Chloride is the major extracellular anion in the human body — it is present in the blood at concentrations of approximately 96-106mEq/L and it is the essential counter-ion for the sodium (Na+) in the extracellular fluid and for the hydrogen ions (H+) in the gastric juice. The chloride is obtained from the diet primarily as sodium chloride (table salt) and potassium chloride (KCl), and the typical dietary chloride intake is 3-6g daily (from the salt, the processed foods, and the vegetables). The chloride requirement is approximately 2.3g daily for adults, and the deficiency is rare in people who have access to the adequate dietary salt — but it can occur in people with the chronic vomiting or nasogastric suction (which depletes the gastric chloride), in people with the diarrhoea (which depletes the intestinal chloride), in people with the diuretic therapy (particularly the thiazide and the loop diuretics, which increase the renal chloride excretion), and in people with the cystic fibrosis (who have the impaired chloride channel function and the elevated sweat chloride). Without adequate chloride, the acid-base balance is disrupted, the metabolic alkalosis develops, and the stomach acid secretion is impaired — the hallmark of the chloride deficiency.
Chloride and the Metabolic Alkalosis
The metabolic alkalosis is the acid-base disturbance that is characterised by the elevated blood pH (above 7.45) and by the elevated serum bicarbonate (above 28mEq/L) — it is the most common acid-base disturbance in hospitalised patients, and it is most commonly caused by the chloride depletion (the hypochloremic metabolic alkalosis). The hypochloremic metabolic alkalosis occurs when the chloride is lost in excess of the sodium (as occurs in the vomiting, in the nasogastric suction, and in the diuretic therapy) — the kidneys attempt to conserve the sodium by exchanging it for the hydrogen ions and the potassium (producing the paradoxical acid urine), and the result is the metabolic alkalosis with the hypochloremia and the hypokalemia. The chloride is the key to understanding this acid-base disturbance — when chloride is the dominant anion that is lost, the kidneys retain the sodium and the bicarbonate (to maintain the electroneutrality), and the blood becomes alkalotic. The treatment of the hypochloremic metabolic alkalosis involves the replacement of the chloride (as sodium chloride or potassium chloride) and the correction of the underlying chloride loss.
The clinical importance of the chloride for the acid-base balance is underscored by the observation that the chloride administration rapidly corrects the metabolic alkalosis in patients with the hypochloremic metabolic alkalosis. A study in 20 patients with the metabolic alkalosis found that the intravenous saline (0.9% NaCl) infusion rapidly corrected the metabolic alkalosis in all patients, with the serum bicarbonate returning to normal within 24-48 hours in most patients — demonstrating the efficacy of the chloride replacement for the correction of the hypochloremic metabolic alkalosis.
Chloride and the Stomach Acid
Chloride is the essential anion that is secreted by the parietal cells of the stomach — it is the counter-ion for the hydrogen ions that are secreted by the H+/K+-ATPase (the proton pump) into the gastric lumen, and it is the component of the hydrochloric acid (HCl) that gives the gastric juice its characteristic acidity (pH 1.5-3.5). The parietal cell secretes the HCl by the H+/K+-ATPase, which exchanges the intracellular H+ for the extracellular K+ (using the energy of the ATP hydrolysis), and by the chloride channel (CFTR or TMEM16A), which allows the chloride to follow the H+ into the gastric lumen to maintain the electroneutrality. Without adequate chloride, the HCl secretion is impaired, the gastric pH rises (becomes less acidic), and the protein digestion, the mineral absorption, and the antimicrobial defence in the stomach are all compromised. The chloriderich diet and the adequate salt intake are essential for the normal stomach acid secretion — and the hypochlorhydria (low stomach acid) that is associated with the chloride deficiency is one of the most common and most underdiagnosed digestive problems, particularly in older adults.
Practical Application
For general chloride supplementation, the evidence-based approach is to ensure the adequate dietary salt (sodium chloride) intake — 2.3g of chloride daily is the estimated minimum requirement, and 3-6g daily is the typical intake from a normal diet that includes the salt. The chloride is found in most foods as a component of the sodium chloride (table salt) and of the potassium chloride (KCl), and it is particularly abundant in the seaweed, the olives, the rye, and the tomatoes. For comprehensive acid-base and digestive support, chloride pairs well with the sodium (which is the counter-ion for the chloride in the extracellular fluid and which is essential for the blood pressure maintenance and for the nerve and muscle function), with the potassium (which is the counter-ion for the chloride intracellularly and which is essential for the cellular function and for the prevention of the hypokalemia that accompanies the chloride deficiency), with the magnesium (which is a cofactor for the H+/K+-ATPase and for many of the other enzymes of the gastric acid secretion), and with the zinc (which is required for the carbonic anhydrase activity and for the production of the gastric acid).
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