1. Diarrhea is a common disease in childhood that can be caused by infections, non-infectious factors, or a combination of both. Infectious causes include viruses like rotavirus and bacteria like E. coli, while non-infectious causes include improper diet, weather factors, and feeding issues. 2. The pathogenesis of infectious diarrhea involves mechanisms like enterotoxins produced by bacteria that increase intestinal fluid secretion, or viruses and bacteria that directly invade and damage the intestinal mucosa. This leads to reduced nutrient absorption and an osmotic diarrhea. 3. Clinical manifestations of diarrhea range from mild cases involving changes in stool frequency and consistency, to more severe cases accompanied by dehydration

1. Diarrhea Disease mbbs.weebly.com

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.

4. General introduction Classification Predisposing factor Etiology Pathogenesis Clinical manifestations Clinical features of several common enteritis Persistent diarrhea Diagnosis Differential Diagnosis Treatment Content

5. General introduction Concept common disease in childhood frequency and characters of stool Ages 6m~2y 50% ＜ 1y Seasons viral origins—late autumn and spring beginning bacterial origins—summer noninfectious diarrhea— every season Multiple sources and factors

6. General introduction Classification Predisposing factor Etiology Pathogenesis Clinical manifestations Clinical features of several common enteritis Persistent diarrhea Diagnosis Differential Diagnosis Treatment Content

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

8. General introduction Classification Predisposing factor Etiology Pathogenesis Clinical manifestations Clinical features of several common enteritis Persistent diarrhea Diagnosis Differential Diagnosis Treatment Content

9. Gastric acid secretion , secretion and activity of enzyme , quality and quantity of diet change quickly. Water metabolism ， tolerance of hydropenia ， easy to body fluid disorder. Nerves, endocrine, circulation, liver and renal function: not mature, easy to digestive tract function disorder. Predisposing factor-1 Development of infancy digestive system : not mature

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

11. Grow and develop , demand for nutrients , burden of the stomach and intestines , easy to indigestion. Artifical feeding: enteritis morbility 10 times higher than breast feeding. milk: nutritional ingredient destroyed milk tool: disinfection. Predisposing factor-3&4 3 4 The lower level of serum immunoglobulin, especially serum IgA located in gastrointestinal tract is smaller than others. Disorder microbial population of digestive tract resulting from using antibacterial drugs for a long time or normal microbial population have not been established in neonates.

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

14. General introduction Classification Predisposing factor Etiology Pathogenesis Clinical manifestations Clinical features of several common enteritis Persistent diarrhea Diagnosis Differential Diagnosis Treatment Content

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

17. Rotavirus Astrovirus Calicivirus: Norwalk virus, sapovirus Enterovirus: Coxsackie virus, echovirus, enteric adenovirus Coronavirus: torovirus Intraenteric infection---virus Virus 80% infantile diarrhea in cold months.

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

21. Bacillus coli enteropathogenic E. coli ………………………EPEC enterotoxigenic E. coli …………………………ETEC enteroinvasive E. coli …………………………..EIEC enterhemorrhagic E. coli ………………………EHEC enteroadherent aggregative E. coli ……………EAEC Campylobacter jejuni, Yersinia enterocolitica, others Fungi ： blastomyces albicans Protozoa (parasite) ： giardia lamblia, amebic protozoa Intraenteric infection---bacterium etc.

22. Disorder intestinal function Infect intestinal tract directly Irritation of rectum (eg. bladder infection) alteration of intestinal flora Much antibiotics used transport of carbohydrate lactase Etiology-2: extraenteric infection Pneumonia, URI, USI, otitis media, skin infection, etc.

23. Dietary factors quality and quantity of food (feeding starch and fat too early) Allergic diarrhea: milk or bean Primary and secondary disaccharidase deficiency Etiology-3: noninfectious causes Weather factors Cool enterokinesia Hot secretion of digestive juice and gastric take milk because of thirsty

24. General introduction Classification Predisposing factor Etiology Pathogenesis Clinical manifestations Clinical features of several common enteritis Persistent diarrhea Diagnosis Differential Diagnosis Treatment Content

25. Osmotic diarrhea : much poorly absorbed and hyperosmotic solute Secretory diarrhea : electrolytes hypersecretion Exudative diarrhea : inflammatory states causing liquor exudation Motility disturbance : dynamic abnormality of intestine Noninfectious diarrhea : feeding factors Pathogenesis Usually combination of several mechanisms

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

34. The RV is composed by 11 geme segments ， NSP4( 非结构蛋白 4 ） is the closeness of Pathogenesis The study progression by RV cause diarrhea

35. A 组 RV 病毒基因组功能 基因片段 : 1 2 3 4 6 9 编码 结构蛋白 : VP1 VP2 VP3 VP4 VP6 VP7 ( 核心 ) ( 核心 ) ( 核心 ) ( 外壳 ) ( 内壳 ) ( 外壳 区分 G 血清型 1-14) 裂解 抗原区分 (A-G 组 ) VP5 VP8 A 组为Ⅰ ,Ⅱ 亚群 （ P 血清型 1-44 ） 基因片段 : 5 7 8 10 11 编码 非结构蛋白 : NS53 NS34 NS35 NS28 NS26 (NSP1 NSP2 NSP3 NSP4 NSP5)

36. General introduction classification Predisposing factor Etiology Pathogenesis Clinical manifestations Clinical features of several common enteritis Persistent diarrhea Diagnosis Differential Diagnosis Treatment Content

37. Dehydration Metabolic acidosis Electrolytes disorder Digestive tract symptom Water, electrolytes and acid-base disorder Diarrhea vomit Abdominal pain Clinical manifestation

38. Mild and severe diarrhea Mild: the times of stool and character change —— stool : frequency ,loose, liquid, color: yellow or greenyellow, smell: sour flavor, shape: egg soup —— vomiting: seldom —— general poisoning symptom: without —— dehydration, electrolytes abnormality and general toxicity symptoms': none

39. Severe: accompany dehydration, electrolytes abnormality and general toxicity symptoms — digestive tract symptom : diarrhea serious ,mucus blood sample stool, anorexia, nausea, abdominal pain and abdominal distention — general poisoning symptom : lethargy, dysphoria, unconsciousness and coma — dehydration, electrolytes abnormality , acid base imbalance Mild and severe diarrhea

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

46. Vomiting and diarrhea : Alkalinity intestinal juice lost Eat :calorie , malabsorption  lipoclasis  keto-bodies Hypovolemia  pachemia  blood flow slowly  hypoxia  anaerobic glycolysis  lactic acid dehydration  blood flow  excluding acid  acid metabolic product Clinical manifestation-2: metabolic acidosis Causes:

47. Dispirited, dysphoria, drowsiness, coma Hypernea (Kussmauls breathing) ， exhalation cool Expiratory gas smells ketone Cherry lips Nausea, vomit Metabolic acidosis--clinical manifestation Mild: breath frequency slightly Severe: occur:

48. K + (potassium)<3.5mmol/L (normal: 3.5 ～ 5.5 mmol/L) causes ： Excessive losses: vomit, diarrhea. Inadequate intake. Renal function of keeping kalium ,it continues excluding kalium when with hypokalemia. Clinical manifestation-3: electrolyte disorder Hypokalemia

49. depressed Tension of skeletal muscle ， tendon reflex ， even respiratory muscle weakness Tension of smooth muscle , abdominal distention intestinal sound or disappear Myocardium excitability , arrhythmia, ECG: T-wave is low or inversion, U-wave occurs, prolonged P-R interval and Q-T interval, ST section descending. Baseosis hypokalemia Clinical manifestation: nerve and muscular excitability

50. Ca 2+ ﹤1.75mmol/L (7mg/dl) ; Mg 2+ ﹤0.6mmol/L (1.5mg/dl). Symptoms usually occur after dehydration and acidosis resolved, or fluid replacement. Clinical manifestation: thrill, tetany, convulsion. If convulsion hasn’t relieved after supplement calcium, pay attention to hypomagnesemia. hypocalcemia & hypomagnesemia

51. General introduction Classification Predisposing factor Etiology Pathogenesis Clinical manifestations Clinical features of several common enteritis Persistent diarrhea Diagnosis Differential Diagnosis Treatment Content

52. Season : cool months (autumn and winter) Age : 6m~2y Symptom : fever, vomit, mild general toxicity symptoms. Stool : frequency, amount, water; yellow-water or egg soup-like; a small amount of mucus. Dehydration : mild/moderate ， isotonic/hypertonic Complication: convulsion, myocardium damaged. Prognosis : self-limited, course: 3~8d. Viral antigen detection : from stool. Several common enteritis-1: Rotavirus enteritis ->human rotavirus (HRV)

53. Season : summer Symptom : vomit and diarrhea, no obvious general toxicity symptoms. Stool : water-like or egg soup-like, without mucus, blood or pus, no WBC (test under microscope). Dehydration : dehydration, electrolyte and acid-base disorder usually occur. Prognosis : self-limited, course: 3~7d. Several common enteritis-2: ETEC enteritis 产毒性细菌 ETEC enteritis

54. Similar with bacillary dysentery. Symptom : diarrhea with fever, nausea, vomit, abdominal pain, tenesmus. Severe general toxicity symptoms, e.g. ardent fever, consciousness change, even septic shock. Stool : with mucus, blood and pus, smell of fish, with WBC (test under microscope). Stool culture : pathogenic bacterium. Several common enteritis-3: EIEC enteritis 侵袭性细菌 EIEC enteritis

55. Pathogen : usually Blastomyces albicans. Age : ﹤2y. Complication by other infection, or after using antibiotics for long time. Persistent course , usually thrush companion. Stool : yellow thin stool, more foam with mucus, sometimes tofukasu-like. test under microscope: fungal spore and hypha. Several common enteritis-4: fungal enteritis fungal enteritis

56. General introduction Classification Predisposing factor Etiology Pathogenesis Clinical manifestations Clinical features of several common enteritis Persistent diarrhea Diagnosis Differential Diagnosis Treatment Content

57. Gastric mucosa analosis  bacterium and yeast fungus Intestinal mucosa thinner  indigestion and malabsorption Bacterium in upper small intestine  enterocyte damaged Dynamic abnormality of intestine. Using antibiotics for long time. Immune function defect  liability to agents Persistent diarrhea acute diarrhea without proper or thorough treatment. Causes:

58. vicious cycle malnutrition diarrhea Diarrhea + malnutrition: mortality 4 times higher than normal children

59. General introduction Classification Predisposing factor Etiology Pathogenesis Clinical manifestations Clinical features of several common enteritis Persistent diarrhea Diagnosis Differential Diagnosis Treatment Content

60. Not difficult According to clinical manifestation, laboratory tests and character of stool. Diagnosis + + Infectious Or Noninfectious Dehydration Degree and quality Electrolyte disturbances And Disturbance of acid-base balance

61. General introduction Classification Predisposing factor Etiology Pathogenesis Clinical manifestations Clinical features of several common enteritis Persistent diarrhea Diagnosis Differential Diagnosis Treatment Content

62. Usually ﹤6m, bloating, breast-feeding. Usually with eczema. Normal appetite, growth and developed. After cofood addition, stool turns to normal. A special type of lactose intolerance Differential diagnosis-1: physiological diarrhea

63. Epidemiology character Stool culture: a dysentery bacillus discovered Differential diagnosis-2: dysentery Bacillary dysentery Amebic dysentery Madder red jam-like stool Stool : ameba trophozoite discovered

64. Symptom : ardent fever, severe toxicity symptoms, abdominal pain and distension, vomit frequently. Stool : first, yellow thin or egg soup-like; then, red pasty or adsuki bean soup-like. X-ray of abdomen : local aerate and expansion in small intestine, intestinal wall pneumatosis. Differential diagnosis-3: necrotic enteritis

65. General introduction Classification Predisposing factor Etiology Pathogenesis Clinical manifestations Clinical features of several common enteritis Persistent diarrhea Diagnosis Differential Diagnosis Treatment Content

66. Adjust and continue feeding, not abrosia or restricting water, prevent malnutrition. Prevent and cure dehydration. Rational administration: proper antibiotics, microecosystem preparation, assist-digestive drugs, mucosa protectant, antivomit drugs. Usually disusing antidiarrheal. Strengthen nursing, symptomatic treatment, prevent complications. Fluid therapy (next week lesson) Treatment

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?

70. Answer diagnosis Acute diarrhea severe dehydration hypokalemia

71. thank you！