Chronic diarrhea is too much stool water, and because normal absorptive efficiency runs near ninety-nine percent, small physiologic insults produce large clinical phenotypes. Episode one builds the four-mechanism framework, osmotic, secretory, fatty, and inflammatory, and lets that mechanism drive a staged workup. History, basic labs, stool studies, and endoscopy sort most patients within a few tests toward a targeted second-stage evaluation. Topics covered Four mechanism categories of chronic diarrhea Stool osmotic gap calculation and cutoffs History, medication, and surgical review Basic labs and celiac serology with total IgA Stool studies: calprotectin, elastase, fecal fat IBS-D overlap traps Secretory workup and neuroendocrine tumors Fatty diarrhea: maldigestion versus malabsorption Key decisions Osmotic gap is 290 minus twice the sum of stool sodium and potassium; under 50 is secretory, over 100 is osmotic, in between is mixed. Order total IgA with celiac serology because IgA deficiency invalidates the IgA-based test, the single most common workup error. Collect a formed stool for fecal elastase because a watery sample falsely lowers it; a low value supports pancreatic insufficiency. Hold acid blockers for a week before gastrin and chromogranin A because PPIs raise both and cause false positives. Random biopsies of normal-looking colon are mandatory in older patients with chronic watery diarrhea to catch microscopic colitis. After cholecystectomy or ileal resection, an empiric cholestyramine trial for bile acid malabsorption is diagnostic and therapeutic in one step. For the full chapter with MCQs, tables, and primary-guideline references, visit www.boardpearls.com. Questions or feedback: [email protected]. (00:00) - Framework and why mechanism drives the workup (00:21) - Too much stool water and the four-week cutoff (02:08) - The osmotic gap and category signatures (05:32) - History, medications, and surgical mapping (08:01) - Stool studies do the mechanism assignment (10:31) - Secretory workup and neuroendocrine tumors (14:56) - Fatty diarrhea: maldigestion versus malabsorption (16:51) - Inflammatory diarrhea and the endoscopic patterns

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