What laboratory tests are needed for a patient with persistent generalized stomach pain, considering potential underlying conditions such as gastrointestinal bleeding, infection, inflammation, hepatobiliary disease, or metabolic disorders?

Laboratory Workup for Persistent Generalized Stomach Pain

For persistent generalized abdominal pain, obtain a complete blood count with differential, comprehensive metabolic panel including liver function tests, C-reactive protein, lipase, urinalysis, and fecal calprotectin, with additional testing for stool pathogens and Clostridioides difficile if diarrhea is present. 1

Initial Essential Laboratory Tests

Core Blood Work

• Complete blood count (CBC) with differential to assess for leukocytosis (suggesting infection or inflammation), anemia (indicating possible chronic GI bleeding), and eosinophilia (raising concern for eosinophilic gastroenteritis) 2, 1, 3
• Comprehensive metabolic panel including electrolytes, renal function (creatinine, urea), and liver function tests (transaminases, alkaline phosphatase, bilirubin) to evaluate for hepatobiliary disease, electrolyte disturbances, and renal impairment 2, 1
• C-reactive protein (CRP) as a marker of inflammation and infection severity 2

Organ-Specific Markers

• Serum lipase for suspected pancreatitis, as it is more specific than amylase 1
• Liver function tests are particularly important given that up to 30% of patients with inflammatory bowel disease have abnormal liver biochemistry 4

Additional Critical Tests

• Urinalysis to exclude urinary tract infection or nephrolithiasis as alternative pain sources 1
• Beta-human chorionic gonadotropin (β-HCG) in all women of reproductive age to rule out ectopic pregnancy before proceeding with further workup 1

Stool Studies (When Diarrhea Present)

If the patient has concurrent diarrhea, obtain stool studies before initiating any immunosuppressive therapy:

• Clostridioides difficile testing using a two-step approach with enzyme immunoassays detecting glutamate dehydrogenase and toxins A/B, or nucleic acid amplification tests 2
• Stool culture for Shigella, Salmonella, Campylobacter, and Shiga toxin-producing E. coli 2
• Stool pathogen panels are a reasonable alternative to traditional cultures where available 2
• Fecal calprotectin to differentiate inflammatory from non-inflammatory causes of abdominal pain, particularly useful when inflammatory bowel disease is suspected (>250 μg/g warrants urgent gastroenterology referral) 2

Interpretation of White Blood Cell Differential

The leukocyte differential provides important prognostic information:

• Neutrophilia with lymphopenia (<1.4 × 10⁹/L) and eosinopenia (<0.04 × 10⁹/L) has 94.9% specificity for severe illness requiring surgical or infectious disease intervention 5
• Neutrophil count >9.0 × 10⁹/L combined with the above pattern strongly suggests serious pathology 5
• Elevated eosinophil count (>1000 cells/μL) should prompt consideration of eosinophilic gastroenteritis, which requires endoscopic biopsy confirmation showing ≥20 eosinophils per high-power field 3

Additional Tests Based on Clinical Context

If Mesenteric Ischemia Suspected

• Serum lactate as a marker of tissue hypoperfusion and bowel ischemia 2, 1
• D-dimer may be helpful though lacks specificity 1
• Blood gases to assess for metabolic acidosis 2

If Sepsis or Systemic Infection Suspected

• Blood cultures (minimum two sets, including from indwelling catheters if present) especially in patients with fever or neutropenia 2
• Procalcitonin (PCT) correlates with intestinal necrotic damage and mortality in acute abdomen 2

If Immunosuppression Planned

Before initiating immunosuppressive therapy for suspected inflammatory conditions:

• Hepatitis B serology (surface antigen, surface antibody, core antibody) 2
• Hepatitis C antibody 2
• HIV testing 2
• Tuberculosis screening with interferon-gamma release assay (QuantiFERON-Gold) and chest X-ray 2
• Cytomegalovirus (CMV) IgG and IgM 2
• Epstein-Barr virus (EBV) IgG and IgM 2
• Varicella zoster serology if no history of chickenpox or vaccination 2

Common Pitfalls to Avoid

• Do not delay obtaining β-HCG in women of reproductive age, as failure to test can lead to missed ectopic pregnancy diagnosis 1
• Do not rely solely on laboratory tests early in disease, as they may be normal initially and have limited value in differentiating causes 1
• Do not start immunosuppressive therapy before excluding infectious causes, particularly C. difficile in patients with diarrhea 2
• Do not overlook fecal occult blood testing in patients with iron-deficiency anemia, as it has 74% positive predictive value for neoplastic lesions 6

When Initial Workup is Negative

If initial laboratory testing is unremarkable but clinical suspicion remains high:

• Consider fecal elastase testing for pancreatic insufficiency, particularly in patients not responding to typical treatments 2
• Tissue transglutaminase IgA and total IgA to exclude celiac disease, especially in patients with chronic symptoms 2
• Proceed to imaging studies (CT or ultrasound) based on pain location and clinical presentation 2, 1