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r isk factors for hyponatremia with treatment of nocturia. Joseph G. Verbalis, MD Professor of Medicine Chief, Endocrinology and Metabolism Director, Georgetown-Howard Universities Center for Clinical and Translational Science Georgetown University Washington, DC USA.
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risk factors for hyponatremia with treatment of nocturia Joseph G. Verbalis, MD Professor of Medicine Chief, Endocrinology and Metabolism Director, Georgetown-Howard Universities Center for Clinical and Translational Science Georgetown University Washington, DC USA
body fluid compartments water is the largest component of our body; the major determinant of body water is AVP-regulated water excretion by the kidneys
AVP stimulation and effects baroreceptors, natriuretic peptides hyperosmolality, hypovolemia, angiotensin II + – AVP V2 Receptors V1a Receptors renal H2O reabsorption vasoconstriction
AQP3 H2O ATP Exocytic Insertion AVP AQP2 GTP(Gs) cAMP PKA H2O AQP2 Endocytic Retrieval Recyclingvesicle AQP4 AVP regulation of water reabsorption from renal tubular cells CollectingDuct Cell Vasa recta Collecting duct AVP V2Receptor basolateralmembrane apical membrane
plasma osmolality (mOsm/kg H2O) plasma AVP (pg/ml) 296 294 292 290 288 286 284 282 280 278 276 9 8 urine osmolality (mOsm/kg H2O) 7 maximal urine excretion rate (ml/h) thirst osmotic threshold 6 5 4 250 3 500 1000 2 1 300 AVP osmotic threshold 0 100
requirements for producing hyponatremia: AVP V2R activation positive water balance
chronic hyponatremia model in rats solid diet + tap water liquid diet Verbalis & Drutarosky, Kidney Int34:351-360 1988
hyponatremia age-associted risks
effects of aging on body fluid homeostasis • body composition • reduced ECF and plasma volume • increased osmotic fluxes • kidney • decreased urine concentrating ability • decreased ability to conserve sodium • brain • decreased thirst perception. • increased vasopressin secretion
age-associated changes in body composition • aging typically leads to a 5-10% decrease in total body water(Beck & Lavizzo-Mourey, Ann Int Med 107:768-9, 1987) • plasma volume decreases as much as 21% relative to body weight and surface area compared to younger individuals(Davy & Seals, J ApplPhysiol 76:2059-62, 1994) • equivalent changes in body water are associated with greater fluxes of plasma osmolality in the elderly (Hodak & Verbalis, Endocrinol Metab Clinics NA 34:1031-1046, 2005)
elderly subjects develop greater degrees of hyperosmolality following 24h fluid deprivation Rolls & Phillips, Nutrition Reviews 48:137, 1990
effects of aging on body fluid homeostasis • body composition • reduced ECF and plasma volume • increased osmotic fluxes • kidney • decreased urine concentrating ability • decreased ability to conserve sodium • brain • decreased thirst perception. • increased vasopressin secretion
variability in age-associated decline in renal function as assessed by creatinine clearance Lindeman et al. J Am Geriatr Soc 33:278, 1985
effects of aging on body fluid homeostasis • body composition • reduced ECF and plasma volume • increased osmotic fluxes • kidney • decreased urine concentrating ability • decreased ability to conserve sodium • brain • decreased thirst perception. • increased vasopressin secretion
elderly subjects drink less following 24h fluid deprivation despite higher plasma osmolalities Phillips et al, Age and Aging 22:26-33, 1993
AVP responses are potentiated in the elderly Helderman et al., J Gerontol 33:39-47, 1978
hyponatremia: sex-associated risks
renal V2R expression is increased in female rats levels of V2R mRNA (top) and protein (bottom) in male versus female rat kidneys Liu et al. Am J Physiol 300:F433, 2011
female rats are more sensitive to lower doses of desmopressin urine osmolality (top) and volume (bottom) in response to graded infusions of desmopressin Liu et al. Am J Physiol 300:F433, 2011
enhanced sensitivity of humanfemales to lower doses of desmopressin Juul et al. Am J Physiol300:F1116, 2011
chracteristics of a high risk patient to develop hyponatremia on desmopressin elderly (>65) female low BMI (<22) eGFR <50 low solute diet likes to drink tea