Can Changes in the Plasma Sodium Concentration Be Predicted Based on the Mass Balance of Sodium, Potassium, and Water in the Face of Osmotically Inactive Sodium Storage?

CONTEXT: Alterations in the plasma sodium concentration ([Na+]p) is predicted based on changes in the mass balance of Na+, K+, and H2O. However, it is well appreciated that Na+ retention results in both osmotically active and osmotically inactive Na+ storage and that only osmotically active Na+ contributes to the modulation of the [Na+]p. Subject of Review: Recent clinical studies suggested that prediction of changes in the [Na+]p based on the mass balance of Na+, K+, and H2O is inaccurate since the osmotically inactive Na+ storage pool is dynamically regulated. In contrast, animal studies demonstrated that changes in the [Na+]p can be predicted if the total body Na+, K+, and H2O were to be accurately accounted for. Second Opinion: Our analysis demonstrated that alterations in the [Na+]p are predictable at the total body level if all sources of input and output of Na+, K+, and H2O can be accurately accounted for despite the paradoxical finding that there are changes in the osmotically inactive Na+ storage pool at the tissue level. However, future prospective clinical studies are needed to corroborate the findings in the animal studies. We proposed that the fundamental question as to whether changes in the [Na+]p can be predicted in the face of osmotically inactive sodium storage is best addressed by serial measurements of total body exchangeable Na+ and K+ and total body water by isotope dilution at different time intervals.

Is the Osmolal Concentration of Ethanol Greater Than Its Molar Concentration?

Background: Recent data suggested that the osmolal gap attributed to ethanol as determined by the difference between measured serum osmolality and calculated serum osmolarity is greater than its molar concentration. The increased osmotic activity of ethanol is thought to be due to its binding to water molecules. This study is conducted to determine the true osmotic contribution of ethanol to serum osmolality. Methods: Baseline serum osmolality and ethanol concentration were measured on each serum sample. Varying amounts of ethanol were added to aliquots of serum in which the baseline serum ethanol concentration was undetectable. Repeat serum osmolality and serum ethanol concentration were measured after addition of ethanol. Results: The range of serum ethanol concentration was 27.3-429.8 mg/dL. The serum osmolal gap attributed solely to ethanol is calculated based on the difference between measured serum osmolality before and measured serum osmolality after addition of ethanol. Our results demonstrated that the contribution of ethanol to serum osmolality can be calculated by dividing the serum ethanol level in mg/dl by 4.6. In addition, the relationship between serum ethanol concentration and osmolal gap due to ethanol was assessed by linear regression analysis. Linear regression analysis relating the osmolal gap due to ethanol and ethanol concentration yielded the following equation: Osmolal Gap (mOsm/kg H2O) = 0.23 (Ethanol [mg/dL]) - 1.43. Conclusion: The osmolal concentration of ethanol can be calculated based on its molar concentration. We found no evidence for ethanol binding to water molecules over the range of ethanol concentration in this study.

Treatment of Cirrhosis-Associated Hyponatremia with Midodrine and Octreotide.

BACKGROUND: Hyponatremia in the setting of cirrhosis is a common electrolyte disorder with few therapeutic options. The free water retention is due to non-osmotic vasopressin secretion resulting from the cirrhosis-associated splanchnic vasodilatation. Therefore, vasoconstrictive therapy may correct this electrolyte abnormality. The aim of this study was to assess the efficacy of midodrine and octreotide as a therapeutic approach to increasing urinary electrolyte-free water clearance (EFWC) in the correction of cirrhosis-associated hyponatremia. METHODS: This observational study consisted of 10 patients with cirrhosis-associated hyponatremia. Hypovolemia was ruled out as the cause of the hyponatremia with a 48-h albumin challenge (25 g IV q6 h). Patients whose hyponatremia failed to improve with albumin challenge were started on midodrine and octreotide at 10 mg po tid and 100 µg sq tid, respectively, with rapid up-titration as tolerated to respective maximal doses of 15 mg tid and 200 µg tid within the first 24 h. We assessed urinary EFWC and serum sodium concentration before and 72 h after treatment. RESULTS: Pretreatment serum sodium levels ranged from 119 to 133 mmol/L. The mean pretreatment serum sodium concentration ± SEM was 124 mmol/L ± 1.6 vs 130 mmol/L ± 1.5 posttreatment (p = 0.00001). The mean pretreatment urinary EFWC ± SEM was 0.33 L ± 0.07 vs 0.82 L ± 0.11 posttreatment (p = 0.0003). CONCLUSION: Our data show a statistically significant increase in serum sodium concentration and urinary EFWC with the use of midodrine and octreotide in the treatment of cirrhosis-associated hyponatremia.

Osmotically inactive sodium and potassium storage: lessons learned from the Edelman and Boling data.

Because changes in the plasma water sodium concentration ([Na(+)]pw) are clinically due to changes in the mass balance of Na(+), K(+), and H2O, the analysis and treatment of the dysnatremias are dependent on the validity of the Edelman equation in defining the quantitative interrelationship between the [Na(+)]pw and the total exchangeable sodium (Nae), total exchangeable potassium (Ke), and total body water (TBW) (Edelman IS, Leibman J, O'Meara MP, Birkenfeld LW. J Clin Invest 37: 1236-1256, 1958): [Na(+)]pw = 1.11(Nae + Ke)/TBW - 25.6. The interrelationship between [Na(+)]pw and Nae, Ke, and TBW in the Edelman equation is empirically determined by accounting for measurement errors in all of these variables. In contrast, linear regression analysis of the same data set using [Na(+)]pw as the dependent variable yields the following equation: [Na(+)]pw = 0.93(Nae + Ke)/TBW + 1.37. Moreover, based on the study by Boling et al. (Boling EA, Lipkind JB. 18: 943-949, 1963), the [Na(+)]pw is related to the Nae, Ke, and TBW by the following linear regression equation: [Na(+)]pw = 0.487(Nae + Ke)/TBW + 71.54. The disparities between the slope and y-intercept of these three equations are unknown. In this mathematical analysis, we demonstrate that the disparities between the slope and y-intercept in these three equations can be explained by how the osmotically inactive Na(+) and K(+) storage pool is quantitatively accounted for. Our analysis also indicates that the osmotically inactive Na(+) and K(+) storage pool is dynamically regulated and that changes in the [Na(+)]pw can be predicted based on changes in the Nae, Ke, and TBW despite dynamic changes in the osmotically inactive Na(+) and K(+) storage pool.