What are the causes of normal anion gap (electrolyte imbalance) metabolic alkalosis (elevated blood pH)?

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 underlying mechanism typically involves either chloride depletion (chloride-responsive) or potassium depletion (chloride-resistant) 1.

Causes of Normal Anion Gap Metabolic Alkalosis

• Vomiting or nasogastric suction, which directly removes gastric acid from the body
• Diuretic use, particularly loop diuretics like furosemide and thiazides like hydrochlorothiazide, which increase renal bicarbonate reabsorption
• Hypokalemia, which promotes hydrogen ion secretion into the urine
• Excessive alkali administration such as sodium bicarbonate
• Primary hyperaldosteronism, Cushing's syndrome, severe hypomagnesemia, Bartter and Gitelman syndromes, and post-hypercapnic states
• Certain medications like carbenoxolone, licorice, and high-dose penicillin derivatives can also induce this condition 1

Mechanism and Treatment

The mechanism involves the loss of hydrogen ions or gain of bicarbonate, leading to an increase in blood pH 1. Treatment should target the underlying cause, such as stopping the offending diuretic, replacing fluid and electrolytes in vomiting patients, or addressing hormonal imbalances in endocrine disorders 1. Understanding these causes is essential for proper diagnosis and management of metabolic alkalosis. It is also important to note that fluid and electrolyte balance is crucial in the management of metabolic alkalosis, and both fluid excess and deficit can have detrimental effects on patient outcomes 1.

From the FDA Drug Label

Potassium depletion will occur whenever the rate of potassium loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of potassium intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of potassium in patients on prolonged parenteral nutrition Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Potassium depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis 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:

• Diuretic therapy 2, 3, 4
• Primary or secondary hyperaldosteronism 2
• Diabetic ketoacidosis 2
• Inadequate replacement of potassium in patients on prolonged parenteral nutrition 2
• Severe diarrhea 2
• Vomiting 2
• Hypochloremic alkalosis 3

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 5, 6, 7
• Mineralocorticoid excess syndromes, such as Cushing's syndrome or hyperaldosteronism 5, 7
• Apparent mineralocorticoid excess syndromes, such as licorice ingestion or the use of certain herbal supplements 5, 7
• Excess alkali administration, such as ingestion of baking soda or other alkaline substances 8, 7
• Other causes, such as the use of loop diuretics, laxative abuse, or surreptitious vomiting 8, 6, 7

Mechanisms of Metabolic Alkalosis

Metabolic alkalosis can result from a gain of bicarbonate or a loss of nonvolatile acid from extracellular fluid 7. The kidney plays a crucial role in maintaining acid-base balance by reabsorbing bicarbonate and generating new bicarbonate 7. Factors that can contribute to the development of metabolic alkalosis include:

• Decreased glomerular filtration rate 7
• Volume contraction 7
• Hypokalemia 6, 7
• Hypochloremia 6, 7
• Aldosterone excess 5, 7

Clinical States Associated with Metabolic Alkalosis

Metabolic alkalosis can be associated with various clinical states, including:

• Vomiting 6, 7, 9
• Mineralocorticoid excess 5, 7
• The adrenogenital syndrome 7
• Licorice ingestion 5, 7
• Diuretic administration 5, 6, 7
• Bartter's and Gitelman's syndromes 7