Diarrhea (1/15) Flashcards
What is diarrhea?
Passage of 3+ loose/liquid stools per day
or
bowel movements more frequently than is normal for the person
What are the 3 types of enteric infections?
Watery (small intestine) = noninflammatory, due to enterotoxin/neurotoxin - Vibrio cholerae, ETEC, clostridium perfringens, Bacillus cereus, Staph aureus
Bloody (colon) = inflammatory, due to invasion of ET cells or cytotoxin – Shigella spp., Salmonella, Campylobacterjejuni, EHEC, Clostridium difficile
Enteric fever (systemic) = penetrating systemic infection, Salmonella typhi, paratyphi, Yersinia enterocolitica
What are the 3 types of toxins that cause diarrheal illness?
Enterotoxin: secreted by the organisms in the gut & don’t cause cellular injury (Vibrio cholerae, ETEC, Clostridium perfringens)
Cytotoxins = types of eterotoxins, but refers to ones that are toxic to cells (sometimes used interchangably with the above) (Shigella dysenteriae, Shiga-like toxin from EHEC)
Neurotoxin: affects CNS (Staph aureus, Bacillus cereus)
What is the relationship between inoculum size & means of transmission?
Inoculum size refers to the # of bacteria required to get diarrhea
Lower inoculum –> easier to spread person to person
If it takes more bacteria to get infection, it will be transmitted through food or water i.e. Vibrio cholerae, Salmonella (nontyphoidal) = 10^5-10^8
If it’s fewer, it will be person to person or food i.e. Shigella, Enterohemorrhagic E. coli = 10-100 organisms
What are 4 host defenses against diarrheal illness?
Normal flora (produce fatty acids, which add to acidic environment & many pathogense are pH sensitive)
Gastric acid
Intestinal motility - impaired motility allows for bacterial overgrowth
Immunity - secretory IgA, systemic IgG, IgM + cell mediated immunity
What is the pathogenic mechanism of Staph aureus enterotoxin? What type of toxin is it?
Heat-stable neurotoxin, incubation is 2-4 hours
Increases peristalsis by autonomic activation resulting in intense vomiting/diarrhea
What is the pathogenic mechanism of Bacillus cereus enterotoxin?
2 enterotoxins:
Emetic toxin = neurotoxin, heat stable, elaborated in starchy foods, incubation period 1-6 hours
Diarrhea: incubation period 10-12 hours
What is vibrio cholerae?
Looks like a sperm with a tail but instead of getting you pregnant it gives you diarrhea
Gram negative facultative bacillus with single polar flagellum
Susceptible to stomach acid so large inoculum required
Clinical presentation is variable: might be strain dependent. 75% asymptomatic, 20% abrupt watery diarrhea, 5% severe diarrhea, vomiting, dehydration. Lasts 1-3 days. No tenesmus, strain, abd pain, or fever
What are the 3 things that a strain must have to cause cholera pathogenesis?
- Cholera toxin
- TCP: toxin-coregulated pilus, a colonizing factor
- ToxR: a virulence factor, transmembrane protein that senses when it’s ok for the cholera to elaborate these toxins and adherence factors
How does the cholera toxin cause diarrhea?
Cholera toxin reaches intestinal lumen & injects it A1 subunit into the membrane. This leads to synthesis of ATP, which causes an influx of Ca, Na, K, and HCO3 into the lumen. Water follows –> dehydration syndrome/diarrhea
How is cholera treated?
Oral rehydration therapy: Best way!! Water + potassium, glucose (bc one of the glucose transporters take glucose & water simultaneously)
Also IV rehydration & doxycycline
What is Shigella?
Small non-motile gram negative rod
Very similar to E. coli, except no flagella & they are non-lactose fermenters
40 serotypes including Shigella sonnei (most cases in US), S. dysenteriae (makes Stx=shiga toxin)
Low inoculum - person to person spread
Invasion of intestinal epithelial cells –> mucosal destruction
Makes enterotoxin and Stx
Penetration beyond mucosa is rare
How does Shigella invade?
Invades the M cells - antigen presenting cells that stick out between ET cells. Shigella takes advangage of this & invades through these first. Then gets into macrophage, where it multiplies & then macrophage does apoptosis
Then the Ipa proteins invade epithelial cells & reorganize cell actin to use it to spread from cell to cell
Now the epithelium is invaded & inflamed- note that it does not become systemic
What is Stx?
Shiga Toxin- a cytotoxin
S. dysenteriae 1 produces it
It’s not necessary for virulence
Facilitates transfer of A subunit, which disrupts protein synthesis & results in destruciton of intestinal cells & villi –> decreased intestinal absorption
What are the clinical manifestations of shigella?
12 h after ingestion, bacterial multiplication begins at sm intestines –> abd pain, cramping, watery diarrhea, fever
As colon is invaded, severe lower abdominal pain + urgency, tenesmus, bloody mucoid stools
Fever resolves in a few days, illness lasts 7 days, colonic shedding lasts 1-4 weeks; you don’t need to treat with antibiotics but it’s given to decrease length of time of shedding to prevent transmission to other people
