DIARRHEA Diarrhea is a common symptom that can range in severity from an acute, self-limited annoyance to a severe, life-threatening illness. Patients may use the term "diarrhea" to refer to increased frequency of bowel movements, increased stool liquidity, a sense of fecal urgency, or fecal incontinence

Definition In the normal state, approximately 10 L of fluid enter the duodenum daily, of which all but 1.5 L are absorbed by the small intestine. The colon absorbs most of the remaining fluid, with only 100 mL lost in the stool. From a medical standpoint, diarrhea is defined as a stool weight of more than 250 g/24 h

The causes of diarrhea are myriad The causes of diarrhea are myriad. In clinical practice, it is helpful to distinguish acute from chronic diarrhea, as the evaluation and treatment are entirely different

Causes of acute infectious diarrhea Noninflammatory Diarrhea Viral - Norwalk virus, Norwalk-like virus, Rotavirus Protozoal - Giardia lamblia, Cryptosporidium Bacterial - Preformed enterotoxin production Staphylococcus aureus, Bacillus cereus, Clostridium perfringens Enterotoxin production; Enterotoxigenic E coli (ETEC), Vibrio cholerae

Inflammatory Diarrhea Viral – Cytomegalovirus Protozoal - Entamoeba histolytica Bacterial - Cytotoxin productio; Enterohemorrhagic E coli, Vibrio parahaemolyticus, Clostridium difficile. Mucosal invasion; Shigella, Campylobacter jejuni Salmonella, Enteroinvasive E coli ,Aeromonas Plesiomonas,Yersinia enterocolitica,Chlamydia Neisseria gonorrhoeae, Listeria monocytogenes

Causes of chronic diarrhea Osmotic diarrhea CLUES: Stool volume decreases with fasting; increased stool osmotic gap 1. Medications: antacids, lactulose, sorbitol 2. Disaccharidase deficiency: lactose intolerance 3. Factitious diarrhea: magnesium (antacids, laxatives)

Secretory diarrhea Large volume ( >1 L/d); little change with fasting; normal stool osmotic gap 1. Hormonally mediated: VIPoma, carcinoid, medullary carcinoma of thyroid (calcitonin), Zollinger-Ellison syndrome (gastrin) 2. Factitious diarrhea (laxative abuse): phenolphthalein, cascara, senna 3. Villous adenoma 4. Bile salt malabsorption (ileal resection; Crohn's ileitis; postcholecystectomy) 5. Medications

Inflammatory conditions Fever, hematochezia, abdominal pain 1. Ulcerative colitis 2. Crohn's disease 3. Microscopic colitis 4. Malignancy: lymphoma, adenocarcinoma (with obstruction and pseudodiarrhea) 5. Radiation enteritis

Malabsorption syndromes Weight loss, abnormal laboratory values; fecal fat > 7-10 g/24 h, tropical sprue, Whipple's disease, eosinophilic gastroenteritis, Crohn's disease, small bowel resection (short bowel syndrome) 2. Lymphatic obstruction: lymphoma, carcinoid, infectious (TB, MAI), Kaposi's sarcoma, sarcoidosis, retroperitoneal fibrosis 3. Pancreatic disease: chronic pancreatitis, pancreatic carcinoma 4. Bacterial overgrowth: motility disorders (diabetes, vagotomy, scleroderma), fistulas, small intestinal diverticula

Motility disorders Systemic disease or prior abdominal surgery 1. Postsurgical: vagotomy, partial gastrectomy, blind loop with bacterial overgrowth 2. Systemic disorders: scleroderma, diabetes mellitus, hyperthyroidism 3. Irritable bowel syndrome

Chronic infections Parasites: Giardia lamblia, Entamoeba histolytica, Cyclospora AIDS-related: Viral: Cytomegalovirus, HIV infection (?) Bacterial: Clostridium difficile, Mycobacterium avium complex Protozoal: Microsporida (Enterocytozoon bieneusi ), Cryptosporidium, Isospora belli

ACUTE DIARRHEA Diarrhea that is acute in onset and persists for less than 3 weeks is most commonly caused by infectious agents, bacterial toxins (either ingested preformed in food or produced in the gut), or drugs

Recent ingestion of improperly stored or prepared food implicates food poisoning, especially if other people were similarly affected. Exposure to unpurified water (camping, swimming) may result in infection with Giardia or Cryptosporidium

TRAVELER'S DIARRHEA Whenever a person travels from one country to another—particularly if the change involves a marked difference in climate, social conditions, or sanitation standards and facilities—diarrhea is likely to develop within 2–10 days

There may be up to ten or even more loose stools per day, often accompanied by abdominal cramps, nausea, occasionally vomiting, and rarely fever. The stools do not usually contain mucus or blood, and aside from weakness, dehydration, and occasionally acidosis, there are no systemic manifestations of infection. The illness usually subsides spontaneously within 1–5 days, although 10% remain symptomatic for a week or longer, and in 2% symptoms persist for longer than a month

Bacteria cause 80% of cases of traveler's diarrhea, with enterotoxigenic E coli, Shigella species, and Campylobacter jejuni being the most common pathogens. Less common causative agents include Aeromonas, Salmonella, noncholera vibrios, Entamoeba histolytica, and Giardia lamblia. Contributory causes may at times include unusual food and drink, change in living habits, occasional viral infections (adenoviruses or rotaviruses), and change in bowel flora

For most individuals, the affliction is short-lived, and symptomatic therapy with opiates or diphenoxylate with atropine is all that is required provided the patient is not systemically ill (fever ł 39 °C) and does not have dysentery (bloody stools), in which case antimotility agents should be avoided. Packages of oral rehydration salts to treat dehydration are available over the counter in the USA and in many foreign countries

Avoidance of fresh foods and water sources that are likely to be contaminated is recommended for travelers to developing countries, where infectious diarrheal illnesses are endemic. Prophylaxis is recommended for those with significant underlying disease (inflammatory bowel disease, AIDS, diabetes, heart disease in the elderly

Prophylaxis is started upon entry into the destination country and is continued for 1 or 2 days after leaving. For stays of more than 3 weeks, prophylaxis is not recommended because of the cost and increased toxicity. For prophylaxis, bismuth subsalicylate is effective but turns the tongue and the stools blue and can interfere with doxycycline absorption, which may be needed for malaria prophylaxis. Numerous antimicrobial regimens for once-daily prophylaxis also are effective, such as norfloxacin 400 mg, ciprofloxacin 500 mg, ofloxacin 300 mg, or trimethoprim-sulfamethoxazole 160/800 mg. daily for 5 days

Because not all travelers will have diarrhea and because most episodes are brief and self-limited, an alternative approach that is currently recommended is to provide the traveler with a 3- to 5-day supply of antimicrobials to be taken if significant diarrhea occurs during the trip. Commonly used regimens include ciprofloxacin 500 mg twice daily, ofloxacin 300 mg twice daily, or norfloxacin 400 mg twice daily. Trimethoprim-sulfamethoxazole 160/800 mg twice daily can be used as an alternative (especially in children), but resistance is common in many areas. Aztreonam, a poorly absorbed monobactam with activity against most bacterial enteropathogens, also is efficacious when given orally in a dose of 100 mg three times

Noninflammatory Diarrhea Watery, nonbloody diarrhea associated with periumbilical cramps, bloating, nausea, or vomiting (singly or in any combination) suggests small bowel enteritis caused by either a toxin-producing bacterium (enterotoxigenic E coli [ETEC], Staphylococcus aureus, Bacillus cereus, C perfringens) or other agents (viruses, Giardia) that disrupt the normal absorption and secretory process in the small intestine.

Prominent vomiting suggests viral enteritis or S aureus food poisoning Prominent vomiting suggests viral enteritis or S aureus food poisoning. Though typically mild, the diarrhea (which originates in the small intestine) may be voluminous (ranging from 10 to 200 mL/kg/24 h) and result in dehydration with hypokalemia and metabolic acidosis due to loss of HCO3– in the stool (eg, cholera). Because tissue invasion does not occur, fecal leukocytes are not present.

Inflammatory Diarrhea The presence of fever and bloody diarrhea (dysentery) indicates colonic tissue damage caused by invasion (shigellosis, salmonellosis, Campylobacter or Yersinia infection, amebiasis) or a toxin (C difficile, E coli O157:H7). Because these organisms involve predominantly the colon, the diarrhea is small in volume (< 1 L/d) and associated with left lower quadrant cramps, urgency, and tenesmus.

Fecal leukocytes are present in infections with invasive organisms Fecal leukocytes are present in infections with invasive organisms. E coli O157:H7 is a toxigenic, noninvasive organisms that may be acquired from contaminated meat or unpasteurized juice and has resulted in several outbreaks of an acute, often severe hemorrhagic colitis. In immunocompromised and HIV-infected patients, cytomegalovirus may result in intestinal ulceration with watery or bloody diarrhea

Enteric Fever A severe systemic illness manifested initially by prolonged high fevers, prostration, confusion, respiratory symptoms followed by abdominal tenderness, diarrhea, and a rash is due to infection with Salmonella typhi or Salmonella paratyphi, which causes bacteremia and multiorgan dysfunction

Evaluation In over 90% of patients with acute diarrhea, the illness is mild and self-limited and responds within 5 days to simple rehydration therapy or antidiarrheal agents Patients with signs of inflammatory diarrhea manifested by any of the following require prompt medical attention: high fever (> 38.5 °C), bloody diarrhea, abdominal pain, or diarrhea not subsiding after 4–5 days. Similarly, patients with symptoms of dehydration must be evaluated (excessive thirst, dry mouth, decreased urination, weakness, lethargy)

Physical examination should note the patient's general appearance, mental status, volume status, and the presence of abdominal tenderness or peritonitis Peritoneal findings may be present in C difficile and enterohemorrhagic E coli. Hospitalization is required in patients with severe dehydration, toxicity, or marked abdominal pain. Stool specimens should be sent in all cases for examination for fecal leukocytes and bacterial cultures

The rate of positive bacterial cultures in patients with dysentery is 60–75%. A wet mount examination of the stool for amebiasis should also be performed in patients with dysentery who have a history of recent travel to endemic areas or those who are homosexuals. In patients with a history of antibiotic exposure, a stool sample should be sent for C difficile toxin. If E coli O157:H7 is suspected, the laboratory must be alerted to do specific serotyping. In patients with diarrhea that persists for more than 10 days, three stool examinations for ova and parasites also should be performed. Rectal swabs may be sent for Chlamydia, Neisseria gonorrhoeae, and herpes simplex virus in sexually active patients with severe proctitis

Treatment Diet :The overwhelming majority of adults have mild diarrhea that will not lead to dehydration provided the patient takes adequate oral fluids containing carbohydrates and electrolytes. Patients will find it more comfortable to rest the bowel by avoiding high-fiber foods, fats, milk products, caffeine, and alcohol. Frequent feedings of fruit drinks, tea, "flat" carbonated beverages, and soft, easily digested foods (eg, soups, crackers) are encouraged

Rehydration In more severe diarrhea, dehydration can occur quickly, especially in children. Oral rehydration with fluids containing glucose, Na+, K+, Cl–, and bicarbonate or citrate is preferred in most cases to intravenous fluids because it is inexpensive, safe, and highly effective in almost all awake patients

An easy mixture is ˝ tsp salt (3. 5 g), 1 tsp baking soda (2 An easy mixture is ˝ 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. Alternatively, oral electrolyte solutions (eg, Pedialyte) are readily available. Fluids should be given at rates of 50–200 mL/kg/24 h depending on the hydration status. Intravenous fluids (lactated Ringer's solution) are preferred acutely in patients with severe dehydration.

Antidiarrheal Agents Loperamide is the preferred drug in a dosage of 4 mg initially, followed by 2 mg after each loose stool (maximum:16 mg/24 h Bismuth subsalicylate (Pepto-Bismol), two tablets or 30 mL four times daily, reduces symptoms in patients with traveler's diarrhea by virtue of its anti-inflammatory and antibacterial properties Anticholinergic agents are contraindicated in acute diarrhea

Antibiotic Therapy Empiric treatment-fluoroquinolones (eg, ciprofloxacin, 500 mg twice daily) for 5–7 days. These agents provide good antibiotic coverage against most invasive bacterial pathogens, including Shigella, Salmonella, Campylobacter, Yersinia, and Aeromonas. Alternative agents are trimethoprim-sulfamethoxazole, 160/800 mg twice daily, or erythromycin, 250–500 mg four times daily

Specific antimicrobial treatment- Antibiotics are not generally recommended in patients with nontyphoid Salmonella, Campylobacter, or Yersinia infection except in severe or prolonged disease because they have not been shown to hasten recovery or reduce the period of fecal bacterial excretion. The infectious diarrheas for which treatment is clearly recommended are shigellosis, cholera, extraintestinal salmonellosis, "traveler's" diarrhea, C difficile infection, giardiasis, amebiasis, and the sexually transmitted infections (gonorrhea, syphilis, chlamydiosis, and herpes simplex infection)

CHRONIC DIARRHEA Etiology The causes of chronic diarrhea may be grouped into six major pathophysiologic categories

Osmotic Diarrheas As stool leaves the colon, fecal osmolality is equal to the serum osmolality, ie, approximately 290 mosm/kg. Under normal circumstances, the major osmoles are Na+, K+, Cl–, and HCO3–. The stool osmolality may be estimated by multiplying the stool (Na+ + K+) × 2 (multiplied by 2 to account for the anions)

The osmotic gap is the difference between the measured osmolality of the stool (or serum) and the estimated stool osmolality and is normally less than 50 mosm/kg An increased osmotic gap implies that the diarrhea is caused by ingestion or malabsorption of an osmotically active substance

The most common causes of osmotic diarrhea are disaccharidase deficiency (lactase deficiency), laxative abuse, and malabsorption syndromes (see below). Osmotic diarrheas resolve during fasting. Osmotic diarrheas caused by malabsorbed carbohydrates are characterized by abdominal distention, bloating, and flatulence due to increased colonic gas production.

Malabsorptive Conditions The major causes of malabsorption are small mucosal intestinal diseases, intestinal resections, lymphatic obstruction, small intestinal bacterial overgrowth, and pancreatic insufficiency In patients with suspected malabsorption, quantification of fecal fat should be performed

Secretory Conditions Increased intestinal secretion or decreased absorption results in a watery diarrhea that may be large in volume (1–10 L/d) but with a normal osmotic gap here is little change in stool output during the fasting state. In serious conditions, significant dehydration and electrolyte imbalance may develop. Major causes include endocrine tumors (stimulating intestinal or pancreatic secretion), bile salt malabsorption (stimulating colonic secretion), and laxative abuse

Inflammatory Conditions Diarrhea is present in most patients with inflammatory bowel disease (ulcerative colitis, Crohn's disease, microscopic colitis). A variety of other symptoms may be present, including abdominal pain, fever, weight loss, and hematochezia

Motility Disorders Abnormal intestinal motility secondary to systemic disorders or surgery may result in diarrhea due to rapid transit or to stasis of intestinal contents with bacterial overgrowth resulting in malabsorption

Chronic Infections Chronic parasitic infections may cause diarrhea through a number of mechanisms. Although the list of parasitic organisms is a long one, agents most commonly associated with diarrhea include the protozoans Giardia, E histolytica, Cyclospora, and the intestinal nematodes Immunocompromised patients, especially those with AIDS, are susceptible to a number of infectious agents that can cause acute or chronic diarrhea Chronic diarrhea in AIDS is commonly caused by Microsporida, Cryptosporidium, cytomegalovirus, Isospora belli, Cyclospora, and Mycobacterium avium complex.

Factitial Diarrhea Approximately 15% of patients with chronic diarrhea have factitial diarrhea caused by surreptitious laxative abuse or factitious dilution of stool

Evaluation Stool Analysis - Twenty-four-hour stool collection for weight and quantitative fecal fat–A stool weight of more than 300 g/24 h confirms the presence of diarrhea, justifying further workup. A weight greater than 1000–1500 g suggests a secretory process. A fecal fat in excess of 10 g/24 h indicates a malabsorptive process

2. Stool osmolality–An osmotic gap confirms osmotic diarrhea 2. Stool osmolality–An osmotic gap confirms osmotic diarrhea. A stool osmolality less than the serum osmolality implies that water or urine has been added to the specimen (factitious diarrhea). 3. Stool laxative screen–In cases of suspected laxative abuse, stool magnesium, phosphate, and sulfate levels may be measured. Phenolphthalein, senna, and cascara are indicated by the presence of a bright-red color after alkalinization of the stool or urine. Bisacodyl can be detected in the urine

4. Fecal leukocytes–The presence of leukocytes in a stool sample implies an underlying inflammatory diarrhea. 5. Stool for ova and parasites–The presence of Giardia and E histolytica is detected in routine wet mounts. Cryptosporidium and Cyclospora are detected with modified acid-fast staining.

Blood Tests Routine laboratory tests–CBC, serum electrolytes, liver function tests, calcium, phosphorus, albumin, TSH, total T4, beta-carotene, and prothrombin time should be obtained. Anemia occurs in malabsorption syndromes (vitamin B12, folate, iron) and inflammatory conditions. Hypoalbuminemia is present in malabsorption, protein-losing enteropathies, and inflammatory diseases. Hyponatremia and non–anion gap metabolic acidosis may occur in profound secretory diarrheas. Malabsorption of fat-soluble vitamins may result in an abnormal prothrombin time, low serum calcium, low carotene, or abnormal serum alkaline phosphatase

Other laboratory tests In patients with suspected secretory diarrhea, serum VIP (VIPoma), gastrin (Zollinger-Ellison syndrome), calcitonin (medullary thyroid carcinoma), cortisol (Addison's disease), and urinary 5-HIAA (carcinoid syndrome) levels should be obtained Proctosigmoidoscopy With Mucosal Biopsy: Examination may be helpful in detecting inflammatory bowel disease (including microscopic colitis) and melanosis coli, indicative of chronic use of anthraquinone laxatives.

Imaging Calcification on a plain abdominal radiograph confirms the diagnosis of chronic pancreatitis. An upper gastrointestinal series or enteroclysis study is helpful in evaluating Crohn's disease, lymphoma, or carcinoid syndrome. Colonoscopy is helpful in evaluating colonic inflammation due to inflammatory bowel disease. Upper endoscopy with small bowel biopsy is useful in suspected malabsorption due to mucosal diseases. Upper endoscopy with a duodenal aspirate and small bowel biopsy is also useful in patients with AIDS and to document Cryptosporidium, Microsporida, and M avium-intracellulare infection. Abdominal CT is helpful to detect chronic pancreatitis or pancreatic endocrine tumors.

Treatment A. Loperamide: 4 mg initially, then 2 mg after each loose stool (maximum: 16 mg/d) Diphenoxylate With Atropine: One tablet three or four times daily Codeine, Paregoric: Because of their addictive potential, these drugs are generally avoided except in cases of chronic, intractable diarrhea. Codeine may be given in a dosage of 15–60 mg every 4 hours as needed; the dosage of paregoric is 4–8 mL after each liquid bowel movement

Clonidine: a2-Adrenergic agonists inhibit intestinal electrolyte secretion. A clonidine patch that delivers 0.1–0.2 mg/d for 7 days may be useful in some patients with secretory diarrheas, cryptosporidiosis, and diabetes. . Octreotide: This somatostatin analog stimulates intestinal fluid and electrolyte absorption and inhibits secretion. Furthermore, it inhibits the release of gastrointestinal peptides. It is very useful in treating secretory diarrheas due to VIPomas and carcinoid tumors and in some cases of diarrhea associated with AIDS. Effective doses range from 50 mg to 250 mg subcutaneously three times daily. A dosage of 4 g one to three times daily is recommended

Cholestyramine: This bile salt binding resin may be useful in patients with bile salt-induced diarrhea secondary to intestinal resection or ileal disease