This document discusses hypernatremia, which is defined as a serum sodium level exceeding 145 mEq/liter. Sodium levels are normally regulated by ADH and the thirst mechanism, but hypernatremia can occur when there is a loss of hypotonic fluid and impaired access to water, such as in infants, elderly patients, or those who are unconscious. This leads to cellular dehydration and neurological issues if sodium levels rise too high. Causes include excessive sodium intake, water loss from vomiting/diarrhea, and certain drugs. Signs may include thirst, lethargy, seizures, or coma depending on the severity. The diagnosis involves checking serum and urine osmolality and electrolyte levels.

2. HypernatremiaHypernatremia
Khalid shawkey mohamedKhalid shawkey mohamed
Internal medicine specialistInternal medicine specialist
ICU unit , Internal medicine departmentICU unit , Internal medicine department
Zagazig UniversityZagazig University

3. Sodium basicsSodium basics
•• Major cation in extracellular fluid (90%)Major cation in extracellular fluid (90%)
•• Attracts fluidsAttracts fluids
•• Helps transmit impulses in nerve andHelps transmit impulses in nerve and
muscle fibersmuscle fibers
•• Combines with chloride and bicarbonate toCombines with chloride and bicarbonate to
regulate acid-base balanceregulate acid-base balance
•• Normal serum level: 135 to 145 mEq/LNormal serum level: 135 to 145 mEq/L

4. Sodium balanceSodium balance
•• Balance is maintained by ADH, which isBalance is maintained by ADH, which is
secreted from the posterior pituitary gland.secreted from the posterior pituitary gland.
•• The balance depends on what's eaten, andThe balance depends on what's eaten, and
how sodium is absorbed in the intestines.how sodium is absorbed in the intestines.
•• Increased sodium intake results inIncreased sodium intake results in
increased extracellular fluid volume.increased extracellular fluid volume.
•• Decreased sodium intake results inDecreased sodium intake results in
decreased extracellular fluid volume.decreased extracellular fluid volume.

5. •• Increased sodium levels result inIncreased sodium levels result in
increased thirst, release of ADH, retention ofincreased thirst, release of ADH, retention of
water by the kidneys, and dilution of blood.water by the kidneys, and dilution of blood.
•• Decreased sodium levels results inDecreased sodium levels results in
suppressed thirst, suppressed ADHsuppressed thirst, suppressed ADH
secretion, excretion of water by the kidneys,secretion, excretion of water by the kidneys,
and secretion of aldosterone to conserveand secretion of aldosterone to conserve
sodium.sodium.

6. Balance is maintained by diffusion, whichBalance is maintained by diffusion, which
moves sodium ions into cells and potassiummoves sodium ions into cells and potassium
out.out.
•• Sodium-potassium pump uses energy toSodium-potassium pump uses energy to
move sodium ions back out of cells andmove sodium ions back out of cells and
return potassium to cells; it also creates anreturn potassium to cells; it also creates an
electrical charge within the cell from theelectrical charge within the cell from the
movement of ions, allowing transmission ofmovement of ions, allowing transmission of
nerve impulses.nerve impulses.

7. Definition of HypernatremiaDefinition of Hypernatremia
 Serum SodiumSerum Sodium exceeds 145 meq/literexceeds 145 meq/liter
 Serum sodium disorders are usually due toSerum sodium disorders are usually due to
change in water balancechange in water balance
 EpidemiologyEpidemiology
IncidenceIncidence:Less common than hyponatremia:Less common than hyponatremia
accounts for 1% of hospitalized elderly patientsaccounts for 1% of hospitalized elderly patients
 Most cases occur in hospitalized patients ,Most cases occur in hospitalized patients ,
Classic outpatient presentation: Elderly nursingClassic outpatient presentation: Elderly nursing
home resident with underlying infectionhome resident with underlying infection
 hypernatremia is associated with mortality rateshypernatremia is associated with mortality rates
as high as 40–60%, mostly due to the severity ofas high as 40–60%, mostly due to the severity of
the associated underlying disease processes.the associated underlying disease processes.

8. PathophysiologyPathophysiology
 Hypernatremia is almost always due toHypernatremia is almost always due to
loss of hypotonic fluid and impairedloss of hypotonic fluid and impaired
access to free water.access to free water.
 The body usually defends against this withThe body usually defends against this with
the potent mechanism of thirst.the potent mechanism of thirst.
 The hypothalamus (with itsThe hypothalamus (with its
osmoreceptors) is the brain's thirst center.osmoreceptors) is the brain's thirst center.
 High serum osmolality (increased soluteHigh serum osmolality (increased solute
concentrations in the blood) stimulates theconcentrations in the blood) stimulates the
hypothalamus and initiates the sensationhypothalamus and initiates the sensation
of thirst.of thirst.

9.  The drive to respond to thirst is so strongThe drive to respond to thirst is so strong
that severe, persistent hypernatremiathat severe, persistent hypernatremia
usually occurs only in people who can'tusually occurs only in people who can't
drink voluntarily, such as infants, confuseddrink voluntarily, such as infants, confused
elderly patients, and immobile orelderly patients, and immobile or
unconscious patients.unconscious patients.
 Hypothalamic disorders, such as a lesionHypothalamic disorders, such as a lesion
on the hypothalamus, may cause aon the hypothalamus, may cause a
disturbance of the thirst mechanism, butdisturbance of the thirst mechanism, but
this condition is rare.this condition is rare.

10.  The body strives to maintain a normalThe body strives to maintain a normal
sodium level by secreting ADH from thesodium level by secreting ADH from the
posterior pituitary gland. This hormoneposterior pituitary gland. This hormone
causes water to be retained, which helpscauses water to be retained, which helps
to lower serum sodium levels.to lower serum sodium levels.
 The cells also play a role in maintainingThe cells also play a role in maintaining
sodium balance. When serum osmolalitysodium balance. When serum osmolality
increases because of hypernatremia, fluidincreases because of hypernatremia, fluid
moves by osmosis from inside the cell tomoves by osmosis from inside the cell to
outside the cell, to balance theoutside the cell, to balance the
concentrations in the two compartments.concentrations in the two compartments.

11.  As fluid leaves the cells, they becomeAs fluid leaves the cells, they become
dehydrated and shrink—especially thosedehydrated and shrink—especially those
of the CNS. When this occurs, patientsof the CNS. When this occurs, patients
may show signs of neurologic impairment.may show signs of neurologic impairment.
They may also show signs ofThey may also show signs of
hypervolemia (fluid overload) fromhypervolemia (fluid overload) from
increased extracellular fluid volume in theincreased extracellular fluid volume in the
blood vessels. If the overload is severeblood vessels. If the overload is severe
enough, subarachnoid hemorrhage mayenough, subarachnoid hemorrhage may
occur.occur.

13.  A water deficit can occur alone or with a sodiumA water deficit can occur alone or with a sodium
loss (but more water is lost than sodium). Inloss (but more water is lost than sodium). In
either case, serum sodium levels are elevated.either case, serum sodium levels are elevated.
This elevation is more dangerous in debilitatedThis elevation is more dangerous in debilitated
patients and those with deficient water intake.patients and those with deficient water intake.
 Insensible water losses of several liters per dayInsensible water losses of several liters per day
can result from fever and heat stroke, with oldercan result from fever and heat stroke, with older
adults and athletes being equally susceptible.adults and athletes being equally susceptible.
Significant water losses also occur in patientsSignificant water losses also occur in patients
with pulmonary infections, who lose water vaporwith pulmonary infections, who lose water vapor
from the lungs through hyperventilation, and infrom the lungs through hyperventilation, and in
patients with extensive burns.patients with extensive burns.

14.  Vomiting and severe, watery diarrhea areVomiting and severe, watery diarrhea are
other causes of water loss andother causes of water loss and
subsequent hypernatremia; either can besubsequent hypernatremia; either can be
especially dangerous in children.especially dangerous in children.
 Patients with hyperosmolar hyperglycemicPatients with hyperosmolar hyperglycemic
nonketotic syndrome can also developnonketotic syndrome can also develop
hypernatremia due to severe water losseshypernatremia due to severe water losses
from osmotic diuresis. Urea diuresis,from osmotic diuresis. Urea diuresis,
another cause of hypernatremia, occursanother cause of hypernatremia, occurs
with administration of high-proteinwith administration of high-protein
feedings or high-protein diets withoutfeedings or high-protein diets without
adequate water supplementation.adequate water supplementation.

15.  Excessive sodium intake including saltExcessive sodium intake including salt
tablets, high-sodium foods, andtablets, high-sodium foods, and
medications such as sodium polystyrenemedications such as sodium polystyrene
sulfonate (Kayexalate).sulfonate (Kayexalate).
 Excessive parenteral administration ofExcessive parenteral administration of
sodium solutions, such as hypertonicsodium solutions, such as hypertonic
saline solutions or sodium bicarbonatesaline solutions or sodium bicarbonate
preparations, and gastric or enteral tubepreparations, and gastric or enteral tube
feedings can also cause hypernatremia.feedings can also cause hypernatremia.

16.  Other causes of increased sodium levelsOther causes of increased sodium levels
include inadvertent introduction ofinclude inadvertent introduction of
hypertonic saline solution into maternalhypertonic saline solution into maternal
circulation during therapeutic abortion andcirculation during therapeutic abortion and
near drowning in salt water. Excessivenear drowning in salt water. Excessive
amounts of adrenocortical hormones (asamounts of adrenocortical hormones (as
in Cushing's syndrome andin Cushing's syndrome and
hyperaldosteronism) also affect water andhyperaldosteronism) also affect water and
sodium balance.sodium balance.

17. DIABETES INSIPIDUS (DI)DIABETES INSIPIDUS (DI)
 collecting tubule is impermeable to water due to absencecollecting tubule is impermeable to water due to absence
of ADH( central) or impaired response to ADHof ADH( central) or impaired response to ADH
(nephrogenic)(nephrogenic)
 EtiologyEtiology
•• central DI: neurosurgery, granulomatous diseases,central DI: neurosurgery, granulomatous diseases,
trauma, vascular events, and malignancytrauma, vascular events, and malignancy
•• nephrogenic DI: lithium (most common), hypokalemia,nephrogenic DI: lithium (most common), hypokalemia,
hypercalcemia, and congenitalhypercalcemia, and congenital
 DiagnosisDiagnosis
•• urine osmolality inappropriately low in patient withurine osmolality inappropriately low in patient with
hypernatremia (Uosm <300 mOsm/kg)hypernatremia (Uosm <300 mOsm/kg)
•• serum vasopressin concentration may be absent or lowserum vasopressin concentration may be absent or low
(central), or elevated (nephrogenic)(central), or elevated (nephrogenic)

18. •• dehydration test: H2O deprivation until loss of 3% of bodydehydration test: H2O deprivation until loss of 3% of body
weight or until urine osmolarity rises above plasmaweight or until urine osmolarity rises above plasma
osmolarity; if fails to concentrate urine, most likely DIosmolarity; if fails to concentrate urine, most likely DI
•• administer DDAVP (exogenous ADH) (10administer DDAVP (exogenous ADH) (10 μμg intranasallyg intranasally
or 2or 2 μμg SC or IV):g SC or IV):
ƒ. central DI: diagnosed if there is rise in urine osmolality,ƒ. central DI: diagnosed if there is rise in urine osmolality,
fall in urine volumefall in urine volume
ƒ.nephrogenic DI: exogenous ADH fails to concentrateƒ.nephrogenic DI: exogenous ADH fails to concentrate
urine as kidneys do not respondurine as kidneys do not respond

19. Drugs associated with hypernatremiaDrugs associated with hypernatremia
 antacids with sodium bicarbonateantacids with sodium bicarbonate
 antibiotics such as ticarcillinantibiotics such as ticarcillin
disodiumclavulanate potassium (Timentin)disodiumclavulanate potassium (Timentin)
 salt tabletssalt tablets
 sodium bicarbonate injections (such assodium bicarbonate injections (such as
those given during cardiac arrest)those given during cardiac arrest)
 I.V. sodium chloride preparationsI.V. sodium chloride preparations
 sodium polystyrene sulfonate(Kayexalate).sodium polystyrene sulfonate(Kayexalate).

20. Signs and SymptomsSigns and Symptoms
 Due to osmotic shrinkage of brain cellsDue to osmotic shrinkage of brain cells
 with acute hypernatremia no time forwith acute hypernatremia no time for
adaptation, therefore more likely to beadaptation, therefore more likely to be
symptomaticsymptomatic
 adaptive response: cells import andadaptive response: cells import and
generate new osmotically active particlesgenerate new osmotically active particles
to normalize sizeto normalize size

21.  Thirst is the main symptom but if [Na+] isThirst is the main symptom but if [Na+] is
>155 mmol/L, lethargy, irritability, fits,>155 mmol/L, lethargy, irritability, fits,
coma, intracranial hemorrhage andcoma, intracranial hemorrhage and
death may occur.death may occur.
 Neuromuscular signs also commonlyNeuromuscular signs also commonly
occur, including twitching, hyperreflexia,occur, including twitching, hyperreflexia,
ataxia, and tremors.ataxia, and tremors.
 Signs according to volume statusSigns according to volume status

22. Diagnostic approachDiagnostic approach
 The history should focus on the presenceThe history should focus on the presence
or absence of thirst, polyuria, and/or anor absence of thirst, polyuria, and/or an
extrarenal source for water loss, such asextrarenal source for water loss, such as
diarrhea.diarrhea.

23.  The physical examination should include aThe physical examination should include a
detailed neurologic exam and andetailed neurologic exam and an
assessment of the ECFV; patients with aassessment of the ECFV; patients with a
particularly large water deficit and/or aparticularly large water deficit and/or a
combined deficit in electrolytes and watercombined deficit in electrolytes and water
may be hypovolemic, with reduced JVPmay be hypovolemic, with reduced JVP
and orthostasis. Accurate documentationand orthostasis. Accurate documentation
of daily fluid intake and daily urine outputof daily fluid intake and daily urine output
is also critical for the diagnosis andis also critical for the diagnosis and
management of hypernatremia.management of hypernatremia.

24.  Laboratory investigation should include aLaboratory investigation should include a
measurement of serum and urine osmolality inmeasurement of serum and urine osmolality in
addition to urine electrolytes.addition to urine electrolytes.
 The appropriate response to hypernatremia andThe appropriate response to hypernatremia and
a serum osmolality >295 mosmol/kg is ana serum osmolality >295 mosmol/kg is an
increase in circulating AVP and the excretion ofincrease in circulating AVP and the excretion of
low volumes (<500 mL/d) of maximallylow volumes (<500 mL/d) of maximally
concentrated urine, i.e., urine with osmolalityconcentrated urine, i.e., urine with osmolality
>800 mosmol/kg; if this is the case, an>800 mosmol/kg; if this is the case, an
extrarenal source of water loss is primarilyextrarenal source of water loss is primarily
responsible for the generation of hypernatremia.responsible for the generation of hypernatremia.

25.  Many patients with hypernatremia areMany patients with hypernatremia are
polyuric; if an osmotic diuresis ispolyuric; if an osmotic diuresis is
responsible, with excessive excretion ofresponsible, with excessive excretion of
Na+-Cl–, glucose, and/ or urea, soluteNa+-Cl–, glucose, and/ or urea, solute
excretion will be >750–1000 mosmol/d.excretion will be >750–1000 mosmol/d.
 More commonly, patients withMore commonly, patients with
hypernatremia and polyuria will have ahypernatremia and polyuria will have a
predominant water diuresis, withpredominant water diuresis, with
excessive excretion of hypotonic, diluteexcessive excretion of hypotonic, dilute
urine.urine.

26.  Adequate differentiation betweenAdequate differentiation between
nephrogenic and central causes of DInephrogenic and central causes of DI
requires the measurement of the responserequires the measurement of the response
in urinary osmolality to DDAVP, combinedin urinary osmolality to DDAVP, combined
with measurement of circulating AVP inwith measurement of circulating AVP in
the setting of hypertonicity.the setting of hypertonicity.

27. Assessment and treatmentAssessment and treatment

28. ManagementManagement
 The underlying cause of hypernatremia shouldThe underlying cause of hypernatremia should
be withdrawn or corrected, whether it is drugs,be withdrawn or corrected, whether it is drugs,
hyperglycemia, hypercalcemia, hypokalemia, orhyperglycemia, hypercalcemia, hypokalemia, or
diarrhea.diarrhea.
 Rate of correction: inRate of correction: in chronic hypernatremiachronic hypernatremia,,
brain cells generate osmoles to minimizebrain cells generate osmoles to minimize
intracellular dehydration. Too rapid correctionintracellular dehydration. Too rapid correction
prompts decrease serum osmolality relative toprompts decrease serum osmolality relative to
high brain osmolality, water passes into the brainhigh brain osmolality, water passes into the brain
with resultant swelling.Therefore, rate ofwith resultant swelling.Therefore, rate of
increase of sodium should not exceed 0.5increase of sodium should not exceed 0.5
meq/L/hmeq/L/h

29.  Monitor fluid balance and electrolytesMonitor fluid balance and electrolytes
closely.closely.
 Hypovolaemic patients :- Give 1-2 L NS IVHypovolaemic patients :- Give 1-2 L NS IV
over 1-3 hours until not orthostatic thenover 1-3 hours until not orthostatic then
give D5W IV to replace half of body watergive D5W IV to replace half of body water
defecit over 1defecit over 1stst
24 hours then maintaing24 hours then maintaing
defecit over next 1-2 days.defecit over next 1-2 days.
 Hypervolaemia :-frusemide 40-80 mg IV orHypervolaemia :-frusemide 40-80 mg IV or
PO qd-bidPO qd-bid
salt poor albumin (25%) 50-100 ml bid –tidsalt poor albumin (25%) 50-100 ml bid –tid
for 48-72 hfor 48-72 h

30.  Central DI: desmopressin (dDAVP) 4 mcgCentral DI: desmopressin (dDAVP) 4 mcg
IV –SQ q 12 hIV –SQ q 12 h
 Nephrogenic DI: treat underlying cause;Nephrogenic DI: treat underlying cause;
salt restriction + thiazide diureticsalt restriction + thiazide diuretic
 Patients with NDI due to lithium mayPatients with NDI due to lithium may
reduce their polyuria with amiloride (2.5–reduce their polyuria with amiloride (2.5–
10 mg/d)10 mg/d)