Of Mice and Men—The Physiology, Psychology, and Pathology of Overhydration

Abstract

The detrimental effects of dehydration, to both mental and physical health, are well-described. The potential adverse consequences of overhydration, however, are less understood. The difficulty for most humans to routinely ingest ≥2 liters (L)—or “eight glasses”—of water per day highlights the likely presence of an inhibitory neural circuit which limits the deleterious consequences of overdrinking in mammals but can be consciously overridden in humans. This review summarizes the existing data obtained from both animal (mostly rodent) and human studies regarding the physiology, psychology, and pathology of overhydration. The physiology section will highlight the molecular strength and significance of aquaporin-2 (AQP2) water channel downregulation, in response to chronic anti-diuretic hormone suppression. Absence of the anti-diuretic hormone, arginine vasopressin (AVP), facilitates copious free water urinary excretion (polyuria) in equal volumes to polydipsia to maintain plasma tonicity within normal physiological limits. The psychology section will highlight reasons why humans and rodents may volitionally overdrink, likely in response to anxiety or social isolation whereas polydipsia triggers mesolimbic reward pathways. Lastly, the potential acute (water intoxication) and chronic (urinary bladder distension, ureter dilation and hydronephrosis) pathologies associated with overhydration will be examined largely from the perspective of human case reports and early animal trials.

Differential effects of sodium chloride and monosodium glutamate on kidney of adult and aging mice

“…Aquaporins are post-transcriptionally downregulated in aging rat kidneys 53 , accounting for a decreased ability of aging kidneys to concentrate urine. AQP2 expression in the kidney is upregulated by water deprivation 53 , 54 and also by protein load 55 , 56 , but neither in young nor in old MSG groups we detected an increase in this protein, if compared to age-matched controls. AQP2 urinary (uAQP2) excretion reflects short-term changes in vasopressin release, being both suppressed by water load and increased by sodium chloride administration, hence uAQP2 represents a marker for collecting duct responses to vasopressin 57 .…”

Is isolated bladder outlet obstruction associated with hydronephrosis? A database analysis

“…We do not have information regarding bladder diary records of these patients. Chronic overhydration may be an independent factor contributing to the development of hydronephrosis 23 . Most (but not all) of our patients undergoing urodynamics have a bladder diary record before resorting to invasive urodynamics.…”

“…Chronic overhydration may be an independent factor contributing to the development of hydronephrosis. 23 Most (but not all) of our patients undergoing urodynamics have a bladder diary record before resorting to invasive urodynamics. It seems improbable that patients would slip through in large enough numbers to influence the conclusions.…”

Management of hyponatraemia and hypernatraemia during the Covid-19 pandemic: a consensus statement of the Spanish Society for Endocrinology (Acqua Neuroendocrinology Group)

“… Difficulties accessing water due to psychosocial factors, such as social isolation during confinement and anxiety or depression linked to outbreaks, can be particularly harmful in CH and DI patients. Futhermore, water intake can activate mesolimbic reward circuits in the central nervous system, which could lead to psychogenic polydipsia in these patients and ultimately worsen water balance [ 15 ]. DI-specific risks during COVID-19 pandemic: Loss of follow-up during the pandemic might lead to undetected hyponatraemia due to desmopressin overdose, particularly when administered through intranasal route [ 16 ].…”

“…Difficulties accessing water due to psychosocial factors, such as social isolation during confinement and anxiety or depression linked to outbreaks, can be particularly harmful in CH and DI patients. Futhermore, water intake can activate mesolimbic reward circuits in the central nervous system, which could lead to psychogenic polydipsia in these patients and ultimately worsen water balance [ 15 ].…”