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r isk factors for hyponatremia with treatment of nocturia

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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r isk factors for hyponatremia with treatment of nocturia

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  1. 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

  2. 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

  3. AVP stimulation and effects baroreceptors, natriuretic peptides hyperosmolality, hypovolemia, angiotensin II + – AVP V2 Receptors V1a Receptors renal H2O reabsorption vasoconstriction

  4. 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

  5. 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

  6. requirements for producing hyponatremia: AVP V2R activation positive water balance

  7. chronic hyponatremia model in rats solid diet + tap water liquid diet Verbalis & Drutarosky, Kidney Int34:351-360 1988

  8. hyponatremia age-associted risks

  9. 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

  10. 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)

  11. elderly subjects develop greater degrees of hyperosmolality following 24h fluid deprivation Rolls & Phillips, Nutrition Reviews 48:137, 1990

  12. 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

  13. Rowe JW. J Gerontol 31:155-63, 1976

  14. variability in age-associated decline in renal function as assessed by creatinine clearance Lindeman et al. J Am Geriatr Soc 33:278, 1985

  15. 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

  16. elderly subjects drink less following 24h fluid deprivation despite higher plasma osmolalities Phillips et al, Age and Aging 22:26-33, 1993

  17. AVP responses are potentiated in the elderly Helderman et al., J Gerontol 33:39-47, 1978

  18. hyponatremia: sex-associated risks

  19. 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

  20. 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

  21. enhanced sensitivity of humanfemales to lower doses of desmopressin Juul et al. Am J Physiol300:F1116, 2011

  22. 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

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