1. IMS : Diarrhoea By Semester 6 and Smester 7

2. Agenda of the day • Overview of diarrhoea -Ambiga and Hui Yan • Acute Diarrhoea (Acute Gastroenteritis) -Wen Jiun and Vanessa

3. Epidemiology of Diarrhoea • Leading cause of illness and death among children in developing countries. • estimated 1.3 thousand million episodes and 4 million deaths occur each year in under-fives. • Main cause of death from acute diarrhoea is dehydration. Other important causes of death are dysentery and undernutrition.

4. Definitions Acute Diarrhoea • sudden onset and lasts less than two weeks • 90% are infectious in etiology • 10% are caused by medications, toxin ingestions, and ischemia Chronic Diarrhoea • Diarrhoea which lasts for more than 4 weeks • Most of the causes are non-infectious Persistent Diarrhoea -Diarrhoea lasting between 2 to 4 weeks

5. Clinical Features • Stools • Loose • Blood stained • Offensive smell • Steatorrhea (floating, oily, difficult to flush) • Sudden onset of bowel frequency • Crampy abdominal pain • Urgency • Fever • Loss of appetite • Loss of weight

6. Classifications of Diarrhoea • Duration- ( Acute, Chronic) • Causes- ( infectious, post-infectious, drugs, endocrine, factitious) • Chronic Dirrhoea- Pathophysiologic mechanism (osmotic, secretory, inflammatory, abnormal motility)

7. Acute Diarrhoea Viral,Bacterial, Protozoa (90%) Medications Laxatives or diuretic abuse Ingestion of environmental preformed toxin such as seafood Ischemic Colitis Graft versus Host Chronic Diarrhoea Irritable Bowel Syndrome Diverticular disease Colorectal Cancer Bowel Resection Malabsorption Inflammatory Bowel Disease Celiac Disease Carcinoid tumour

8. Mechanism of Diarrhoea • Osmotic Diarrhoea • Secretory Diarrhoea • Inflammatory Diarrhoea • Abnormal Motility Diarrhoea

9. Osmotic Diarrhoea • Mechanism : -retention of water in the bowel as a result of an accumulation of non‐absorbable water‐soluble compounds -cease with fasting, discontinue oral agents • Causes : -Purgatives like magnesium sulfate or magnesium containing antacids -especially associated with excessive intake of sorbitol and mannitol. -Disaccharide intolerance -Generalized malabsorption

10. Secretory Diarrhoea • Mechanism : • Active intestinal secretion of fluid and electrolytes as well as decreased absorption. • Large volume, painless, persist with fasting • Causes : • Cholera enterotoxin, heat labile E.coli enterotoxin • Vasoactive Intestinal Peptide hormone in Verner-Morrison syndrome • Bile salts in colon following ileal resection • Laxatives like docusate sodium • Carcinoid tumours

11. Inflammatory Diarrhoea • Mechanism : -damage to the intestinal mucosal cell leading to a loss of fluid and blood -pain, fever, bleeding, inflammatory manifestations • Causes : -- Immunodeficiency patient • Infective conditions like Shigella dysentary • Inflammatory conditions • Ulcerative colitis and Crohns disease

12. Abnormal Motility Diarrhoea • Mechanism : -Increased frequency of defecation due to underlying diseases -large volume, signs of malabsorption (steatorrhoea) • Causes : • Diabetes mellitus- autonomic neuropathy • Post vagotomy • Hyperthyroid diarrhoea • Irritable Bowel Syndrome

13. ACUTE GASTROENTERITIS

14. Acute Gastroenteritis • Gastroenteritis is the inflammation of the lining of stomach, small and large intestine. • >90% of cases are infectious, although acute gastroenteritis may follow ingestion of drugs and chemical toxins (10%). • Acute gastroenteritis is common among children, elderly, and those who are immunocompromised.

15. InfectiousAgents • Acquired by • fecal-oral route via direct personal contact • ingestion of food or water contaminated with pathogens from human or animal feces • Acute infection occurs when the ingested agent overwhelms the host’s mucosal immune and non-immune (gastric acid, digestive enzymes, mucus secretion, peristalsis, and suppressive resident flora) defenses.

17. Aetiology: Causative Pathogens • Bacteria • Viral • Protozoa

18. Bacterial • Campylobacter jejuni • Salmonella sp. • Shigella • Escherichia coli • Staphylococcal enterocolitis • Bacillus cereus • Clostridium perfringens • Clostridium botulinum • Gastrointestinal tuberculosis

19. Viral Protozoa • Rotavirus • Norovirus • Adenovirus • Entamoeba histolytica • Cryptosporidium • Giardia intestinalis • Schistosomiasis

20. High Risk Groups • Travelers • Consumers of certain foods • Immunodeficient person • Daycare participants • Institutionalized person

21. 1. Travelers • Tourists to Latin America, Africa, and Asia develop “traveler's diarrhea” commonly due to enterotoxigenic Escherichia coli, Campylobacter, Shigella, and Salmonella. • Visitors to Russia may have increase risk of Giardia-associated diarrhea. • Visitors to Nepal may acquire Cyclospora. • Campers, backpackers, and swimmers in wilderness areas may become infected with Giardia.

22. 2. Consumers of Certain Food • Diarrhea closely following food consumption may suggest infection with • Salmonella or Campylobacter from chicken; • Enterohemorrhagic Escherichia coli (O157:H7) from undercooked hamburger • Bacillus aureus from fried rice • S. aureus from mayonnaise or creams • Salmonella from eggs • Vibro species, acute hepatitis A or B from (raw) seafood

23. 3. Immunodeficiency Persons • Primary immunodeficiency • IgA deficiency, common variable hypogammaglobulinemia, chronic granulomatous disease • Secondary immunodeficiency • AIDS, senescence, pharmacologic suppression

24. 4. Daycare Participants • Infections with Shigella, Giardia, Cryptosporidium, rotavirus, and other agents are very common and should be considered.

25. 5. Institutionalized Persons • Most frequent cause of nosocomial infections in many hospitals and long-term care facilities • The causes are a variety of microorganisms but most commonly Clostridium difficile.

26. Pathophysiology • Infectious agents cause diarrhoea in 3 different ways as follows: • Mucosal adherence • Mucosa Invasion • Toxin Production

27. Mucosal adherence • Bacteria adhere to specific receptors on the mucosa, e.g. adhesions at the tip of the pili or fimbriae • Mode of action: effacement of intestinal mucosa causing lesions, produce secretory diarrhoea as a result of adherence • Causing moderate watery diarrhoea • e.g. enteropathogenic E.coli

28. Mucosa Invasion • The bacteria penetrate into the intestinal mucosa, destroying the epithelial cells and causing dysentery • e.g. Shigella spp. Enteroinvasive E.coli Campylobacter spp

29. Toxin Production • Enterotoxins - toxin produced by bacteria adhere to the intestinal epithelium, induce excessive fluid secretion into the bowel lumen, results in watery diarrhoea without physically damaging the mucosa. • Some enterotoxin preformed in the food can cause vomiting • e.g Staph.aureus (enterotoxin B) Bacillus cereus Vibrio cholerae • Cytotoxins - damage the intestinal mucosa and sometimes vascular endothelium, leads to bloody diarrhoea with inflammatory cells, decreased absorptive ability. • e.g. Salmonella spp. Campylobacter spp. Enterohaemorrhagic E.coli 0157

30. Bacterial causes of watery diarrhoea and dysentery Watery diarrhoeaDysentery • Vibrio cholerae - Shigella spp • Enterotoxigenic E.coli (ETEC) - Yersinia enterocolitica • Enteropathogenic E.coli (EPEC) - Campylobacter spp • Salmonella spp. - Salmonella spp. • Clostridium difficile - Clostridium difficile • Clostridium perfringens - Enteroinvasive E.coli • Campylobacter jejuni - Enterohaemorrhagic • Bacillus cereus E.coli (EHEC) • Staphylococus aureus + profuse vomiting

31. Clinical Features • Diarrhoea • Watery • Bloody • Cramping abdominal pain • Nausea, +/- Vomiting • Fever • Loss of appetite • Lethargy • Shock

32. Investigations • FBC • U&E, BUN • Stool culture • Stool examination, microscopy for ova, cysts, parasites and fecal WBC • ELISA test ** For unresolved diarrhoea: sigmoidoscopy, rectal biopsy and radiological studies to rule out other organic causes

33. Management Aims/Goals of management: • Prevent, identify and treat dehydration • Eradicate causative pathogens • Tetracycline, Ciprofloxacin • Prevent spread by early recognition and institution of infection-control measures • immunization, chemoprophylaxis, good hygiene, improve sanitation

34. Prevent, Identify & Treat Dehydration • Moderate to severe dehydration need referral to hospital • Oral Rehydration Solution (ORS) • Glucose, Na, Cl, K, bicarbonate or citrate • encourage fluid intake e.g. salt + glucose drink to assist in co-transport of sodium into the epithelial cells via the SGLT1 protein, which enhances water and sodium re-absorption in small intestines. • IV fluids (lactate Ringer’s solution) are preferred in those with severe dehydration.

35. Chronic Diarrhea

36. Causes • Chronic Fatty Diarrhea (Diarrhea due to Malabsorption) • Chronic Inflammatory Diarrhea • Chronic Watery Diarrhea • Secretory Diarrhea • Osmotic Diarrhea • Drug-Induced Diarrhea • Infectious Diarrhea • Malignancy • Functional Diarrhea (diagnosis of exclusion) • Irritable Bowel Syndrome

37. History • Age • Diarrhea pattern • Differentiating small bowel from large bowel • Stool characteristics • Diurnal variation • Weight Loss • Medication and dietary intakes • Recent travel to undeveloped areas

38. Age • Young patients • Inflammatory Bowel Disease • Tuberculosis • Functional bowel disorder (Irritable bowel) • Older patients • Colon Cancer • Diverticulitis

39. Diarrhea pattern • Diarrhea alternates with Constipation • Colon Cancer • Laxative abuse • Diverticulitis • Functional bowel disorder (Irritable bowel) • Intermittent Diarrhea • Diverticulitis • Functional bowel disorder (Irritable bowel) • Malabsorption • Persistent Diarrhea • Inflammatory Bowel Disease • Laxative abuse

40. Differentiating small bowel from large bowel • Small intestine or proximal colon involved • Large stool Diarrhea • Abdominal cramping persists after Defecation • Distal colon involved • Small stool Diarrhea • Abdominal cramping relieved by Defecation

41. Stool characteristics • Water: Chronic Watery Diarrhea • Blood, pus or mucus: Chronic Inflammatory Diarrhea • Foul, bulky, greasy stools: Chronic Fatty Diarrhea

42. Diurnal variation • No relationship to time of day: Infectious Diarrhea • Morning Diarrhea and after meals • Gastric cause • Functional bowel disorder (e.g. irritable bowel) • Inflammatory Bowel Disease • Nocturnal Diarrhea (always organic) • Diabetic Neuropathy • Inflammatory Bowel Disease

43. Weight Loss • Despite normal appetite • Hyperthyroidism • Malabsorption • Associated with fever • Inflammatory Bowel Disease • Weight loss prior to Diarrhea onset • Pancreatic Cancer • Tuberculosis • Diabetes Mellitus • Hyperthyroidism • Malabsorption

44. Medication and dietary intakes • Drug-Induced Diarrhea • Food borne Illness • Waterborne Illness • High fructose corn syrup • Excessive Sorbitol or mannitol • Excessive coffee or other caffeine

45. Recent travel to undeveloped areas • Traveler's Diarrhea • Infectious Diarrhea

46. Colorectal Carcinoma • Colorectal carcinoma • Colorectal cancer is second commonest cancer causing death in the UK • 20,000 new cases per year in UK - 40% rectal and 60% colonic • 3% patients present with more than one tumour (=synchronous tumours) • A previous colonic neoplasm increases the risk of a second tumour (=metachronous tumour) • Some cases are hereditary • Most related to environmental factors - dietary red fat and animal fat • Adenoma - carcinoma sequence • Of all adenomas - 70% tubular, 10% villous and 20% tubulovillous • Most cancers believed to arise within pre-existing adenomas • Risk of cancer greatest in villous adenoma • Series of mutations results in epithelial changes from normality, through dysplasia to invasion • Important genes - APC, DCC, k-ras, p53.

47. Colorectal Carcinoma • Clinical presentation • Right-sided lesions present with • Iron deficiency anaemia due occult GI Blood loss • Weight loss • Right iliac fossa mass • Left-sided lesions present with • Abdominal pain • Alteration in bowel habit • Rectal bleeding • 40% of cancers present as a surgical emergency with either obstruction or perforation

48. Colorectal Carcinoma • Developed by Cuthbert Duke in 1932 for rectal cancers • Dukes staging of colorectal cancer • Stage A - Tumour confined to the mucosa • Stage B - Tumour infiltrating through muscle • Stage C - Lymph node metastases present • Five year survival - 90%, 70% and 30% for Stages A, B and C respectively

49. Chronic Inflammatory Diarrhea • Inflammatory Bowel Disease • Ulcerative Colitis • is a form of colitis, a disease of the intestine, specifically the large intestine or colon • usually present with diarrhea mixed with blood and mucus, of gradual onset • also may have signs of weight loss, and blood on rectal examination • Crohn's Disease • is an inflammatory disease which may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. • It primarily causes abdominal pain, diarrhea (which may be bloody), vomiting, or weight loss, but may also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis and inflammation of the eye • Diverticulitis

50. Drug-induced diarrhea