Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea

Abstract

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.

Figure 1. Cellular mechanisms accounting for intestinal absorption and secretion

Factors that reduce the amount or function of a specific transporter are shown in red boxes; those that increase levels of activity are shown in green boxes. Long vertical arrows indicate the paracellular absorption or secretion of water, with or without an appropriate counterion.

Figure 2. Interaction of mechanisms in chronic watery diarrhea

Although most reductionist research models focus on a single parameter of intestinal function, in fact there is an intricate network of agonists and effectors with a promiscuous interaction among autocrine, luminal, paracrine, immune, neural and endocrine (ALPINES) inputs that may alter the paracellular pathway, epithelial cell function, intestinal smooth muscle and blood flow. Diarrhea can result from a change in one or many of these pathways and alterations in permeability, transport, and motility. Figure adapted from ref. , Schiller LR, Sellin JH. Diarrhea. In: Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 10^th ed. Feldman M, Friedman LS, Brandt LJ, Eds. Elsevier:New York, 2015, pp. 221–241 (permission not required by Elsevier, as Dr. Sellin is author of original work and of this work).

Figure 3. Algorithm for management of chronic diarrhea

Patients undergo an initial evaluation based on different symptom presentations, leading to selection of patients for imaging, biopsy analysis, and limited screens for organic diseases.