Osmolality, sodium, potassium, chloride, and bicarbonate

Osmolality and volume regulation


Osmolality in plasma is related to the number of solutes (soluble particles) dissolved in a kg of plasma water, with a normal osmolality between 280 and 295 mOsm/kg. Measurement of serum osmolality is used to evaluate the body’s regulation of water and sodium balance, while urine osmolality evaluates the kidney’s ability to concentrate urine. In a steady state, our total body water (TBW) and salt content remain relatively constant. An increase or decrease in water and salt intake will affect the water and salt retention and excretion in the kidney.

The TBW is defined as the fluid that occupies the intracellular (∼65% of TBW) and extracellular spaces (∼10% intravascular; ∼25% interstitial) of the body. In general, while TBW fluctuates hourly due to loss via the kidneys, lungs, and skin, and gain by food and fluid intake, plasma osmolality is more closely regulated and remains relatively constant ( , ) .

Note that the term “osmolarity” is related to the number of solutes per liter of plasma volume and is expressed in mmol/L. Another term is the oncotic or colloid osmotic pressure, which is related to the water-retaining effect of proteins. Clinically, this is most relevant in the intravascular fluid (blood) where the high protein concentration in blood plasma prevents excess water movement to the interstitial fluid. Disturbance to this equilibrium can cause edema, which is an accumulation of fluid in the interstitial space.

Water excretion in the kidneys is largely controlled by antidiuretic hormone (ADH) also called vasopressin, which is a peptide secreted by the posterior pituitary. To increase water reabsorption, ADH opens water channels in the membranes of cells lining the collecting ducts in the kidney ( ) .

Several factors affect ADH secretion: (1) receptors in the hypothalamus stimulate ADH production and secretion in the posterior pituitary in response to increasing osmolality; (2) Stretch receptors located in the atria of the heart sense increased blood pressure due to increased blood volume and inhibit ADH secretion; and (3) stretch receptors in the arteries stimulate ADH secretion when blood pressure falls due to decreased blood volume.

The sodium concentration in blood is affected by the regulation of both the plasma osmolality and the blood volume. As we will see later, osmolality and volume are regulated by separate mechanisms, although both mechanisms involve ADH: osmolality (sodium) is regulated by changes in water balance via ADH, whereas volume is regulated by changes in sodium balance via the renin–angiotensin–aldosterone system and ADH ( , ) . In a person with normal water and osmolality homeostasis, if a large volume of hypotonic fluid such as water is consumed, to prevent volume overload the kidneys respond by rapidly excreting dilute urine, even before the intra- and extracellular fluids equilibrate ( ) .

Calculation of osmolality

The osmolality of plasma is related to the concentration of ions (Na, K, Cl, albumin, etc.) and neutral solutes such as glucose and urea. The contribution of the ions can be fortuitously estimated as 2 × [Na] (in mmol/L), for three reasons:

  • NaCl in plasma is 75% “osmotically active.” Therefore, 1 mmol of NaCl behaves as if it dissociates into 1.75 mmol of osmotic particles (0.75 Na + + 0.75 Cl + 0.25 NaCl) ( ) .

  • Plasma is 93% water and 7% proteins and lipids (with ions mostly confined to the plasma H 2 O space).

  • Other ions such as K + , Ca 2+ , and Mg 2+ account for ∼8% of the osmotic activity relative to sodium ion.

Therefore, sodium contribution to osmolality is

<SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='(1.75/0.93)×1.08×[Na]=2×[Na]’>(1.75/0.93)×1.08×[Na]=2×[Na](1.75/0.93)×1.08×[Na]=2×[Na]

Calculated osmolality (mOsm/kg) =

<SPAN role=presentation tabIndex=0 id=MathJax-Element-2-Frame class=MathJax style="POSITION: relative" data-mathml='(2×[Na])+[BUN(mg/dL)/2.8]+[glucose(mg/dL)/18]’>(2×[Na])+[BUN(mg/dL)/2.8]+[glucose(mg/dL)/18](2×[Na])+[BUN(mg/dL)/2.8]+[glucose(mg/dL)/18]
where BUN is blood urea nitrogen.

Note: Because concentrations of sodium, urea, and glucose are in molarity, calculations of “osmolality” are actually calculations of osmolarity.

Regulation of osmolality

The response to increased osmolality is described in the following and shown in Fig. 8.1 .

Figure 8.1

Responses to changes in blood volume and osmolality . Loss of water causes both hypovolemia and increased blood osmolality. Hypovolemia decreases blood pressure, which stimulates both the renin–angiotensin–aldosterone system and secretion of ADH, with ADH being a common response to both hypovolemia and hyperosmolality. Volume receptors located in the afferent renal arterioles, the heart, the arteries, and the distal tubule, by sensing decreased blood pressure, stimulate the secretion of renin.

Increased blood osmolality is detected by osmoreceptors in the hypothalamus, which produces ADH that is stored and released through the posterior pituitary gland. ADH has several actions that normalize blood osmolality. It activates the kidney tubules of the collecting duct to reabsorb more water by producing water channel proteins called aquaporins. ADH causes vasoconstriction to temporarily increase blood pressure. ADH also leads to increased thirst that should cause increased water intake to normalize blood osmolality.

This is an original drawing.

Renal water regulation by ADH and thirst each play important roles in regulating plasma osmolality. To maintain a normal plasma osmolality [∼280–300 mmol/kg (∼280–300 mOsm/kg) of plasma H 2 O)], both thirst and ADH are activated. Osmoreceptors in the hypothalamus respond quickly to small changes in osmolality: A 1%–2% increase in osmolality causes a fourfold increase in the circulating concentration of ADH and a strong desire to drink fluid. Conversely, a 1%–2% decrease in osmolality shuts off ADH production entirely ( ) . ADH acts by increasing the reabsorption of water in the cortical and medullary collecting tubules of the kidney. The action is short-lived because ADH has a half-life in the circulation of only 15–20 min. The adrenal cortex also affects aldosterone secretion by shutting off secretion when plasma osmolality increases ( ) .

Renal water excretion is more important in controlling water excess, whereas thirst is more important in preventing water deficit or dehydration. Consider what happens in the following conditions:

  • Water Load . Excess intake of water (either done normally or in a condition such as polydipsia) is handled by several mechanisms. As plasma osmolality declines, both ADH and thirst are suppressed. In the absence of ADH, a very large volume of dilute urine can be excreted (10 L or more per day), well above any normal intake of water. If blood volume increases, stretch receptors located along the circulatory system stimulate the production of natriuretic peptides, including atrial (ANP) and “brain” (BNP) natriuretic peptides. These mechanisms are so effective that hypoosmolality and hyponatremia occur almost exclusively in patients with excess ADH and/or impaired renal excretion of water ( ) .

  • Water Deficit . As a deficit of water begins to increase plasma osmolality, both ADH secretion and thirst are activated. Even though ADH minimizes renal water loss, thirst is the major defense against hyperosmolality and hypernatremia because it stimulates a person to seek an external source of water. As an example of the effectiveness of thirst in preventing dehydration, a patient with diabetes insipidus (no ADH) may excrete 10 L of urine per day. However, because thirst persists, water intake matches output to maintain a normal plasma sodium concentration ( ) .

This is why hypernatremia rarely occurs in a person with a normal thirst mechanism and access to water. However, it becomes a concern in infants, unconscious patients, or anyone who is unable to either drink or ask for water. In people over the age of 60 years, osmotic stimulation of thirst diminishes. Particularly in the older patient with illness and diminished mental status, dehydration becomes increasingly likely.

Regulation of blood volume

The response to decreased blood volume is described in the following and shown in Fig. 8.1 .

Blood volume is the total amount of fluid within the arteries, capillaries, veins, and chambers of the heart. The blood volume also includes red blood cells (erythrocytes), white blood cells (leukocytes), platelets, and plasma. Plasma accounts for about 60% of total blood volume while erythrocytes and the other cells make up roughly 40% ( ) .

Adequate blood volume maintains blood pressure and ensures good perfusion to tissues and organs. Multiple organ systems are involved in regulating blood volume by the interrelated control of both sodium and water. The kidneys are primarily responsible for regulating blood volume by adjusting the solute and water content of the blood through filtration, reabsorption, and secretion.

Changes in blood volume are initially detected as changes in blood pressure by a series of stretch receptors in areas such as the cardiopulmonary circulation, the carotid sinus, the aortic arch, and the glomerular arterioles. In the kidney nephrons, Na + and K + are actively reabsorbed in the proximal tubules, with Cl and water “following” the reabsorption of the cations. The amounts of water and solute reabsorbed primarily regulate blood volume. If blood volume is too low, more filtrate is reabsorbed; if blood volume is too high, less filtrate is reabsorbed ( ) .

The renin-angiotensin-aldosterone system responds primarily to approximately a 5% decrease in blood volume. While a potent thirst response is also stimulated, it requires a 5%–10% decrease in blood volume and arterial pressure. While this response to decreased blood volume is less sensitive than the thirst response to only a 1%–2% decrease in plasma osmolality, once activated, this response to decreased volume dominates the response to changes in osmolality ( ) .

The effects of blood volume and osmolality on sodium and water metabolism are listed in the following and also shown in Fig. 8.1 .

  • In response to decreased blood volume and blood pressure, the kidneys respond by decreasing GFR and secreting renin near the renal glomeruli (juxtaglomerular cells). Renin converts angiotensinogen to angiotensin I, which then becomes angiotensin II.

  • Angiotensin II stimulates thirst, causes vasoconstriction to quickly increases blood pressure, stimulates the adrenal cortex to secrete aldosterone, and increases renal reabsorption of Na.

  • Aldosterone promotes distal tubular reabsorption of Na + and HCO 3 in exchange for K + and H + .

  • In volume depletion, aldosterone increases blood volume by increasing renal retention of sodium and bicarbonate, and the water that accompanies these ions. In this process, both Cl and H + are lost ( ) .

  • Both thirst and ADH are stimulated by low blood volume, independent of osmolality.

  • Natriuretic peptides (ANP and the now-famous BNP) are released from the myocardium in response to excess blood volume and promote sodium excretion in the kidney.

  • Epinephrine and norepinephrine are secreted in response to decreased blood volume.

  • All other things being equal, an increased plasma sodium will increase urinary sodium excretion, and vice versa.

The renal retention of sodium has a profound effect on blood volume because whenever a sodium ion is reabsorbed, a water molecule follows. While large amounts of sodium are filtered in the 150 L of glomerular filtrate produced daily, the renal tubules reabsorb 98%–99% of this sodium along with most of the water. Thus, even a 1%–2% reduction in tubular reabsorption of Na + can increase water loss by several liters per day.

Urine osmolality values may vary widely depending on water intake and the circumstances of collection. However, it is generally decreased in diabetes insipidus (inadequate ADH) and polydipsia (excess H 2 O intake due to chronic thirst) and increased in conditions where ADH secretion is increased by hypovolemia or hyperosmolality or in conditions such as inappropriate ADH.

Reference interval

The reference intervals for osmolality, electrolytes, and other parameters are shown in Table 8.1 .

Table 8.1

Reference intervals for serum/plasma electrolytes and osmolality a .

SI units Conventional units
(2 years–adult) 135–145 mmol/L 135–145 mEq/L
0–30 days 4.0–6.0 mmol/L 4.0–6.0 mEq/L
1 month–2 years 4.0–5.5 mmol/L 4.0–5.5 mEq/L
2–18 years 3.8–5.2 mmol/L 3.8–5.2 mEq/L
18 years–adult 3.5–5.0 mmol/L 3.5–5.0 mEq/L
0–2 years 96–110 mmol/L 96–110 mEq/L
2 years–adult 98–108 mmol/L 98–108 mEq/L
Total CO 2
0–17 years 18–27 mmol/L 18–27 mEq/L
18 years–adult 21–30 mmol/L 21–30 mEq/L
Anion gap
Na, Cl, HCO 3 4–12 mmol/L 4–12 mEq/L
Na, K, Cl, HCO 3 8–16 mmol/L 8–16 mEq/L
Osmolality, plasma
Adult 280–300 mmol/kg 280–300 mOsm/kg
Osmolality, urine
(24-h collection) 300–900 mmol/kg 300–900 mOsm/kg

a All values are plasma values unless noted otherwise.


Physiology of sodium balance

As an electrolyte, sodium is vital for the transmission of nerve impulses and activation of muscle movements. Neurons generate electrical signals through brief, controlled changes in the permeability of their cell membrane to ions such as Na + and K + ( ) . Sodium is the most abundant cation in the ECF, representing 90% of all extracellular cations, and largely determines the osmolality of the ECF. To maintain the much higher sodium concentration in the ECF relative to the intracellular concentration, an active transport mechanism involving a Na-K-ATPase pump maintains this large gradient between ECF and ICF. This Na-K-ATPase pump exchanges three sodium ions moving out of cells for two potassium ions moving into cells ( ) .

The plasma sodium concentration depends greatly on the intake and excretion of water and, to a somewhat lesser degree, the renal regulation of sodium. Three processes are of primary importance:

  • The intake of water in response to thirst, as stimulated or suppressed by plasma osmolality

  • The excretion of water, largely affected by ADH release in response to changes in either blood volume or osmolality

  • The blood volume status, which affects sodium excretion through aldosterone, angiotensin II, and ANP

As people age, they are less able to maintain fluid and sodium balance for several reasons. Their thirst sensation diminishes so they may not drink fluids when needed. Kidney function diminishes, such that kidneys may become less able to regulate water and electrolytes in the blood. Also with age, the body contains less fluid, which means that a slight loss of fluid and sodium, as from a fever or from lost thirst or appetite, can be more serious.

People who have physical or mental illnesses may not drink fluids even when they are thirsty. Commonly used drugs for high blood pressure, diabetes mellitus, or heart disorders can affect fluid excretion and magnify the effects of fluid loss ( ) .

The kidneys have the ability to conserve or excrete large amounts of sodium, depending on the osmolality (mostly sodium) of the ECF and the blood volume. Normally, the kidney reabsorbs 98%–99% of filtered sodium: 60%–75% is reabsorbed in the proximal tubule, with the remainder reabsorbed along with Cl in the loop and distal tubule and exchanged for K + in the connecting segment and cortical collecting tubule. These ion movements are under the control of aldosterone, which regulates the final handling of Na ions in the distal nephron by its control of a Na + -Cl cotransporter (NCC) and an Epithelial Na + Channel, both of which promote reabsorption of Na ion in the distal tubule ( ) .

Frequency of hyponatremia and hypernatremia

Mild hyponatremia is quite common among hospitalized patients, with 15%–20% having a serum sodium level of <135 mmol/L, but only 1%–4% have a serum sodium level of less than 130 mmol/L ( ) . A large study of hospitalized patients found that even mild degrees of hyponatremia were associated with increased 1-year and 5-year mortality rates. Mortality was particularly increased in those with cardiovascular disease, metastatic cancer, and those undergoing orthopedic procedures ( ) .

Hypernatremia on admission to the hospital has an estimated incidence from about 2% to 25% ( ) . A seemingly more appropriate incidence found that among patients admitted to the ICU, 11% developed mild hypernatremia and 4.2% developed moderate-to-severe hypernatremia within 24 h after admission ( ) .


Causes of hyponatremia

Hyponatremia is defined as a plasma sodium concentration <135 mmol/L, with its duration also an important consideration in treatment ( ) . Symptoms include anorexia, nausea, confusion, lethargy, easy agitation, and headache. At values below 120 mmol/L, general weakness and mental confusion are typical. Paralysis and severe mental impairment may occur at plasma sodium <115 mmol/L ( ) . Guidelines that classify hyponatremia based on the plasma sodium concentration have been published in Europe ( ) :

  • Mild: 130–134 mmol/L

  • Moderate: 125–129 mmol/L

  • Profound: <125 mmol/L

In hyponatremia, water moves into cells, causing them to swell. If the onset of hyponatremia is longer than 48 h, treatment must be gradual to avoid osmotic demyelination from overly rapid correction. This is especially dangerous for brain cells because expansion increases intracranial pressure. Cerebral edema may lead to respiratory insufficiency and hypoxia, which can cause death ( , ) .

Most patients with hyponatremia have an excess of ADH, either from an inappropriate secretion of ADH or in response to a decreased blood volume ( ) , as shown in Fig. 8.2 . History is important in evaluating patients with hyponatremia for conditions such as heart failure, cirrhosis, GI losses, burns, endocrine disorders, excessive sweating, or certain drugs. Chronic hyponatremia is a common clinical problem in the elderly.

Figure 8.2

Conditions that lead to ADH release and possible hyponatremia. CHF , congestive heart failure; SIADH , syndrome of inappropriate secretion of antidiuretic hormone.

From Fig. 3.2 in 2nd ed.

Laboratory evaluation of hyponatremia

Detecting, monitoring, and treating abnormal electrolyte concentrations are critically important in many patients, with rapid results often reducing therapeutic intervention time ( ) . The most important laboratory tests for evaluating patients with hyponatremia are:

  • Plasma Na, K, Cl, HCO 3 , glucose, creatinine, and urea.

  • Serum osmolality

  • Urine osmolality and Na

The diagnostic approach to hyponatremia is shown in Table 8.2 . The initial decreased plasma Na should be confirmed by a decreased serum osmolality.

Table 8.2

Evaluation of hyponatremia.

Measure plasma Na, K, Cl, HCO 3 , and urea; osmolality and uric acid if needed.
Plasma Na and osmolality decreased:
Measure urine Na:
Urine Na <15 mmol/L (<15 mEq/L); plasma AG, urea, and uric acid normal to increased.
Hypovolemia with hypotonic fluid replacement (diarrhea, vomiting,
sweating, renal losses, etc.)
Polydipsia (chronic thirst)
Hypervolemia with arterial hypovolemia (congestive heart failure, cirrhosis)
Urine Na >20 mmol/L (>20 mEq/L); plasma AG, urea, and uric acid normal to decreased.
Inappropriate excess secretion of ADH (carcinoma of lung, adrenal insufficiency, etc.)
Renal salt loss (thiazides, aldosterone deficiency)
Reset osmostat
Renal failure with water overload

Serum osmolality confirms true hyponatremia versus pseudohyponatremia due to hyperlipidemia or hyperproteinemia, or hypertonic hyponatremia from elevated glucose, urea, or administration of some osmotic substance such as mannitol.

The urine osmolality and sodium help differentiate between renal and neurogenic causes of hyponatremia, such as polydipsia. If the urine osmolality is greater than about 150 mOsm/kg, it indicates the impaired ability of the kidneys to produce dilute urine.

Clinical diagnosis of hyponatremia

A clinical history, symptoms, and physical exam are required along with the initial laboratory parameters that indicated hyponatremia. Symptoms include anorexia, nausea, confusion, lethargy, easy agitation, and headache ( ) . The history should evaluate the following:

  • Duration of the hyponatremia, with 48 h a typical cutoff between acute and chronic hyponatremia.

  • Edema (heart failure, cirrhosis)

  • GI losses (diarrhea, vomiting)

  • Skin losses (burns, sweating)

  • Renal losses (low aldosterone, diuretics, salt-losing syndromes)

  • Drugs (carbamazepine, SSRIs)

  • Cancer (oat-cell carcinoma of the lung is associated with SIADH)

  • Check blood pressure and examine skin:

    • Volume depletion: decreased BP; skin has decreased turgor, and is cool and pale

    • Volume overload: elevated BP, pitting edema in lower extremities

The pathogenesis of hyponatremia is often related to volume status and excess ADH that is secreted in response to changes in volume or osmotic stimuli, as shown in Table 8.3 and Fig. 8.2 . Volume status may be assessed by skin turgor, jugular venous pressure, and urine Na concentration, with a low urine Na indicating hypovolemia ( , , ) .

Table 8.3

Hyponatremia differential diagnosis related to volume status.

Hypovolemic Na loss in excess of H 2 O
Thiazide diuretics
Loss of hypertonic fluid: GI, burns, sweat
Potassium depletion
Aldosterone deficiency
Salt-losing nephropathies
Euvolemic Problem with water balance
Excess or inappropriate ADH secretion
Artifactual—severe hyperlipidemia
Hyperosmolar from substance other than sodium
Adrenal insufficiency
Altered regulatory set point for osmolality
Hypervolemic Movement of fluid from intravascular to interstitial space
Congestive heart failure, hepatic cirrhosis
Advanced renal failure (decreased glomerular filtration rate) with excess water intake
Nephrotic syndrome—decreased colloid osmotic pressure

Hyponatremia is classified according to volume status, as follows:

Hypovolemic hyponatremia : a decrease in intravascular (plasma) water with a greater decrease in plasma sodium. Among the more common causes of hypovolemic hyponatremia are the following:

  • Use of thiazide diuretics (but not loop diuretics), which induce Na and K loss without interfering with ADH-mediated water retention.

  • With prolonged vomiting, diarrhea, or sweating, as hypotonic fluids are lost they are replaced by a relatively greater volume of hypotonic fluid by ingestion of water in response to thirst and ADH, which are stimulated by hypovolemia (see Fig. 8.2 ).

  • In potassium depletion, cellular loss of K + promotes Na + movement into the cell with an associated decrease in plasma Na and volume.

  • Aldosterone deficiency from adrenal insufficiency or drugs increases both urinary Na loss and urine osmolality.

  • Salt-wasting nephropathy may infrequently develop in renal tubular and interstitial diseases, such as medullary cystic and polycystic kidney diseases, usually as renal insufficiency becomes severe [serum creatinine >610 μmol/L (>8 mg/dL)].

Normovolemic hyponatremia : little or no increase in plasma water with some loss of plasma sodium. It typically indicates a problem with water balance and may be related to one of the following:

  • Polydipsia (chronic thirst with excess intake and excess excretion of water) eventually leads to hyponatremia that is usually mild but occasionally severe.

  • Excess ADH may be secreted in response to drugs, surgery, tumors, central nervous system disorders, endocrine disorders, or pulmonary conditions ( , ) . The excess ADH causes mild hypervolemia, which then leads to excretion of Na + and water by the release of ANP (see Fig. 8.2 ).

  • Pseudohyponatremia can occur with severe hyperlipidemia or hyperproteinemia. Methods that dilute plasma before Na analysis by the ion-selective electrode (ISE) or other methods give erroneously low Na results on such samples by measuring the Na concentration per liter of plasma. “Direct” methods by ISE (typically on blood gas analyzers), which do not dilute plasma or whole blood, give accurate Na results because they detect the Na concentration in the plasma water.

  • A significant degree of hyperglycemia generally causes a lower plasma sodium to maintain a normal plasma osmolality.

  • In adrenal insufficiency, the decreased aldosterone (mineralocorticoid) and cortisol (glucocorticoid) promote ADH release ( ) .

  • In pregnancy, osmotic regulation in the hypothalamus may be offset such that plasma Na is regulated ∼5 mmol/L (∼5 mEq/L) lower than normal. This effect on the hypothalamus may be initiated by vasodilation, which mimics hypovolemia by lowering blood pressure.

  • Drugs: desmopressin, psychoactive agents, anticancer agents ( ) .

Hypervolemic hyponatremia : total body sodium is increased, but with an even greater increase in TBW. This condition is nearly always a problem of water overload as excess water accumulates from renal failure, heart failure, or liver failure. It is usually associated with one or more of the following conditions:

  • Excess secretion of ADH. For example, congestive heart failure or hepatic cirrhosis increases venous back-pressure in the circulation, which promotes the movement of fluid from the blood to the interstitium, causing edema and arterial hypovolemia. The arterial hypovolemia stimulates ADH secretion, which eventually leads to hypervolemia and hyponatremia, as indicated in Fig. 8.2 .

  • Inability of the kidneys to excrete excess water along with excess fluid intake. This is more likely in elderly patients.

  • Aldosterone secretion stimulates renal Na ion and Cl ion reabsorption in the distal convoluted tubule (DCT) by controlling both a sodium-chloride cotransporter (NCC) and an epithelial Na channel (ENaC) in the DCT. Aldosterone also regulates a sodium channel in the collecting duct and the chloride-reabsorbing protein pendrin in the cortical collecting duct ( ) .

Treatment of hyponatremia

The treatment of hyponatremia depends on the cause, the severity, and how rapidly the hyponatremia develops ( , , , , ) . In patients with good kidney function and less severe symptoms, fluid restriction is usually effective ( ) .

Acute hyponatremia is less common than chronic hyponatremia and is typically seen in patients with a sudden ingestion of free water. The danger for such patients is herniation of the brainstem if sodium concentrations fall below 120 mmol/L ( ) . The therapeutic goal in acute hyponatremia is to increase the serum sodium level rapidly by 4–6 mmol/L over the first 1–2 h. In addition, the source of free water must be identified and eliminated. In patients with healthy renal function and without severe symptoms, the plasma sodium may correct without further intervention. However, patients with seizures, severe confusion, coma, or signs of brainstem herniation should receive hypertonic (3%) saline to rapidly correct the serum sodium concentration, but only enough to alleviate the symptoms ( ) .

Patients with chronic hyponatremia and more severe symptoms, such as severe confusion, coma, or seizures, should receive hypertonic saline, but only enough to raise the serum sodium level by 4–6 mmol/L and to arrest seizure activity. After this increase, no further correction of the sodium during the next 24 h is recommended ( ) .

Hypervolemic hyponatremia or asymptomatic hyponatremia is usually treated effectively with water restriction. This would be the case with advanced renal disease, where the inability to excrete water promotes hypervolemia whenever fluid intake is excessive.


Causes of hypernatremia

Hypernatremia is defined as an abnormal plasma sodium concentration above 145 mmol/L. Hypernatremia is usually a problem of water regulation more than a problem of sodium homeostasis so that hypernatremia usually results from excessive loss of water relative to sodium ( ) . Hypotonic fluid may be lost through several common routes: by the kidney, by profuse sweating, or by GI loss such as diarrhea. About 1 L of water per day is normally lost through the skin and by breathing (insensible losses). Any condition that increases water loss, such as fever, burns, or exposure to heat, will increase the likelihood of developing hypernatremia. Because an increase in osmolality of only 1%–2% stimulates thirst, hypernatremia rarely occurs in persons with a normal thirst mechanism and access to water.

Hypernatremia and hyperosmolality from the water loss can cause neuronal cell shrinkage and brain injury, while the loss of volume can lead to circulatory problems, such as tachycardia and hypotension ( ) . Severe symptoms usually occur with an acute increase in sodium concentration to approximately 158–160 mmol/L ( ) . Cerebral dehydration can lead to demyelination, cerebral bleeding, coma, and death ( ) . Because the brain can adapt to the slower (chronic) onset of hypernatremia by restoring normal cell volume, chronic hypernatremia is less likely to induce neurologic symptoms ( ) .

Acute hypernatremia, which is defined as occurring in a period of less than 24 h, should be corrected rapidly. Chronic hypernatremia occurring over a period of longer than 48 h should be corrected more gradually to avoid cerebral edema during treatment. Hypernatremia should be corrected at a rate no faster than about 0.5 mmol/L/h ( ) .

Laboratory and clinical evaluation of hypernatremia

Following the detection of hypernatremia as a serum sodium concentration above 145 mmol/L, the following laboratory studies may be helpful in evaluating the cause:

  • Serum electrolytes (Na + , K + , Ca ++ , Cl ), glucose, urea, and creatinine

  • Urine and plasma osmolality; also urine Na + and K + may be helpful

  • 24-h urine volume

  • In more challenging cases, measuring plasma ADH may be helpful.

Severe hypernatremia occurs when the plasma sodium concentration reaches ∼158–160 mmol/L, or when symptoms due to hypernatremia are severe. The measurement of urine osmolality is necessary to evaluate the cause of hypernatremia, as shown in Table 8.4 . In renal losses of water, the urine osmolality is low or normal. In nonrenal losses, the urine osmolality is increased.

Nov 21, 2021 | Posted by in CRITICAL CARE | Comments Off on Osmolality, sodium, potassium, chloride, and bicarbonate

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