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Electrolyte series

Sodium and chloride

Rowe, Amy BSN, RN, CCRN

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doi: 10.1097/01.CCN.0000532360.64613.10
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This article in our series on serum electrolytes and disorders of electrolyte balance explores sodium and chloride. Sodium is the major extracellular fluid (ECF) cation (positively charged ion) and chloride is the major ECF anion (negatively charged ion). Chloride provides electroneutrality, especially in relation to sodium; chloride's transport is generally passive, following the active transport of sodium. As a result, increases or decreases in serum chloride concentration are proportional to changes in serum sodium concentration. Concentrations of chloride are generally inversely related to the concentration of serum sodium.1 Because of this relationship, sodium and chloride are generally discussed together.

The normal serum concentration of sodium is 135 to 145 mEq/L.2 The normal serum concentration of chloride is 97 to 107 mEq/L, though the normal range at different labs may vary slightly.2

Electrolytes serve many functions in the body, one of the most important being fluid distribution throughout the different body compartments. Water crosses cell membranes freely, moving from an area of low solute concentration to high solute concentration. The degree of solute concentration, referred to as osmolality, determines fluid movement across the fluid compartments. Osmolality equalizes across fluid compartments because of water movement, not solute movement. Sodium and chloride are the two main electrolytes responsible for most fluid movement, accounting for 80% of the ECF osmolality.3 Normal serum osmolality is 275 to 290 mOsm/kg.3,4

Tonicity describes how the effective osmolality of the ECF influences cellular hydration. When the ECF has a lower osmolality than the intracellular fluid (ICF), the ECF is considered hypotonic. In a hypotonic state, water shifts from the ECF into the cells, causing them to swell. When the osmolality of the ECF is high, it is considered hypertonic. Hypertonic states dehydrate the cells, shifting water out of the cell and into the ECF.3,4 Changes in ECF and ICF osmolality are followed by water movement and determine changes in cell volume.3

Regulation of sodium and chloride balance Neurologic, hormonal, and renal factors combine to regulate sodium levels and preserve fluid volume homeostasis. Decreases in renal blood flow and ECF and low ECF sodium levels stimulate the juxtaglomerular cells of the kidneys to release renin, an enzyme that acts on an inactive circulating plasma protein called angiotensinogen and converts it to angiotensin I. Angiotensin I travels to the lungs, where angiotensin-converting enzyme converts it to angiotensin II. Angiotensin II reduces sodium excretion by increasing sodium reabsorption by the renal proximal tubules. It also stimulates aldosterone secretion from the adrenal gland. Aldosterone stimulates the kidneys to retain sodium, causing the reabsorption of water and resulting in ECF volume expansion. In summary, activation of the renin-angiotensin-aldosterone system results in increased sodium and water reabsorption, ECF expansion, and increased BP.5 (See The renin-angiotensin-aldosterone system.)

The renin-angiotensin-aldosterone system

The brain plays a role in the neurohormonal regulation of sodium and fluid volume as well. An increase in ECF sodium concentration increases osmolality, which stimulates the thirst center in the hypothalamus, resulting in increased water intake.4 The posterior pituitary gland releases antidiuretic hormone (ADH) in response to stimulation of osmoreceptors or baroreceptors. Osmoreceptors sense high osmolality, while baroreceptors sense hypovolemia and accompanying low arterial BP. ADH acts on the renal distal and collecting ducts, resulting in water reabsorption and decreased osmolality.5 (See Pathways for regulation of extracellular water volume.)

An increase in blood volume from water retention stimulates atrial stretch receptors, causing release of atrial natriuretic peptide (ANP) from the cardiac muscle fibers. ANP increases the excretion of sodium by the distal and collecting tubules in the kidneys. The resulting natriuresis and diuresis reduces blood volume and BP.

Pathways for regulation of extracellular water volume

The distal and collecting tubules of the kidneys respond to increased circulating volume by releasing the renal vasodilatory natriuretic peptide urodilatin, which stimulates natriuresis and diuresis, resulting in reduced ECF volume.5

Chloride regulation is tightly tied to acid-base balance. The gastrointestinal (GI) tract increases chloride absorption from food sources when serum chloride is low.6 The kidneys play a central role in chloride metabolism, reabsorbing nearly all filtered chloride to maintain desired concentrations.7 Chloride and bicarbonate ions reciprocally adjust up-and-down concentration gradients to maintain acid-base balance.2 Chloride is lost through GI sources, such as vomiting, and is excreted by the kidneys in response to acidosis.6


Critically ill patients are at risk for both sodium and chloride imbalances related to their comorbidities and subsequent treatments.8 Many studies have reported both mortality and morbidity associated with sodium and chloride imbalances in critically ill patients.8-14 Dysnatremia is independently associated with mortality in the ICU and is often associated with significant hormonal responses to injury and inflammation.9,14 Even small variations in serum sodium levels may be associated with an increase in mortality, which is a concern because most I.V. fluids administered to deliver medications or keep lines open contain sodium.15 Abnormal serum chloride levels have been associated with an increased risk of mortality in critical care patients, particularly those with systemic inflammatory response syndrome and postsurgical patients.16,17 Increased serum chloride levels are associated with increased risk of acute kidney injury (AKI).16,17

Manifestations of hyponatremia and hypernatremia


Hypernatremia occurs when the serum sodium is greater than 145 mEq/L, resulting in a water-deficit concentration relative to sodium. The sodium-water imbalance may result from an intake of more sodium compared with water or a loss of more water compared with sodium.5

Causes. Common causes of hypernatremia related to sodium gain include tube feeding, hypertonic I.V. fluids, salt water near-drowning, food intake without adequate fluids, limited access to water, and decreased thirst stimulus. Hypernatremia causes related to water losses include diuresis (medications), prolonged vomiting/diarrhea without adequate intake, and lack of ADH (as seen in diabetes insipidus).5,8

Signs and symptoms. Early neurologic signs and symptoms of hypernatremia are a result of water loss in neuronal cells, which are the most sensitive to osmolality changes.5,15 (See Manifestations of hyponatremia and hypernatremia.) Rapid changes in serum sodium levels in either direction can cause permanent, severe, and sometimes fatal brain injury.8

Treatment. Balancing the solute-to-water ratio is the basis of treatment for hypernatremia. To restore balance, increasing free water intake may be considered (for example, scheduled water flushes for patients receiving tube feedings), reducing use of saline infusions (including medication dilution and keep-vein-open rate solutions), switching to hypotonic I.V. solutions for medication dilutions (for example, D5W), administering desmopressin if diabetes insipidus is the cause of ADH suppression, or modifying or discontinuing diuretics.18


Hyponatremia results when there is a gain of more water relative to sodium concentration or a loss of more sodium relative to water. It is often classified according to volume status and tonicity (see Types of hyponatremia).5

Causes. Examples of excess water gain compared with sodium include excessive ADH, excessive hypotonic I.V. fluid administration, hypotonic irrigation solutions used during prostate and hysterectomy procedures, tap water enemas, psychogenic polydipsia, excessive beer ingestion, near-drowning in fresh water, and certain selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine.5,14,21,22 Examples of losing more sodium than water include use of diuretics (thiazides), salt-wasting renal disease, adrenal insufficiency, and replacement of water (but not sodium) lost from GI sources, diaphoresis, or burn injuries.5,4,14,21 Hyponatremia usually equals hypotonicity, with the exception of disorders such as hyperglycemic hyponatremia.19,21 Patients with excessively high levels of serum lipids or proteins may falsely appear to have hyponatremia (pseudohyponatremia) related to lab test inefficiencies with these disorders.4,21 (Visit to see an animation illustrating water movement between fluid compartments.)

Types of hyponatremia4,19,20

Signs and symptoms. The signs and symptoms of hyponatremia are primarily neurologic in nature. (See Manifestations of hyponatremia and hypernatremia.) The most severe signs and symptoms of hyponatremia are caused by cerebral edema, and profound hyponatremia may lead to cerebral herniation.5,21

Treatment. When considering treatment for hyponatremia, it is important to determine how long hyponatremia has been present. Acute hyponatremia is considered as present for less than 48 hours, while chronic hyponatremia is considered as present for greater than 48 hours.4 Physical assessment findings should determine if acute correction is required.21 Aggressive interventions are appropriate when serum sodium levels decrease rapidly and when signs and symptoms are severe.4 Acute symptomatic hyponatremia can be treated with I.V. boluses of hypertonic saline, such as 3% sodium chloride.4 Administration of these boluses should be based on symptomology, not an arbitrary lab value.21 Chronic hyponatremia should be treated with fluid restriction, salt tablets, slow continuous infusions of 3% sodium chloride, urea, vasopressin antagonists, or diuretics for hypervolemic states.4

Critical care nurses should use caution when replacing sodium, as brain injury is associated with rapid reversal of hyponatremia.4,19,21 When initiating treatment for correction of hyponatremia, the goal rate for rise of sodium levels is no more than 8 mEq/L in the first 24 hours, 14 mEq/L by 48 hours, and 18 mEq/L by 72 hours.4 When sodium levels are less than 120 mEq/L or the patient has risk factors for osmotic demyelination, avoid correcting sodium faster than 8 mEq/L/day and consider replacing lost water or administering medications that prevent water loss.4

Osmotic demyelination is a devastating disorder that results in progressive quadriplegia, dysarthria, dysphagia, and alteration of consciousness after days of hyponatremia correction.4,19,21 Water diffusion and cell shrinkage lead to a loss of oligodendrocytes and myelin in central and extrapontine areas.19,21 Alcoholism, malnutrition, hypokalemia, liver failure, and malignancies increase the risk of osmotic demyelination.19,21 Signs and symptoms may be delayed for several days after treatment, making the recognition and diagnosis difficult for those unfamiliar with the disorder.4 Retrospective studies show osmotic demyelination more commonly occurs when sodium correction exceeds 10 to 12 mEq/L per day.21 Osmotic demyelination occurs less commonly if hyponatremia is acute and the sodium level is greater than 120 mEq/L.19


Hyperchloremia is present when the serum concentration of chloride ions exceeds 108-110 mEq/L.

Causes. Excessive chloride intake or excessive water loss leads to hyperchloremia.7,10,23,24 Excess chloride intake occurs with large volume resuscitation with 0.9% sodium chloride (sepsis, trauma), hypertonic saline administration, near-drowning in salt water, or an increase in dietary acid load with concomitant chronic kidney dysfunction.7,24 Increased water loss relative to chloride concentration occurs with fever, diaphoresis, inability to access water, decreased thirst sensation, diabetes insipidus, some forms of diarrhea, osmotic diuresis (mannitol therapy), or renal dysfunction.7,24 Hyperchloremia is associated with decreased renal blood flow, reduced glomerular filtration rate, decreased renal cortical perfusion, increased interstitial edema (GI and kidney), altered coagulation, impaired immune function, increased mortality and morbidity in critically ill patients, and decreased survival in patients diagnosed with AKI.7,23,25,26

Excess chloride concentration disproportionate to sodium leads to hyperchloremic metabolic acidosis.10 Hyperchloremic acidosis is commonly reported with large volume 0.9% sodium chloride resuscitation for shock states, especially shock related to sepsis and trauma.7,2,26 A variety of severe complications have been associated with hyperchloremic acidosis, including increased hospital mortality, decreased days of survival, proinflammatory modulation, renal dysfunction, and increased bleeding and transfusion after major surgery.2,10,12,25,26

Signs and symptoms. Rather than imbalances of chloride itself, the signs and symptoms of hyperchloremia are related to acid-base disturbances, serum sodium levels, and fluid overload. Hyperchloremia related to free water loss will result in signs and symptoms of dehydration: increased thirst, dry mucous membranes, hypotension, and tachycardia. This is in contrast to signs and symptoms seen with hyperchloremia related to increased chloride concentration (as seen in 0.9% sodium chloride fluid resuscitation): hypertension, edema, congestive heart failure, and pulmonary edema.5-7

Treatment. Sources of excess chloride should be removed, including further use of chloride-containing I.V. solutions; switching to balanced I.V. fluids or administering free water should be considered if water loss was the cause.7 In the case of hyperchloremic metabolic acidosis, bicarbonate replacement should be considered.7


Hypochloremia, a serum chloride concentration less than 95 mEq/L, results when there is an excess of extracellular volume (ECV) relative to chloride concentration or when there has been an excess loss of chloride.

Causes. Hypochloremia is commonly observed with GI losses from protracted emesis, gastric suction, high-dose acid suppression therapy, and some types of diarrhea.6 Cardiovascular patients are likely to have hypochloremia related to use of loop and thiazide diuretics, which disproportionally excrete chloride in relation to sodium leading to hypochloremic alkalosis.10 Neurologically injured patients may experience hypochloremia as a result of fluid loss with osmotic diuretic therapy. Renal sources of hypochloremia include chronic renal failure and adrenal insufficiency.5-7

Hypochloremia may result in a metabolic alkalosis as a result of primary chloride losses or as a result of respiratory acidosis.6 Hypochloremic metabolic alkalosis has been associated with increased risk of cardiac dysrhythmias and decreased neutrophil function.10,23

Signs and symptoms. Clinical manifestations of hypochloremia are related to acid-base disturbances and fluid losses rather than derangements of serum chloride levels. Signs and symptoms associated with hypochloremia secondary to total body chloride depletion present as dehydration, hypotension, tachycardia, and orthostatic hypotension. Signs and symptoms associated with hypochloremia related to an increased ECV are related to elevated BP and fluid overload.5-7

Treatment. Treatment goals include restoration of fluid balance, replacement of associated electrolytes, and restoration of acid-base balance.6

Evidence-based practice

Today, normal saline is the most commonly used crystalloid worldwide, but many clinicians do not recognize the potentially harmful effects associated with its administration.12,16,25 The “isotonic” crystalloid 0.9% sodium chloride is actually hypertonic and acidic, with a pH range of 4.5 to 7.0 (lower when stored in polyvinyl chloride bags, higher when stored in glass bottles).16 Additionally, 0.9% sodium chloride provides a chloride load of 154 mEq/L, nearly 1.5 times greater than normal blood concentration.25

Over the last 10 years, there has been an increased interest in studying the effects of I.V. solutions on the outcomes of critically ill patients. One source of sodium and chloride derangement is the use of 0.9% sodium chloride for resuscitation of shock states, medication dilution, and prevention of contrast-related injuries from radiologic imaging.3,15,26-29 Researchers have also begun evaluating the difference in outcomes associated with 0.9% sodium chloride administration versus “balanced” crystalloids, which are solutions with an electrolyte composition closer to that of plasma.28

Balanced fluids present their own challenges during resuscitation because most are not compatible with blood products due to their calcium content. Non-calcium-containing balanced solutions are often perceived as being too expensive for resuscitation administration.29


Traditionally, hyponatremia was the most common form of sodium imbalance in critically ill patients.8 Now, acquired hypernatremia occurs more commonly, as does severe hypernatremia (sodium levels greater than 155 mEq/L).8 The relationship between sodium and mortality has been reported in medical/surgical, mixed ICU, cardiovascular, cardiovascular surgery, trauma, and neurointensive care units.8 The incidence of dysnatremia in critically ill patients has been reported at 25% to 45%, with even mild variations outside of normal ranges associated with higher mortality and increased length of stay.27 There is a growing body of evidence to support the theory that chloride-rich I.V. fluids lead to a greater occurrence of AKI, metabolic acidosis, and hyperkalemia.27 Post-ICU admittance chloride elevation has been linked to increased hospital mortality and a decrease in days of survival.10 Some researchers suggest that control of sodium and chloride, maintaining each within the normal physiologic range, may be the next critical care quality initiative.9


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    chloride; extracellular fluid compartment; hyperchloremia; hypernatremia; hypochloremia; hyponatremia; osmolality; renin-angiotensin-aldosterone system; sodium; tonicity

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