Red Blood Cell Sodium Transport Research Articles

Red blood cell sodium transport in patients with cirrhosis.

Patients with advanced cirrhosis have abnormal sodium homoeostasis. The study was undertaken to quantify the sodium transport across the plasma membrane of red blood cells (RBC) in patients with cirrhosis. RBC efflux and influx of sodium were studied in vitro with tracer (22) Na(+) according to linear kinetics in 24 patients with cirrhosis and 14 healthy controls. The sodium efflux was modified by ouabain (O), furosemide (F) and a combination of O and F (O+F). RBC sodium was significantly decreased (4·6 versus control 6·3mmoll(-1) , P<0·001) and directly related to serum sodium (r=0·57, P<0·05). The RBC fractional sodium efflux was higher in patients with cirrhosis (+46%, P<0·01) compared to controls. Inhibition in both high (145mmoll(-1) )- and low (120mmoll(-1) )-sodium buffers showed that the F-insensitive sodium efflux was twice as high in cirrhosis as in controls (P=0·03-0·007), especially the O-sensitive, F-insensitive efflux was increased (+ 225%, P=0·01-0·006). Fractional F-sensitive transport was normal in cirrhosis. RBC sodium influx was largely normal in cirrhosis. In conclusion, RBC sodium content is reduced in patients with cirrhosis with a direct relation to serum sodium. Increased RBC sodium efflux is especially related to ouabain-sensitive, furosemide-insensitive transport and thus most likely due to upregulated activity of the sodium-potassium pump. The study gives no evidence to an altered intracellular/extracellular sodium ratio or to a reduced fractional furosemide-sensitive sodium transport in cirrhosis.

The effect of long-term treatment with spironolactone on sodium pump abnormalities in the red blood cells of patients with Bartter's syndrome.

To elucidate the possible sodium transport alterations across the cell membranes in Bartter's syndrome and their influencing by spironolactone treatment Na+-K+-ATPase activity was studied by means of radioactive 86Rubidium influx into red blood cells (RBC) of patients with Bartter's syndrome prior to and after a long-term spironolactone administration. As compared with the control subjects and patients with primary aldosteronism the patients with Bartter's syndrome had a more than 5 times higher 86Rb uptake by the RBC, especially in the ouabain-sensitive component. A long-term spironolactone treatment led to the decrease of this high influx. Serum of patients with Bartter's syndrome incubated with healthy RBC distinctly increased their 86Rb influx. The increase nevertheless did not reach the values in the RBC of untreated patients with Bartter's syndrome. Even if our results do not allow to explain fully the mechanism responsible for the Na+-K+-ATPase changes in the RBC of these patients, analysis of the studied parameters demonstrated that none of the known humoral factors as aldosterone, renin, prostaglandins, or changes of the serum potassium were responsible for these abnormalities. The changes of sodium transport in RBC of patients with Bartter's syndrome could be a part of a more general disturbance of the transport mechanism and could significantly participate in the pathogenesis of this disease.

Effects of L-carnitine on sodium transport in erythrocytes from dialyzed uremic patients

Red blood cell (RBC) sodium transport systems were studied by cation flux methodology, measuring both the ouabain-sensitive Na-K pump and the ouabain-insensitive Na-K cotransport (CoT), as well as the Na-lithium (Li) countertransport (CTT), in eight patients on chronic hemodialysis and a control group of eight normal individuals. Intracellular sodium content and passive Na permeability were also determined. The effect of L-carnitine on RBC sodium transport in the uremic group was evaluated by supplementation with oral (1 g/day) and i.v. (1 g post-hemodialysis) L-carnitine for 60 days. Mean Na efflux through the ouabain-sensitive Na-K pump was 30.7% lower in uremic patients than in controls (3.49 +/- 1.52 vs. 5.04 +/- 0.72 mmol/liter RBCxhr; P less than 0.025). Intracellular Na content was higher in uremic patients (11.57 +/- 3.38 vs. 8.86 +/- 0.88 mEq/liter RBC; P less than 0.05), but no differences were found in Na-K CoT, Na-Li CTT or passive Na permeability. L-carnitine treatment increased the ouabain-sensitive Na efflux in uremic patients (4.76 +/- 1.6 vs. 3.49 +/- 1.52 mmol/liter RBCxhr; P less than 0.05), with no change in CoT, CTT, intracellular Na content or passive Na permeability. We conclude that L-carnitine deficiency may play a major role in uremic Na-K pump disfunction.

Kinetic aspects of red blood cell sodium transport systems in essential hypertension.

A kinetic study of the interaction of internal sodium with four different erythrocyte sodium transport pathways (ouabain-sensitive Na+-K+ pump, bumetanide-sensitive Na+-K+ cotransport system, Na+-Li+ countertransport, and Na+leak) has facilitated the distinction of the following subgroups of patients with essential hypertension: 1) Leak (+), exhibiting increased passive sodium permeability; 2) Co (-), showing low apparent affinity of the Na+-K+ cotransport system for internal sodium; 3) Counter (+), characterized by increased maximal rates of Na+-Li+ countertransport; and 4) Pump (-), characterized by an abnormally low apparent affinity of the Na+-K+ pump for internal sodium. We present here a new and simple sodium-loading method that allows a simultaneous kinetic study of the above abnormalities. The use of this kinetic assay may improve estimation of the frequencies, clinical features, and other properties of each subgroup of hypertensive patients in different populations.

Uremia and Red Blood Cell Sodium Transport

Uremia and Red Blood Cell Sodium Transport

Red blood cell sodium transport and phosphate release in uremia.

Red blood cell (RBC) phosphate release was linear for more than 1 h and dependent on the intracellular hydrolysis of organic phosphate esters. In uremics on chronic hemodialysis total phosphate release was significantly increased suggesting an elevated RBC energy metabolism. Ouabain-sensitive phosphate release, however, was decreased. For RBCs of controls and uremic subjects approximately 80% of inorganic phosphate liberated within the cell was recycled. Thus, RBC phosphate release represents 20% of intracellular phosphate ester metabolism. In uremia active electrolyte transport was diminished, suggesting an impaired Na-K-ATPase activity. It resulted in an increased RBC sodium and a decreased potassium concentration. The positive correlation between ouabain-sensitive rate constant for sodium efflux and ouabain-sensitive RBC phosphate release indicates that ouabain inhibition of phosphate elimination might be related to Na-K-ATPase. In RBCs of uremic subjects almost 4% of the increased energy metabolism was needed for active electrolyte transport mechanisms, in control RBCs 12% was required.

Effect of saliva from cystic fibrosis patients and from normal subjects on red blood cell sodium transport.

Saliva, whether taken from patients with cystic fibrosis or from normal subjects, caused an increase in red blood cell Na+ efflux (in the presence or absence of ouabain) of 19-29% as compared with non-saliva controls. However, there was no significant difference between the effects of cystic fibrosis saliva and normal saliva.

Functional and metabolic studies on red blood cell sodium transport in chronic uremia.

Red blood cells from 7 out of 13 patients with chronic uremia were found to have increased intracellular concentrations of sodium associated with a reversible inhibition of ouabain-sensitive Na efflux when incubated in control plasma. Although mean Na-K-ATPase activity of RBC hemolysates was only moderately decreased (21.8 +/- 1.5 vs. 26.5 +/- 1.8 nmol Pi/mg protein/h), enzyme kinetics revealed a significant increase in KmATP values for this enzyme in uremic RBCs (1.01 +/- 0.1 vs. 0.58 +/- 0.03; p less than 0.001) which was closely correlated to serum creatinine concentration (r = 0.9034). While aerobic glycolysis was unaltered, an increase in glucose-6-phosphate dehydrogenase activity was observed, i.e. the enzyme initiating the pentose-phosphate cycle. In addition, intracellular ATP concentrations of uremic RBCs were significantly higher than ATP concentrations of control RBCs (2.13 +/- 0.22 vs. 1.32 +/- 0.06 mmol/l RBC; p less than 0.01). These data suggest that high intracellular concentrations of Na and ATP in uremic RBCs partially result from a competitive reversible inhibition of the transport ATPase by uremic toxins.

Alterations of red blood cell sodium transport during malarial infection.

Previous studies have suggested that malaria induces changes in erythrocytic membrane permeability and susceptibility to osmotic lysis. The present study investigated erythrocytic transport of sodium with cells from Rhesus monkeys infected with Plasmodium knowlesi. Red blood cell sodium concentration was significantly elevated in 37 parasitized animals (21.8+/-1.2 mM; mean +/-SEM), as compared to 23 control animals (10.0+/-0.38 mM). The cellular sodium increased with the density of parasitemia and the cellular potassium decreased in proportion to the elevation of sodium. Nonparasitized as well as parasitized erythrocytes possessed this abnormality of cation metabolism. Effective chloroquine therapy reversed the changes over a period of 4 days. Active sodium outflux rate constants were depressed in animals with malaria (0.202+/-0.012), as compared to controls (0.325+/-0.027). Passive sodium influx rate constants were higher in infected monkeys (0.028+/-0.002) than in control animals (0.019+/-0.002). The cross incubation of malarial plasma with normal red blood cells induced a 22% diminution in active sodium outflux but no changes were observed in sodium influx. It is concluded that malaria alters erythrocytic sodium transport in all erythrocytes. The elevated intracellular sodium concentration is the net result of decreased sodium outflux and increased sodium influx. The plasmodium organism or the affected host may produce a circulating substance that is deleterious to erythrocytic membrane cation transport.