Approach to Hyponatremia

1. HYPONATREMIA

2. DEFINE HYPONATREMIA
mild 130 - 134
moderate 125 - 129
profound <125

3. DEFINE HYPONATREMIA
Acute < 48 hrs
Chronic > 48 hrs or if cannot be classified

4. PLASMA OSMOLALITY & DYSNATREMIA

5. PHYSIOLOGY OF WATER BALANCE
• Plasma osmolality – 285 to 290 mOsm/kg
Governs the excretion of water by its effect in
renal collecting system

6. VASOPRESSIN
• supraoptic & paraventricular magnocellular nuclei in
hypothalamus
• OSMOTIC STIMULI
• NONOSMOTIC STIMULI
– Decreased effective circulatory volume (Heart failure,
cirrhosis, vomiting)
– Hypovolemia
– Nausea, Postoperative pain, pregnancy

7. THIRST & WATER BALANCE
• Osmotic threshold for thirst – 290 to 295 mOsm/kg
H20
• Stimulus for thirst
1. Hypertonicity
2. Hypovolemia
3. Hypotension
4. Angiotensin II

8. PSEUDOHYPONATREMIA
• Occurs when the solid phase of plasma is increased
(Hypertriglyceredemia and paraproteinemias
• Serum osmolality is normal
• Direct ISE

9. APPROACH TO HYPONATREMIA
• HISTORY ( RECENT DRUGS)
• EXAMINATION & ASSESSMENT OF VOLUME STATUS
• LABORATORY VALUES

12. ADH – CENTRAL MECHANISM
HYPOVOLEMIA HYPERVOLEMIA
EUVOLEMIA
INCREASED WATER
REABSORPTION

13. HYPOVOLEMIC HYPONATREMIA
HYPOVOLEMIA
LOSS OF Na+ > LOSS OF WATER

14. HYPOVOLEMIC HYPONATREMIA
1. Gastrointestinal & Third space loss
– Kidney responds to volume contraction by conserving Na+
and Cl-
– Urine Na+ is < 10mmol/L, urine is hyperosmloar
– Except in vomiting with Met Alkalosis – HC03- excretion
obligates Na+ may exceed 20mmol/L, but urine cl- <10mmol/l
2. Diuretics
– High Urine Na+
– Mechanism
• Hypovolemia  vasopressin release
• K+ depletion directly stimulating thirst

15. 3. Salt losing Nephropathy
– Salt losing state in advanced renal impairement (GFR<15ml/min)
particularly interstitial disease
– In proximal type 2 RTA, Bicarbonaturia obligates Urine Na+ excretion
4. Mineralocorticoid deficiency
– ECF contraction, Urine Na>20, High serum K+
5. Osmotic diuresis
– Osmotically active non reabsorbable solute obligates renal excretion
of Na > 20
6. Cerebral salt wasting
– Patients with SAH
– Salt wasting from kidney , volume contraction stimulating
vasopressin
– Mechanism unknown, probably brain natriuretic peptide

16. EUVOLEMIC HYPONATREMIA
EUVOLEMIA
RETENTION OF WATER WITH
LOSS OF Na+

17. EUVOLEMIC HYPONATREMIA
1. Glucocorticoid deficiency
– Impaired water excretion and elevated vasopressin
2. Hypothyroidism
– Occurs in severe myxoedema
– Decrease in cardiac output leads to non osmotic release of
vasopressin
3. Psychosis
– Increased thirst perception
– Mild defect in osmoregulation and enhanced renal
response to vasopressin

18. 4. Drugs

19. 5. SIADH(Syndrome of Inappropriate ADH)
– Diagnosis of exclusion
– Defect in osmoregulation causing inappropriate
vasopressin release
– Mechanism
• 1/3 – resetting the osmostat
• 2/3 – inappropriate vasopressin release
• 10% - SIAD  gain of function in vasopressin receptors

20. SIADH CRITERIA
• Serum osmolality <275 mOsm/kg
• Urine osmolality >100 mOsm/kg
• Urine Na+ >30 mEq/l
• Diagnosis of exclusion
• Sr. uric acid <4mg/dl
• Improves with fluid restriction
• Refractory to NS

21. CAUSES OF SIADH

22. CAUSES OF SIADH

23. HYPERVOLEMIC HYPONATREMIA
HYPERVOLEMIA
RETENTION OF WATER >
RETENTION OF Na+

24. HYPERVOLEMIC HYPONATREMIA
1. Heart failure
– Decreased systemic MAP and low cardiac output
Non osmotic pathways
Vasopressin and Renin Angiotensin system
Impaired water excretion and increased thirst

25. 2. Hepatic failure
Increased ECF (Ascites, Edema)
Multiple av fistulas & splanchnic vasodilation
Increased cardiac output, decrease in mean arterial
pressure
Increase in renin, vasopressin, expression of AQP2
3. CKD
– Edema develops when the Na+ intake exceeds the
capacity to excrete
– If water intake exceeds  positive water balance and
hyponatremia

26. BASIC LAB INVESTIGATIONS
• Serum Electrolytes
• Serum Urea & Creatinine
• Serum Osmolality
• Urine Osmolality / Urine sp. gravity
• Urine spot Na+
• Serum Uric acid

27. LOW HIGH/NORMAL
<100mOsm/L
>100mOsm/L
>4 mmol/L <4 mmol/L
<20mEq >40mEq
20 – 40 mEq
DECREASED
WATER
EXCRETION

28. CLINICAL MANIFESTATION OF
HYPONATREMIA
• Asymptomatic usually when Na+>125
• Symptomatic Na+ below 125
– Symptoms range from Headache, yawning,
lethargy, nausea, reversible ataxia, psychosis,
seizures and coma may occur as a result of
cerebral edema
– Cerebral edema  tentorial herniation,
respiratory depression and death.

30. OSMOTIC DEMYELINATION
• Complication of rapid correction of chronic
hyponatremia
• Affects the central pons
• Rarely occurs when Na+> 120
• Symptoms are biphasic
– Initially there is a encephalopathy
– After 2 to 3 days, behavioral changes, cranial N palsy,
progressive weakness, quadriplegia and locked in syndrome
• Mechanism – sodium coupled amino acid transporter
are downregulated by hypotonicity thereby delaying
the return of osmolytes to brain. This temporary
imbalance cause cerebral dehydration and breakdown
of blood brain barrier

32. TREATMENT

33. ACUTE HYPONATREMIA
• Hypertonic saline 1 to 2ml/kg/hr
• Corrected at the rate of 2mEq/l/hr
• Loop diuretics enhances free water excretion
• Can be infues at rates of 4 – 6ml/kg/hr in
neurologic symptoms with obtundation and
coma
• Neurologic and pulmonary status and
electrolytes monitored every 2 hrs

34. • Infusion rate = Body wt x desired rate of
correction(mEq/l/hr)
• 3% Nacl Infusion end point
– Neurological symptoms improved
– Na >120
– 12 mEq/l in 24hrs or 18mEq/l in 48 hrs

35. CHRONIC HYPONATREMIA
HYPOVOLEMIA EUVOLEMIA HYPERVOLEMIA
LOSS OF Na+ > LOSS OF
WATER
RETENTION OF WATER
WITH LOSS OF Na+
RETENTION OF WATER
> RETENTION OF Na+
1. FLUID - ISOTONIC
SALINE
2. SALT
SUPPLEMENT
1. FLUID
RESTRICTION
2. SALT
SUPPLEMENT
3. DIURETICS
4. VAPTANS
1. FLUID & SALT
RESTRICT
2. LOOP DIURETICS

36. VAPTANS
• V2 receptor antagonists that block vasopressin
• Conivaptan v2 and v1a antagonist, i.v use, in
hospitalised patients limited to 4 days
– 20mg loading over 30 mins f/b 20mg infusion/day
• Tolvaptan oral
– 15 to 60 mg/day
– Monitor liver function and creatinine kinase
• Response raise of 5 mEq/day

37. CASE REPORT
• 58 yrs old Gentleman
• H/o Fever 2 days
• H/o vomiting 3 episodes – 1 day before admission
• H/o Jaundice 1 month ago taken indigenous treatment
• Altered Sensorium , GCS -12/15
• Volume status – Hypo or Euvolemia
• O/E – No jaundice or edema
• CVS- N , RS – N, BP- 110/70, HR- 96/min
Day 1

38. LAB VALUES
• TC – 6400, N- 76, L-18, M- 4, E-2; Plt – 2.43
• ABG – pH-7.584, pCO2-21.9, pO2-153.1
• Hb – 9.5, HCT- 31.2
• Electrolytes Na- 104, K- 3.8, cl- 78, Hco3- 14, Mg-2.1
• Serum Urea - 17.45 & Creatinine - 0.45
• Bilirubin T- 2.05 , D-1.18 , I- 0.87
• SGOT -77, SGPT- 69, ALP- 76, GGT- 14, NH4-63
• RBS - 96
Day 1

39. Provisional diagnosis
• ACUTE GASTROENTERITIS
• SEVERE HYPONATREMIA
• METABOLIC ENCEPHALOPATHY
Day 1

40. INITIAL MANAGEMENT
• Treated with 3% Nacl – 10ml/hr, NS- 100ml/hr
• Supportive treatment
Day 1

41. • Rpt Na- 106
• Total Intake – 3000, output – 1850
• Refractory Hyponatremia to Normal saline
Day 2

42. HYPONATREMIA WORKUP
• Serum Osmolality = 207.07
• Urine Osmolality / Urine sp. Gravity = 143.46 / 1.004
• Urine spot Na+ = 93
• Serum Uric acid = 2.10
• Urine spot cl =100
• TSH = 2.3
Day 2

43. LOW HIGH/NORMAL
<100mOsm/L
>100mOsm/L
>4 mmol/L <4 mmol/L
<20mEq >40mEq
20 – 40 mEq
207.07
153.46 /
1.004
93
2.10
2.3

44. SIADH
• Treated with 3 % Nacl – 10ml/hr
• Fluid restriction < 500 ml/day
• Tolvaptan 15mg OD
Day 2

45. • Na – 120, K- 4.0
• Hemodynamics stable
• Pt drowsy GCS – 12/ 15
• CT Brain/ Lumbar puncture – Normal
• CT Chest – Right Lower lobe subtle consolidation
Day 3

46. MRI brain
• Cortical vein thrombosis
• Treated with Anticoagulants
• Now SIADH explained
Day 4

47. SCREENING FOR INHERITED
THROMBOPHILIA
• ANTITHROMBIN III DEFICIENCY – 2mg/dl (17-30)
• D-dimer – 1100mcg/l
• Anticardiolipin, Antiphospholipid, Protein C S, Lupus
Anticoagulant - Normal

48. FINAL DIAGNOSIS
 REFRACTORY HYPONATREMIA
 SIADH
 CVT
 ANTITHROMBIN III DEFICIENCY
Pt improved with treatment and was on oral Anticoagulants