Metabolic Alkalosis
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.
Keep reading — start your free trial
You've read your 2 free diagnosis previews. Create your free account to unlock the full Metabolic Alkalosis outline — plus all 514 diagnoses, 5,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Risk factors
- Saline-responsive (chloride-depleted): vomiting, nasogastric suction, diuretic use (loop or thiazide), post-hypercapnic alkalosis, cystic fibrosis sweat loss, congenital chloridorrhea
- Saline-resistant (volume-expanded, mineralocorticoid excess): primary hyperaldosteronism (Conn syndrome), Cushing syndrome, exogenous mineralocorticoid (fludrocortisone), licorice (glycyrrhizic acid), 11-beta-hydroxysteroid dehydrogenase deficiency, Liddle syndrome, Bartter and Gitelman syndromes, severe hypokalemia, severe hypomagnesemia, refeeding syndrome, milk-alkali syndrome
Pathophysiology
Generation: H+ loss (vomiting, NG suction, renal H+ secretion in mineralocorticoid excess) OR HCO3 gain (bicarbonate infusion, citrate metabolism in massive transfusion, milk-alkali) OR contraction alkalosis (loss of chloride-rich, bicarbonate-poor fluid raises serum HCO3 by volume contraction). Maintenance: requires impaired renal HCO3 excretion — typically from chloride depletion (reabsorbed Na+ requires another anion → HCO3 reabsorption increases), volume depletion (enhances proximal Na/HCO3 reabsorption), aldosterone excess (distal H+ secretion), or hypokalemia (intracellular shift of H+, ammoniagenesis). Respiratory compensation: hypoventilation raises PaCO2 ~0.7 mmHg per 1 mEq/L rise in HCO3 (max PaCO2 ~55).
Clinical presentation
Symptoms
- Often asymptomatic until severe (pH >7.55)
- Confusion, lethargy, seizures from cerebral vasoconstriction
- Paresthesias, muscle cramps, tetany (alkalosis lowers ionized calcium)
- Arrhythmias (atrial and ventricular)
- Hypoventilation with secondary hypoxemia
Signs / physical exam
- 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
- Gitelman syndrome — Genetic thiazide-like defect — hypokalemia, hypomagnesemia, hypocalciuria, alkalosis, normotension
- Surreptitious vomiting (bulimia) — Low urine Cl, low K, elevated HCO3, no obvious cause; consider patient population
Diagnostic workup
Diagnostic criteria
Step 1: confirm metabolic alkalosis (high pH + high HCO3). Step 2: assess respiratory compensation. Step 3: measure urine chloride — <20 mEq/L = saline-responsive (chloride-depleted: vomiting, NG suction, post-diuretic); >20 mEq/L = saline-resistant (mineralocorticoid excess or current diuretic use). Step 4: assess volume status and blood pressure to subdivide saline-resistant causes.
Labs
- ABG or VBG — confirm pH >7.45 and HCO3 >26 mEq/L
- BMP — anion gap, chloride, potassium, magnesium
- Urine electrolytes — particularly urine chloride (key for saline-responsive vs saline-resistant distinction)
- Plasma renin and aldosterone if hypertension and hypokalemia coexist (suspect primary hyperaldosteronism if aldo/renin ratio >20)
- 24-hour urine cortisol or overnight dexamethasone suppression if Cushing suspected
- Genetic testing for Bartter/Gitelman/Liddle in young, normotensive patients with unexplained alkalosis
- Calculate expected PaCO2 compensation: PaCO2 = 0.7 × ΔHCO3 + 40 (± 5)
Imaging
- Adrenal CT or MRI if mineralocorticoid excess suspected
- Renal vein sampling for lateralizing aldosterone-producing adenoma
Diagnostic algorithm
| Subtype | Urine Cl | BP / volume | Classic causes | Treatment |
|---|---|---|---|---|
| Saline-responsive | <20 mEq/L | Volume-depleted, normal BP | Vomiting, NG suction, prior diuretic, CF | Normal saline + KCl |
| Saline-resistant with HTN | >20 mEq/L | Volume-expanded, hypertensive | Hyperaldosteronism, Cushing, licorice, Liddle | Treat cause; spironolactone or amiloride |
| Saline-resistant without HTN | >20 mEq/L | Volume-normal, normotensive | Bartter, Gitelman, severe hypoK/hypoMg | Replace K/Mg; K-sparing diuretic; NSAIDs (Bartter) |
| Current diuretic use | >20 mEq/L during diuresis, <20 after withdrawal | Variable | Loop or thiazide diuretic | Stop diuretic; add K-sparing agent |
Treatment
First-line
- Treat the underlying cause — antiemetics, discontinue diuretics, address mineralocorticoid excess
- Saline-responsive: isotonic saline (0.9% NaCl) corrects volume and chloride deficit, allowing renal bicarbonate excretion
- 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)
- Acetazolamide 250-500 mg IV/PO daily — promotes renal HCO3 excretion (also causes hypokalemia, so replace K)
- Hydrochloric acid 0.1-0.2 N infusion via central line — last resort for life-threatening pH >7.6
- Hemodialysis with low-bicarbonate dialysate in ESKD
Second-line / adjunct
- Ammonium chloride PO (rarely used; can precipitate hepatic encephalopathy)
- Arginine hydrochloride IV (specialty use)
- Adjust ventilator settings to allow permissive hypercapnia in ICU patients with mixed disorders
Complications
- Cardiac arrhythmias from alkalosis-induced hypokalemia and reduced ionized calcium
- Reduced cerebral perfusion (cerebral vasoconstriction); seizures
- 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.
- Bartter syndrome ≈ loop diuretic phenotype (hypercalciuria); Gitelman syndrome ≈ thiazide phenotype (hypocalciuria).
- Mineralocorticoid excess produces saline-resistant alkalosis with hypertension; Bartter/Gitelman produce saline-resistant alkalosis with normotension.
- Acetazolamide is the go-to drug for metabolic alkalosis in patients with heart failure or edema where saline is unsafe.
References
- Galla 2000 — Galla JH. Metabolic alkalosis (JASN 2000;11:369-375)
- Emmett 2020 — Emmett M. Metabolic alkalosis: a brief pathophysiologic review (CJASN 2020;15:1848-1856)
- Endocrine Society 2016 — Funder JW et al. The management of primary aldosteronism: case detection, diagnosis, and treatment (JCEM 2016;101:1889-1916)
Practice Renal/Urology questions on FirstPassPA
Turn this outline into retention. 5,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Start studying free → Browse all 514 diagnosesEducational 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.