenty-six patients with chronic renal failure. 2. Mean arterial blood pressure was positively correlated with total exchangeable sodium, blood volume and plasma renin activity: there was no significant correlation with either total body water or extracellular fluid volume. 3. Multiple regression analysis revealed that plasma renin activity combined with total exchangeable sodium, blood volume, red cell mass or total body water provided a better means of predicting blood pressure than any of the variables taken alone. 4. In a second study performed after a period of regular dialysis treatment no correlation was found between mean arterial pressure and either body fluid compartment volumes or plasma renin activity.