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Dysnatremias

Dysnatremias

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Dysnatremias

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  1. Dysnatremias

  2. Case Presentation 1 19 year old female with a history of depression is referred for polyuria and polydipsia. Over the past 2 years she developed polydipsia rather abruptly, frequently drinking 5 gallons of water per day. Medications included fluoxetine 20 mg daily and famotidine 20 mg daily.

  3. Case Presentation 1 Cont’d Physical Exam Obese, depressed affect BP 126/80 HR 100 Trace edema 24 hr urine volume 13 liters Urine osm 80 mosm/kg Serum Sodium 144 Chloride 106 Potassium 4.4 CO2 29 BUN 5 Creat 0.6 Glucose 92 Osm312

  4. Polyuria • Urine output exceeding 3 L per day • Etiology • Water diuresis • diabetes insipidus • central • nephrogenic • primary polydipsia • Solute diuresis

  5. Evaluation of Polyuria Urine Osmolality < 250 mosm/kg 300-400 mosm/kg Water Diuresis Solute Diuresis

  6. Water Restriction Test • No intake 2-3 hours prior to test • Measure: • Hourly BP and weight • Hourly urine volume and osmolality • Plasma sodium and osmolality every 2 hour • Give dDAVP 5 mcg sc if no change in urine osm despite rising serum osm or if plasma osm > 295 mosm/kg

  7. Case Presentation 1 Cont’d Water Deprivation Test TimeWt. BP Sosm Uosm (hr) (lb) (mmHg) (mosm/kg) 0 234 120/80 305 87 2 232 115/70 313 113 4 230 118/60 325 125 6 227 110/80 323 138 8 227 118/70 305 655 dDAVP 5 u sc

  8. Regulation of ADH Release Posm Effective Circulating Volume Thirst ADH Water Excretion Water Intake Water Retention Posm Effective Circulating Volume Figure 5

  9. Sensitivities of Osmo- and Baroreceptor Regulation of ADH Release 20 Pressure Basal Volume Osmolality 15 10 Plasma Vasopressin (pg/mL) 5 0 -30 -15 0 +15 +30 Percent Change Figure 6

  10. Effects of Hemodynamic Variables on the Osmo-regulation of ADH Release 10 Hypovolemia or Hypotension Hypervolemia or Hypertension -20 -15 5 -10 Plasma Vasopressin (pg/ml) N +10 +15 +20 0 300 340 260 Plasma Osmolality (mOsm/kg) Figure 7

  11. Figure 3 Regulation of ADH Release Angiotensin SFO PVN OVLT SON VLM OC Pituiatry Osmolality Baroreceptors ADH

  12. Central DI • Deficient secretion of ADH • Sudden onset of polyuria • Serum sodium tends to be > 142 mEq/L

  13. Triphasic Changes in Water Balance after Hypothalmic Surgery DI SIADH DI 5 ADH release from degenerating posterior pituitary 4 3 Hypothalamic Dysfunction 2 1 0 2 4 6 8 10 12 14 16 Urine Output (L/day) Post-operative Day

  14. Causes of Central DI • Idiopathic • Familial • Neurosurgery or trauma • Malignancy • Hypoxic encephalopathy • Sheehan’s syndrome • Infiltrative disorders

  15. Treatment of Central DI • dDAVP • Nasal spray 5-20 mcg every 12-24 hours • Tablet 0.1-1.2 mg daily • Follow serum Na+ and urine volume • Chlorpropamide 125-250 mg daily • Carbamezepine 100-300 mg BID • Clofibrate 500 mg QID • Thiazide diuretics • NSAIDs

  16. Case Presentation 2 39 y.o. female with a history of schizo-phrenia and bipolar disorder is referred for polyuria and polydipsia. Found to be drinking out of bathtub and commode. Had been treated with lithium in the past (>1 year ago).

  17. Case Presentation 2 Cont’d Physical Exam BP 156/80 HR 92 Trace edema 24 hr urine volume 6000 ml Urine osm 68 mosm/kg Serum Sodium 144 Chloride 100 Potassium 3.8 CO2 24 BUN 14 Creat 1.5 Glucose 98 Osm292

  18. Case Presentation 2 Cont’d Water Deprivation Test TimeWt. BP Sosm Uosm (hr) (lb) (mmHg) (mosm/kg) 0 196 148/80 292 115 2 195 145/85 312 170 4 194.5 145/80 321 225 6 194 140/80 322 235 8 193 138/70 324 255 dDAVP 5 u sc

  19. Factors Complicating the Diagnosis of DI • Medullary washout • Central DI is often partial • Decrement in ADH activity in nephrogenic DI is often partial • Elevated residual bladder capacity

  20. Indirect Testing Spontaneous Posm > 295 Spontaneous PNa+ > 143 Water Deprivation Test Uosm > 500 U/Posm < 1.5 dDAVP 5 mcg sc Primary Polydipsia Uosm < 300 mosm/kg Nephrogenic DI Uosm Rises > 150 mosm/kg Central DI

  21. ADH and Plasma Osmolality in Central DI with 5% Saline Infusion 10 Normal Plasma ADH (pg/ml) 5 Central DI 0 280 295 310 Posm (mmol/kg)

  22. ADH and Urine Osmolality in Nephrogenic DI with 5% Saline Infusion 1000 Urine Osmolality (mosm/kg) 500 Normal Nephrogenic DI 0 0 5 10 Plasma ADH (pg/ml)

  23. Nephrogenic DI • Normal ADH secretion, but renal resistance to ADH activity • Gradual onset • Serum sodium tends to be > 142 mEq/L

  24. Effect of ADH on Principle Cells in the Collecting Ducts Tubular Lumen ADH V2 Receptor cAMP Aquaporin-2 PKC PKA H2O Aquaporins-3 and 4 H2O H2O Hypertonic Medulla Figure 4

  25. Causes of Nephrogenic DI • Hereditary X-linked V2 receptor defect • Hereditary AR Aquaporin-2 defect • Lithium toxicity • Hypercalcemia • Hypokalemia • Cidofovir and Foscarnet • Advanced age • Renal failure

  26. Aquaporin-2 Excretion • Aquaporin-2 excretion is several-fold higher in normals compared with those with central DI • Aquaporin-2 excretion increases with exogenous ADH in patients with central DI and not in patients with nephrogenic DI

  27. Treatment of Nephrogenic DI • Diuretics • thiazides • amiloride (lithium) • Low salt, low protein diet • NSAIDS • prostaglandins normally antagonize ADH activity • dDAVP

  28. Relationship Between Solute Intake and Urine Output Solute intake (mosm/day) 8 6 900 4 Water Clearance (L/day) 600 2 300 0 130 140 100 110 120 Urine Osmolarity (mosm/kg)

  29. Case Presentation 3 47 year old female referred for polyuria. She initially presented to her urologist for urinary incontinence. A bladder neck suspension was performed, and the patient was subsequently found to have large post-void residuals of 300-400 ml. She denied nocturia, history of head trauma, and was on no medications.

  30. Case Presentation 3 Cont’d Physical Exam Normal blood pressure and pulse. No edema. 24 hr urine volume 5000 ml Urine osm 178 mosm/kg Serum Sodium 141 Chloride 104 Potassium 4 CO2 26 BUN 10 Creat 0.8 Glucose 77 Osm288

  31. Case Presentation 3 Cont’d Water Deprivation Test Time Wt. BP UVol. Sosm Uosm ADH (hr) (lb) (mmHg) (L) (mosm/kg) (pg/ml) 0 118 110/60 .15 285 335 < 2.5 1 118 98/65 .1 288 450 2 117 102/60 .125 289 550 3 117.5 102/70 .075 290 580 4 117.25 112/70 .1 297 600 < 2.5

  32. Radioimmunoassay of ADH • Assay is cumbersome • High incidence of falsely low values • Sample preparation • Collect in chilled 7 ml EDTA tubes • Centrifuge 1000 g X 20 min • Freeze at -20oC • Extract in acetone and petrol-ether • Freeze at -80oC • Dessicate and store at -20oC

  33. Mechanisms of Thirst Regulation 1. Cerebral cortex Nonessential drinking Thirst 3. Hypothalamic Osmoreceptors 2. Oropharnygeal mechanoreceptors Stimulated by im- bibing large volumes of water

  34. Osmotic Regulation of Thirst and ADH Release Thirst 6 Plasma ADH (pg/ml) 3 0 280 290 275 285 295 Plasma Osmolality (mosm/kg)

  35. Primary Polydipsia • Central defect in thirst regulation • osmotic threshold thirst < ADH • continue to drink until the plasma osm is less than the threshold • Neuroleptic therapy

  36. Treatment of Primary Polydipsia • Clozapine may correct the central disturbance in thirst regulation • Limit use of drugs that cause dry mouth • ACE inhibitors

  37. Urine and Plasma Osmolality in Disorders of Water Balance Normal 1000 Water Deprivation dDAVP 800 Primary polydipsia Uosm(mosm/kg) 600 Central DI 400 Nephrogenic DI 200 280 285 290 295 300 Posm(mosm/kg)

  38. Case Presentation 4 29 y.o. female with a 31 week intrauterine pregnancy admitted with a 2 week history of polyuria and polydipsia. She reported 6-8 liters of daily fluid intake and voided urine every 30 minutes to an hour.

  39. Case Presentation 4 Cont’d Physical exam BP 130/80, HR 150, trace pretibial edema 24 hr urine volume 7000 ml Urine osm 162 mosm/kg Serum Sodium 168 Chloride 133 Potassium 3.6 CO2 21 BUN 5 Creat 2.8 Glucose 77 Osm348

  40. Polyuria in Pregnancy • Vasopressinases are released from the placenta resulting in a four-fold rise in ADH catabolism • May be treated with dDAVP which is resistant to vasopressinase • Polyuria often seen in patients with decreased ADH secretory reserve • Central DI in Sheehan’s syndrome

  41. Case Presentation 5 A 16 y.o. male was treated for the “flu” at home. Despite improvement in his fever and cough, worsening lethargy prompted his mother to bring him to the E.R. Physical Exam Afebrile BP 140/85 no edema Disoriented No focal neurologic deficits

  42. Case Presentation 5 Cont’d Laboratory data 24 hr urine volume 4000 ml Urine osm 400 mosm/kg Serum Sodium 170 Chloride 128 Potassium 3.9 CO2 29 BUN 8 Creat 0.8 Glucose 85 Osm360

  43. Solute (Osmotic) Diuresis • Etiology • Glucose • High-protein feedings (urea) • Expanded ECF volume • Release of urinary tract obstruction • Urine osm > 300 mosm/kg • Osmolar excretion > 900 mosm per day

  44. Postobstructive Diuresis • Urine output after release of obstruction may initially exceed 500-1000 ml/hr • This solute diuresis is appropriate • Administer normal replacement fluids (e.g. 1/2 NS at 75 ml/hr) • Replacing fluids at a rate greater than replacement level will only exacerbate the solute diuresis