1. Disorders of Water Balance Hypo/Hypernatremia

2. Water-drinking contestants say they weren't told of health risks From Associated Press 7:18 PM PST, January 15, 2007 SACRAMENTO (AP) -- Two people who competed in a radio station's water drinking contest with a 28-year-old mother of three who later died said they were never warned they were putting their health at risk, a newspaper reported Monday. Gina Sherrod said that family members listening in on KDND-FM's "Hold Your Wee for a Wii" contest told her that a nurse called into the program to warn that drinking too much water was dangerous, but that she did not worry until she learned of Jennifer Lea Strange's death.

3. Outline Hyponatremia: Physiology, differential, treatment. Case. Hypernatremia. Physiology, differential, treatment. Case

4. Question How is water balance achieved in the face of increased water intake? By the excretion of dilute urine.

5. Changes in Urinary Volume and Osmolality along the Nephron

6. Defense against hyponatremia

8. Control of Serum Na

9. Retain 1L Water

10. Serum Na Falls by 5meq/l

11. Decreases Vasopression Release

12. Approach to the hyponatremic patient Hyponatremia High Osmolality Normal Osmolality Low Osmolality

13. Hyponatremia with high or Nml Osmolality TRANSLOCATION GLUCOSE MANNITOL GLYCINE MALTOSE PSEUDOHYPONATRE PROTEIN LIPIDS

14. Pseudohyponatremia Normally serum is 93%water and 7% lipids. If non aqueous portion of serum rose to 20% Serum measured Na would be: 150x0.8=120 as opposed to 150x0.93

15. Pseudohyponatremia

16. Approach to the hyponatremic patient with Low plasma osm Hyponatremia with low Osm Normally Dilute urine <100mosm Psychogenic Polydipsia Low Solute intake Uosm>100mosm

17. Low Solute intake Urine flow= urinary solute excretion urinary osmolality

18. Sources of urinary solutes

20. Psychogenic Polydipsia Usually acute Common in institutionalized schizophrenics Abnormal weight gains (as much as 10%) Episodic symptoms that resolve with water restriction

22. Beer Potomania Large intake of fluid with beer as sole source of nutrition Beer sodium content <2meq/L Beer Potassium content 10-12meq/L

23. Beer Potomania Assume Beer consumption of 5L Na intake10mM K intake 50mM Obligatory urea excre80mM V=Soluteexcretion5=200 Uosm40

24. Approach to the hyponatremic patient with low plasma osm Low plasma osm Normally dilute urine Uosm<100 Uosm>100mosm Almost always vasopressin mediated

27. Diuretic Induced Hyponatremia Thiazides block diluting segment May appear euvolemic Most common in small elderly women Associated with increased water intake and low protein intake

30. Hyponatremia in Edematous disorders Reflects advanced disease and poor prognosis Decreased delivery to diluting sites Increased vasopressin levels Increased AQP2 expression

32. Cerebral Salt wasting Most common in subarachnoid hemorrhage Increased ANP and BNP Loss of sodium, volume depletion which then leads to increased ADH. Different from SIADH as volume depleted. Treat with saline

36. Hyponatremia and SSRIs Four fold higher incidence than non users First 2 weeks More common in elderly Not related to drug levels

40. Features of SIADH Clinically euvolemic Uosm>100mosm Una=Na intake usually >20meq/L Low bun and Uric acid

41. Malignancies and SIADH Most common with small cell lung ca (10-15%) mRNA for AVP in tumor Head and neck tumors Other isolated cases

43. Treatment of Hyponatremia

44. Three key Questions How long has the hyponatremia been present? Does the patient have symptoms? Does the patient have risk factors for the development of neurologic complications?

45. Duration of Hyponatremia acute <48hrs Severe brain edema Rapid correction is well tolerated BUT WHEN IN DOUBT…Treat as chronic

47. SXS of Hyponatremia Seizures Herniation Coma Respiratory depression death

48. Patients at increased risk for neurologic complications Post op menstruant females Elderly women on HCTZ Children Hypoxemic patients Psychogenic polydipsia

49. Duration of Hyponatremia Chronic 48hrs or unknown duration Mild cerebral edema <10% Sensitive to correction

51. SXS of Chronic hyponatremia Nausea and vomitting Muscle cramps and weakness Ataxia Confusion and personality changes Seizure

52. Symptomatic vs Asymptomatic Symptomatic hyponatremia warrents aggressive correction. (sz, severe neuro abnormalities). Most likely to occur in acute setting such as: Post op menstruating females Exercise induced hyponatremia Hyponatremia associated with ecstasy Hyponatremia in patients with intracerebral pathology, Self induced water intoxication

53. Symptomatic hyponatremia Aggressive correction at a rate of 1.5-2meq/L per hour for 3-4 hrs or until sxs resolve. Usually with hypertonic saline at 0.5ml/kg/hr However no more than 10-12meq/24hrs and 18meq/48hrs.

54. Asymptomatic but <115 or 110 Such patient if they have sxs such as confusion, lethargy, gait disturbances will benefit from rise of 1meq/L/hr for 3-4 hrs but no faster than 8meq/24hrs. IF asymptomatic and >120meq/L then would benefit from free water restriction or treatment of volume depletion but no faster than 6-8meq/24hrs.

56. Risk factors for Development of Osmotic demyelination Alcoholism Malnutrition Burns Severe Potassium depletion Elderly women on thiazide diuretics

57. Case: acute Hyponatremia 31 yo female weighing 60Kg was admitted for elective hysterectomy. Normal preop exam and electrolytes. Underwent surgery with minimal intraop blood loss. During a 4 hr course in recovery she received 2 L NS and then ½ NS at 125cc/hr. At 12 hrs post op she made 1500cc urine. She complained of nausea and vomitting complicated by pain for which she received demerol. No record of oral intake. ½ NS continued.

58. Case: acute Hyponatremia 30 hrs post op mental status changes developed. Serum Na was measured at 114meq/L. IV changed to NS at 200cc/hr for 5hrs during which she put out 750cc of urine. Una was 140meq and Uk was 52meq/L. The patient had a sz with respiratory arrest and death. Repeat Na was 112 meq/L

74. Urine flow= urinary solute excretion urinary osmolality

80. V2 Receptor antag Conivaptan is the only IV antagonist available in the US FDA approved for hospitalized euvolemic SIADH Unclear of the rate of rise Suggest use with 3% saline is symptomatic hyponatremia. Contraindicated in Liver patients as increased variceal bleed and hypotension

81. Hypernatremia

82. Causes of hypernatremia 1. Inappropriately high water losses 2. Insufficient water intake 3. High Na intake without adequate water 4. Thirst center/osmoreceptor lesion

83. 4. Impaired thirst or osmoreceptors Causes usually tumor, granulomatous dz, ischemia, primary aldosteronism, age. Na>146 but not thirsty. Dilute urine after any H20 with impaired osmoreceptors

84. 3. High NaCl intake without water Rare Seawater ingestion NaCl poisoning Hypertonic Na or bicarb boluses.

85. 2. Insufficient water Intake Usually when ill or in the hospital setting Inadequate Free water Common after surgery, high nutrient intake

86. 1. Inappropriately high water losses Sites of water loss 1. insensible (sweat, breath) 2. GI (vomitting, NG, Diarrhea) 3. Kidney

87. 1. Inappropriately high water losses Renal losses Osmotic diuresis- urea, mannitol, glucose, diuretics DI

89. Vasopressinase production Central (neurogenci) DI Nephrogenic DI

90. Vasopressin (ADH) Receptors V2 Makes collecting duct permeable to water V1 Increases systemic BP Expressed in vasculature, liver and brain

91. DI – lack of vasopressin Gestational DI Central DI

92. Gestational DI 1 in 300,000 pregnancies Increased action of vasopressinase normally from the placenta Vasopressinase does not attack DDAVP as rapidly

93. Central (neurogenic) DI Acquired- tumor, trauma, autoimmune, granulomatous, vascular Congenital- autosomal dominant

94. Nephrogenic Congenital Acquired Drugs- LI, demeclocycline Hypercalcemia Hypokalemia Uretral obstruction Renal insufficiency

95. Treatment Acute<24hrs Osmotic loss of brain water Accumulation of electrolytes: Na, K Chronic >24hrs Accumulation of organic solutes such as myo- inositol, sorbitol, others.

103. Conclusions Hyponatremia and hypernatremia are critical. Understand the physiology. Slower correction unless the patient is decompensting. Always assume chronic when in doubt. Multiple formulas but always recheck values at several time points. New drugs on the horizon. Unclear of benefit.