Digestive system infections: Barriers to infection: 1-The stomach acid of a pH less than or equal to 4. 2-Shedding of mucosal epithelium lining the alimentary system. 3-A variety of local defense mechanisms; mucus formation and gut motility( Peristalsis). 4- The normal flora of intestinal tracts. 5-The glycocalyx (mucin-rich layer) of epithelial-cells surface. (Clostridium difficile produces anti-mucin toxins)

N 6-The Bile salts detergent action. 7-The secreted antimicrobial peptides. (Enterotoxigenic E.coli produces heat-labile toxin that suppress these peptides. 8-M cells of Peyer patches have surveillance function. 9-Secretory IgA.

Establishment of infectious diseases in the digestive system: The defense barriers are changed in favor of the microbe due to: 1-Anatomic alterations: A-Obstructions to the flow of intestinal secretions (gallbladder stones). B-Surgery may create intestinal “blind loops” that are isolated from the moving stream of intestinal contents. Absence of flushing action of intestinal secretions. Bacterial overgrowth syndrome; malabsorption.

N 2-Changes in stomach acidity; due to proton-pump inhibitors: -Decreased pathogenic dose results in colonization of intestinal mucosa; Example Salmonella species. -Shigella species and E.coli O157:H7 are acid resistance. 3-Alterations to the normal flora; due to broad-spectrum antibiotics. Pseudomembrane colitis; Clostridium difficile. 4-Invasion of Gut by virulent microbial strains.

Intestinal invasive diseases, inflammation and damage: 1-Invasive Enteritis, and dysentery (bloody diarrhea): A-Shigella dysenteriae infection: -Pathogenic dose: less than 200 CFU. -Reservoir: human colon only (no animal carriers). -Transmission: Fecal-Oral, Person to Person. Pathogenesis: - Endotoxin triggers inflammation. - Shiga toxin type I: Enterotoxic and cytotoxic activities. It is interfering with 60S ribosomal subunit; necrosis. -The microbe invades the M cell in the lumen of Gut.

N -Multiply inside these cells, using actin polymerization to infect neighboring epithelial cells. -Released, engulfed by intestinal macrophages. -Escape from APC, infects other epithelial cells. -Very Shallow ulceration of intestinal mucosa.

N -Enterocolitis, shigellosis (most severe form is dysentery). -Fever, lower abdominal cramps; diarrhea first watery, then bloody with mucus. -Invasive infection: shallow ulcerative Enterocolitis. -Hemolytic-Uremic syndrome. B-Entamoeba histolytica (dysentery). Microbiology: -Gram-negative short bacilli, -Nonmotile, Non-spore formers. -Enterobacteriaceae grow best on XLD. -Facultative anaerobic, non-Lactose fermenters. -Can not produce H 2 S and identify by API 20E

2-Invasive Enteritis and Hemorrhagic Colitis: Enterohemorrhagic E. coli: - Transmission: food (hamburger), milk, Fecal-Oral. - Incubation period: 3-5 days. - Reservoir: Cattle; bovine feces, pork. - Pathogenic dose: CFU. - Toxin: Verotoxin : Exotoxin - Pathogenesis: - EHEC bind to cells in the large intestinal mucosa(Caecum,Colon). - Verotoxin-Epithelial receptor interaction. - Decrease protein synthesis by interfering with 60 S ribosomal subunit.

N - Intracellular localization inside lysozyme. - Cell death; apoptosis. - Mucosal necrosis; Hemorrhagic Colitis with bloody diarrhea. - Shiga like exotoxins; Hemolytic-uremic syndrome. Microbiology: -Gram negative short bacilli. -Lactose fermenters. - Metallic green sheen on EMB medium. - Indole positive.

N 3-Invasive Enteritis and Bloody watery diarrhea: A- Campylobacter jejuni infection: Reservoir: intestinal tracts of humans, cattle, sheep, dogs, cats, and Poultry. Transmission: -Fecal-Oral (direct cont.), Ingestion of contaminated meat (poultry), contaminate water, or unpasteurized milk. Incubation period: 3-5 days. Microbiology: Gram-negative curved helical rods with polar flagella.

N - Microaerophilic ( 10% CO2, 5% O2, and 85% N2) microbe with an optima of 42˚C temp. - Humidity should be > 95%. - Resistance for Cephalothin. - Sensitive for Nalidixic acid. - Catalase and oxidase positive.

Pathogenesis of Campylobacter jejuni: Pathogenic dose: as few as 500 CFU. -The microbe invades the small and large intestinal mucosa. -Colonization of intestinal epithelial layer, engulfed by intestinal dendritic cells(DC). -DC release inflammatory mediators, chemotaxis, cellular infiltration. -Ulcerative, inflammatory lesions in the jejunum, and ileum. -Ulcerative Colitis. -Pus and RBCs in stool; Acute Enteritis (common cause of infectious diarrhea worldwide). - Traveler’s diarrhea and pseudo-appendicitis.

N n

Infective Ulcerative Colitis and dysentery: n

B-Salmonella enteriditis and Salmonella typhimurium : Reservoir: -Human: Large intestinal tracts: Carriage state. -Animals: most important: Chicken. Transmission: 1-Fecal-Oral from carrier person. 2-Ingestion of contaminated chicken products (raw chicken, eggs). Incubation period: 6-48 hours.

Pathogenesis: The Microbe invades the ileocecal region lymphoid tissue. Invasion of Lamina propria; endotoxin activity. Dendritic cell activation; production of TNF and IL-8. PMN cells chemotaxis and PG response. PG stimulate cellular cAMP of epithelial cells. Release of NaCl from intestinal epithelial cells; dehydration. PMN cells prevent mesenteric lymph node and RES invasion. Bloody watery diarrhea. Diagnosis: Clinical: abdominal symptoms and fever. Laboratory: Stool culture: similar to Salmonella typhi.

C- Listeria monocytogenes : Associated food and Transmission: -Unpasteurized milk products, undercooked meat & raw vegetables -Fresh soft cheese. -Ready-to-eat meat. Incubation period: hrs. Pathogenesis: Invasion of intestinal epithelium. Intracellular survival: Listeriolysin-O. Cell-mediated immunity. Watery bloody diarrhea. listeriolysi n host actin Division Jet formatio n