Chloride

Chloride is the predominant anion that exists in the extracellular space. It maintains cellular integrity via its effects on osmotic pressure and water balance, in addition to maintaining acid-base balance. ^[1] Chloride daily requirements for adults are 80-120 mEq/d as sodium chloride (NaCL). ^[2]

Normal findings ^[3] :

• Adult/elderly: 98-106 mEq/L or 98-106 mmol/L (SI units)
• Child: 90-110 mEq/L
• Newborn: 96-106 mEq/L
• Premature infant: 95-110 mEq/L

Possible critical values: < 80 or > 115 mEq/L

Chloride is an extracellular fluid anion that plays an important role in maintaining normal acid-base balance and along with sodium maintains water balance and serum osmolality. ^[4] It mainly exists as sodium chloride or hydrochloric acid. ^{[4, 5]} Hyperchloremia means high levels serum chloride and hypochloremia means low levels of serum chloride. ^[4] Chloride usually reflects changes in sodium, except in acid-base disorders in which changes in chloride are independent from sodium. ^[6]

Hyperchloremia occurs in a wide variety of conditions, including renal failure, nephrotic syndrome, renal tubular acidosis, dehydration, overtreatment with saline, hyperparathyroidism, diabetes insipidus, metabolic acidosis from diarrhea (loss of HCO₃^–), respiratory alkalosis, hyperadrenocorticism, and the use of certain drugs like acetazolamide (hyperchloremic acidosis), androgens, hydrochlorothiazide, salicylates (intoxication). ^{[5, 6]}

Hypochloremia also occurs in a wide variety of conditions, including vomiting, diarrhea, gastrointestinal suction, renal failure combined with salt deprivation, overtreatment with diuretics, chronic respiratory acidosis, diabetic ketoacidosis, excessive sweating, syndrome of inappropriate antidiurectic hormone excretion (SIADH), salt-losing nephropathy, acute intermittent porphyria, water intoxication, expansion of extracellular fluid volume, adrenal insufficiency, hyperaldosteronism, metabolic alkalosis, and the use of certain drugs like chronic laxative or bicarbonate ingestion, corticosteroids, and diuretics. ^{[5, 6]}

Serum chloride is helpful in the assessment of normal or high anion gap metabolic acidosis and in making the differentiation between hypercalcemia secondary to primary hyperparathyroidism versus hypercalcemia secondary to malignancy (elevated vs low chloride respectively). ^[5] It is usually used along with sodium, potassium, and CO₂ to assess electrolyte, acid-base, and water balance. ^[6]

See the list below:

• Specimen: blood

• Container: Green-top tube

• Collection method: Obtain a 5-mL blood sample in a green-top tube then gently invert tube several times (do not agitate to prevent RBC hemolysis). Keep specimen cool as elevated temperatures can alter the result. No specific condition exists under which the specimen should be drawn.

Description

Chloride is the predominant anion that exists in the extracellular space. It maintains cellular integrity via its effects on osmotic pressure and water balance, in addition to maintaining acid-base balance. ^[1] Chloride daily requirements for adults are 80-120 mEq/d as NaCL. ^[2]

In general, chloride reabsorption follows sodium reabsorption. 1 liter of filtrate in kidney tubules contains around 140 mEq of sodium. To maintain electroneutrality, it should also contain around the same amount of anions, which are mainly chloride (110 mEq) and bicarbonate (24 mEq). Sixty-five to seventy percent of the total amount of filtered chloride is reabsorbed, which is close to the fractional reabsorption of sodium and water. ^[7]

Chloride is mainly transported via electroneutral cation-Cl cotransporters, which allow Cl to always follow cations mainly Na and K across cellular membranes. ^[7] Cation-Cl cotransporters are transmembrane proteins that include thiazide-sensitive Na-Cl co-transporter, loop diuretic-sensitive Na-K-2Cl co-transporters, and K-Cl co-transporters. ^[8] “These membrane proteins are involved in several physiological activities including transepithelial ion absorption and secretion, cell volume regulation, and setting intracellular Cl concentration below or above its electrochemical potential equilibrium. In addition, members of this family play an important role in cardiovascular and neuronal pharmacology and pathophysiology.” ^[8]

Indications

Serum chloride is mainly used to assess the following: ^[1]

• Acid-base status

• Water balance

Interferences

Serum chloride levels can be affected by the following factors: ^[1]

• Infants have higher levels than adults and children.

• Excessive IV saline infusions can results in high values.

• Certain drugs can also alter chloride levels (ie, loop diuretics, thiazide diuretics).

Considerations

See the list below:

• Excessive intake or inadequate excretion of chloride can result in hyperchloremic metabolic acidosis, in which case bicarbonate, acetate, citrate, or phosphate salts should be substituted for chloride salts when administering infusions to such patients. ^[9]

• Hyperchloremia can result in weakness, lethargy, unconsciousness (usually a late sign), and Kussmaul respirations. ^[4]

• Hypochloremia can result in hyperirritability, tetany or muscular excitability, slowed respirations, and hypotension secondary to fluid loss. ^[4]