Metabolic Alkalosis

Description

Metabolic alkalosis is a pathophysiologic state of high plasma pH (>7.45) that can be caused by the:
- Accumulation of base.
- Loss of acid.
- Loss of fluid containing chloride ion than bicarbonate from the extracellular space (1).
It may be classified as either:
- Acute versus chronic.
- With or without pulmonary compensation: The lungs attempt to blunt the pH change by decreasing exhalation of carbon dioxide; however, it cannot completely restore homeostasis.
- Chloride depletion, potassium depletion, volume contraction, or iatrogenic. The literature, however, discusses several other methods to classify metabolic alkalosis based upon the etiology (e.g., organ dependent) (2).
Because pH homeostasis is essential for the proper function of enzymes and protein, organ dysfunction (e.g., impaired inotropy, decreased cerebral blood flow) and impaired drug clearance may be seen (3).

Epidemiology

Mortality

Medical and surgical inpatients with an arterial blood pH of 7.55 have been shown to have a 45% mortality (2).
Medical and surgical inpatients with an arterial blood pH of 7.65 have been shown to have an 80% mortality (2).

Etiology/Risk Factors

Chloride depletion (2,4):
- Gastric losses: Vomiting, nasogastric suctioning, bulimia, or pyloric stenosis
- Diarrheal states: Villous adenoma, congenital chloridorrhea, inflammatory bowel disease
- Use of chloruretic diuretics: Chlorothiazide, bumetanide
- Cystic fibrosis
Potassium depletion (5)
Volume depletion: (Often results in, or is secondary to, chloride or potassium depletion). This is also referred to as "contraction alkalosis" in the literature (2).
Iatrogenic: Sodium bicarbonate administration.

Physiology/Pathophysiology

Metabolic alkalosis can be classified by the:
- Underlying pathophysiology: Chloride or potassium depletion, volume contraction, mineralocorticoid excess
- Primary organ system involved (2)
Hypokalemia can cause or maintain metabolic alkalosis due to:
- Intracellular shifting of hydrogen ions.
- Stimulation of H⁺/K⁺ ATPase receptors at the collecting ducts. To re-establish normal potassium levels, the receptor increases potassium ion reabsorption while secreting hydrogen ion into the urine.
- An increase in renal ammonia production with resultant net acid excretion as NH₄⁺; the exact mechanism is unknown (2,6).
Chloride depletion enhances absorption and impairs excretion of bicarbonate in the kidneys.
- Low levels are sensed by the macula densa and stimulate the renin–angiotensin–aldosterone system (RAAS). The RAAS functions to increase volume, retain sodium, and excrete potassium. At the level of the collecting duct, sodium is retained at the cost of hydrogen secretion into the urine.
- Impairs the Cl^-/HCO₃^- exchanger at the level of the collecting duct (2).
Decreased volume
- Decreases in glomerular filtration rate (GFR) will decrease the filtered load of bicarbonate at the glomerulus and hence excretion in urine (2).
- Stimulates the renin–angiotensin–aldosterone system. At the level of the collecting duct, sodium is retained at the cost of hydrogen secretion into the urine. The maintenance of volume supersedes pH homeostasis (2).
Gastrointestinal
- Gastric fluid contains 60–140 mM HCl. It can be quickly depleted with vomiting or suctioning. In addition, extracellular fluid (ECF) volume contraction, as well as sodium and potassium loss can stimulate renin and aldosterone production with renal compensation (4).
- Villous adenomas secrete chloride rather than potassium and bicarbonate (4).
Skin: Cystic fibrosis is a genetic defect that causes an abnormal chloride channel protein and impaired cAMP-regulated chloride transport across epithelial cells leading to metabolic alkalosis by chloride depletion (2).
Compensation: Increases in pH depress central and peripheral receptors with resultant hypoventilation/hypercapnia. The ability to compensate, however, is limited due to:
- Hypoxia from rising alveolar carbon dioxide partial pressures can stimulation chemoreceptors and result in hyperventilation.
- Mechanical ventilation: Unless recognized and adjusted for, ventilator settings can result in a "relative" hyperventilatory state.
- Pain in patients who are breathing spontaneously.

The presence of symptoms such as cardiac arrhythmias, confusion, neuromuscular irritability or weakness, and hypoventilation (hypoxia and increased PaCO₂) may suggest a metabolic alkalosis (2).
Arterial blood gases:
- Elevated pH
- Increased bicarbonate concentration
- Differentiate between acute and chronic processes
- Identify the presence of a mixed disorder. The expected PaCO₂ = 0.7[HCO₃^-] + 20, range ±5; the large range is the result of factors that can impair hypoventilation (see above). When the expected PaCO₂ is increased or decreased, consider the possibility of a concomitant respiratory acidosis or alkalosis.
The measurement of urinary chloride and potassium can aid with narrowing the diagnosis (however, this is not routinely performed in the perioperative setting) (2,4).
- Urinary chloride <10 mEq/L
  - Chloride depletion alkalosis
  - Gastric losses
  - Cystic fibrosis
  - Colonic villous adenoma
  - Dietary chloride deprivation
- Urinary potassium concentration >30 mEq/L
  - Renal potassium wasting
  - Diuretics
  - High circulating aldosterone
- Urinary potassium <20 mEq/L
  - Extrarenal potassium loss

Differential Diagnosis

Metabolic alkalosis is a unique disorder that is always a sign of some other underlying disease; thus, the etiology is, in itself, the differential diagnosis.

Treatment should be aimed at the underlying etiology. Replacement of chloride, potassium, and volume may also be indicated, as appropriate.
Chloride responsive alkalosis (2)
- Volume depleted/contracted: Administer normal saline ([Cl^-] = 154 mEq/L). When severely dehydrated, reabsorption of chloride takes precedence over acid reabsorption (also known as paradoxical aciduria). The base is eventually excreted by the kidneys as volume is replenished and chloride becomes available.
- Normovolemic patients: The chloride deficit can be calculated by: ([0.2 × body weight (kg)] × [difference between desired and current plasma chloride (mEq/L)]). The deficit can be replaced intravenously; ensure that chronic electrolyte disturbances are not rapidly corrected.
- Volume overload: In patients with congestive heart failure, chloride should be repleted with KCl, instead of NaCl. If hyperkalemia exists, then intravenous HCl may be indicated.
- Potassium concentration must be monitored closely during the course of treatment and repleted as necessary. Hypokalemia is a common occurrence with rehydration.
- Acetazolamide can be given to patients with normal renal function or when normal saline infusion is not effective; it promotes diuresis of NaHCO₃ by the inhibition of carbonic anhydrase.
Chloride-resistant alkalosis/hypokalemia (2):
- Oral or intravenous KCl:
  - Mild to moderate hypokalemia: oral KCl 40–60 mEq 4–5 times per day.
  - Severe or life-threatening hypokalemia up to 40 mEq per hour IV potassium may be used (central line administration). Patients should have continuous EKG monitoring when high rates of IV KCl are used.

Medarov BI. Milk-alkali syndrome. Mayo Clin Proc. 2009;84(3):261–267.
Galla JH. Metabolic alkalosis. J Am Soc Nephrol. 2000;11(2):369–375.
anderson LE , Henrich WL. Alkalemia-associated morbidity and mortality in medical and surgical patients. South Med J. 1987;80(6):729–733.
Gennari FJ , Weise WJ. Acid–base disturbances in gastrointestinal disease. Clin J Am Soc Nephrol. 2008;3(6):1861–1868.
Assadi F. Diagnosis of hypokalemia: A problem-solving approach to clinical cases. Iran J Kidney Dis. 2008;2(3):115–122.
Weinstein AM. A mathematical model of distal nephron acidification: Diuretic effects. Am J Physiol Renal Physiol. 2008;295(5):F1353–1364.

See Also (Topic, Algorithm, Electronic Media Element)

ICD9

276.3 Alkalosis

ICD10

E87.3 Alkalosis

Perioperative metabolic alkalosis can be seen with:
- In patients with chronic respiratory failure (respiratory acidosis), a compensatory metabolic alkalosis may develop.
- Administration of hypernatremic solutions (e.g., normal saline) results in an increased strong ion deficit due to sodium gain. Sodium is buffered by bicarbonate.
Metabolic alkalosis can result in:
- Electrolyte disturbances leading to arrhythmias, cardiovascular collapse, altered mental status, and delayed emergence.
- pH abnormalities can decrease inotropy and increase cerebral blood flow.
- Increased affinity of oxygen to hemoglobin, shifting the oxygen–hemoglobin dissociation curve to the left.
- Altered efficacy and clearance of medications.
- Increased mortality.

Kanishka Monis , MD

Michael Grover , MD

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Mortality

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Treatment ⬆ ⬇

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