Lecture
15-month-old with vomiting, diarrhea, and poor appetite
Patient will present as → an 11-year-old boy who is brought to the clinic for diarrhea and vomiting. He has no fever but complains of intermittent, cramping, and abdominal pain. They just returned from a family picnic, where about two hours ago the child ate potato salad. The mother reports other family members had become ill after the meal as well.
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Causes of diarrhea may be infectious, toxic, dietary (excessive laxative use) or other GI disease. Inflammatory diarrhea (bloody diarrhea with fever) indicates an invasive organism or inflammatory bowel disease.
- Traveler's diarrhea: e-coli
- Diarrhea after a picnic and egg salad: Staphylococcus Aureus
- Diarrhea from shellfish: Vibrio cholerae
- Diarrhea from poultry or pork: Salmonella
- Diarrhea in a patient post antibiotics: C. Difficile
- Diarrhea in poorly canned home foods: C. perfringens
- Diarrhea breakout in a daycare center: Rotavirus
- Diarrhea on a Cruise Ship: Norovirus
- Diarrhea after drinking (not so) fresh mountain stream water: Giardia lamblia - incubates for 1-3 weeks, causes foul-smelling bulky stool and may wax and wane over weeks before resolving
White blood cells in stool indicate an inflammatory process
- Culture for bacterial agents, microscopy for parasites or toxin identification (E Coli or C.diff is suspected)
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 CBC and measurement of electrolytes, BUN, and creatinine.
Stool samples should be collected for microscopy, culture, fecal leukocyte testing, and, if antibiotics have been taken recently,C. difficile toxin assay.
Severe diarrhea requires fluid and electrolyte replacement to correct dehydration, electrolyte imbalance, and acidosis.
Parenteral fluids containing NaCl, KCl, and glucose are generally required. Salts to counteract acidosis (Na lactate, acetate, HCO 3 ) may be indicated if serum HCO 3 is < 15 mEq/L. An oral glucose-electrolyte solution can be given if diarrhea is not severe and nausea and vomiting are minimal. Oral and parenteral fluids are sometimes given simultaneously when water and electrolytes must be replaced in massive amounts (eg, in cholera).
Diarrhea is a symptom. When possible, the underlying disorder should be treated, but symptomatic treatment is often necessary.
Diarrhea may be decreased by
- oral loperamide 2 to 4 mg tid or qid (preferably given 30 min before meals)
- diphenoxylate 2.5 to 5 mg (tablets or liquid) tid or qid
- codeine phosphate 15 to 30 mg bid or tid
- or paregoric (camphorated opium tincture) 5 to 10 mL once/day to qid.
Because antidiarrheals may exacerbate C. difficile colitis or increase the likelihood of hemolytic-uremic syndrome in Shiga toxin-producing Escherichia coli infection, they should not be used in bloody diarrhea of unknown cause. Their use should be restricted to patients with watery diarrhea and no signs of systemic toxicity. However, there is little evidence to justify previous concerns about prolonging excretion of possible bacterial pathogens with antidiarrheals.
 Osmosis |
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Rotavirus is a non-enveloped, double-stranded, linear RNA virus that is the most common cause of severe diarrhea in infants and young children. This virus is in the family of reoviridae and contains a segmented genome of 10-12 segments. Each gene segment encodes for one protein, except segment 9, which codes for two. The RNA is surrounded by a triple icosahedral protein capsid, and viral particles are not enveloped. By five years of age, nearly every child in the word has been infected with rotavirus at least once. With each infection, immunity develops and following infections are less severe. Therefore, adults are rarely affected. The virus is transmitted via fecal-oral route and damages the lining of the small intestine, leading to villous atrophy. The incidence of disease is more common in winter months and in day care centers from increased fecal-oral contact. The disease is usually easily managed, but more than 450,000 children under five years old continue to die from rotavirus infection each year in developing countries. Public health campaigns focus on oral rehydration therapy for management of disease. |
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Norovirus is a genus of virus in the calicivirus family, which leads to acute gastroenteritis in the infected. It is the most common cause of viral gastroenteritis in the world, and disease is typically self-limited. |
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Salmonella enterica spp. is a gram negative rod that causes salmonellosis. Animals and humans can both serve as reservoirs for this bacterium; it can also be spread through uncooked poultry and raw eggs. Patients infected with Salmonella enterica have an immune responsive increase in PMNs. Symptoms of salmonellosis include GI distress, with potentially bloody diarrhea. Antibiotics are not recommended for treatment, as they prolong the carrier state. Moreover, there are no vaccines to prevent this infection, unlike Salmonella typhi. |
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Clostridium difficile is a gram-positive bacilli of the genus Clostridium, which are anaerobic, spore forming bacteria. This bacteria is known to cause severe diarrhea and other intestinal disease when the normal gut flora is killed by antibiotics, allowing proliferation of Clostridium difficile in the gut. Clostridium difficile releases two toxins that can damage the intestine. Toxin A is an enterotoxin that damages the brush border of the gut, and toxin B is a cytotoxin that induces actin depolymerization, leading to damage of the cytoskeletal structure. Together, these toxins are responsible for the inflammation and diarrhea seen in infected patients. Clostridium difficile infections almost always occur after use of broad-spectrum antibiotics like clindamycin or ampicillin. The use of antibiotics destroy the normal gut flora, allowing the gut to become overrun with C. difficile with release of large amounts of toxin. C. difficile infections are the most common cause of pseudomembranous colitis and can also lead to toxic megacolon in extreme cases. Because this bacteria is part of the normal gut flora in many patients, Clostridium difficile infection should be diagnosed via detection of toxins in the stool as opposed to culture. Treatment includes metronidazole and vancomycin. |
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Giardia lamblia is a protozoan parasite that infects the small intestine, causing giardiasis. The life cycle of Giardia begins with a cyst that is excreted in the feces of an infected individual. The cyst can survive for weeks to months, and can contaminate food or water sources. In addition to food and water sources, fecal-oral transmission can occur. This is commonly observed in day care centers or mental hospitals. where there may be poor hygiene practices. Once ingested by a host, trophozoites are released in an active state in the small intestine and undergo replication via binary fission. Colonization of the gut results in severe inflammation and villous atrophy, causing reduced absorptive capability. Symptoms of infection include bloating, flatulence and foul-smelling, fatty diarrhea. This condition is usually self-limiting but can cause prolonged symptoms in the immunocompromised. Individuals with lack of IgA are especially prone to recurring Giardia infections and can develop chronic disease. Metronidazole is the current first-line therapy for Giardia infections. |
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Clostridium perfringens is a species of the clostridia genus, a group of gram-positive, spore-forming bacteria. C. perfringens is a non motile bacillus that prefers to grow in an anaerobic environment and is capable of forming spores when in an unfavorable environment. It is known for its quick onset of disease, as it can multiply in less than a day and causes disease in skin and soft tissue, or the GI tract. This bacteria produces hydrogen and carbon dioxide as a byproduct of its replication, which results in the characteristic gas formation in tissues. C. perfringens is also known for its ability to produce multiple exotoxins. The most clinically important toxin is alpha toxin, which contains a phospholipase that is capable of destroying phospholipids. In particular, the phospholipid lecithin, which is in cell walls of RBCs, WBCs, and muscle cells, can be damaged. This produces the characteristic hemolysis and myonecrosis. The myonecrosis with accompanying gas formation is known as gas gangrene. C. perfringens produces multiple other pathogenic toxins, including heat-labile enterotoxin which causes clostridial food poisoning manifested by abdominal pain and diarrhea. The typical scenario involves meat that is kept warm for long periods of time, allowing spores to germinate and produce bacteria in a vegetative state that produce the enterotoxin. Clostridial food poisoning is rarely fatal, but gas gangrene can be rapidly lethal and lead to shock unless treated. Placement of the patient in a hyperbaric oxygen chamber can increase the oxygen content of tissues, and slow the rate of growth of bacteria. Debridement of dead tissue is essential. Antibiotics may also be useful. |
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Staphylococcus aureus is a gram-positive cocci that literally means “golden grape cluster berry” due to its clustered appearance on gram stain. It is frequently found as normal flora on the skin and nasal passages but can cause a wide range of illnesses from minor skin infections to life-threatening diseases like pneumonia, osteomyelitis, and endocarditis. Staph aureus can cause a variety of skin infections including pimples, impetigo, furuncles, cellulitis, and abscesses. It can also cause severe pneumonia. Individuals are particularly susceptible to pneumonia caused by Staph aureus following viral influenza. This bacteria can also cause disease mediated by toxins. Some strains produce the exotoxin TSST-1, which causes toxic shock syndrome. This toxin acts as a super antigen which simultaneously binds MHC II and T cell receptors causing polyclonal T cell activation. Some strains produce an enterotoxin causing food poisoning. Staph aureus food poisoning presents as a rapid onset of symptoms due to ingestion of preformed toxins. Some produce exfoliative toxin, which are proteases that cleave desmoglein-1, which can cause detachment of the granulosum and spinosum layers in the epidermis. Staph aureus can also cause a life threatening acute bacterial endocarditis and osteomyelitis. |
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Enterohemorrhagic Escherichia coli (EHEC), commonly called E. coli O157:H7 is an important cause of foodborne illness in the United States. In addition to bloody diarrhea, individuals can develop hemolytic uremic syndrome with anemia, thrombocytopenia, and acute renal failure, especially in young children and elderly persons. This bacterial strain is most commonly transmitted via the fecal-oral route and typically associated with eating contaminated ground beef in undercooked hamburgers. It is a specific serotype of E. coli. The O refers to the cell wall antigen water, while H refers to the flagella antigen. This strain may produce Shiga-like toxin, which catalytically inactivates the 60S ribosomal subunit of eukaryotic cells. This blocks mRNA translation and causes cell death in the mucosal cells of the GI tract. The toxin also enhances cytokine release, which can cause hemolytic uremic syndrome (HUS). Strains of E. coli that express Shiga-like toxins gained this ability through lysogeny, meaning infection with a prophage that contained the coding for the toxin. E. coli O157:H7 can be differentiated from other E. coli strains because it is typically non-sorbitol fermenting, whereas the majority of other E. coli strains are sorbitol fermenters. In patients, antibiotics are not part of the treatment of patients with EHEC disease and may possibly increase the risk of subsequent HUS. As toxins may be released by dead and dying bacterial cells, the risk of endotoxin release could add to the patient's already potentially lethal burden. |
Question 1 |
A 30-year old lady complains to you that she’s been having diarrhea, abdominal pain and vomiting for the past 48 hours. 8 hours prior to onset of symptoms, she ingested 3 raw eggs. Which of the following is most like responsible for her diarrhea?
Salmonella | |
Staphylococci Hint: Causes diarrhea following ingestion of improperly stored food with high salt content. | |
C. perfringens Hint: Causes diarrhea following ingestion of inadequately cooked meat, poultry, or legumes. | |
Giardia lamblia Hint: Causes diarrhea following ingestion of contaminated water. |
Question 1 Explanation:
Diarrhea following ingestion of raw eggs is most likely due to Salmonella.
Question 2 |
A 65-year old man who is being managed for lung cancer on the ward makes a complaint of a 2-day history of passage of non bloody watery stool up to 4 times per day, anorexia, cramping abdominal pain, and fever. Meanwhile he had a 10-day course of antibiotic 4 weeks ago on account of a lung infection. Which of the following is the most likely cause of his diarrhea:
Salmonella Hint: Is a cause of diarrhea following food poisoning. | |
Rotavirus Hint: Is a common cause of diarrhea in children. Less common in adults. Doesn’t occur as a result of recent use of antibiotics. | |
Clostridium difficile | |
E. coli Hint: Is a cause of diarrhea following food poisoning. |
Question 2 Explanation:
Clostridium difficile colitis results from a disturbance of the normal bacterial flora of the colon, colonization by C. difficile, and the release of toxins that cause mucosal inflammation. Antibiotic therapy is the key factor that alters the colonic flora.
Question 3 |
A 16-year old female presents to you on account of a 3-day history of passage of nonbloody watery stool up to 3 times per day with mild abdominal pain, nausea and vomiting. No history of fever. No significant findings on examination. Which of the following is most the appropriate in managing this patient?
Empirical antibiotic therapy. Hint: Not necessary as the diarrhea is likely not infectious/non inflammatory. | |
Prescribe an antidiarrheal agent. | |
Stool culture. Hint: See B for explanation | |
Stool for ova and parasite. Hint: See B for explanation |
Question 3 Explanation:
In over 90% of patients with acute non inflammatory diarrhea, the illness is mild and self-limited, responding within 5 days to simple rehydration therapy or antidiarrheal agents; diagnostic investigation is unnecessary.
Question 4 |
A 2-year old child was brought in by her mother on account of a 2-day history of profuse watery diarrhea, vomiting, anorexia and lethargy? On examination, child appears lethargic, eyes are very sunken, dry buccal mucosa, decreased skin turgor, drinks water poorly when given, capillary refill: 3s, Pulse rate: 152/min. What is the first step you would take in the management of this patient?
Oral rehydration | |
Intravenous rehydration | |
Stool culture | |
Empirical antibiotics |
Question 4 Explanation:
The first and most important step in managing a severely dehydrated patient is intravenous rehydration in order to rapidly restore circulatory volume and prevent acute kidney injury, cardiogenic shock, and even death. Be careful so as not to overhydrate the patient.
Question 5 |
Which of the following represents the composition per liter of an ideal rehydration solution for moderate dehydration?
45 mmol Na+, 20 mmol K+, 70 mmol Cl−, 100 mmol citrate, and 110 mmol glucose | |
50 mmol Na+, 30 mmol K+, 80 mmol Cl−, 10 mmol citrate, and 100 mmol glucose | |
90 mmol Na+, 20 mmol K+, 80 mmol Cl−, 10 mmol citrate, and 111 mmol glucose | |
90 mmol Na+, 30 mmol K+, 80 mmol Cl−, 20 mmol citrate, and 111 mmol glucose |
Question 5 Explanation:
Oral rehydration therapy effectively resolves most cases of pediatric gastroenteritis. The World Health Organization–recommended standard for oral rehydration therapy is 90 mmol Na+, 20 mmol K+, 80 mmol Cl−, 10 mmol citrate, and 111 mmol glucose. Among the common oral rehydration solutions used, Rehydralyte has the closest composition to the World Health Organization’s recommended formula. Pedialyte is less ideal because it contains only 45 mEq/L of sodium instead of 90 mEq/L. Although these solutions are best suited as maintenance solutions, they can satisfactorily rehydrate children who are mildly or moderately dehydrated. Clear liquids should not be given to infants with diarrhea because they have a low sodium content, a low potassium content, and a high carbohydrate content. Examples of clear liquids include apple juice, carbonated beverages, and sports beverages
Question 6 |
What is the most common bacterial cause of diarrhea in children?
Salmonella | |
Shigella | |
Campylobacter | |
Escherichia coli | |
Enterococcus |
Question 6 Explanation:
The most common cause of bacterial gastroenteritis in both children and adults is Campylobacter jejuni. Campylobacter gastroenteritis typically begins with fever and malaise, followed by nausea, vomiting, diarrhea, fever, and abdominal pain. The diarrhea is often profuse and may contain blood. The illness is self-limited, lasting less than 1 week in 60% of cases. Recurrences and chronic symptoms can develop, especially in infants. Symptoms caused by C. jejuni usually result from endotoxin production. Invasive strains also occur and produce disease. Campylobacter is treated effectively with erythromycin, although the infection is usually self-limited and clears up when it is left untreated.
Question 7 |
Which of the following infectious agents may produce bloody diarrhea in infants and children?
Shigella | |
Salmonella | |
enteroinvasive E. coli | |
all of the above |
Question 7 Explanation:
Salmonella gastroenteritis begins with watery diarrhea and is accompanied by fever and nausea. Like Campylobacter, Salmonella produces disease both by mucosal invasion and by endotoxin production, and the diarrhea may be bloody. Most cases of Salmonella gastroenteritis do not require antibiotic therapy.
Shigella gastroenteritis begins with watery diarrhea, high fever, and malaise; this is usually followed in 24 hours by tenesmus and frank dysentery. Mucosal invasion with frank ulceration and hemorrhage often occurs. Dehydration is common. Shigella gastroenteritis should be treated with azithromycin, levofloxacin, ciprofloxacin, or ceftriaxone.
E. coli gastroenteritis may occur as an enteropathic, enterohemorrhagic, enterotoxigenic, or enteroinvasive infection. Enteropathic E. coli usually produces a mild, self-limited illness. Enterohemorrhagic E. coli produces diarrhea that is initially watery and later becomes bloody. Enterotoxigenic E. coli is the most common cause of traveler’s diarrhea. Enteroinvasive E. coli invades the mucosa and produces a dysentery-like illness with bloody stool.
In infants and children, Yersinia enterocolitica may produce acute and chronic gastroenteritis and mesenteric lymphadenitis. On occasion, mesenteric lymphadenitis is extremely difficult to distinguish from acute appendicitis. Diarrhea, fever, and crampy abdominal pain are the most common presenting symptoms. Treatment is symptomatic only; antibiotic therapy is unnecessary and may actually increase the chance of hemolytic-uremic syndrome from enterohemorrhagic E. Coli infection.
Question 8 |
Which of the following statements about enterohemorrhagic E. coli O157:H7 is false?
infection is transmitted by undercooked ground beef, unpasteurized milk, and other vehicles contaminated with bovine feces Hint: See C for answer | |
outbreaks have been linked to contaminated apple cider, raw vegetables, and drinking water Hint: See C for answer | |
person-to-person transmission is uncommon in outbreaks | |
the dose necessary to cause infection is low Hint: See C for answer | |
hemolytic-uremic syndrome is a serious complication of infection Hint: See C for answer |
Question 8 Explanation:
E. coli O157:H7 infections in the United States have become more common. Outbreaks have been linked to contaminated water, apple cider, salami, yogurt, undercooked beef, and raw vegetables. Person-to-person transmission is high during outbreaks, and the infectious dose is low (approximately 100 organisms). Enterohemorrhagic E. coli infection can progress to hemolytic-uremic syndrome (especially O157:H7). Enteropathic E. coli infection is seen primarily in infants. Enterotoxigenic E. coli infection is usually brief and self-limited. This is the most common cause of traveler’s diarrhea.
Question 9 |
Which of the following is (are) a common cause(s) of antibiotic-associated diarrhea in infants and children?
ampicillin | |
clindamycin | |
amoxicillin | |
cephalosporins | |
all of the above |
Question 9 Explanation:
Diarrhea is one of the most common complications associated with antibiotic therapy. The most common cause of antibiotic-associated diarrhea is ampicillin. Amoxicillin, ampicillin, other penicillins (including β-lactamase–stable agents), cephalosporins (second- and third-generation), and clindamycin are some of the agents most frequently associated with antibiotic-associated diarrhea. These are common and generally self-limited cases, and most resolve on discontinuation of the drug. However, a pseudomembranous colitis may occasionally develop because of an overgrowth of Clostridium difficile or release of its toxin. The prognosis of severe C. difficile–induced pseudomembranous colitis is poor, with a 20% to 30% fatality rate and a 10% to 20% relapse rate. Treatment of severe cases consists of oral vancomycin or metronidazole.
Question 10 |
A 23-month-old infant is brought to the emergency department by his mother. He has had diarrhea and vomiting for the past 3 days and appears to be at least 15% dehydrated. His eyeballs are sunken, and his skin is doughy. The child has no satisfactory veins in which to place an intravenous line.
What should you do now?
attempt oral rehydration therapy Hint: See C for explanation | |
perform a venous cutdown in the ankle Hint: See C for explanation | |
begin an interosseous infusion | |
begin a subcutaneous infusion Hint: See C for explanation |
Question 10 Explanation:
In a young infant or child who presents with severe dehydration, it is often difficult to establish good intravenous access. A skull vein is a possibility, but even that is difficult. An excellent alternative is an interosseous infusion (usually placed in the tibia). A large-bore needle is used after local anesthesia has been infiltrated around the bone. This allows easy access and affords an excellent alternative to venous access.
Question 11 |
All except which of the following investigations should be performed on any child who has ongoing diarrhea and suspected severe dehydration?
urine specific gravity Hint: See D for explanation | |
stool evaluation for blood Hint: See D for explanation | |
stool evaluation for fecal leukocytes Hint: See D for explanation | |
stool cultures | |
serum electrolytes Hint: See D for explanation |
Question 11 Explanation:
The investigations that should be performed on all children who have ongoing diarrhea include urine specific gravity, stool analysis for blood, and stool analysis for fecal leukocytes. A urine specific gravity of less than 1.015 suggests adequate hydration. If a patient presents with bloody diarrhea, high fever, persistent symptoms, tenesmus, or a history of foreign travel, a stool culture and examination of the stool for ova and parasites should be performed. Routine stool culture, however, is not cost-effective. Other investigations that should be considered in a toxic child include complete blood count, serum electrolytes, and serum osmolality.
Question 12 |
A patient was treated for community acquired pneumonia with amoxicillin-clavulanate (Augmentin). On day 7 of therapy he develops fulminate diarrhea. The diarrhea is described as greenish and foul-smelling. He admits to associated abdominal cramps. Which of the following is the treatment of choice for this patient?
Metronidazole (Flagyl) | |
Diphenoxylate/atropine (Lomotil) Hint: See A for explanation | |
Clindamycin (Cleocin) | |
Ciprofloxacin (Cipro) |
Question 12 Explanation:
Patients with C. difficile colitis should be treated with Flagyl for 10-14 days following cessation of the diarrhea-inducing antibiotics.
There are 12 questions to complete.
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