From the Guidelines
Hypochloremia is primarily caused by excessive chloride loss, dilution, or inadequate intake, with the most common causes being vomiting, gastric suction, and diuretic medications, particularly loop diuretics like furosemide and thiazides like hydrochlorothiazide, as well as certain kidney disorders and metabolic alkalosis 1.
Causes of Hypochloremia
- Excessive chloride loss through vomiting and gastric suction, which directly remove chloride-rich gastric acid from the body
- Diuretic medications, such as loop diuretics (e.g., furosemide) and thiazides (e.g., hydrochlorothiazide), that cause significant urinary chloride excretion
- Certain kidney disorders, including salt-losing nephropathies and renal tubular acidosis, which contribute to chloride wasting
- Metabolic alkalosis, which often accompanies hypochloremia as the body compensates for acid-base imbalances
- Excessive sweating, particularly in hot environments or during intense physical activity, which can deplete chloride levels
- Dilutional hypochloremia, which may develop when large volumes of hypotonic fluids are administered, effectively diluting electrolyte concentrations
- Adrenal insufficiency, congestive heart failure, and syndrome of inappropriate antidiuretic hormone secretion (SIADH), which are additional conditions associated with low chloride levels
Treatment and Management
Treatment focuses on addressing the underlying cause while carefully replacing chloride, typically through normal saline (0.9% sodium chloride) administration in symptomatic cases. However, recent evidence suggests that buffered intravenous solutions may be preferred over normal saline in certain situations, such as perioperative fluid management, to avoid hyperchloraemic acidosis and renal vasoconstriction 1.
Key Considerations
- Chloride balance is closely related to sodium balance, but can also be influenced by independent factors, such as bicarbonate status 1
- The daily turnover of chloride is high, and renal conservation occurs through tubular reabsorption of 60-70% of the filtrated chloride 1
- Chloride is involved in maintaining osmotic pressure, hydration, and ionic neutrality, and is a major ion influencing the "strong ion difference" (SID), which helps explain metabolic acid-base abnormalities associated with changes in chloride concentration 1
From the Research
Causes of Low Chloride (Hypochloremia)
- Hypochloremia can be caused by various factors, including:
- Depletion of electrolytes, such as chloride and sodium, due to diuretic treatment 2
- Diuretic resistance, which can lead to poor diuretic response and worsening heart failure 3, 4
- Renal salt sensing and neurohormonal activation, which can contribute to diuretic resistance and poor outcomes in heart failure patients 3, 4
- Disease processes, such as leukemia, which can cause electrolyte disturbances, including hypochloremia, due to the release of electrolytes from malignant cells or drug therapy 5
- Gastrointestinal loss through nausea, vomiting, and malnutrition, which can exacerbate electrolyte imbalances 5
- Certain medications, such as cyclophosphamide and vincristine, which can induce SIADH and lead to hypochloremia 5
Relationship between Hypochloremia and Heart Failure
- Hypochloremia has been associated with poor outcomes in heart failure patients, including increased mortality and diuretic resistance 3, 6, 4
- Low serum chloride levels have been linked to impaired decongestion and poor diuretic response in heart failure patients 3
- Hypochloremia has been shown to be a prognostic factor in patients with heart failure, with higher incidence of intravenous diuretic rescue, emergency department visits, and readmission for heart failure 6
Mechanisms of Hypochloremia
- Chloride depletion has been proposed as a candidate mechanism for diuretic resistance and poor outcomes in heart failure patients 4
- Sodium-free chloride supplementation has been shown to increase serum chloride levels and improve cardiorenal parameters in heart failure patients 4
- Renal salt sensing and neurohormonal activation play a critical role in the development of hypochloremia and diuretic resistance in heart failure patients 3, 4