Diarrhea, Chronic



  • Chronic diarrhea refers to a sustained change in stool consistency, characterized by loose stools (consistency between types 5 and 7 on the Bristol stool chart), and an increase in frequency of defecation (typically >3 loose stools per day) for >4 weeks (1),(2).
  • Etiologies include osmotic, secretory, malabsorptive, inflammatory, infectious, and hypermotility (2).


Difficult to estimate as definitions vary

Varies by etiology; worldwide prevalence is ~3–20% (2). U.S. prevalence is ~6.6%.

Etiology and Pathophysiology

Disturbances in luminal water and electrolytes cause increased water volume in the stool.

  • Osmotic (fecal osmotic gap >100 mOsm/kg) (3); resolves with fasting (2); less voluminous than secretory diarrhea
    • Carbohydrate malabsorption: disaccharides (e.g., lactose), monosaccharides (e.g., fructose), and polyols (sugar substitutes); Mg, citrates, phosphate, and sulfate ingestion
  • Secretory (fecal osmotic gap <50 mOsm/kg) (1),(4); does not resolve with fasting (2); characterized by watery stools that persist at night and during fasting
    • Alcoholism, stimulant laxative ingestion; bacterial enterotoxins (i.e., cholera); postcholecystectomy/ileal resection <100 cm: Excessive intestinal bile salts cause choleretic diarrhea.
    • Disordered motility: postvagotomy, autonomic neuropathy, hyperthyroidism
    • Neuroendocrine tumors: VIPoma; carcinoid syndrome, gastrinoma, somatostatinoma
    • Metastatic medullary thyroid cancer; adrenal insufficiency
    • Noninvasive infection: giardiasis, cryptosporidiosis
    • Microscopic colitis; protein-losing enteropathy
  • Fatty diarrhea: characterized by bulky, foul-smelling stools
    • Hepatobiliary disorders, cystic fibrosis (CF), chronic pancreatitis, diabetes mellitus
  • Malabsorptive (1),(4): characterized by higher than average stool volumes
    • Celiac disease, Whipple disease; tropical sprue, giardiasis, amyloidosis
    • Chronic mesenteric ischemia, lymphatic obstruction (e.g., heart failure, lymphoma)
    • Short bowel syndrome: Ileal resection of >100 cm leads to insufficient bile salts.
    • Small intestinal bacterial overgrowth (SIBO); pancreatic exocrine insufficiency
  • Inflammatory (1),(4): characterized by loose liquid stool with occasional blood
    • Inflammatory bowel disease (IBD)—ulcerative colitis; Crohn disease
    • Microscopic colitis; diverticulitis; vasculitis; radiation enterocolitis
    • Infections: Clostridium difficile, Entamoeba histolytica, cytomegalovirus, tuberculosis, salmonella
    • Neoplasms: colon cancer, lymphoma
  • Hypermotility (normal fecal osmotic gap; 50 to 100 mOsm/kg) (1)
    • Irritable bowel syndrome (IBS); functional diarrhea (Pain differentiates IBS from functional diarrhea.) (2),(3)
  • Drugs (1),(4): confirmed by resolution of symptoms following withdrawal of medication
    • NSAIDs, PPIs, colchicine, metformin, digoxin, ACE inhibitors, β-blockers, gliptins, theophyllines, antibiotics, SSRIs, antineoplastic agents, excessive laxative use (factitious diarrhea)
    • Herbal products: St. John’s wort, echinacea, garlic, saw palmetto, ginseng, etc.
  • Infectious (1)
    • Bacterial: C. difficile, M. avium intracellulare; viral: cytomegalovirus; parasitic: Giardia lamblia, Cryptosporidium, Isospora, E. histolytica, Strongyloides
  • Food allergies (1)


  • Celiac disease is associated with HLA-DQ2 and HLA-DQ8 haplotypes (3).
  • IBD is polygenic. First-degree relative of IBD patients have 10-fold increased risk (3).
  • CF transmembrane conductance regulator (CFTR) mutation contributes in CF.

Risk Factors

  • Osmotic
    • Excess ingestion of nonabsorbable carbohydrates (i.e., artificial sweeteners); magnesium-containing antacids (3)
    • Excess ingestion poorly absorbed ions (phosphate, sulfate, magnesium) (1)
    • Lactose intolerance, celiac disease
    • Medications (i.e., citrates, phosphates, sulfates, magnesium-containing laxatives, sugar alcohols)
  • Secretory (1)
    • Postsurgical: small bowel resection/ileal surgery, vagotomy, bile acid malabsorption; history of neuroendocrine disease or stimulant laxative abuse; dysmotility syndromes
    • Medications (i.e., NSAIDs, caffeine, metformin, colchicine, carbamazepine, antibiotics, calcitonin) (3)
  • Malabsorptive
    • CF; chronic alcohol abuse, celiac disease
    • Chronic pancreatitis/pancreatic insufficiency (fat malabsorption); medications (e.g., orlistat, acarbose, aminoglycosides, thyroid supplements)
  • Inflammatory
    • IBD, NSAID use, antibiotics, radiation; HIV/AIDS, colorectal cancer, invasive infection (tuberculosis, Yersinia)
    • Pseudomembranous colitis (C. difficile)
    • Antineoplastic drugs (i.e., 5-fluorouracil, methotrexate, irinotecan), radiation
    • Immunosuppressant therapy
  • Hypermotility
    • Psychosocial stress, preceding infection
    • Stimulant medications (i.e., macrolides, metoclopramide, senna, bisacodyl [Dulcolax]) (3)
  • Genetic predisposition
Diabetes mellitus and cholecystectomy can cause secretory and osmotic diarrhea.

General Prevention

Varies by etiology; treat the underlying cause.

Commonly Associated Conditions

  • Extraintestinal manifestations of IBD include arthralgias, aphthous stomatitis, uveitis/episcleritis, erythema nodosum, pyoderma gangrenosum, perianal fistulas, rectal fissures, ankylosing spondylitis, and PSC.
  • Celiac disease is associated with dermatitis herpetiformis, T1DM, and IgA deficiency.
  • Latex-food allergy syndrome: allergies to latex, banana, avocado, kiwi, and walnut (1)

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