chloride

Chloride is the principal extracellular anion, moving with sodium and water and playing a critical role in maintaining plasma osmolality, blood volume, and electrical neutrality across cell membranes. It is central to acid-base physiology, particularly via the chloride-bicarbonate exchange in red blood cells (the 'chloride shift') and renal handling.

Hyperchloremia (Cl⁻ >106 mEq/L) commonly occurs with normal anion gap metabolic acidosis (e.g., diarrhea, renal tubular acidosis, excessive normal saline administration) and can be seen in dehydration. Hypochloremia (Cl⁻ <96 mEq/L) is associated with metabolic alkalosis, often from vomiting (loss of HCl), diuretic use (loop/thiazide), or nasogastric suction. It also occurs with SIADH or heart failure via dilution.

Chloride is critical in calculating the anion gap [Na - (Cl + HCO3)] to classify metabolic acidosis: a normal anion gap suggests concurrent hyperchloremia (loss of HCO3 replaced by Cl retention), while an elevated anion gap suggests accumulation of unmeasured anions (e.g., lactate, ketones) without chloride change.

Clinically, chloride is measured on basic metabolic panels alongside sodium, potassium, and bicarbonate. Urine chloride is useful in distinguishing causes of metabolic alkalosis: chloride-responsive (low urine Cl, e.g., vomiting, diuretic use - responds to saline) versus chloride-resistant (high urine Cl, e.g., hyperaldosteronism, Bartter/Gitelman syndrome).

Cystic fibrosis involves a defective CFTR chloride channel, leading to abnormal chloride and water transport across epithelial cells, causing thick mucus secretions - diagnosed via elevated sweat chloride test (>60 mEq/L).