ELECTROLYTE IMBALANCE

HYPONATREMIA

Hyponatremia

• Defined as sodium concentration < 135 mEq/L• Generally considered a disorder of water as

opposed to disorder of salt• Results from increased water retention• Normal physiologic measures allow a person

to excrete up to 10 liters of water per day which protects against hyponatremia

• Thus, in most cases, some impairment of renal excretion of water is present

Remember the basics of the body’s fluid compartments.

• TBW = WEIGHT x .5 (women) or .6 (men)• TBW x 1/3 = ECF• TBW x 2/3 = ICF• ECF x 2/3 = Interstitial compartment• ECF x 1/4 = Intravascular compartment• Water will move freely to balance osmolalities:

Therefore all compartments have equal osmolalities.

• Sodium is the major extracellular cation.

The Axis of Sodium

• The kidney controls the size of the ECFV by controlling Na excretion.

• Kidney is programmed to keep the ECFV within an acceptable range. The kidney will use 3 systems to regulate ECFV (afferent sensory arm to sense ECFV and efferent arm to effect change).– Renin – AT II – Aldosterone axis

– ANP system

– Sympathetic nervous system

King Sodium : Rules the ECFV

• The total amount of Na in the ECF is the main determinant of the size of the ECFV.

• If ECF Na increases so will the ECFV. • The edematous states: CHF, liver cirrhosis,

and nephrotic syndrome are examples of increased total body Na in the extracellular compartment causing volume overload.

Osmolality vs. Tonicity

• Osmolality: total solute concentration in a fluid compartment.

• Tonicity: the combined ability of solutes to produce a osmotic driving force that causes water to move from one compartment to another. – Solutes that are capable of moving water are called “effective

osmoles”. – These are solutes that are unable to cross from the extracellular to

the intracellular compartment: sodium, glucose, mannitol, sorbitol. NOT UREA. 

– The control of tonicity will determine the normal state of cellular hydration and cell size. This is of particular concern in the case of brain cells.

To regulate water excretion and keep the tonicity (Na concentration) of ECFV constant there must be: • Adequate GFR.• Delivery of GF to the concentrating and

diluting segments of the loop of Henle and distal nephron.

• Intact tubular concentrating and diluting mechanisms,

• Appropriate turning on/off of ADH. • ADH responsiveness of the kidney.

ETIOLOGY

Causes

• Normal ADH response to low sodium is to be suppressed to allow maximally dilute urine to be excreted thereby raising serum sodium level

• Psuedohyponatremia – High blood sugar (DKA) or protein level (multiple myeloma) can cause falsely depressed sodium levels

• Causes of Hyponatremia can be classified based on either volume status or ADH level– Hypovolemic, Euvolemic or Hypervolemic– ADH inappropriately elevated or appropriately

suppressed

ADH suppresion

• Conditions which ADH is suppressed– Primary Polydipsia

– Low dietary solute intake “Tea and Toast syndrome” or “Beer Potomania”

– Advanced Renal Failure

ADH elevation

• Conditions which ADH is elevated– Volume Depletion

• True volume depletion (i.e. bleeding)• Effective circulating volume depletion (i.e. heart

failure and cirrhosis)

– Exercised induced hyponatremia– Thiazide Diuretics– Adrenal insufficiency– SIADH

First step in Assessment: Are symptoms present?

• Hyponatremia can be asymptomatic and found by routine lab testing

• It may present with mild symptoms such as nausea and malaise (earliest) or headache and lethargy

• Or it may present with more severe symptoms such as seizures, coma or respiratory arrest

Presentation determines if immediate action is needed

• If severe symptoms are present, hypertonic saline needs to be administered to prevent further decline

• If severe symptoms are not present, can start by initiating fluid restriction and determining cause of hyponatremia

• Oral fluid restriction is good first step as it will prevent further drop in sodium

• NOTE: This does not mean that you can’t give isotonic fluids to someone who is truly volume depleted

WHAT NEXT?

• With no severe symptoms and fluid restriction started, next step is to assess volume status to help determine cause

• Hypovolemic – urine output, dry mucous membranes, sunken eyes

• Euvolemic – normal appearing

• Hypervolemic – Edema, past medical history, Jaundice (cirrhosis), S3 (CHF)

Workup for Hyponatremia

• 3 mandatory lab tests– Serum Osmolality– Urine Osmolality– Urine Sodium Concentration

• Additional labs depending on clinical suspicion– TSH, cortisol (Hypothryoidism or Adrenal

insufficiency)– Albumin, BMP, triglycerides and SPEP

(psuedohyponatremia, cirrhosis, MM)

How to interpret the tests?

• Serum Osmolality– Can differentiate between true hyponatremia,

pseudohyponatremia and hypertonic hyponatremia

• Urine Osmolality– Can differentiate between primary polydipsia and

impaired free water excretion

• Urine Sodium concentration– Can differentiate between hypovolemia

hyponatremia and SIADH

Additional Tests

• TSH – high in hypothyroidism• Cortisol – low in adrenal insufficiency, though

may be inappropriately normal in infection/stressful state, therefore should get Corti-Stim test to confirm

• Head CT and Chest Xray – May see evidence of cerebral salt wasting or small cell carcinoma which can both cause hyponatremia

Chronic Hyponatremia

• Keep in mind that to develop progressive hyponatremia you need an impairment of water excretion as well as continued water intake. (ESRD patient).

• Before you diagnose a specific etiology you can always restrict free water intake to 800 cc / day as a temporizing / stabilizing measure

Treatment

• The rapidity of the development of hyponatremia is more important than the actual value of the serum sodium concentration.

• In the chronic / slow setting the cells have time to transport intracellular solutes to the extracellular space to account for the hypotonicity of the extracellular space. – If this is corrected rapidly osmotic demyelination

syndrome can occur. – The most severe form of ODS will be quadriplegia (the

locked in syndrome).

Treatment is based on symptoms

• Patients with serum sodium above 120 are generally asymptomatic

• Symptoms tend to occur at serum sodium levels lower than 120 or when a rapid decline in sodium levels occur

• Patients can have mild symptoms at sodium concentrations of 110-115 mEq/L when this level is reached gradually

Severe symptoms present

• As stated earlier, symptoms dictate treatment• If severe symptoms are present, starting bolus

of 100 ml of 3% hypertonic saline which generally raise serum sodium level by 2-3 mEq/L

• Goals for correction:– 1.5 to 2 mEq/L per hour for first 3-4 hours until

symptoms resolve– Increase by no more than 10 mEq/L in first 24 hrs– Increase by no more than 18 mEq/L in first 48 hrs

What if little to no symptoms are present?

• Oral fluid restriction is the first step– No more than 1500 mL per day – NOTE: This only pertains to oral fluid, isotonic IV

fluids do not count towards fluid intake

• If volume depletion is present, isotonic (0.9%) saline can be given intravenously

• Careful monitoring should be used whether symptoms are present or not– Serum sodium levels should be drawn every 4-6 hours

or more frequently if hypertonic saline is used

Formulas that may help: How much sodium does the patient need?

• Sodium deficit = Total body water x (desired Na – actual Na)

• Total body water is estimated as lean body weight x 0.5 for women or 0.6 for men

How about an example:

• 60 kg woman with sodium level of 116

• How much sodium will bring him up to 124 in the next 24 hours?

• Sodium needed = 0.5 x 60 x (124-116) = 240

• Hypertonic saline contains 500 mEq/L of sodium

• Normal saline contains 154 mEq/L of sodium

Example (continued)

• The patient needs 240 mEq in next 24 hours

• That averages to 10 mEq per hour or 20 mL of hypertonic saline per hour

• However, this will only raise the serum sodium by 0.33 per hour therefore, increasing the rate 60 mL to 90 mL will produce the desired rate of serum sodium increase of 1.0 to 1.5 mEq per hour until symptoms resolve

Volume overloaded states

• Water restriction is also the appropriate treatment for hyponatremia.– This will deal with the water excretion problem and loop

diuretics will deal with the hypervolemia state (sodium overload problem).

– Thiazides can acutely worsen the situation. – IF THERE IS NO HYPONATREMIA IN THE VOLUME

OVERLOAED STATE THEN THERE IS NO NEED TO RESTRICT WATER.

– IF EDEMA IS THE SOLE PROBLEM THEN IT IS A PROBLEM OF SODIUM EXCRETION – AND YOU WILL NEED TO INCREASE SODIUM EXCRETION AND RESTRICT SODIUM INTAKE.

Acute / Symptomatic Hyponatremia

• Correct Na no faster than 1 meq / L per hour until achieving a 6-8 meq / L increase, then .5 meq / L / hour or less.

• Permit no more than 10-12 meq/ L increase in Na over 1st 24 hours.

• Slow or stop infusions when symptoms improve. • The goal is not correct the serum sodium, but to

correct the cerebral edema.

What if the sodium increases too fast?

• The dreaded complication of increasing sodium too fast is Central Pontine Myelinolysis which is a form of osmotic demyelination

• Symptoms generally occur 2-6 days after elevation of sodium and usually either irreversible or only partially reversible

• Symptoms include: dysarthria, dysphagia, paraparesis, quadriparesis, lethargy, coma or even seizures

Risk Factors for demyelination

• Rate of correction over 24 hours more important than rate of correction in any one particular hour

• More common if sodium increases by more than 20 mEq/L in 24 hours

• Very uncommon if sodium increases by 12 mEq/L or less in 24 hours

• CT but preferably MRI to diagnose demyelination if suspected, though imaging studies may not be positive for up to 4 weeks after initial correction

Treatment Options

• CPM is associated with poor prognosis

• Prevention is key

• Small studies have shown that plasmapharesis done immediately after diagnosis may improve clinical outcomes

Summary of Hyponatremia

• Hyponatremia has variety of causes• Treatment is based on symptoms

– Severe symptoms = Hypertonic Saline– Mild or no symptoms = Fluid restriction

• Overcorrection, more than 12 mEq increase in 24 hours must be avoided with monitoring

• Serum Osmolality, Urine Osmolality and Urine sodium concentration are initial tests to order

Moving on to Hypernatremia

• Produced by either administration of hypertonic fluids or much more frequently, loss of thirst

• Because of extremely efficient regulatory mechanisms such as ADH and thirst, hypernatremia generally occurs only in people with prolonged lack of thirst mechanism

• Patients with loss of ADH (Diabetes Insipidus) usually can compensate with increased fluid intake

Causes of Hypernatremia

• Insensible and sweat losses• GI losses• Diabetes Insipidus (both central and nephrogenic)• Osmotic Diuresis – DKA or HHNK• Hypothalamic lesions which affect thirst function –

Causes include tumors, granulomatous diseases or vascular disease

• Sodium Overload – Infusion of Hypertonic sodium bicarbonate for metabolic acidosis

Symptoms of Hypernatremia

• Initial symptoms include lethargy, weakness and irritability

• Can progress to twitching, seizures, obtundation or coma

• Resulting decrease in brain volume can lead to rupture of cerebral veins leading to hemorrhage

• Severe symptoms usually occur with rapid increase to sodium concentration of 158 mEq or more

• Sodium concentration greater than 180 mEq are associated with high mortality

Diagnosis of Hypernatremia

• Same labs as workup for hyponatremia: Serum osmolality, urine osmolality and urine sodium

• Urine sodium should be lower than 25 mEq/L if and water and volume loss are cause. It can be greater than 100 mEq/L when hypertonic solutions are infused or ingested

• If urine osmolality is lower than serum osmolality then DI is present– Administration of DDAVP will differentiate

• Urine osmolality will increase in central DI, no response in nephrogenic DI

Treatment of Hypernatremia

• First, calculate water deficit• Water deficit = CBW x ((plasma Na/desired

Na level)-1)• CBW = current body water assumed to be 50%

of body weight in men and 40% in women• So let’s do a sample calculation:

– 60 kg woman with 168 mEq/L– How much water will it take to reduce her sodium

to 140 mEq/L

Calculation continued

• Water deficit = 0.4 x 60 ([168/140]-1) = 4.8 L• But how fast should I correct it?• Same as hyponatremia, sodium should not be

lowered by more than 12 mEq/L in 24 hours– Overcorrection can lead to cerebral edema which can

lead to encephalopathy, seizures or death• So what does that mean for our patient?

– The 4.8 L which will lower the sodium level by 28 should be given over 56-60 hours, or at a rate of 75-80 mL/hr

– Typical fluids given in form of D5 water

Summary of Hypernatremia

• Loss of thirst usually has to occur to produce hypernatremia

• Rate of correction same as hyponatremia• D5 water infusion is typically used to lower

sodium level • Same diagnostic labs used: Serum osmolality,

Urine osmolality and Urine sodium• Beware of overcorrection as cerebral edema

may develop

Questions?