Hyponatremia and hypernatremia are electrolyte disorders commonly seen in clinical practice that affect sodium and water balance. Hyponatremia refers to a serum sodium level below 135 mEq/L and is usually due to hypotonicity, while hypernatremia is a serum sodium above 145 mEq/L and is always associated with hyperosmolality. The clinical features of both conditions depend on the severity and rapidity of onset and can range from mild symptoms to severe neurological issues like seizures or cerebral edema. Treatment involves correcting the underlying cause and slowly restoring sodium and fluid levels to avoid complications like osmotic demyelination syndrome.

1. Hyponatremia and Hypernatremia

2. Introduction
• Most common electrolyte disorder in clinical practice
• Sodium and water disorders occur simultaneously
• Most commonly affect the neurologic system and
can potentially lead to devastating outcomes
Sterns RH. Disorders of Plasma Sodium - Causes, Consequences, and Correction. N Engl J Med 2015

3. Relationship of fluid compartments to total
body weight
Harring TR, et al. Disorders of Sodium and Water Balance. Emerg Med Clin N Am 2014

4. • Serum sodium is closely related with S. osmolality
• S. osmolality = 2 Na+ + BUN (mg/dl)/2.8 + Glu (mg/dl)/18
• By controlling water intake and excretion, the
osmoregulatory system normally prevents the S. Na from
staying outside its normal range (135 -145 mEq/l)
• Failure of the system to regulate within this range
exposes cells to hypotonic or hypertonic stress
Sodium & osmolarity
Sterns RH. Disorders of Plasma Sodium - Causes, Consequences, and Correction. N Engl J Med 2015

5. • Serum sodium is closely related with S. osmolality
• S. osmolality = 2 Na+ + BUN (mg/dl)/2.8 + Glu (mg/dl)/18
• By controlling water intake and excretion, the
osmoregulatory system normally prevents the S. Na from
staying outside its normal range (135 -145 mEq/l)
• Failure of the system to regulate within this range
exposes cells to hypotonic or hypertonic stress
Sodium & osmolarity
Sterns RH. Disorders of Plasma Sodium - Causes, Consequences, and Correction. N Engl J Med 2015

6. S. Na regulation
• Regulation of H2O intake (Thirst)
• Regulation of H2O excretion (Vasopressin)
• Regulation of Na intake (Not regulated)
• Regulation of Na excretion (Tubular Na reabsorption)
Harring TR, et al. Disorders of Sodium and Water Balance. Emerg Med Clin N Am 2014

7. HYPONATREMIA

8. Introduction
• S. Na <135 mEq/l; Severe <120-125 mEq/l
• Very common, 22% hospitalized patients
• HypoNa usually indicates hypotonicity (true hypoNa), but there
are exceptions
Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med 2000
Sterns RH. Disorders of Plasma Sodium - Causes, Consequences, and Correction. N Engl J Med 2015

9. Non-hypotonic hyponatremia
• Hypertonic (or translocational) hyponatremia
When hyperglycemia +, the underlying S. Na (corrected S. Na)
can be estimated by adding 1.6 - 2.4 mEq/l (≃2 mEq/l) to the
reported S. Na for every 100 mg/dl ↑ in BS >100 mg/dl
• Isotonic hyponatremia
Isotonic irrigation solutions during hysteroscopy, laparoscopy,
or TURP
• Pseudohyponatremia
Severe hyperproteinemia (myeloma) or severe hyperlipid

10. Hypovolemic Hyponatremia
• HypoNa with ↓ POSM and ↑UOSM
• Clinical hypovolemia triggering AVP release
• Can be due to renal volume losses (UNa >20 mmol/L), or
extrarenal losses (UNa <20 mmol/L)
• Renal - diuretic use and mineralocorticoid deficiency
• Extrarenal - GI (vomiting, diarrhea), third spacing (burns,
pancreatitis)

11. Hypervolemic Hyponatremia
• HypoNa with ↓ POSM and ↑UOSM
• Ch/by low effective arterial volume triggering thirst & AVP
• TBW ↑↑, total body Na↑ - Usually significant edema
• UNa usually low (<20 mmol/l), if renal function is normal
• Often, degree of hypoNa correlates with severity & prognosis
of the underlying ds (esp. in CHF & cirrhosis)

12. Euvolemic hyponatremia
• HypoNa with ↓ POSM and ↑UOSM
• TBW ↑, total body Na ⟷, No edema (as 2/3 water is
intracellular)
• UNa usually >20 mmol/l, if renal function is normal
• SIAD, hypothyroidism, glucocorticoid deficiency

13. SIAD causes
Ellison DH, et al. The Syndrome of Inappropriate Antidiuresis. N Engl J Med 2007
Harrison’s Principles of Internal Medicine, 20th ed

14. Hyponatremia with ↓POsm & ↓UOsm
• HypoNa with ↓POsm despite a max dilute urine and
suppressed AVP
• ↓Uosm <100 mOsm/kg
• ↑↑fluid ingestion (primary polydipsia) can overwhelm the
max renal diluting capacity
• ↓solute intake (malnourished states like excessive beer
drinkers) limits the renal ability to excrete water independent
of AVP

15. Diagnostic approach
The Washington Manual of Medical Therapeutics, 35th ed
Spasovski G, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endo 2014

17. Clinical features
• Depend on serum levels, rapidity of development, baseline
mental state (e.g., age)
Harring TR, et al. Disorders of Sodium and Water Balance. Emerg Med Clin N Am 2014

18. Clinical features
• Depend on serum levels, rapidity of development, baseline
mental state (e.g., age)
Harring TR, et al. Disorders of Sodium and Water Balance. Emerg Med Clin N Am 2014

19. Treatment
• Type of hypoNa, serum level, C/F, rapidity of development
• Nonhypotonic hypoNa usually requires management of
underlying condition
• Hypovol. hypoNa - careful volume expansion with isotonic
fluids
• Hypervol. & euvol. hypoNa usually require fluid restriction,
loop diuretics, oral or IV (3% NaCl), vaptans

20. Treatment: Vaptans
• Vasopressin antagonists
• Blocks the binding of AVP to V2 receptors at basolateral
membrane of principal cells of collecting duct
• Electrolyte free water excretion
• Not the mainstay of treatment in hypoNa

21. Treatment: Vaptans
Berl T. Vasopressin Antagonists. N Engl J Med 2015

22. Treatment: IV correction
• Acute severe hyponatremia: cerebral edema
• Main risk of rapid correction: osmotic demyelination synd
• Adrogue-Madias formula to guide rate of infusion
Change in S. Na per liter infusion = (Infusate Na – S. Na) ÷ (TBW* + 1)
*TBW: Body wt X % of body water (0.6 - pediatric age & adult male, 0.5 -
adult female & elderly male, and 0.45 - elderly female)
Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med 2000
Sterns RH. Disorders of Plasma Sodium - Causes, Consequences, and Correction. N Engl J Med 2015

23. Treatment: IV correction
1 ml of 3% saline/kg body wt will ↑ S. Na by ≃ 1 mEq/l
(In the absence of urinary loss of water)

24. Treatment: Algorithm
Spasovski G, et al. Clinical practice guideline. Eur J Endo 2014
Williams DM, et al. The clinical management of hyponatraemia. Postgrad Med J 2016

25. Treatment: Algorithm
Sterns RH. Disorders of Plasma Sodium - Causes, Consequences, and Correction. N Engl J Med 2015

27. HYPERNATREMIA

28. • S. Na >145 mmol/l
• Invariably a/w hyperosmolality and always causes cellular
dehydration
• Sustained hyperNa occurs only when thirst or access to water
is impaired, i.e., usually in very old, very young, critically ill, or
neurologically impaired
• First step is to assess the volume status
Introduction
Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med 2000

29. Diagnostic approach
Uvol ↓ (<800 ml)
Uosm ↑ (>800 mOsm/l)
Uvol in 24 hr X Uosm
Harrison’s, 20th ed
Washington MMT, 35th ed

30. Clinical features
• Depend on serum levels, rapidity of onset, baseline mental
state (e.g., age)
• Similar to hypoNa – neurological symptoms (AMS, seizures)
• During hypernatremia water moves into the extracellular
space → brain cells shrink substantially → can cause ICH as a
result of tearing of cerebral blood vessels
Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med 2000
Harring TR, et al. Disorders of Sodium and Water Balance. Emerg Med Clin N Am 2014

31. • Type of hyperNa, serum level, C/F, rapidity of development
• Acute severe hypernatremia (in hours) → rapid correction @ 1
mEq/l/hr
• Chronic hypernatremia (over days) → @ 0.5 meq/l/hr
• T/t goals: replacement of FWD and ↓ ongoing water loss
Treatment: objectives

32. • Calculate FWD (in liter)= TBW* x ([Serum Na+ / 140] – 1)
• Administer the FWD over 48-72 hrs with a goal ≯10 mEq/l/d
• As this formula can underestimate the amount of FWD,
Adrogue-Madias formula remains standard
• *TBW: Because hypernatremia suggests a contraction in water
content (estimated to ↓ by ≃10%), the correction factor is 0.5
in male (rather than 0.6) and 0.4 in female
Treatment: PO/IV correction
Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med 2000
Harring TR, et al. Disorders of Sodium and Water Balance. Emerg Med Clin N Am 2014

33. • HyperNa with ⟷ ECF: Only water repletion may be sufficient,
either by water PO/RT or by IV D5W
• HyperNa with ↓ECF: Both water & Na replacement is required,
by hypotonic saline (0.45%)
• HyperNa with ↑ECF: Cessation of iatrogenic Na, use of
diuretics along with replacement of FWD
• Central DI: Desmopressin
• Nephrogenic DI: Thiazides (paradoxical antidiuretic effect)
Treatment: underlying cause

34. Take Home Message

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