Overview and Hypo/HyperNATREMIA

what is the primary electrolyte in ECF

Sodium (140 mEq/L)

what is the primary electrolyte in the ICF?

Potassium (150 mEq/L)

which fluid space is serum concentration based on?

ECF!!!!!!!!

Why should you repeat labs and be skeptical when values are unexpected?

A trend in labs is better than one lab/test - must think through if the labs done would be a good reflection of electrolyte total in the body/serum

normal value of sodium

140 mEq/L

normal value of chloride

100 mEq/L

normal value of BUN

15 mg/dL

normal value of glucose

~ 90 mg/dL

normal value of potassium

4 mEq/L

normal value of CO2

24 mEq/L

normal value of SCr

1 mg/dL

which electrolyte is not on the BMP and usually needs to be specifically ordered?

Magnesium

Disorders of sodium are really disorders of _________________________

water homeostasis

what is the highest solute concentration in the loop of Henle

up to 1,100-1,200 mOsm/kg

T/F: water balance determines the sodium concentration while sodium balance determines the water status

True

which electrolyte is best friends with water

Sodium (Julia and Sam<3)

what is the sodium range for mild hyponatremia?

125-135 mEq/Lwhat

what is the sodium range for moderate hyponatremia?

120-125 mEq/L

what is the sodium range in severe hyponatremia?

< 120 mEq/L

which stage of hyponatremia is almost never symptomatic?

mild hyponatremia

which stage of hyponatremia can be characterized by presence of neurologic complications such as seizures?

Severe hyponatremia

Symptoms associated with hyponatremia are dependent on what?

the concentration of sodium and the rate of change of the concentration of sodium

Which type of hyponatremia may be asymptomatic?

Chronic and/or mild hyponatremia

What are the neurologic symptoms associated with hyponatremia

headache, confusion, lethargy, seizures, coma

T/F: hyponatremia is only associated with decreased or normal ECF volumes

False

What are the broad steps to take the determine type and severity of hyponatremia?

1. determine the patient has low sodium (< 135 mEq/L)

2. determine the patient’s plasma tonicity (isotonic, hypertonic, hypotonic)

3. determine the patient’s ECF volume status (isovolemic, hypervolemic, hypovolemic)

which plasma tonicity is most commonly associated with hyponatremia?

hypotonic

What is isotonic hyponatremia?

a low serum sodium concentration with normal measured serum osmolality

causes of isotonic hyponatremia

hyperlipidemia/hyperproteinemia (not a real clinical problem)

treatment of isotonic hyponatremia?

repeat lab - lipids and proteins can sometimes cause volume displacement in the serum reducing the volume of plasma available for measurement of sodium (leading to falsely low sodium concentrations)

what is hypertonic hyponatremia?

a low serum sodium concentration with increased measured serum osmolality

what causes hypertonic hyponatremia?

hyperglycemia (500-600 mg/dL)

how to calculate for corrected sodium in hypertonic hyponatremia?

Na measured + 1.6 x (every 100 mg/dL glucose > 100)

treatment for hypertonic hyponatremia?

reduce serum glucose (insulin) and re-check sodium

once blood glucose is corrected to 100 mg/dL in hypertonic hyponatremia, the patient’s serum sodium will be _________________

~137 mEq/L

clinical assessment of mild to moderate volume loss:

thirst, delay in capillary refill, postural dizziness, weakness, dry mucous membranes and axillae, cool clammy extremities and collapsed peripheral veins, tachypnea, tachycardia with pulse rate > 100 beats/min or postural pulse increment of 30 beat/min or more, postural hypotension, low JVP, oliguria

clinical assessment of severe volume loss and hypovolemic shock:

depressed mental status (or loss of consciousness), peripheral cyanosis, reduced skin turgor (in young patients), marked tachycardia, low pulse volume, supine hypotension (systolic BP < 100 mmHg)

what is hypotonic euvolemic hyponatremia

increase in total body free water with relative to no change in total body sodium

causes of hypotonic euvolemic hyponatremia

SIADH-Syndrome of inappropriate AntiDiuretic Hormone, Drug-induced SIADH, and psychogenic polydipsia

what is antidiuretic hormone and what does it do?

pulls free water out of the urine and back into the blood stream via aquaporin channels

what is SIADH

over-activity of ADH which concentrates urine and leads to excess free water in ECF… cause of hyponatremia

what is psychogenic poldipsia?

psychological disorder that causes patients to intake > 20 liters of free water per day which the kidneys cannot excrete and leads to edema 😐

treatment for hypotonic euvolemic hyponatremia

address/treat the underlying disorder/cause, water restriction 1000-1200 mL/day, vasopressin receptor antagonists, sodium chloride and loop diuretics

what should be the first treatment of hypotonic euvolemic hyponatremia if the underlying cause is unknown or will take a long time to treat

water restriction and vasopressin receptor antagonists

Examples of vasopressin receptor antagonists?

Tolvaptan, conivaptan, demeclocycline

what is the last resort treatment for hypotonic euvolemic hyponatremia?

sodium chloride and loop diuretic because it does not last long-term as a solution but is useful to bridge whole trying to address underlying disorder

which drugs can cause SIADH?

SSRIs (and SNRIs), Carbamazepine, Opiates

what does demeclocycline induce?

nephrogenic diabetes insipidus (blocks AVP at the collecting duct)

dosing of demeclocycline?

300 mg PO BID-QID

risks associated with demeclocycline use

renal tubular damage and AKI

when should demeclocycline be avoided?

in children < 8 years and pregnancy due to changes in tooth development

which vasopressin antagonists are V2 receptor antagonists?

demeclocycline and tolvaptan

which vasopressin antagonists are V1 and V2?

Conivaptan

how is conivaptan administered?

IV only

FDA indication for conivaptan

acute euvolemic hyponatremia

how is tolvaptan administered?

PO

FDA indications for tolvaptan?

hyper and euvolemia hyponatremia due to HF, cirrhosis, or SIADH; autosomal dominant polycystic kidney disease

What is tolvaptan a substrate of?

CYP3A4 and P-glycoprotein

dosing for tolvaptan

15-60 PO once a day

ADRs for tolvaptan

thirst, polyuria, constipation

BBW for tolvaptan

Hepatotoxicity (assess LFTs if used for more than 1-2 weeks)

what is hypotonic hypervolemic hyponatremia

increase in sodium and water but a greater increase in free water than sodium (lower tonicity but expansion of both ICF and ECF)

causes of hypotonic hypervolemic hyponatremia:

cirrhosis, HF, nephrotic syndrome (losing tons of proteins due to glomerular damage)

treatment for hypotonic hypervolemic hyponatremia

treat underlying disorder, water restriction 1000-1200 mL/day AND salt restriction 2000 mg/day, loop diuretics, V2 receptor antagonist (Tolvaptan)

why can loop diuretics be helpful in hypotonic hypervolemic hyponatremia

it helps with edema and helps concentrate sodium

symptoms of hypotonic hypervolemic hyponatremia?

JVD, edema, elevated BNP……

what is hypotonic hypovolemic hyponatremia

loss of sodium and water but lose more sodium than water (there is a reduction in tonicity and a decrease in the ECF volume)

Non-renal causes of hypotonic hypovolemic hyponatremia

GI losses such as diarrhea/vomiting; Urinary Na < 20 mEq/L

why do GI losses such as diarrhea and vomiting lead to hypotonic hypovolemic hyponatremia?

isotonic or hypotonic fluid loss leads to stimulation of thirst (AVP) which leads to the patient drinking more hypotonic fluid and continuing fluid loss

renal causes of hypotonic hypovolemic hyponatremia

thiazide diuretics (causes patient to continue to lose more sodium and decrease in [Na]); urinary Na > 20 mEq/L

treatment for hypotonic hypovolemic hyponatremia

0.9% sodium chloride to replace fluid and sodium loss

what is the process of hyponatremia assessment

1. obtain medical history including medications

2. obtain vital signs (BP, HR, temp, RR)

3. measure serum [Na] and consider rate of decline of [Na]

4. measure and calculate serum osmolality

5. determine osmolality category

6. assess ECF volume status

7. determine likely cause

8. define treatment goal

Do not exceed [Na] increase of _______________________

> 0.5 mEq/L/hr

how to tell if hyponatremia is caused by renal or non-renal

based on urinary Na: renal = > 20 mEq/l; non-renal = < 20 mEq/L

what can happen if hyponatremia is corrected too rapidly?

ODS (osmotic demyelination syndrome) also known as central pontine myelinolysis

What is the first goal of hyponatremia correction?

stop symptoms and prevent seizures for the first 6-12 hours

What is the second goal of hyponatremia correction?

correct [Na] to normal range 135-145 mEq/L in the next 2-3 days (weeks, months….) of treatment

what determines how long you can take/how quickly you can correct hyponatremia?

dependent on how long it took for the hyponatremia to develop (if it took a while you have longer to correct, if happened quickly can move quicker)

what are the maximums for hyponatremia correction

6-8 mEq/L/day up to 12 mEq/L/day if acute OR 0.25-0.5 mEq/L/hr

which type of hyponatremia is a medication emergency?

hypotonic hypovolemic hyponatremia

patients who have acute, severe, hypotonic hypovolemic hyponatremia experience a rapid decline in serum [Na] of _____

< 110 mEq/L

what are severe symptoms of acute, hypotonic hypovolemic hyponatremia

seizures

What can be used to initially manage acute severe hypotonic hypovolemic hyponatremia

hypertonic saline (3% or 23.4%)

dosing of hypertonic saline for patients with severe hypotonic hypovolemic hyponatremia

50 mL of 3% NaCl and then check the patient’s serum sodium; repeat if sodium has not gone up; STOP once serum [Na] is >= 120 mEq/L or severe symptoms resolve)

once a patient experiencing hypotonic hypovolemia gets their Na up to 120 or seizures stop what types of fluids are given next?

Isotonic

What can be combined with the hypertonic saline fluid to help treat severe hypotonic hypovolemic hyponatremia

loop diuretics to enhance free water clearance

what can cause osmotic demyelination

rapid onset of acute hypernatremia or rapid correction of chronic hyponatremia because they lead to rapid increases in plasma sodium concentrations

what leads to cerebral edema?

rapid onset of acute hyponatremia or rapid correction of chronic hypernatremia because they cause a rapid decrease in plasma sodium concentrations

what is usually the fluid status in hypertonic hypernatremia

hypovolemia

what occurs in hypertonic hypernatremia

tonicity increases and water shifts from ICF to ECF (water loss exceeds Na+ loss)

what happens to sodium and water in hypovolemic hypernatremia

water and sodium loss with a great water loss

what causes hypovolemic hypernatremia

over-diuresis (usually loop diuretics)

clinical presentation of hypovolemic hypernatremia

orthostasis, hypotension, tachycardia, dry mucous membranes.

Treatment for hypovolemic hypernatremia

normal saline given IV until the BP/HR are stable, then give free water replacement (D5W)

what is happening to sodium and water in euvolemic hypernatremia

only water loss, sodium concentration stays the same

causes of euvolemic hypernatremia

diabetes insipidus (salty urine)

clinical presentation of euvolemic hypernatremia

polyuria, polydipsia, lethargy, seizures

treatment for euvolemic hypernatremia

free water replacement (D5W) and vasopressin (DDAVP)

what is happening with sodium and water in hypervolemic hypernatremia

sodium and water gain - there is more sodium gained than water

causes of hypervolemic hypernatremia

sodium overload