🔍 Metabolic Alkalosis

Chloride-responsive vs resistant: The urine chloride key

📊 Metabolic Alkalosis: Definition & Recognition

Diagnostic Criteria

HCO₃⁻ > 26 mEq/L + pH > 7.40

Mild Alkalosis

HCO₃⁻ 26-30 mEq/L

pH 7.40-7.45

Moderate Alkalosis

HCO₃⁻ 30-40 mEq/L

pH 7.45-7.55

Severe Alkalosis

HCO₃⁻ > 40 mEq/L

pH > 7.55

⚠️ Clinical Consequences

Cardiovascular

  • Arrhythmias (especially with hypokalemia)
  • Coronary vasoconstriction
  • Increased digitalis toxicity

Neurological

  • Altered mental status
  • Seizures (severe cases)
  • Muscle cramps and weakness

Metabolic

  • Hypokalemia (almost universal)
  • Hypocalcemia (ionized)
  • Hypomagnesemia
  • Hypophosphatemia

🔬 Pathophysiology: Generation vs Maintenance

🔬 Two-Step Process

1. Generation of Alkalosis

  • Net acid loss (vomiting, gastric suction)
  • Net alkali gain (bicarbonate, citrate)
  • Contraction around fixed bicarbonate
  • Kidney generates new bicarbonate

2. Maintenance of Alkalosis

  • Volume depletion → ↑ sodium reabsorption
  • Chloride depletion → non-Cl⁻ anion reabsorption
  • Hypokalemia → ↑ H⁺ secretion
  • Mineralocorticoid excess → ↑ H⁺ secretion

💧 Contraction Alkalosis: Key Mechanism

The Process:

  1. Volume loss (diuretics, vomiting) with relatively more sodium and chloride loss than bicarbonate
  2. ECF contraction concentrates the remaining bicarbonate
  3. Volume depletion stimulates renin-angiotensin system
  4. ↑ Aldosterone → ↑ sodium reabsorption with H⁺/K⁺ loss
  5. Hypokalemia → intracellular H⁺ shift and ↑ renal H⁺ secretion
  6. Chloride depletion → bicarbonate reabsorption instead of chloride
Clinical Pearl: This explains why saline is therapeutic - it provides both volume (shuts off RAAS) and chloride (allows bicarbonate excretion).

🔑 The Urine Chloride Key: Diagnostic Gold Standard

Urine Chloride: The Ultimate Discriminator

"The urine chloride tells you everything you need to know about metabolic alkalosis"

🔹 Urine Cl⁻ < 20 mEq/L

CHLORIDE-RESPONSIVE

Pathophysiology: Volume and/or chloride depletion

Kidney response: Conserving sodium and chloride

Treatment: Saline administration

Prognosis: Readily correctable

🔸 Urine Cl⁻ > 20 mEq/L

CHLORIDE-RESISTANT

Pathophysiology: Ongoing mineralocorticoid activity

Kidney response: Continuing to waste sodium and chloride

Treatment: Address underlying cause

Prognosis: Persistent until cause corrected

🔹 Chloride-Responsive (UCl < 20)

GI Losses

  • Vomiting/gastric suction (most common)
  • Villous adenoma
  • Congenital chloridorrhea
  • Cystic fibrosis

Previous Diuretic Use

  • Loop diuretics (after effect wears off)
  • Thiazide diuretics (after effect wears off)
  • Post-hypercapnic alkalosis

Other Causes

  • Low chloride intake (rare)
  • Sweat losses with hypotonic fluid replacement
  • Recovery from starvation
Treatment: Normal saline administration
Mechanism: Provides volume and chloride, allowing kidney to excrete excess bicarbonate

🔸 Chloride-Resistant (UCl > 20)

Hyperaldosteronism

  • Primary hyperaldosteronism (Conn's syndrome)
  • Adrenal adenoma
  • Bilateral adrenal hyperplasia
  • Glucocorticoid-remediable aldosteronism

Secondary Hyperaldosteronism

  • Renal artery stenosis
  • Malignant hypertension
  • Renin-secreting tumor
  • Renovascular disease

Other Causes

  • Current diuretic use
  • Bartter/Gitelman syndrome
  • Severe hypokalemia (< 2.0 mEq/L)
  • Hypercalcemia
  • Hypermagnesemia
Treatment: Address underlying cause
Note: Saline alone will NOT correct the alkalosis

🫁 Respiratory Compensation: The Protective Response

Expected Respiratory Response

For every 1 mEq/L ↑ in HCO₃⁻

pCO₂ ↑ by 0.7 mmHg

Expected pCO₂ = 0.7 × (HCO₃⁻ - 24) + 40

Normal Compensation

  • Mechanism: Hypoventilation to retain CO₂
  • Limitation: Limited by hypoxemic drive
  • Maximum: pCO₂ rarely > 55 mmHg
  • Time course: Hours to days
Pearl: Compensation is less predictable than for metabolic acidosis

Inadequate Compensation

  • Lung disease: COPD, restrictive disease
  • CNS depression: Sedatives, neurologic disease
  • Neuromuscular: Weakness, paralysis
  • Mechanical ventilation: Fixed rate/volume
Risk: More severe alkalemia and complications

Contraction vs Compensation

Contraction Alkalosis:

  • Primary problem: Volume/chloride loss
  • Compensation: Appropriate respiratory response
  • Treatment: Saline administration

vs Primary Respiratory Acidosis:

  • Primary problem: CO₂ retention
  • Compensation: Renal HCO₃⁻ generation
  • Treatment: Improve ventilation

🧮 Interactive Metabolic Alkalosis Calculator

💊 Treatment Algorithms

🔹 Chloride-Responsive (UCl < 20) Treatment

Step-by-Step Treatment Protocol

  1. Calculate chloride deficit: 0.2 × weight(kg) × (103 - current Cl⁻)
  2. Give normal saline: Replace 50-75% of deficit over 12-24 hours
  3. Correct hypokalemia: Essential - often requires large amounts
  4. Correct hypomagnesemia: Must be >1.7 mg/dL for K⁺ correction
  5. Monitor response: UCl should increase >20 mEq/L when responding

Saline Therapy

  • Mild alkalosis: 0.9% NaCl at maintenance rate
  • Severe alkalosis: More aggressive replacement
  • Monitor: Volume status, electrolytes q6-8h
  • Endpoint: UCl >20 mEq/L, normalizing HCO₃⁻

Potassium Replacement

  • Preferred form: KCl (provides both K⁺ and Cl⁻)
  • Severe depletion: May need 200-400 mEq total
  • Rate: 10-20 mEq/hr max (central line)
  • Goal: K⁺ >3.5 mEq/L for alkalosis correction

🔸 Chloride-Resistant (UCl > 20) Treatment

Address Underlying Cause

  • Hyperaldosteronism: Spironolactone, amiloride
  • Current diuretics: Discontinue if possible
  • Bartter/Gitelman: High-dose K⁺ and Mg²⁺ supplementation
  • Severe hypokalemia: Aggressive K⁺ replacement
Important: Saline administration alone will NOT correct chloride-resistant alkalosis. Must address the underlying cause of ongoing mineralocorticoid activity.

🚨 Severe Alkalosis (pH > 7.55) Emergency Treatment

Consider Acid Administration (Rare!)

Indications:
  • pH > 7.55 with life-threatening symptoms
  • Inability to correct underlying cause rapidly
  • Severe complications (arrhythmias, seizures)

HCl Administration

  • Concentration: 150 mEq/L in D5W
  • Route: Central line only
  • Rate: 25-50 mEq/hr max
  • Goal: Reduce HCO₃⁻ by 5-10 mEq/L

Alternative: Hemodialysis

  • Low bicarbonate bath (< 25 mEq/L)
  • Safer than acid infusion
  • Consider for: Refractory cases
  • Advantage: Also corrects volume overload

📋 Clinical Case Studies

Case 1: Pyloric Stenosis

Patient: 3-month-old infant with projectile vomiting

Labs: pH 7.52, HCO₃⁻ 38, pCO₂ 48, Na 135, K 2.1, Cl 88, UCl 5

Physical: Dehydrated, palpable "olive"

Analysis:

  1. Metabolic alkalosis with appropriate respiratory compensation
  2. UCl < 20 = chloride-responsive
  3. Severe hypokalemia and hypochloremia
  4. Classic presentation of pyloric stenosis

Treatment: IV fluids (NS), aggressive KCl replacement, surgical pyloromyotomy

Case 2: Primary Hyperaldosteronism

Patient: 45F with hypertension, muscle weakness

Labs: pH 7.48, HCO₃⁻ 32, pCO₂ 46, K 2.4, UCl 45

Additional: Aldosterone 35 ng/dL, PRA suppressed

Analysis:

  1. Metabolic alkalosis with hypertension
  2. UCl > 20 = chloride-resistant
  3. Severe hypokalemia
  4. Elevated aldosterone with suppressed PRA = primary hyperaldosteronism

Treatment: Spironolactone, aggressive K⁺ replacement, imaging for adenoma

Case 3: Post-Diuretic Alkalosis

Patient: 78M, CHF, on furosemide 80mg BID

Labs: pH 7.46, HCO₃⁻ 34, K 2.9, UCl 12 (24h after last dose)

Clinical: Volume depleted, stopped diuretics yesterday

Analysis:

  1. Contraction alkalosis from chronic diuretic use
  2. UCl now <20 (was >20 when on diuretics)
  3. Volume and chloride depletion
  4. Need to balance CHF management with alkalosis correction

Treatment: Careful saline administration, KCl, consider acetazolamide

🎯 Key Learning Points

Urine Chloride is King

  • UCl < 20: Volume/chloride depletion → Saline responsive
  • UCl > 20: Ongoing mineralocorticoid activity → Address cause
  • Serial UCl measurements guide therapy effectiveness
  • Remember timing: Check UCl when not on active diuretics

Contraction Alkalosis

  • Volume loss concentrates existing bicarbonate
  • Chloride depletion prevents bicarbonate excretion
  • RAAS activation perpetuates the alkalosis
  • Saline provides both volume and chloride for correction

Treatment Essentials

  • Always correct hypokalemia and hypomagnesemia
  • Chloride-responsive: Saline is curative
  • Chloride-resistant: Saline alone won't work
  • Severe alkalosis (pH >7.55): Consider emergency measures

📚 For Educational Purposes Only

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