감염성 위장관 질환 소 화 기 내 과 권 광 안

차 례 장관내 감염 발생에서 숙주측 인자와 미생물측 인자 소장세균 과증식의 증상과 의의 콜레라의 설사 기전 차 례 장관내 감염 발생에서 숙주측 인자와 미생물측 인자 소장세균 과증식의 증상과 의의 콜레라의 설사 기전 흔히 설사를 일으킬 수 있는 세균성 질환 장독소의 정의 항생제 관련 설사의 진단과 치료

Gut mucosal barrier 1) Non-immunologc gut defense mechanism 2) gastric acid, protease, peristalsis, mucin, 3) epithelical tight junction, normal flora 4) Non-specific Immunologic gut defense mechanism 5) Secretory IgA mucosal immunity, cell-mediated immunity 6) Ag-specific Immune systems

Host factors 1] 유전과 나이 O형; 콜레라 A형; 람블 편모충증이 잘 발생 소아: 장관상피세포의 미성숙, 정상 장관총의 변화, 병원균에 노출증가 2] 위 산 위산(pH<4)은 30분 이내에 섭취된 세균의 99.9% 사멸 감수성 증가; 제산제, H2 blocker 복용자 무위산증(achlorohydria), 위장 절제술 환자  적은 접종량으로 발병 3] 장 운동성 장의 정상 연동운동 정상 장관총의 적절한 유지 병원성 세균의 체외배출에 중요 게실, 누공, afferent syndrome, 당뇨병 장 운동성의 저하로 인한 세균의 과증식은 설사를 유발 심한 경우에는 독성 거대결장( toxic megacolon)을 유발 급성 설사환자에서 지사제의 투여는 오히려 감염을 악화

Host factors 4] 정상 장관총 99.9%는 혐기성 세균 병원성 세균이 장관내에 정착하여 증식하는 것을 억제 병원성 세균이 장관내에 정착하여 증식하는 것을 억제  colonization resistance 광범위 항생제의 사용 정상 장관총의 성장을 억제  clostridium difficile, 다약제 내성 병원성 세균이 장관에 정착 증식  장염, 전신 감염 5] 장관 면역능 세포면역능과 항체 생산 AIDS 환자- 박테리아, 바이러스, 원충 감염 빈도 증가 secretory Ig A – 세균 항원, 내독소, 바이러스 등을 중화 항원에 대한 정보를 소장 말단의 장관내 림프조직의 M 세포에 전달  림프구의 증식을 유발  체내 모든 점막 조직에서 IgA-secreting plasma cell로 작용

Microbiologic factors 1] 접종량 (inoculum size) Vibrio cholerae: 105-108 개 Shigella, E.coli O157:H7, G. lambulia, Entamoeba Histolytica : 10~100개 (위산에 쉽게 사멸하지 않음 ) 2] 독소의 생산 1) 신경 독소: (1) S. aureus, Bacillus cereus: 열에 파괴되지 않음. 섭취후 곧바로 구토와 복통 유발 (2) Clostridium botulinum: 신경전달물질의 유리를 억제 마비 증상 유발 2) 장독소 콜레라 독소  cAMP 높여서 설사 유발 3) 세포독소 shigella dysenteriae type 1 이 생산하는 Shiga 독소 EHEC: Shiga독소와 유사한 세포독소(Stx1, Stx2, STx2v, etc)를 생산  이질증상과 용혈성 요독증 유발 Clostridium difficile:세포독소생산장관상피세포를 파괴설사유발

Microbiologic factors 3] 장침입 Shigella, 장침입성 대장균(EIEC), Salmonella  장관상피세포를 사멸  이질양 설사 S.typhi, S.paratypi, Yersinia enterocolitica 장관 상피세포를 통과 장관내 림프절에서 증식후 전신으로 퍼짐  발열, 복통, 비장비대, 백혈구 감소증

Esophageal infection Fungal infections Viral infections Mycobacterial infections

Esophageal infection Rare in immunocompetent persons Risk factors Reduced peristalsis, DM, scleroderma, achalasia, antibiotic use, steroids use, spread from local infection. Candidiasis Clinical features Dysphagia, odynophagia Can be a feature of AIDS Rarely fistula, stricture Combined with oral candidiasis

Esophageal infection Candia albicans Normal oral flora, most common Become pathogenic if their numbers increase or the patient is immunosuppressed Upper GI endoscopy: most sensitive diagnostic tool Management Empirical treatment Fluconazole, Nystatin for oral thrush (oropharyngeal), Amphotericin Must use azole drug for esophageal candidiasis Aspergillosis, histoplasmosis, and blastomycosis are rare  

Viral infections Herpes simplex virus 1 Both immunocompromised and healthy patients Discrete vesicles, hemorrhagic ulcerations Cytomegalovirus In immunocompromised hosts Esophageal ulcers Inclusion body Varicella-zoster virus Differential diagnosis

Viral infections Clinical features Odynophagia, hemorrhage, perforation, fistula Self limited course in immunocompetent hosts Associated with other organ involvement HSV-1 Immunocompetent host- Oral viscous lidocaine or acyclovir Immunocompromised host- IV acyclovir for 7-10 days Viral infections CMV Usually immunocompromised host Ganciclovir, foscarnet Can be difficult in differentiating from HSV esophagitis Differential diagnosis

Bacterial overgrowth syndrome 1. Etiology and pathogenesis 1) Intestinal stasis (Blind loops, bypass surgery, stricture, hypomotility) 2) Abnormal proximal connections to the colon (Fistula, resected ileocecal valve) 3) Reduced acid secretion: hypochlorhydria 4) Advanced age 5) Immune deficiency Differential diagnosis

Bacterial overgrowth syndrome 2. Consequences of bacterial overgrowth 1) Malabsorption; fats and fat soluble Vitamins, carbohydrates, proteins 2) Toxic bacterial metabolites causing mucosal damage Villous atrophy, inflammatory cells 3) Bacterial competition for ingested proteins, vitamin B12 Differential diagnosis

Bacterial overgrowth syndrome 3. Clinical features Diarrhea, weight loss Anemia, neurologic changes, osteomalacia, edema, dermatitis Differential diagnosis

Bacterial overgrowth syndrome 4. Findings on diagnostic tests 1) Microbiological studies Microbiological culture from the intestinal aspirates (Gold standard method) 105 CFU/ml in the duodenum (Diagnostic of bacterial overgrowth) Breath tests Measurement of H2 or CO2 produced by intraluminal bacterial metabolism Hydrogen breath test 14C-D-xylose test Differential diagnosis

Bacterial overgrowth syndrome 5. Management Fluid and nutritional support Antibiotics: quinolones, metronidazole, tetracycline, ampicillin Surgical corrections Differential diagnosis

Infectious diarrhea 1. 종류 Enterotoxigenic, non-invasive Vibrio cholerae Enterotoxigenic E. coli - traveler’s diarrhea Staphylococcus aureus Bacillus cereus Invasive and/or destructive Shigella Enterohemorrhagic E. coli- E.coli O157:H7 Campylobacter jejuni Yersinia enterocolitica Vibrio parahemolyticus Salmonella typhi Entameba histolytica Non-invasive, non-enterotoxigenic Giardia lamblia Differential diagnosis

Infectious diarrhea 2. Mechanisms and clinical features 1) Diarrhea induced by enterotoxin enterotoxin -> adenyl cyclase activation -> Increase in cyclic AMP -> secretion of isotonic fluid No mucosal damage Watery, voluminous, effortless diarrhea Stool WBC (-), protein (-), fever (-) 2) Invasive diarrhea Mucosal damage and destruction Not voluminous, more frequent bowel movement Abdominal pain, tenesmus, fever Stool WBC (+), blood (+), protein (+) Differential diagnosis

3. 콜레라 Infectious diarrhea 위산에 민감, 소장에서 군집화 Acute diarrheal dz, result in profound, rapidly progressive dehydration and death Vibrio cholerae : motile, facultatively anaerobic, gram-negative rod with flagella 위산에 민감, 소장에서 군집화   Cholera toxin (CTX) enterotoxin분비 A subunit B subunit 1) Clinical feature 잠복기: 24 – 48 시간 Diarrhea > 250mL/kg in 1st 24 h  hypovolemia, shock, death if not supply fluid, electroyte 2) Diagnosis 3) Treatment (1) Fluid, electrolyte supply Ringer’ lactate (2) Antibiotics: Tetracyclin Differential diagnosis

4. Campylobacter spp. Infectious diarrhea Gram (-) rod Most common pathogen of infectious diarrhea Fecal-oral route, 감염된 동물의 분비물에 오염된 물 음식이 주범, 우유, 육류 및 닭고기 두통, 근육통, 구토가 선행 또는 동반되어 설사, 복통, 열이 발생  이질 이나 급성 충수돌기염으로 오인 Incubation period 1~7 d Self-limiting course Lasting 4-10 d Diagnosis Endoscopic finding Non-specific hyperemia, hemorrhagic mucosal lesions Dark-field microscopy of fresh stool Stool culture Complications Reactive arthropathy Guillian-Barre’s syndrome Differential diagnosis

5. Salmonella spp. - Typhoid fever Infectious diarrhea 5. Salmonella spp. - Typhoid fever 1st week Rising("stepwise") fever and bacteremia. 2nd week Abdominal pain and rash (rose spots on the trunk and abdomen) 3rd week hepatosplenomegaly, intestinal bleeding and perforation may occur with secondary bacteremia and peritonitis Diagnosis of Typhoid fever Culture Blood: 1st wk 90%-> 3rd wk 50% Urine: 3-4th wk 25% Stool: after 4th wk Widal test Antibody for O, H, Vi antigen (+) at 2nd wk, or increasing tighter Affecting ileum, appendix, right colon DDx with IBD Differential diagnosis

Abdominal pain with tenesmus S. dysenteriae : m/c Infectious diarrhea 6. Shigella spp. Abdominal pain with tenesmus S. dysenteriae : m/c Invading colonic mucosa (most severe on Lt colon) No other organ invasion Incubation period< 48 hrs 갑자기 시작되는 복부경련, 설사, 발열이 특징 1~3일 경과후 대변 양이 줄고 혈성, 점액성 설사 Complications Perforation, Hemolytic Uremic Syndrome(HUS) 확진: 대변배양 균 동정 Need repeated trial PCR, serology Differential diagnosis Shigella flexneri Stool OB 양성, Stool WBC many

7. Yersinia spp. Infectious diarrhea Y. enterocolitica, Y. Pseudotuberculosis DDx with acute appendicitis ( invading ileum, Rt colon, appendix) & with CD. Often undergo operation. Mesenteric lymphadenitis Culture, serology, PCR Differential diagnosis

8. EHEC Infectious diarrhea O157: H7, major EHEC. Endemic cause of 1993, USA, Hamburger party Non-invading, but by Cytotoxin Meat, water, milk, person to person HUS, TTP, intestinal obstruction, bleeding Stool culture: before 7th day. Differential diagnosis

9. Antibiotics- associated colitis Infectious diarrhea 9. Antibiotics- associated colitis Spectrum of colitis due to antibiotics, including PMC 5-25 % in the patients with antibiotics on admission Destroyed balance with normal flola & Clostridium difficile, enterotoxin. Any type of antibiotics: clindamycin, lincomycin, cephalosporin Culture, toxin assay, colonoscpic biopsy Tx: causing anti 중단 Metronydazole 경구 Vancomycin Recurrence: 15-30% Differential diagnosis

Protozoal infections 1. Amoebiasis Entamoeba histolytica Male homosexual: major sauce Mostly asymptomatic or minor Sx Early stage: sallow ulcer ->flask shaped ulcers Mostly infecting Cecum Dx with biopsy (amoeba) Serology: high negative predictive value. Tx: Metronidazole. Differential diagnosis

Protozoal infections 2. Giardiasis G. Lamblia Tropical & subtropical. Dwelling on duodenum. causing minimal Sx. Tx; Metronidazole Albendazole Differential diagnosis

Helminthic infections 1. ascariasis A. Lumbricoides 10-15 cm in length. Invading small bowel, pulmonary circulation Intestinal bleeding, obstruction, cholangitis, incidental endoscpic finding. Dx: Stool ova. Tx: Metronidazole, albendazole Differential diagnosis

Helminthic infections 2. Anisakiasis Raw fish ingestion Mostly invade stomach mucosa GI trouble on several hours-days after ingestion or Urticaria, anaphylxis Dx: Endoscopy, Serology for A. Simplex. Tx: Endoscopic biopsy focep removal, albendazole Differential diagnosis