eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Critical Care

Alkalosis, Metabolic

Author: Lennox H Huang, MD, Associate Clinical Chair, Assistant Professor, Department of Pediatrics, McMaster University; Deputy Chief of Pediatrics, McMaster Children's Hospital
Coauthor(s): Margaret A Priestley, MD, Assistant Professor of Clinical Anesthesiology and Critical Care, University of Pennsylvania School of Medicine; Clinical Director, Pediatric Intensive Care Unit, The Children's Hospital of Philadelphia
Contributor Information and Disclosures

Updated: Aug 13, 2008

Introduction

Background

Metabolic alkalosis is an acid-base disturbance caused by an elevation in plasma bicarbonate (HCO₃) concentration. This condition is not a disease; it is a sign or state encountered in certain disease processes. Although metabolic alkalosis may not be referred to as often as metabolic acidosis, it is the most common acid-base abnormality in hospitalized adults. Alkalosis refers to a loss of acid or gain of base in the extracellular fluid (ECF); alkalemia refers to a change in blood pH. Alkalosis is not necessarily accompanied by alkalemia.

The 2 types of metabolic alkalosis (ie, chloride-responsive, chloride-resistant) are classified based on the amount of chloride in the urine.

Chloride-responsive metabolic alkalosis involves urine chloride levels of less than 10 mEq/L and is characterized by decreased ECF volume and low serum chloride levels, such as occurs with vomiting. This type responds to administration of chloride salt.

Chloride-resistant metabolic alkalosis involves urine chloride levels of more than 20 mEq/L and is characterized by increased ECF volume. As the name implies, this type resists administration of chloride salt. Primary aldosteronism is an example of chloride-resistant metabolic alkalosis.

Pathophysiology

In most cases, metabolic alkalosis is caused by loss of hydrochloric acid (HCl) through the kidney or GI tract, especially due to vomiting. Occasionally, the condition is caused by disproportionate loss of chloride. Metabolic alkalosis is rarely caused by actual gain from administered HCO₃.

Other causes of metabolic alkalosis include (1) loss of hydrogen ions (eg, due to vomiting or renal acid losses that exceed acid production from cellular metabolism), (2) disproportionate chloride loss compared with HCO₃ loss (ie, the plasma concentration of HCO₃ increases upon restriction to a smaller space of distribution), and (3) HCO₃ administration (unusual because additional HCO₃ is very quickly eliminated by the kidneys).

The consequences of metabolic alkalosis on organ systems depend on the severity of the alkalemia and the degree of respiratory compensation. If the elevated plasma HCO₃ concentration is not accompanied by a rise in PCO₂, the elevation of pH is much more severe.

• Effects of severe alkalemia
  • Respiratory: An increase in blood pH shifts the oxygen-hemoglobin dissociation curve to the left. This creates a tighter bond between hemoglobin and oxygen, causing decreased oxygen delivery to tissues. Hypoxemia is worsened by a compensatory hypoventilation to elevate PCO₂. Hypoventilation may be severe enough to cause apnea and respiratory arrest.
  • Cardiovascular system: Life-threatening arrhythmias are the most significant adverse effect of metabolic alkalosis. Direct arteriolar constriction is further worsened by electrolyte disturbances. Ventricular and supraventricular arrhythmias that are often unresponsive to antiarrhythmic agents can occur.
  • Neuromuscular system: Patients with severe metabolic alkalosis can develop headache, seizures, and obtundation and marked muscle weakness that resolve only with correction of the pH.
  • Electrolytes: Metabolic alkalosis may cause a decrease in ionized calcium levels due to increased binding of calcium to plasma proteins; consequences include tetany and seizures. Total-body potassium loss may contribute to alkalemia, and serum potassium is intracellularly shifted in alkalemia. Weakness and cardiac arrhythmias may result from severe hypokalemia.
  • Other effects: Metabolic alkalosis may also increase lactic acid production by stimulating the action of phosphofructokinase, with conversion of fructose-6-phosphate to fructose-1,6-diphosphate. Alkalemia also increases renal tubular reabsorption of calcium, resulting in decreased renal excretion.
• Compensation mechanisms
  • Buffering of excess HCO₃: Intracellular buffering occurs through sodium/hydrogen and potassium/hydrogen ion exchange, with eventual formation of CO₂ and water from HCO₃.
  • Hypoventilation: Within several hours, elevated levels of HCO₃ and metabolic alkalosis stimulate a chemoreceptor inhibition of the respiratory center, resulting in hypoventilation and increased PCO₂ levels. This mechanism produces a rise in PCO₂ of as much as 0.7 mm Hg for each 1-mEq/L increase in HCO₃. Hypoventilation may cause hypoxemia.

Frequency

United States

Because metabolic alkalosis is a manifestation of a disease process rather than a disease itself, the incidence is unknown. In a review of 2000 hospitalized adults, Hodgkin et al noted that metabolic alkalosis was the most common acid-base disorder.¹

Mortality/Morbidity

Severe metabolic alkalosis is associated with increased morbidity and mortality, probably because of its profound influences on multiple organ systems and, more importantly, because of tissue anoxia caused by hypoventilation and shift of the oxygen-dissociation curve to the left.

Race

No racial predilection has been reported.

Sex

Incidence is equal in males and females.

Age

Metabolic alkalosis can occur in people of any age. A higher incidence of metabolic alkalosis after cardiac surgery in younger children has been reported.

Clinical

History

Obtain historical data to pinpoint the nature of the disease causing metabolic alkalosis.

• Ask the patient about history of vomiting, other gastric fluid loss, and diuretic use. Loss of gastric fluid and HCl due to vomiting is the most common cause of metabolic alkalosis.
  • Vomiting may be caused by pyloric stenosis or ulcers. Occasionally, it may be self-induced.
  • Significant gastric fluid loss can occur via long-term nasogastric (NG) tube drainage.
  • Diuretic use may lead to increased chloride losses.
• Obtain information about specific disease states such as primary hyperaldosteronism, reninism, hyperglucocorticoidism, Bartter syndrome, and deoxycorticosterone (DOC) excess syndromes.
• Because hypokalemia may lead to metabolic alkalosis, ask about the use of diuretics because these lead to potassium loss.

Physical

Increased neuromuscular excitability sometimes causes tetany or seizures. Generalized weakness may be noted if the patient also has hypokalemia. Signs and symptoms observed with metabolic alkalosis usually relate to the specific disease process that caused the acid-base disorder.

• Patients who develop metabolic alkalosis from vomiting can have symptoms related to severe volume contraction, with signs of dehydration that include tachycardia, dry mucous membranes, decreased skin turgor, postural hypotension, poor peripheral perfusion, and weight loss.
• Although diarrhea typically produces a hyperchloremic metabolic acidosis, diarrheal stools may rarely contain significant amounts of chloride, as in the case of congenital chloride diarrhea. Children with this condition present at birth with watery diarrhea, metabolic alkalosis, and hypovolemia.
• Weight gain and hypertension may accompany metabolic alkalosis that results from a hypermineralocorticoid state.

Causes

• Chloride-responsive type
  • Gastric fluid loss (eg, vomiting, NG drainage)
  • Volume contraction (eg, secondary to loop or thiazide diuretics)
  • Congenital chloride diarrhea
  • Posthypercapnia syndrome (especially in mechanically ventilated patients with chronic lung disease)
  • Cystic fibrosis (in toddlers)
• Chloride-resistant type
  • Primary aldosteronism
  • Bartter syndrome (renal sodium, potassium, and chloride wasting; often presents as failure to thrive)
  • DOC excess syndrome (congenital adrenal hyperplasia variant)
  • Liddle syndrome (autosomal dominant; unregulated sodium resorption in renal collecting duct)
  • Excessive ingestion of licorice
  • Chronic potassium depletion (eg, anorexia nervosa)
  • Primary reninism
  • Hyperglucocorticoidism
  • Milk-alkali syndrome (excess calcium plus bicarbonate intake and vomiting)
• Further discussion
  • Gastric losses (eg, vomiting, NG drainage): One mEq of HCO₃ is generated in response to each mEq of hydrogen ion produced by the gastric mucosa. Although this can generate a large amount of HCO₃, it is counteracted by the gastric stimulation of the pancreas to produce HCO₃. When gastric acid is removed by suctioning or lost through vomiting, the stimulus for the pancreas is lost, thus allowing plasma HCO₃ levels to increase. In addition, the loss of potassium and volume contraction due to vomiting potentiate metabolic alkalosis.
  • Diuretics: This class of drugs produces increased renal losses of sodium, which is followed by excretion of chlorides. To maintain electrical neutrality in the ECF, HCO₃ reabsorption in renal tubules increases. Additionally, increased sodium in the distal tubules increases sodium-potassium exchange. The loss of potassium, in turn, leads to intracellular accumulation of hydrogen ions and its secretion in the distal tubules. Diuretics also promote the loss of magnesium in the urine, which further lowers potassium levels through an unknown mechanism.
  • Decrease in ECF volume (ie, volume contraction): Volume contraction concentrates the existing levels of HCO₃ and stimulates release of renin-angiotensin, which causes increased potassium and hydrogen ion losses in the kidney.
  • Posthypercapnia syndrome: Chronic CO₂ retention causes a compensatory increase in HCO₃ levels. Metabolic alkalosis becomes evident when a patient with chronic CO₂ retention receives treatment that abruptly drops the CO₂ level.

• Search for CME/CE on This Topic »

• Metabolic Alkalosis (Nephrology)
• Hypochloremic Alkalosis (Pediatrics: Genetics and Metabolic Disease)
• Respiratory Alkalosis (Pulmonology)
• Metabolic Acidosis (Nephrology)

• Metabolic Syndrome Linked to Inflammation, Physical Inactivity in COPD
• Metabolic Syndrome in Heart Failure Ups Risk of Death
• Lower Urinary Tract Symptoms Associated With Metabolic Syndrome

• Anorexia Nervosa: Perioperative Implications
• Anorexia Nervosa: Perioperative Implications
• Multiple Myeloma and Hyperammonemic Encephalopathy: Review of 27 Cases

• Cardiometabolic Risk Factor Management (Metabolic Syndrome) Resource Center
• Hypothyroidism Resource Center