Diarrhea is defined as an increase in daily stool weight above 200 grams.¹ In clinical practice, the term is used to describe increased liquidity of the stools, usually associated with increased stool weight and frequency (more than 3 times per day). For most individuals eating a Western-type diet, normal daily stool weight ranges between 100 and 200 grams. Normal bowel frequency ranges from 3 times a day to 3 times a week.

Diarrhea must be distinguished from fecal incontinence, which is seen in pelvic muscle weakness or anorectal dysfunction. Pseudo-diarrhea or hyperdefecation represents increased frequency of defecation without an increase in stool weight above normal, as seen in irritable bowel syndrome or hyperthyroidism. Factitious diarrhea is self-induced by the addition of water or urine to stool, or self-medication with laxatives. It is predominantly seen in women with psychiatric disorders.

Diarrhea can be classified based on factors such as duration of the illness (acute versus chronic), pathophysiologic mechanisms (osmotic versus secretory), severity (small versus large), or stool characteristics (watery, fatty, or bloody). In clinical practice, duration of the illness and stool characteristics are most useful in the evaluation and treatment of patients with diarrhea.

Acute diarrhea is defined as a diarrheal illness lasting for less than 4 weeks. If the illness persists for more than 4 weeks, it is considered chronic diarrhea. The most common causes of acute diarrhea are infectious agents (viruses, bacteria, and parasites). Other important causes include food poisoning (preformed toxins), medications, inflammatory or ischemic bowel disease, fecal impaction, pelvic inflammation (eg, rectosigmoid abscess), and recent ingestion of poorly absorbable sugars (eg, lactulose).

Most infectious diarrheas are acquired through the fecal-oral route by way of food or water contamination. Viruses (eg, adenovirus, rotavirus, Norwalk virus) are the most common cause of diarrhea in the United States. Escherichia coli, Clostridium difficile, and Campylobacter, Salmonella, and Shigella organisms are common causes of bacterial diarrhea. Bacillus cereus, Clostridium perfringens, Staphylococcus aureus, Salmonella species, and others cause food poisoning. Entamoeba histolytica, Giardia, Cryptosporidium, and Cyclospora are parasitic/protozoal agents that cause diarrhea.

Diarrhea is one of the most frequent adverse effects of prescription medications; the list of implicated agents is endless. It is important to note that drug-related diarrhea usually occurs after a new drug is initiated or the
dosage increased.

Diarrhea is one of the most common diagnoses in general practice. It is estimated that each year US adults experience 99 million episodes of acute diarrhea or gastroenteritis.² In the United States, there are about 8 million physician visits and more than 250,000 hospital admissions each year (1.5% of adult hospitalizations) due to diarrhea or gastroenteritis.³ Most of the deaths associated with diarrheal illness occur in the very young and the elderly populations, whose health may be put at risk from a moderate amount of dehydration. The rate of diarrheal illnesses is 2 to 3 times greater in developing countries.

The prevalence of diarrhea is not uniform in the general population. Food-and water-borne outbreaks involving a relatively small subset of population and recurrent bouts of illness in others make up the bulk of the cases. Diarrhea is more prevalent among adults who are exposed to children and non-toilet-trained infants, particularly in a daycare setting; travelers to tropical regions; homosexual males; persons with underlying immunosuppression; and those living in unhygienic environments and having exposure to contaminated water or foods.

Approximately 8 to 9 L of fluid enters the intestines daily; 1 to 2 L represents food and liquid intake, and the rest is from endogenous sources such as salivary, gastric, pancreatic, biliary, and intestinal secretions. Most of the fluid, about 6 to 7 L, is absorbed in the small intestine, and only about 1 to 2 L is presented to the colon. Most of this is absorbed as it passes through the colon, leaving a stool output of about 100 to 200 grams daily.⁴

Water is absorbed passively in the gut, dependent on the osmotic gradient. Consequently, diarrhea is due to excess osmotically active substances in the stool, the result of either decreased absorption of nutrients and electrolytes or excess secretion of electrolytes, or both.

There are 4 mechanisms of diarrhea; the major ones are osmotic and secretory:⁵

Osmotic Diarrhea
This type of diarrhea is due to the presence of an unabsorbable or poorly absorbable solute that exerts an osmotic pressure effect across the intestinal mucosa, resulting in excessive water output. Because the diarrhea is caused by the solute, it tends to stop during fasting.

In addition, there is an increased stool "osmotic gap." The total stool osmolality is close to the serum osmolality, ie, 290 mOsm/kg. Normally, most of the stool osmolality is accounted for by the sum of stool sodium and potassium concentrations multiplied by 2 (to account for associated anions). Products of colonic fermentation, such as short-chain fatty acids, account for the remaining osmolality-ie, the osmotic gap. Stool osmotic gap is calculated as follows:

Osmotic gap = 290 - [2 (stool Na + stool K)]

In osmotic diarrhea, the presence of unabsorbable solute contributes significantly to the stool osmolality and the concentration of electrolytes is lower, resulting in an increased osmotic gap. The osmotic gap in all forms of osmotic diarrhea is greater than 50 mOsm/kg, whereas in secretory diarrhea it is less than 50 mOsm/kg.⁶
Measurement of osmotic gap is more relevant in cases of chronic diarrhea as osmotic diarrhea is mainly seen in chronic cases.

Causes of osmotic diarrhea include disaccharidase deficiency (lactose intolerance), malabsorption, poorly absorbed sugars (lactulose, sorbitol, mannitol), laxatives (magnesium, sodium citrate, sodium phosphate), and magnesium-containing antacids. A fecal fluid pH of less than 5.6 is seen in malabsorption of sugars (eg, lactose) and helps to distinguish this cause from others.

Secretory Diarrhea
In this type of diarrhea there is abnormal ion transport across the intestinal epithelial cells, which results in increased secretion, decreased absorption, or both. There is no osmotic gap, and as the diarrhea is not related to intestinal contents, it typically does not stop with fasting.

A classic example of acute secretory diarrhea is cholera, and is also seen in infections like enterotoxigenic E coli. Chronic secretory diarrhea is seen in celiac sprue, collagenous colitis, VIPoma, carcinoid tumor, and hyperthyroidism. Stimulant laxatives (phenolphthalein, senna, bisacodyl) also cause secretory diarrhea.

Altered Motility
Abnormal motility can cause diarrhea by the following mechanisms:

• Enhanced motility, resulting in rapid gut transit and decreased contact time between luminal contents and absorptive epithelial cells. Causes include hyperthyroidism, carcinoid syndrome, irritable bowel syndrome, and post-gastrectomy and
  post-vagotomy status.
  
  
• Slow motility, caused by diseases such as scleroderma, may result in bacterial overgrowth, which causes deconjugation of bile acids and results in steatorrhea and diarrhea.

Altered motility as the primary cause of diarrhea is mostly seen in cases of chronic diarrheas. Dysmotility-induced diarrhea is often a diagnosis of exclusion, as proving dysmotility as the sole cause of diarrhea is very difficult.

Exudative Diarrhea
Extensive injury of the small bowel or colon mucosa may result in fluid and protein loss into the intestinal lumen and ensuing diarrhea. Exudation is rarely the only mechanism accounting for diarrhea.

Causes of exudative diarrhea include invasive bacterial infections (Shigella, Salmonella) and inflammatory
bowel disease.

It is important to note that more than one mechanism may coexist. For example, in infectious and inflammatory conditions, malabsorption leading to osmotic diarrhea and active secretion can coexist.

Patients with diarrhea present with various clinical features depending on the underlying cause. Diarrhea due to small-intestinal disease is typically high-volume, watery, and often associated with malabsorption, and dehydration is frequent. Diarrhea due to colonic involvement is more often associated with frequent small-volume stools, with the presence of blood and a sensation of urgency.

Patients with acute infectious diarrhea typically present with nausea, vomiting, abdominal pain, fever, and frequent stools, which may be watery, malabsorptive, or bloody depending on the specific pathogen. In general, small-intestinal pathogens are noninvasive, and ileocolonic pathogens are more likely to be invasive.

Patients ingesting toxins or those with toxigenic infection typically have nausea and vomiting as prominent symptoms along with watery diarrhea but rarely have a high fever. Vomiting that begins within several hours of ingesting a food should suggest food poisoning due to preformed toxin. Parasites that do not invade the intestinal mucosa, such as Giardia lamblia and Cryptosporidium, usually cause only mild abdominal discomfort. Giardiasis may be associated with mild steatorrhea, gaseousness, and bloating.

Invasive bacteria such as Campylobacter, Salmonella, and Shigella organisms, and organisms that produce cytotoxins such as Clostridium difficile and enterohemorrhagic E coli (serotype O157: H7), cause severe intestinal inflammation, abdominal pain, and often fever; occasionally peritoneal signs may suggest a surgical abdomen. Yersinia organisms often infect the terminal ileum and caecum and present with right lower-quadrant pain and tenderness, suggestive of acute appendicitis.

Watery diarrhea is a typical symptom of organisms that invade the intestinal epithelium with minimal inflammation, such as enteric viruses, or organisms that adhere to but do not destroy the epithelium, such as enteropathogenic E coli, protozoa, and helminths. Some organisms such as Campylobacter, Aeromonas, Shigella, and Vibrio species (eg, V parahemolyticus) both produce enterotoxins and also invade the intestinal mucosa; patients therefore often present with watery diarrhea followed within hours or days by bloody diarrhea.

Hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura can occur in infections with enterohemorrhagic E coli and Shigella organisms, particularly in young children and the elderly. Yersinia infection and other enteric bacterial infections may be accompanied by Reiter's syndrome (arthritis, urethritis, and conjunctivitis), thyroiditis, pericarditis, or glomerulonephritis. Enteric fever, caused by Salmonella typhi or Salmonella paratyphi, is a severe systemic illness manifested initially by prolonged high fevers, prostration, confusion, and respiratory symptoms, followed by abdominal tenderness, diarrhea, and rash.

Dehydration can occur if diarrhea is severe and oral intake is limited due to nausea and vomiting, particularly in very young and elderly patients. It is manifested as increased thirst, decreased urinary output with dark urine, inability to sweat, and orthostatic changes. In severe cases, it may lead to acute renal failure and mental status changes like confusion and drowsiness.

Conducting a careful interview can provide valuable clues that will aid in diagnosing and choosing the most appropriate and cost-effective investigations. Acute diarrheas are usually infectious in origin, and for the most part resolve with or without intervention before a diagnosis is made.

The presence of blood is a useful clue, suggesting infection by invasive organisms, inflammation, ischemia, or neoplasm. Large-volume diarrhea suggests small-bowel or proximal colonic disease, while small, frequent stools associated with urgency suggest left colon or rectal disease. All current and recent medications should be reviewed, specifically new medications, antibiotics, antacids, and alcohol abuse. Nutritional supplements should also be reviewed, including the intake of "sugar free" foods (containing nonabsorbable carbohydrates), fat substitutes, milk products, shellfish, or heavy intake of fruits, fruit juices, or caffeine. The social history should include travel, source of drinking water (treated city water or well water), rural conditions with consumption of raw milk, exposure to farm animals that may spread Salmonella or Brucella organisms, and sexual orientation. Sexual history is important, as specific organisms can cause diarrhea in homosexual men and HIV patients. Familial occurrence of celiac disease, inflammatory bowel disease, or multiple endocrine neoplasia syndromes should be checked as well.

The physical examination in acute diarrhea is helpful in determining severity of disease and hydration status. Further evaluation may be by laboratory tests, and the appropriate selection of tests depends to a great extent on the duration and severity of diarrhea, systemic symptoms, and the presence of blood, overt or occult, in the stool. If a patient is seen early in the course of illness, has no systemic symptoms or blood in the stool, and diarrhea is mild, then symptomatic treatment with observation and follow-up are most appropriate, but stool cultures could be done and treated if positive.

Medical evaluation of diarrhea is indicated if symptoms are severe or prolonged, if the patient appears "toxic," if there is evidence of colitis (occult or gross blood in the stools, severe abdominal pain or tenderness, and fever), or if empiric therapy has failed. Evaluation of diarrhea is also advised for patients with immunosuppression or severe comorbid conditions, and in the elderly.⁷

Stool evaluation for fecal leukocytes (or lactoferrin, a byproduct of white blood cells) is a useful initial test as it may support a diagnosis of inflammatory diarrhea. If the test is negative, stool culture may not be necessary. Stool culture is indicated if the test is positive. However, clinicians should remember that inflammatory diarrheas with noninfectious causes such as inflammatory bowel disease, ischemic or radiation-induced colitis, and diverticulitis, can all have positive stool leukocytes.

Indications for stool culture are bloody diarrhea, toxic-appearing patient (fever, severe abdominal pain), a possible epidemic, traveler's diarrhea, immunosuppression, or persistent diarrhea. The culture media routinely used identify Campylobacter, Salmonella, Shigella, and Aeromonas organisms. Hence, the laboratory should be alerted when other pathogens such as E coli O157: H7, Vibrio, or Yersinia are suspected. The rapid ELISA for Clostridium difficile toxins A and B is most often used in high-risk patients who have taken antibiotics or have hospital-acquired diarrhea. Stool testing for ova and parasites should be done if the patient is at risk for parasitic infection.

If organisms are not identified on stool cultures or on the ova and parasites test, then sigmoidoscopy should be performed and biopsies obtained. Mucosal biopsy is helpful in differentiating infectious colitis from inflammatory bowel disease. Crypt architecture is usually normal in infectious colitis, whereas in inflammatory bowel disease it is distorted. Further investigations will depend on the results of sigmoidoscopy, severity of diarrhea, immune status of the host, and the presence of systemic toxicity. A general algorithm for the evaluation of acute diarrhea is shown
in Figure 1.

The principal components of the treatment of acute diarrhea are fluid and electrolyte replacement, dietary modifications, and drug therapy. All recommendations are in agreement with guidelines on acute infectious diarrhea in adults, published by the American College of Gastroenterology.⁷

Rehydration
If patients are otherwise healthy and do not have dehydration, adequate fluid intake can be achieved with soft drinks, fruit juice, broth, soup, and salted crackers. In those with excessive fluid losses and dehydration, more aggressive measures like intravenous fluids or oral rehydration therapy with isotonic, electrolyte solutions containing glucose or starch should be given. Oral rehydration therapy is less expensive, often just as effective, and more practical than intravenous fluids. A number of oral rehydration solutions are available, including Pedialyte, Rehaldehyte, Ricelyte, Resol, and the World Health Organization formula. An equally effective homemade mixture is 1/2 tsp salt (3.5 g), 1 tsp baking soda (2.5 g NaHCO₃), 8 tsp sugar (40 g), and 8 oz orange juice (1.5 g KCl), diluted to 1 L with water. Fluids should be given at rates of 50 to 200 ml/kg/24 hr, depending on the hydration status. Intravenous fluids (lactated Ringer's solution) are preferred acutely for patients with severe dehydration and in those who cannot tolerate oral fluids.

Diet
Total food abstinence is unnecessary and not recommended. Patients should be encouraged to take frequent feedings of fruit drinks, tea, "flat" carbonated beverages, and soft, easily digested foods such as bananas, rice, crackers, and soups. Dairy products should be avoided because transient lactase deficiency can be caused by enteric viral and bacterial infections. Caffeinated beverages and alcohol, which can enhance intestinal motility and secretions, should be avoided.

Antidiarrheal Agents
These can be very useful in amelioration of symptoms.⁸ The most effective agents are the opioid derivatives—loperamide, diphenoxylate-atropine, and tincture of opium. Loperamide is preferred in most cases because it is nonaddictive and has fewer side effects than the others. Bismuth subsalicylate is another useful agent, but it is contraindicated in HIV-infected patients since it may cause bismuth encephalopathy. The antimotility agents should not be used in febrile dysentery patients (eg, those infected by Shigella), as these agents may prolong the disease.

Antimicrobial Therapy
Because the majority of patients have mild, self-limited disease due to viruses or noninvasive bacteria, empiric treatment of all patients is not warranted. Empiric treatment is indicated in those patients with suspected invasive bacterial infection, traveler's diarrhea, or immunosuppression. The drugs of choice are quinolones (eg, ciprofloxacin, 500 mg twice daily for 5 to 7 days). These agents have good coverage against most invasive bacterial pathogens, including Campylobacter, Shigella, Salmonella, Yersinia, and Aeromonas species. Alternatives are trimethoprim/sulfamethoxazole, 160/800 mgs twice daily, or erythromycin, 250 to 500 mg 4 times daily. Metronidazole, 250 mg 3 times daily for 7 days, is given for suspected giardiasis. For selected travelers to high-risk destinations, a quinolone (eg, ciprofloxacin, 500 mg per day) is a preferred prophylactic agent, offering a protection rate of around 90%. Other prophylactic agents include trimethoprim-sulfamethoxazole and bismuth subsalicylate.

Specific pathogens that should be treated include Shigella, Vibrio cholerae, Clostridium difficile, parasites, extraintestinal salmonellosis, traveler's diarrhea, and sexually transmitted infections (gonorrhea, syphilis, chlamydiosis, and herpes simplex infections). Pathogens that should probably be treated include noncholera Vibrio, Yersinia, and Campylobacter, and if the symptoms are prolonged with Aeromonas, Plesiomonas and enteropathogenic E coli.

The preferred treatment for patients with Clostridium difficile diarrhea is oral metronidazole, 250 to 500 mg 4 times a day for 7 to 10 days.⁹ Vancomycin is an alternative agent, but it is more expensive and has to be taken orally because it is not effective when administered parenterally. Intravenous metronidazole is given for patients who cannot tolerate oral intake.

Diarrhea is one of the most common illnesses in all age groups and is second only to the common cold as a cause of lost days of work or school. It is estimated that there are almost 100 million cases of acute diarrhea per year in adults in the United States. Adults experience an average of more than one bout of diarrhea per year. Most of the patients with acute diarrhea have a mild and self-limited illness; the majority treat their illness at home and usually get better without medical intervention. But diarrhea is responsible for more than 300 deaths each year in North America. Diarrhea and related complications can cause severe illness especially in high-risk groups, such as patients with severe comorbid conditions, underlying immunosuppression, and advanced age.

1. Soffer EE. Diarrhea. In: Andreoli TE, et al, eds. Cecil Essentials of Medicine. 5th ed. Philadelphia, WB Saunders, 2001:316-320.
   
   
2. Garthright WE, Archer DL, Kvenberg JE. Estimates of incidence and costs of intestinal infectious diseases in the United States. Public Health Rep. 1988;103:107-115.
   
   
3. Gangarosa RE, Glass RI, Lew JF, Boring JR. Hospitalizations involving gastroenteritis in the United States, 1985: the special burden of disease among the elderly. Am J Epidemiol. 1992;135:281-290.
   
   
4. Sellin JH. Intestinal electrolyte absorption and secretion. In: Feldman M, et al, eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 6th ed. Philadelphia, WB Saunders, 1998:1451-1471.
   
   
5. Fine KD. Diarrhea. In: Feldman M, et al, eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 6th ed. Philadelphia, WB Saunders, 1998:128-152.
   
   
6. Schiller LR. Diarrhea. Med Clin North Am. 2000;84:1259-1274.
   
   
7. Dupont HL. Guidelines on acute infectious diarrhea in adults. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol. 1997;92:1962-1975.
   
   
8. Scheidler MD, Giannella RA. Practical management of acute diarrhea. Hosp Pract. 2001;36:49-56.
   
   
9. Fekety R. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 1997;92:739-750.

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