Disorders of Serum Sodium

Fernanda Payan Schober, MD

Assistant Professor
Nephrology and Hypertension
Fernanda.payan-schober@ttuhsc.edu
Hypernatremia and Hyponatremia

It’s not about the salt;

it’s about the water.
Mostly K Mostly Na
 Plasma osmolality
Serum osmolality= (2 x Sodium) + (Glucose/18) + (Bun/2.8)
– normal aprox 285mOsm/kg

Effective osmolality/ tonicity: changes in Na and glucose (effective

osmoles)
– result in movement of H2O between ICF and ECF compartments.
= (2x Sodium) + (Glucose/18)

Osmolar gap: difference between measured and calculated

osmolality
– >10mosm/kg is elevated and reflects the presence of unmeasured
solutes (ex.ethylene glycol)
 ADH (Antidiuretic Hormone)
aka. Vasopressin or AVP (arginine vasopressin)

Osmolality is only
allowed to vary by
aprox. 1-2%

Tightly regulated
by ADH
• ADH is synthesized
in the supraoptic
and paraventricular
nuclei of the
hypothalamus.

• It is transported in
granules down the
axons to the
posterior pituitary
for storage.
• An increase in osmolality will lead to increased
thirst and ADH secretion from the posterior
pituitary
– which will INCREASE water absorption in the kidney.
– Plasma osmolality will then return to normal.

• Hypovolemia will also lead to ADH secretion

• which will INCREASE water absorption in the kidney.
• will increase blood volume
 Hyponatremia
(serum Na < 135meq/L)
1. Plasma sodium

2. Plasma osmolality

3. Urine sodium

4. Urine Osmolality

5. Assessment of patient’s fluid state

 Signs and symptoms of
Hyponatremia
• Fatigue
• Headache
• Nausea/vomiting
• Confusion
• Seizures
• Coma

• The presence and severity of symptoms are related to:

– Severity of derangement
– Speed at which the derangement developed
* Urine Osm in mOsm/kg
* Urine Na in mmol/L

HYPONATREMIA ([Na] <135mEq/l)

Serum Osmolality

Hypertonic Isotonic Hypotonic

• High glucose “pseudohyponatremia”
• Mannitol • Hyperproteinemia
Look at patient’s volume status (physical exam)
• Glycine • Hyperlipidemia

Hypovolemic Euvolemic Hypervolemic

Urine Osm >100
(↑ ADH)
Urine Osm >100
(↑ ADH)
Urine Na Urine Osm >100 Urine Osm <100
Urine Na <20 (↑ ADH) (No ADH) and Urine Na <20
>20
Extra-renal losses • SIADH • Primary • Systolic Heart Failure
• Vomiting • Adrenal Polydipsia • Cirrhosis
Renal losses
• Diarrhea • Low Solute (“tea •
• Diuretic excess insufficiency Nephrotic syndrome
• Increased • and toast” diet or
• Mineralocorticoid Hypothyroidism
insensible losses Beer potomania)
deficiency
• Salt-wasting
nephropathy
• Cerebral Salt wasting
* Urine Osm in mOsm/kg
* Urine Na in mmol/L

HYPONATREMIA ([Na] <135mEq/l)

Serum Osmolality

Hypertonic Isotonic Hypotonic

“pseudohyponatremia”
• High
glucose
• Mannitol
• Glycine
 Hypertonic Hyponatremia
• The tonicity is increased
– Tonicity = 2Na + Gluc/18

• These can increase the tonicity:

– Glucose
– Mannitol
– Sorbitol

As tonicity increases, fluid shifts from the ICF -> ECF

– this decreases the serum sodium concentration
– [Na] decreases by aprox 1.6meq/L for every 100mg/dL
increase in serum glucose above 100mg/dL.
* Urine Osm in mOsm/kg
* Urine Na in mmol/L

HYPONATREMIA ([Na] <135mEq/l)

Serum Osmolality

Hypertonic Isotonic Hypotonic

“pseudohyponatremia
”

• Hyperproteinemia
• Hyperlipidemia
 Isotonic Hyponatremia
(pseudohyponatremia)
• Lab error
– hyperlipidemia or hyperproteinemia

• The patient does not really have hyponatremia.

• Patients are not symptomatic.

* Urine Osm in mOsm/kg
* Urine Na in mmol/L

HYPONATREMIA ([Na] <135mEq/l)

Serum Osmolality

Hypertonic Isotonic Hypotonic

“pseudohyponatremia”
* Urine Osm in mOsm/kg
* Urine Na in mmol/L

Hypotonic Hyponatremia

Look at patient’s volume status (physical exam)

Hypovolemic Euvolemic Hypervolemic

Urine Osm >100
(↑ ADH)

Urine Na <20 Urine Na >20

Extra-renal losses Renal losses

• Diuretic excess
• Vomiting
• Mineralocorticoid
• Diarrhea deficiency
• Increased • Salt-wasting
insensible nephropathy
losses • Cerebral Salt wasting
 Signs and symptoms of
Hypovolemic Hyponatremia
• Symptoms
Thirst
Fatigue
Weakness
Orthostatic Dizziness

• Signs
BP – Orthostatic Changes
Pulse - elevated
Mucous Membranes - dry
JVP - low
Lungs - clear
Extremities – no edema
* Urine Osm in mOsm/kg
* Urine Na in mmol/L

Hypotonic Hyponatremia

Look at patient’s volume status (physical exam)

Hypovolemic Euvolemic Hypervolemic

Urine Osm >100

(↑ ADH)
and Urine Na <20

• Systolic Heart Failure

• Cirrhosis
• Nephrotic syndrome
 Signs and symptoms of
Hypervolemic Hyponatremia
• Symptoms
Dyspnea on exertion/ Shortness of breath
Paroxysmal Nocturnal Dyspnea
Fatigue
Swelling

• Signs
BP – normal or low
Pulse – normal or elevated if blood pressure is low
JVP – high
Lungs – crackles
Abdomen- possible ascites
Extremities – edema
* Urine Osm in mOsm/kg
* Urine Na in mmol/L

Hypotonic Hyponatremia

Look at patient’s volume status (physical exam)

Hypovolemic Euvolemic Hypervolemic

Urine Osm >100 Urine Osm <100

(↑ ADH) (No ADH)

• SIADH • Primary Polydipsia

• Adrenal • Low Solute (“tea
insufficiency and toast” diet or
• Hypothyroidism Beer potomania)
 Signs and symptoms of
Euvolemic Hyponatremia

Signs
BP – no orthostatic
Changes
Pulse - normal
Mucous Membranes –
normal
Skin turgor- normal
JVP - normal
Lungs - clear
Extremities – no edema
Syndrome of Inappropriate ADH (SIADH)

• Pain
• Nausea
• Emotional distress
• Psychosis
• Malignancy (eg. Small cell carcinoma of the lung)
• Intracranial pathology
• Pulmonary diseases
• Several drugs
– Ex. SSRIs, carbamazepine, cyclophosphamide
Treatment of Hyponatremia
Depends on the acuity and severity of the hyponatremia
– Acute < 24hrs
– Chronic > 48hrs

Hypovolemic Hyponatremia  fluid resuscitation with IV normal saline

Euvolemic Hyponatremia
SIADH  fluid restriction and treat underlying cause; consider loop diuretic,
salt tablets, or ADH antagonist (tolvaptan, conivaptan)
Primary polydipsia  fluid restriction
Low solute diet/beer potomania  normal saline to increase solute load

Hypervolemic Hyponatremia  Fluid restriction, loop diuretic, consider ADH

antagonist
 Rate of correction

• Correct serum Na to 120meq/L at

a rate of 1-2meq/L/hr
• Do not exceed >6 meq/24hrs
• Over correction can lead to
osmotic demyelination
 Osmotic Demyelination
• Decrease in serum tonicity causes astrocytes to swell.

• Increased intracranial pressure forces interstitial Na and H2O out of

the brain into the CSF.

• Astrocytes lose intracellular solutes as well

• (K, organic solutes).

• Organic osmolytes cannot be as quickly replaced when the brain

volume begins to shrink in response to correction of the
hyponatremia

• As a result, brain volume can fall from a value that is initially

somewhat above normal to one below normal with rapid correction
of hyponatremia.
 Osmotic Demyelination Symptoms
• Dysarthria,
dysphagia,
paralysis, seizures,
lethargy,
confusion,
disorientation,
obtundation, and
coma

• Occurs 2-6 days

after rapid Na
correction
 Hypernatremia

Pure water hypotonic

Na gain
loss water loss
Symptoms of Hypernatremia
• Weakness

• Lethargy

• Seizures

• Coma
 Hypernatremia

Pure water loss hypotonic water Na gain

loss

Increased insensible loss

with no fluid replacement
Increased insensible
Diabetes insipidus
loss • inability to obtain
• nephrogenic
• fever water,
• hypothalamic
such as when trapped
in a
collapsed building, or
having suffered a
stroke
 Diabetes Insipidus
Central DI
– deficient secretion of
antidiuretic hormone
(ADH)
– Causes: autoimmune
injury to the ADH-
producing cells, trauma,
pituitary surgery, or
hypoxic or ischemic
encephalopathy. Rare
familial cases have been
described.
 Diabetes Insipidus
Nephrogenic DI
– normal ADH secretion, but
resistance to its water-
retaining effect.
– Causes:
• Childhood -> due to
inherited defects affecting
the V2 receptor or aquaporin
channel
• Adulthood -> acquired;
chronic lithium or
hypercalcemia
How can we differentiate between Central
and Nephrogenic DI?

Give Desmopressin!
 Hypernatremia

hypotonic water
Pure water loss loss Na gain

Gastrointestinal losses
Renal losses
• vomiting
• diuretic use
• nasogastric suction
• osmotic diuresis
• enterocutaneous
• post obstructive diuresis
fistula
• non-oliguric acute renal
• diarrhea
failure
 Hypernatremia

hypotonic water
Pure water loss Na gain
loss

Gastrointestinal losses Renal losses

• vomiting • diuretic use
• nasogastric suction • osmotic diuresis
• enterocutaneous fistula • post obstructive diuresis
• diarrhea • non-oliguric acute renal
failure
 Treatment Hypernatremia
Calculate Water deficit=
Total Body Water – Current Na - Desired Na
Current Na
Cerebral Edema
74 y/o man presents to ED with fatigue after 5 days of gastroenteritis characterized
by n/v/d . BP 85/40, P 110. Physical exam is notable for dry mucous membranes,
flat neck veins, lungs clear to auscultation.

BMP significant for Na+ of 118 meq/L, baseline unknown. Serum osmolality is 266.
Urine osmolality is 377.

Which of the following is the most appropriate next step in this patient’s
management?

A. 3% saline infusion
B. Fluid restriction
C. Intravenous furosemide
D. Normal saline infusion
74 y/o man presents to ED with fatigue after 5 days of gastroenteritis characterized
by n/v/d . BP 85/40, P 110. Physical exam is notable for dry mucous membranes,
flat neck veins, lungs clear to auscultation.

BMP significant for Na+ of 118 meq/L, baseline unknown. Serum osmolality is 266.
Urine osmolality is 377.

Which of the following is the most appropriate next step in this patient’s
management?

A. 3% saline infusion
B. Fluid restriction
C. Intravenous furosemide
D. Normal saline infusion
A 22-year-old woman is evaluated at an on-site medical center after collapsing while
running a marathon. She is disoriented. During the evaluation, she experiences a
generalized tonic-clonic seizure lasting 3 minutes. A wristband indicates that she has
diabetes mellitus.

On physical examination, temperature is normal, blood pressure is 120/60 mm Hg,

pulse rate is 100/min, and respiration rate is 28/min. There is no evidence of
hypovolemia or edema. Cardiopulmonary examination is normal. On neurologic
examination, she is confused but has no evidence of a focal neurologic deficit.

On laboratory studies, the glucose level is 120 mg/dL (120 mmol/L) and the sodium
level is 118 meq/L (118 mmol/L).

Which of the following is the most appropriate next step in this patient’s management?

A. 3% saline infusion
B. 50% glucose by intravenous bolus
C. Intravenous furosemide
D. Normal saline infusion
A 22-year-old woman is evaluated at an on-site medical center after collapsing while
running a marathon. She is disoriented. During the evaluation, she experiences a
generalized tonic-clonic seizure lasting 3 minutes. A wristband indicates that she has
diabetes mellitus.

On physical examination, temperature is normal, blood pressure is 120/60 mm Hg,

pulse rate is 100/min, and respiration rate is 28/min. There is no evidence of
hypovolemia or edema. Cardiopulmonary examination is normal. On neurologic
examination, she is confused but has no evidence of a focal neurologic deficit.

On laboratory studies, the glucose level is 120 mg/dL (120 mmol/L) and the sodium
level is 118 meq/L (118 mmol/L).

Which of the following is the most appropriate next step in this patient’s
management?

A. 3% saline infusion
B. 50% glucose by intravenous bolus
C. Intravenous furosemide
D. Normal saline infusion