Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea

Gastroenterology. 2017 Feb;152(3):515-532.e2. doi: 10.1053/j.gastro.2016.10.014. Epub 2016 Oct 20.


Chronic watery diarrhea poses a diagnostic and therapeutic challenge and is often a disabling condition for patients. Although acute diarrhea is likely to be caused by infection, the causes of chronic diarrhea (>4 weeks in duration) are more elusive. We review the pathophysiology, diagnosis, and treatment of chronic diarrhea. Drawing on recent insights into the molecular mechanisms of intestinal epithelial transport and barrier function, we discuss how diarrhea can result from a decrease in luminal solute absorption, an increase in secretion, or both, as well as derangements in barrier properties. We also describe the various extraepithelial factors that activate diarrheal mechanisms. Finally, clinical evaluation and tests used in the assessment of patients presenting with chronic diarrhea are reviewed, and an algorithm guiding therapeutic decisions and pharmacotherapy is presented.

Keywords: Diarrhea; Management; Pathophysiology.

Publication types

  • Review

MeSH terms

  • C-Reactive Protein / metabolism
  • Chromogranins / metabolism
  • Chronic Disease
  • Diarrhea / diagnosis
  • Diarrhea / metabolism*
  • Diarrhea / physiopathology
  • Diarrhea / therapy
  • Feces / chemistry
  • Gastrointestinal Motility
  • Humans
  • Inflammation
  • Intestinal Absorption*
  • Intestinal Mucosa / metabolism*
  • Intestinal Secretions*
  • Intestines / physiopathology
  • Irritable Bowel Syndrome / metabolism
  • Lactoferrin / metabolism
  • Leukocyte L1 Antigen Complex / metabolism
  • Osmolar Concentration
  • Permeability
  • Prostaglandins / metabolism
  • Serotonin / metabolism
  • Substance P / metabolism


  • Chromogranins
  • Leukocyte L1 Antigen Complex
  • Prostaglandins
  • Serotonin
  • Substance P
  • C-Reactive Protein
  • Lactoferrin