From the Guidelines
Normal anion gap metabolic alkalosis is primarily caused by excessive loss of hydrogen ions or gain of bicarbonate, with the main causes including vomiting or nasogastric suction, diuretic use, hypokalemia, and excessive alkali administration. The causes of normal anion gap metabolic alkalosis can be understood by considering the role of electrolytes in maintaining acid-base balance, as discussed in the study by 1.
Key Causes
- Vomiting or nasogastric suction, which directly removes gastric acid from the body
- Diuretic use, particularly loop and thiazide diuretics like furosemide and hydrochlorothiazide, which increase renal bicarbonate reabsorption
- Hypokalemia, which promotes hydrogen ion secretion in exchange for potassium reabsorption
- Excessive alkali administration such as sodium bicarbonate
- Primary hyperaldosteronism, Cushing's syndrome, severe hypomagnesemia, Bartter and Gitelman syndromes, and post-hypercapnic states
Role of Chloride
Chloride depletion plays a crucial role in maintaining metabolic alkalosis, as the kidneys normally excrete excess bicarbonate but cannot do so when chloride is deficient, as explained by 1. This is why saline administration often corrects metabolic alkalosis by providing chloride ions.
Treatment Approach
Treatment should address the underlying cause while correcting fluid and electrolyte imbalances, particularly potassium and chloride deficiencies, which are often present and perpetuate the alkalotic state, as supported by the guidelines from 1. It is essential to manage fluid and electrolyte balance carefully to avoid complications, as highlighted in the study by 1, which recommends maintaining near-zero fluid and electrolyte balance to reduce the risk of developing complications. In addition, the use of certain medications, such as K-sparing diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, can help ameliorate the electrolyte abnormalities in conditions like Bartter syndrome, as discussed in the study by 1. Overall, the management of normal anion gap metabolic alkalosis requires a comprehensive approach that takes into account the underlying causes, electrolyte imbalances, and the need for careful fluid management, as emphasized by the studies 1, 1, and 1.
From the FDA Drug Label
Patients should be observed for signs of fluid or electrolyte disturbances, i. e. hyponatremia, hypochloremic alkalosis, and hypokalemia and hypomagnesemia. Supplemental potassium chloride and, if required, an aldosterone antagonist are helpful in preventing hypokalemia and metabolic alkalosis
The causes of normal anion gap (electrolyte imbalance) metabolic alkalosis (elevated blood pH) include:
- Hypochloremic alkalosis 2
- Hypokalemia 2, 3 Key factors that may contribute to the development of metabolic alkalosis include:
- Brisk diuresis 2
- Severe cirrhosis 2
- Concomitant use of corticosteroid or adrenocorticotropic hormone (ACTH) 2
- Prolonged therapy 2
- Interference with adequate oral electrolyte intake 2
From the Research
Causes of Normal Anion Gap Metabolic Alkalosis
The causes of normal anion gap metabolic alkalosis can be divided into several categories, including:
- Chloride depletion alkalosis, which can be caused by vomiting, nasogastric suction, or the use of diuretics 4, 5, 6
- Mineralocorticoid excess syndromes, such as hyperaldosteronism 4, 5, 6
- Apparent mineralocorticoid excess syndromes, such as licorice ingestion 4, 6
- Excess alkali administration, such as ingestion of baking soda or other alkali-containing substances 7, 6
- Other causes, such as genetic diseases like Bartter syndrome, Gitelman syndrome, and cystic fibrosis 6
Mechanisms of Metabolic Alkalosis
Metabolic alkalosis can result from a loss of fixed acid or a net accumulation of bicarbonate within the extracellular fluid 6. The loss of acid may be via the gastrointestinal tract or the kidney, whereas the sources of excess alkali may be via oral or parenteral alkali intake 6. Factors that interfere with the kidney's ability to eliminate excess bicarbonate, such as volume contraction, low glomerular filtration rate, potassium deficiency, hypochloremia, aldosterone excess, and elevated arterial carbon dioxide, can promote the generation or impair the correction of metabolic alkalosis 5, 6.
Diagnosis and Evaluation
The evaluation of metabolic alkalosis requires measurement of urine chloride concentration, plasma levels of renin and aldosterone, and assessment of volemic status 5. The urinary chloride level can help establish the mechanism of alkalosis, with low levels indicating saline-responsive alkalosis and higher levels indicating saline-resistant alkalosis 8.
Clinical States Associated with Metabolic Alkalosis
Major clinical states associated with metabolic alkalosis include vomiting, aldosterone or cortisol excess, licorice ingestion, chloruretic diuretics, excess calcium alkali ingestion, and genetic diseases such as Bartter syndrome, Gitelman syndrome, and cystic fibrosis 6.