Everything You Need to Know About Metabolic alkalosis for Step 1

Metabolic alkalosis is one of those acid–base topics that feels deceptively “simple” until UWorld starts mixing vomiting, diuretics, hyperaldosteronism, and urine chloride in the same vignette. The key to owning it for Step 1 is understanding how alkalosis is generated and (even more important) why the kidney fails to get rid of it. Once you can explain maintenance, the diagnosis and treatment basically fall into place.

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What Is Metabolic Alkalosis?

Metabolic alkalosis is a primary increase in serum bicarbonate ($\text{HCO}_3^-$) leading to increased arterial pH.

• Primary change: $\uparrow \text{HCO}_3^-$
• pH: $\uparrow$ (alkalemia)
• Compensation: hypoventilation $\rightarrow \uparrow \text{PaCO}_2$ (limited by hypoxemia)

Expected Respiratory Compensation (High-Yield Formula)

For metabolic alkalosis, expected $\text{PaCO}_2$ rises about 0.7 mmHg per 1 mEq/L rise in $\text{HCO}_3^-$:

$\text{Expected PaCO}_2 \approx 40 + 0.7 \times (\text{HCO}_3^- - 24) \pm 5$

If the measured $\text{PaCO}_2$ is way off, suspect a mixed disorder.

First Aid cross-reference: Acid–base disorders and compensation formulas (Renal/Respiratory physiology section, “Acid–Base Disorders”).

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The Core Concept: Generation vs Maintenance (The Step Trick)

Metabolic alkalosis usually requires two steps:

1. Generation: add base or lose acid
2. Maintenance: kidney can’t excrete the excess bicarbonate

1) How Alkalosis Is Generated

Common ways:

• Loss of H⁺ from GI tract: vomiting / NG suction (loss of gastric HCl)
• Loss of H⁺ from kidney: loop/thiazide diuretics, mineralocorticoid excess
• Gain of bicarbonate (less common clinically): excessive antacids, bicarbonate administration, citrate load (massive transfusion)

2) Why Alkalosis Is Maintained (High Yield)

The kidney normally dumps excess $\text{HCO}_3^-$—unless:

• Volume depletion (“contraction alkalosis”) → increases proximal $\text{HCO}_3^-$ reabsorption
• Chloride depletion → impaired bicarbonate secretion by β-intercalated cells (pendrin, Cl⁻/HCO₃⁻ exchanger)
• Hypokalemia → drives H⁺ into cells and increases renal ammoniagenesis/H⁺ secretion
• High aldosterone/ENaC activity → increases distal H⁺ secretion by α-intercalated cells

A memorable Step line:
“Metabolic alkalosis sticks around when the patient is volume-depleted, chloride-depleted, or potassium-depleted.”

First Aid cross-reference: Renal tubular physiology (collecting duct cell types, aldosterone effects), Diuretics.

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Pathophysiology You Actually Need (Without Getting Lost)

Vomiting / NG Suction → “Chloride-Responsive” Alkalosis

Mechanisms:

• Loss of HCl → net gain of bicarbonate in blood
• Volume depletion → RAAS activation
• Aldosterone ↑ → Na⁺ reabsorption, H⁺ secretion ↑ (α-intercalated cells) and K⁺ secretion ↑
• Cl⁻ depletion → kidney can’t excrete bicarbonate efficiently

Classic Step pairing: vomiting → metabolic alkalosis + hypochloremia + hypokalemia

Loop/Thiazide Diuretics → “Contraction Alkalosis” (Chloride-Responsive)

Mechanisms:

• NaCl wasting → volume depletion → RAAS ↑
• Increased distal Na⁺ delivery + aldosterone → ↑ K⁺ secretion (principal cells) and ↑ H⁺ secretion (α-intercalated)

First Aid cross-reference: Loop/thiazide adverse effects (metabolic alkalosis, hypokalemia).

Mineralocorticoid Excess → “Chloride-Resistant” Alkalosis

Examples:

• Primary hyperaldosteronism (Conn)
• Secondary hyperaldosteronism (renin-driven)
• Cushing syndrome (cortisol activating mineralocorticoid receptors)
• Licorice (inhibits 11β-HSD2 → cortisol stimulates mineralocorticoid receptors)
• Liddle syndrome (ENaC gain-of-function; looks like aldosterone excess but low aldosterone)

Mechanisms:

• ENaC-mediated Na⁺ reabsorption → lumen negative
• Drives K⁺ secretion and H⁺ secretion → alkalosis
• Typically with hypertension

First Aid cross-reference: Hyperaldosteronism, Liddle, Apparent mineralocorticoid excess (11β-HSD2), licorice.

Hypokalemia as a Driver (Not Just a Consequence)

Hypokalemia worsens alkalosis by:

• Shifting H⁺ into cells (to maintain electroneutrality) → alkalemia
• Increasing renal H⁺ secretion and new bicarbonate generation

This is why repleting K⁺ is often essential for correction.

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Clinical Presentation (What the Vignette Actually Looks Like)

Many symptoms come from electrolytes and volume status, not the pH itself.

Symptoms/Signs

• Neuromuscular excitability (often via ↓ ionized Ca²⁺ in alkalemia):
  • Paresthesias, cramps, carpopedal spasm
• Weakness (often from hypokalemia)
• Arrhythmias (hypokalemia ± hypomagnesemia)
• Hypoventilation (compensation; limited)
• Signs of volume depletion:
  • Orthostasis, tachycardia, dry mucous membranes

High-yield association: Alkalosis can decrease ionized calcium by increasing albumin binding → tetany-like symptoms.

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Diagnosis: A Stepwise Approach That Works Every Time

Step 1: Confirm Primary Metabolic Alkalosis on ABG/BMP

• BMP: $\uparrow \text{HCO}_3^-$ (total CO₂)
• ABG: pH > 7.45 with elevated $\text{HCO}_3^-$

Step 2: Check Compensation (Rule Out a Mixed Disorder)

Use the expected $\text{PaCO}_2$ equation above.
If actual $\text{PaCO}_2$ is lower than expected, there’s a concurrent respiratory alkalosis.
If higher than expected, concurrent respiratory acidosis.

Step 3 (High Yield): Use Urine Chloride to Classify the Cause

Urine chloride ($U_{\text{Cl}^-}$) is the exam’s favorite discriminator.

Pro tip: If they’re actively taking diuretics, $U_{\text{Cl}^-}$ is often high. If it was days ago, it may look chloride-responsive.

Step 4: Look at Blood Pressure + Renin/Aldosterone When Appropriate

If hypertensive metabolic alkalosis, think mineralocorticoid/ENaC problems:

First Aid cross-reference: RAAS patterns, hypertensive disorders, diuretic-like syndromes.

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Treatment: Fix the “Maintenance” Problem

Treatment depends on whether it’s chloride-responsive or chloride-resistant, and whether the patient is volume depleted.

Chloride-Responsive Metabolic Alkalosis (Low Urine Cl⁻)

Mainstays:

• Normal saline (0.9% NaCl): restores volume + provides chloride → allows bicarbonate excretion
• Potassium repletion (KCl): corrects hypokalemia and reduces renal H⁺ secretion

If severe and symptomatic:

• Consider acetazolamide (carbonic anhydrase inhibitor) to increase bicarbonate excretion (especially if volume overloaded and you can’t give saline).

Chloride-Resistant Metabolic Alkalosis (High Urine Cl⁻)

Treat the cause:

• Mineralocorticoid excess:
  • Spironolactone/eplerenone (aldosterone antagonists)
  • Remove adrenal adenoma if indicated
• Liddle syndrome:
  • Amiloride or triamterene (ENaC blockers) — spironolactone won’t help because aldosterone is low
• Ongoing diuretics: stop/reduce if possible; replace volume/electrolytes as needed

Life-Threatening or Refractory Cases (Rare on Step, but good to know)

• HCl infusion (ICU-level) or dialysis in select scenarios (renal failure, severe alkalemia)

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High-Yield Associations & Classic Vignette Triggers

1) Vomiting + Hypochloremia + Hypokalemia

• Metabolic alkalosis with low $U_{\text{Cl}^-}$
• Treat with NS + KCl

2) Diuretics → Metabolic Alkalosis + Hypokalemia

• Loop/thiazide: volume contraction + RAAS
• If current use → $U_{\text{Cl}^-}$ often high

3) Hyperaldosteronism: Hypertension + Hypokalemia + Metabolic Alkalosis

• High urine chloride
• Check renin/aldosterone pattern

4) Licorice (Glycyrrhizic acid) = Apparent Mineralocorticoid Excess

• Inhibits 11β-HSD2
• Hypertension, hypokalemia, metabolic alkalosis
• Low renin, low aldosterone

5) Bartter vs Gitelman (Step 1 favorite)

Both can cause metabolic alkalosis + hypokalemia with high urine chloride.

First Aid cross-reference: Bartter/Gitelman and diuretic mechanisms.

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Mini “Step-Style” Framework to Use on Test Day

When you see metabolic alkalosis, ask:

1. Is the patient volume depleted? (vomiting, diuretics)
2. What is the urine chloride?
   • Low → give chloride + volume + K⁺
   • High → think mineralocorticoids, ongoing diuretics, tubulopathies
3. Is there hypertension?
   • Yes → work through renin/aldosterone patterns (Conn vs RAS vs Liddle/licorice)
4. Is K⁺ low?
   • Replace it (often required to correct alkalosis)

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Rapid Review Table (High Yield)

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First Aid Cross-References (Where This Lives in FA)

You’ll see metabolic alkalosis show up across a few “clusters” in First Aid:

• Acid–base disorders & compensation (renal/respiratory physiology)
• Diuretics (loop/thiazide adverse effects; K⁺/H⁺ wasting)
• RAAS + hyperaldosteronism patterns
• Bartter & Gitelman syndromes
• Collecting duct physiology (principal vs α/β-intercalated cells)

If you connect those pages mentally, metabolic alkalosis becomes a pattern-recognition question instead of a math problem.