Hypernatremia, defined as a serum sodium concentration greater than 145 mEq/L, is one of the most common and clinically significant disturbances of water balance in both inpatient and outpatient settings and is associated with significant morbidity and mortality [1]. The prevalence of in-hospital hypernatremia, whether present at admission or acquired during hospitalization, varies according to different patient populations, hospital settings and serum sodium cut-offs, affecting approximately 4–7 % of inpatients [2], [3], [4]. In a retrospective cohort of 103 inpatients with hypernatremia, 86 % lacked unrestricted access to water and 74 % had enteral water intake < 1liter/day; many also exhibited impaired renal water conservation due to reduced concentrating capacity, most often related to diuretic therapy [5].

Older age is a risk factor for hypernatremia as aging is associated with reduced sensation of thirst leading to a compromised drinking response in older individuals [6]. A recent large U.S. population-based study evaluating the data of 1.9 million adult inpatients (2000–2018) revealed that those with hypernatremia were older than normonatremic patients and the odds of in-hospital mortality of patients with hypernatremia increased with aging [4]. Hypernatremia in the pre-operative setting has also been shown to be associated with increased morbidity (e.g., major coronary events, pneumonia and venous thromboembolism) and mortality, as demonstrated by a cohort study using the American College of Surgeons National Surgical Quality Improvement Program [7].

In the critically ill, hypernatremia is not merely a marker of disease severity but an independent predictor of mortality, with risk rising proportionally with sodium levels and rapidity of onset. This underscores the importance of close monitoring of sodium balance and fluid therapy in this vulnerable population. In a prospective observational study of 981 critically ill adults, hypernatremia was observed in 9 % of them: 2 % on admission and 7 % developing during the intensive care unit stay, indicating that most cases arose after admission and suggesting an iatrogenic contribution [8].

Hypernatremia is considered acute when lasting less than 48 h and chronic when persisting or presumed to persist for a longer duration. In the acute setting, even modest elevations in serum sodium can produce severe neurological symptoms due to water movement out of brain cells and subsequent cellular shrinkage [9] (Fig. 1). Therefore, an impaired thirst response (e.g., due to neurological disorders—primarily those involving a hypothalamic lesion that affects the thirst centre—or advanced age) and/or a lack of free access to water (e.g., in children, the elderly, or critically ill patients in whom inappropriate fluid administration, mechanical ventilation with dry air, and sedation-induced thirst suppression may occur) are significant risk factors for the development of hypernatremia [10].

Despite its’ clinical relevance, the underlying mechanisms of hypernatremia are often poorly understood by clinicians, which hinders accurate diagnosis and effective management of the broad spectrum of conditions that disrupt the finely tuned balance between water and solute [11]. This article aims to provide a comprehensive review of the aetiologies and pathophysiological mechanisms of hypernatremia, highlighting recent advances and emerging concepts.