Metabolic alkalosis is one of those Step-style diagnoses that feels “easy” until the answer choices start weaponizing details: urine chloride, volume status, potassium level, and whether the patient can excrete bicarbonate. The trick is that each distractor is usually correct in a different alkalosis scenario—so your job is to recognize which mechanism is operating in this patient.
Clinical Vignette (Q-bank style)
A 27-year-old woman comes to the ED with dizziness and weakness. She has had 2 days of severe vomiting after a “stomach bug.” She is not taking any medications. Vitals show HR 112/min, BP 94/58 mm Hg. Exam reveals dry mucous membranes and decreased skin turgor. Labs:
| Test | Value |
|---|---|
| Na⁺ | 140 mEq/L |
| K⁺ | 2.8 mEq/L |
| Cl⁻ | 88 mEq/L |
| HCO₃⁻ | 38 mEq/L |
| ABG | pH 7.53, PaCO₂ 48 mm Hg |
Urine electrolytes: urine chloride 8 mEq/L.
Question: Which of the following is the most likely mechanism maintaining her acid-base disorder?
Answer choices
A. Increased aldosterone secretion causing increased H⁺ secretion in α-intercalated cells
B. Decreased effective arterial blood volume causing increased proximal bicarbonate reabsorption
C. Impaired pendrin (β-intercalated cell) function preventing bicarbonate secretion
D. Increased distal Na⁺ delivery leading to metabolic alkalosis via ENaC activation
E. Increased organic acid production causing an anion gap metabolic acidosis
Step 1: Diagnose the acid-base disorder (fast, but defensible)
- pH 7.53 → alkalemia
- HCO₃⁻ 38 → primary metabolic alkalosis
- PaCO₂ 48 → respiratory compensation
Check compensation (high-yield)
Expected PaCO₂ in metabolic alkalosis:
Plug in:
Measured PaCO₂ = 48 → appropriate compensation (no mixed disorder).
The key discriminator: Urine chloride
Urine Cl⁻ = 8 mEq/L (low) → classic chloride-responsive metabolic alkalosis.
This pattern points to:
- Vomiting / NG suction (loss of HCl)
- Remote diuretic use (if off diuretics long enough)
- Volume depletion → RAAS on → kidney avidly reabsorbs NaCl → low urine chloride
In contrast, chloride-resistant alkalosis (urine Cl⁻ typically > 20) suggests mineralocorticoid excess, ongoing diuretics, Bartter/Gitelman, etc.
Correct Answer: B. Decreased effective arterial blood volume causing increased proximal bicarbonate reabsorption
Why B is correct (what “maintains” the alkalosis)
Vomiting creates metabolic alkalosis by losing gastric HCl, but the kidney should be able to dump excess bicarbonate—unless something prevents it.
Here’s what maintains it:
- Volume depletion (“contraction alkalosis”)
- Decreased effective arterial blood volume → ↑ RAAS + ↑ sympathetic tone
- Proximal tubule increases Na⁺ reabsorption
- More Na⁺ reabsorption via Na⁺/H⁺ exchanger (NHE3) → more H⁺ secretion
- Filtered bicarbonate gets reclaimed along with Na⁺ → increased HCO₃⁻ reabsorption
- Hypochloremia
- You need chloride to excrete bicarbonate effectively (e.g., via pendrin in β-intercalated cells as a Cl⁻/HCO₃⁻ exchanger)
- Low chloride + volume depletion = kidney “holds on” to bicarbonate
- Hypokalemia
- Drives H⁺ into cells and K⁺ out → alkalemia
- Also increases renal ammoniagenesis and H⁺ secretion → worsens alkalosis
Translation: Vomiting generates the alkalosis, but volume depletion (low EABV) locks it in.
Systematic Distractor Breakdown (why every answer choice matters)
A. Increased aldosterone secretion causing increased H⁺ secretion in α-intercalated cells
Why it’s tempting: Volume depletion activates RAAS → ↑ aldosterone. Aldosterone:
- ↑ ENaC in principal cells → lumen negative
- ↑ H⁺ secretion (α-intercalated cells) and ↑ K⁺ secretion → metabolic alkalosis + hypokalemia
Why it’s not the best answer here:
This vignette screams chloride-responsive alkalosis from vomiting (low urine chloride). Aldosterone may contribute, but the core maintaining mechanism in vomiting-related alkalosis is low EABV → increased proximal HCO₃⁻ reabsorption and impaired bicarbonate excretion due to chloride depletion.
When A would be the best answer: Primary mineralocorticoid excess (Conn syndrome, ectopic ACTH with mineralocorticoid effects, licorice, Liddle-like physiology), typically with:
- Hypertension
- Metabolic alkalosis
- Hypokalemia
- Urine chloride usually high (chloride-resistant)
C. Impaired pendrin (β-intercalated cell) function preventing bicarbonate secretion
Why it’s tempting: Pendrin is a real Step concept:
- β-intercalated cells secrete HCO₃⁻ via Cl⁻/HCO₃⁻ exchange (pendrin)
- In alkalosis, pendrin helps dump bicarbonate if chloride is available
Why it’s wrong:
This patient doesn’t have a congenital pendrin issue; she has chloride depletion. Pendrin can’t work well without chloride, but that’s not the same as “impaired pendrin function” as a primary defect.
High-yield association: Pendrin is linked to Pendred syndrome (classically sensorineural hearing loss + thyroid issues). It’s not a common test answer for acute vomiting alkalosis unless they explicitly give congenital clues.
D. Increased distal Na⁺ delivery leading to metabolic alkalosis via ENaC activation
Why it’s tempting: This is the diuretic/Bartter/Gitelman logic:
- More Na⁺ delivered to the collecting duct → ENaC reabsorbs Na⁺
- Lumen becomes more negative → promotes K⁺ secretion and H⁺ secretion
- → metabolic alkalosis + hypokalemia
Why it’s wrong here:
No diuretic use, no chronic salt-wasting tubulopathy history, and urine chloride is low (suggesting kidneys are avidly reabsorbing chloride, not losing it).
When D is correct:
- Loop or thiazide diuretics (ongoing) → usually urine chloride high while taking them
- Bartter syndrome (loop-like): hypokalemic metabolic alkalosis, normal/low BP, ↑ renin/aldosterone, hypercalciuria
- Gitelman syndrome (thiazide-like): hypokalemic metabolic alkalosis, hypomagnesemia, hypocalciuria
E. Increased organic acid production causing an anion gap metabolic acidosis
Why it’s tempting: It’s a common distractor because patients with vomiting can also be dehydrated and ketotic.
Why it’s wrong:
This patient is alkalemic with elevated bicarbonate. No anion gap data are provided, but the ABG/labs clearly fit metabolic alkalosis with compensation.
When E is correct:
DKA, alcoholic ketoacidosis, lactic acidosis, toxic alcohols—typically low HCO₃⁻, acidemia (unless mixed), and clinical triggers.
High-Yield: Chloride-responsive vs chloride-resistant metabolic alkalosis
| Feature | Chloride-responsive (“saline-responsive”) | Chloride-resistant (“saline-resistant”) |
|---|---|---|
| Urine Cl⁻ | Low (< 10–20 mEq/L) | High (> 20 mEq/L) |
| Common causes | Vomiting/NG suction, remote diuretics | Primary hyperaldosteronism, Cushing/ACTH, ongoing diuretics, Bartter/Gitelman, Liddle |
| Volume status | Often hypovolemic | Often euvolemic or hypervolemic; may be hypertensive |
| Best initial treatment | Normal saline + K⁺ repletion | Treat cause (e.g., mineralocorticoid antagonists); sometimes acetazolamide |
High-Yield Mechanism Map (vomiting → alkalosis)
1) Generation
- Loss of HCl from stomach → net gain of bicarbonate in blood (“alkaline tide” becomes unopposed)
2) Maintenance (why kidney doesn’t fix it)
- Low EABV → ↑ proximal Na⁺ reabsorption → ↑ H⁺ secretion → ↑ HCO₃⁻ reabsorption
- Low chloride → can’t secrete HCO₃⁻ effectively (pendrin needs chloride)
- Low potassium → drives more H⁺ secretion and bicarbonate generation/reabsorption
Treatment Pearls (Step 2-leaning but Step 1-friendly)
For vomiting-associated, chloride-responsive metabolic alkalosis:
- 0.9% normal saline (restores volume + chloride)
- Replete potassium (often KCl)
- Stop the loss (antiemetics, treat obstruction, etc.)
In contrast, if urine chloride is high and BP is high:
- Think mineralocorticoid excess → spironolactone/eplerenone (or address the source)
Rapid-Fire Exam Pearls
- Metabolic alkalosis + low urine chloride = vomiting or remote diuretics until proven otherwise.
- “Contraction alkalosis”: volume depletion increases proximal bicarbonate reabsorption.
- Hypokalemia both causes and maintains alkalosis (cell shifts + renal mechanisms).
- Compensation for metabolic alkalosis is hypoventilation; PaCO₂ should rise roughly with the formula above.
- If they give hypertension + metabolic alkalosis + hypokalemia, strongly consider mineralocorticoid excess (and expect higher urine chloride).