Lab It Up: Hypochloremia

Hypochloremia

Chloride <96 mEq/L

Hypochloremia can be caused by a total chloride deficit, dilutional condition, or acid-base disorder.
Chloride is the most abundant anion in the extracellular fluid compartment.
The primary drivers of chloride homeostasis are:
- Passive equilibration with sodium
- Chloride-bicarbonate anion exchange in the kidney, such that bicarbonate excretion is exchanged for chloride resorption (and vice versa)

Causes [1]

Total chloride deficit

Often associated with metabolic alkalosis, because (1) renal absorption of sodium shifts towards the form of sodium bicarbonate instead of sodium chloride and (2) contraction alkalosis

Renal causes
- Diuretic overuse
- Salt-losing nephropathies (e.g., adrenal insufficiency)
Gastrointestinal causes
- Vomiting or gastric fluid drainage (gastric contents contain hydrochloric acid)
- Decreased NaCl intake
- Small bowel fistula
Skin
- Burns

Net free water gain (dilutional)

Hyponatremia often concurrently exists.

Infusion of IV hypotonic fluids
Pathologic water drinkers
Edema states (cirrhosis, congestive heart failure, nephrotic syndrome)
Intrinsic renal diseases
Hypothyroidism
Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
Medications (barbiturates, chlorpropramide, clofibrate, morphine, nicotine, tricyclics)

Acid-base abnormality

Increased renal resorption of bicarbonate results in increased excretion of chloride (and potassium).

Primary metabolic alkalosis
Compensatory respiratory acidosis

Special Populations

Pediatrics

Consider the below conditions with hypochloremia, specifically in the setting of metabolic alkalosis. A urinary chloride level will help differentiate these conditions [2].

Gastrointestinal
- Nasogastric tube suction, such as in NICU and PICU settings
- Severe gastroesophageal reflux
- Pyloric stenosis
- Laxative abuse
- Congenital chloride diarrhea
Renal
- Diuretic use
- Chloride-losing nephropathy
- Bartter Syndrome: Genetic defect in chloride transport in kidney
- Gitelman Syndrome: Familial hypokalemia-hypomagnesemia from renal inability to resorb salts
Skin
- Cystic fibrosis

The lower end of the normal reference range for chloride levels are slightly different than for adults, especially for those older than 2-3 months old [3].

Pediatric Age	Hypochloremia definition
Premature infant	Cl <95 mEq/L
Newborn	Cl <96 mEq/L
Child	Cl <90 mEq/L

Pregnancy

There are no pregnancy-specific causes for hyperchloremia, although the lower end of the normal reference range may be slightly higher in the first trimester [4].

Trimester Stage	Hypochloremia definition
First	Cl <101 mEq/L
Second	Cl <97 mEq/L
Third	Cl <97 mEq/L

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Originally published Feb 12, 2023 (updated February 13, 2023)

References

Morrison G. Serum Chloride. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 197.
Desai J. Hypochloremic Metabolic Acidosis. Medscape Section on Pediatrics: Genetics and Metabolic Disease. Published Aug 30, 2018.
Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic and Laboratory Test Reference. 14th ed. St. Louis, MO: Elsevier; 2019.
Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009 Dec;114(6):1326-1331. doi: 10.1097/AOG.0b013e3181c2bde8. Erratum in: Obstet Gynecol. 2010 Feb;115(2 Pt 1):387. PMID: 19935037.