What conditions can cause hyponatremia, hypokalemia, and leukocytosis (elevated white blood cell count) in a patient with persistent abdominal pain, normal lipase, and negative H. pylori?

Differential Diagnosis: Hyponatremia, Hypokalemia, and Leukocytosis with Persistent Abdominal Pain

The most likely diagnosis in this patient is ileus (potentially from Clostridioides difficile infection or other severe colitis), mesenteric ischemia, or severe intra-abdominal sepsis—all of which can present with this exact constellation of findings and require urgent intervention.

Primary Diagnostic Considerations

Ileus with Systemic Inflammatory Response

• Ileus is directly associated with leukocytosis as part of the systemic inflammatory response, and the Infectious Diseases Society of America (IDSA) specifically notes that C. difficile infection can present with ileus and marked leukocytosis (>15 × 10^9/L) even without diarrhea 1
• The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recognizes ileus as a sign of severe colitis, often accompanied by significant leukocytosis 1
• This combination of ileus and leukocytosis is considered an unfavorable prognostic factor requiring aggressive management 1
• The hyponatremia (122) and hypokalemia (2.8) likely result from fluid shifts, poor oral intake, and the systemic inflammatory state 2

Mesenteric Ischemia (Non-Occlusive or Occlusive)

• Patients with acute mesenteric ischemia classically present with "pain out of proportion to physical findings" and frequently have leukocytosis (>90% of cases) and metabolic acidosis 3
• The ACC/AHA guidelines emphasize that patients with acute abdominal pain out of proportion to physical findings should be suspected of having acute intestinal ischemia 3
• Elevated lactate occurs in 88% of mesenteric ischemia cases, though it may also result from dehydration 3
• Hyponatremia and hypokalemia can occur from fluid losses, decreased oral intake, and the metabolic derangements associated with intestinal ischemia 2
• D-dimer >0.9 mg/L has 82% specificity and 60% sensitivity for intestinal ischemia 3

Severe Intra-Abdominal Sepsis

• The combination of leukocytosis (16.6), electrolyte abnormalities, and persistent abdominal pain suggests possible occult infection 2
• Hyponatremia affects approximately 35% of hospitalized patients and is associated with increased mortality, often occurring in the context of systemic illness 4
• Hypokalemia can result from poor oral intake, gastrointestinal losses, or redistribution in the setting of metabolic alkalosis 5

Critical Laboratory and Imaging Evaluation

Essential Immediate Tests

• Serum lactate level: Elevated lactate (>2 mmol/L) is associated with irreversible intestinal ischemia with hazard ratio of 4.1 3
• D-dimer: Normal D-dimer essentially excludes mesenteric ischemia; elevated levels warrant urgent imaging 3
• C-reactive protein and procalcitonin: Elevated levels suggest severe infection or inflammation 2
• Stool testing for C. difficile toxin: Given the ileus-leukocytosis combination, this is mandatory 1
• Blood cultures: Should be obtained if sepsis is suspected 2

Imaging Requirements

• CT angiography (CTA) of the abdomen is the diagnostic test of choice for suspected mesenteric ischemia, as plain radiographs and ultrasound are inadequate 3
• CTA should be performed urgently if lactate is elevated in combination with abdominal pain, even if the patient does not appear critically ill 3
• Duplex ultrasound is contraindicated in acute intestinal ischemia due to time constraints and technical limitations with abdominal distention 3

Electrolyte Abnormalities: Specific Considerations

Hyponatremia (122 mEq/L) - Moderate Severity

• This represents moderate hyponatremia (125-129 mEq/L range) and requires assessment of volume status 4, 5
• In the context of abdominal pathology, this likely represents hypovolemic hyponatremia from poor oral intake and fluid losses 5
• The syndrome of inappropriate antidiuresis (SIAD) can occur with severe illness and pain 4
• Treatment depends on symptom severity: If severely symptomatic (confusion, seizures), 3% hypertonic saline boluses are indicated; otherwise, treat the underlying cause and correct volume status 5

Hypokalemia (2.8 mEq/L)

• Hypokalemia in this context suggests either gastrointestinal losses (if vomiting occurred) or redistribution 2
• Severe hypokalemia (<3.0 mEq/L) requires urgent correction with potassium supplementation while monitoring cardiac rhythm 2
• Check for concurrent hypomagnesemia, which impairs potassium repletion 2

Common Pitfalls to Avoid

• Do not dismiss normal lipase as excluding all serious pathology: Mesenteric ischemia, severe colitis, and ileus all present with normal lipase 3, 1
• Do not rely on plain radiographs: They have limited sensitivity for early mesenteric ischemia and only become positive when bowel infarction has developed 3
• Do not delay imaging while pursuing extensive laboratory workup: If mesenteric ischemia is suspected, CTA should be performed urgently 3
• Do not assume diarrhea must be present for C. difficile infection: Fulminant C. difficile can present with ileus and no diarrhea 1
• Do not correct hyponatremia too rapidly: Overly rapid correction can cause osmotic demyelination syndrome; aim for 4-6 mEq/L increase in first 1-2 hours if severely symptomatic, but no more than 10 mEq/L in 24 hours 4, 5

Immediate Management Algorithm

1. Assess hemodynamic stability and neurologic status related to electrolyte abnormalities 5
2. Obtain urgent lactate, D-dimer, CRP, procalcitonin, and blood cultures 3, 2
3. Order stool C. difficile testing given the ileus-leukocytosis combination 1
4. Proceed to CT angiography if lactate is elevated or clinical suspicion for mesenteric ischemia is high 3
5. Begin fluid resuscitation with normal saline for hypovolemic hyponatremia while correcting potassium 5
6. Consider empiric broad-spectrum antibiotics (e.g., ceftriaxone and metronidazole) if sepsis is suspected while awaiting diagnostic confirmation 3
7. If C. difficile is confirmed with ileus and leukocytosis, initiate aggressive treatment with vancomycin and consider intravenous metronidazole 1