APPROACH to diarrhoea. Includes history examination

Approach to diarrhoea involves detailed history, examination, hydration assessment, identifying underlying cause, and appropriate investigations with supportive or specific treatment.

1. APPROACH TO DIARRHEA Dr S unil Pathak

2. Content Epidemiology Definition Introduction Normal Physiology Defecation History Physical examination Investigation Treatment References

3. Diarrhea Diarrhea is loosely defined as passage of abnormally liquid or unformed stools at an increased frequency . Stool weight >200 g/d Classified as A cute - <2 weeks, Persistent - 2–4 weeks, C hronic - >4 weeks.

4. Acute Persistent Chronic <2 weeks 2 -4 weeks > 4 weeks Infectious (90 %) Acute with late recovery Non infectious usually

5. Small vs Large intestinal diarrhea Features Small bowel diarrhea Large bowel diarrhea Volume Large small Color Light Dark Smell Very foul Foul Nature Watery/greasy (fat ) Mucoid Steatorrhea Present Absent Blood in stool Rare Common Pus in stools Rare Common Abdominal pain Colic(mid abdomen ) Continous (lower abdomen) Tenesmus Absent Present Urgency Absent Often present Pathogens V. cholera, E coli, viral , giardia , TB (ileum), crohns (ileum) Shigella , E histolytica , UC, rectal colitis

6. Pseudo-diarrhea -frequent passage of small volumes of stool.(<200g/day ) ( increase frequency and increase liquidity ) e.g IBS/ proctitis Fecal incontinence -involuntary discharge of rectal contents and is most often by neuromuscular disorders or structural ano -rectal problems . Overflow diarrhea- occur in nursing home patients due to fecal impaction that is readily detectable by rectal examination ( impaction + overflow)

7. EPIDEMIOLOGY-Diarrhea Worldwide, >1 billion individuals suffer one or more episodes of acute diarrhea each year . The annual economic burden to society may exceed $20 billion . Acute infectious diarrhea remains one of the most common causes of mortality in developing countries 1.8 million deaths per year.

8. I ntrinsic innervation (enteric nervous system ) : LOCAL BOSS -comprises myenteric , submucosal , and mucosal neuronal layers - modulated by interneurons through the actions of neurotransmitter amines or peptides, including Ach, VIP, opioids , NE, serotonin , ATP, and NO. Myenteric plexus regulates smooth-muscle function through intermediary pacemaker-like cells called the interstitial cells of Cajal Submucosal plexus affects secretion, absorption, and mucosal blood flow. The enteric nervous system receives input from the extrinsic nerves , but it is capable of independent control of these functions.

9. E xtrinsic innervations -ANS(modulate motor and secretory functions) The PNS convey visceral sensory pathways from and excitatory pathways to the small intestine and colon . The chief excitatory neurotransmitters ACH and substance P. The sympathetic nerve supply modulates motor functions and reaches the small intestine and colon alongside their arterial vessels . Sympathetic input to the gut is generally excitatory to sphincters and inhibitory to non- sphincteric muscle.

10. Physiology GI tract -9 L of fluid enters Colon-∼ 1 Lof residual fluid reaches Stool excretion -0.2 L/d. Colon -large capacitance and functional reserve ( recover up to four times its usual volume of 0.8 L/d)

11. SMALL-INTESTINAL MOTILITY F asting period- motility of the small intestine is characterized by a cyclical event ( MMC ) MMC- the intestinal “housekeeper ” This organized, propagated series of contractions lasts, on average, 4 min, occurs every 60–90 min, and usually involves the entire small intestine. After food ingestion, the small intestine produces irregular, mixing contractions of relatively low amplitude, except in the distal ileum where more powerful contractions occur intermittently and empty the ileum by bolus transfers.

12. Stomach and Small Bowel -Synchronized MMC in fasting - Accommodation , trituration, mixing, transit -Stomach ∼3 h -Small bowel ∼3 h - Ileal reservoir empties boluses Colon -Irregular Mixing, Fermentation, Absorption, Transit -Ascending , transverse: reservoirs -Descending : conduit -Sigmoid/rectum : volitional reservoir

13. ILEOCOLONIC STORAGE AND SALVAGE The distal ileum acts as a reservoir, emptying intermittently by bolus movements . Segmentation by haustra compartmentalizes the colon and facilitates mixing, retention of residue, and formation of solid stools. Anaerobic bacteria, in the colon are necessary for the digestion of unabsorbed carbohydrates that reach the colon even in health, thereby providing a vital source of nutrients to the mucosa . Normal colonic flora also keeps pathogens at bay by a variety of mechanisms . A scending and Transverse colon function as reservoirs (average transit time-15 h ) D escending colon acts as a conduit (average transit time-3 h).

14. COLONIC MOTILITY AND TONE Short duration or phasic contractions mix colonic contents and high-amplitude (>75 mmHg) propagated contractions ( HAPCs) are sometimes associated with mass movements through the colon O ccur approximately five times per day usually on awakening in the morning and postprandially . Increased frequency of HAPCs may result in diarrhea or urgency . It is an important cofactor in the colon’s capacitance ( volume accommodation ) and sensation.

15. COLONIC MOTILITY AFTER MEAL INGESTION Colonic phasic and tonic contractility increase for a period of ∼2 h. The initial phase (∼ 10min ) is mediated by the vagus nerve in response to mechanical distention of the stomach . The subsequent response of the colon requires caloric stimulation(e.g ., intake of at least 500 kcal) and is mediated, at least in part, by hormones (e.g., gastrin and serotonin).

16. DEFECATION Tonic contraction of the puborectalis muscle , which forms a sling around the recto-anal junction, is important to maintain continence during defecation Sacral parasympathetic nerves relax muscle , facilitating the straightening of the recto-anal angle Distention of the rectum results in transient relaxation of the internal anal sphincter via intrinsic and reflex sympathetic innervation . As sigmoid and rectal contractions, as well as straining ( Valsalva maneuver), which increases intraabdominal pressure , increase the pressure within the rectum, the rectosigmoid angle opens by >15 °. Voluntary relaxation of the external anal sphincter (striated muscle innervated by the pudendal nerve) in response to the sensation produced by distention permits the evacuation of feces. Defecation can also be delayed voluntarily by contraction of the external anal sphincter.

17. Continence is maintained by normal rectal sensation and tonic contraction of the internal anal sphincter and the puborectalis muscle which wraps around the anorectum maintaining an anorectal angle between 80° and 110°. During defecation, the pelvic floor muscles (including the puborectalis ) relax , allowing the anorectal angle to straighten by at least 15°, and the perineum descends by 1–3.5 cm. The external anal sphincter also relaxes and reduces pressure on the anal canal

18. Acute Diarrhea 90% of cases - caused by infectious agents accompanied by - Vomiting - Fever and - Abdominal pain Remaining 10 %- caused by medications, toxic ingestions, ischemia, food indiscretions, and other conditions.

19. Non infectious Medications Antibiotics, NSAID, ANTACID, LAXATIVES, anti depressant, chemo drugs Ischemic colitis GVHD Toxins OP, mushroom poisoning , arsenic

20. Toxin induced Inflammatory Presence of toxin Exudation and pus in lumen Increase electrolyte and water secretion into lumen Preformed toxin Entero toxin ( release in intestine ) Mild (only mucosa ) Moderate ( submucosa ) Severe (deeper) B. Cereus (<6 hr) S aureus (<6 hr) C. Perfringes (12 -16 hr) IP (1 -2 days ) ETEC V. CHOLERAE Rota virus Noro virus Salmonella c jejuni Yersinia enterocolitica Shigella ( shiga toxin) : HUS E histolytica (flask shape ulcer )

21. B .cereus 2 form of food poisoning Ip ( 1 -6 hr ) IP ( 6 -12 hr ) Uncooked fried rice ( chinese restaurant diarrhea ) Pudding, meat ball, dried potato Preformed toxin Toxins is formed in small intestine Vomiting predominant Diarrhea predominant Require only conservative management

22. Staph aureus Preformed toxins IP: 1-6 hr Pork,canned meat, custard Vomiting : with cramp due to preformed toxins i.e vagal stimulation Fever, hypotension: never seen Diarrhea: rare No role of antibiotics

23. Enterotoxigenic E coli MCC of Traveller diarrhea Community acquired diarhea Toxigenic diarrhea Produces heat labile toxins ; increases CAMP EHEC produces O157 :H7 ( shiga like toxin ) leads to HUS

24. Vibrio cholera Pathogenesis Toxin A : activate Camp (inhibit Na in villus cell + activate CL in crypt cell ) Toxin B : bind to toxin receptor Clinical featue : IP : 1 to 2 days Cholera gravis( severe form) Rice watery stool Loss of K and HCO3 : hypokalemia and metabolic acidosis Treatment : IV: RL DOC : doxycycline and in pregnancy: azithromycin

25. Salmonella Risk factors Clinical feature Investigation and treatment decrease stonach acid Fever(>75%): last for 4 weeks if untreated Blood culture: 40 -80 % sensitivity IBD Abd pain (30 -40%) ,cough(30%),diarrhea(25%),constipation(15%), hepatosplenomegaly (5%) >15 org /ml should be present to be culture positive Antibiotics use Rose spot(30%) Bone marrow culture : 55 to 90 % positive ( positive upto 5 days even after antibiotics use) Gi bleed(10-20%) Culture of intestinal secretions ( duodenal string test) Neurological: muttering delirium Meningitis,GBS Chronic asymptomatic carrier(1 -4%) Doc: ceftriaxone

26. Association Between Pathobiology of CA and C/F in Acute Infectious Diarrhea

27. APPROACH TO THE PATIENT Indications for evaluation include - profuse diarrhea with dehydration - grossly bloody stools - fever ≥38.5°C (≥101°F ) - duration >48 h without improvement - recent antibiotic use - new community outbreaks - associated severe abdominal pain in patients >50 years and elderly (≥70 years) or immunocompromised patients. associated with fecal leukocytes (or increased fecal levels of the leukocyte proteins, such as calprotectin ) or with gross blood.

28. Diagnosis Microbiologic analysis of the stool Cultures for bacterial and viral pathogens Immunoassays Direct inspection for ova and parasites Molecular diagnosis of pathogens in stool Microarray technologies -rapid , sensitive, specific, and cost effective diagnosis. Flexible sigmoidoscopy with biopsies C olonoscopy Abdominal computed tomography (CT) scanning

29. Fluid and electrolyte replacement are of central importance to all forms of acute diarrhea . Fluid replacement alone may suffice for mild cases. Oral sugar-electrolyte solutions -instituted promptly with severe diarrhea to limit dehydration-major cause of death . Profoundly dehydrated patients- require IV rehydration. In moderately severe nonfebrile and nonbloody diarrhea- antimotility and antisecretory agents ( loperamide can be useful adjuncts to control symptoms) while avoided with febrile dysentery

30. Febrile dysentery -ciprofloxacin (500 mg bid for 3–5 d G iardiasis – metronidazole (400mg for 5-7 d ) Immunocompromised,mechanical heart valves or recent vascular grafts or are elderly – Antibiotics Coverage Travellers diarrhea- Bismuth Subsalicylate / Rifaximin Use of ciprofloxacin, azithromycin, or rifaximin may reduce bacterial diarrhea in such travelers by 90 %.

31. Algorithm for the management of acute diarrhea.

32. CHRONIC DIARRHEA Diarrhea lasting >4 weeks most of the causes of chronic diarrhea are noninfectious

33. Secretory Causes Exogenous stimulant laxatives Chronic ethanol ingestion Other drugs and toxins Endogenous laxatives ( dihydroxy bile acids) Idiopathic secretory diarrhea or bile acid diarrhea Certain bacterial infections Bowel resection, disease, or fistula (↓ absorption) Partial bowel obstruction or fecal impaction Hormone-producing tumors (carcinoid, VIPoma , medullary cancer of thyroid, mastocytosis , gastrinoma , colorectal villous adenoma) Addison’s disease Congenital electrolyte absorption defects

34. Osmotic Causes Osmotic laxatives (Mg2+, PO4, SO4) Lactase and other disaccharide deficiencies Nonabsorbable carbohydrates (sorbitol, lactulose, polyethylene glycol) Gluten and FODMAP intolerance

35. Steatorrheal Cause Intraluminal maldigestion (pancreatic exocrine insufficiency, bacterial overgrowth, bariatric surgery, liver disease) Mucosal malabsorption (celiac sprue , Whipple’s disease, infections, abetalipoproteinemia , ischemia , drug-induced enteropathy ) Postmucosal obstruction (1° or 2° lymphatic obstruction)

36. Inflammatory Causes Idiopathic inflammatory bowel disease ( Crohn’s , chronic ulcerative colitis) Lymphocytic and collagenous colitis Immune-related mucosal disease (1° or 2° immunodeficiencies , food allergy, eosinophilic gastroenteritis, graft-versus-host disease) Infections (invasive bacteria, viruses, and parasites, Brainerd diarrhea) Radiation injury Gastrointestinal malignancies

37. Dysmotile Causes Irritable bowel syndrome (including postinfectious IBS) Visceral neuromyopathies Hyperthyroidism Drugs ( prokinetic agents) Postvagotomy

38. Iatrogenic Causes Cholecystectomy Ileal resection Bariatric surgery Vagotomy , fundoplication

39. APPROACH TO THE PATIENT: Chronic Diarrhea History -onset -duration - pattern -aggravating (especially diet) and relieving factors - stool characteristics -presence/absence of fecal incontinence -fever -weight loss -pain - certain exposures (travel, medications) common extraintestinal manifestations (skin changes, arthralgias , oral aphthous ulcers) should be noted.

40. Physical findings -Thyroid mass - W heezing -Heart murmurs - E dema - H epatomegaly - A bdominal masses -Lymphadenopathy - M ucocutaneous abnormalities - P erianal fistulas - A nal sphincter laxity

41. Physical Examination in Patients With Chronic Diarrhea 1. Are there general features to suggest malabsorption or inflammatory bowel disease (IBD) such as anemia, dermatitis herpetiformis , edema, or clubbing ? 2. Are there features to suggest underlying autonomic neuropathy or collagen-vascular disease in the pupils, orthostasis , skin, hands, or joints? 3. Is there an abdominal mass or tenderness? 4. Are there any abnormalities of rectal mucosa, rectal defects, or altered anal sphincter functions? 5 . Are there any mucocutaneous manifestations of systemic disease such as dermatitis herpetiformis (celiac disease), erythema nodosum ( ulcerative colitis ), flushing (carcinoid), or oral ulcers for IBD or celiac disease?

42. Laboratory Leukocytosis / Elevated ESR/CPR - inflammation B lood loss or nutritional deficiencies- reflects anemia Measuring IgA tissue transglutaminase antibodies – detects celiac disease Bile acid diarrhea is confirmed by a scintigraphic radiolabeled bile acid retention test

43. A- Initial management B- Evaluation

44. Treatment Lactose intolorence -chronic watery diarrhea that ceases with fasting in an otherwise healthy young adult may justify a trial of a lactose-restricted diet Giardiasis- bloating and diarrhea persisting may warrant a trial of metronidazole Bile acid malabsorption -postprandial diarrhea persisting following resection of terminal ileum and treated with cholestyramine or colesevelam Idiopathic IBDs- use of glucocorticoids or other anti-inflammatory agents Gastrinomas - PPIs M alignant carcinoid syndrome- somatostatin analogues such as octreotide M edullary carcinoma of the thyroid- prostaglandin inhibitors such as indomethacin P ancreatic enzyme replacement - pancreatic insufficiency.

45. Treatment Mild opiates- diphenoxylate or loperamide are often helpful in mild or moderate watery diarrhea Severe diarrhea - codeine or tincture of opium may be beneficial 5-HT3 receptor antagonists ( alosetron )- may relieve diarrhea and urgency in patients with IBS diarrhea For all patients with chronic diarrhea- fluid and electrolyte repletion is an important component of management Replacement of fat-soluble vitamins may also be necessary in patients with chronic steatorrhea

46. Reference Harrison’s Uptodate 2023 FA 2020

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