Evaluation of hyponatraemia: too much water or too little sodium?
Context
Hyponatraemia is the commonest electrolyte abnormality encountered in clinical practice. 1 Sodium is measured as part of the core renal profile, and doctors usually encounter hyponatraemia in this context. Very low sodium results are likely to be phoned by laboratory staff.
Normally, the concentration of sodium in blood is about 135–145 mmol/L. A reduced concentration is referred to as hyponatraemia. It is very common and potentially serious. It is therefore important to understand how to evaluate it.
The sodium concentration is a ratio, of sodium, in millimoles, to water, in litres. So the unit of sodium measurement is millimoles per litre (mmol/L). Why is this important? Because the finding of a reduced sodium concentration means one of two things. Either there is too little sodium, or too much water. Deciding which is at the heart of the evaluation of hyponatraemia. Assessing the patient’s volume status is the most useful thing to do in making this decision.
Assessment of volume status requires some background knowledge. Water is present inside and outside cells; thus there is intracellular and extracellular fluid (ICF and ECF). The volume of ICF is double the volume of ECF. ECF is further subdivided into blood and interstitial fluid. The sodium concentration in ECF is typically about 140 mmol/L. In ICF it is about 4 mmol/L. There is therefore a very large sodium concentration gradient across the plasma membrane. (The distribution of potassium in the body is the mirror image of sodium, and thus a correspondingly large potassium concentration gradient exists in the other direction). Figure 1 below shows the relative volumes of ICF and ECF in someone who weighs 70kg.
© 2018 Elsevier Ltd. From Murphy et al. Clinical Biochemistry: an ICT, 6e. Reproduced with permission.
Three further pieces of information are required to understand the changes in volume that occur in different body fluid compartments in hyponatraemia.
First, water gain or loss occurs to/from the combined volume of all body fluid compartments. This is because water can move between all of these compartments.
Second, sodium is largely confined to the extracellular fluid (ECF). There’s a pump in the plasma membrane of every cell – the Na+/K+-ATPase – that keeps it there. It pumps sodium (Na+) and potassium (K+) against their respective concentration gradients, using energy released from ATP to do so. Sodium loss or gain is solely from/to the ECF.
Third, water follows solute by osmosis. Since the sodium concentration in ECF vastly exceeds that of other electrolytes, water largely follows sodium. The kidneys utilise this property to regulate blood volume, by varying the urinary excretion of sodium.
With this information, it can readily be appreciated why a gain of, say, 5L of pure water in a 70kg patient would cause minimal clinical signs of volume change, since the added volume of water will be distributed evenly across all body compartments. By contrast, if a patient lost enough sodium from the ECF to cause associated loss of 5L water, this would give rise to clinically obvious dehydration, since the water would also be lost exclusively from the ECF. (In a 70kg patient, the ECF volume is 14L – loss of 5L amounts to more than one-third of the total ECF volume. The patient would be in extremis).
The animated Figures 2(a) and (b) below show the exact changes in volume that would be seen in different body compartments if 5L fluid was gained [Figure 2(a) – too much water], or lost [Figure 2(b) – too little sodium].
Click or tap on each figure to start the animation.
As stated earlier, the most useful thing to do therefore when faced with a very low sodium result is to assess the patient’s volume status. If the patient shows no evidence of dehydration (i.e. ECF volume depletion), then you are likely to be dealing with too much water. If the patient has clear signs of dehydration, then too little sodium is the likely explanation. The clinical course of sodium loss is much faster than that of water gain, and even in the absence of any symptoms due to the hyponatraemia, should be treated with urgency.
The question considered here is only part of the evaluation of hyponatraemia. Other issues that must be considered include the seriousness of the result, the cause of the hyponatraemia, and how it should be treated. These will all be dealt with in subsequent posts.
Clinical note
ECF volume can readily be assessed by clinical examination. Reduced ECF volume gives rise to the clinical signs of dehydration: low blood pressure, high pulse rate, dry tongue and mucous membranes, reduced skin elasticity (turgor). Increased ECF volume may be associated with raised jugular venous pressure, bibasal crepitations, and the clinical signs of ascites and pleural effusions. (These are also seen in cardiac failure).
ICF volume is much harder to assess. Changes in cognitive function may be seen as well as fatigue and malaise.
Q&A
Which one of the following statements is true?
- Sodium is the main contributor to the serum osmolality; as a result, hyponatraemia is always associated with a reduced serum osmolality.
- False Sodium is indeed the main contributor to serum osmolality, and in most cases of hyponatraemia, measurement of serum osmolality confirms a hypo-osmolal state. However, if another osmolyte increases acutely, there may be an increase in serum osmolality despite a normal or even low sodium concentration; this is most often seen when severe hyperglycaemia develops in diabetic patients. Rarely a large increase in lipids or proteins (neither of which contributes to serum osmolality) can produce artefactual hyponatraemia; serum osmolality is normal. This is called pseudohyponatraemia.
- The cause of sodium loss from the body is always clinically obvious.
- False Whilst loss of sodium will produce obvious clinical dehydration as outlined above, irrespective of the cause, the cause of the loss may not be obvious. Sodium can be lost from kidneys, gut, or skin (gut fluids and sweat contain a similar sodium concentration to blood). Loss of gut fluids, in e.g. gastroenteritis, is clinically obvious, and readily recognised as the cause of sodium depletion, which is also a well-recognised complication of serious burns. Urinary loss is less obvious and requires the clinician actively to consider it.
- The clinical course of water gain is much slower than that of sodium depletion; hyponatraemia due to too much water has to be more severe before symptoms of hyponatraemia appear.
- False This is quite a challenging question. The clinical course of water gain is indeed much slower than that of sodium depletion, and if the decline in sodium concentration due to water excess is sufficiently gradual, then symptoms of hyponatraemia may not be prominent. A patient with an equivalent degree of hyponatraemia due to sodium depletion is likely to have other symptoms besides, due to hypovolaemia. Adding to the difficulty of assessment, symptoms of mild or moderate hyponatraemia are non-specific – sometimes subtle changes in cognitive function are the only manifestation. However, any given degree of hyponatraemia is liable to be associated with symptoms irrespective of the mechanism – it is simply not possible to state categorically that symptoms of hyponatraemia occur at different sodium concentrations depending on the mechanism. It is important to be aware that severe hyponatraemia may be associated with a reduced level of consciousness up to and including coma, as well as seizures. The appearance of any of these in a patient with severe hyponatraemia is immediately life-threatening; treatment must be instituted with extreme urgency.
- Postural hypotension (a fall in blood pressure when a patient stands from sitting or lying) in a hyponatraemic patient makes sodium depletion (too little sodium) more likely than water excess.
- True Postural hypotension is defined as a fall in blood pressure of more than 20/10 from sitting or lying to standing. It is not specific to sodium depletion but in the presence of hyponatraemia makes it much more likely; a reduced ECF volume interferes with the baroreceptor (vasoconstriction) reflex that normally limits the lowering effect on blood pressure of the blood redistribution that occurs on standing.
- The most likely explanation for the simultaneous finding of low sodium and high potassium concentrations is that the Na+/K+-ATPase pump in the plasma membrane is not working normally, leading to ‘leakage’ across the concentration gradients (i.e. Na+ into, and K+ out of, cells).
- False This explanation has been used in the past to explain this combination of findings (the so-called ‘sick cell’ syndrome), but despite its biological plausibility, robust evidence of its existence is limited. Low sodium and high potassium together should make one think of primary adrenal insufficiency (Addison’s disease). Hormones normally produced by the adrenal glands act on the renal tubules, reabsorbing sodium and water in exchange for potassium or hydrogen. This is how the kidneys vary sodium excretion. When they are not produced, this does not happen, resulting in low sodium, high potassium (and if it is measured), a low bicarbonate reflecting buffering of retained hydrogen ions.
Clinical Case
A 24-year-old student presents with a six-month history of malaise, tiredness, poor appetite and one stone weight loss. She has developed a craving for salty foods – crisps in particular. She has had a number of dizzy spells particularly while in warm places. On examination, she is thin. Blood pressure is 110/64 which falls further on standing. You have the impression that she is tanned, and you find increased pigmentation in her mouth and hand creases. Her bloods show low sodium [122 mmol/L] and high potassium [5.8 mmol/L].
- Which do you think is more likely explanation for her hyponatraemia – too little sodium or too much water?
- This presentation is more typical of sodium depletion (too little sodium) than water excess. The craving for salt is not universally seen with sodium depletion, although there is at least one case report of a patient effectively ‘self-medicating’ by means of excessive dietary salt consumption. 2 Blood pressure in patients with water excess would be higher than this, and the abnormal pigmentation is a big clue as to the likely cause of hyponatraemia (see below).
- What is the most useful piece of information from the history and examination in deciding?
- The finding of low-normal blood pressure and – especially – reported postural drop is highly suggestive of sodium depletion, and should prompt urgent requesting of electrolytes and renal profile ± acute referral. Dizzy spells probably reflect hypotension. Weight loss probably reflects urinary loss of water (accompanying sodium). Malaise and tiredness are non-specific and common and not especially useful.
- Why is this important?
- Don’t forget that the doctor seeing the patient will only have information from the history and examination. If the connection is not made between the symptoms and the lowish blood pressure and postural hypotension, then electrolytes may not be requested. (As outlined in previous answer, some of the symptoms are non-specific, and common). In the absence of electrolytes, the diagnosis of sodium depletion may be missed, with potentially fatal consequences: the patient may develop a salt-losing crisis leading to severe ECF volume depletion and circulatory collapse.
- Can you explain the pigmentation?
- Pigmentation is a very useful clinical sign in the context of hyponatraemia. If the clinical impression is of too little sodium, then the cause must be sought. In the absence of gut or skin loss, urinary loss should be suspected. Urinary excretion of sodium is controlled by hormones secreted by the adrenal glands, and adrenal insufficiency is characterised by excessive urinary loss sodium and water. In the absence of negative feedback by the hormones normally secreted by the adrenal glands, the controlling organ (the anterior pituitary) secretes more of the trophic hormone (adrenocorticotrophic hormone or ACTH). This peptide hormone contains within its amino acid sequence another hormone (melanocyte-stimulating hormone or MSH). As soon as it is released, ACTH is broken down by proteases in the blood, exposing the MSH sequence which then acts on melanocytes in the skin resulting in pigmentation/tanning.