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Hyponatremia in patients undergoing CAPD: role of water gain and/or malnutrition.

BACKGROUND: Hyponatremia has a number of different causes; some may have serious untoward implications for patients undergoing chronic ambulatory peritoneal dialysis (CAPD). OBJECTIVE: To determine the pathophysiology of hyponatremia in patients on CAPD. METHODS: A retrospective analysis was carried out on 210 patients on CAPD. We selected patients with 2-4 consecutive periods when the plasma sodium concentration was < or =130 mmol/L and again when it was > 133 mmol/L. Exclusion criteria included hyperglycemia, orthostatic hypotension, edema, and inadequate records. RESULTS: An electrolyte-free water gain appeared to be the main cause of hyponatremia in only 1 of 5 patients because this was the only patient with a significant increase in body weight. In 1 patient, there was weight loss in the hyponatremic period, suggesting tissue catabolism was present. In 3 patients, there was neither weight gain nor evidence for a contracted extracellular fluid volume in the hyponatremic period, suggesting that intracellular potassium and phosphate loss could be the major mechanism for their hyponatremia. CONCLUSION: When hyponatremia is due to a catabolic state, its management should aim to restore intracellular fluid composition (i.e., to correct malnutrition).

Female↗

Vasopressin supplementation in a porcine model of brain-dead potential organ donors.

The use of vasopressin to limit the polyuria of the brain-dead organ donor is a controversial subject. It is held that the associated vasoconstriction may result in ischemic damage to transplantable organs. However, the derangements in the intravascular--and thereby interstitial and intracellular--fluid and electrolyte balances associated with diabetes insipidus may lead to gross fluid shifts in the organ donor. Aggressive resuscitation with crystalloid solutions may aggravate these fluid shifts, contribute to the development of interstitial and intracellular edema, and ultimately result in cardiovascular failure and the rejection of the organs for transplantation. Theoretically, a minute amount of vasopressin is required for the maintenance of normal intravascular fluid and electrolyte balance, and it is best administered as a continuous i.v. infusion. We report on our study of an animal model of a brain-dead organ donor, in which polyuria, hypernatremia, and hyperosmolality developed. The administration of low-dose (2-10 microU/kg/min) vasopressin by continuous infusion maintained plasma sodium and osmolality in the normal range over the course of the experiments (24 hr) in the experimental group. Cardiovascular function remained stable in both control and experimental vasopressin-infusion) groups, with the only significant difference being a moderate rise in pulmonary artery pressure. It would appear that early low-dose vasopressin supplementation by continuous i.v. infusion may improve donor management. The maintenance of intravascular homeostasis may contribute to the quality and number of organs for transplantation.

Animals↗

Uptake of nicotine and extracellular space markers by isolated rat ganglia in relation to receptor activation.

1. Uptake of (3)H-nicotine by isolated rat superior cervical sympathetic (SCG) and nodose (NG) ganglia was measured in vitro. Depolarization of the ganglia by nicotine was measured electrically.2. Nicotine depolarized the SCG but not the NG. The mean ED50 for depolarization was 5.3 x 10(-6)M.3. Both ganglia accumulated nicotine when incubated in 3.1 x 10(-5)M(3)H-nicotine: after 30 min incubation the ratios of tissue to medium concentrations were (mean +/- S.E. of mean): SCG, 3.49 +/- 0.13; NG, 2.50 +/- 0.09.4. Total water contents, estimated by drying to constant weight, were: SCG, 83.8 +/- 0.12%; NG, 80.1 +/- 0.21%. Extracellular spaces, measured as (3)H-mannitol space, were: SCG, 38.8 +/- 1.3; NG, 40.3 +/- 0.8% wet weight. These values were not significantly altered by nicotine.5. Correction for tissue fluid spaces indicated that the ratio of the mean intracellular fluid concentration to the extracellular fluid concentration for (3)H-nicotine at 3.1 x 10(-5)M were: SCG, 7.4; NG, 5.6. The ratios were not altered in any consistent manner on varying the nicotine concentration between 3.1 x 10(-7) and 1.6 x 10(-4)M.6. When the nicotine concentration was sufficiently great (6.2 x 10(-6)M or more) to evoke large SCG depolarizations, hexamethonium (2.5 x 10(-3)M) reduced (3)H-nicotine uptake by the SCG by up to 19% without affecting uptake by the NG, and thereby reduced the uptake difference between the two ganglia. With nicotine concentrations <6.2 x 10(-6)M, hexamethonium did not modify uptake by either ganglion.7. It was concluded that nicotine may be concentrated within neurones, and that such intracellular accumulation may be augmented during depolarization induced by nicotine.

Animals↗

Body fluid and hematologic adjustments during resting heat acclimation in rhesus monkey.

The purpose of this study was to examine body fluid adjustments during prolonged resting heat exposure in primates. Rhesus monkeys were acclimated for 35 days at 35 degrees C and 30% rh. Red cell mass, extracellular fluid volume (ECF), and total body water (TBW) were determined with 51Cr, 35SO4, and 3H2O, respectively, prior to and at intervals during heat exposure. Heat acclimation was characterized by a fluid shift from the interstitial compartment. In relation to TBW, interstitial fluid volume and ECF decreased 10.3 and 8.3%, respectively, while plasma volume (PV) and intracellular fluid were increased an average of 5.8 and 3.8%. TBW increased 4.8% during heat exposure. Hematocrit and hemoglobin decreased significantly on day 3 (7.9 and 6.5%) followed by a return toward control values. PV in relation to TBW remained elevated throughout the exposure. An increased drinking (25.0%) was associated with a decrease in caloric intake (30.7%) during heat acclimation. This study has provided a complete body fluid compartment analysis during resting heat acclimation in the rhesus monkey. Our results are consistent with the hypothesis that heat acclimation in primates is characterized by a protein and fluid shift from the interstitial fluid compartment to the cardiovascular system and to the intracellular compartment.

Adaptation, Physiological↗

The potential use of dual frequency bioimpedance in predicting the distribution of total body water in health and disease.

The distribution of water between extracellular fluid (ECF; measured by the inulin dilution technique) and intracellular fluid (ICF; calculated as the difference between total body water, which was measured by the deuterium dilution technique, and ECF) was measured in 12 healthy subjects. The results were compared with predictions made by anthropometry and whole body impedance obtained at 1kHz (Z(1)) and 50 kHz (Z(50)). Z(1) and Z(50) were also measured in 82 health subjects and 27 patients without clinically detectable oedema, and in 10 patients with oedema. Anthropometry and height(2)/Z(1) showed similar correlations with inulin space (r = 0.64, SEE = 1.74 L and r = 0.65, SEE = 1.75 L respectively). The ratios of Z (1)Z (50) in oedematous patients (1.03 +/- 0.02), which were universally lower than those obtained in normal subjects (1.18 +/- 0.04), overlapped with those obtained in patients without oedema (1.11 +/- 0.05). The study suggests that in this group of normal subjects low frequency bioimpedance measurements are not superior to anthropometric estimates of ECF. They also suggest a limitation in the use of the dual frequency bioimpedance meter to distiguish between patients with and without oedema.

Journal Article↗

Fluid volume control during short-term space flight and implications for human performance.

Space flight exerts substantial effects on fluid volume control in humans. Cardiac distension occurs during the first 1-2 days of space flight relative to supine and especially upright 1g conditions. Plasma volume contraction occurs quickly in microgravity, probably as a result of transcapillary fluid filtration into upper-body interstitial spaces. No natriuresis or diuresis has been observed in microgravity, such that diuresis cannot explain microgravity-induced hypovolemia. Reduction of fluid intake occurs irrespective of space motion sickness and leads to hypovolemia. The fourfold elevation of urinary antidiuretic hormone (ADH) levels on flight day 1 probably results from acceleration exposures and other stresses of launch. Nevertheless, it is fascinating that elevated ADH levels and reduced fluid intake occur simultaneously early in flight. Extracellular fluid volume decreases by 10-15% in microgravity, and intracellular fluid volume appears to increase. Total red blood cell mass decreases by approximately 10% within 1 week in space. Inflight Na(+) and volume excretory responses to saline infusion are approximately half those seen in pre-flight supine conditions. Fluid volume acclimation to microgravity sets the central circulation to homeostatic conditions similar to those found in an upright sitting posture on Earth. Fluid loss in space contributes to reduced exercise performance upon return to 1g, although not necessarily in flight. In-flight exercise training may help prevent microgravity-induced losses of fluid and, therefore, preserve the capacity for upright exercise post-flight. Protection of orthostatic tolerance during space flight probably requires stimulation of orthostatic blood pressure control systems in addition to fluid maintenance or replacement.

Astronauts↗

Electrolytes of breast-cyst fluid.

We constructed an electrolyte balance sheet for 11 individual specimens and two pooled specimens of breast-cyst fluid. Na+ and K+ ranged in concentrations from those representative of extracellular fluids (147 and 9 mmol/L, respectively) to those of intracellular fluid or a high K+ secretion (23 and 168 mmol/L, respectively). Cl- concentrations ranged from 9 to 98 mmol/L (mean, 31), bicarbonate concentrations from 0 to 34 mmol/L (mean, 16). Ca2+ concentrations did not exceed 2.1 mmol/L. Total protein ranged from 14.7 to 35.8 gL. Fluid osmolality ranged from 249 to 300 mOsm/kg of water (mean, 280). The difference between measured cations and anions indicates an "anion gap" of 140 mmol/L, which must be carried by 46 mOsm/kg of water. We suggest that tricarboxylic acids of the Krebs cycle may account for the missing trivalent anions.

Bicarbonates↗

Dehydration-induced drinking in humans.

Mechanisms of drinking have been studied extensively in laboratory mammals, but comparatively little information is available on human consumption of fluids. The assumption that osmotic disequilibrium between extra- and intracellular fluid can be rectified within seconds may not be true for plasma and red blood cell (RBC) fluid in humans inasmuch as stress-induced hyperosmotemia to +13 mosmol/kg does not cause a significant change in mean RBC corpuscular volume. Unlike some mammals, humans have a delay in rehydration (involuntary dehydration) after fluid loss. Two factors unique to humans that probably contribute to involuntary dehydration are 1) upright posture and 2) extracellular fluid and electrolyte loss by sweating from exercise and heat exposure. If drinking is influenced by upright postural changes, it may be related to increased plasma renin activity (PRA) but not to increases in plasma osmolality or arginine vasopressin concentration. Under combined stresses of heat, exercise, and prior dehydration, exercise is the greatest inhibiting factor and heat exposure has the least inhibitory effect on voluntary water intake. The rate of drinking during exercise in heat has a high correlation with sweat rate but is essentially unrelated to the well-established dipsogenic factors of plasma volume, osmolality, and PRA. However, it is likely that some or all of these dipsogenic factors act to initiate drinking in humans.

Arginine Vasopressin↗

Prohevein is poorly processed but shows enhanced resistance to a chitin-binding fungus in transgenic tomato plants.

In latex of rubber tree (Hevea brasiliensis), prohevein, homologous to potato win gene-encoded proteins, is processed to yield mature hevein. This mature hevein is composed of one chitin-binding domain and the C-terminal polypeptide homologous to pathogenesis-related proteins such as tobacco PR-4 and tomato P2 proteins. In contrast, prohevein was poorly cleaved to form the C-terminal polypeptide in transgenic tomato plants expressing hevein gene (HEV1)-driven polypeptides. However, mature hevein, the N-terminal cleavage form, was not found in this system. Immunoblot analysis of extracellular and intracellular fluid proteins showed that HEV1-encoded polypeptides accumulated intracellularly. In addition, retardation of growth of Trichoderma hamatum was observed in transgenic tomatoes constitutively expressing HEV1-encoded proteins.

Allergens↗

Equivalence of information from single versus multiple frequency bioimpedance vector analysis in hemodialysis.

BACKGROUND: In suspended cells, low-frequency current only passes through extracellular fluids, while current at higher frequencies passes through extra- and intracellular fluids. Cells in soft tissues are in contact with each other, which causes tissue anisotropy, meaning that impedance changes along different cell directions, with part of low-frequency current also passing through cells. Hence, equivalent information on body impedance change is expected at all frequencies, which we proved in a dynamic condition of fluid removal with hemodialysis. METHODS: We performed whole-body impedance spectroscopy (496 frequencies from 4 to 1024 kHz, SEAC SFB3 analyzer; Brisbane, Australia) before and during fluid removal (0, 60, 120, 180 min, 2.5 kg) in 67 hemodialysis patients. With increasing current frequency, resistance (R) decreases and reactance (Xc) moves along the Cole's semicircle on the R-Xc plane. RESULTS: The Cole's semicircles progressively enlarged and moved to the right on the R-Xc plane following fluid removal (increase in both R and Xc values at any given frequency). Xc values at 5 kHz (expected values close to 0 Ohm) were 70% of the maximun Xc, indicating an intracellular current flows at low frequencies. The correlation coefficient between R at 50 kHz (standard frequency) and R at other frequencies ranged from 0.96 to 0.99, and the correlation coefficient between Xc at 50 kHz and Xc at other frequencies at any time point ranged from 0.65 to 0.99. CONCLUSION: From high Xc values at low frequency, tissue anisotropy is inferred. Intra- and extracellular current flow causes equivalence of information based on functions of R and Xc measurements made at 50 kHz versus other frequencies.

Aged↗

The effect of insulin on free amino acid pools and protein synthesis in rat skeletal muscle in vitro.

1. The effects of insulin in vitro on tissue pools and incorporation into protein of glycine and leucine in the extensor digitorum longus muscle of the rat are reported. 2. It was found that insulin decreased the lag period before the establishment of a linear rate of incorporation of radioactive glycine into protein. 3. The hormone increased the size of the free intracellular glycine pool. No such effect was found for leucine. The accumulation of radioactive glycine in the intracellular fluid compartment was increased. The content of radioactive leucine in the intracellular compartment was decreased. 4. Insulin decreased the specific radioactivity of both glycine and leucine in the extracellular fluid. 5. The hormone also decreased protein catabolism. 6. The effect on protein synthesis was not caused by an increase in the specific radioactivity of the extracellular pool but was possibly related to increased amino acid concentrations in this pool, which could in turn have affected the aggregation of ribosomes.

Amino Acids↗

Facilitating an understanding of integrative physiology: emphasis on the composition of body fluid compartments.

As a teaching exercise, we used deductive reasoning and a quantitative analysis to convert a number of facts into a series of concepts to facilitate an understanding of integrative physiology and shed light on the composition of the different body fluid compartments. The starting point was the central need to regenerate ATP to perform biologic work. Because a large quantity of O2 must be delivered to cells at a sufficiently high concentration to aid its diffusion into mitochondria, approximately one third of the O2 in inspired air was extracted; this led to a P(CO2) in arterial blood of 40 mmHg (1 mmHg = 133.322 Pa). Blood flow to individual organs must be adjusted precisely to avoid having too low or too high a P(O2) in mitochondria--the latter augments the formation of reactive O2 species. The extracellular fluid (ECF) bicarbonate concentration (E(HCO3)) must be high to minimize H+ buffering by proteins. This high E(HCO3) sets the ECF concentrations of ionized calcium (Ca2+) and inorganic phosphate (HPO4(2-)) because of solubility issues. Three features defined the intracellular fluid (ICF) volume and composition. First, expelling monovalent anions minimized its mass (volume). Second, controlling the tissue P(CO2) ensured a relatively constant net valence on intracellular proteins. Third, the range of ICF Ca2+ concentrations must both induce regulatory signals and avoid Ca3(PO4)2 formation. All the above were incorporated into the integrated response that optimized the capacity for vigorous exercise.

Animals↗

The short-term influence of catecholamines on acid-base balance of rat soleus muscle in vitro.

The short-term influence of catecholamines on surface pH (pHs) and intracellular pH (pHi) of superficial muscle fibres has been investigated in rat soleus in vitro using single-barrelled and double-barrelled glass micro-electrodes. pHs means the pH recorded at the surface of a muscle fibre. All measurements were performed in high-Ca2+ (10 mM) Ringer's solutions. Adrenaline caused an intracellular and surface acidification which increased with concentration in the range 6 X 10(-9)-6 X 10(-6) M. The effect was inhibited by propranolol (10(-5)M) but not by phentolamine (1.5 X 10(-7) M). Noradrenaline and isoproterenol (6 X 10(-6) M) also acidified the intracellular fluid. The relative effect of catecholamines on steady-state pHi was: adrenaline = isoproterenol greater than noradrenaline. Adrenaline (6 X 10(-9)-6 X 10(-6) M) did not accelerate pHi recovery following intracellular acid-loading by NH+4 or CO2. It is concluded that activation of beta-adrenoceptors by catecholamines causes an early intracellular acidosis presumably by enhancing synthesis of metabolic acids. The surface acidification seems at least partly due to non-ionic permeation of sarcolemma by metabolic acids, secondarily inducing accumulation of H+ ions at the cell surface.

Acid-Base Equilibrium↗

Might distal renal tubular acidosis be a proximal tubular cell disorder?

Incomplete renal tubular acidosis (RTA) and overt distal RTA may be different stages of the same underlying pathophysiology in certain individuals. The rationale that draws these conditions together is the relatively alkaline pH of the urine, hypocitraturia, and a possible familial association. The rate of excretion of ammonium (NH4+), on the other hand, suggests that these conditions stem from fundamentally different lesions. To explain this difference, we suggest that two possible disorders may result in the evolution from incomplete RTA to overt distal RTA. One subgroup could have gradient-limited distal RTA, while the other subgroup may have a lower pH of the intracellular fluid of the proximal convoluted tubular epithelium. Indices of proximal intracellular pH (rates of excretion of NH4+, NH3, and citrate) were culled from the literature spanning the years 1959 to 1991 on patients with incomplete RTA and overt distal RTA. Three points emerge: (1) the rate of excretion of NH4+ was lower in patients with overt distal RTA than in normals following an acute acid load (23 +/- 1 v 49 +/- 3 mumol/min); (2) the concentration of NH3 in the urine was almost 25-fold higher in incomplete RTA than in normals (69 +/- 14 v 3 +/- 0.4 nmol/min); and (3) in incomplete RTA, the pH of the urine fell to very low values (4.9 +/- 0.1) when high urine flows were induced with furosemide. The low pH of the urine would therefore suggest that many of these patients do not gradient-limited distal RTA, but more likely have proximal renal epithelial cell acidosis. We hypothesize that this high rate of excretion of NH4+ and low rate of excretion of citrate in the absence of acidosis or hypokalemia is consistent with proximal cell acidosis. To explain a transition from incomplete RTA to overt distal RTA, we speculate that toxicity of high concentrations of NH3 in the medullary interstitium as well as nephrolithiasis and nephrocalcinosis due to low urinary citrate and possibly an alkaline medullary interstitium may lead to damage of structures in this region.

Acid-Base Equilibrium↗

Effect of the exercise of seven consecutive days hill-walking on fluid homeostasis.

1. The effect of 7 consecutive days of strenuous exercise, hill-walking, on water balance and distribution was studied in five subjects. The exercise was preceded and followed by 3 control days. The diet was fixed throughout but water was allowed ad libitum. 2. Packed cell volume was measured daily. Serum electrolytes and arginine vasopressin were measured twice daily. Daily water, sodium and potassium balances were calculated. 3. During exercise there was a fall in packed cell volume, reaching a maximum of 11% by day 5 and a retention of sodium reaching a cumulative maximum of 358 mmol by day 6. During and immediately after exercise there was a retention of potassium, reaching a total of 120 mmol by day 3 after stopping exercise. 4. There was a loss of 650 ml of water on day 1 of exercise, followed by a modest retention reaching a cumulative maximum of 650 ml on day 5 of exercise. 5. Neither arginine vasopressin nor serum electrolyte concentrations were affected by exercise. 6. From the packed cell volume, sodium and water balances it was calculated that by day 5 of exercise there was an increase in plasma volume of .068 litre (22%), an increase in interstitial fluid volume of 2.0 litres (17%) and a decrease in intracellular fluid volume of 1.8 litres (8%). 7. These changes, together with the clinical observation of facial and ankle oedema during the experiemnt, suggest that continuous exercise may cause oedema and thus may be a factor in the aetiology of high-altitude oedema.

Adult↗

Monitoring relative fluid balance alterations in haemodialysis of diabetic patients by electrical impedance.

Measurements of total-body electrical impedance in the frequency range between 200 Hz and 300 kHz were performed on 37 diabetic patients undergoing chronic haemodialysis. Special attention was paid to the instrument design, where a self-balancing differential current source was used, reducing considerably the common-mode voltage at the amplifier input. The patient-instrument interface includes screened leads, separately driven by unity-gain buffers. The measurement error was < 1% for the impedance within the range of 20 to 1000 omega and < 0.3 degree (mean) for the phase angle. Impedance/phase and ultrafiltration measurements were carried out throughout the entire procedure. Total and extracellular water were computed and compared with extracted fluid volumes. The trends of change of the extracellular and intracellular fluid volumes during and immediately after dialysis corresponded to the respective clinical condition of the patients and enabled us to divide them into four groups. This approach is a step toward continuous monitoring and adaptive treatment, tailored to the individual patient needs.

Adult↗

Effect of pregnancy on tissue distribution of salicylate in rats.

The effect of pregnancy on tissue distribution of salicylate was studied by comparing both pharmacokinetic and protein-binding parameters between 20-day-pregnant rats and nonpregnant (control) rats. In the pregnant rats, the volume of distribution increased significantly (p less than 0.05) from 164 ml/kg of the control to 225 ml/kg, and the total body clearance also increased significantly (p less than 0.05) from 12.1 ml/hr/kg of the control to 19.8 ml/hr/kg. But these changes did not affect the plasma disappearance half-life of salicylate in the pregnant rats. The serum unbound fraction (fs) of the pregnant rats at 8 hr after iv administration of salicylate increased remarkably from 0.14 of the control to 0.67. The fs in the fetal serum (0.41) was lower than that in the maternal serum in spite of the lower albumin concentration in the fetal serum. A nonlinear serum protein binding was observed both in the control and in the fetal rats, but not observed in the pregnant rats. In the pregnant rats, the tissue-to-serum concentration ratios (Kp) of all tissues studied were larger than those in the control rats, and the values of Kp in the fetal were larger than those in the maternal. To elucidate these difference in Kp values between the pregnant and control rats, a mathematical model was proposed, where salicylate was distributed in the interstitial fluid, bound to the interstitial albumin, and translocated into the intracellular fluid according to the pH partition theory. The Kp values of most tissues in the control and pregnant rats were predicted successfully by using this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A theoretical analysis of water transport through chondrocytes.

Because of the avascular nature of adult cartilage, nutrients and waste products are transported to and from the chondrocytes by diffusion and convection through the extracellular matrix. The convective interstitial fluid flow within and around chondrocytes is poorly understood. This theoretical study demonstrates that the incorporation of a semi-permeable membrane when modeling the chondrocyte leads to the following findings: under mechanical loading of an isolated chondrocyte the intracellular fluid pressure is on the order of tens of Pascals and the transmembrane fluid outflow, on the order of picometers per second, takes several days to subside; consequently, the chondrocyte behaves practically as an incompressible solid whenever the loading duration is on the order of minutes or hours. When embedded in its extracellular matrix (ECM), the chondrocyte response is substantially different. Mechanical loading of the tissue leads to a fluid pressure difference between intracellular and extracellular compartments on the order of tens of kilopascals and the transmembrane outflow, on the order of a nanometer per second, subsides in about 1 h. The volume of the chondrocyte decreases concomitantly with that of the ECM. The interstitial fluid flow in the extracellular matrix is directed around the cell, with peak values on the order of tens of nanometers per second. The viscous fluid shear stress acting on the cell surface is several orders of magnitude smaller than the solid matrix shear stresses resulting from the ECM deformation. These results provide new insight toward our understanding of water transport in chondrocytes.

Biological Transport↗