1. Invasive Enteritis (Local Invasion)

2. Barriers to GIT infection: Stomach acidity (low pH). Mucus layer and gut motility (peristalsis)→ prevent adhesion. The glycocalyx (mucin rich layer) covers the epithelial cells surface→ entrap invading bacteria. Shedding of mucosal epithelium lining the GIT. Bile secretion prevent the growth of non-enteric bacteria and enveloped viruses. M cells (microfold) of Peyer’s patches which have a surveillance function (sampling). Normal flora of intestinal tract. Secretory IgA.

3. Establishment of Infections in the Digestive System: Changes in the defense mechanisms: o Changes in stomach acidity: Shigella species and E.coli O157:H7 (Enterohemorrhagic E. coli) are acid resistance → need low pathogenic dose. Increase of gastric pH by surgery or proton-pump inhibitors: decrease pathogenic dose of acid sensitive pathogen. e.g. Salmonella species and V. cholerae. o Alterations of normal flora; broad spectrum antibiotics. - Invasion of gut by virulent microbial strains. - Pseudomembrance colitis; Clostridium difficile.

4. N o Anatomic alterations: Obstructions of secretions flow (gallbladder stones). Surgery may create intestinal “blind loops” where there is no moving stream of intestinal contents. - Absence of flushing action of intestinal secretions will lead to bacterial overgrowth syndrome (fat malabsorption, diarrhoea, vitamins deficiency).

6. Infection and type of diarrhea SiteEtiology Secretory warty diarrhea: Copious, no tissue invasion, no blood, no pus. Small intestineV. cholerae, Enterotoxigenic E. coli, EPEC, ETEC, B. cereus (diarrheal syndrome), C. perfringens. Bloody watery diarrhea: copious, tissue invasion, few pus, blood-tinged, Ileum, colonSalmonella, Campylobacter jejuni, Yersinia. Hemorrhagic colitis: copious, bloody, no pus, no tissue invasion. ColonEHEC, EIEC Dysentery: small volume, blood, mucus, pus stool. Tissue invasion. ColonShigella, Entamoeba histolytica (no pus in the stool).

7. Dysentery Causative agents of dysentery: Entamoeba histolytica (amoebic dysentery, protozoa). Shigella dysenteriae (bacillary dysentery). Shigella dysentery: -Gram negative, non motile, non capsulated bacilli. -Four serotypes: -S. dysentery. -S. flexneri. -S. boydii. -S. sonnei. S. dysentery type 1 is the most sever.

8. -Reservoir: human colon only (no animal carriers). -Transmission: person to person fecal-oral. -Pathogenic dose: less than 200 CFU. -Incubation period: 2-3 days. Pathogenesis of Shigella dysenteriae:  Shigella resist stomach acidity and pass the small intestine to reach the colon → invade M cells → engulfed by the microphage where they multiply until they rupture → infect the epithelia and pass from cell to cell by actin polymerization → cell death and slough (shallow ulcers→ mucus+ blood in the stool).  Dying macrophages release IL-1→ neutrophils attraction (pus in stool) and marked inflammation.

9.  Shigella produce shiga toxin type I which inhibit protein synthesis → epithelial and endothelial death→ more bleeding ulcers.  If shiga toxin reach the blood: hemolytic-uremic syndrome: about 5–10 days after onset of diarrhea, oliguria, hematuria, kidney failure, thrombocytopenia and destruction of red blood cells. Symptoms: Fever, lower abdominal pain, tenesmus, small volume diarrhea bloody with mucus.

12. Hemorrhagic Colitis: Enterohemorrhagic E. coli: Reservoir: cattle; bovine feces, pork. Transmission: food (hamburger, beef burger), contaminated water and milk, person- person fecal-oral. Pathogenic dose: 10-100 CFU. Incubation period: 3-5 days. Pathogenesis:  EHEC resist stomach acidity, bind to the colon cells and multiply outside the cells, damage the cells in the same way as EPEC.  Produce verotoxin (shiga like toxin)→ inhibit protein synthesis → epithelial and endothelial death → hemorrhagic colitis (profuse bloody diarrhea, no pus cells in the stool). Shiga like exotoxins; Hemolytic-uremic syndrome. No tissue invasion so no pus cells in the stool.  Symptoms: hemorrhagic diarrhea without fever.

14. Bloody Watery Diarrhea: Salmonella, C. jejuni, Yersinia A- Campylobacter jejuni infection: Microbiology: gram negative spiral, microaerophilic bacilli. Reservoir: intestinal tracts of animals esp. poultry, cattle, sheep, pigs. Transmission: fecal-oral (direct contact), ingestion of contaminated meat (poultry), contaminate water, or unpasteurized milk. Incubation period: 3-5 days. Pathogenic dose: 500- 9000 CFU.

15. Pathogenesis: invasion and sloughing of the intestinal cells (jejunum, ilium then colon)→ pus and blood in the stool. Symptoms: fever, abdominal pain, diarrhea ranging from watery to bloody. Symptoms may resemble acute appendicitis or ulcerative colitis. Complications: 1-2 weeks after diarrhea (Ag cross reactivity)  Aseptic arthritis.  Guillian-Barr syndrome: demyelination → progressive, fairly symmetric muscle weakness

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17. B- Salmonella Enteriditis and Salmonella Typhimurium: Reservoir: -Animals: poultry; chicken, reptiles, and cattle. -Human: short term carriage. Transmission: Ingestion of infected chicken products (under cooked chicken, eggs). Fecal-oral from patients and carriers. Pathogenic dose: 10 6 – 10 8 (less in achlrohydria and in those who on antibiotics) Incubation period: 6-48 hours.

18. Pathogenesis: Invade the ileocecal epithelia, M cells and the lymphoid tissue→ multiply and produce vacuoles → cells death → watery diarrhea. Salmonella survive inside the macrophage →production of TNF & IL-8 → PMN cells infiltration prevent mesenteric lymph node and RES invasion and damage the intestinal epithelial cells→ fever, abdominal pain and bloody diarrhoea. Salmonella Typhimurium can reach the blood stream in sickle cell patients.

19. C- Yersinia enterocolitica & Y. pseudotuberculosis Microscopy and cultural characteristics: Gram negative short coccobacilli. Can grow in room temperature and refrigerator. -Invade terminal ileum→ necrotic lesions in Peyer’s patches (ileitis simulate acute appendicitis). Engulfed by dendritic cells→ mesenteric lymphadenopathy. - Occasionally cause sever typhoid like illness which is usually fatal.

20. Laboratory Diagnosis: Specimens: - Stool samples, occasionally rectal swabs. Use Cary-Blair transport media if delay ≥ 30 minutes is expected. - Macroscopic, microscopic and culture. Macroscopic: - Consistency (formed, unformed (soft) or liquid) - Color (white, yellow, brown or black) - Presence of any abnormal components (e.g. mucus or blood).

21. N Microscopy: For the presence of pus cells, RBCs and bacteria in stool. - Pus cells >50 cells/ HPF + RBCs → shigellosis. - Pus cells < 20 cells /HPF + RBCs → salmonellosis, Campylobacter, Yersinia and invasive E. coli. - Pus cells 2–5 cells / HPF + RBCs → Enterohemorrhagic E. coli. - Pus cells 2–5 cells / HPF without RBCs→ cholera, Enterotoxigenic and Enteropathogenic E. coli, and viral diarrhoea. - In amoebic dysentery the pus cells are mostly degenerated (ghost cells).

22. N Culture: Culture media: Mildly selective: MacConkey agar. Highly selective: XLD (xylose-lysine-deoxycholate). Campylobacter agar: for isolation of Campylobacter. Incubate in 37C o for 48 hours. Incubate Campylobacter agar at 42 o C and microaerophilic conditions.

23. N Identification: o E. Coli → Lactose fermenter→ yellow colonies on XLD. o Shigella, and Yersinia → non-lactose fermenters →pale colonies on XLD. o Salmonella → non-lactose fermenters → pale colonies with black dots. o Campylobacter jejuni: gram negative spiral shaped bacilli that is microaerophilic. (10% CO2, 5% O2, and 85% N2). o Yersinia: motile when grown at 25C, but not at 37C. Enterobacteriaceae family: gram negative bacilli that are oxidase negative. Can be identified by ordinary tests (oxidase, motility, indole, sugar fermentation…..) or API 20E. Serological identification and serotyping.

24. Shigella on XLD (non lactose fermenter, non H2S producer) E. coli on XLD (lactose fermenter, non H2S producer) Salmonella on XLD (non lactose fermenter, H2S producer) API test

25. Treatment of bloody diarrhea: -Rehydration, electrolyte replacement and good nutrition. -Drugs to control the hyper-motility are contraindicated→ septicemia and death. -Antibiotics: A. 3 rd generation cephalosporins (ceftriaxone or cefotaxime) given for very young infants, very old patients and immunocompromised. B. Quinolones as ciprofloxacin for adult patients.