Clinical Information

The concentration of electrolytes in fecal water and their rate of excretion are dependent upon 3 factors:

-Normal daily dietary intake of electrolytes

-Passive transport from serum and other vascular spaces to equilibrate fecal osmotic pressure with vascular osmotic pressure

-Electrolyte transport into fecal water due to exogenous substances and rare toxins (eg, cholera toxin)

Fecal osmolality is normally in equilibrium with vascular osmolality, and sodium is the major effector of this equilibrium. Fecal osmolality is normally 2 x (sodium + potassium) unless there are exogenous factors inducing a change in composition, such as the presence of other osmotic agents (magnesium sulfate, saccharides) or drugs inducing secretions, such as phenolphthalein or bisacodyl.

Osmotic diarrhea is caused by ingestion of poorly absorbed ions or sugars.(1) There are multiple potential causes of osmotic diarrhea. Measurement of phosphate and/or magnesium in liquid stool can assist in identifying intentional or inadvertent use of magnesium and/or phosphate containing laxatives as the cause.(2-4) The other causes of osmotic diarrhea include ingestion of osmotic agents such as sorbitol or polyethylene glycol laxatives, or carbohydrate malabsorption due most commonly to lactose intolerance. Carbohydrate malabsorption can be differentiated from other osmotic causes by a low stool pH (<6).(5,6)

Non-osmotic causes of diarrhea include bile acid malabsorption, inflammatory bowel disease, endocrine tumors, and neoplasia.(1) Secretory diarrhea is classified as non-osmotic and is caused by disruption of epithelial electrolyte transport when secretory agents such as anthraquinones, phenolphthalein, bisacodyl, or cholera toxin are present. The fecal fluid usually has elevated electrolytes (primarily sodium and chloride) and a low osmotic gap (<50 mOsm/kg). Infection is a common secretory process; however, it does not typically cause chronic diarrhea (defined as symptoms >4 weeks). Differentiating osmotic from non-osmotic causes of diarrhea is the goal of liquid stool testing.(1,7) The primary way this is accomplished is through the measurement of sodium and chloride and calculation of the osmotic gap, which uses an assumed normal osmolality of 290 mOsm/kg rather than direct measurement of the osmolality.

Measurement of osmolality can be useful in the evaluation of chronic diarrhea to help identify whether a specimen has been diluted with hypotonic fluid to simulate diarrhea.(1,8)

Chronic diarrhea with elevations in fecal chloride concentrations are caused by congenital chloridorrhea. This is a rare condition associated with a genetic defect in a protein responsible for transport of chloride ions across the mucosal membranes in the lower intestinal tract in exchange for bicarbonate ions. It plays an essential part in intestinal chloride absorption, therefore mutations in this gene have been associated with congenital chloride diarrhea.(9)

Acquired chloridorrhea is a rare condition which has been described as causing profuse, chloride-rich diarrhea and a surprising contraction metabolic alkalosis rather than metabolic acidosis often associated with typical diarrhea. Contributors to acquired chloridorrhea include chronic intestinal inflammation and reduction of chloride/bicarbonate transporter expression in genetically susceptible persons post-bowel resection and ostomy placement. Acquired chloridorrhea is rare but may be an under-recognized condition in post-bowel resection patients.(10)