Alkalosis is an abnormal pathophysiological condition characterized by the buildup of excess base or alkali in the body. It results in an abnormally high serum pH (arterial pH greater than 7.45), which is termed alkalemia and forms one end of the spectrum of acid-base disorders. There is generally a loss of hydrogen ions (H) or an excess of bicarbonate ions (OH), and multiple factors can cause either of these. In general, alkalosis is less life-threatening than acidosis, but severe electrolyte derangements can accompany alkalosis due to transcellular shifts, potentially resulting in rare but severe clinical disorders. Alkalosis can be either respiratory or metabolic in origin, but metabolic alkalosis is far more common than respiratory causes.
The etiology of alkalosis can subdivide into metabolic and respiratory causes:
- Excess loss of hydrogen ion—this occurs primarily due to gastric losses (prolonged and severe gastric aspiration, excessive emesis of gastric contents as in pyloric stenosis, congenital chloridorrhea).
- Increased bicarbonate in the extracellular compartment—this occurs due to excess enteral intake of bicarbonate or alkali (milk-alkali syndrome) or increased parenteral intake of citrate or acetate. Increased renal reabsorption of bicarbonate can also cause metabolic alkalosis (severe hypokalemia, primary hyperaldosteronism, Cushing syndrome, Bartter syndrome, Gitelman syndrome, toxic ingestion of licorice, excessive chloruretic diuretic use).
- Diuretic-induced alkalosis—diuretics (loop and thiazide) that block sodium and chloride reabsorption can cause increased bicarbonate absorption at the proximal tubule leading to increased serum bicarbonate concentration, also called contraction alkalosis.
- Low production of CO2—hypometabolic conditions like severe coma, particularly when supported by mechanical ventilation.
- Excess pulmonary loss of CO2—this results in alkalosis when the production of CO2 in the body is normal (psychogenic hyperventilation, iatrogenic hyperventilation in patients on assisted mechanical ventilation or extracorporeal membrane oxygenation, early stages of salicylate overdose due to overstimulation of the respiratory center).
Among the various acid-base disorders, metabolic alkalosis is the most frequently occurring derangement in hospitalized patients, with an incidence of 51% in this group. Respiratory alkalosis is also commonly seen in the hospitalized patient population. Prevalence has shown to be 22.5% to 44.7% in inpatient studies in the United States. An Italian study has shown a prevalence of 24% respiratory alkalosis at the time of admission.
The incidence of mixed respiratory and metabolic alkalosis is estimated to be around 29%.
There does not appear to be a significant gender distribution to alkalosis, except in cases of infantile pyloric stenosis, where there is an overwhelming male predominance noted.
The body has a robust buffering system that acts to minimize pH change in the initial stages of acid-base derangements. When these buffering systems are overwhelmed, alkalosis may result.
The kidney attempts to maintain normal acid-base balance by the dual mechanisms of bicarbonate reabsorption, mainly in the proximal tubule, and bicarbonate production in the distal nephron. Reabsorption of bicarbonate is mediated by a Na-H (sodium-hydrogen) antiporter and also by the H (+)-ATPase (adenosine triphosphate-ase). Influences on bicarbonate reabsorption include effective arterial blood volume, glomerular filtration rate, chloride, and potassium concentrations in the serum. In conditions resulting in respiratory alkalosis, the kidney acts to both decrease bicarbonate reabsorption and bicarbonate production as a compensatory mechanism. This process helps maintain the pH of the extracellular compartment to neutralize the effect of the low pCO2 that is the primary derangement of respiratory alkalosis. However, the kidneys' complex buffering mechanisms may take several days to achieve full effect, with an eventual expected fall of bicarbonate by 4 to 5 mmol/L for every 10 mmHg fall in pCO2.
On the other hand, respiratory depression resulting in increased PaCO2 occurs promptly and predictably to buffer the alkalemia resulting from metabolic conditions (while this is variable, expectations are that there will be a 0.5 mmHg increase in PaCO2 per 1 mmol/L increase in HCO). Alkalemia also causes a shift in the oxyhemoglobin dissociation curve towards the left, thus increasing hemoglobin's affinity for oxygen and decreasing oxygen release to the tissues.
When the intake of potassium is suboptimal, this can correlate with metabolic alkalosis due to intracellular sodium and proton levels rising as well as a consequent depression in aldosterone levels. When protons shift into the cellular compartment, metabolic alkalosis ensues; this is followed by respiratory center depression of respiratory drive and ultimately, the purging of bicarbonate by the kidney.
There are no specific histopathological features that are pathognomonic for alkalosis. However, the primary cause of alkalosis may be established by histopathological studies, especially when related to kidney or adrenal disorders.
History and Physical
Alkalosis can present with a myriad of signs and symptoms, based on the etiology of alkalosis (respiratory versus metabolic) and the primary condition leading to alkalosis.
Metabolic alkalosis can have central nervous system manifestations ranging from confusion to coma, peripheral neuropathic symptoms of tremor, tingling and numbness, muscle weakness and twitching, and arrhythmias, particularly when associated with hypokalemia and hypocalcemia. Nonhypochloremic metabolic alkalosis associates with hypertension and is usually the result of syndromes of excess mineralocorticoid production. These generally correlate with signs of volume expansion, hypertension, and hypokalemia. Persistent and projectile, non-bilious emesis in a two to six week old, otherwise well-appearing infant is a hallmark presentation of pyloric stenosis.
Respiratory alkalosis can have associated syncope, tremors, and signs of hyperventilation, along with chest pain and dyspnea.
A blood gas analysis, preferably arterial, is needed to establish alkalosis and whether it appears to be metabolic or respiratory in origin. Ancillary blood tests are necessary; these are serum chemistries with electrolytes, blood urea nitrogen, and creatinine. While the bicarbonate concentration being high can indicate the possibility of metabolic alkalosis, it is not confirmatory, as both the carbon dioxide concentration and the concentration of H+ ions will affect the presence or absence of alkalosis. Hence, a blood gas estimate of pH and pCO2 is also needed. However, in mixed acid-base disorders, complex calculations are necessary to establish multiple disturbances and whether they are primary and/or coexistent abnormalities or compensatory buffering mechanisms.
Associated electrolyte abnormalities need to be identified, including hypochloremia, hypokalemia, and hypocalcemia. An EKG may be necessary to evaluate for arrhythmias. Urine chemistry is required to assess the kidney's response to alkalosis. Hypertension requires assessment and other tests for hyperaldosteronism when indicated. Volume depletion also requires evaluation as a coexisting condition.
When associated with hypoxia or an increased alveolar-arterial (A-a) gradient, respiratory alkalosis requires a search for a cause of hypoxia. However, pulmonary embolism may cause respiratory alkalosis without associated hypoxia and must be ruled out before attributing hyperventilation to pain or anxiety.
Since alkalosis has a broad spectrum of manifestations, the differential diagnosis for its wide range of signs and symptoms can be confusing. Associated electrolyte disturbances can also complicate the diagnosis, like hypochloremia, hypokalemia, and hypocalcemia.
Whether respiratory or metabolic, alkalosis is usually compensated by the body's innate buffering mechanisms in the acute and subacute phase. When the alkalosis is uncorrected or chronic, the buffering mechanisms may become overwhelmed, potentially leading to a poor prognosis. Prognosis depends on associated problems of volume depletion, electrolyte, and hormonal disturbances and varies based on the primary etiology of the alkalosis.
Patients with metabolic alkalosis have been found to have increased ICU duration of stay, more days on mechanical ventilation, and higher hospital mortality. An increase of 5-mEq/L in the serum bicarbonate level over 30 mEq/L correlated with an odds ratio of 1.21 for hospital mortality. The association between metabolic alkalosis and mortality occurs independently of the etiology of alkalosis.
Alkalosis can lead to life-threatening arrhythmias (atrial and ventricular tachyarrhythmias), especially when associated with hypokalemia and hypocalcemia. These associated electrolyte abnormalities can also cause carpopedal spasms, muscle weakness, and altered mental status.
Depending upon the primary etiology of the alkalosis, consultation may be necessary with various subspecialties. A nephrological consult may be needed to elucidate the cause of metabolic alkalosis and management. A cardiologist and an endocrinologist may help with blood pressure control and hormonal correction in conditions of hyperaldosteronism. The patient may require admission under the care of an intensivist for severe electrolyte correction. Infants with pyloric stenosis will need surgical evaluation and correction.
Deterrence and Patient Education
Patients require education about the significance of severe alkalosis and the primary etiology that is causing their alkalosis. Patients and families need to understand the link between causes of alkalosis, such as anxiety disorders, severe emesis or excessive alkali ingestion, and resultant alkalosis.
Pearls and Other Issues
Alkalosis is a common finding in hospitalized patients but is rarely life-threatening in itself. While the body's buffering systems initially correct alkalosis, ongoing alkalosis may cause clinical problems due to associated electrolyte disturbances.
Enhancing Healthcare Team Outcomes
Managing alkalosis requires an interprofessional team of healthcare professionals, including a nurse, laboratory technologists, pharmacists, and several physicians in different specialties.
Immediately upon identifying alkalosis, the primary clinician is responsible for coordinating the care, which includes the following:
- Ordering serial blood gas analysis, blood, and urine chemistries.
- Monitor the patient for signs and symptoms of neuromuscular depression, cardiac arrhythmias, hypertension, and volume depletion.
- Performing various maneuvers to help limit the severity of alkalosis and boost the body's buffering mechanisms.
- Consult with the pharmacist about the correct dose and method of correcting electrolyte abnormalities.
- Consult with a nephrologist on further management, which may include dialysis.
- Consult with the radiologist about imaging tests to evaluate the causes of persistent emesis.
- Consult with the intensivist about ICU care and monitoring while in hospital.
- Nurses monitoring the patient with metabolic alkalosis should be aware of the potential complications, including arrhythmias, and promptly inform the team members.
The management of alkalosis does not stop with the correction of alkalosis. Once the patient achieves a stable state, one has to determine how and why the patient became alkalotic and also determine risk factors for recurrence of alkalosis. The morbidity and mortality of alkalosis in hospitalized patients are significant.
Only by working as an interprofessional team can the morbidity of alkalosis be decreased. This process will include ongoing monitoring by the nursing staff, who will alert the attending regarding any change in status. The pharmacist can perform medication reconciliation and be involved in the ordering and administration rate of fluids, bicarbonate, and other pharmaceutical measures to correct alkalosis. Their expertise should be used as a tool by the clinicians managing the case in a collaborative interprofessional effort with the primary aim of achieving optimal patient outcomes.