What is the diagnostic approach for an older adult patient presenting with metabolic alkalosis, potentially caused by underlying medical conditions or medications such as diuretics or corticosteroids?

Diagnostic Approach to Metabolic Alkalosis

The diagnosis of metabolic alkalosis requires systematic evaluation starting with arterial blood gas confirmation (pH >7.45, HCO3- >26 mEq/L), followed by urinary chloride measurement to distinguish chloride-responsive from chloride-resistant causes, which fundamentally directs all subsequent diagnostic and therapeutic decisions. 1

Initial Laboratory Confirmation

Obtain arterial blood gas or venous blood gas to confirm metabolic alkalosis with pH >7.45 and elevated bicarbonate, while simultaneously calculating the anion gap: (Na+) - (Cl- + HCO3-), with normal being 10-12 mEq/L. 2, 3 The presence of compensatory respiratory acidosis (elevated pCO2) indicates chronicity and severity. 4

Essential initial laboratory panel includes:

• Serum electrolytes with particular attention to potassium, chloride, and bicarbonate levels 2
• Blood urea nitrogen and creatinine to assess renal function 2
• Serum osmolality (values >300 mOsm/kg indicate dehydration) 3
• Complete blood count 2

Critical Diagnostic Step: Urinary Chloride Measurement

Measure urinary chloride concentration immediately after confirming metabolic alkalosis, as this single test distinguishes chloride-responsive (<20 mEq/L) from chloride-resistant (>20 mEq/L) causes and determines the entire treatment strategy. 1, 5

Chloride-Responsive Alkalosis (Urine Cl- <20 mEq/L)

Common causes include:

• Vomiting or nasogastric suction (loss of gastric HCl) 1, 6
• Remote diuretic use (after drug effect has worn off) 1, 7
• Volume depletion with hypochloremia 1, 6
• Post-hypercapnic alkalosis (after rapid correction of chronic respiratory acidosis) 8

Chloride-Resistant Alkalosis (Urine Cl- >20 mEq/L)

Indicates ongoing renal losses or mineralocorticoid excess:

• Current diuretic therapy (loop or thiazide diuretics) 2, 1, 7
• Primary hyperaldosteronism 8, 6
• Cushing's syndrome 8
• Bartter or Gitelman syndrome (genetic salt-wasting tubulopathies) 1, 8, 6

Assessment of Volume Status and Blood Pressure

Physical examination must determine effective circulatory volume status, as this distinguishes between volume-depleted states (vomiting, diuretics) and volume-expanded states (mineralocorticoid excess). 6, 5

Key clinical findings:

• Hypovolemia with orthostatic hypotension suggests GI losses or remote diuretic use 5
• Normal to low blood pressure despite metabolic derangements is characteristic of Bartter or Gitelman syndrome 1
• Hypertension with metabolic alkalosis suggests mineralocorticoid excess 8, 6

Evaluation of Concurrent Electrolyte Abnormalities

Hypokalemia (<3.5 mmol/L) is nearly universal in metabolic alkalosis and both contributes to and perpetuates the alkalosis by promoting bicarbonate reabsorption and hydrogen secretion. 1, 8, 6 Severe hypokalemia (<2.5 mmol/L) suggests either severe GI losses, aggressive diuretic therapy, or genetic tubulopathies. 4, 5

Assess the sodium-chloride relationship: A narrow Na-Cl difference suggests chloride retention or metabolic acidosis, while a wide difference suggests alkalosis. 3 Hypochloremia is the hallmark of chloride-responsive alkalosis and limits the kidney's ability to excrete bicarbonate. 8, 6

Special Diagnostic Considerations for Older Adults

In older adults on diuretics or corticosteroids, consider:

• Medication review for loop diuretics, thiazides, or corticosteroids as primary causes 2, 7
• Assessment for heart failure, where diuretic-induced alkalosis is the most common acid-base disorder 7
• Evaluation for occult vomiting or laxative abuse, particularly in patients with borderline urine chloride concentrations 9

Advanced Diagnostic Testing for Unclear Cases

When the diagnosis remains unclear despite initial workup:

Measure urine pH and anion gap to identify surreptitious alkali ingestion (baking soda), which presents with alkaline urine pH and elevated urine anion gap. 9

Consider genetic salt-wasting disorders (Bartter or Gitelman syndrome) only if there is persistent metabolic alkalosis with paradoxically elevated urinary chloride (>20 mEq/L), hypokalemia, hypomagnesemia, and normal to low blood pressure despite no obvious external losses. 1, 3, 8

Obtain renal ultrasound to assess for nephrocalcinosis or kidney stones if Bartter syndrome is suspected. 1

Genetic testing provides definitive diagnosis of Bartter or Gitelman syndrome when clinical suspicion is high. 1

Common Diagnostic Pitfalls

Do not confuse metabolic alkalosis with hyperchloremic metabolic acidosis, which presents with low bicarbonate and normal anion gap—the opposite laboratory pattern. 3

Avoid overlooking Bartter or Gitelman syndrome in patients with unexplained metabolic alkalosis, especially with history of polyhydramnios and premature birth, as this represents a genetic disorder requiring lifelong management. 1

In heart failure patients on diuretics, hypochloremia is more typical, but during decongestion phases, relative chloride elevation can occur as volume contracts—do not misinterpret this as hyperchloremia. 3

Borderline urine chloride concentrations (15-25 mEq/L) require additional investigation including urine pH and consideration of surreptitious behaviors (vomiting, alkali ingestion, diuretic abuse). 9

Severity Assessment

Severe metabolic alkalosis (pH >7.55 or HCO3- >40 mEq/L) carries significant mortality risk and requires urgent intervention beyond diagnostic workup. 4, 5 These patients may present with altered mental status, respiratory depression requiring mechanical ventilation, or cardiac arrhythmias. 4, 5