Renal/Urology · PANCE / PANRE

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.

🔒 Free preview limit reached

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, 3,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.

Start your 7-day free trial → Sign in

Free to start · No credit card · Cancel anytime

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

Metabolic alkalosis subclassification by urine chloride and blood pressure.

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. 3,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.

Start studying free → Browse all 514 diagnoses

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. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants.