Hypernatremia is a common electrolyte problem that is defined as a rise in serum sodium concentration to a value exceeding 145 mmol/L.[1, 2, 3] It is strictly defined as a hyperosmolar condition caused by a decrease in total body water (TBW)[4] relative to electrolyte content. Hypernatremia is a “water problem,” not a problem of sodium homeostasis.
Community-acquired hypernatremia generally occurs in elderly people who are mentally and physically impaired, often with an acute infection. Patients who develop hypernatremia during the course of hospitalization have an age distribution similar to that of the general hospital population. In both patient groups, hypernatremia is caused by impaired thirst and/or restricted access to water, often exacerbated by pathologic conditions with increased fluid loss.
The development of hyperosmolality from the water loss can lead to neuronal cell shrinkage and resultant brain injury. Loss of volume can lead to circulatory problems (eg, tachycardia, hypotension).
Acute symptomatic hypernatremia, defined as hypernatremia occurring in a documented period of less than 24 hours, should be corrected rapidly. Chronic hypernatremia (>48 h), however, should be corrected more slowly due to the risks of cerebral edema during treatment.
Hypernatremia results from a net water loss or a sodium gain, and it reflects too little water in relation to total body sodium and potassium. In a simplified view, the serum sodium concentration (Na+) can be seen as a function of the total exchangeable sodium and potassium in the body and the total body water.[5] The formula is expressed below:
Na+ = Na+ total body + K+ total body/total body water
Consequently, hypernatremia can only develop as a result of either a loss of free water or a gain of sodium or a combination of both. Hypernatremia by definition is a state of hyperosmolality, because sodium is the dominant extracellular cation and solute.[6]
The normal plasma osmolality (Posm) lies between 275 and 290 mOsm/kg and is primarily determined by the concentration of sodium salts. (Calculated plasma osmolality: 2(Na) mEq/L + serum glucose (mg/dL)/18 + BUN (mg/dL)/2.8). Regulation of the Posm and the plasma sodium concentration is mediated by changes in water intake and water excretion. This occurs via two mechanisms:
In a healthy individual, thirst and AVP release are stimulated by an increase in body fluid osmolality above a certain osmotic threshold, which is approximately 280-290 mOsm/L and is considered to be similar if not identical for both thirst and AVP release. An increased osmolality draws water from cells into the blood, thus dehydrating specific neurons in the brain that serve as osmoreceptors or “tonicity receptors.” It is postulated that the deformation of the neuron size activates these cells (thus acting like mechanoreceptors). On stimulation, they signal to other parts of the brain to initiate thirst and AVP release, resulting in increased water ingestion and urinary concentration, rapidly correcting the hypernatremic state.
Urinary concentration - AVP and the kidney [10]
Conservation and excretion of water by the kidney depends on the normal secretion and action of AVP and is very tightly regulated. The stimulus for AVP secretion is an activation of hypothalamic osmoreceptors, which occurs when the plasma osmolality reaches a certain threshold (approximately 280 mOsm/kg). At plasma osmolalities below this threshold level, AVP secretion is suppressed to low or undetectable levels. Other afferent stimuli, such as a decrease in effective arterial blood volume, pain, nausea, anxiety, and numerous drugs, can also cause a release of AVP.
AVP is synthesized in specialized magnocellular neurons whose cell bodies are located in the supraoptic and paraventricular nuclei of the hypothalamus. The prohormone is processed and transported down the axon, which terminates in the posterior pituitary gland. From there, it is secreted as active AVP hormone into the circulation in response to an appropriate stimulus (hyperosmolality, hypovolemia).
AVP binds to the V2 receptor located on the basolateral membrane of the principal cells of the renal collection ducts. The binding to this G-protein coupled receptor initiates a signal transduction cascade, leading to phosphorylation of aquaporin-2 and its translocation and insertion into the apical (luminal) membrane, creating "water channels" that enable the absorption of free water in this otherwise water-impermeable segment of the tubular system
Thirst is the body’s mechanism to increase water consumption in response to detected deficits in body fluid. As with AVP secretion, thirst is mediated by an increase in effective plasma osmolality of only 2-3%. Thirst is thought to be mediated by osmoreceptors located in the anteroventral hypothalamus. The osmotic thirst threshold averages approximately 288-295 mOsm/kg. This mechanism is so effective that even in pathologic states in which patients are unable to concentrate their urine (diabetes insipidus) and excrete excessive amounts of urine (10-15 L/d), hypernatremia does not develop because thirst is stimulated and body fluid osmolality is maintained at the expense of profound secondary polydipsia.
Developing hypernatremia is virtually impossible if the thirst response is intact and water available. Thus, sustained hypernatremia can occur only when the thirst mechanism is impaired and water intake does not increase in response to hyperosmolality or when water ingestion is restricted.
Significant hypovolemia stimulates AVP secretion and thirst. Blood pressure decreases of 20-30% result in AVP levels many times those required for maximal antidiuresis.
Hypernatremic states can be classified as isolated water deficits (which are generally not associated with intravascular volume changes), hypotonic fluid deficits, and hypertonic sodium gain.
Acute hypernatremia is associated with a rapid decrease in intracellular water content and brain volume caused by an osmotic shift of free water out of the cells. Within 24 hours, electrolyte uptake into the intracellular compartment results in partial restoration of brain volume. A second phase of adaptation, characterized by an increase in intracellular organic solute content (accumulation of amino acids, polyols, and methylamines), restores brain volume to normal. Some patients complete this adaptive response in less than 48 hours. The accumulation of intracellular solutes bears the risk for cerebral edema during rehydration. The brain cell response to hypernatremia is critical. See the image below.
View Image | Figure A: Normal cell. Figure B: Cell initially responds to extracellular hypertonicity through passive osmosis of water extracellularly, resulting in.... |
United States
Although the incidence of hypernatremia on admission to the hospital has been estimated at 0.12-1.4%, a review by Tsipotis et al of 19,072 unselected hospitalized adults found that community-acquired hypernatremia occurred in 21%. Hospital-acquired hypernatremia developed in 25.9% of patients.[34]
International
A retrospective, single-center study from Austria, which included 981 patients, found that 2% of patients had hypernatremia on admission to the intensive care unit (ICU) and 7% developed hypernatremia during their stay in the ICU.[12] Analysis of data on 8140 patients from 12 French ICUs found that 11.1% developed mild hypernatremia and 4.2% developed moderate to severe hypernatremia 24 hours or more after ICU admission.[34]
A Canadian study of 8142 adult patients identified ICU-acquired hyponatremia in 11% of them and ICU-acquired hypernatremia in 26% of these patients.[13] The report found that the mortality rate in patients with ICU-acquired hyponatremia or hypernatremia was greater than that of study patients with normal serum sodium levels, being 28% versus 16% (P < 0.001), and 34% versus 16%, p < 0.001, respectively.
In patients with community-acquired hpernatremia, Tsipotis et al reported an adjusted odds ratio (OR) of 1.67 (95% confidence interval [CI], 1.38-2.01) for in-hospital mortality and 1.44 (95% CI, 1.32-1.56) for discharge to a short-/long-term care facility and an adjusted 10% (95% CI, 7-13) increase in length of stay. Patients with hospital-acquired hypernatremia had an adjusted OR of 3.17 (95% CI, 2.45-4.09) for in-hospital mortality and 1.45 (95% CI, 1.32-1.59) for discharge to a facility, and an adjusted 49% (95% CI, 44-53) increase in length of stay.[34]
Mortality rates of 30-48% have been shown in patients in ICUs who have serum sodium levels exceeding 150 mmol/L.[11, 14] A review of 256 patients presenting to a Turkish emergency department with severe hypernatremia (serum sodium >160 mmol/L) determined that the following factors were independently associated with mortality[15] :
Comparing hospital mortality rates for the patients without hypernatremia with those for cohort members with the condition, Darmon et al determined that the subdistribution hazard ratio for mortality from ICU-acquired hypernatremia was 2.03 for mild hypernatremia and 2.67 for moderate–to-severe hypernatremia.[11] However, whether the association of ICU-acquired hypernatremia with an increased risk for death reflects a direct effect of hypernatremia or is a marker for suboptimal quality of care is uncertain.
One study confirmed that maximum daily sodium amount is a significant risk factor for the development of acute kidney injury in patients with subarachnoid hemorrhage (SAH) who are receiving hypertonic saline therapy. Such therapy is often used to control intracranial hypertension and manage symptomatic hyponatremia. Of 736 patients in one study, 9% (64) developed acute kidney injury. For each 1 mEq/L increase in the running maximum daily serum sodium rate, the risk of developing acute kidney injury increased by 5.4 %, and the risk of death was more than twofold greater for patients who developed acute kidney injury.[16]
Early acquired hypernatremia in the ICU has been found to be a frequent complication in patients with severe sepsis and is associated with the volume of 0.9% saline received during the first 48 hours of admission in the ICU. In one study, of 95 patients with severe sepsis, 29 (31%) developed hypernatremia within 5 days. For every 50 ml/kg increase in 0.9% saline intake during the first 48 hours, the odds of hypernatremia increased by 1.61 times. Patients who developed hypernatremia had increased duration of mechanical ventilation and increased mortality.[17]
According to a study by Leung et al, preoperative hypernatremia is associated with increased perioperative 30-day morbidity and mortality. In their study, 20,029 patients with preoperative hypernatremia (>144 mmol/L) were compared with 888,840 patients with a normal baseline sodium (135-144 mmol/L). The odds of morbidity and mortality increased according to the severity of hypernatremia (P< .001 for pairwise comparison for mild [145-148 mmol/L] vs severe [>148 mmol/L] categories). Hypernatremia, versus normal baseline sodium, was associated with a greater odds for perioperative major coronary events (1.6% vs 0.7%), pneumonia (3.4% vs 1.5%), and venous thromboembolism (1.8% vs 0.9%).[18]
The groups most commonly affected by hypernatremia are elderly people and children.[19] Breastfeeding-associated neonatal hypernatremia has been recognized in infants ≤ 21 days of age who have lost ≥10% of birth weight.[20]
Patients developing hypernatremia outside of the hospital setting are generally elderly and debilitated, and often present with an intercurrent acute (febrile) illness. Hospital-acquired hypernatremia affects patients of all ages.
The history should be used to discover why the patient was unable to prevent hypernatremia with adequate oral fluid intake. For example, the clinician should determine whether the patient is suffering from an altered mental status or whether there are any factors causing increased fluid excretion (eg, diuretic therapy; diabetes mellitus; or fever, diarrhea, and vomiting). The history should also cover the symptoms and causes of possible diabetes insipidus (eg, the presence of preexisting polydipsia or polyuria, a history of cerebral pathology, or medication use [lithium]).
It is important to find out if the hypernatremia developed acutely or over time, because this will guide treatment decisions.
Risk factors for hypernatremia include the following:
Hospitalized patients may develop hypernatremia because of any of the following:
The examination should include an accurate assessment of volume status and cognitive function. Symptoms can be related to volume deficit and/or hypertonicity and shrinkage of brain cells, which can tear cerebral blood vessels in severe cases, leading to cerebral hemorrhage.
The worsening symptoms associated with hypernatremia may go unnoticed in elderly patients who have a preexisting impairment of their mental status and decreased access to water.
Table 1. Characteristics and symptoms of hypernatremia
View Table | See Table |
In a prospective, case-control, multicenter study, Chassagne and colleagues looked at the symptoms associated with hypernatremia in 150 geriatric patients.[22] The likelihood that patients with hypernatremia would have low blood pressure, tachycardia, dry oral mucosa, abnormal skin turgor, and a recent change in consciousness was significantly greater than that of the controls. The only clinical findings to occur in at least 60% of patients with hypernatremia were orthostatic blood pressure and abnormal subclavicular and forearm skin turgor (poor specificity and sensitivity for all physical findings).
Several risk factors exist for hypernatremia. The greatest risk factor is age older than 65 years. In addition, mental or physical disability may result in impaired thirst sensation, an impaired ability to express thirst, and/or decreased access to water.[23, 24]
Hypernatremia often is the result of several concurrent factors. The most prominent is poor fluid intake. Again, developing hypernatremia is virtually impossible if the thirst response is intact and water is available. Normally, an increase in osmolality of just 1-2% stimulates thirst, as do hypovolemia and hypotension. For clinical purposes, hypernatremia can, in a simplified view, be classified on the basis of the concurrent water loss or electrolyte gain and on corresponding changes in extracellular fluid volume, as follows:
Patients who lose hypotonic fluid have a deficit in free water and electrolytes (low total body sodium and potassium) and have decreased extracellular volume. In these patients, hypovolemia may be more life threatening than hypertonicity. When physical evidence of hypovolemia is present, fluid resuscitation with normal saline is the first step in therapy.
Renal hypotonic fluid loss results from anything that will interfere with the ability of the kidney to concentrate the urine or osmotic diuresis, such as the following:
Nonrenal hypotonic fluid loss can result from any of the following:
Patients with pure-water deficits in the majority of cases have a normal extracellular volume with normal total body sodium and potassium. This condition most commonly develops when impaired intake is combined with increased insensible (eg, respiratory) or renal water losses.
Free-water loss will also result from an inability of the kidney to concentrate the urine. The cause of that can be either from failure of the hypothalamic-pituitary axis to synthesize or release adequate amounts of AVP (central diabetes insipidus) or a lack of responsiveness of the kidney to AVP (nephrogenic diabetes insipidus). Patients with diabetes insipidus and intact thirst mechanisms most often present with normal plasma osmolality and serum NA+, but with symptoms of polyuria and polydipsia.
Water intake less than insensible losses may result from any of the following:
Central diabetes insipidus[26] can be caused by any pathologic process that destroys the anatomic structures of the hypothalamic-pituitary axis involved in AVP production and secretion. Such processes include the following:
Causes include the following:
Medications that induce nephrogenic diabetes insipidus include the following:
Medications that possibly cause nephrogenic diabetes insipidus include the following:
This is caused by a combination of damage to the osmoreceptors regulating thirst sensation and central diabetes insipidus (see above).[28] Etiologies include the following:
In this form of diabetes insipidus, AVP is rapidly degraded by a high circulating level of oxytocinase/vasopressinase. It is a rare condition, because increased AVP secretion will compensate for the increased rate of degradation. Gestational diabetes insipidus occurs only in combination with impaired AVP production.
Patients with hypertonic sodium gain have a high total-body sodium and an extracellular volume overload (rare, mostly iatrogenic). When thirst and renal function are intact, this condition is transient. Causes include the following:
Water shifts into muscle cells during extreme exercise or seizures because of increased intracellular osmoles). In clinical practice, a combination of the two may be present. For example, an intubated patient in the ICU develops hypernatremia due to hypertonic sodium gain caused by normal saline volume resuscitation and, in addition, increased free water excretion due to recovering renal failure and/or osmotic urea-diuresis caused by high-protein tube feeding.
The diagnosis of hypernatremia is based on an elevated serum sodium concentration (Na+ >145 mEq/L). In addition, the following lab studies are used to determine the etiology of hypernatremia:
The first step in the diagnostic approach is to estimate the volume status (intravascular volume) of the hypernatremic patient. The associated volume contraction may be mirrored in a low urine Na+ (usually < 10 mEq/L).
In the hypovolemic patient, a hypertonic urine (urine osmolality usually greater than 600 mOsm/kg) with a low UNa+ (usually less than 10–20 mEq/L) will point toward extrarenal fluid losses (eg, gastrointestinal, dermal), whereas an isotonic or hypotonic urine (urine osmolality 300 mOsm/kg or less) with a UNa+ higher than 20–30 mEq/L indicates renal fluid loss (eg, from diuretics, osmotic diuresis, intrinsic renal disease).
In the euvolemic patient with preserved intravascular volume, hypernatremia is most likely due to pure-water losses. In the presence of hypernatremia, urine osmolality normally should be maximally concentrated (>800 mOsm/kg H2O). Measurement of the urine osmolality will allow differentiation of the following:
Caveat: Unfortunately, concentrating ability tends to fall with age; the maximum Uosm in an elderly patient may be only 500-700 mOsm/kg.
To distinguish between central and nephrogenic diabetes insipidus, first obtain a plasma AVP level and then determine the response of the urine osmolality to a dose of AVP (or preferably, the V2-receptor agonist DDAVP). Generally, an increase in urine osmolality of greater than 50% reliably indicates central diabetes insipidus, while an increase of less than 10% indicates nephrogenic diabetes insipidus; responses between 10% and 50% are indeterminate. Hyperosmolar patients with an elevated AVP level have nephrogenic diabetes insipidus; those with central diabetes insipidus will have inadequately low AVP level.
If the patient has polyuria without hypernatremia and will be evaluated for diabetes insipidus, the plasma sodium has to be above 145 mOsm/kg H2O prior to testing (via water deprivation test, hypertonic saline).
Calculating the free-water clearance (cH2O), which measures the amount of solute-free water excreted by the kidney, is usesful. However, this includes all osmoles, including urea, which does not contribute to the plasma tonicity because it freely equilibrates across cell membranes. To more accurately assess the effect of the urine output on osmoregulation, calculate the electrolyte–free-water clearance (cH2Oe), to estimate the ongoing renal losses of hypotonic fluid (cH2O = Vurine [1-(UOsm/SOsm)]; cH2Oe = Vurine [1-(UNa +UK)/SNa])
An example of the use of he above calculations is as follows: An 80-year-old, partially demented man with poor nutritional status is admitted to the hospital because of pneumonia. Hyperalimentation with high protein supplementation is started (containing 30 mEq/L each of Na+ and K+). Laboratory results over the ensuing 5 days are as follows:
The free-water clearance is calculated as follows:
cH2O = 4 x ( 1 - [510 ÷ 342] ) = –2 L/day
By this calculation, taking all osmoles into account, the patient retains 2 liters of water, improving hypernatremia; however, he is actually getting worse.
The electrolyte free-water clearance is calculated as follows:
eCH2O = 4 (1 - [(10 + 41) ÷ 156] ) = 2.7 L/day
The etiology of the hypernatremia is now apparent; the patient is losing approximately 2.7 L of free water per day in his urine, likely secondary to osmotic urea diuresis caused by hyperalimentation.
A magnetic resonance imaging (MRI) or computed tomography (CT) scan of the brain may be helpful in cases of central diabetes insipidus eventuating from head trauma or infiltrative lesions.
Histologic findings usually are noncontributory (although they may be helpful in central diabetes insipidus).
The goals of management in hypernatremia are as follows[29] :
Correcting the hypertonicity requires a careful decrease in serum sodium and plasma osmolality with the replacement of free water, either orally or parenterally. The rate of sodium correction depends on how acutely the hypernatremia developed and on the severity of symptoms.
Acute symptomatic hypernatremia, defined as hypernatremia occurring in a documented period of less than 24 hours, should be corrected rapidly. Chronic hypernatremia (>48 h), however, should be corrected more slowly due to the risks of brain edema during treatment. The brain adjusts to and mitigates chronic hypernatremia by increasing the intracellular content of organic osmolytes. If extracellular tonicity is rapidly decreased, water will move into the brain cells, producing cerebral edema, which may lead to herniation, permanent neurologic deficits, and myelinolysis.
Recommendations are as follows:
Total body water (TBW) refers to the lean body weight of the patient (percentage of TBW decreases in morbidly obese patients). The TBW deficit in the hyperosmolar patient that needs to be replaced can be roughly estimated using the formula following formula:
TBW deficit = correction factor x premorbid weight x (1 - 140/Na+)
Ongoing losses (insensible, renal) need to be added.
However, the formulae below, by Adrogué–Madias, are preferred over the conventional equation for water deficit, because the older equation underestimates the deficit in patients with hypotonic fluid loss and is not useful in situations in which sodium and potassium must be used in the infusate. Formulas used to manage hypernatremia are outlined below.
Equation 1: TBW = weight (kg) x correction factor
Correction factors are as follows:
Equation 2: Change in serum Na+ = (infusate Na+ - serum Na+) ÷ (TBW + 1)
Equation 3: Change in serum Na+ = ([infusate Na+ + infusate K+] – serum Na+) ÷ (TBW + 1)
Equation 2 allows for the estimation of 1 L of any infusate on serum Na+ concentration. Equation 3 allows for the estimation of 1 L of any infusate containing Na+ and K+ on serum Na+.
Common infusates and their Na+ contents include the following:
An example of the use of the above calculations is as follows: An obtunded 80-year-old man is brought to the emergency room with dry mucous membranes, fever, tachypnea, and a blood pressure of 134/75 mm Hg. His serum sodium concentration is 165 mmol/L. He weighs 70 kg. This man is found to have hypernatremia due to insensible water loss.
The man's TBW is calculated by the following:
(0.5 x 70) = 35 L
To reduce the man's serum sodium, D5 W will be used. Thus, the retention of 1 L of D5 W will reduce his serum sodium by (0 - 165) ÷ (35 + 1) = -4.6 mmol. The goal is to reduce his serum sodium by no more than 10 mmol/L in a 24-hour period. Thus, (10 ÷ 4.6) = 2.17 L of solution is required. About 1-1.5 L will be added for obligatory water loss to make a total of up to 3.67 L of D5 W over 24 hours, or 153 cc/h.
A clinically important study by Lindner and colleagues found that all the above formulae correlated significantly with measured changes in serum sodium in the patient cohort as a whole, but the individual variations were extreme.[30] Thus, although the above formulae can guide therapy, serial measurements of serum sodium are prudent. That finding is no surprise, considering that interindividual variables make it difficult to precisely estimate the individual TBW and its distribution in different body compartments.[31] For example, the degree to which interindividual differences in body fat percentage affect TBW is very large.[4]
If hypernatremia is accompanied by hyperglycemia with diabetes, take care when using a glucose-containing replacement fluid. However, the appropriate use of insulin will help during correction.
In hypervolemic and hypernatremic patients in the ICU who have an impaired renal excretion of sodium and potassium (eg, after renal failure) an addition of a loop diuretic to free water boluses increases renal sodium excretion. Fluid loss during loop diuretic therapy must be restored with the administration of fluid that is hypotonic to the urine.
Use of thiazide diuretics to enhance sodium excretion has been suggested as a treatment for hypernatremia acquired in the ICU. However, a randomized, placebo-controlled trial in 50 ICU patients found that hydrochlorothiazide, 25 mg/day for up to 7 days, did not have a significant effect on serum or urinary sodium concentration.[32]
Hypernatremia in the setting of volume overload (eg, heart failure and pulmonary edema) may require dialysis for correction.
Although water can be replaced by oral and parenteral routes, an obtunded patient with a large free water deficit likely requires parenteral treatment. If the deficit is small and the patient is alert and oriented, oral correction may be preferred.
Once hypernatremia is corrected, efforts are directed at treating the underlying cause of the condition. Such efforts may include free access to water and better control of diabetes mellitus. In addition, correction of hypokalemia and hypercalcemia as etiologies for nephrogenic diabetes insipidus may be required. Vasopressin (AVP, DDAVP) should be used for the treatment of central diabetes insipidus.
Surgical treatment may be required in the setting of severe central nervous system trauma and associated central diabetes insipidus.
Consultations include the following:
Diet should be altered as applicable to diabetes mellitus and need for increased water intake during increased insensible loss. A low-sodium diet will reduce oral solute intake and therefore diminish renal water loss.
Some patients with nephrogenic diabetes insipidus—particularly those in whom it is mild or incomplete—may benefit from diuretic therapy (eg, thiazides, loop-diuretics) in an effort to increase proximal tubular reabsorption and decrease delivery to diluting segments where water may be lost. Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the polyuria in these patients. In addition, any medications that may cause nephrogenic diabetes insipidus (such as lithium) may require discontinuation.
In patients with central diabetes insipidus, desmopressin administered orally or intranasally may be used. Pharmacologic agents can be used in partial central diabetes insipidus to increase circulating AVP. These drugs include chlorpropamide, clofibrate, and carbamazepine.
Clinical Context: Inhibits the reabsorption of sodium in the distal tubules, causing increased excretion of sodium and water, as well as of potassium and hydrogen ions.
Clinical Context: Loop diuretic that increases excretion of water by interfering with chloride-binding cotransport system, which in turn inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Increases renal blood flow without increasing filtration rate. Onset of action generally is within 1-h. Increases potassium, sodium, calcium, and magnesium excretion.
Clinical Context: Increases cellular permeability of collecting ducts, resulting in the reabsorption of water by the kidneys.
Outpatient care is related to water intake and medication treatment.
Inpatient care is appropriate only as it relates to the correction of underlying diseases that may lead to hypernatremia (diabetes mellitus).
Transfer may only be necessary in the setting of severe head trauma with central diabetes insipidus.
Figure A: Normal cell. Figure B: Cell initially responds to extracellular hypertonicity through passive osmosis of water extracellularly, resulting in cell shrinkage. Figure C: Cell actively responds to extracellular hypertonicity and cell shrinkage in order to limit water loss through transport of organic osmolytes across the cell membrane, as well as through intracellular production of these osmolytes. Figure D: Rapid correction of extracellular hypertonicity results in passive movement of water molecules into the relatively hypertonic intracellular space, causing cellular swelling, damage, and ultimately death.
Figure A: Normal cell. Figure B: Cell initially responds to extracellular hypertonicity through passive osmosis of water extracellularly, resulting in cell shrinkage. Figure C: Cell actively responds to extracellular hypertonicity and cell shrinkage in order to limit water loss through transport of organic osmolytes across the cell membrane, as well as through intracellular production of these osmolytes. Figure D: Rapid correction of extracellular hypertonicity results in passive movement of water molecules into the relatively hypertonic intracellular space, causing cellular swelling, damage, and ultimately death.
Characteristics of hypernatremia Symptoms related to the characteristics of hypernatremia Cognitive dysfunction and symptoms associated with neuronal cell shrinkage Lethargy, obtundation, confusion, abnormal speech, irritability, seizures, nystagmus, myoclonic jerks Dehydration or clinical signs of volume depletion Orthostatic blood pressure changes, tachycardia, oliguria, dry oral mucosa, abnormal skin turgor, dry axillae, Other clinical findings Weight loss, generalized weakness