INFANTILE DIARRHEA

1. INFANTILE DIARRHEA INFANTILE DIARRHEA CHCUMS DIVISION OF INFECTIOUS DISEASE AND GASTROENTEROLOGY

2. Background • Diarrhea is a clinical syndrome of diverse etiology associated with many influencing factors. • It is the most frequent childhood disease second only to the respiratory infection. • The major cause of death among world’s children and the number one killer of children under five in many developing countries.

3. Disease Burden Worldwide • 3-5 billion episodes/year • 4-5 million deaths/year Children are the predominant populations. • 3.2 billion episodes/year in <5y children • 1.3 million deaths/year in <5y children In China • 836 million episodes of diarrhea every year • 1/4-1/3 of all outdoor patients and a large amount of hospitalizations of children are due to diarrhea

4. Definition In pediatrics, diarrhea is defined as an increase in the Fluidity Volume Number of stools relative to the usual habits of each individual

5. Normal Stool of Children Breastfed babies:pass stools 3-4 times a day yellow loose (soft to runny) but textured sweet-smelling Bottlefed babies:once a day pale yellow or yellowish-brown bulkier and more formed pretty pungent Babies on solids:thicken and darken slightly have a stronger odor

6. Mortality Why diarrhea is more dangerous for children ? Dehydration Malnutrition

7. Malnutrition and Child Mortality

8. If: Diarrhea + Malnutrition TheRISKofDEATHis4 foldhigher thanthat of well nourished children

9. Why children are highly vulnerable to diarrhea? Immature digestive system More nutrition demand Weakness of defense system The normal intestinal flora have not built up well Bottle feeding

10. Etiology of Diarrhea

11. Etiology of Diarrhea Non infective Infective Allergic Symptomatic InappropriatefeedingFoodintoleranceClimate Viruses Bacteria Parasites Fungi

12. Viral Enteropathogens Viral enteropathogens cause most illnesses in pediatric population. • Rotavirus(morn than 50% acute diarrhea) • Astrovirus • Norwalk virus • Coronavirus • Calicivirus • Enteric adenovirus (serotypes 40 and 41)

13. Rotavirus

14. Bacterial Enteropathogens The most common cause of childhood diarrhea second only to the viral enteropathogens • Escherichia coli EPEC; ETEC; EITC; EHEC; EAEC • Campylobacter jejuni • Shigella species • Salmonella typhimurium • Yersinia enterocolitica • Staphylococcus aureus • Clostridium difficile • Vibrio cholerae

15. Parasites Pathogens Rare etiologic pathogen of diarrhea • Cryptosporidium parvum • Entamoeba histolytic • Giardia lamblia

16. Fungous Pathogens Rare etiologic pathogen of diarrhea • Candida albicans • Aspergillus • Mucor

17. The most important infective causes of acute diarrhea in developing countries in children are: • Rotavirus • Enterotoxigenic escherichia coli • Shigella • Campylobacter jejuni • Salmonella typhimurium

18. Etiology of Diarrhea Non infective Infective Allergic Symptomatic InappropriatefeedinglactoseintoleranceClimate Viruses Bacteria Parasites Fungi

19. Dietary Diarrhea Inappropriate feeding: • Overfeeding • Indigestible diet • Sudden change of formula • Inappropriate feeding for a milk-fed baby shifting into solid food (too much, too early, too rapid…)

20. Allergic Diarrhea Primary food hypersensitivity:3 months after birth Second food hypersensitivity: Infection→ injury and hyperpermeability of intestinal mucosa →large molecular protein entering bloodstream →allergic state • Cow's milk protein • Soy bean protein • Egg white • peanuts, meat, and fish etc.

21. Symptomatic Diarrhea • Diarrhea is only one of the symptoms of primary disease. Problem is not originally located in intestinal tract. • Respiratory tract infection • Otitis media • Some infectious diseases, etc. • Always be mild, and recover with the primary disease getting better • The younger the children, the more chance to get a symptomatic diarrhea accompanied by other diseases.

22. Lack of Disaccharidase LactoseIntolerance Primary Disaccharidase Deficiency is a rare disease (congenital defects of carbohydrate hydrolysis). Second Diaccharidase Deficiency: Rotavirus infection→ Injures the enterocytes of villi → Transient disaccharidase deficiency → Malabsorption of lactose in the milk →Typical loose and watery stools

23. Climate • Seasonal variationaffects the digestive function of small children : incidence of diarrhea is highest during the early raniny season • Cold weathercauses increasing of enterokinesia • Hot weathercauses decreasing of digestive enzyme and malfunction of digestive tract ……

24. Pathophysiological Mechanisms of Diarrhea

25. Pathophysiological Mechanisms of Diarrhea • Virus Diarrhea- Rotavirus • Enterotoxigenic Enteritis – • ETEC, Vibrio Cholerae • Entero-Invasive Organisms – • Shigella Species, EIEC • Dietary Diarrhea

26. Pathogenesis of Virus Diarrhea Rotavirus Virus invades the absorptive enterocytes of villi but spares crypt cells The viruses replicates and infected enterocytes are destroyed

27. Pathogenesis of Virus Diarrhea OsmoticDiarrhea • 1- Infected absorptive enterocytes are killed causing patchy epithelial cell destruction and villous shortening • 2- Destroyed absorptive cells are rapidly replaced by cells that migrate from the crypts. • Villi become covered with immature non-absorptive secretory cells having: • - no brush border • - no brush border enzymes

28. Pathogenesis of Virus Diarrhea(Osmotic Diarrhea) Rotaviruses attach and replicate in the mature enterocytes at the tips of small intestinal villi Destroy villus tip cells, variable degrees of villus blunting mononuclear inflammatory infiltrate in the lamina propria Impairment of absorptive functions the transport of water and electrolytes via glucose and amino acid co-transporters Impairment of digestive functions discreasing hydrolysis of disaccharides Malabsorption of complex carbohydrates, particularly lactose An imbalance in the ratio of intestinal fluid absorption to secretion Other than degested into monosaccharide, lactose be lysis into organic acid, hyperosmosis Watery stool

29. Pathophysiological Mechanisms of Diarrhea • Virus Diarrhea- Rotavirus • Enterotoxigenic enteritis – • ETEC, Vibrio Cholerae • Entero-Invasive Organisms – • Shigella Species, EIEC • Dietary diarrhea

30. Pathogens: Vibrio cholerae (cholera) ETEC Staphylococcus aureus Clostridium difficile Pathogenesis of EnterotoxigenicDiarrhea

31. Pathogenesis of Enterotoxigenic Diarrhea (Secretory Diarrhea) Ingestion small bowel mucosa and proliferate enterotoxigenic organisms Heat-labile enterotoxin Heat-stable enterotoxin binds to receptors of epithelial cells activates cellularguanylatecyclase activates cellular adenylcyclase increased intracellular concentrations of cAMP increased intracellular concentrations of cGMP promote the net secretion of water and chloride decrease absorption of sodium and chloride by villous cells Secretorydiarrhea

32. --- +++ Pathogenesis of Enterotoxigenic Diarrhea (Secretory Diarrhea) 1 1- Enterotoxigenic Bacteria secrete Enterotoxins 2- Toxin stimulates the production of C-AMP Increased C-AMP leads to : 3 - Inhibition of absorption of Na and Cl from the cells of villi 4 - Stimulation of secretion of Cl from crypt cells 1 2 3 3 4 2 4

33. Pathogenesis of Enterotoxigenic Diarrhea (Secretory Diarrhea) The mucosa is not destroyed during this process

34. An imbalance in the ratio of intestinal fluid absorption to secretion, so watery stool may occur in clinical observation Pathogenesis of Enterotoxigenic Diarrhea (Secretory Diarrhea)

35. Clinical finding: Watery diarrhea and vomiting develop after an incubation period of 6 hr- 5 days(2-3days, average) Low-grade fever occurs in some children Profuse, painless, watery diarrhea, sometimes with flecks of mucus but no blood Fluid and electrolyte losses, tachycardia, tachypnea, a sunken anterior fontanel, progress to circulatory collapse EnterotoxigenicDiarrhea

36. Pathophysiological Mechanisms of Diarrhea • Virus Diarrhea- Rotavirus • Enterotoxigenic enteritis – • ETEC, Vibrio Cholerae • Entero-Invasive Organisms – • Shigella Species, EIEC • Dietary diarrhea

37. Invasive Diarrhea The central event in pathogenesis is invasion of colonic mucosa • Entero-Invasive Organisms: • Shigella species • EIEC (enteroinvasive E. coli) • Campylobacter jejuni • Salmonella typhimurium • Yersinia enterocolitica

38. Pathogenesis of Invasive Diarrhea Ingestion Gut lumen Colon and rectum mucous membrane proper Invasive enteropathogen Extensive destruction of the epithelial layer Inflammation: Hyperemia, swelling, heavy neutrophil infiltration, inflammatory exudate The desquamation, ulceration, and formation of microabscesses in the colonic mucosa inhibit absorption of water stools that are frequent and scanty and that contain bloodinflammatory cells and mucus

39. Pathogenesis of Invasive Diarrhea

40. Invasive Diarrhea • Clinical finding: • Stools that are frequent and scanty and that contain blood inflammatory cells, and mucus • Stool examination: large amount of WBC, pus cell , and RBC • Dehydration and electrolyte disturbances are less frequent because of less loss of digestive fluid

41. Pathophysiological Mechanisms of Diarrhea • Virus Diarrhea- Rotavirus • Enterotoxigenic enteritis – • ETEC, Vibrio Cholerae • Entero-Invasive Organisms – • Shigella Species, EIEC • Dietary diarrhea

42. Pathogenesis of Dietary Diarrhea Dyspepsia Inappropriate diet Indigested food accumulate in the upper part of intestine Acidity decreasing Give the chance to the bacteria which lived in lower part of bowel coming up Endogenous infection Indigested foodferment and putrescence Decomposed product amineslactic acidacetic acid Aggravate the intestinal function disturbance Hyperosmosis Irritates the bowel Promote the peristalsis Water entering the lumen Diarrhea

43. Morphology of Intestinal Mucosa

44. Morphology of Intestinal Mucosa Villi covered mainly (90%) by tall columnar absorptive cells(Enterocytes) having a micrevillar brush border Crypts of lieberkuhn Covered mainly by short columnar secretory cells Goblet cells without brush border

45. Defense Barriers of the Enterocytes 3 1 2 1. Physical barrier: mucus 2. Bacteriological (flora) 3. Immunological: Secretory IgA

46. Normal Flora Breast-fed: A Gram-positive population: Bifidobacteria and Lactobacilli Bottle-fed: A Gram-negative flora: Enterobacteriaceae

47. Clinical Manifestations

48. Clinical manifestations • Gastrointestinal symptom • Systemic symptom • Dehydration and electrolyte disturbances

49. Assessment of a child with dehydration & electrolyte disturbances

50. Dehydration Excessive loss of water, especially loss of extracellular fluid.