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Diarrhea: Etiology and Pathophysiology

Last updated on November 21st, 2021

Diarrhea is a common symptom that can range in severity from an acute, self-limited annoyance to a severe, life-threatening illness. The frequency and consistency of bowel move-ments vary within and between individuals. Some individuals may normally defecate as many as three times a day, while others only two to three times per week. Diarrhea is defined as increased volume, fluidity, or frequency of fecal discharges compared with the patient’s normal stools. Clinical features vary greatly depending on the cause, duration, and severity of the diarrhea, on the area of bowel affected, and on the patient’s general health.

Etiology and Pathophysiology

While there are many causes of diarrhea (see Tables 1 and 2), it is most often due to an enteritis (inflammation of the small intestine) of infectious or noninfectious etiology. In the U.S., most cases of infectious diarrhea are of viral and bacterial origin. Most infectious diarrheas are acquired by fecal-oral transmission via contaminated food or water. Improperly cooked meats may also be the source of infection.

Diarrhea results from an imbalance in the absorption and secretion properties of the intestinal tract; if absorption decreases or secretion increases beyond normal, diarrhea results.

Diarrhea may be acute or chronic. Acute diarrhea is the abrupt onset of frequent, watery, loose stools. It may be accompanied by flatulence, malaise and abdominal pain. Some clinicians consider acute diarrhea to be the passage of three or more loose stools in a 24-hour period, continuing for less than two weeks. Usually, acute diarrheal episodes subside within 72 hours of onset. In the U.S., common diarrhea-producing pathogens are Shigella, Salmonella, Campylobacter, Staphylococcus, Bacillus cereus, Norwalk viruses and rotaviruses.

Toxigenic Escherichia coli and S. aureus cause diarrhea through an enterotoxin, while Shigella, Salmonella, Campylobacter and invasive E. coli directly invade the mucosal epithelial cells. Toxin-producing pathogens usually cause a watery, large-volume diarrhea. Nausea, vomiting, cramps and fever may also occur. Invasive organisms may invade the large intestine and produce frequent small-volume stools that may contain mucus or blood.

Diarrhea may be classified into four general types, based on the mechanism: osmotic diarrhea, secretory diarrhea, exudative diarrhea and motility disorder diarrhea (see Table 3).Osmotic diarrhea occurs when ingested solute which is not fully absorbed in the small intestine draws fluid into the intestinal lumen. The nonabsorbed material can be a maldigested or malabsorbed nutrient or drug. Diarrhea of this type may result from disorders such as chronic pancreatitis, bile duct obstruction, celiac disease (nontropical sprue), or Whipple’s disease. Acute osmotic diarrhea may result from ingestion of certain fruits or candy, gum, dietetic foods, lactose or the sweeteners sorbitol or fructose.

Secretory diarrhea occurs when the small and large bowel secrete rather than absorb electrolytes and water. Bacterial toxins, viruses and some drugs (e.g., prostaglandins) may cause this type of diarrhea. Mucosal inflammation and ulceration caused by inflammatory diseases and cancers may result in the outpouring of plasma, proteins, mucus and blood into the stool, resulting in exudative diarrhea. Loose stools can result when intestinal contents are not exposed to the absorptive surface of the GI tract for a sufficient amount of time. Diarrhea due to motility disorders is caused by conditions such as diabetic neuropathy or irritable bowel syndrome.

A more common cause of osmotic diarrhea is intolerance to lactose. Lactose intolerance may cause bloating, abdominal pain or cramps, gas, or diarrhea. An estimated 50 million Americans experience some form of gastrointestinal discomfort shortly after consuming lactose-containing dairy products. Lactose intolerance is caused by a deficiency of the intestinal enzyme lactase and is more common in African-Americans, Indians and Asians.

Patients who are lactose intolerant should avoid or limit their consumption of products that contain milk, lactose, dry milk solids, or whey. Patients should be instructed to consume one serving at a time along with solid food to help limit or offset the symptoms of lactose intolerance. Tablets and capsules that contain lactase (e.g., DairyEase, Lactaid) can be taken up to 30 minutes before ingestion of a milk product.



Diarrhea in infants and young children is often caused by a viral infection of the intestinal tract. It is estimated that approximately half of all infantile diarrhea is caused by rotaviruses. Infection is seen most often during the winter months, and children aged 6 to 24 months are most susceptible. After an incubation period of 12–48 hours, vomiting, watery diarrhea, and a low-grade fever develops.

The signs and symptoms of Norwalk viruses resemble those of rotaviruses. Low-grade fever, malaise, mild nausea and abdominal cramps often accompany the sudden onset of diarrhea. Norwalk virus outbreaks may be seen when municipal water supplies are contaminated. The most common nonviral organisms involved in day-care outbreaks of diarrhea are Shigella, Giardia lamblia and Cryptosporidium.

Diarrhea lasting for more than two weeks may be difficult to diagnose due to its often multifactorial etiology and the fact that patients with chronic diarrhea may not always have frequent daily passage of watery stools. Chronic diarrhea may be caused by gastrointestinal disease, may be secondary to systemic disease, or may be psychogenic in nature. Pathophysiologically, chronic diarrhea may be categorized as inflammatory diarrhea, osmotic diarrhea (malabsorption), secretory diarrhea, intestinal dysmotility and factitious (self-induced, e.g., from laxative abuse) diarrhea.

Chronic laxative abuse can result in serious fluid and electrolyte loss, protein wasting (hypoalbuminemia) and colitis. Patients who experience persistent or recurrent diarrhea and are unaware of its cause should seek medical treatment; a change in bowel habits is one of the seven danger signals of cancer (e.g., colon cancer).

Table 1. Etiology of Diarrhea

Bacterial Malabsorptive Inflammatory
Salmonellae Tropical sprue Regional enteritis Saline cathartics
Shigellae Symptomatic sprue Ulcerative colitis Magnesium antacids
Staphylococci Celiac disease (nontropical sprue) Irritative Psychogenic and/or Neurogenic
Streptococci Whipple’s disease Fecal impaction Vagal
Escherichia coli Chronic pancreatitis Foreign body Sacral
Campylobacter Bile duct obstruction   Neoplasm
Bacillus cereus     Irritable bowel syndrome
Clostridia   Surgical Chemical
Parasitic Endocrine and Metabolic Vagotomy Poisons
Amebiasis Hyperthyroidism Gastrectomy Cathartics
Trichinosis Adrenal cortical insufficiency Dietary
Ascariasis Carcinoid tumors that secrete Cyclospora certain NTs, e.g., serotonin Food intolerance (lactose intolerance) Vitamin deficiencies
Giardia AIDS Coarse food Sorbitol/fructose
  Diabetes mellitus Viral Allergenic
    Norwalk viruses Drug or food sensitivity

Table 2. Medications That May Cause Diarrhea

Antibiotics Gastrointestinal Drugs
Clindamycin Laxatives
Ampicillin Antacids
Cephalosporins Misoprostol
Erythromycin Olsalazine
Any broad-spectrum antibiotic  
Antihypertensives Hypolipidemic agents
Reserpine Clofibrate
Guanethidine Gemfibrozil
Methyldopa HMG–CoA reductase inhibitors (e.g., lovastatin, fluvastatin, pravastatin)
Cardiac Drugs Neuropsychiatric drugs
Quinidine Lithium
Digitalis Fluoxetine
Digoxin Alprazolam
Procainamide Valproic acid
Hydralazine Ethosuximide
Beta blockers L–Dopa
ACE inhibitors  
Cholinergics Miscellaneous
Bethanechol Theophylline
Metoclopramide Thyroid hormones
Neostigmine Colchicine
  Some chemotherapeutic agents

Patient Assessment

In order to assess the patient with diarrhea, the pharmacist should ascertain the duration, onset, frequency and severity of the diarrheal episodes and whether or not the diarrhea is accompanied by abdominal pain, vomiting, fecal overt or occult blood, steatorrhea (excessive amounts of fat in feces), weight loss, tenesmus (painful, ineffectual straining to defecate) or appetite changes, or is associated with the consumption of certain foods or products (including dietetic food, candy or chewing gum). In addition, it is important to determine whether the patient has recently traveled to a foreign country or has otherwise consumed nonchlorinated water.

Elderly people, young children, individuals with certain underlying medical problems requiring diuretics and persons with severe diarrhea are at higher risk for dehydration. Preschool children, adults over 60 years of age, persons with multiple medical conditions or chronic illnesses and pregnant women with diarrhea should be referred to a physician for a complete diagnostic evaluation. In addition, patients with the following symptoms should be advised to see their physician: moderate to severe abdominal tenderness or cramping, presence of bloody or mucoid stools, evidence of dehydration, high fever (·101F or 38C), weight loss of greater than 5% and/or diarrhea that has lasted two days or more.

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