1. HYPONATREMIA

2.  51 y/o, F  CC: vomiting

3. HISTORY OF PRESENT ILLNESS  1 week PTA– fever, dysuria and urgency. Self medicated and an antibiotic which relieved the fever 2 days PTA Headache, body malaise and nausea 3 episodes of vomiting (50 cc/episode) Vomiting persisted prompting consultation and subsequent admission

4. PAST MEDICAL/SOCIAL HISTORY  Known hypertensive--- 10 years  Have had bipedal edema  amlodipine was discontinued  Telmisartan 40 mg daily for the past month  HCTZ 12.5 daily for the past month

5. PHYSICAL EXAMINATION  Weak-looking, wheelchair-borne  Wt: 50 kg (usual: 53 kg)  Poor skin turgor, dry mouth, tongue and axillae  BP: supne-120/80, sitting: 90/60 (usual 130/80)  CR: supine-90 bpm; sitting-105 bpm  JVP: <5 cm H2O at 45 degrees.

6. REVIEW OF SYSTEMS  UNREMARKABLE

7. LABORATORY TESTS  Hgb=132 mg/dL  WBC=12.5  Plasma Na=123 mEq/L  Plasma K=3.7 mEq/L  Chloride=71/mEq/L  Urine Na=100mmol/L mEq/L  Uosm=540 mosm/L  hematocrit= 0.35  Neutrophils= 0.88  Lymphocyte= 0.12  BUN= 22mg/dL  Serum Crea= 0.9 mg/dL  Glucose= 98 mg/dL

8.  Urinalysis:  Yellow, slightly turbid, pH 6.0, Sp.Gr. 1.020  (-) Albumin and Sugar  Hyaline cast 5/hpf  Pus cells 10-15/hpf  RBC: 2-5/hpf (not dysmorphic  ABG  Ph =7.3  CO2 = 35  HCO3 = 18

12. Diagnosis

13. -vomiting

14. HYPOVOLEMIA  2-day history of vomiting (3 episodes, 50cc/episode)  Has been taking HCTZ daily for 1 month  Orthostatic hypotension  Poor skin turgor, dry mouth, yongue and axillae  patient is dehydrated  Low JVP

15. Urinary tract infection  fever, dysuria and urgency  Hyaline cast 5/hpf  Pus cells 10-15/hpf  RBC: 2-5/hpf (not dysmorphic

17. Factors that contributed to hyponatremia  Vomiting and dehydration  HCTZ (Hydrochlorothiazide)

19. OSMOLALITY  Count of the total number of osmotically active particles in a solution  Equal to the sum of the molalities of all the solutes present in that solution  affected by changes in water content

20. EFFECTIVE PLASMA OSMOLALITY  Tonicity  Shift of water through biomembranes produced by osmotically active particles  Effective osmolality determined by restricted solutes Na= reflection of ECF volume K= reflection of ICF volume  In the ECF: Na+ : 145 mEq/L  Major cation Cl-:105 mEq/L HCO3-:25 mEq/L  Major anions  Ineffective osmoles Don’t contribute to water shifts Urea

21. Plasma Osmolality  Serum Na+ = 123 mEq/L  Glucose = 98 mg/dL  BUN = 22 mg/dL  Serum Osmolality  = {Serum Na (mEq/L) x 2} + {Glucose (mg/dL)/18} + {Urea (mg/dL)/2.8}  = {123 mEq/L x 2} + {98 mg/dL ÷ 18} + {22 mg/dL ÷ 2.8}  = 259.30 mOsm/Kg H2O

22. Effective Plasma Osmolality  Effective Plasma Osmolality  = {Serum Na (mEq/L) x 2}  = {123 mEq/L x 2}  = 246 mOsm/Kg H2O  LOW   Normal Plasma Osmolality 285 – 295 mOsm/Kg H2O

23. Importance  Serum Osmolality Useful when dealing with patients with an elevated plasma [Glucose] secondary to DM and in patients with CRF whose plasma [Urea] is increased  Investigation of Hyponatremia  Identification of Osmolar gap

24. Hyponatremia  Hypotonic Hyponatremia: < 280 ECF volume status may be: Low, Normal or High  Isotonic Hyponatremia: 280 – 295 Very high blood levels of lipid or protein Pseudohyponatremia  Hypertonic Hyponatremia: > 295 associated with shifts of fluid due to osmotic pressure Diabetes Mellitus

25. Osmolar Gap  Measured Osmolality – Calculated Osmolality  If > 10 mmol/L presence of unmeasured osmotically active substances in the plasma (ethanol, methanol, ethylene glycol, acetone, or isopropyl alcohol)

27. Urine Osmolality  An important test of renal concentrating ability  Identification of disorders of the ADH mechanism  Identification of causes of hyper-or hyponatremia  Reflects the total number of osmotically active particles in the urine, without regard to the size or weight of the particles  Evaluate electrolyte and water balance  Used in work-up for renal disease  Normal Urine Osmolality: 50-1200 mOsm/kg H2O

28. Regualtion of Osmolality  Osmoreceptors Found in anterolateral hypothalamus Stimulated by tonicity, effective osmolality, ECF volume Threshold ○ 295 mOsm/kg H2O, thirst, suppress AVP ○ 280-290 mOsm/kg H2O, enhance AVP secretion  AVP/ADH Stimulates insertion of water channels in basolateral membrane of principal cells in the collecting ducts Passive water reabsorption

29. In the Patient  Plasma Osmolality  = {Serum Na (mEq/L) x 2} + {Glucose (mg/dL)/18} + {Urea (mg/dL)/2.8}  = {123 mEq/L x 2} + {98 mg/dL ÷ 18} + {22 mg/dL ÷ 2.8}  = 259 mOsm/Kg H2O Normal Values Patient Uosm 50-1200 540 Posm 275-290 259

30. Urine Osmolality Serum Osmolality Urine Osmolality Clinical Significance Normal or increased IncreasedFluid volume deficit Decreased Fluid volume excess NormalDecreased Increased fluid intake or diuretics Increased or normal Decreased (with no increase in fluid intake) Kidneys unable to concentrate urine or lack of ADH (diabetes insipidus) DecreasedIncreasedSIADH

31.   Serum and Urine Osmolality Levels  Hypoosmolality Sodium loss due to diuretic use and a low salt diet Hyponatremia Adrenocortical insufficiency SIADH Excessive water replacement/ overhydration/water intoxication   Serum and Urine Osmolality levels  Hyperosmolality  Renal disease  Congestive heart failure  Addison's disease  Dehydration  Diabetes insipidus  Hypercalcemia  Diabetes mellitus/ hyperglycemia  Hypernatremia  Alcohol ingestion  Mannitol therapy  Azotemia

32. Normal Value of Urine Sodium: 10-40 mEq/L  Higher-than-normal Urine Sodium levels may indicate:  EXCESSIVE SALT INTAKE  Lower-than-normal Urine Sodium levels may indicate:  ALDOSTERONISM  CONGESTIVE HEART FAILURE  DIARRHEA AND DEHYDRATION STATUS  RENAL FAILURE

33. Hyponatremia  Urine sodium <10 mmol/L may indicate Extra-renal Depletion: Dehydration (gastrointestinal or sweat loss) Congestive heart failure Liver disease Nephrotic syndromes

34. Patient Urine Sodium: 100 mmol/L  Urine sodium >10 mmol/L may indicate: diuretics, emesis, intrinsic renal diseases, Addison disease, hypothyroidism, or syndrome of inappropriate antidiuretic hormone (SIADH)  In SIADH Urinary Sodium is usually >20 mmol/L

36. Sodium Deficit  Target Sodium  = 125 – 135 mEq/L (130 mEq/L)  Sodium Deficit  = 0.6 x weight in kg X (desired Na – actual Na)  = 0.6 x 50 kg x (130 – 123)  = 210 mEq/L

38. Goals of Therapy  Raise the plasma Na+ concentration by restricting water intake and promoting water loss; and  Correct the underlying disorder

39.  Mild asymptomatic hyponatremia requires no treatment  Asymptomatic hyponatremia associated with ECF volume contraction Na repletion, generally in the form isotonic saline restoration of euvolemia removes the hemodynamic stimulus for AVP release, allowing the excess free water to be excreted  Hyponatremiaassociated with edematous states restriction of Na and water intake, correction of hypokalemia, and promotion of water loss in excess of Na  Hyponatremiaassociated with primary polydipsia, renal failure, and SIADH Water restriction

41. Osmotic Demyelination Syndrome  “central pontine myelinolysis”  Demyelinating lesion in the brain that occurs with overly rapid correction of hyponatremia  Characterized by acute paralysis, dysphagia, and dysarthria  Most common in those with chronic hyponatremia (usually caused by alcoholism)

42. Osmotic Demyelination Syndrome In normal individuals Neurons adjust their osmolarities by changing levels of osmolytes (Inositol, Glutamine, etc.) Hyponatremia Levels of osmolytes fall which prevents entry of free-water into cells Chronic Hyponatremia Neurons adapt (moves water out and equilibrates extracellular and intracellular tonicities)

43. Osmotic Demyelination Syndrome Rapid correction of Sodium Tonicities are changed again Causes extracellular fluid to be relatively hypertonic Free water moves out Too quick correction does not allow enough time for the neurons to adapt to the new tonicity Osmotic Demyelination Syndrome The rapid change in tonicity will continue to drive out water leading to cell shrinkage and dysfunction Manifests as paralysis

44. Osmotic Demyelination Syndrome  Prevention: Correction rate=0.5- 1.0meq/L/hr, with not more than 12meq/l correction in 24 hrs; should receive no more than 8-10mmol of sodium per day  Management: Supportive  Prognosis is poor

46. INTRAVENOUS FLUID  0.9% NaCl (contains 154 meq/L)  Correct at a rate in which Na concentration be raised no more than 0.5 – 1 meq/L per hour  175 meq (sodium deficit)  175 meq/154 meq/L = 1.14 L  1140 mL x 15 gtt/min = 8 gtts/min  24 hrs x 60 min/hr