A 32-year-old man comes to the office for a follow-up appointment. The patient recently returned from a 10-day trip to Honduras. On the fifth day of his trip, he developed malaise, anorexia, and abdominal cramps, quickly followed by watery diarrhea. The patient had 5 or 6 stools daily but no fever. He took no medications and remained hydrated by drinking bottled water and soup. The patient felt better after 2 days and has had no additional symptoms since. He has no other medical conditions. Vital signs are within normal limits and the physical examination shows no abnormalities. Which of the following was most likely involved in producing this patient's gastrointestinal symptoms?

Question

A 32-year-old man comes to the office for a follow-up appointment.  The patient recently returned from a 10-day trip to Honduras.  On the fifth day of his trip, he developed malaise, anorexia, and abdominal cramps, quickly followed by watery diarrhea.  The patient had 5 or 6 stools daily but no fever.  He took no medications and remained hydrated by drinking bottled water and soup.  The patient felt better after 2 days and has had no additional symptoms since.  He has no other medical conditions.  Vital signs are within normal limits and the physical examination shows no abnormalities.  Which of the following was most likely involved in producing this patient's gastrointestinal symptoms?

Quizplus · Accepted Answer

Enterotoxigenic Escherichia coli (ETEC), a gram-negative, motile, enteric rod, is the most common cause of self-limited "traveler's diarrhea." Patients traveling to developing regions with poor sanitation are at greatest risk. Following ingestion, ETEC colonizes and adheres to small intestine enterocytes (mediated by pili). The subsequent elaboration of plasmid-encoded heat-labile (LT) and/or heat-stable (ST) enterotoxin results in the typical manifestations of abdominal cramping, nausea/vomiting, and (occasionally) low fever. The LT enterotoxin, which resembles cholera toxin in structure and mode of action, increases intracellular cyclic AMP in gut mucosal cells by activating the stimulatory Gs membrane G protein, thereby activating adenylate cyclase. The ST enterotoxin is not inactivated by heat (likely due to its small molecular size); it causes an increase in cyclic GMP in the host cell cytoplasm by activating guanylate cyclase located on the apical membranes of host gut mucosal cells. As a result of both these enterotoxins, there is decreased reabsorption and increased secretion of sodium, water, and electrolytes, resulting in watery diarrhea. (Choice A) Endotoxin is a lipopolysaccharide found in gram-negative bacteria that is released upon cell lysis. In the bloodstream, endotoxin causes a severe inflammatory response mediated by tumor necrosis factor-alpha and interleukin-1 secreted from activated macrophages. (Choice C) Intestinal invasion is a property of gastroenteritis caused by Salmonella, Shigella, enteroinvasive E coli (EIEC), and Campylobacter jejuni, as well as the protozoan Entamoeba histolytica. Invasion frequently leads to bloody or hemorrhagic diarrhea (due to mucosal cell necrosis). (Choice D) Shiga-like toxin is produced by enterohemorrhagic E coli (EHEC) and shares many properties with Shiga toxin. It acts by inactivating the 60S ribosomal subunit in human cells, thereby inhibiting human cell protein production, leading to cell death. Patients with EHEC usually have bloody diarrhea due to mucosal cell death. (Choice E) "Stacked-brick" intestinal adhesion is characteristic of enteroaggregative E coli (EAEC). These organisms adhere to human jejunal, ileal, and colonic mucosa in an aggregative, or stacked-brick, pattern and do not invade. EAEC is implicated in persistent diarrhea in infants in developing countries and in those with advanced immunosuppression (eg, AIDS). Educational objective: Traveler's diarrhea is most frequently due to enterotoxigenic Escherichia coli. This pathogen produces plasmid-encoded, heat-labile (LT, choleragen-like) and heat-stable (ST) enterotoxins. LT activates adenylate cyclase, leading to increased intracellular cyclic AMP; ST activates guanylate cyclase leading to increased intracellular cyclic GMP. Both cause water and electrolyte loss and watery diarrhea. __________ References: Cholera-like enterotoxins and regulatory T cells. (http://www.ncbi.nlm.nih.gov/pubmed/22069660)

A 32-Year-Old Man Comes to the Office for a Follow-Up