Review Article 51 Evaluation and Treatment of Alkalosis in Children Matjaž Kopač1 1 Division of Pediatrics, Department of Nephrology, University Address for correspondence Matjaž Kopač, MD, DSc, Division of Medical Centre Ljubljana, Ljubljana, Slovenia Pediatrics, Department of Nephrology, University Medical Centre Ljubljana, Bohoričeva 20, 1000 Ljubljana, Slovenia J Pediatr Intensive Care 2019;8:51–56. (e-mail: [email protected]). Abstract Alkalosisisadisorderofacid–base balance defined by elevated pH of the arterial blood. Metabolic alkalosis is characterized by primary elevation of the serum bicarbonate. Due to several mechanisms, it is often associated with hypochloremia and hypokalemia and can only persist in the presence of factors causing and maintaining alkalosis. Keywords Respiratory alkalosis is a consequence of dysfunction of respiratory system’s control ► alkalosis center. There are no pathognomonic symptoms. History is important in the evaluation ► children of alkalosis and usually reveals the cause. It is important to evaluate volemia during ► chloride physical examination. Treatment must be causal and prognosis depends on a cause. Introduction hydrogen ion concentration and an alkalosis is a pathologic Alkalosis is a disorder of acid–base balance defined by process that causes a decrease in the hydrogen ion concentra- elevated pH of the arterial blood. According to the origin, it tion. Therefore, acidemia and alkalemia indicate the pH can be metabolic or respiratory. Metabolic alkalosis is char- abnormality while acidosis and alkalosis indicate the patho- acterized by primary elevation of the serum bicarbonate that logic process that is taking place.3 can result from several mechanisms. It is the most common Regulation of hydrogen ion balance is basically similar to form of acid–base balance disorders. This was confirmed in a the regulation of other ions in the body. There must be a study on 3,300 patients where gas analysis of the arterial blood balance between the intake or production of hydrogen ions was done in 13,000 samples.1 Respiratory alkalosis is a con- and their net removal from the body to achieve homeostasis. sequence of dysfunction of respiratory system’s control cen- The kidneys play a key role in regulating hydrogen ion ter.2 The pH of the arterial blood is elevated in metabolic removal but much more is needed to achieve precise control alkalosis and lowered or normal in respiratory acidosis of extracellular fluid hydrogen ion concentration. There are although there is increased concentration of bicarbonate and also several other acid–base buffering systems involved, such hypercapnia (elevation of partial pressure of carbon dioxide– as the blood, cells, and lungs that are crucial for maintaining 1 pCO2) in both disorders. normal hydrogen ion concentrations in both the extracellu- 4 The relationship between the pCO2, the bicarbonate con- lar and the intracellular fluid. centration, and the hydrogen ion concentration can be pre- To determine the primary acid–base disorder, we must Downloaded by: University Library of Southern Denmark. Copyrighted material. sented by rearranged Henderson–Hasselbach equation: examine the pCO2 and the bicarbonate concentration. In þ À [H ] ¼ 24 Â pCO2/(HCO3 ) general, there ispCO2 below 35 mm Hg in respiratoryalkalosis, An increase in the bicarbonate concentration or a decrease serum bicarbonate concentration above 26 mm Hg in meta- in the pCO2 decreases the hydrogen ion concentration and bolic alkalosis, pCO2 above 45 mm Hg in respiratory acidosis, the pH increases. On the other hand, a decrease in the and serum bicarbonate concentration below 22 mm Hg in 5 bicarbonate concentration or an increase in the pCO2 increases metabolic acidosis. However, acid–base disorders are not the hydrogen ion concentration and the pH decreases.3 accompanied by appropriate compensatory responses in Regarding terminology, acidemia is a pH below normal some instances. When this occurs, the abnormality is referred (< 7.35), and alkalemia is a pH above normal (> 7.45). An to as a mixed acid–base disorder. This means that there are two acidosis is a pathologic process that causes an increase in the or more underlying causes for the acid–base disturbance.4 received Copyright © 2019 by Georg Thieme DOI https://doi.org/ June 25, 2018 Verlag KG, Stuttgart · New York 10.1055/s-0038-1676061. accepted after revision ISSN 2146-4618. October 17, 2018 published online November 18, 2018 52 Alkalosis in Children Kopač Physiological Aspects Pathogenesis Increased concentration of bicarbonate in metabolic alkalo- Metabolic alkalosis can only persist in the presence of factors sis elevates serum pH which triggers alveolar hypoventila- causing alkalosis (there is a source of base) and factors tion, leading to hypercapnia. The pCO2 in metabolic alkalosis maintaining alkalosis, when there is impaired ability to rarely exceeds value 7.3 kPa (55 mm Hg) because there is no excrete excess bicarbonate in the urine due to different full response with hypoventilation due to hypoxia. Respira- causes, such as: hypovolemia, reduced effective arterial tory compensation of metabolic alkalosis is impaired in some blood volume, chloride depletion, hypokalemia, reduced diseases, such as obstructive airway diseases, severe liver glomerular filtration rate, hyperaldosteronism, or combina- diseases, cardiac failure, and others. Metabolic alkalosis is tions of these factors. Normally, bicarbonate is excreted often associated with hypochloremia and hypokalemia.1 through the kidneys regardless of the cause.1,8 Addition of chloride (ClÀ) is therefore often important part of alkalosis treatment. Base excess is at least 2 mmol/L.6 Factors Causing Alkalosis Carbon dioxide (CO2) production is fairly constant in the body. During hypoventilation the amount of CO2 excreted Loss of Acid from the Extracellular Fluid exceeds the amount formed in the metabolic processes. The Gastrointestinal causes: The most common cause of hydro- potassium (Kþ) loss is also important for generation and gen loss is the loss of gastric secretions due to vomiting or maintenance of alkalosis because it enhances excretion of nasogastric suction. Other causes are diarrhea in patients hydrogen ions and bicarbonate reabsorption. This is impor- with rare disorders that block intestinal chloride absorption tant clinically in mineralocorticoid excess.7 (such as congenital chloridorrhea) and villous adenomas. Increased concentration of bicarbonate is a consequence There is a good response to infusion of normal saline (con- of gastrointestinal hydrogen loss, excessive renal hydrogen taining chloride), therefore it is named saline-responsive or loss, administration and retention of bicarbonate ions, chloride-depletion.1 Gastric secretions can be significantly volume contraction, or intracellular shift of hydrogen ions. enhanced with appropriate stimuli (even 20 times or more). Normally, gastric hydrogen ion secretion does not lead to One mEq of bicarbonate is formed per 1 mEq of hydrogen ion. metabolic alkalosis, since the hydrogen ions are not lost from In vomiting the equilibrium is disturbed because hydrogen is the body but instead are neutralized by bicarbonate secreted removed and bicarbonate remains. In this way metabolic by the pancreas, liver, and intestines in response to the acid alkalosis is generated that can be accentuated by hypovole- that enters the small bowel. The hydrogen and bicarbonate mia and hypokalemia.7 ions combine within the intestinal lumen to form carbonic Renal causes: It is the most common cause of meta- acid and water, and the secreted chloride, sodium, and bolic alkalosis due to acid loss from the extracellular potassium ions are reabsorbed into the systemic circulation. fluid. It is most commonly due to diuretic therapy, either When vomiting or nasogastric tube suction removes hydro- with loop or thiazide diuretics. These drugs stimulate acid gen chloride from the body and prevents it from reaching the excretion via increased distal sodium delivery and tubular duodenum, the bicarbonate that is added to the extracellular flow which then causes secondary hyperaldosteronism.1 fluid is not neutralized by the subsequent secretion of Additionally, diuretics increase secretion of some electro- bicarbonate into the more distal gastrointestinal lumen.8 lytes (Naþ,Kþ,ClÀ) more compared with bicarbonate.7 Hyperventilation reduces pCO2 in blood and consequently Other renal causes of metabolic alkalosis are Bartter amount of carbonic acid in respiratory alkalosis. Non-bicar- syndrome, hypoparathyroidism, posthypercapnic meta- bonate buffer system releases hydrogen ions that bind to bolic alkalosis, and hypersecretion of mineralocorticoids. serum bicarbonate. This reduces its amount which corrects In the latter group, we should mention primary hyper- Downloaded by: University Library of Southern Denmark. Copyrighted material. or attenuates incipient alkalosis. The bicarbonate concentra- aldosteronism, such as Liddle syndrome, or the combina- tion decreases in this way while concentrations of other tion of secondary mineralocorticoid secretion with a buffer systems increase. Therefore, there is no base excess.2 diuretic whose site of action is proximal to the site of Respiration is regulated through central chemoreceptors in hydrogen ion secretion.1,8 the respiratory center which respond to changes in pCO2 and Intracellular shift of hydrogen: Hydrogen ions move from blood pH, and through peripheral chemoreceptors in the the extracellular fluid into