1. Division of Nephrology
Hyponatremia
Management
Ganesh Shidham, MD
Division of Nephrology

2. Outline …… Role of ADH in Hyponatremia Incidence and Mortality
Mechanism of Hyponatremia
Identifying types of Hyponatremia
Clinical features and Brain Adaption
Treatment
Complications of treatment

3. Hyponatremia
Sodium
Water
“Hyper-acquemia”

4. ADH Normal water balance Normal water intake 1-1.5 L/d Water Water Of
Cellular
Metabol
L/d
Water
intake
Intracellular Extracellular
Compartment compartment
28 L L
42 L TBW
60% of body
weight
ADH
Fixed water excretion
Stool Sweat Lungs
0.1 L/d L/d L/d
Variable water excretion
Kidney
Water
excretion
Total insensible losses
0.5 L/d
Total urine output
1-1.5 L/d

5. AVP = Vasopressin = ADH

6. Neurohypophysis Consists of: Supraoptic Nucleus
Para ventricular nucleus
Axons of Pituitary stalk
Neuron terminals in
posterior pituitary

7. ADH stimuli:
1-3% ↑ osmolality
10-15% ↓ vol /BP
Other stimuli:
Pain
Nausea
Stress
Medications

8. Changes in urinary volume and Osmolality along the Nephron
Maximal ADH
No ADH

9. ADH action on distal nephronV2
receptor
AQP 2 – Aquaporins
Lumen
ADH action on distal nephron

10. Hyponatremia

11. Incidence
And
Mortality

12. Prevalence of Dysnatremia
Acute Hospital care
Ambulatory hospital care
Community care
Na < Na < Na > Na > 165
28.2 21
7.2
Prevalence of Dysnatremia
303,577 samples from 120,137 patients
Hawkins. Clin Chim Acta 337: , 2003
Prevalence %

14. Hyponatremia and Mortality

15. Mortality (due to change in Brain volume)
Hyponatremia
Mortality (due to change in Brain volume)

16. Mechanism of
Hyponatremia

17. free water intake >> free water excretion
Hyponatremia
Supervenes when
free water intake >> free water excretion
Main defense
excretion of free water by kidneys

18. Hypotonic Hyponatremia
caused by:
Dilution from retained water OR
Depletion of electrolytes in
excess of water

19. Identifying
types of
Hyponatremia

20. (Pseudohyponatremia)
Serum
Osmolality
Normal
Low
High
(280 -
295
mOsm
/kg)
(<280
mOsm
/kg)
(>295
mOsm
/kg)
Isotonic
Hypotonic
Hypertonic
Hyponatremia
(Pseudohyponatremia)
Hyponatremia
Hyponatremia
(Translocational)
1.Hyperglycemia 
2.Mannitol, Sorbitol
Glycine
3.Radiocontrast agent
1.Hyperproteinemia
2.Hyperlipidemia
Volume status

21. Hypotonic Hyponatremia
Hypovolemic Euvolemic Hypervolemic
Urine Na
1.SIADH 
2.Glucocorticoid def
3.Hypothyroidism
4.Poor solute intake 
-Tea Toast syndrome
- Beer potomania
5.Post op / Hospital acquired
1.CHF
2.Cirrhosis
3.Nephrotic synd
4.Advanced CRF
< >30
ExtraRenal Renal
1.Diarrhea
2.Vomiting
3.Hemorrhage
4.Sweating
1.Diuretics
2.Mineralocorticoid def
3.Salt loosing Nephropathies
4.Cerebral salt wasting 

22. Hypertonic Hyponatremia Effect of Glucose on Serum Na
Correction factor: Increase Na by 1.6 to 2.4 per 100 glucose

23. Hypotonic hyponatremia (Vol status indeterminate)
Urine Na <30 :
Respond to 0.9 NS
Volume depleted
Urine Na > 30 :
No response to 0.9 NS
Likely to have SIADH

24. Euvolemic Hypotonic Hyponatremia
SIADH
Criteria for diagnosis:
1. P osm <275 mOsm/kg
2. U osm >100 mOsm/kg
3. Clinical euvolemia
4. Urine Na > 30mmol/L while on normal salt intake
5. Normal thyroid, adrenal and renal functions
6. Inappropriately elevated AVP levels in 85-90%

25. Euvolemic Hypotonic Hyponatremia
SIADH : Common Causes
Tumors
small cell CA, Head & Neck
CNS
Trauma, tumors, meningitis, CVA
Pulmonary
Pneumonia, PTB, resp failure, asthma
Mechanical ventilation, COPD
Drugs
DDAVP, Diabinese, NSAIDS, opiates,
Carbamazepine, SSRI, Tricyclic, Thiazides
Ecstasy, ACE-I, Omeprazole
Miscellaneous
Pain, Nausea, surgery, stress,
Alcohol withdrawal

26. Euvolemic Hypotonic Hyponatremia SIADH : Treatment
Discontinue offending agent
Treatment of etiology (infection, pain)
Fluid restriction (for Chronic asymptomatic Hyponatremia)

27. Euvolemic Hypotonic hyponatremia Poor solute Intake Beer Potomania, Tea Toast syndrome
Urine Volume =
Urinary solute excretion
in person on normal diet-
mM/day
Urinary solute excretion
Urinary Osmolality
Normal Urinary Electrolytes
Normal Urinary Urea
Na+ , K+ = = 200
Catabolism=
Accompanying anions= 200
Diet ~50 mM/10 gm of dietary protein
Total 400 mM/day
Total mM/day
Clinical setting of low solute intake:
- Alcoholism (Beer Potomania)
- Anorexia (Tea and Toast Diet)

28. Euvolemic Hypotonic hyponatremia Poor solute Intake Beer Potomania, Tea Toast syndrome
Normal Solute excretion = 900 mOsm/d
Assume maximal urine dilution= 60 mOsm/kg
Urine Volume = 900/60 = 15 L/d
With solute excretion of 300 mOsm
Urine Volume = 300/60 = 5 L/d
With solute excretion of 300 mOsm and
maximal urine dilution of 150 mOsm/kg
Urine volume = 300/150 = 2 L/d

29. Euvolemic Hypotonic hyponatremia Poor solute Intake Beer Potomania
Assume Beer consumption of 5 L:
Na intake mM
K intake mM
Obligatory urea excretion 90 mM
Total solutes mOsm
Assume urine dilution of 50 mOsm/kg
Urine volume = 150/50 = 3 L
2 L of fluids (hypotonic) is retained to produce hyponatremia
Beer:
Na 2 mM/L
K 10 mM/L

30. Euvolemic Hypotonic hyponatremia Poor solute Intake Treatment
Increase solute intake –
High protein diet
Salt tablets or high dietary salt
Urea
2. Fluid restriction

31. Hospital acquired Hyponatremia
Virtually every hospitalized patient has potential stimulus for AVP excess
Administration of hypotonic fluid with excess AVP are at risk for Hyponatremia
Chung HM et al, Arch Inter Med 2002

32. Hospital acquired hyponatremia
Series of 15 women with Hyponatremia and permanent neurological damage
Following elective surgery
11 had received 5% Dextrose post surgery
Arieff AI et al, NEJM 1986

33. Hospital acquired hyponatremia
Series of 65 patients with Hyponatremia and encephalopathy
Following elective surgery
All had received hypotonic fluid
Ayus JC et al, Ann Intern Med, 1992

34. Hospital acquired hyponatremia
Odds ratio for developing hyponatremia was 3.7 for each liter of electrolyte-free water given to 70 kg patient
Aronson D et al, Am J Kid Dis. 2002

35. Hospital acquired hyponatremia
Ringer’s Lactate (Sodium 77) is hypotonic and can produce hyponatremia
No justification for Ringers lactate in post op period
Administration of 0.9 saline is safe
No reports of 0.9 Saline causing neurological complications of hyponatremia
Steele A et al, Ann Intern Med 1997
Moritz ML et al, J Am Soc Nephrol 2005

36. Clinical features
And
Brain Adaption

37. Hyponatremia
Symptoms

39. Cerebral adaption to decrease cerebral edema
Early 1-3 hrs
CSF distribution
Later (> 3 hrs)
Loss of Osmolytes and electrolytes:
Glutamate, Inositol, Taurine,
Urea, K, Na, Creatinine

40. IDIOGENIC

41. Treatment

42. Chronic Hyponatremia:
Acute Hyponatremia:
Less than 48 hrs
Neurologic symptoms due to brain edema
Rapid correction well tolerated
Chronic Hyponatremia:
More than 48 hrs or unknown time
Mild brain edema (<10%)
Sensitive to Na correction rate
Aim to increase Na by 10% (not more than 12 in 24 hrs)

43. Treatment of
Hyponatremia:
Balance –
Risk of
Hyponatremia Vs
Correction

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

45. Monitoring of patients:
Volume status
Daily weight
Frequent Serum Na, K
Plasma Osmolality
Urine Na, K, osmolality
Strict Input and Output

46. Treatment of Hyponatremia Basic concept
Free water intake << Free water output
AND
Na, K intake >> Na, K output
2. Needed Info:
Serum Na , osmolality
Urine Na, K, Osmolality
Strict Input/ Output
3. Rate of correction

47. Treatment Symptomatic Hyponatremia
Treatment based on neurological symptoms and not on Sodium
Needs aggressive management with 3%NaCl
No role of fluid restriction alone
Treatment should precede any neuroimaging
Treatment in monitored setting
Sodium levels measured every 2 hours

48. Treatment Symptomatic Hyponatremia
Impending herniation: Sz, resp arrest,, obtundation, Decorticate posturing, dilated pupils:
ml of 3% NaCl as a bolus over 10 min to rapidly
reverse brain edema.
- Repeat bolus as required till symptoms improve
Encephalopathy: Headache, N/V, Altered mental status:
% ml/hr
Calculating 3% saline rate:
Weight in kg x desired rate of increase in Serum Na

49. Treatment Symptomatic Hyponatremia
4. Monitor [Na] every 2-4 hrs
5. Stop active correction when appropriate end point is reached:
- Patient becomes asymptomatic
- Safe Na levels reached (generally 120)
- Total correction 12 mmol in 24 hrs or
18-20 mmol in 48 hrs
6. Complete rest of correction with - fluid restriction

50. Asymptomatic Hyponatremia
Treatment
Asymptomatic Hyponatremia
Attend to underlying cause
No immediate correction needed
Fluid restriction
Urine Na + K
Plasma Na
Recommended water intake
>1
< 500 ml/day -1
500 to 700 ml/day
< 1
< 1000 ml/day
D Ellison, T Berl. NEJM 2007;356:

51. Asymptomatic Hyponatremia
Treatment
Asymptomatic Hyponatremia
Treatment
Mechanism
Dose
Advantage
Limitations
Fluid
restriction
Decreases availability of free water
Variable
Effective
Inexpensive
Non compliance
Encourage dietary salt and protein
Solutes required for free water excretion
Demeclocycline
↓ ADH response
mg BID
Effective Unrestricted water intake
Nephrotoxic, Polyuria, Photosensitive
V-2 Receptor antagonist -
Conivaptan
Antagonize ADH receptor
20-40 mg/day
IV (Vaprisol)
Available only as IV

53. Conivaptan (Vaprisol)
Only Vaptan, FDA approved for :
Hospitalized patients with asymptomatic chronic hyponatremia (Euvolemic or Hypervolemic)
Available only in IV form
Given as 20 mg bolus over 4 hrs followed by continuous infusion of mg/day for 4 days
At end of 4 days, Serum Na ↑ by 6.1 mmol/L
Time to ↑ Serum Na by 4 mmol/L was 23 hrs
Should not be used as an alternate to 3% sodium chloride in symptomatic Hyponatremia
Commonest side effect was increased thirst

54. Complications of treatment

55. Risk of Neurological Complications
Acute Cerebral edema
Post-op: menstruating F
(Risk 30 X men)*
(Risk 25 X postmenopausal F)*
Children
Brain injury
(No safe degree of ↓ Na)
Hypoxemia
Elderly F on HCTZ
Psych Polydipsia
Osmotic Demyelination
Alcoholics
Malnourished
Hypokalemia
Hypoxemia
Elderly F on HCTZ
* Ayus JC et al, Ann Intern Med 1992

56. Osmotic demyelination
Iatrogenic brain damage when chronic hyponatremia
is treated rapidly
Biphasic course
Brain damage presents clinically in 1-7 days after treatment
Shows pontine and extrapontine myelinolysis
Clinically presents as pseudobulber palsy and quadriparesis,
behavioral changes, mutism, locked in syndrome, seizures
Uremia protects against myelinolysis
Reinduction of hyponatremia – aborts development of
subsequent myelinolysis (Oya, Neurology 2001)
(Brown WD, Curr Opin Neurol 2000; Lampl, Eur Neurol 2002)

57. Take home message 1. In presence of ADH concentrated urine is formed
Treatment – Basic concept:
Free water Input << Free water Output
Na+K Input >> Na+K Output
3. Symptomatic hyponatremia –
Symptoms due to brain swelling
Treat aggressively with hypertonic saline
4. Asymptomatic Hyponatremia – Identify why ADH is high
Osmotic demyelination - if correction is >12 mEq/day
Identify patients at risk