Sodium – interpretation of measurements

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Sodium is the most abundant extracellular cation in humans. The concentration in the extracellular fluid is highly influenced by the amount of fluid it is dissolved in – the reason why we always say that most low sodium problems are actually problems of too much water.

There is an important difference between sodium concentration and sodium activity. The concentration simply refers to the total amount of sodium present per unit volume, whereas the activity refers to the amount of free sodium ions that are free to enter a chemical reaction and are not complexed to other plasma constituents, e.g. proteins. Due to historical convention sodium tends to be reported in terms of it’s concentration rather than true activity.
Believe it or not, if we were able to measure the exact amount of sodium in a litre of blood, it would only be in the region of 84mmol. This is because blood contains around 40% red cells, which have little or no sodium content.
If we then tried to figure out the concentration of sodium in the remaining 0.6 litres of ‘fluid’ in blood (84/0.6) we would get a figure of 140mmol/L.
However, remember that in normal circumstances plasma is only 93% fluid; the remainder being composed of proteins, lipids etc.. So, in actual terms, the true plasma water sodium concentration is (140/0.93), or around 151mmol/L.
This knowledge will help explain the concept of pseudohyponatraemia associated with hyperlipidaemia or hyperproteinaemia. In these scenarios, the plasma water content per litre of plasma is reduced from 93% to let’s say 80% for example.
If the lab reported that our patient’s sodium was 120mmol/L then we can try to calculate what the true plasma water sodium concentration is:
120/0.8 = 150
This is similar to the true plasma water figure in our normal patient, who had a sodium of 140mmol/L and plasma water content of 93%.
This should also explain why we call ‘normal saline (0.9%)’ an isotonic fluid, even though when you read the chemical composition label, you will find that it contains 154mmol/L of sodium ions and 154mmol/L of chloride ions.
Next week I’ll try to delve into the various ways that sodium has been measured in clinical laboratories.


  1. There are several issues here that should be discussed. First as mentioned, the convention is to report a serum sodium concentration as mEq/L of serum (normal = 140) rather than mEq/kg of serum water (normal = 151). The latter is probably preferable for theoretical reasons but historically we have decided to stick with the former to avoid confusion. Serum sodium concentration in mEq/L is now measured in most labs using an ion electrode which actually measures sodium activity as mentioned in the earlier posts. Clinical labs will do this in two ways – 1) Diluting the sample and then measuring activity and then back calculating concentration by multiplying by the dilution factor. Unfortunately one has to assume the a certain fraction of serum is water – hence this technique is prone to pseudohyponatremia just as much as old fashioned flame photometry. In fact, most clinical use this method so pseudohyponatremia is still a problem. Why would labs dilute the sample? There are probably two reasons: 1) Use of less blood and 2) As solutions become dilute, the activity coefficient approaches 1 and activity and concentrations are nearly equal. The second approach is to directly measure sodium activity in serum – many blood gas analyzers actually use this technique and some hospital labs. The only issue with this technique besides the blood volume is that one needs to know the activity coefficient to convert the measured activity to a concentration. The activity coefficient in serum is around 0.75 so that the direct electrode measures an activity around 105 which is converted to 140 mEq/L (105/0.75). There is some extra quality control that may be required, but my guess is that practical or financial issues may lead hospitals to use the theoretically less attractive indirect (dilution) electrode method – first hospitals with labs processing pediatric samples may want to conserve blood volume – for instance, surprisingly our VA uses direct electrode measurement for all blood samples since kids are not an issue. Second, there may also be contractual issues with certain equipment manufacturers.

    Bottom line: Pseudohyponatremia is still a concern in most labs. Direct electrode measurement gets around this and is typically used (not always) by blood gas analyzers. You will need to know where to go to get this at your hospital.

  2. I also have the same doubt… If the direct electrode measures exact plasma water concentration (so as to eliminate false reading from pseudohyponatremia) then how does it report as 140? It should be 151

  3. If there is direct electrode measurement of sodium in plasma then why does it come back as 140meq/L and not 154?

  4. "Next week I’ll try to delve into the various ways that sodium has been measured in clinical laboratories."

    Will wait for that post on measurements because with the newer techniques of direct electrode measurements, pseudohyponatremia is virtually non existent as it measures direct sodium concentration and not relative to plasma.

    Given the advances in measurement techniques, pseudohyponatremia should be buried in history books.


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