Decrease In Sodium Concentration Research Articles

Major salivary gland dysfunction in patients with hematological malignancies receiving interleukin-2-based immunotherapy post-autologous blood stem cell transplantation (ABSCT).

lnterleukin-2 (IL-2) is known to cause xerostomia and skin manifestations similar to graft-versus-host disease (GVHD). We therefore evaluated major salivary gland function in patients with hematological malignancies treated with IL-2 and interferon-alpha (IFN-alpha) after ABSCT. Eleven patients (seven male, four female) of median age 40 (24-47) were evaluated, seven with non-Hodgkin lymphoma (NHL); one with Hodgkin's disease (HD) and three with acute myelogenous leukemia (AML). Parotid and submandibular salivary gland function was assessed before, during and after IL-2/IFN-alpha administration by evaluation of the salivary flow rate and the composition of secreted saliva. Significant reductions in both the resting and stimulated parotid and submandibular salivary flow rates were observed during IL-2/IFN-alpha immunotherapy compared with the pre- and post-therapy values (P < 0.01), while no hyposalivation was observed in the control patients who underwent ABSCT and did not received IL-2. Sialochemical evaluation revealed a significant increase in potassium concentration (24.4+/-0.6 mEq/l to 28.9+/-1.4 mEq/l) and a significant decrease in sodium concentration (6.7+/-2.1 mEq/l to 3.3+/-1.0 mEq/l) (P < 0.05) in the stimulated parotid gland saliva secreted during IL-2/IFN-alpha administration. Salivary protein concentrations were not altered by the IL-2/IFN-alpha immunotherapy. Similar changes were previously observed in mice and humans with chronic GVHD. We conclude that IL-2 immunotherapy induces major salivary gland dysfunction in humans, similar to our previous observations in patients with chronic GVHD, which may indicate similar pathophysiologic mechanisms.

Lack of major hypoxia and significant brain damage in rats despite dramatic hyponatremic encephalopathy

Brain myelinolysis could complicate the excessive correction of chronic hyponatremia. Recently it was suggested that hypoxia rather than correction of hyponatremia would be responsible for myelinolysis. We analyzed the incidence and the severity of potentially associated hypoxia and its consequences on survival and on the development of brain damage in rats in which major hyponatremic encephalopathy had developed after either pure acute hyponatremia (serum sodium concentration: −40 mEq/L/3 hr, group I, n = 8) or acute hyponatremia (serum sodium concentration: −30 mEq/L/3 hr, group II, n = 12) superimposed on chronic hyponatremia of 3 days' duration (serum sodium concentration: 113 mEq/L). Our study revealed the following: (1) Despite dramatic hyponatremic encephalopathy (convulsions, coma), hypoxia (PO 2 < 70 mm Hg) was present, but the PO 2 was not decreased below 40 mm Hg. All of these rats died rapidly if they remained hyponatremic. (2) In the animals rescued by NaCl, the incidence of brain myelinolysis was low (10%), whatever the duration (pure acute or chronic plus acute) of the hyponatremia and despite the combination of hypoxia with major hyponatremic encephalopathy. (3) When acute hyponatremia is superimposed on a chronic preexisting hyponatremic state, the acute component of serum sodium concentration decrease could be rapidly corrected (serum sodium concentration: +35 mEq/ L/21 hr) without fear of permanent brain damage. Our results suggest that even in the presence of dramatic hyponatremic encephalopathy and associated hypoxia, neuropathologic sequelae are uncommon. Brain lesions related to post-anoxic encephalopathy probably develop only after respiratory arrest occurs.

Rapid decrease in cellular sodium and chloride content during cold incubation of cultured liver endothelial cells and hepatocytes.

Hypothermia, as used for organ preservation in transplantation medicine, is generally supposed to lead to an intracellular accumulation of sodium, and subsequently of chloride, via inhibition of the Na+/K+-ATPase. However, on studying the cellular sodium concentration of cultured liver endothelial cells using fluorescence microscopy, we found a 55% decrease in the cellular sodium concentration after 30 min of cold incubation in University of Wisconsin (UW) solution. To confirm this surprising result, we set up a capillary electrophoresis method that allowed us to determine the cellular contents of inorganic cations and of inorganic anions. Using this method we measured a decrease in the cellular sodium content from 104+/-11 to 55+/-4 nmol/mg of protein, accompanied by a decrease in the chloride content from 71+/-9 to 25+/-5 nmol/mg of protein, after 30 min of cold incubation in UW solution. When the endothelial cells were incubated in cold Krebs-Henseleit buffer or in cold cell culture medium instead of UW solution, similar early decreases in cellular sodium and chloride contents were observed, thus excluding the possibility of the decreases being dependent on the preservation solution used. Furthermore, experiments with cultured rat hepatocytes yielded a similar decrease in sodium content during initiation of cold incubation in UW solution, so the decrease does not appear to be cell-specific either. These results suggest that, contrary to current opinion, sodium efflux predominates over sodium influx during the early phase of cold incubation of cells.

Finoptin effect on electrolyte metabolism of diabetics with essential hypertension

It is universally acknowledged that some hypotensive agents may have a negative impact on electrolyte metabolism. This study was aimed at investigating the baseline status of electrolyte metabolism in patients with types I and II diabetes and concomitant essential hypertension and at following up the changes in this parameter over the course of verapamil (finoptin) therapy. Fifty-six patients were followed up. Levels of potassium and sodium in the plasma and red cells, total and ionized calcium in the plasma were measured before therapy and after 0.5, 1.5, and 6 months of finoptin therapy. Higher levels of plasma potassium and red cell sodium were revealed in patients with type I diabetes in comparison with those with type II condition. In patients with noninsulin-dependent diabetes potassium concentrations in red cells and ionized calcium in the plasma were higher. Finoptin therapy promoted a decrease of sodium concentration in the red cells in diabetics with both types I and II condition and a reduction of the level of ionized calcium in the plasma of patients with type II diabetes. Changes in the electrolyte metabolism were transitory and do not require special laboratory monitoring.

Mechanism of water and sodium removal in CAPD with low sodium dialysate (LNaD).

Although clinical benefits associated with low sodium dialysate in CAPD such as higher removal of sodium and water have been reported elsewhere, its mechanism is still speculative.To assess mass transport characteristics by this unique dialysate composition we utilized mathematical model being reported previously. In this computer simulation 8.3ml/min, 9.4ml/min and 10ml/min of mass transfer area coefficients (MTAC) for sodium, chloride and glucose were cited from the literatures. Sodium concentrations in dialysate were varied from 76mEq/l to 129mEq/l, compensating its associated decreases of osmolarity by glucose.An increase of approximately 22ml of net ultrafiltration volume at 6hr dwell time could be achieved by reduction of 1mEq/l of serum sodium concentration in the range of 130mEq/l-150mEq/l of serum sodium concentration while only 2.3-0.5ml of net UF volume increase per 1mEq/l of dialysate sodium concentration decrease could be estimated in the range of 76mEq/l-129mEq/l of dialysate sodium concentration. 20% and 41% of sodium were transported by diffusion in standard dialysate (129mEq/l) and LNaD (102mEq/l), respectively.It is clearly indicated that diffusive transport becomes dominant in sodium removal as sodium concentration in dialysate decreases, while both increase of reflection coefficient and decrease of MTAC of sodium tend to reduce water removal.

The influence of acetazolamide and amlodipine on the intracellular sodium content of rat proximal tubular cells

1. This investigation set out to use 23Na n.m.r. spectroscopy to measure changes in intracellular levels of sodium in isolated suspensions of rat proximal tubules. The effects of temperature, an inhibitor of the sodium pump and known natriuretic drugs on intracellular sodium content of such tubular preparations were measured and compared with calcium channel antagonists where action at this level is unclear. 2. Rat kidneys were perfused with collagenase, roughly chopped, subjected to mechanical dispersion and washed to remove all traces of the enzyme. The proximal tubules were then purified and concentrated by Percoll density gradient centrifugation and then resuspended in buffer containing dysprosium tripolyphosphate shift reagent. 3. Distinct peaks corresponding to intracellular and extracellular sodium signals were observed when the tubules were placed into the n.m.r. spectrometer. As the temperature of the suspension rose to 37 degrees C, there was an exponential decrease in sodium content, with a decay constant of 0.15 +/- 0.02 min-1, which reached a stable level within 20 to 25 min. Addition of ouabain, 10(-3) M, resulted in a significant (P < 0.01) 30% increase in intracellular sodium content within 5 min which peaked at 70% 20 min later. Although acetazolamide (10(-3) M) significantly (P < 0.01) increased intracellular sodium content by 45%, amlodipine (10(-4) M) had no effect. 4. These data show that changes in the activity of the Na+/K+/ATPase have a considerable influence on the intracellular levels of sodium in proximal tubule cells. Inhibition of carbonic anhydrase activity resulted in a rise in intracellular sodium content which is compatible with its action to reduce the turnover rate of the Na+/(HCO3-)3 symporter. The lack of effect of amlodipine was consistent with the suggestion that it does not have a direct action on the sodium handling processes at the level of the proximal tubule.

Osmotic regulation of sodium pump in rat brain synaptosomes: the role of cytoplasmic sodium

The effect of hypoosmolality of incubation medium on the rat of ouabain-sensitive 86Rb + transport in rat brain synaptosomes was studied. A decreased osmolality from 310 to 250 mOsm increased the rate of 86Rb + uptake from 3.72 to 6.23 nmol/mg of protein min. To evaluate the involvement of cytoplasmic sodium in sodium pump stimulation inhibitors of ion channels and transport pathways able to increase [Na +] in were used. Tetrodotoxin (1 μM), amiloride (0.5 mM) and verapamil (0.1 mM) had no influence on the osmotic response of the sodium pump. The decrease of sodium concentration in incubation medium to 15 mM, leading to a practical loss of its transmembrane gradient, did not abolish stimulation of pump. No increase in 22Na + influx or intrasynaptosomal sodium content was registered at hypotonic conditions. It is suggested that osmotic regulation of Na +,K +-ATPase is not connected with an increase of internal sodium through opening of sodium channels, or with activation of other membrane sodium-transporting systems.

Effects of chlorthalidone on ventricular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats.

Diuretics have been the mainstay of long-term treatment of hypertension, but there is no evidence suggesting that diuretics may be effective in reducing cardiac hypertrophy associated with hypertension. Thus, the present study was carried out to elucidate if long-term treatment with chlorthalidone (8 mg per animal per day added to food) affects the development of and reverses the ventricular hypertrophy in deoxycorticosterone acetate (DOCA) (8 mg/kg SC twice a week)-salt hypertensive rats. Chlorthalidone was given to one group during all 20 days of DOCA administration (preventive regimen) and to another group 20 days after DOCA treatment was initiated until the 40th day (therapeutic regimen). Chlorthalidone was found to reduce or prevent the development of ventricular hypertrophy, as assessed by a reduction in ventricular mass and cardiac protein as well as arterial hypertension. Both chlorthalidone regimens prevented the increase or induced a significant decrease in the plasma concentration of sodium and in cardiac sympathetic tone, which were both increased in DOCA-salt-treated rats. These data provide evidence that long-term chlorthalidone treatment is effective in preventing or reducing ventricular hypertrophy along with arterial hypertension. However, whether this is due to a reduction in plasma sodium or other additional mechanisms, such as a reduction in cardiac sympathetic tone, remains to be determined.

Fire and the chemistry of a South African mountain stream

The effects of a late-summer prescribed burn on the chemistry of a second-order mountain stream in the south-western Cape, South Africa, were investigated. Nitrate concentrations in stream water were significantly higher during the winter of the post-burn year. Increased concentrations of chloride, bicarbonate, polyphenols and potassium and decreased sodium concentrations were also recorded. Concentrations of ammonium, phosphate, calcium, magnesium, total dissolved solids and hydrogen ions were not significantly affected by the burn. Ionic export from the catchment was generally greater in the post-burn year. Apart from nitrate, however, values probably lie within the natural range of year-to-year variation. It is predicted that enhanced losses of nitrate will decrease progressively with the recovery of the vegetation and the re-establishment of soil/plant nutrient cycles. Atmospheric losses of nutrients in smoke were unquantified, but may be of more significance to site productivity than losses through surface runoff, which, in the case of nitrogen, appear to be compensated by precipitation inputs.

Changes of Isolated Cardiac Muscle Function in Response to Extracellular Sodium Reduction

The effects of low extracellular sodium concentration [( Na+]0, 76 mmol/l) on force of contraction, transmembrane action potentials and on calcium, sodium and potassium contents were studied in guinea-pig heart muscle using sucrose or lithium as substitutes for sodium. In papillary muscle, the positive inotropic response to low [Na+]0 was accompanied by shortening in action potential duration, in atrial muscle, prolongation at 90% of repolarization was observed. After 30 min. in low [Na+]0 solution (Ca2+ 1.8 mmol/l), the net uptake of calcium in left atria was larger in sucrose- than in lithium-substituted solution, i.e. 0.45 and 0.2 mmol Ca2+/kg wet weight, respectively. The net sodium content decreased monophasically; but the potassium content did not change consistently. The uptake of lithium by the atria was at least partially compensated for by a loss in potassium and by a transient decrease in sodium content. Increase in stimulation frequency from 0.1 to 1 Hz accelerated the time course of change by a factor of 2. In low [Na+]0, post-rest adaptation of twitch tension appeared abolished in atria because of high amplitude contractions. The recovery pattern of post-rest twitch amplitude was greatly accelerated in papillary muscle. In conclusion, low [Na+]0 elevates the cellular calcium content; this extra calcium is probably located in cellular stores that are involved in the regulation of twitch amplitude.

Inhibition of neuronal noradrenaline transport (uptake1) and desipramine binding by amiloride and ethylisopropylamiloride

The diuretic amiloride and its N-5 substituted analogue ethylisopropylamiloride (EIPA) inhibit both the specific high affinity desipramine binding to isolated plasma membranes of PC12 rat phaeochromocytoma cells and the carrier-mediated neuronal uptake of noradrenaline into PC12 cells. The inhibition by EIPA of both desipramine binding (Ki = 5.6 mumol/l) and noradrenaline uptake (Ki = 24 mumol/l) inversely depend on the extracellular sodium concentration. The degree of inhibition increased with decreasing sodium concentration. A more detailed analysis of the mode of interaction revealed a competitive interaction between EIPA and desipramine binding but an "uncompetitive" interaction between EIPA and noradrenaline uptake. EIPA is the first inhibitor of uptake1 known so far, which reduces both Km and Vmax of neuronal noradrenaline transport. Extracellular alkalinization from pH 7.4 to 7.9 during incubation with EIPA markedly increased the effects on the kinetics of noradrenaline transport. A model has been proposed to explain the kinetic phenomena. It is based on the hypothesis that EIPA diffuses through the plasma membrane and binds to the inward facing sodium binding site of the neuronal noradrenaline carrier.

Accidental carbadox overdosage in pigs in an Irish weaner-producing herd.

A weaner ration containing carbadox at concentrations of 331 to 363 mg/kg was accidentally fed to suckling and weaned pigs in an 84 sow herd. Discarded ration was fed to 36 sows. One hundred and sixty five weaner pigs died in a 10 week period with clinical signs including refusal to eat, ill thrift, the passing of hard pelleted faeces, posterior paresis and death in seven to nine days. The surviving weaners did not thrive and some males showed poor testicular development. Sows and suckling pigs that consumed the ration also failed to thrive as did the progeny of affected sows. The main pathological finding was obliteration of the zona glomerulosa of the adrenal cortex. Increased potassium and decreased sodium concentrations in serum were the most notable and consistent biochemical findings.

Effect of ethanol on serum electrolytes and osmolality

Rats and rabbits were injected ethanol 2 g/kg intraperitoneally. One hour after injection blood was analyzed for serum electrolytes and osmolality. Administration of ethanol caused decrease in serum sodium (p < 0.0005), potassium (p < 0.0005), calcium (p < 0.0005), chloride (p < 0.0005), magnesium (p < 0.0005), phosphorus (p < 0.005) and glucose (p < 0.0005) in rabbits. Further studies of intraperitoneal administration of ethanol in rats showed decrease in concentration of sodium (p < 0.025), potassium (p < 0.025), calcium (p < 0.01) chloride (p < 0.005) magnesium (p < 0.005), phosphorus (p < 0.025) and glucose (p < 0.005). Administration of ethanol caused an increase in serum osmolality in both rabbits and rats (p < 0.005, p < 0.05). It is concluded that ethanol ingestion is probably the commonest cause of the hyperosmolar state. Although the osmotic and sedative effects of ethanol are pharmacologically unrelated, the presence of ethanol should be considered in comatose patients in whome the measured plasma osmolality appreciably exceeds that predicted on the basis of plasma glucose, urea and electrolytes concentration.

Hypothalamic Control during Hypogravity

Hypogravity (low G) has been known to elicit many changes in automatic and endocrine functions which may be regulated by the hypothalamus. We investigated hypothalamic neuron activity during low-G simulation and its involvement on regulation of muscle electrolytes and Ca metabolism. 1) In unanesthetized rats, about 50% of neurons of the lateral hypothalamic area (LHA) showed changes in activity during horizontal suspension. About 40% of neurons of the paraventricular necleus (PVN) showed changes in activity during head-down tilt suspension. Inputs from barorecestors and/or vestibular system seem to affect both LHA and PVN neuron activities, while proprioceptive information mainly affect LHA activity. 2) Electrophysiological experiments revealed that polysynaptic excitation from the vestibular nucleus and monosynaptic inhibition from the fastigial nucleus were main inputs to the LHA. 3) Rats under conditions of long-term hypokinesia, potassium-deficient diet or DOCA (deoxy corticosteron acetate) -salt hypertension show increase and decrease in intracellular concentration of sodium and potassium ions, respectively, in muscles. Lesion of the ventromedial hypothalamus (VMH) or PVNreduced the electrolyte changes in the muscle. VMH activity through sympathetic nerve are involved in regulation of Na-K pump activity in the slow muscles, while endogenous Na-K ATPase inhibitor in the PVN and the anteroventral region of the III ventricle is involved in regulation of Na-K pump activity in the fast muscles. 4) LHA neurons have calcitonine sensitivity and central injection of calcitonin reduced plasma concentration of Ca. These findings suggest that the hypothalamus is involved in regulation of calcium as well as other electrolytes.

The effect of intracerebroventricular hypertonic infusion on sodium appetite in rats after peritoneal dialysis

Sixty minute peritoneal dialysis (PD) against isotonic glucose decreased sodium concentration [Na +] in serum and cerebrospinal fluid (CSF) to 14% and 7% of their initial values, respectively. About 3 to 4 hours after PD, [Na +] began to increase slowly, reaching the initial level 24 hr afterwards. Central restoration of Na + was made by infusing isotonic or hypertonic fluid into the 3rd brain ventricle (3BV) of rats different times after dialysis. Continuous infusion (1 μl/hr) of artCSF, 150 mM Na +, from −1 to 24 hr after PD decreased sodium intake as compared with uninfused control or control receiving Na +-free infusate or distilled water. Hypertonic central sodium infusions (1 μ//hr) administered from −1 to 8 hr after PD, did not modify sodium intake; however an infusion made from 8 to 24 hr or from 16 to 24 hr post-dialysis decreased sodium intake by 38% and 67%, respectively. The volumes of sodium ingested were compared with those of the same animal infused with CSF 150 mM Na +. The results suggest that the fall in CSF [Na +] after sodium depletion by itself does not seem to be a critical factor in the onset of specific sodium appetite.

Real and artefactual erythrocyte swelling in hyperglycaemia.

The mean erythrocyte volume of patients with acute diabetic decompensation was determined by Coulter measurement and found to be elevated above normal (mean increase 5.5 mu3). Experiments in vitro revealed this to be an artefact associated with Coulter determination. A more reliable estimate of in vivo erythrocyte volume can be obtained from centrifugated haematocrit and erythrocyte count. With this method, true erythrocyte swelling parallel to glucose concentration was observed when erythrocytes were exposed to isotonic glucose-NaCl solutions. This volume increase resulted from decreased sodium concentration and was in the order of 0.5-1.0 mu3 per mmol/l of sodium. Glucose was osmotically ineffective. Similar volume changes were documented in a diabetic patient parallel to his daily variations of blood glucose. In severe diabetic decompensation, dehydration usually prevents an increase in erythrocyte volume. We conclude that hyperglycaemia is associated with erythrocyte swelling if total serum tonicity remains within the normal range.

Cation excretion and kallikrein secretion by the rat parotid gland in various hypertensive models.

The major salivary glands are distinguished by a high kallikrein content, localized particularly in regions with intense electrolyte transport (the apical border of striated duct cells and the luminal border of the main excretory ducts). For this reason we used the parotid gland as a test model for investigations on electrolyte (sodium and potassium) and kallikrein transport in various forms of experimental hypertension [spontaneously hypertensive rats, renovascular (two-kidney one-clip) hypertension, and deoxycorticosterone trimethylacetate (DOCA)-salt hypertension]. As compared with values for the controls, the sodium concentration in parotid saliva was decreased in all hypertensive models studied, indicating enhanced sodium reabsorption in the glandular duct system. In DOCA-salt hypertension the flow rate dependency of the sodium concentration was preserved. In contrast, in genetic and renovascular hypertension, the decreased sodium concentration was independent of the salivary flow rate. Salivary potassium concentration showed an inverse relationship to sodium level and was slightly increased in DOCA-salt and renovascular hypertension. In genetic hypertension potassium concentration in saliva was lowered. Salivary kallikrein activity was enhanced in all forms of hypertension studied, with the highest increase in genetic hypertension (factor 3.5), followed by DOCA-salt hypertension (factor 3.0) and finally by renovascular hypertension (factor 2.5). The pathogenesis of the exaggerated kallikrein secretion observed in hypertension is discussed with regard to a counterregulatory mechanism as well as sympathicoadrenergic activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Age influence on D-Glucose absorption depending on sodium concentration in the lumen of rat small intestine

The influence of decreased sodium concentration on D-Glucose jejunal and ileal absorption has been investigated in rats of three groups of different ages: 21–23 days, 2–3 months and 18 months old, using a perfusion system in vivo. In all the cases studied there was a decrease of D-Glucose absorption with reduced sodium concentrations. The ileum of 21–23 days old animals showed the greatest inhibition of D-Glucose absorption when sodium was substituted partially or totally by Tris-HCl.

SOME EFFECTS OF TOPDRESSING PASTURE WITH SODIUM CHLORIDE ON PLANT AND ANIMAL NUTRITION

A long term study is being made of the effects of replacing all or part of the fertiliser input of potassium chloride (muriate of potash - KCI) with sodium chloride (common salt - NaCI) on plant and beef animal nutrition. The ryegrass-white clover pasture which is growing on a sodium deficient pumice derived soil (Taupo sandy silt), had received heavy applications of KCI over the preceeding 10 years. Results from the first two years show that because of the already high potassium status of the pasture, neither KCI or NaCl had any effect on pasture dry matter production or species composition, but did effect the chemical composition. Topdressing with NaCl at rates of 100-200 kg/ha/vr significantly increased the herbage sodium concentrations, while similar rates of 'KC1 increased potassium concentrations but decreased sodium concentrations. However, the depressing affects of KC1 on sodium concentrations were offset by applying 50 kg/ha/yr of NaCI. increasing the sodium concenrrarron In me neruaye au"ve V, I 70 VI LIIG UIY IUU~LLXZI with NaCl had a beneficial effect on the growth of weaner beef animals. However, increasing the sodium intake of beef breeding cows grazing pastures high in potassium had a detrimental effect on the concentration of magnesium in the blood serum. Thus, as a relatively high intake of sodium may induce metabolic problems in breeding cows, topdressing pastures or direct supplementation of animals with NaCI, should not be undertaken without sound evidence of its necessity particularly in areas prone to grass staggers (hypomagnesaemic tetany). Key Words: animal nutrition, herbage sodium; plant nutrition; potassium chloride; ryegrass-white clover pasture, sodium chloride, serum magnesium.

Red blood cell sodium content and permeability changes in hemorrhagic shock

Recent studies of cellular function have demonstrated significant alterations of cell homeostasis during hemorrhagic shock. The progressive depolarization of cell membranes demonstrated in several organs has been attributed to failure of energy-dependent active ion transport. Similar changes in intracellular electrolyte composition have been observed in the red blood cells of some patients in late hemorrhagic shock and in other severely ill patients. The ready availability of isolated cells that do not require extracellular fluid space assessment makes the red blood cell an attractive model for investigating the factors controlling ion movements across the cell wall. It has been suggested that the red blood cell ion abnormalities may represent a generalized cellular response to severe illness. Red blood cell sodium concentration was measured in 145 patients during severe hemorrhagic shock. The direction and magnitude of changes in red blood sodium concentration was correlated with the time course of the shock state. The initial decrease in sodium content was a function of the diminished red blood cell membrane permeability due to a decrease in plasma bicarbonate levels. The subsequent red blood cell sodium uptake above the normal range, not associated with an increase in sodium influx, indicated an impairment of energy-dependent active transport. The observed high sodium concentrations associated with a potassium decrease in the red blood cell appeared to be only one manifestation of a generalized defect in cellular function and composition during severe hemorrhagic shock.