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

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.