Thoughts on dysnatremia

Abstract

Osmoregulation is the result of the complex interplay of several physiological processes, which control the water fluxes in the human body. A concise overview is presented in Chapter 1. The plasma sodium concentration is the most important determinant of plasma tonicity and therefore regulates the osmotic movement of water between the fluid compartments in the human body. Somewhat counter intuitively, the plasma sodium concentration is primarily a reflection of the water homeostasis in the human body and only to a lesser extent of its total amount of sodium. A key player in maintaining the plasma sodium concentration within its reference range is the antidiuretic hormone (ADH), which stimulates renal reabsorption of pure water, back into the circulation. Pathological ADH secretion is one of the main culprits in the disorders of the plasma sodium concentration, collectively known as dysnatremia. Dysnatremia is divided in hyponatremia (a decreased plasma sodium concentration as a result of dilution of the plasma due to a water excess) and hypernatremia (an increased plasma sodium concentration as a result of concentration of the plasma due to a water deficit). The clinical ramifications of dysnatremia are especially noticeable in the brain. This thesis zooms in on clinical aspects of disorders of the osmoregulation and the struggles for physicians they entail. In Chapter 2, some important pitfalls in their analysis and treatment are highlighted, and the attitude of clinicians towards dysnatremia is investigated by means of a survey. In order to facilitate the initial “bed-side analysis” of monofactorial dysnatremia, a novel clinical nomogram is presented in Chapter 3 as a practical tool for the often intractable clinical practice. In Chapter 4, an attempt is made to derive a governing dysnatremia equation, based on an electrolyte-free water balance, and integrating urine osmolality and urine tonicity. In a similar vein, a transparent and clinically applicable equation that can be used to calculate the estimated effect of different types and volumes of crystalloid infusate on the plasma sodium concentration in the frequently encountered syndrome of inappropriate ADH secretion is derived in Chapter 5, and retrospectively validated and compared to the widely used Adrogue-Madias equation in Chapter 6. Because this equation is derived on the premise of tonic ADH release, it would theoretically be a well-suited model for the prediction of the plasma sodium response to hypertonic saline boluses in the context of a proactive desmopressin clamp to prevent osmotic demyelination syndrome during the correction of hyponatremia. We have expounded on this alternative clinical application of our equation in Chapter 7. In Chapter 8, the theoretical relationship between extracellular volume depletion and resultant hypotonic hyponatremia is discussed. Chapter 9 presents the results of a retrospective chart study, which investigates the occurrence of dysnatremia in coronavirus infectious disease 2019 (COVID-19) patients as compared to non-COVID-19 respiratory illness, rather than healthy controls. Disorders of the water and sodium balance –and especially hypernatremia, contrary to the findings of several previously published studies– seem to be a very common extra-pulmonary occurrence in COVID-19 patients.