Background

Acute diarrhea is defined as the abrupt onset of 3 or more loose stools per day. The augmented water content in the stools (above the normal value of approximately 10 mL/kg/d in the infant and young child, or 200 g/d in the teenager and adult) is due to an imbalance in the physiology of the small and large intestinal processes involved in the absorption of ions, organic substrates, and thus water. A common disorder in its acute form, diarrhea has many causes and may be mild to severe. Childhood acute diarrhea is usually caused by infection of the small and/or large intestine; however, numerous disorders may result in diarrhea, including a malabsorption syndrome and various enteropathies. Acute-onset diarrhea is usually self-limited; however, an acute infection can have a protracted course. By far, the most common complication of acute diarrhea is dehydration. Although the term "acute gastroenteritis" is commonly used synonymously with "acute diarrhea," the former term is a misnomer. The term gastroenteritis implies inflammation of both the stomach and the small intestine, whereas, in reality, gastric involvement is rarely if ever seen in acute diarrhea (including diarrhea with an infectious origin); in addition, enteritis is also not consistently present. Examples of infectious acute diarrhea syndromes that do not cause enteritis include Vibrio cholerae induced diarrhea and Shigella -induced diarrhea. Thus, the term acute diarrhea is preferable to acute gastroenteritis. Diarrheal episodes are classically distinguished into acute and chronic (or persistent) based on their duration. Acute diarrhea is thus defined as an episode that has an acute onset and lasts no longer than 14 days; chronic or persistent diarrhea is defined as an episode that lasts longer than 14 days. The distinction, supported by the World Health Organization (WHO), has implications not only for classification and epidemiological studies but also from a practical standpoint because protracted diarrhea often has a different set of causes, poses different problems of management, and has a different prognosis.

Pathophysiology
Diarrhea is the reversal of the normal net absorptive status of water and electrolyte absorption to secretion. Such a derangement can be the result of either an osmotic force that acts in the lumen to drive water into the gut or the result of an active secretory state induced in the enterocytes. In the former case, diarrhea is osmolar in nature, as is observed after the ingestion of nonabsorbable sugars such as lactulose or lactose in lactose malabsorbers. Instead, in the typical active secretory state, enhanced anion secretion (mostly by the crypt cell compartment) is best exemplified by enterotoxin-induced diarrhea. In osmotic diarrhea, stool output is proportional to the intake of the unabsorbable substrate and is usually not massive; diarrheal stools promptly regress with discontinuation of the offending nutrient, and the stool ion gap is high, exceeding 100 mOsm/kg. In fact, the fecal osmolality in this circumstance is accounted for not only by the electrolytes but also by the unabsorbed nutrient(s) and their degradation products. The ion gap is obtained by subtracting the concentration of the electrolytes from total osmolality (assumed to be 290 mOsm/kg), according to the formula: ion gap = 290 [(Na + K) 2]. In secretory diarrhea, the epithelial cells ion transport processes are turned into a state of active secretion. The most common cause of acute-onset secretory diarrhea is a bacterial infection of the gut. Several mechanisms may be at work. After colonization, enteric pathogens may adhere to or invade the epithelium; they may produce enterotoxins (exotoxins that elicit secretion by increasing an intracellular second messenger) or cytotoxins. They may also trigger release of cytokines attracting inflammatory cells, which, in turn, contribute to the activated secretion by inducing the release of agents such as prostaglandins or platelet-activating factor. Features of secretory diarrhea include a high purging rate, a lack of response to fasting, and a normal stool ion gap (ie, 100 mOsm/kg or less), indicating that nutrient absorption is intact.

Epidemiology

Frequency
United States In the United States, one estimate before the introduction of specific antirotavirus immunization in 2006 assumed a cumulative incidence of 1 hospitalization for diarrhea per 23-27 children by age 5 years, with more than 50,000 hospitalizations. By these estimates, rotavirus was associated with 45% of all childhood hospitalizations and a cost of nearly $ 1 billion. [1] Furthermore, acute diarrhea is responsible for 20% of physician referrals in children younger than 2 years and for 10% in children younger than 3 years. The impact of vaccination on rotavirus morbidity has been remarkable, with significant reduction of diarrhea-associated hospitalizations and visits to emergency departments in children in the years 2007-2008 compared with the prevaccine period.[2] International In developing countries, an average of 3 episodes per child per year in children younger than 5 years is reported; however, some areas report 6-8 episodes per year per child. In these settings, malnutrition is an important additional risk factor for diarrhea, and recurrent episodes of diarrhea lead to growth faltering and substantially increased mortality. [3] Childhood mortality associated with diarrhea has constantly but slowly declined during the past 2 decades, mostly because of the widespread use of oral rehydration solutions; however, it appears to have plateaued over the past several years. Because the single most common cause of infectious diarrhea worldwide is rotavirus, and because a vaccine has been in use for over 3 years now, a reduction in the overall frequency of diarrheal episodes is hoped for in the near future.

Mortality/Morbidity
Mortality from acute diarrhea is overall globally declining but remains high. Most estimates have diarrhea as the second cause of childhood mortality, with 18% of the 10.6 million yearly deaths in children younger than age 5 years. Despite a progressive reduction in global diarrheal disease mortality over the past 2 decades, diarrhea morbidity in published reports from 1990-2000 slightly increased worldwide compared with previous reports. In the United States, an average of 369 diarrhea-associated deaths/year occurred among children aged 1-59 months during 1992-1998 and 2005-2006.[4] The vast majority of diarrheaassociated infant deaths were reported in 2005-2007, with 86% of deaths occurring among lowbirthweight (< 2500 g) infants.[5] Furthermore, in countries in which the toll of diarrhea is highest, poverty also adds an enormous additional burden, and long-term consequences of the vicious cycle of enteric infections, diarrhea, and malnutrition are devastating.[3]

Sex
Most cases of infectious diarrhea are not sex specific. Females have a higher incidence of Campylobacter species infections and hemolytic uremic syndrome (HUS).

Age
Viral diarrhea is most common in young children. Rotavirus and adenovirus are particularly prevalent in children younger than 2 years. Astrovirus and norovirus usually infect children younger than 5 years. Yersinia enterocolitis typically infects children younger than 1 year, and the Aeromonas organism is a significant cause of diarrhea in young children. Very young children are particularly susceptible to secondary dehydration and secondary nutrient malabsorption. Age and nutritional status appear to be the most important host factors in determining the severity and the duration of diarrhea. In fact, the younger the child, the higher is the risk for severe, life-threatening dehydration as a result of the high body-water turnover and limited renal compensatory capacity of very young children. Whether younger age also means a risk of running a prolonged course is an unsettled issue. In developing countries, persistent postenteritis diarrhea has a strong inverse correlation with age.

History
Acute diarrhea in developed countries is almost invariably a benign, self-limited condition, subsiding within a few days. The clinical presentation and course of illness depend on the etiology of the diarrhea and on the host. For example, rotavirus is more commonly associated with vomiting, dehydration, and a greater number of work days lost than nonrotavirus gastroenteritis. A prospective study conducted in the United States in 604 children aged 3-36 months in community settings before the introduction of rotavirus vaccine found that the highest incidence of acute diarrhea was in January and August, with an overall incidence of 2.21 episodes per personyear.[6] Close to 90% of episodes were acute (ie, lasting < 14 d, with a median duration of 2 d and a median of 6 stools per day). Diarrhea implies an increase in stool volume and diminished stool consistency. o In children younger than 2 years, diarrhea is defined as daily stools with a volume greater than 10 mL/kg. o In children older than 2 years, diarrhea is defined as daily stools with a weight greater than 200 g. In practice, this typically means loose-to-watery stools passed 3 or more times per day. o Individual stool patterns widely vary; for example, breastfed children may normally have 5-6 stools per day. Flatulence associated with foul-smelling stools that float suggests fat malabsorption, which can be observed with infection with Giardia lamblia. Knowledge of the characteristics of consistency, color, volume, and frequency can be helpful in determining whether the source is from the small or large bowel. Table 1 outlines these characteristics and demonstrates that an index of suspicion can be easily generated for a specific set of organisms. Table 1. Stool Characteristics and Determining Their Source (Open Table in a new window)
Stool Characteristics Appearance Volume Frequency Blood pH Reducing substances WBCs Serum WBCs Organisms Small Bowel Watery Large Increased Possibly positive but never gross blood Possibly < 5.5 Possibly positive < 5/high power field Normal Viral Large Bowel Mucoid and/or bloody Small Highly increased Commonly grossly bloody >5.5 Negative Commonly >10/high power field Possible leukocytosis, bandemia Invasive bacteria Escherichia Coli (enteroinvasive, enterohemorrhagic) Shigella species Salmonella species Campylobacter species Yersinia species Aeromonas species Plesiomonas species Toxic bacteria Clostridium difficile

Rotavirus Adenovirus Calicivirus Astrovirus Norovirus

Enterotoxigenic bacteria E coli Klebsiella Clostridium perfringens Cholera species Vibrio species

Parasites Giardia species Cryptosporidium species

Parasites Entamoeba organisms

Associated systemic symptoms include the following: Some enteric infections commonly have systemic symptoms, whereas others less commonly are associated with systemic features. o Table 2 outlines the frequency of some of these symptoms with particular organisms. It also outlines incubation periods and usual duration of symptoms of common organisms. Certain organisms (eg, C difficile, Giardia, Entamoeba species) may be associated with a protracted course. Table 2. Organisms and Frequency of Symptoms (Open Table in a new window)
Organism Rotavirus Adenovirus Norovirus Astrovirus Calicivirus Aeromonas species Campylobacter species C difficile C perfringens Enterohemorrhagic E coli Enterotoxigenic E coli Plesiomonas species Salmonella species Shigella species Vibrio species Y enterocolitica Giardia species Cryptosporidium species Entamoeba species Incubation 1-7 d 8-10 d 1-2 d 1-2 d 1-4 d None 2-4 d Variable Minimal 1-8 d 1-3 d None 0-3 d 0-2 d 0-1 d None 2 wk 5-21 d 5-7 d Duration 4-8 d 5-12 d 2d 4-8 d 4-8 d 0-2 wk 5-7 d Variable 1d 3-6 d 3-5 d 0-2 wk 2-7 d 2-5 d 5-7 d 1-46 d 1+ wk Months 1-2+ wk Vomiting Yes Delayed Yes +/Yes +/No No Mild No Yes +/Yes No Yes Yes No No No Fever Low Low No +/+/+/Yes Few No +/Low +/Yes High No Yes No Low Yes Abdominal Pain No No No No No No Yes Few Yes Yes Yes +/Yes Yes Yes Yes Yes Yes No

Daycare considerations are as follows: Certain organisms are spread quickly in daycare. These organisms include rotavirus; astrovirus; calicivirus; and Campylobacter, Shigella, Giardia, and Cryptosporidium species. o Increase in daycare usage has raised the incidence of rotavirus and Cryptosporidium species. Food history can be helpful. o Ingestion of raw or contaminated food is a common cause of infectious diarrhea. o Organisms that cause food poisoning include the following: o

Dairy food -Campylobacter and Salmonella species Eggs -Salmonella species Meats -C perfringens and Aeromonas, Campylobacter, andSalmonella species Ground beef - Enterohemorrhagic E coli Poultry -Campylobacter species Pork -C perfringens, Y enterocolitica Seafood - Astrovirus and Aeromonas, Plesiomonas, and Vibriospecies Oysters - Calicivirus and Plesiomonas and Vibrio species Vegetables -Aeromonas species and C perfringens Water exposure can contribute to diarrhea. o Water is a major reservoir for many organisms that cause diarrhea. o Swimming pools have been associated with outbreaks of infection withShigella species; Aeromonas organisms are associated with exposure to the marine environment. o Giardia, Cryptosporidium, and Entamoeba organisms are resistant to water chlorination; therefore, exposure to contaminated water should raise index of suspicion for these parasites. A history of camping suggests exposure to water sources contaminated withGiardia organisms. Travel history may indicate a cause for diarrhea. o Enterotoxigenic E coli is the leading cause of traveler's diarrhea. o Rotavirus and Shigella, Salmonella, and Campylobacter organisms are prevalent worldwide and need to be considered regardless of specific travel history. o Risk of contracting diarrhea while traveling is, by far, highest for persons traveling to Africa. o Travel to Central and South America and Eastern European countries is also associated with a relatively high risk of contracting diarrhea. o Other organisms that are prevalent in particular parts of the world include the following: Nonspecific foreign travel history - Enterotoxigenic E coli andAeromonas, Giardia, Plesiomonas, Salmonella, and Shigellaspecies Underdeveloped tropical visit -C perfringens Travel to Africa -Entamoeba species, Vibrio cholerae Travel to South America and Central America -Entamoebaspecies, V cholerae, enterotoxigenic E coli Travel to Asia -V cholerae Travel to Australia -Yersinia species Travel to Canada -Yersinia species Travel to Europe -Yersinia species Travel to India -Entamoeba species, V cholerae Travel to Japan -Vibrio parahaemolyticus Travel to Mexico -Aeromonas, Entamoeba, Plesiomonas, andYersinia species New Guinea -Clostridium species Animal exposure can contribute to diarrhea. o Exposure to young dogs or cats is associated with Campylobacterorganisms. o Exposure to turtles is associated with Salmonella organisms. Certain medical conditions predispose patients to infection, including the following: o C difficile - Hospitalization, antibiotic administration o Plesiomonas species - Liver diseases or malignancy o Salmonella species - Intestinal dysmotility, malnutrition, achlorhydria, hemolytic anemia (especially sickle cell disease), immunosuppression,malaria o Rotavirus - Hospitalization o Giardia species -Agammaglobulinemia, chronic pancreatitis, achlorhydria, cystic fibrosis o Cryptosporidia species - Immunocompromised or immunosuppressed state

Physical
The following may be observed: o o Dehydration Dehydration is the principal cause of morbidity and mortality. Assess every patient with diarrhea for signs, symptoms, and severity.

Lethargy, depressed consciousness, sunken anterior fontanel, dry mucous membranes, sunken eyes, lack of tears, poor skin turgor, and delayed capillary refill are obvious and important signs of dehydration. Table 3 below details dehydration severity and symptoms. Table 3. Dehydration Severity, Signs, and Symptoms (Open Table in a new window)
Hydration 0-5% Dehydration 5-10% Dehydration 10% or More

(Mild)

(Moderate)

(Severe)

General Eyes Tears Mouth Thirst Skin

Well Normal Present Moist Drinks normally Pinch retracts immediately

Restless Sunken Absent Dry Thirsty Pinch retracts slowly

Lethargic Very sunken Absent Very dry Drinks poorly Pinch stays folded

o o o o o o o o

Failure to thrive and malnutrition Reduced muscle and fat mass or peripheral edema may be clues to the presence of carbohydrate, fat, and/or protein malabsorption. Giardia organisms can cause intermittent diarrhea and fat malabsorption. Abdominal pain Nonspecific nonfocal abdominal pain and cramping are common with some organisms. Pain usually does not increase with palpation. With focal abdominal pain worsened by palpation, rebound tenderness, or guarding, be alert for possible complications or for another noninfectious diagnosis. Borborygmi: Significant increases in peristaltic activity can cause an audible and/or palpable increase in bowel activity. Perianal erythema Frequent stools can cause perianal skin breakdown, particularly in young children. Secondary carbohydrate malabsorption often results in acidic stools. Secondary bile acid malabsorption can result in a severe diaper dermatitis that is often characterized as a "burn."

Causes
Although infectious agents are by far the most common cause for sporadic or endemic episodes of acute diarrhea, one should not dismiss other causes that can lead to the same presentation. Causes of diarrhea with acute onset include the following: Infections Enteric infections (including food poisoning Extraintestinal infections o Drug-induced Antibiotic-associated Laxatives Antacids that contain magnesium Opiate withdrawal Other drugs o Food allergies or intolerances Cow's milk protein allergy Soy protein allergy Multiple food allergies Olestra o

Methylxanthines (caffeine, theobromine, theophylline) Disorders of digestive/absorptive processes Glucose-galactose malabsorption Sucrase-isomaltase deficiency Late-onset (adult-type) hypolactasia, resulting in lactose intolerance o Chemotherapy or radiation-induced enteritis o Surgical conditions Acute appendicitis Intussusception o Vitamin deficiencies Niacin deficiency Folate deficiency o Vitamin toxicity Vitamin C Niacin, vitamin B3 o Ingestion of heavy metals or toxins (eg, copper, tin, zinc) o Ingestion of plants (eg, hyacinths, daffodils, azalea, mistletoe, Amanitaspecies mushrooms Infectious causes of acute diarrhea in developed countries o Viruses Rotavirus - 25-40% of cases Norovirus - 10-20% of cases Calicivirus - 1-20% of cases Astrovirus - 4-9% of cases Enteric-type adenovirus - 2-4% of cases o Bacteria Campylobacter jejuni - 6-8% of cases Salmonella - 3-7% of cases E Coli - 3-5% of cases Shigella - 0-3% of cases Y enterocolitica - 1-2% of cases C difficile - 0-2% of cases Vibrio parahaemolyticus - 0-1% of cases V cholerae - Unknown Aeromonas hydrophila - 0-2% of cases o Parasites Cryptosporidium - 1-3% of cases G lamblia - 1-3% of cases o