Elevated serum bicarbonate from H+ loss or HCO3 gain, subdivided by chloride responsiveness.
Also known as: metabolic alkalosis, alkalemia, contraction alkalosis, saline-responsive alkalosis, saline-resistant alkalosis
Overview
A primary acid-base disorder characterized by elevated serum bicarbonate (>26-28 mEq/L) and arterial pH >7.45, resulting from either net loss of hydrogen ions, net gain of bicarbonate, or loss of fluid containing chloride in excess of bicarbonate (contraction alkalosis). Classified by urine chloride: saline-responsive (UCl <20 mEq/L) and saline-resistant (UCl >20 mEq/L).
Epidemiology
Among the most common acid-base disturbances in hospitalized patients. Often iatrogenic (diuretics, nasogastric suction, transfusion of citrate-rich blood products). Mortality of severe metabolic alkalosis (pH >7.55) approaches 45-65% in critically ill patients — reflects severity of underlying illness.
Try two board-style Metabolic Alkalosis questions
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
Question 1RenalMedium
A 48-year-old woman is evaluated for hypertension that remains poorly controlled on three antihypertensive agents. She reports no vomiting, diarrhea, or diuretic use. Blood pressure is 168/102 mm Hg and she has no edema. Laboratory studies show sodium 144 mEq/L, potassium 2.9 mEq/L, chloride 96 mEq/L, and bicarbonate 33 mEq/L; arterial pH is 7.49. A spot urine chloride is 38 mEq/L. Which of the following is the most appropriate next diagnostic test?
APlasma free metanephrine levels
BGenetic testing for Gitelman syndrome
CPlasma aldosterone-to-renin ratio
DOvernight dexamethasone suppression
EAdrenal-protocol CT of the abdomen
Reveal answer & full explanation
Correct answer: C — Plasma aldosterone-to-renin ratio
APlasma free metanephrine levels
BGenetic testing for Gitelman syndrome
CPlasma aldosterone-to-renin ratio✓
DOvernight dexamethasone suppression
EAdrenal-protocol CT of the abdomen
Why Plasma aldosterone-to-renin ratio is correct
This patient has a saline-resistant metabolic alkalosis (high pH, high HCO3) with hypokalemia, hypertension, and a urine chloride >20 mEq/L, which points away from chloride-depletion causes (vomiting, diuretics) and toward mineralocorticoid excess.
The combination of hypertension + hypokalemic alkalosis is the classic screen for primary hyperaldosteronism; an aldosterone-to-renin ratio >20 (with elevated aldosterone) supports the diagnosis and is the correct next step before adrenal imaging or confirmatory testing.
Why the others are wrong
Plasma free metanephrine levels — screen for pheochromocytoma, which causes resistant or paroxysmal hypertension with episodic headache, sweating, and palpitations but does not typically produce a hypokalemic metabolic alkalosis with a high urine chloride; that pattern points to mineralocorticoid excess, so the aldosterone-to-renin ratio comes first.
Genetic testing for Gitelman syndrome — Bartter/Gitelman cause saline-resistant alkalosis but with NORMAL blood pressure; hypertension makes a tubulopathy unlikely, and genetic testing is reserved for young normotensive patients with unexplained alkalosis.
Overnight dexamethasone suppression — screens for Cushing syndrome, a much less common cause of mineralocorticoid-excess alkalosis; it is pursued only when cushingoid features are present or aldosterone testing is unrevealing.
Adrenal-protocol CT of the abdomen — primary aldosteronism often stems from an aldosterone-producing adenoma, but adrenal imaging comes only after biochemical diagnosis; nonfunctioning adrenal incidentalomas are common in middle-aged adults and bilateral hyperplasia may look normal, so CT cannot establish the diagnosis and is reserved for subtype evaluation after confirmation.
Question 2RenalMedium
A 34-year-old woman with hyperemesis gravidarum has been vomiting for 5 days and has had a nasogastric tube to low suction for 2 days. Vitals: BP 98/62 mm Hg, HR 104/min, with dry mucous membranes. Labs: Na 138 mEq/L, K 2.9 mEq/L, Cl 88 mEq/L, HCO3 38 mEq/L. Arterial pH is 7.52. Urine chloride is 8 mEq/L. Her vomiting has now stopped and the tube has been clamped, yet the elevated bicarbonate persists. Which of the following best explains the maintained alkalosis?
DVolume contraction concentrates a fixed mass of extracellular bicarbonate
EHypokalemia stimulates renal ammoniagenesis and acid excretion
Why Chloride depletion forces renal bicarbonate reabsorption is correct
Vomiting and NG suction lose HCl-rich fluid, generating the alkalosis and depleting chloride and volume.
Maintenance is the key: with chloride scarce, the proximal and distal nephron must reabsorb Na+ alongside another anion, so HCO3- reabsorption rises and the kidney cannot excrete the excess bicarbonate.
Volume depletion (BP 98/62, HR 104) adds secondary hyperaldosteronism and enhanced proximal Na/HCO3 reabsorption, but the urine chloride of 8 mEq/L (<20) marks this as a saline-responsive, chloride-depleted process.
Isotonic saline plus KCl repairs the chloride and volume deficits, after which the kidney can excrete HCO3- and correct the pH.
Why the others are wrong
Pendrin exchange drives collecting duct bicarbonate secretion - pendrin in type B intercalated cells secretes HCO3- in exchange for luminal Cl-, so it disposes of bicarbonate rather than retaining it; with urine chloride only 8 mEq/L there is almost no luminal chloride to drive the exchange, and that stalled secretion is part of why the alkalosis persists rather than a cause of it.
Hypokalemia stimulates renal ammoniagenesis and acid excretion - hypokalemia does contribute to maintaining alkalosis, but it is a secondary perpetuator here; the dominant driver in a vomiting, chloride-depleted patient with urine Cl 8 mEq/L is chloride depletion, and KCl is given precisely because Cl- (not just K+) must be restored.
Aldosterone excess promotes distal sodium-for-hydrogen exchange - this is the mechanism of saline-RESISTANT alkalosis (Conn syndrome, Cushing); those patients are volume-expanded and hypertensive with urine chloride >20 mEq/L, the opposite of this hypovolemic, hypotensive picture.
Volume contraction concentrates a fixed mass of extracellular bicarbonate - her low blood pressure, tachycardia, and dry mucous membranes make contraction alkalosis tempting, but shrinking the extracellular space around a fixed bicarbonate mass raises HCO3 only modestly and cannot by itself sustain it; a normally functioning kidney would excrete the excess, and here it is chloride depletion that forces the kidney to keep reabsorbing bicarbonate.
Per standard acid-base teaching, urine chloride is the single most useful test to subclassify metabolic alkalosis: <20 mEq/L indicates the saline-responsive, chloride-depletion mechanism.
That's 2. Get 7,700+ more.
Unlock the full FirstPassPA bank: 7,700+ board-style questions, flashcards, and an AI tutor that explains every answer. Your 7-day free trial includes everything, and there's no credit card required.
You've read your 2 free diagnosis previews. Create your free account to unlock the full Metabolic Alkalosis outline — plus all 514 diagnoses, 7,700+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Trousseau and Chvostek signs (functional hypocalcemia)
Hyperreflexia, fasciculations
Volume status varies — depleted in saline-responsive, expanded in mineralocorticoid excess
Hypertension in mineralocorticoid-excess states
Classic findings
Vomiting patient with hypochloremic, hypokalemic metabolic alkalosis and low urine chloride. Hypertensive patient with hypokalemic alkalosis and aldosterone:renin ratio >20 suggests primary hyperaldosteronism.
Differential diagnosis
Respiratory acidosis (compensated) — Chronic hypercapnia raises HCO3, but pH is low or low-normal — not alkalotic
Laboratory error / contamination — Air bubble in ABG sample can falsely lower PaCO2 and raise pH; repeat sample if implausible
Mixed acid-base disorder — Use anion gap, delta-delta, and expected compensation to detect coexisting disturbances
Bartter syndrome — Genetic loop-diuretic-like defect — hypokalemic, hypochloremic alkalosis with normotension and hypercalciuria
Replace potassium (KCl) and magnesium aggressively — both perpetuate alkalosis when depleted
Saline-resistant with mineralocorticoid excess: surgical removal of adenoma, OR mineralocorticoid receptor antagonist (spironolactone, eplerenone), OR ENaC blocker (amiloride, triamterene) for Liddle syndrome
Discontinue exogenous alkali (excessive antacids, bicarbonate-containing dialysate, citrate from transfusion or CRRT)
Persistent vomiting / NG suction
IV normal saline with KCl
H2 blocker (famotidine) or PPI (pantoprazole, omeprazole) to reduce HCl loss
Antiemetic — ondansetron, metoclopramide
Diuretic-induced
Discontinue or reduce diuretic if clinically feasible
Replace K and Mg; add K-sparing diuretic (spironolactone, eplerenone, amiloride)
If diuretic necessary (e.g., heart failure), accept mild alkalosis and treat aggressively
Primary hyperaldosteronism
Adrenalectomy for aldosterone-producing adenoma
Spironolactone or eplerenone for bilateral adrenal hyperplasia
Address HTN aggressively
Severe alkalosis with edema or renal failure (cannot tolerate saline)
Hypoventilation with hypoxemia — particularly dangerous in patients with underlying lung disease
Difficulty weaning from mechanical ventilation
Increased mortality in critically ill patients (especially pH >7.55)
PANCE pearls
Urine chloride is the single most useful test to subclassify metabolic alkalosis — vomiting and recent diuretic use can both lower it; consider timing.
You cannot fully correct metabolic alkalosis until chloride, potassium, and magnesium deficits are repaired.
Emmett 2020 — Emmett M. Metabolic alkalosis: a brief pathophysiologic review (CJASN 2020;15:1848-1856)
Endocrine Society 2025 — Adler GK et al. Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline (J Clin Endocrinol Metab 2025;110(9):2453-2495)
Practice Renal/Urology questions on FirstPassPA
Turn this outline into retention. 7,700+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.