4.9: Colligative Properties

A patient is suspected of having dilutional hyponatremia, that is a low serum sodium concentration caused by excess water retention leading to dilution of the serum sodium. The emergency room resident asks for a renal profile (sodium, potassium, chloride, total CO₂, glucose, and BUN) and a measured osmolality. The results of this analysis are as follows: Na = 127 mmol/L; K = 3.5 mmol/L; chloride = 107 mmol/L (all of these three analytes by dilutional ion selective electrodes); CO₂ = 19 mmol/L (by enzymatic analysis); glucose = 740 mg/L (by rate glucose oxidase); BUN = 130 mg/L (by enzymatic conductimetric analysis), and measured osmolality = 365 mOsm/L (by vapor pressure osmometry).

The resident questions the results and asks for a repeat analysis of the osmolality. Repeat analysis is reported out as 367 mOsm/L. The resident, still believing that the patient has dilutional hyponatremia and wanting to treat the patient, asks if the medical technologist can check the osmolality in some other way.

QUESTIONS

1. How can the technologist verify that the measured osmolality is accurate?
2. After looking at the specimen, the technologist decides to calculate the estimated osmolality by using the data from the renal profile and obtains a result of 266 mOsm/L. Why does this result help in the estimation of the accuracy of the measured osmolality?
3. The clinical chemist suggests that the physician accept the calculated osmolality as the more valid result and, in addition, that the physician order an alcohol quantitation — not a screen - because the chemist, based on the osmolality of 318 mOsm/L obtained by freezing point depression in the laboratory, calculates that the patient’s alcohol level is very high. Is this information helpful for explaining the initial discrepancy? Why?

Questions to Consider

1. What property of solutions does osmolality measure?
2. What is the principle of measuring osmolality by vapor pressure? By freezing point depression? By calculation?
3. How did the medical technologist arrive at the value of 266 mOsm/L?
4. Why is the calculated osmolality so different from the osmolality measured by vapor pressure depression?
5. Would a similar difference be obtained if a freezing point depression osmometer were used?
6. How can the alcohol (e.g., ethanol) concentration in serum be estimated from the osmolality derived from the freezing point depression osmometry?
7. How can the presence of an alcohol be confirmed?

Answer

1. The technologist can verify the osmolality value by repeating the assay with a freezing point depression osmometer or by calculating the expected osmolality. In addition, the technologist must look at the specimen to see if significant hypertriglyceridemia exists since very lipemic samples can result in pseudohyponatremia (see SODIUM measurement on CD-ROM).
2. The difference between the calculated osmolality and the osmolality measured by vapor point depression suggests an interferent in one of the results, most likely the vapor point assay. The results suggest that there may be an unexpected substance in the serum.
3. Yes. The presence of alcohol in high quantity would explain the discrepancy of the results and indicate that the resident’s assessment of dilutional hyponatremia is probably correct.

Answers to Questions to Consider

1. Osmolality is a measure of the number of moles of dissolved solute per kilogram of water. Osmolality does not distinguish the types of solute present, just the number of moles of solute (p. 267).
2. Vapor pressure osmometry is based on the fact that the greater the number of particles dissolved in a solvent (or moles of solute), the less solvent vapor will exist in the atmosphere over the solution. The decrease in vapor pressure is directly related to the osmolality of the solution, and is monitored by a thermocouple above the solution (pp. 270).
   
   Freezing point osmometry is based on the ability of the dissolved solutes to lower the point at which the solution will freeze. The more solutes dissolved, the lower the temperature at which the solution will freeze. The actual freezing point is determined from the heat released upon freezing; the heat is measured by a sensitive thermocouple (pp. 269).
3. The equation used to estimate serum osmolality is equation 14-1 (p. 267) as follows: $$\text{Calculated osmolality} = 2\; Na\; (mmol/L) + \frac{\text{glucose}\; (mg/L)}{180\; mg/mol} + \frac{BUN\; (mg/L)}{28\; mg/mmol}$$Thus $$\begin{split} \text{the calculated osmolality} &= 2 (127) + 740/180 + 180/28 \\ &= 254 + 4.11 + 6.4 = 265\; mOsm/L \ldotp \end{split}$$This osmolality is more consistent with the physician’s diagnosis of dilutional hyponatremia.
4. The very large difference between the calculated and measured osmolality is probably because caused by the presence of some volatile substance in the patient’s blood. Such a volatile substance would naturally increase the mass of vapor or the vapor pressure above the solution and falsely increase the vapor pressure and measured osmolality. A common type of volatile positive interferent would be an alcohol. (pp. 268).
5. No. Freezing point osmometry measures the presence of all solutes directly. Therefore, It would measure the volatile component accurately. There is no interference resulting from the vapor phase of a volatile component.
6. One can estimate the alcohol levels by assuming that only ethanol is present (the usual volitile) and using the calculated the OSMOLAR GAP, which is the difference between the measured osmolality by freezing-point depression. One could use Table 14-1 (p 268) or the equation described in the Alcohol chapter on the Methods CD-ROM to estimate the concentration of ethanol. Using the equation, one calculates as follows: $$\begin{split} [\text{Measured osmolality} - 290] \times 46.07\; g/mol \times 0.92 &= \text{estimated concentration of alcohol} \\ [318 - 290] \times 46.07\; g/mol \times 0.92 &= [alcohol] \\ 1187\; mg/L &= [alcohol] \end{split}$$The term 290 mol/L is the normal serum osmolality.
7. The presence of alcohol should be confirmed by either an enzyme based assay or by gas chromatography. The latter would be preferable since it would also indicate which alcohol was present.