Electrolyte

disturbances
By Dr. Haitham Nabeel

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 Normal physiology

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Normal physiology

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Normal physiology

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Normal physiology

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Normal physiology

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Normal physiology

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Normal physiology

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Normal physiology

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Normal physiology

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 Hypernatremia

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Definition

• Eunatremia: a normal concentration of sodium in the

blood (i.e., 136–145 mEq/L).
• Hypernatremia: elevated serum sodium
concentration (> 145 mEq/L)

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Pathophysiology

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 In hypernatremia, serum osmolality is always
increased, resulting in a hypertonic state. This
is either due to a free water deficit (due to
low intake or loss) or increased sodium (due
to high intake or retention).

Clinical pearl!

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Pathophysiology

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Etiology

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 Whatever the underlying cause,
sustained or severe hypernatraemia
generally reflects an impaired thirst
mechanism or responsiveness to thirst.

Clinical pearl!

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Overview of fluid compartment changes

Volume status Total body water Total body sodium

Hypovolemic hypernatremia ↓↓ ↓
Euvolemic hypernatremia ↓ Normal
Hypervolemic hypernatremia ↑ ↑↑

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Clinical features
• Acute hypernatremia (onset < 48 hours)
• Symptoms are primarily neurological and depend on the severity of
hypernatremia.
• Mild symptoms: signs of dehydration
• Decreased salivation
• Dry mucous membranes and skin
• Moderate symptoms
• Confusion
• Irritability, restlessness
• Lethargy
• Muscle weakness
• Hyperreflexia

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Clinical features

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Clinical features
• Acute hypernatremia (onset < 48 hours)
• Severe symptoms: typically occur only with severe hypernatremia (serum
concentration > 160 mEq/L)
• Focal neurological deficits
• Seizures
• Altered consciousness
• Stupor
• Coma
• Chronic hypernatremia (onset > 48 hours ago)
• Often asymptomatic or nonspecific, mild symptoms
• Commonly: signs of dehydration (especially in hypovolemic hypernatremia)
• Rarely: irritability, anorexia, nausea, weakness, and/or altered mental status

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Diagnosis
• Approach
• Confirm hypernatremia (repeat BMP).
• Determine the etiology through clinical evaluation, and, if
unclear, perform diagnostic studies.
• Patient history (e.g., low fluid intake, diarrhea)
• Clinical assessment of volume status (i.e., hypovolemia, euvolemia,
versus hypervolemia) and fluid balance monitoring
• Urine osmolality and urine sodium concentration help differentiate
renal causes from extrarenal causes.
• Additional studies as needed (e.g., water deprivation
test for diabetes insipidus)

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 The etiology of hypernatremia is often
clear from the clinical history and physical
examination alone, and further diagnostic
evaluation may not be needed.

Clinical pearl!

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Diagnosis

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Diagnosis

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Treatment
• Approach
• Identify and treat underlying causes
• Prevent ongoing fluid loss: e.g., fever control, symptomatic
management of gastrointestinal symptoms
• Treat underlying conditions: e.g., desmopressin for central diabetes
insipidus, insulin for hyperglycemia
• Hypernatremia correction
• Determine Na+ correction rates based on whether hypernatremia is
acute or chronic.
• Replace the free water deficit orally with water or IV via an effective
hypotonic solution (typically D5W, or hypotonic 0.45% saline).

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Treatment
• Approach
• Treat complications
• Of disease: Treat acute seizures.
• Of treatment: Begin ICP management if cerebral edema develops
• Hypovolemic patients: volume resuscitation
• Severe volume depletion or shock: Restore euvolemia with isotonic
solutions (e.g., normal saline) before correcting hypernatremia.
• Mild to moderate volume depletion: simultaneous volume
resuscitation and hypernatremia correction (Fluids such as
0.45% normal saline or dextrose 5% with 0.45% normal saline may be
used)

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 The cornerstone
of hypernatremia management is
replacing the free water deficit

Clinical pearl!

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Treatment
• Calculation of free water deficit in hypernatremia
• Calculations of the free water deficit and ongoing water losses are
more accurate than rough estimates. Electrolytes must be carefully
monitored during treatment and regimens should be individually
tailored.
• Combine free water deficit (FWD) and ongoing losses.
• Estimate the patient's total body water (TBW): TBW (L) = k x weight (kg).
• Calculate FWD (L) = TBW (L) x ((serum Na+ concentration/140)-1).
• Estimate ongoing free water losses (input/output chart, insensible
losses).
• Timeframe of volume replacement
• Acute hypernatremia: over 24 hours
• Chronic hypernatremia: over 48– 72 hours

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Treatment
• Correction of free water deficit
• Acute hypernatremia (onset within < 48 hours)
• Decrease Na+ concentration by 1–2 mEq/L/hour (i.e., replace entire free water
deficit in < 24 hours).
• Estimated fluid replacement regimen: ∼ 3 mL/kg/hour of IV D5W or enteral water
• Chronic hypernatremia (onset within > 48 hours)
• Gradually restore a normal Na+ level by decreasing Na+ concentration by 0.5
mEq/L/hour (max. 10–12 mEq/L per 24 hours).
• Oral rehydration with free access to water may be sufficient in stable and alert patients.
• Estimated fluid replacement regimen: 1.35 mL/kg/hour of IV D5W or enteral water
• Adjustment of infusion rate
• Fluids other than D5W or sterile water require a different flow rate to provide the same
amount of free water.
• Depending on serial Na+ concentration

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Complications
• Complications of hypernatremia
• Intracranial hemorrhage
• Cell dehydration and shrinkage of brain tissue can cause intracranial vessels to rupture.
• Hemorrhages may lead to irreversible neurological deficits.
• Osmotic demyelination syndrome
• Demyelinating brain lesions from the acute rise in serum sodium levels and serum
osmolality
• More commonly seen with overcorrection of hyponatremia
• Rhabdomyolysis: Severe hypernatremia can damage the cell membranes of muscle
cells.
• Complications of hypernatremia treatment
• Cerebral edema: may develop from rapid correction of chronic hypernatremia
• Hypervolemia complications: secondary to hypernatremia correction with large-
volume IV fluid administration (e.g., noncardiogenic pulmonary edema)

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 Hyponatremia

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Hyponatremia
• Eunatremia: a normal concentration of sodium in the blood
(i.e., 136–145 mEq/L).
• Hyponatremia: reduced serum sodium concentration (< 135
mEq/L)
• Classification
• Severity
• Mild hyponatremia: 130–135 mEq/L
• Moderate hyponatremia: 125–129 mEq/L
• Severe hyponatremia (profound): < 125 mEq/L
• Disease onset
• Acute hyponatremia: < 48 hours
• Chronic hyponatremia: ≥ 48 hours
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Pathophysiology

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Etiology

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 Thiazide diuretic use and SIADH are the
most common causes of hyponatremia in
the emergency department.

Clinical pearl!

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Etiology
• Hypertonic hyponatremia
• Definition: low measured serum Na+ concentration and high serum osmolality
• Serum osmolality: > 295 mOsm/kg H2O
• Causes (Hyperglycemia, IV mannitol, IV radiocontrast use)
• Isotonic hyponatremia (pseudohyponatremia)
• Definition: low measured serum Na+ concentration and normal serum osmolality
• Serum osmolality: 280–295 mOsm/kg H2O
• Asymptomatic laboratory artifact falsely indicating hyponatremia when sodium has
not been reduced or diluted
• Due to very high amounts of protein or lipids in the plasma
(e.g., hyperlipidemia, multiple myeloma), which then alter the plasma water
concentration

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 Isotonic hyponatremia should always be
excluded as a cause of hyponatremia to
avoid unnecessarily aggressive treatment.

Clinical pearl!

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Pathophysiology

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Pathophysiology
Volume status Serum osmolality Total body water Total body sodium
Hypovolemic hypotonic ↓ ↓ ↓↓
hyponatremia
Euvolemic hypotonic ↓ ↑ ↓ or Normal
hyponatremia
Hypervolemic hypotonic ↓ ↑↑ ↑
hyponatremia
Isotonic hyponatremia Normal ↑ Normal

Hypertonic ↑ ↓ Normal
hyponatremia

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Clinical features

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Clinical features

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 The likelihood of symptoms occurring is related to
the speed at which hyponatraemia develops rather
than the severity of hyponatraemia. Most patients
with chronic hyponatremia are asymptomatic
and symptoms typically only occur
with serum sodium concentration < 120 mEq/L.

Clinical pearl!

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Diagnosis
• Diagnostic approach to hyponatremia
• Confirm hyponatremia: Repeat BMP.
• Exclude hyperglycemia: Check serum glucose.
• Check the serum osmolality (SOsm): first step in the evaluation of
confirmed hyponatremia
• Low serum osmolality (< 280 mOsmol/kg H2O): hypotonic
hyponatremia (true hyponatremia; most common)
• High serum osmolality (> 295 mOsmol/kg H2O): hypertonic hyponatremia
• Normal serum osmolality (280–295 mOsmol/kg H2O): isotonic
hyponatremia or pseudohyponatremia
• Consider additional focused diagnostic evaluation to identify the
underlying cause.

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Diagnosis
• Interpretation of urine osmolality (UOsm): to determine antidiuretic hormone (ADH)
activity
• UOsm ≤ 100 mOsm/kg H2O: Dilute urine (ADH is suppressed)
• UOsm > 100 mOsm/kg H2O: concentrated urine (ADH is appropriately or inappropriately
elevated)
• Determination of volume status: to determine if ADH activity is appropriate (i.e., in
response to low effective arterial blood volume) or inappropriate (e.g., in SIADH)
• History: e.g., significant nausea/vomiting or recent hemorrhage might suggest low effective
arterial volume due to hypovolemia
• Clinical assessment of volume status
• Laboratory studies
• Interpretation of UNa and/or FENa : to determine if the cause is renal or extrarenal
• UNa < 20–30 mEq/L and/or FENa < 1%: may suggest extrarenal loss of sodium
• UNa ≥ 20–30 mEq/L and/or FENa > 1%: may suggest renal loss of sodium

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 Serum
osmolality measurement is the
first step in the evaluation of
verified hyponatremia.

Clinical pearl!

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Treatment
• Approach
• The rate of sodium correction depends on acuity and severity of
symptoms.
• Acute hyponatremia and/or severely symptomatic hyponatremia
• Initial aggressive treatment with IV hypertonic saline to prevent cerebral edema
• Aim to initially increase serum sodium by 4–6 mEq/L.
• Once stabilized, identify and treat the underlying cause.
• Chronic hyponatremia
• Careful correction by treating the underlying cause
• Avoid sodium overcorrection to minimize the risk of osmotic demyelination
syndrome (ODS).
• Recommended sodium correction rates for chronic hyponatremia depend on the
presence of high-risk factors for ODS.

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 Once specific treatment is given (e.g.,
discontinuation of diuretics, corticosteroids
for hypocortisolism), there is a high risk of rapid
autocorrection causing a dangerous increase
in sodium.

Clinical pearl!

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Treatment
• Acute hyponatremia and/or severely symptomatic hyponatremia
• The goal of treating acute and/or severely symptomatic hyponatremia is the rapid increase of
serum sodium with hypertonic saline to reverse neurological symptoms and prevent brain
herniation.
• Indications (any of the following):
• Severely symptomatic hyponatremia (regardless of onset)
• Symptomatic acute hyponatremia (< 48 hours)
• Asymptomatic acute hyponatremia (< 48 hours) with decrease in Na+ concentration of > 10
mEq/L
• Initial sodium goal: ↑ serum sodium 1–2 mEq/L/hour until an increase of 4–6 mEq/L has
been reached within 6 hours
• Regimens for rapid correction
• Severely symptomatic hyponatremia: hypertonic saline bolus (e.g., 3% NaCl). A common approach
is to give an initial bolus of 150 mL over 20 minutes, which may be repeated once or twice over the
initial hours of observation, depending on the neurological response and rise in plasma sodium
• Acute hyponatremia without severe symptoms: hypertonic saline infusion (e.g., 3% NaCl infusion)

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Treatment
• Chronic hyponatremia without severe symptoms
• The goal of treating chronic hyponatremia is a slow correction of
serum sodium levels to prevent overcorrection and subsequent osmotic cell
damage. Treatment depends on the underlying cause
• Goal: The goal correction rate depends on the risk of ODS
Patients at normal risk Patients with high-risk
for ODS factors for ODS
Minimum correction 4–8 mEq/L within 24 4–6 mEq/L within 24
rate (goal) hours hours
Maximum correction 10–12 mEq/L within 24 8 mEq/L within 24 hours
rate (limit) hours
18 mEq/L within 48 hours

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 Rapid correction of chronic
hyponatremia can cause osmotic
demyelination syndrome! Do not exceed
hourly or daily maximum correction
limits.

Clinical pearl!

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Treatment
• Cause-specific treatment for hyponatremia
• Recommended in the following situations:
• Chronic hyponatremia without severe symptoms
• Acute and/or severely symptomatic hyponatremia after
stabilization and resolution of symptoms
• Stop all medications that may be causing hyponatremia.
• Hypovolemic hyponatremia: Isotonic saline (e.g., 0.9% NaCl)
• Euvolemic hyponatremia: Fluid restriction (all fluids, not just
free water)
• Hypervolemic hyponatremia: Strict fluid restriction with or
without cautious use of loop diuretics

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Treatment

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Complications
• Edema: sudden decrease in intravascular Na+ level
→ reduced intravascular osmotic pressure → water moving into
the interstitium and intracellular space → edema
• Cerebral edema → elevated intracranial pressure → risk of brain
herniation
• Noncardiogenic pulmonary edema
• Bone fractures
• Permanent neurological damage
• Death
• Treatment-associated complications
• Intracranial hemorrhage
• Osmotic demyelination syndrome (ODS)
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 Correcting hyponatremia too rapidly may cause two
complications: From low to high,
your pons will die (osmotic demyelination
syndrome); from high to low, your brain
will blow (cerebral edema).

Clinical pearl!

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Complications
• Osmotic demyelination syndrome (ODS)
• Definition: damage to the myelin sheath of the white matter in the CNS
caused by a sudden rise in serum osmolality
• Central pontine myelinolysis
• Most common type
• Affects the central region of the pons
• Extrapontine myelinolysis: can affect the cerebellum, lateral geniculate
body, thalamus, putamen, cortical, and/or subcortical white matter
• Causes
• Iatrogenic: rapid correction of chronic hyponatremia
• High-risk factors for ODS: alcohol use disorder, malnutrition, liver disease, hypokalemia,
initial sodium concentration ≤ 105 mEq/L
• Rapid changes in other osmotically active solutes (e.g., glucose)
• Acute severe hypernatremia

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Complications
• Osmotic demyelination syndrome (ODS)
• Clinical features
• Symptoms first develop several days after the correction of hyponatremia.
• There can be a wide range of symptoms, depending on the degree and location
of demyelination
• Central pontine myelinolysis
• Altered level of consciousness, including coma
• Locked-in syndrome
• Impaired cranial nerve function: dysarthria, dysphagia , and diplopia
• Worsening quadriparesis (initially flaccid, later spastic)
• Extrapontine myelinolysis: parkinsonism (tremor, rigidity), dystonia,
chorea or choreoathetosis, myoclonus, opsoclonus, ataxia, gait disorders
• Other general symptoms: seizures, encephalopathy, catatonia, mutism, frontal
release signs, depression

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Complications
• Osmotic demyelination syndrome (ODS)
• Diagnostics: Imaging may only show signs of ODS days to weeks after
the onset of symptoms.
• MRI: imaging technique of choice
• CT: easier to conduct in ventilated patients
• Treatment: supportive care (with close monitoring of electrolytes);
prevention is key to improving patient outcomes.
• Prognosis: variable; ranging from fatal to residual deficits or a
complete recovery
• Prevention
• Avoid overcorrection of chronic hyponatremia
• Frequent reevaluation of the serum sodium concentration
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Central pontine
myelinolysis
Cranial MRI (axial section; T2-weighted)
A hyperintense signal in the central pons is
visible (green overlay). This hyperintensity
has a characteristic trident shape that is
pathognomonic of central pontine
myelinolysis (CPM), which predominantly
affects the transverse pontine fibers and
spares the corticospinal tracts. CPM is caused
by the rapid correction of chronic
hyponatremia.

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 SIADH

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Etiology
• Increased pituitary ADH secretion
• CNS conditions (Stroke, Trauma, bleeding, Infection)
• Following neurosurgery (e.g., transsphenoidal pituitary
surgery)
• Psychosis
• Chronic disease
• Pulmonary
• Pneumonia
• COPD
• HIV
• Acute intermittent porphyria
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Etiology
• Drugs
• Anticonvulsants (e.g., carbamazepine, valproate)
• Antidepressants
• SSRIs (e.g., sertraline)
• MAO inhibitors
• TCAs (e.g., amitriptyline)
• Antineoplastic agents
• Mitotic inhibitors (e.g., vincristine)
• Alkylating agents (e.g., cyclophosphamide, cisplatin)
• Antipsychotics (e.g., haloperidol)
• Analgesics (e.g., NSAIDS, opioids)
• Illicit substances (e.g., MDMA)

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Etiology

• Paraneoplastic ectopic ADH production

• Small cell lung carcinoma
• Head and neck cancer
• Extrapulmonary small cell carcinoma
• Olfactory neuroblastoma
• Nephrogenic SIADH
• Mutation of vasopressin-2 receptor gene

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Etiology

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Pathophysiology
• ↑ ADH secretion → receptor-mediated signaling cascade in the distal
convoluted tubules and the collecting ducts of the kidneys → build-up
of additional water canals (aquaporin-2) in the luminal cell membrane
• Water is drawn out of the urine and into the
hyperosmolar kidney tissue → concentration of urine and ↑ urine
osmolality (becomes higher than serum osmolality)
• Water retention → ↓ serum osmolality with transient volume
expansion → ↑ ANP, ↑ BNP, and ↓ aldosterone → ↑
urinary sodium and water excretion → euvolemic hyponatremia
• Osmotic fluid shifts → cerebral edema and ↑ intracranial
pressure (may occur in patients with extremely low Na+ levels)

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Clinical features
• Symptoms of hyponatremia
• Chronic hyponatremia may be asymptomatic and CNS symptoms are
less common.
• Mild
• Anorexia, Nausea, vomiting, Headache, Muscle cramps
• Moderate
• Muscle weakness, Lethargy, Confusion
• Severe
• Seizures, Altered consciousness
• Other clinical features
• Normotension
• Symptoms of the underlying condition
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 SIADH patients are
usually euvolemic, normotensive, and have
no edema. A hyponatremic patient
with edema should raise suspicion for other
conditions (e.g. congestive heart failure).

Clinical pearl!

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Diagnosis
• Approach
• Follow the diagnostic approach to hyponatremia to
confirm euvolemic hypotonic hyponatremia.
• Order initial blood studies (e.g., CMP, serum osmolality) and urine
studies (e.g., sodium, creatinine, osmolality).
• Order additional studies to exclude other causes of euvolemic
hypotonic hyponatremia
• Confirm the patient meets the diagnostic criteria for SIADH
• Consider additional tests for possible underlying causes of
SIADH, e.g.:
• X-ray and/or CT chest
• CT or MRI head

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Diagnosis

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Treatment
• Approach
• The following management applies to patients with
nonacute, nonsevere hyponatremia associated with
SIADH and after the initial stabilization of patients with
acute and/or severely symptomatic hyponatremia.
• Management
• Restrict all fluids; do not limit salt or protein intake.
• If initial measures fail, consider pharmacotherapy.
• Manage the underlying cause (e.g., nausea, infection, cancer,
offending medications).

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 In patients with acute and severely
symptomatic hyponatremia, immediate use
of hypertonic saline can treat and/or prevent
serious neurologic complications (e.g., cerebral
edema, brain herniation, seizures, altered mental
status).

Clinical pearl!

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Treatment

• Fluid restriction
• Restriction of all fluids (e.g., PO intake, IV fluids,
medications, IV flushes) is the first-line treatment for
SIADH.
• Recommend < 1000 mL/day for most patients.
• Adjust based on the patient's response (i.e.,
serum sodium levels and urine output).
• Ideally, daily fluid intake should be 500 mL less than daily
urine output.
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Treatment
• Pharmacotherapy
• These agents are used to increase free water excretion. Medications
should be ordered in consultation with a specialist.
• Indications
• Fluid restriction fails to increase serum sodium.
• Agents
• Vaptans, e.g.:
• Conivaptan
• Tolvaptan
• Urea
• Demeclocycline
• Low-dose loop diuretics (e.g., furosemide) combined with oral salt tablets

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THANK YOU!

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