2. Major cause of children’s(﹤5y) death in developing countries in 2002 ARI diarrhea Malaria measles AIDS Disease in perinatal stage others 18% 25% 23% 4% 5% 10% 15% WHO/UNICEF. Clinical management of acute diarrhea Sources: The world health report 2003, WHO,Geneva.

7. Causes Course Degree Infectious diarrhea: virus, bacterium, fungi, parasites Noninfectious diarrhea: diet, weather, others Acute ： <2w persistent ： 2w  2m chronic ： >2m Mild: the times of stool and character change Severe: accompany dehydration, electrolytes abnormality and general toxicity symptoms Classification

10. Predisposing factor-2 Defense system: not mature Three defense system ( ): microflora, epithelium, immunity

12. Relation between feeding and infection in infants(﹤3m) （ Howie et al 1990 ） Artificial feeding: easy to intestinal infection Pure breast milk n=95 Partial breast milk n=126 Laboratory milk n=257 p Gastrointestinal infection 2.9 % 5.1 % 15.7 % <0.001 Respiratory infection 25.6 % 24.2 % 37.0 % <0.05

13. Breast feeding Days % of total faecal micro-organisms Artificial feeding Days % of total faecal micro-organisms Bacillus bifidus Bacillus coli Bacillus faecalis 5 10 15 20 0 10 15 20 25 5 0 10 15 20 25 According to Harmsen et al., 2000 Artificial feeding: easy to disorder microbial population 0 10 20 30 40 50 60 70 80 90 100 0 10 20 30 40 50 60 70 80 90 100

15. Infectious animal Infectious human water Susceptible population food fecal - oral way Etiology-1: intraenteric infection

16. From Kapikian AZ, Chanock RM. Rotaviruses. In: Fields Virology 3rd ed. Philadelphia, PA: Lippincott-Raven; 1996:1659. Developed country Bacterium Uncertain reason Rotavirus Calicivirus Rotavirus Bacillus coli Parasite Other bacterium Adenovirus Calicivirus Astrovirus Adenovirus Astrovirus Uncertain reason Developing country Distribution of etiological agent Intraenteric infection

18. Death for rotavirus infection in children ﹤ 5y （‰） Intraenteric infection---rotavirus 0.0-0.1 0.6-0.9 1.0-1.9 2.0-3.4 0.2-0.5

19. Intraenteric infection---rotavirus 20-side body(65-75nm) Nucleus: 45-50nm Shape: wheel Life: 7m Bear acid -20℃: keep long

20. Photo Credit : F.P. Williams, U.S. Environmental Protection Agency; Adapted from Parashar et al, Emerg Inft Dis 199814(4) 561–570 Rotavirus in stool by electronmicroscop Intraenteric infection---rotavirus

26. Pathogenesis-1: enterotoxin Adenylate cyclase Intestinal juice secretion  Labile toxin （ LT ） CAMP  H 2 O, Na + , Cl - transfer into enteric cavity Stable toxin （ ST ） Guanylate cyclase GTP CGMP  ATP activate activate Volume of intestinal juice diarrhea

27. 产毒性大肠杆菌 附着到小肠粘膜上进行繁殖 在小肠上部，通过 菌毛上的粘附因子 肠毒素 不耐热肠毒素 Labile toxin, LT 耐热肠毒素 stable toxin, ST 腺苷酸环化酶 鸟苷酸环化酶 细胞内 ATP cAMP  GTP cGMP  抑制小肠绒毛上皮细胞吸收 Na + 、 Cl - 和水，并促进 Cl - 分泌 肠液中 Na + 、 Cl - 和水总量增多，超过结肠吸收限度 大量水样腹泻 激活 激活 肠毒素引起的肠炎发病机理 —— 以产毒性大肠杆菌为例

28. Pathogenesis-2: bacterium invades enteron invade Small intestine colon Enteron wall mucosa: congestion, edema, effusion, ulser and hemorrhage Poorly absorption of H 2 O and electrolyte diarrhea

29. 侵袭性细菌 在肠粘膜侵袭和繁殖 炎症改变 （充血、肿胀、炎性细胞浸润、渗出和溃疡） 水和电解质不能完全吸收 腹泻 便中 WBC, RBC 大量增加 严重中毒症状 侵袭性肠炎发病机制

30. Virus invasion Pathogenesis-3: virus infection recrement  Disacchride Poorly decomposed lactose  Osmotic diarrhea Na + transport block H 2 O  electrolyte  disaccharidase

31. 病毒性肠炎发病机理 病毒侵入小肠粘膜绒毛上皮细胞并复制 粘膜受累，绒毛被破坏 绒毛缩短 微绒毛肿胀，紊乱并脱落 线粒体、内质网膨胀 双糖酶活性下降 载体减少 消化吸收面积减少 双糖（乳糖）吸收减少 葡萄糖钠与载体结合 偶联转运吸收障碍 营养物质吸收减少 部分乳糖分解为小分子的乳酸 渗透压增加 水样腹泻

32. Pathogenesis-4: noninfectious diarrhea Food fermn mydesis Enteric osmotic pressure  Digestive function disorder Osmotic diarrhea Over-feeding, No proper dietary

33. 饮食不当引起腹泻发生机理 食物质、量不当 食物消化吸收障碍而积滞在上消化道 胃酸度下降 肠道下部细菌上移并繁殖 内源性感染 发酵、腐败 有机酸（乳酸、乙酸） 胺类 肠腔内渗透压增高 肠蠕动增强 腹泻、脱水、电解质紊乱、酸中毒 分解食物 中毒症状 肝解毒功能不全 毒素进入血循环

40. Degree Quality mild moderate Hypotonic dehydration.Na + ﹤ 130mmol/L Hypertonic dehydration.Na + ﹥150mmol/L Clinical manifestation-1: dehydration severe Isotonic dehydration.Na + :130~150mmol/L

41. Severity clinical signs of dehydration Dehydration mild moderate severe Water loss By weight Spirit Skin Mucous Anterior fontanel and eye ball Tear thirst Urine output Peripheral circulation ＜ 50ml/kg ＜ 5% Slightly dispirited slightly agitated Slightly dry Slightly dry Slightly depressed Normal slightly decreased normal 50 ～ 100ml/kg 5% ～ 10% Dispirited Agitated Dry, pale Very dry depressed Reduced increased Little or no Little cool 100 ～ 120ml/kg ＞ 10% Extremely dispirited apathy, hypnody, coma Gray mottled Parched depressed greatly No Greatly increased No urine output Cool, weak pulse, shock

42. Anuria tachypnea Anterior fontanel and eye ball Depressed No Tear Cool, weak pulse, shock Dry, pale, Gray mottled apathy ,dispirited Skin and Mocous dry Weight decrease

43. Eye socket depressed, rima oculi not closed

44. Xerocheilia, chap

45. Dehydration Same proportion loss P IF C P IF C Electrolyte loss more P hypotonic, IF+C hypertonic Cell expansion Severe Easy to shock P: plasma, IF: interstitial fluid, C: cell Isotonic P IF C Water loss more P hypertonic IF+C hypotonic Cell hydration Mild Thirsty Acute diarrhea after vomiting greatly Hypotonic Hypertonic

68. Emphasis Etiology (in/ex/no) Pathogenesis (4+ex/b/v/no) Clinical manifestation Diagnosis Differential Diagnosis (p/d/n) Treatment Predisposing (4)

69. Case example An 8 – month boy had diarrhea and vomited for 3 days, urine stream reduced, irritability. PE: Pulse rate 150/min, weight loss was 10%, blood pressure 65/40mmHg, skin color showed grey and skin turgor looked like tents. Mucous membranes were very dry; eye ball was sunken greatly, anterior fontanel depressed greatly. Abdomen distended, bowel sound diminished. Questions: 1.What is the diagnosis? 2.How to administer the fluid therapy?

71. thank you！