By Sachin J. Shah, MD
Metabolic alkalosis is the most common acid-base disorder found in hospitalized patients. In a study performed examining 13,430 arterial blood samples, 51% of the acid-base disorders were categorized as metabolic alkalosis.1 Its prevalence is related to the fact that vomiting, nasogastric suctioning and diuretic use are so common. The mortality with severe alkalosis is very high. In patients with pH greater than 7.55, the mortality rate is close to 45%. In patients with pH greater than 7.65 the mortality increases to 80%.2 The diagnosis and treatment of metabolic alkalosis are important for all emergency physicians to understand.
Metabolic alkalosis occurs with either a net excess of base or a net loss of acid. In a pure disorder, this leads to an increase in the pH as well as the plasma bicarbonate concentration. The body’s normal response is hypoventilation to drive the pCO2 higher to compensate for the increased bicarbonate. Hypoxia secondary to hypoventilation is a dangerous sequela.3 The PaCO2 increases from 0.5 to 0.7 mmHg for every 1 mmol increase in the plasma HCO3 concentration.4 Alkalemia results in decreased oxygen delivery as well due to the Bohr effect. The shift in the oxygen (O2) dissociation curve decreases the ability of hemoglobin to release O2.5
Metabolic alkalosis can be classified by the response to therapy, the underlying pathophysiology or the primary organ system involved. The most straightforward grouping is by response to therapy and will be discussed here. The two categories are the chloride- responsive and chloride-resistant varieties. The chloride-responsive causes are more common. (See Table.)
Chloride-Responsive. Chloride is lost by many mechanisms and through many organs. It can be lost through the gut, kidney, or skin. Gastric fluid contains 60-140 mmol of hydrocholoric acid (HCl).6 Vomiting or nasogastric suctioning results in alkalosis because the bicarbonate generated during the production of gastric acid is released into the circulatory system.3
Diuretics such as furosemide or hydrochlorothiazide may cause metabolic alkalosis as well. They produce a direct loss of chloride, sodium, and fluid in the urine.7 There are several proposed mechanisms as to why this leads to metabolic alkalosis: 1) increased sodium delivery to the distal nephron accelerates potassium and proton secretion;8 2) renin and aldosterone are secreted in response to decreased intravascular volume, which in turn causes less sodium loss but greater secretion of potassium and protons;3 and 3) potassium secretion will increase bicarbonate reabsorption and ammonia production which will increase net acid excretion by the kidney.9,10
A less common presentation of metabolic alkalosis is in patients with chronic respiratory acidosis who have rapid correction of their hypercapnea. These patients are chloride depleted and as the acidosis is corrected, the kidney will inappropriately reabsorb bicarbonate if sufficient chloride is not available resulting in a persistent metabolic alkalosis.11
Usually, the kidney filters out excess bicarbonate to return to baseline levels after the inciting events are resolved. Impaired kidney function is responsible for persistent metabolic alkalosis. The kidney either reabsorbs more bicarbonate than it should, filters out less due to a decreased glomerular filtration rate, or both.3
Early hypotheses held that decreased intravascular volume was responsible for maintaining metabolic alkalosis. One widely accepted hypothesis for the maintenance of alkalosis went as follows: Volume contraction stimulates fluid resabsorption along with bicarbonate in the proximal tubule, maintaining alkalosis. To correct this, volume expansion is needed. As volume expansion takes place with fluids, bicarbonate and chloride are delivered to the distal tubule, which preferentially reabsorbs chloride. This results in resolution of the alkalosis.3
Newer hypotheses suggest that chloride depletion plays a much greater role than fluid status. Studies show that chloride administration by many means, despite persistently low glomerular filtration rate (GFR), decreased plasma volume, or continued bicarbonate loading helped reverse the alkalosis.12
Chloride depletion seems to maintain alkalosis via certain renal mechanisms. GFR appears to be decreased due to a tubuloglomerular feedback mechanism. Bicarbonate secretion does not occur because insufficient chloride is available for exchange. Chloride depletion also increases renin secretion that results in increased aldosterone, which results in potassium wasting.3
Chloride-Resistant. The chloride-resistant alkaloses usually result from dietary potassium deficiency or mineralocorticoid excess. Multiple factors contribute to the net gain in bicarbonate. Potassium depletion results in an intracellular shift of protons. It also is associated with enhanced renal ammonia production.13 Whether primary (adenoma, hyperplasia) or secondary, mineralocorticoid excess acts to promote sodium retention by secreting potassium. Aldosterone stimulates proton secretion and bicarbonate reabsorption in the collecting tubule.14 The kidney also engages in potassium conservation by reabsorbing bicarbonate.
Another cause of metabolic alkalosis that may be seen in the emergency department (ED) is the milk-alkali syndrome, in which both bicarbonate and calcium are ingested. This may lead to vomiting and hypercalcemia, which increases bicarbonate reabsorption, and a reduced GFR.3
Patients may present to the ED with apathy, confusion, cardiac dysrhythmias, and hypoventilation. History of recent vomiting, medication use (both prescription and over-the-counter), as well as other substances used (i.e., licorice, chewing tobacco) can be very helpful. Also, history of other medical conditions such as Cushing’s disease or renal artery stenosis, if known, can help in diagnosing the cause.3
After initial assessment of the ABCs and resuscitation, blood work is necessary in the diagnosis and treatment of metabolic alkalosis. The two key laboratory tests are the arterial blood gas and the basic chemistry panel. Urine electrolytes also may help differentiate a chloride-responsive from a chloride-resistant alkalosis. In patients not taking diuretics, urine chloride levels less than 10 mEq/L indicate a chloride depletion state. Urine chloride levels greater than 30 mEq/L are more indicative of chloride-resistant alkalosis.15
In addition to treating the underlying cause to prevent further alkalosis, existing deficits must be addressed to improve the patient’s condition. In patients with chloride-responsive alkalosis, chloride therapy is essential. The selection of the type of fluid, however, depends on the patient’s volume status as well as other deficits. A patient with a volume deficit would benefit from 0.9% normal saline solution. Potassium levels should be monitored closely, as well. If necessary, potassium can be replaced by adding potassium chloride to the other intravenous fluids. If fluid overload is an issue, then potassium chloride can be used alone, provided that the patient’s potassium level is low or normal.3
In settings where the patient’s pH is greater than 7.55 and they display signs of severe toxicity such as dysrhythmias, change in mental status, or encephalopathy, immediate correction is the rule. In this scenario, HCl can be used. It can be given as a 100 mmol/L solution. The correction can be estimated by the formula: amount of HCl needed = 0.5 ´ weight (kg) ´ desired decrement of bicarbonate. The HCl should be run in no faster than 0.2 mmol/kg/h, and it should be infused in a central vein.3
In patients with renal failure, modified dialysis can be pursued. The dialysate must be changed for the process to work effectively. This exchanges bicarbonate for chloride, helping to correct the patient’s alkalosis. In patients who are vomiting, proton pump inhibitors may be used to help blunt the production of gastric acid.3
In patients whose primary derangement is mineralocorticoid excess, the source of the excess must by found and treated. Patients can be given a potassium sparing diuretic to help reverse the potassium deficit and the sodium overload. Dietary changes will help the patient correct the alkalosis as well. Sodium restriction and potassium supplement also may help reverse the hypertension.3
When potassium depletion alone is associated with the alkalosis, repletion is the rule. Depending on the severity of depletion, oral or intravenous repletion may be chosen. Glucose solutions should be avoided initially because this may stimulate the body to release insulin and push potassium into the cell. Frequent chemistry determinations should be undertaken to monitor sodium and potassium levels.3
In summary, a systematic approach with an understanding of the pathophysiology can help the clinician correctly diagnose and treat metabolic alkalosis, a condition that carries a high morbidity and mortality rate. Beware the elderly patient with chronic renal insufficiency who presents with a few days of a "sour stomach" and taking large amounts of bicarbonate for relief. This is the perfect setup for metabolic alkalosis.
(Dr. Shah is an Assistant Professor of Emergency Medicine at Temple University Hospital and School of Medicine, Philadelphia, PA.)
1. Hodgkin JE, et al. Incidence of metabolic alkalemia in hospitalized patients. Crit Care Med 1980;8:725-732.
2. Anderson LE, Henrich WL. Alkalemia associated morbidity and mortality in medical and surgical patients. South Med J 1987;80:729-733.
3. Galla JH. Metabolic alkalosis. J Am Soc Nephrol 2000;11:369-375.
4. Javaheri S, Kazemi H. Metabolic alkalosis and hypo-ventilation in humans. Am Rev Respir Dis 1987;136: 1101-1016.
5. Lee GR. Wintrobe’s Clinical Hematology, 10th ed. Baltimore, MD: Lippincott Williams & Wilkins; 1999: 212-214.
6. Johnson LR. Physiology of the Gastrointestinal Tract. New York: Raven;1987.
7. Ellison DH. The physiologic basis of diuretic synergism: Its role in treating diuretic resistance. Ann Intern Med 1991;114:886-894.
8. Hropot M, et al. Tubular action of diuretics: Distal effects on electrolyte transport and acidification. Kidney Int 1985;28:477-489.
9. Chan YL, et al. Control mechanism of bicarbonate transport across the rat proximal convoluted tubule. Am J Physiol 1982;242:F532-F543.
10. Rosen RA, et al. On the mechanism by which chloride corrects metabolic alkalosis in man. Am J Med 1988; 84:449-458.
11. Levitan H, et al. The pathogenesis of hypochloremia in respiratory acidosis. J Clin Invest 1958;37:1667-1675.
12. Galla JH, et al. Adaptations to chloride-depletion alkalosis. Am J Physiol 1991;261:R771-R781.
13. Nakamura S, et al. NH4+ secretion in inner medullary collecting duct in potassium deprivation: Role of colonoic H+-K+- ATPase. Kidney Int 1999;56:2160-2167.
14. Sabatini S. The cellular basis of metabolic alkalosis. Kidney Int 1996;49:906-917.
15. Williamson JC. Acid-base disorder: Classification and management strategies. Am Fam Phys 1995;52:584-591.