Electrolyte Biomarkers: Chloride

Optimal Takeaways

Chloride is an essential mineral and major electrolyte with an active role in blood pressure regulation, fluid balance, acid-base balance, muscle contraction, digestion, and immunity. It is a component of sodium chloride, i.e., common table salt, and is also a component of gastric hydrochloric acid and neutrophil-generated hypochlorite.

Standard Range: 98 - 110 mEq/L

The ODX Range: 100 - 108 mEq/L

Low chloride levels can be associated with diuretic use, overhydration, CHF, excess ADH, vomiting, metabolic alkalosis, respiratory acidosis, aldosteronism, burns, hypokalemia, and Addison’s disease. Medications that decrease chloride include aldosterone, bicarbonates, loop and thiazide diuretics, and corticosteroids (Pagana 2021).

High chloride levels can be associated with anemia, dehydration, eclampsia, kidney dysfunction, metabolic acidosis, respiratory alkalosis, hyperparathyroidism, Cushing syndrome, and multiple myeloma. Medications that increase chloride include androgens, estrogens, NSAIDs, cortisone, and methyldopa (Pagana 2021).

Overview

Chloride is a major electrolyte and a key anion inside and outside the cell. It plays a significant role in acid-base balance, blood pressure regulation, cell volume regulation, muscle contraction, and digestion as a component of hydrochloric acid. The gastrointestinal tract and kidneys regulate blood levels of chloride (McCallum 2015).

Chloride is also a factor in fluid and pH balance. As the ionic form of chlorine, chloride also plays a vital role in innate immunity as a substrate for the phagocytic production of antimicrobial hypochlorite (bleach) (Wang 2015). Myeloperoxidase catalyzes the conversion of chloride and hydrogen peroxidase to hypochlorite, one of the most potent reactive oxygen species produced by neutrophils (Akong-Moore 2012).

Low chloride levels can cause excessive excitability of nerves and muscles, low blood pressure, shallow breathing, and tetany, while high levels can cause weakness and lethargy (Pagana 2021).

A retrospective study of 76,719 adult hospitalized patients found that a serum chloride of 105-108 mmol/L was optimal and that hospital mortality and increased length of stay were associated with a chloride below 100 mmol/L or above 108 mmol/L (Thongprayoon 2017).

In a data review of 12,968 hypertensive individuals, those with chloride levels 100 mEq/L or below had a 20% higher all-cause mortality rate than those above 100. Individuals with chloride above 100 mEq/L and sodium above 135 mEq/L had the most significant rate of survival (McCallum 2013).

The severity of congestive heart failure (CHF) was noted to increase as serum chloride decreased. A cut-off of 102.8 mEq/L was determined to predict mortality in those with CHF. Those with sodium of 138.4 mEq/L or below and chloride of 104.2 mEq/L or below had the most significant mortality risk. Increasing sodium to chloride ratio was also associated with an increasing risk of mortality. Researchers note that increasing chloride concentrations were associated with increasing albumin and ejection fraction and a decreasing trend for RDW, NT-pro BNP, BUN, total bilirubin, uric acid, and diuretic use. Diuretics can interfere with the retention of chloride and can exacerbate hypochloremia (Zhang 2018).

References

McCallum, Linsay et al. “Serum chloride is an independent predictor of mortality in hypertensive patients.” Hypertension (Dallas, Tex. : 1979) vol. 62,5 (2013): 836-43. doi:10.1161/HYPERTENSIONAHA.113.01793

McCallum, Linsay et al. “The hidden hand of chloride in hypertension.” Pflugers Archiv : European journal of physiology vol. 467,3 (2015): 595-603. doi:10.1007/s00424-015-1690-8

Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.

Thongprayoon, Charat et al. “Chloride alterations in hospitalized patients: Prevalence and outcome significance.” PloS one vol. 12,3 e0174430. 22 Mar. 2017, doi:10.1371/journal.pone.0174430

Wang, Guoshun, and William M Nauseef. “Salt, chloride, bleach, and innate host defense.” Journal of leukocyte biology vol. 98,2 (2015): 163-72. doi:10.1189/jlb.4RU0315-109R

Zhang, Yang et al. “Serum chloride as a novel marker for adding prognostic information of mortality in chronic heart failure.” Clinica chimica acta; international journal of clinical chemistry vol. 483 (2018): 112-118. doi:10.1016/j.cca.2018.04.028