Diarrhea Mechanisms, IBS & Microscopic Colitis

Classifying diarrhea by mechanism

Five mechanisms. Most chronic diarrhea fits one or more of five patterns: osmotic, secretory, inflammatory (exudative), motility-related, and fatty (steatorrhea). Naming the mechanism narrows the differential faster than listing causes.

The stool osmotic gap. Stool water equilibrates with plasma, so its osmolality is taken as 290 mOsm/kg (measured values drift upward as bacteria ferment the sample). Gap = 290 − 2(stool Na+ + K+), doubling the cations to account for their anions. A large gap means an unmeasured solute is holding water; a small gap means sodium and potassium salts explain it.

Osmotic and secretory diarrhea

Osmotic. Poorly absorbed solutes hold water in the lumen: lactose in lactase deficiency, magnesium-containing antacids and laxatives, PEG, lactulose, and sugar alcohols such as sorbitol and mannitol. The diarrhea stops when the patient fasts. Carbohydrate causes add gas, bloating, and acidic stool, because colonic bacteria ferment the sugar to short-chain fatty acids and hydrogen (the basis of the hydrogen breath test).

Secretory: the toxin model. Cholera toxin is the prototype.

Enterotoxigenic E. coli (ETEC), the classic cause of traveler's diarrhea, has a heat-labile toxin that works like cholera toxin and a heat-stable toxin that activates guanylyl cyclase C, raising cGMP with the same end result. Because Na+-glucose cotransport through SGLT1 is untouched, oral rehydration solution restores fluid even at the height of secretion.

Other secretory causes. Secretory diarrhea is typically large volume and continues during fasting and overnight. VIPoma causes watery diarrhea, hypokalemia, and achlorhydria; carcinoid releases serotonin; gastrinoma, medullary thyroid carcinoma (calcitonin), stimulant laxatives, and unabsorbed bile acids entering the colon (after limited ileal resection) also drive secretion.

Factitious diarrhea. Surreptitious laxative use, classically in health care workers or people with eating disorders, produces a secretory profile with stimulants (senna, bisacodyl) and an osmotic profile with magnesium or PEG. Stool laxative screens and stool magnesium reveal it.

Chronic anthraquinone use (senna, cascara) causes melanosis coli: brown-black mucosa from lipofuscin-laden macrophages in the lamina propria.

Inflammatory, motility, and fatty diarrhea

Inflammatory. Mucosal destruction releases blood, mucus, pus, and protein, with fever, tenesmus, and frequent small-volume stools. Fecal leukocytes, lactoferrin, and calprotectin (a neutrophil cytosolic protein) are elevated, which makes calprotectin useful for separating IBD from IBS. Causes include IBD, invasive bacteria (Shigella, Campylobacter, Salmonella), C. difficile, amebiasis, and ischemic or radiation colitis.

Motility-related. Rapid transit shortens contact time: hyperthyroidism, post-vagotomy and post-gastrectomy states, diabetic autonomic neuropathy, IBS-D, and carcinoid. Slow transit can also cause diarrhea when stasis allows small-intestinal bacterial overgrowth, as in scleroderma or diabetic neuropathy.

Steatorrhea. Fat malabsorption gives pale, bulky, foul, greasy stools that float, with deficiency of vitamins A, D, E, and K. A Sudan stain screens for fat; more than 7 g/day on a 72-hour collection confirms it. Low fecal elastase (below about 200 μg/g) indicates exocrine pancreatic insufficiency, as in chronic pancreatitis or cystic fibrosis. Other causes are bile acid deficiency (cholestasis, extensive ileal loss) and mucosal disease such as celiac disease.

Irritable bowel syndrome

Definition. IBS is a disorder of gut-brain interaction diagnosed clinically. Rome IV requires recurrent abdominal pain on at least 1 day per week over the last 3 months, with onset at least 6 months before diagnosis, plus two or more of: pain related to defecation, change in stool frequency, and change in stool form. Subtypes (IBS-C, IBS-D, IBS-M) follow the predominant Bristol stool form.

Pathophysiology. There is no structural lesion. Visceral hypersensitivity (pain at lower rectal balloon volumes than in controls), altered motility, and dysregulated gut-brain signaling, often with anxiety or depression, are central. Post-infectious IBS can follow bacterial gastroenteritis (Campylobacter, Salmonella, Shigella), and low-grade mucosal immune activation and microbiome shifts contribute. It is most common in women under 50.

Alarm features argue against IBS and require investigation, usually colonoscopy: onset at 50 or older, rectal bleeding, nocturnal symptoms that wake the patient, unintentional weight loss, iron-deficiency anemia, fever, family history of colorectal cancer or IBD, and raised calprotectin or CRP.

Workup and care. Without alarm features, limited testing suffices: CBC, CRP or fecal calprotectin, and celiac serology in diarrhea-predominant or mixed disease. Treatment starts with explanation and diet (soluble fiber, a low-FODMAP trial), then symptom-directed drugs such as antispasmodics or low-dose tricyclic antidepressants.

Microscopic colitis

Presentation. Chronic nonbloody watery diarrhea, often with urgency, nocturnal stools, and incontinence, typically in women in their 60s. The colon looks normal at colonoscopy, so diagnosis depends on random biopsies from both right and left colon.

Triggers and associations. Implicated drugs include NSAIDs, proton pump inhibitors (especially lansoprazole), and SSRIs (notably sertraline); smoking adds risk. Autoimmune links include celiac disease and thyroid disease, so celiac serology belongs in the workup, and celiac patients with diarrhea despite a strict gluten-free diet should be evaluated for coexisting microscopic colitis.

Treatment. Stop culprit drugs and smoking. Oral budesonide induces and maintains remission; its extensive first-pass hepatic (CYP3A4) metabolism limits systemic steroid effects. Loperamide or bismuth subsalicylate helps mild disease. Unlike ulcerative colitis and Crohn disease, microscopic colitis does not raise colorectal cancer risk.