Chloride is the major anion in the extracellular water space; its physiological significance is in maintaining proper body water distribution, osmotic pressure, and normal anion-cation balance in the extracellular fluid compartment.
Chloride is increased in dehydration, renal tubular acidosis (hyperchloremia metabolic acidosis), acute renal failure, metabolic acidosis associated with prolonged diarrhea and loss of sodium bicarbonate, diabetes insipidus, adrenocortical hyperfunction, salicylate intoxication, and with excessive infusion of isotonic saline or extremely high dietary intake of salt. Hyperchloremia acidosis may be a sign of severe renal tubular pathology.
Chloride is decreased in overhydration, chronic respiratory acidosis, salt-losing nephritis, metabolic alkalosis, congestive heart failure, Addisonian crisis, certain types of metabolic acidosis, persistent gastric secretion and prolonged vomiting, aldosteronism, bromide intoxication, syndrome of inappropriate antidiuretic hormone secretion, and conditions associated with expansion of extracellular fluid volume.
Urine sodium and chloride excretion are similar and, under steady state conditions, both the urinary sodium and chloride excretion reflect the intake of sodium chloride (NaCl). During states of extracellular volume depletion, low values indicate appropriate renal reabsorption of these ions, whereas elevated values indicate inappropriate excretion (renal wasting). Urinary sodium and chloride excretion may be dissociated during metabolic alkalosis with volume depletion where urine sodium excretion may be high (due to renal excretion of NaHCO3) while urine chloride excretion remains appropriately low.