4.10: Ion Selective Electrodes

During a routine analysis of electrolytes, a technologist notes that one set of results is unusually low: sodium = 118 mmol/L; potassium = 3.8 mmolL. Upon repeat analysis, similar results are obtained. Both cations are measured by dilutional ion selective electrodes. A check in the laboratory information system (“computer”) shows that a previous sample taken after an overnight fast had sodium and potassium concentrations within the laboratory reference ranges.

QUESTIONS

1. How can the technologist determine if the analysis is correct?
2. The medical technologist repeats the analysis on a flame emission photometer and gets essentially the same results, Na = 118 mmol/L, K = 3.9 mmol/L. Should an alternative method for sodium analysis be employed for this sample?

Questions to Consider

1. What are the principles of the most commonly used techniques for measuring Na and K?
2. What is the difference between “activity” and mass concentration measurements?
3. What is the most likely cause of such low and, most probably factitious, sodium results?
4. How can one quickly determine if one of the causes of factitious hyponatremia is present?
5. Are the results from the flame emission analysis unexpected? Why?
6. Why is the potassium result not as proportionally low as the result for sodium?
7. What are the alternatives available for a proper analysis of this sample?

Answer

1. The technologist should immediately look at the sample to determine if lipemia is present. Typically, the sample will be very turbid because of the high concentration of large lipoprotein molecules. If the sample is not lipemic, a total protein measurement (such as by refractometry) can be performed to see if the specimen has a large protein concentration.
2. Yes. An alternative method for sodium analysis which does not employ a dilution step should be used, such as an instrument with a non-dilution, ion-selective electrode. If such an instrument is not available, reject the sample.

Answers to Questions to Consider

1. Flame photometry (FAES) measures the light emitted from gaseous Na and K atoms after they have been raised to excited states in a propane-air flame (p. 97). Ion selective electrodes (ISE) measure the activity (p 274) of Na, K, and Cl, which is related to concentration. The activity measurement is based on the voltage difference established on the ISE in the presence of the specific ion (see pp. 273-279). The ISEs perform the analysis directly on the sample (non-dilutional ISE) or following a dilution of the sample (dilutional ISE); FAES measurements are performed on diluted sample.
2. Mass measurements by FAES are dependent upon sampling an exact volume, and therefore mass of Na or K, which is introduced into the flame. Usually the mass of Na or K will be evenly dispersed throughout the sample and dilutions will be accurate. In activity measurements, only the amount of material that is physiologically and chemically available - i.e., active - is measured (p. 274). If the sample is prediluted before being brought into contact with the ISE, that dilution must also be accurately performed.
3. One of the most likely causes of these very abnormal results is the presence of large amounts of lipid particles (very low density lipoproteins or chylomicrons) in the serum. The lipid expands the volume of the plasma although the concentration of sodium and potassium in the plasma water remains constant, as the cations do not readily dissolve in the lipid fraction of blood. The ion selective electrodes (ISE) measure the activity of sodium and potassium and therefore would respond only to their concentration in the water fraction of plasma. However, the instruments used in this laboratory dilute the sample prior to the analysis by the ISEs. The calculation of the concentration of sodium and potassium and plasma water depends on an accurate dilution of the plasma water . Since a significant percentage of this highly lipemic sample was lipid and not plasma, the instrument is actually sampling and diluting less plasma water, and less sodium and potassium, than expected from the volume aspirated. The calculation thus produces erroneously low values. This result is known as “pseudohyponatremia” (See p 280 and also Methods Sodium and Potassium in CD-ROM). Very elevated concentrations of serum protein may also be a cause of pseudohyponat:remia.
4. If pseudohyponatremia is caused by hyperlipidemia, the technologist can simply look at the specimen. If it is extremely milky, one can assume pseudohyponatremia is the cause of the very low sodium result. If it is clear, one should measure serum protein concentration; the quickest way is by refractometry. This will determine if the sodium result is caused by pseudohyponatremia resulting from hyperproteinemia.
5. No. Flame photometers also predilute the specimen prior to analysis and thus are prone to the same dilutional error with turbid samples.
6. The erroneously low values of sodium and potassium concentrations are dependent upon the proportional error of the volume of lipid taken up with the sample. If 10% of the sample were lipid and contained 140 mmol/L of Na in the plasma water and no Na in the lipid fraction, a 10% error would be introduced yielding an erroneously low result of 126 mmol/L. Because the physiological concentration of sodium is restricted to a narrow range (approximately 7% range of concentration), the magnitude of the analytical error becomes medically significant, i.e. outside the typically encountered physiological concentration of serum sodium. For potassium, serum concentrations in normal individuals extend over a 33% range. Thus the 10% error will yield a lower result, but not the grossly abnormal result that is found for sodium (See Methods Sodium and Potassium in CD-ROM).
7. Analyzers employing ion selective electrodes that do not perform a dilution on the sample prior to analysis (direct or nondilutional ISEs) will yield accurate results. By measuring the activity of the ions directly in the sample, these instruments report the true plasma water concentrations of sodium and potassium. Alternatively, one can use a high speed centrifuge, such as the Beckman Airfuge, to separate chylomicrons from the plasma and allow sampling of the plasma free of large lipid particles. If neither of these alternatives is available, the sample should be rejected as inappropriate for analysis (Link to Methods CD Sodium and Potassium)