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  1. 1. Dr. Simon Prince, FACP, FASN Assistant Professor of Medicine NYU School of Medicine North Shore Nephrology Hyponatremia
  2. 2. Sodium The problems with sodium has little to do with direct effects of the ion.   Disregulation of sodium causes changes in cell volume.                   WATER PROBLEM
  3. 3. OSMOSIS
  4. 4. Why we care about osmolality Alterations in cell size disrupt tissue function.
  5. 5. Sodium is an indicator of osmolality The clinically important variable is       tonicity .
  6. 6. Tonicity vs. Osmolality <ul><ul><li>Osmolality </li></ul></ul><ul><ul><ul><li>Total concentration of all particles </li></ul></ul></ul><ul><ul><li>Tonicity </li></ul></ul><ul><ul><ul><li>Only impermeable particles contribute to tonicity. </li></ul></ul></ul>Only impermeable particles cause changes in cell volume.
  7. 7. Why are we interested in TONICITY? <ul><li>  </li></ul><ul><ul><ul><li>When elevated, water leaves the cells causing cell shrinkage and dysfunction. </li></ul></ul></ul><ul><ul><ul><li>When decreased water moves into the cells causing cellular swelling and dysfunction. </li></ul></ul></ul><ul><li>  </li></ul><ul><ul><li>We are interested in sodium because it usually tells us the plasma tonicity . </li></ul></ul>
  8. 8. Pseudohyponatremia: high osmolality <ul><ul><li>Elevated glucose  raise plasma tonicity which draws water from the intracellular compartment diluting plasma sodium. </li></ul></ul>Hillier TA, Abbott RD, Barrett EJ. Am J Med 1999; 106: 399-403.
  9. 9. Pseudohyponatremia: high osmolality <ul><ul><li>Correcting the sodium for hyperglycemia. </li></ul></ul><ul><li>  </li></ul><ul><ul><ul><li>Add 1.6 to the sodium for every 100 mg/dL the glucose is over 100. </li></ul></ul></ul><ul><ul><ul><li>Example: Na = 126 mEq/L. Glucose = 600 mg/dL: </li></ul></ul></ul><ul><ul><ul><ul><li>600 - 100 = 500. So the glucose is five 100’s over 100 </li></ul></ul></ul></ul><ul><ul><ul><ul><li>5 x 1.6 = 8 </li></ul></ul></ul></ul><ul><ul><ul><ul><li>126 + 8 =134 </li></ul></ul></ul></ul><ul><ul><ul><ul><li>True sodium equals 134 mEq/L </li></ul></ul></ul></ul><ul><ul><ul><ul><li>To remember 1.6 think “Sweet 16” </li></ul></ul></ul></ul>
  10. 10. <ul><ul><li>If a person drinks more water than the kidney is capable of clearing the excess water will dilute the plasma. </li></ul></ul>Causes of hyponatremia:  Increased fluid intake <ul><ul><li>To exceed the maximal renal clearance of water an adult needs to drink about 18 liters a day . </li></ul></ul>
  11. 11. True hyponatremia <ul><ul><li>Hyponatremia does not occur when sodium excretion exceeds sodium intake. </li></ul></ul>Negative salt balance causes hypovolemia
  12. 12. Causes of Hyponatremia: Defect in Free H2O clearance <ul><li>  </li></ul>
  13. 13. Etiology of Hyponatremia:  3 steps to generating dilute urine <ul><ul><li>1. Delivery of water to the diluting segments of the nephron. </li></ul></ul><ul><ul><li>2. Functional diluting segments. </li></ul></ul><ul><ul><li>3. Collecting tubule impermeable to water (lack of ADH) </li></ul></ul>1400 285 100 50
  14. 14. Failure to Generate dilute urine Lack of water delivery to the diluting segments. <ul><ul><li>Renal Failure </li></ul></ul><ul><ul><li>Volume deficiency </li></ul></ul><ul><ul><li>Cirrhosis </li></ul></ul><ul><ul><li>Heart failure </li></ul></ul><ul><ul><li>Nephrotic syndrome </li></ul></ul>
  15. 15. Failure to Generate dilute urine <ul><ul><li>Ineffective solute reabsorption diluting segments: </li></ul></ul><ul><ul><ul><li>Thick ascending limb of the loop of Henle (TALH) </li></ul></ul></ul><ul><ul><ul><li>Distal convoluted tubule. </li></ul></ul></ul><ul><ul><ul><ul><li>Diuretics </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Non-oliguric ATN </li></ul></ul></ul></ul>
  16. 16. Failure to Generate dilute urine <ul><li>Permeable collecting ducts (ADH) </li></ul><ul><ul><ul><li>Volume related ADH </li></ul></ul></ul><ul><ul><ul><li>SIADH </li></ul></ul></ul><ul><ul><ul><ul><li>Drug induced </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Paraneoplastic </li></ul></ul></ul></ul><ul><ul><ul><ul><li>CNS </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Pulmonary disease </li></ul></ul></ul></ul><ul><ul><ul><li>Adrenal insufficiency </li></ul></ul></ul><ul><ul><ul><li>Hypothyroidism </li></ul></ul></ul>
  17. 17.       AD ds H ydration to the body. ADH Osmolality
  18. 18. ADH is normally used to regulate osmolality We start with an increase in the plasma osmolality This is detected by the brain The brain releases ADH ADH acts on the kidney The kidney reacts by retaining water and producing a small amount of concentrated urine. The retained water goes here not here
  19. 19. Clinical Approach  
  20. 20. What Studies Are Needed?  
  21. 21. Tests to send... <ul><ul><ul><li>UA, Urine: Na and Osmolality </li></ul></ul></ul><ul><ul><ul><li>BMP </li></ul></ul></ul><ul><ul><ul><li>Serum osmolality, TSH, uric acid, BNP, cortisol </li></ul></ul></ul><ul><ul><ul><li>CXR </li></ul></ul></ul><ul><ul><ul><li>Head CT </li></ul></ul></ul>
  22. 22. What is the Volume Status? <ul><ul><li>Hypovolemic </li></ul></ul><ul><ul><li>Euvolemic </li></ul></ul><ul><ul><li>Hypervolemic </li></ul></ul>
  23. 23. Hypovolemic Hyponatremia     <ul><li>Volume expansion with SALINE </li></ul>
  24. 24. Hypervolemic Hyponatremia <ul><ul><li>Fluid restrict </li></ul></ul><ul><ul><li>Diurese </li></ul></ul>
  25. 25. EUVOLEMIC HYPONATREMIA <ul><ul><li>Excess intake in Free Water </li></ul></ul><ul><ul><li>Defect in Free Water Clearance </li></ul></ul><ul><ul><li>ADH problem </li></ul></ul>
  26. 26. ADH Should NOT Be Present When... <ul><ul><li>Euvolemic / Hypervolemic states </li></ul></ul><ul><ul><li>Serum Osmolality is low - normal range </li></ul></ul><ul><li>If ADH is elevated... that would be INAPPROPRIATE </li></ul>
  27. 27. Diagnostic Criteria for SIADH <ul><ul><li>Hypoosmolar hyponatremia </li></ul></ul><ul><ul><li>Euvolemic </li></ul></ul><ul><ul><li>Urine Na >25 </li></ul></ul><ul><ul><li>Urine Osmolality elevated  </li></ul></ul><ul><ul><ul><li>>350 mOsm </li></ul></ul></ul><ul><ul><ul><li>>200 higher than Serum Osmolality </li></ul></ul></ul>
  28. 28. Causes of SIADH <ul><ul><li>Neurological: </li></ul></ul><ul><ul><ul><li>Meningitis </li></ul></ul></ul><ul><ul><ul><li>Tumors </li></ul></ul></ul><ul><ul><ul><li>Trauma </li></ul></ul></ul><ul><ul><ul><li>SAH </li></ul></ul></ul><ul><ul><li>Pulmonary disease: </li></ul></ul><ul><ul><ul><li>Asthma </li></ul></ul></ul><ul><ul><ul><li>Mechanical ventilation </li></ul></ul></ul><ul><ul><ul><li>Pneumonia </li></ul></ul></ul><ul><ul><ul><li>TB </li></ul></ul></ul><ul><ul><li>Stress </li></ul></ul><ul><ul><ul><li>Pain </li></ul></ul></ul><ul><ul><ul><li>Vomiting </li></ul></ul></ul><ul><ul><ul><li>Post-surgical </li></ul></ul></ul><ul><ul><li>Medication </li></ul></ul><ul><ul><ul><li>Antipsychotics </li></ul></ul></ul><ul><ul><ul><li>SSRI </li></ul></ul></ul><ul><ul><ul><li>First generation sulfonylureas </li></ul></ul></ul><ul><ul><ul><li>Pitocin/Oxytocin </li></ul></ul></ul><ul><ul><ul><li>Narcotics </li></ul></ul></ul><ul><ul><ul><li>Cyclophosphamide </li></ul></ul></ul><ul><ul><ul><li>Ecstasy  </li></ul></ul></ul><ul><ul><li>AIDS </li></ul></ul>
  29. 29. TREATMENT      <ul><li>Conservative vs. Aggressive </li></ul><ul><li>Who should get treated and why? </li></ul>
  30. 30. Symptomatic Hyponatremia <ul><ul><ul><li>Mental status changes </li></ul></ul></ul><ul><ul><ul><li>Nausea </li></ul></ul></ul><ul><ul><ul><li>Vomitting </li></ul></ul></ul><ul><ul><ul><li>Head ache </li></ul></ul></ul><ul><ul><ul><li>Movement abnormalities </li></ul></ul></ul><ul><ul><ul><li>Seizures </li></ul></ul></ul><ul><ul><ul><li>Hypoxia / respiratory failure </li></ul></ul></ul>
  31. 31. Symptomatic vs. Asymptomatic <ul><li>Symptomatic </li></ul><ul><li>    HYPERTONIC SALINE </li></ul><ul><li>Asymptomatic </li></ul><ul><li>    Conservative approach is best </li></ul>
  32. 32. Acute symptomatic hyponatremia <ul><ul><li>In patients with neurologic symptoms due to hyponatremia: 3%. </li></ul></ul><ul><ul><li>Increase sodium until symptoms abate or 6 mmol/L, which ever comes first. </li></ul></ul><ul><ul><li>Increase Na < 24 mEq/L in the first 24 hours. </li></ul></ul><ul><ul><li>Goal is not more than 0.5 mEq/L/hour </li></ul></ul>
  33. 33. The problem with compensation The starting point is after compensation has reduced the amount of intracellular solute and the ICP Now, an over-eager intern sees the low sodium and starts an infusion of 3% NaCl to raise the sodium to normal. Sodium 108 Sodium 134 The sodium draws water from the inside of the cells causing the brain to shrivel.
  34. 34. C entral P ontine M yelinolysis <ul><ul><li>Brain Shrinkage </li></ul></ul><ul><ul><ul><li>Quadriplegia </li></ul></ul></ul><ul><ul><ul><li>Respiratory paralysis </li></ul></ul></ul><ul><ul><ul><li>Mental status changes </li></ul></ul></ul><ul><ul><ul><li>Usually fatal within three to five weeks </li></ul></ul></ul><ul><ul><li>Risk factors: </li></ul></ul><ul><ul><ul><li>Hyponatremia for > 24 hours </li></ul></ul></ul><ul><ul><ul><li>Over-correction of hyponatremia (> 24 mEq/L/day) </li></ul></ul></ul><ul><ul><ul><li>Rapid correction (greater than 1–2 meq/hr) </li></ul></ul></ul><ul><ul><ul><li>Alcoholism </li></ul></ul></ul><ul><ul><ul><li>Malnutrition </li></ul></ul></ul><ul><ul><ul><li>Liver disease </li></ul></ul></ul>
  35. 35. Damned if you do. Damned if you don’t <ul><ul><li>Without treatment patients have cerebral edema. </li></ul></ul><ul><ul><li>With mistreatment patients are at risk of CPM. </li></ul></ul>
  36. 36. TAKE HOME POINTS <ul><ul><li>Hyponatremia is a WATER problem, not sodium problem </li></ul></ul><ul><ul><li>In general best strategy in ER if not symptomatic... DO NOTHING (Primum non nocere) ... including holding NS unless dehydrated </li></ul></ul><ul><ul><li>Repeat blood tests to confirm and watch for psuedohyponatremia, send off urine studies </li></ul></ul><ul><ul><li>Careful hypertonic saline (3%) if symptomatic </li></ul></ul><ul><ul><ul><li>rule of thumb start hourly rate @0.5 LBM (kg) </li></ul></ul></ul>
  37. 37. CASE REPORTS