Hyponatremia is the most common electrolyte disorder in hospitalized patients. If not treated adequately, it can lead to serious consequences. Despite its high prevalence, hyponatremia is considered one of the hardest electrolyte disorders to grasp. In this review, we aim to give a simplified overview of the key points to be taken into consideration when addressing hyponatremia.
Hyponatremia is a reduced sodium concentration in the blood, defined as a serum sodium level below 135 mmol/l1. Patients with hyponatremia may have a great variety of symptoms, ranging from headache, nausea and dizziness to more extreme symptoms like seizures or coma2. As these symptoms are non-specific, the clinician should keep a keen eye for the possibility of hyponatremia and request laboratory tests even with a low degree of suspicion.
The first step: hypotonic vs. hypertonic
The first distinction to be made is whether the hyponatremia is a true hypotonic state (i.e. a condition of low serum osmolality) or whether hyponatremia has developed secondary to the presence of another osmotically active molecule. In the latter case, serum osmolality is actually increased and has resulted in a shift of water from the intracellular to the extracellular compartment, thus lowering serum sodium concentration. In most cases hypertonic hyponatremia is the result of diabetic ketoacidosis, but it can also follow the intravenous administration of high doses of mannitol or sucrose.
Hence, as a first step, it is essential to obtain a serum osmolality and serum glucose in order to exclude hypertonic hyponatremia. In most cases however, patients will present with a hypotonic hyponatremia. Therefore, this article will address hypotonic hyponatremia only.
Hypotonic hyponatremia; three types
Hypotonic hyponatremia can be classified into three types according to the underlying mechanism. Classification is based on the fluid status of the patient. For this reason, it is mandatory to obtain a full physical examination with special attention for signs of hypovolemia (weight loss, orthostatic hypotension, dry axilla, decreased skin turgor, delayed capillary refill) or hypervolemia (ascites, edema, weight gain, hypertension). In patients admitted to the hospital, fluid balances and weight development over the course of the admission will advance the quest for the cause of the hyponatremia. However, the diagnostic value of physical examination alone to evaluate fluid status is limited3-6. Therefore, the mere absence of physical signs cannot rule out hypo- or hypervolemia and laboratory testing is almost always required to provide additional information5,6. As a minimum, serum and urine osmolality, sodium and creatinine levels should be obtained1. The combination of history, physical examination and laboratory findings can be used to assess fluid status and to identify the underlying cause.
The most common causes of hyponatremia will be discussed below.
1. Hypovolemic hyponatremia
There is a loss of extracellular fluid (ECF) volume. This type of hyponatremia develops as an adequate response to the loss of water (and sodium), for instance in patients with diarrhea and/or vomiting. In response to the loss of ECF, the body will try to retain sodium and water, and will do so by the release of renin and antidiuretic hormone (ADH), respectively. When the patient ingests and/or receives hypotonic fluids (e.g. tea, water or glucose i.v. solutions) in this situation, more water than sodium will be ingested. As a consequence, the patient will dilute the extracellular water compartment, as excretion of water is limited due to the actions of renin and ADH. Patients present with low urine volume. Laboratory results include both low serum and urine sodium levels1,7.
2. Euvolemic hyponatremia
There is a (sub)normal ECF volume. This is most commonly caused by an inadequate retention of water. In most cases, the kidneys fail to excrete water due to the activity of ADH. Too much water stays within the body and therefore the serum sodium level drops. The release of ADH is inadequate for the situation, which is why this condition is referred to as the syndrome of inappropriate secretion of ADH (SIADH). Important causes of SIADH are pneumonia and meningitis. However, ADH excretion is also increased in pain and nausea and therefore SIADH is a common finding in hospitalized patients. Other conditions leading to hyponatremia with a near-normal ECF volume are hypothyroidism and adrenal insufficiency: both thyroid hormone and cortisol are required for the excretion of electrolyte free water by the kidneys2,7. In all such cases, the urinary sodium level is commonly greater than 30 mmol/l, as the kidneys are unable to excrete electrolyte free water (in other words: to dilute the urine)1. The high level of urinary sodium found in these patients does not imply a loss of sodium; a finding that many consider counterintuitive.
3. Hypervolemic hyponatremia
ECF volume is increased. Hypervolemic hyponatremia develops in patients with a low effective circulating volume, most typically in persons with congestive heart failure. Due to forward failure, renal perfusion is compromised and consequently the kidneys respond by retaining both water and sodium. Therefore, both body water and sodium are elevated: ECF is increased. Edema is a common finding in these patients. Other conditions associated with edema, like liver cirrhosis, renal failure and nephrotic syndrome, also lead to this type of hyponatremia. The concentration of sodium in urine is generally below 30 mmol/l1. In this situation, the urine should always be tested for protein to rule out nephrotic syndrome.
What to do in the clinic
We have discussed the three different types of hypotonic hyponatremia. What to do when a patient presents with a reduced serum sodium concentration? First, hypertonic hyponatremia should be ruled out by measurement of serum osmolality and glucose. Secondly, physical examination must be performed in order to assess the patient’s fluid status. In the hospitalized patient, fluid and weight charts will provide additional information regarding fluid status and the underlying cause. Thirdly, a urinary sample should be obtained for the assessment of urinary osmolality, creatinine and sodium. Also, nephrotic syndrome must be ruled out.
Finally, an attempt should be made to determine whether the patient suffers from an acute or a chronic hyponatremia. This can be determined on basis of the progression of symptoms and laboratory results over time. As a rule, true acute hyponatremia should be expected when severe symptoms are seen. Examples include seizures, pulmonary edema and coma8. In such cases, hypertonic saline should be infused immediately. In all other patients, the direct infusion of hypertonic saline can result in acute demyelination and is therefore contra-indicated2,9. In the majority of patients, the hyponatremia should be corrected more gradually, based on the time-period in which it has developed7. In addition to the correction of hyponatremia, treatment should be targeted at the underlying disease. Depending on the cause, different therapeutic options exist, ranging from fluid restriction (i.e. for patients with SIADH) to pharmacological treatment (e.g. diuretics for patients with heart failure)1.
A. Zwagemaker & M.J.S. Oosterveld
- Dutch guideline electrolyte disorders. Richtlijn elektrolytstoornissen. Nederlandse Internisten Vereniging (NIV),
- Stehouwer CDA, Koopmans RP, Meer van de J. Interne Geneeskunde. Bohn Stafleu van Loghum, 2010; 14th edition.
- Fortes MB, Owen JA, Raymond-Barker P et al. Is this elderly patient dehydrated? Diagnostic accuracy of hydration assessment using physical signs, urine, and saliva markers. J Am Med Dir Assoc, 2015; 16(3): 221-8.
- Hooper L, Abdelhamid A, Attreed NJ et al. Clinical symptoms, signs and tests for identification of impending and current water-loss dehydration in older people. Cochrane Database Syst Rev, 2015; Apr 30: 4: CD009647. doi: 10.1002/14651858.CD009647.pub2.
- Kalantari K, Chang JN, Ronco C et al. Assessment of intravascular volume status and volume responsiveness in critically ill patients. Kidney Int, 2013; 83: 1017-1028.
- McGee S, Abernethy WB 3rd, Simel DJ. The rational clinical examination. Is this patient hypovolemic? JAMA, 1999; Mar 17: 281(11): 1022-9.
- Yeates KE, Singer M, Morton AR. Salt and water: a simple approach to hyponatremia. CMAJ, 2004; 170 (3): 365-369.
- Hoorn EJ, Kaasjager KAH, Zietse R. Hyponatriëmie: stel de juiste vragen. Ned Tijdschr Geneeskd, 2014; 158: A7139.
- Vervoort G, Wetzels JFM. Hyponatriëmie: adequate behandeling op geleide van te berekenen uitkomsten. Ned Tijdschr Geneeskd, 2006; 150(39): 2121-6.