Another Salt Problem: Hypernatremia

We often talk about Hyponatremia, but Hypernatremia primarily occurs in patients who do not experience and/or respond to thirst normally, often due to impaired mental status (i.e. elderly, critically ill patients). It occurs in patients with impaired access to water, those with loss of hypotonic fluid and infrequently, due to infusion of a hypertonic fluid. It is defined as a serum Na>145 mmol/L. It constitutes a deficit of water relative to salt. 

·       Hypernatremia is a powerful stimuli for thirst! Salt intake and water loss seldom result in hypernatremia, because the ensuing rise in plasma osmolality stimulates both the release of ADH and thirst. Note that older adults experience a change in their thirst stimulus (it is not as robust as people get older)!

Symptoms: intense thirst (+/-), muscle weakness, confusion, coma; brain shrinkage could potentially cause vascular rupture, leading to cerebral bleeding, SAH, permanent neurological deficit and death

ETIOLOGY- 3 Major mechanisms: Un-replaced water loss (*common), water loss into cells, Na+ overload

1.Hypovolemic Hypernatremia

·       Renal water loss (Urine Osmol 300-600): loop diuretics, osmotic diuresis (i.e. mannitol, urea, glucose)

o   Osmotic diuresis: due to non-reabsorbed, non-electrolyte solutes (i.e. glucose, mannitol, urea)àincrease urine output

§  Initially: Mannitol in serum causes osmotic water movement out of cellsàlowering [Na]; in absence of impaired renal functionà mannitol is excreted in the urineà associated osmotic diuresisà raise [Na]

§  Urea: an inefficient osmoleàas urea is excreted in the urine, the loss of water will raise the serum [Na]

·       Extra-renal water loss (Uosm>600): diarrhea, insensible loss (fever, exercise)

·       Decreased access to water

·       Decreased thirst stimuli

o   Hypothalamic lesions affecting thirst or osmoRC functionàhypodipsia!

o   i.e. in children +/- DI, if congenital or acquired structural lesion (i.e. dysplasia of midline structures); older adults have a reduced thirst response with normal aging processes

2.Euvolemic Hypernatremia (Diabetes Insipidus)

·       Nephrogenic DI: renal resistance to the effect of ADH à cause excretion of dilute urine

o   i.e. renal disorders (PCKD, infiltration, infection, ischemia), meds (Lithium, demeclocycline, amphotericin B), idiopathic, hypercalcemia, amyloid

·       Central DI: impaired ADH release

o   i.e. trauma, tumors, infections (TB, meningitis, encephalitis), infiltrative disease of hypothalamus or PP (sarcoidosis), vascular, idiopathic

·       Most: have a normal thirst mechanism, thus present with polydipsia AND polyuria, high serum [Na]

·       Water loss into cells/Transientà serum [Na] rises by 10-15 mmol/L within minutes

o   i.e. severe exercise, electro-shock induced seizures

o   due to breakdown of large complex organic molecules into numerous small componentsè increases cell osmolality

3.Hypervolemic Hypernatremia

·       Hypertonic saline administration (IVF)- i.e. NaHCO3 during resuscitation

·       Drink seawater!

·       Primary Hyperaldosteronism (mineralocorticoid excess)

Work-Up

Physical: VS (orthostatic VS), CDV, JVP, skin turgor, MM, peripheral edema

Investigations: CBC, Cr, Urea, Lytes, Extended lytes, glucose, UA, Serum & Urine osmolality, Urine lytes

Hypovolemic Hypernatremia	Euvolemic Hypernatremia	Hypervolemic Hypernatremia
Urine Osm>300-600 & UNa>20: Renal loss Urine Osm>600, UNa<20: Extra-renal losses	Urine Osm<300: Complete DI Urine Osm 300-600: ? Partial DI Urine Osm>600: intracellular osmole generation	Exogenous Hypertonic Saline Mineralcorticoid excess
Urine Osmolality- Patterns to Consider
Uosm: LOW (<300)à DI	Uosm: INTERMEDIATE (300-600)à DI or Osmotic Diuresis	Uosm: HIGH (>600)à endogenous ADH is intact…both the response and the secretion!

·       If the urine osmolality is <600 mosmol/kg, observe the change in urine osmolality after administration of exogenous ADH

o   If both renal and hypothalamic function are intact, Urine Osmol in the presence of hypernatremia should be >600

§  If given exogenous ADH: should NOT produce a further rise in urine osmol

o   If urine osmolality is low (<300), less than serum osmolality, the patient has DI (central or nephrogenic)

§  Distinguish: administer exogenous ADH, followed by monitoring urine osmolality and volume q30 minutes over the next 2 hours

o   If urine osmolality is intermediate (300-600): hypernatremia is d/t an osmotic diuresis or to DI

§  Osmotic Diuresis: confirm by measuring total solute excretion (= urine osmol x daily urine volume); normal 600-900 mosmol/d (Na, K, Ammonium, Urea)

·       Value >1000: suggests a contribution from increased solute excretion

·       Do NOT respond to exogenous ADH (since endogenous effect is max)

§  If NO osmotic diuresis, consider DI

o   If urine osmolality is high (>600): both secretion and response to endogenous ADH are intact!

Treatment

·       Restore access to water (>1L/day), replace free water deficits and losses

1.Calculate TBW (0.6 x kg, men; 0.5 x kg for women)= i.e. 0.6 x 100 kg= 60 L

2. Water deficit: TBW x [(Na current/Na goal) -1]

3.Choose Fluid (i.e. D5W—0 Na)

4. Na infusate – Na serum/ (TBW-1)= (0-160)/(60-1)= 2.7= each 1 L of D5 lowers Na by 2.7 mmol/L

5. Correction Rate: maximum decrease of 10 mmol/L over 24 h

NOTE: study by Linder et al., found that the predictive potential of the above formula (and other formulas) are not perfect. The formulae correlated significantly with measured changes in serum Na in the patient cohort as a total. However; the individual variations were extreme! Thus, these formulas ONLY GUIDE therapy. Serial measurements are prudent!!

NOTE: 1.35 ml/h x patients wt in kg (for chronic, >48h hypernatremia)

CAUTION

·       D5 IVF can lead to hyperglycemia (especially if DM or physiologically stressed)à risk of osmotic diuresis à electrolyte and free fluid loss, limiting tx of hypernatremia (can use a 2.5% Dextrose!)

·       Rate of correction: 10 mmol in 24 h= max. Otherwise, risk cerebral edema!

Polyuria with Water Diuresis

·       DDx: DI (Na>140) versus Primary Polydipsia (Na<140)

o   DI work-up: Uosm<300 suggests complete DI while 300-600 may be a Partial DI

o   Water Deprivation test: deprive until serum osmol <295 and Urine osmol <300, then administer vasopressin (5U SC) or DDAVP (10 mcg intranasal)

§  Urine Osmol increases by >50%: central DI

§  Urine Osmol unchanged: Nephrogenic DI


Interesting Read: Clinical presentation of hypernatremia in elderly patients: a case control study. Journal Am Geriatric Soc. 2006 Aug;54(8): 1225-30. Chassagne, P. et al. 

http://www.ncbi.nlm.nih.gov/pubmed/16913989