Diarrhea

Diarrhea occurs when unabsorbable, water-soluble solutes remain in the bowel and retain water. Such solutes include polyethylene glycol, magnesium salts (hydroxide and sulfate), and sodium phosphate, which are used as laxatives. Osmotic diarrhea occurs with sugar intolerance (eg, lactose intolerance Carbohydrate Intolerance Carbohydrate intolerance is the inability to digest certain carbohydrates due to a lack of one or more intestinal enzymes. Symptoms include diarrhea, abdominal distention, and flatulence. Diagnosis... read more caused by lactase deficiency). Ingesting large amounts of hexitols (eg, sorbitol, mannitol, xylitol) or high fructose corn syrups, which are used as sugar substitutes in candy, gum, and fruit juices, causes osmotic diarrhea because hexitols are poorly absorbed. Lactulose, which is used as a laxative, causes diarrhea by a similar mechanism. Overingesting certain foodstuffs ( see Table: Some Causes of Diarrhea* Some Causes of Diarrhea* ) can cause osmotic diarrhea.

Diarrhea occurs when the bowels secrete more electrolytes and water than they absorb. Causes of increased secretions include infections, unabsorbed fats, certain drugs, and various intrinsic and extrinsic secretagogues.

Infections (eg, gastroenteritis Overview of Gastroenteritis Gastroenteritis is inflammation of the lining of the stomach and small and large intestines. Most cases are infectious, although gastroenteritis may occur after ingestion of drugs, medications... read more ) are the most common causes of secretory diarrhea. Infections combined with food poisoning are the most common causes of acute diarrhea (< 4 days in duration). Most enterotoxins block sodium-potassium exchange, which is an important driving force for fluid absorption in the small bowel and colon.

Unabsorbed dietary fat and bile acids (as in malabsorption syndromes Overview of Malabsorption Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats)... read more and after ileal resection) can stimulate colonic secretion and cause diarrhea.

Drugs may stimulate intestinal secretions directly (eg, quinidine, quinine, colchicine, anthraquinone cathartics, castor oil, prostaglandins) or indirectly by impairing fat absorption (eg, orlistat).

Various endocrine tumors produce secretagogues, including vipomas Vipoma A vipoma is a non-beta pancreatic islet cell tumor secreting vasoactive intestinal peptide (VIP), resulting in a syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome). Diagnosis... read more (vasoactive intestinal peptide), gastrinomas Gastrinoma A gastrinoma is a gastrin-producing tumor usually located in the pancreas or the duodenal wall. Gastric acid hypersecretion and aggressive, refractory peptic ulceration result (Zollinger-Ellison... read more (gastrin), mastocytosis Mastocytosis and Mast Cell Activation Syndrome Mastocytosis is mast cell proliferation with infiltration of skin or other tissues and organs. Mast cell activation syndrome is increased and inappropriate activation of mast cells without clonal... read more (histamine), medullary carcinoma of the thyroid Medullary Thyroid Carcinoma There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more (calcitonin and prostaglandins), and carcinoid tumors Overview of Carcinoid Tumors Carcinoid tumors develop from neuroendocrine cells in the gastrointestinal tract (90%), pancreas, pulmonary bronchi, and rarely the genitourinary tract. More than 95% of all gastrointestinal... read more (histamine, serotonin, and polypeptides). Some of these mediators (eg, prostaglandins, serotonin, related compounds) also accelerate intestinal transit, colonic transit, or both.

Impaired absorption of bile salts, which can occur with several disorders, can cause diarrhea by stimulating water and electrolyte secretion. The stools have a green or orange color.

Rapid intestinal transit and diminished surface area impair fluid absorption and cause diarrhea. Common causes include small-bowel or large-bowel resection or bypass, gastric resection, and inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more . Other causes include microscopic colitis (collagenous or lymphocytic colitis) and celiac disease Celiac Disease Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption... read more . Hyperthyroidism may cause diarrhea due to rapid transit.

Stimulation of intestinal smooth muscle by drugs (eg, magnesium-containing antacids, laxatives, cholinesterase inhibitors, selective serotonin reuptake inhibitors) or humoral agents (eg, prostaglandins, serotonin) also can speed transit.

History of present illness should determine duration and severity of diarrhea, circumstances of onset (including recent travel, food ingested, source of water), drug use (including any antibiotics within the previous 3 months), abdominal pain or vomiting, frequency and timing of bowel movements, changes in stool characteristics (eg, presence of blood, pus, or mucus; changes in color or consistency; evidence of steatorrhea), associated changes in weight or appetite, and rectal urgency or tenesmus should be noted. Simultaneous occurrence of diarrhea in close contacts should be ascertained. Physicians should ask specifically about any changes in drugs that may cause diarrhea.

Review of systems should seek symptoms suggesting possible causes, including joint pains (inflammatory bowel disease, celiac disease), flushing (carcinoid, vipoma, mastocytosis), chronic abdominal pain (irritable bowel, inflammatory bowel disease, gastrinoma), and GI bleeding (ulcerative colitis, tumor).

Past medical history should identify known risk factors for diarrhea, including inflammatory bowel disease, irritable bowel syndrome, HIV infection, and previous GI surgical procedures (eg, intestinal or gastric bypass or resection, pancreatic resection). Family and social history should query about simultaneous occurrence of diarrhea in close contacts.

Fluid and hydration status should be evaluated. A full examination with attention to the abdomen and a digital rectal examination for sphincter competence and occult blood testing are important.

Certain findings raise suspicion of an organic or more serious etiology of diarrhea:

Acute, watery diarrhea in an otherwise healthy person is likely to be of infectious etiology, particularly when travel, possibly tainted food, or an outbreak with a point-source is involved.

Acute bloody diarrhea with or without hemodynamic instability in an otherwise healthy person suggests an enteroinvasive infection. Diverticular bleeding and ischemic colitis also manifest with acute bloody diarrhea. Recurrent bouts of bloody diarrhea in a younger person suggest inflammatory bowel disease Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, is a relapsing and remitting condition characterized by chronic inflammation at various sites in the gastrointestinal... read more .

In the absence of laxative use, large-volume diarrhea (eg, daily stool volume > 1 L/day) strongly suggests an endocrine tumor cause in patients with normal GI anatomy. A history of oil droplets in stool, particularly if associated with weight loss, suggests malabsorption Overview of Malabsorption Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats)... read more .

Diarrhea that consistently follows ingestion of certain foods (eg, fats) suggests food intolerance. Recent antibiotic use should raise suspicion for antibiotic-associated diarrhea, including Clostridioides difficile colitis Clostridioides (formerly Clostridium) difficile–Induced Diarrhea Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more (formerly Clostridium difficile).

Diarrhea with green or orange stools suggests impaired absorption of bile salts.

The symptoms can help identify the affected part of the bowel. Generally, in small-bowel diseases, stools are voluminous and watery or fatty. In colonic diseases, stools are frequent, sometimes small in volume, and possibly accompanied by blood, mucus, pus, and abdominal discomfort.

In irritable bowel syndrome Irritable Bowel Syndrome (IBS) Irritable bowel syndrome is characterized by recurrent abdominal discomfort or pain with at least two of the following characteristics: relation to defecation, association with a change in frequency... read more (IBS), abdominal pain is related to defecation, associated with changes in stool frequency or consistency, or both. However, these symptoms alone do not discriminate IBS from other diseases (eg, inflammatory bowel disease). Functional diarrhea is characterized by loose or watery stools with onset at least 6 months before diagnosis and present during the previous 3 months. These patients do not meet the criteria for IBS; they may have abdominal pain and/or bloating, but these are not predominant symptoms (1 Evaluation reference Stool is 60 to 90% water. In Western society, stool amount is 100 to 200 g/day in healthy adults and 10 g/kg/day in infants, depending on the amount of unabsorbable dietary material (mainly... read more ). IBS with diarrhea sometimes develops in patients after an acute enteric infection (postinfectious IBS).

Extra-abdominal findings that suggest an etiology include skin lesions or flushing (mastocytosis Mastocytosis and Mast Cell Activation Syndrome Mastocytosis is mast cell proliferation with infiltration of skin or other tissues and organs. Mast cell activation syndrome is increased and inappropriate activation of mast cells without clonal... read more ), thyroid nodules (medullary carcinoma of the thyroid Medullary Thyroid Carcinoma There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more ), right-sided heart murmur (carcinoid), lymphadenopathy (lymphoma Overview of Lymphoma Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems. The major types are Hodgkin lymphoma Non-Hodgkin lymphoma See table Comparison of Hodgkin... read more , AIDS Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more ), and arthritis (inflammatory bowel disease, celiac disease Celiac Disease Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption... read more ).

Acute diarrhea (< 4 days) typically does not require testing. Exceptions are patients with signs of dehydration, bloody stool, fever, severe pain, hypotension, or toxic features—particularly those who are very young or very old. These patients should have a complete blood count and measurement of electrolytes, blood urea nitrogen, and creatinine. Stool samples should be collected for microscopy, culture, and, if antibiotics have been taken recently, C. difficile toxin assay.

Chronic diarrhea (> 4 weeks) requires evaluation, as does a shorter (1 to 3 weeks) bout of diarrhea in immunocompromised patients or those who appear significantly ill. Diagnostic evaluation should be directed by the history and physical examination when possible. If this approach does not provide a diagnosis or direction, a broader approach is needed. Initial testing should include stool for occult blood, fat (by Sudan stain or fecal elastase), electrolytes (to calculate the stool osmotic gap), and Giardia antigen or polymerase chain reaction test; complete blood count with differential; celiac serology (IgA tissue transglutaminase); thyroid-stimulating hormone (TSH) and free thyroxine (T4); and fecal calprotectin or fecal lactoferrin (to screen for inflammatory bowel disease [IBD]). The 2019 American Gastroenterological Association's guidelines on the laboratory evaluation of functional diarrhea and diarrhea-predominant IBS (IBS-D) recommend a threshold value of 50 mcg/g for fecal calprotectin or a range of 4.0 to 7.25 mcg/g for fecal lactoferrin to optimize sensitivity for IBD. Microscopic examination for ova and parasites should be done for patients with recent travel history to or recent immigration from high-risk areas. Stool tests for C. difficile should be done in patients with recent antibiotic exposure or suspected C. difficile infection. Sigmoidoscopy or colonoscopy with biopsies should follow to look for inflammatory causes.

If no diagnosis is apparent and Sudan stain or fecal elastase is positive for fat, fecal fat excretion should be measured. Additional testing, including small-bowel CT enterography (structural disease) and endoscopic small-bowel biopsy (mucosal disease), can be considered (eg, if symptoms persist or are severe such as weight loss). If evaluation still yields negative findings, assessment of pancreatic structure and function ( see Laboratory tests Laboratory tests Acute pancreatitis is acute inflammation of the pancreas (and, sometimes, adjacent tissues). The most common triggers are gallstones and alcohol intake. The severity of acute pancreatitis is... read more ) should be considered for patients who have unexplained steatorrhea. Infrequently, capsule endoscopy may uncover lesions, predominantly Crohn disease or nonsteroidal anti-inflammatory drug enteropathy, not identified by other modalities.

The stool osmotic gap, which is calculated 290 − 2 × (stool sodium + stool potassium), indicates whether diarrhea is secretory or osmotic. An osmotic gap < 50 mEq/L indicates secretory diarrhea; a larger gap suggests osmotic diarrhea. Patients with osmotic diarrhea may have covert magnesium laxative ingestion (detectable by stool magnesium levels) or carbohydrate malabsorption (diagnosed by hydrogen breath test, lactase assay, and dietary review).

Undiagnosed secretory diarrhea requires testing (eg, plasma gastrin, calcitonin, vasoactive intestinal peptide levels, histamine, urinary 5-hydroxyindole acetic acid [5-HIAA]) for endocrine-related causes. A review for symptoms of adrenal insufficiency should be done. Surreptitious laxative abuse must be considered; it can be ruled out by a fecal laxative assay.