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1 By Semester 6 and Smester 7 IMS : DiarrhoeaBy 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 Chronic Diarrhoea Persistent Diarrhoea sudden onset and lasts less than two weeks90% are infectious in etiology10% are caused by medications, toxin ingestions, and ischemiaChronic DiarrhoeaDiarrhoea which lasts for more than 4 weeksMost of the causes are non-infectiousPersistent Diarrhoea-Diarrhoea lasting between 2 to 4 weeks
5 Clinical Features Stools Sudden onset of bowel frequency LooseBlood stainedOffensive smellSteatorrhea (floating, oily, difficult to flush)Sudden onset of bowel frequencyCrampy abdominal painUrgencyFeverLoss of appetiteLoss of weight
7 Acute DiarrhoeaViral,Bacterial,Protozoa (90%)MedicationsLaxatives or diuretic abuseIngestion of environmental preformed toxin such as seafoodIschemic ColitisGraft versus HostChronic DiarrhoeaIrritable Bowel SyndromeDiverticular diseaseColorectal CancerBowel ResectionMalabsorptionInflammatory Bowel DiseaseCeliac DiseaseCarcinoid tumour
8 Mechanism of Diarrhoea Osmotic DiarrhoeaSecretory DiarrhoeaInflammatory DiarrhoeaAbnormal Motility Diarrhoea
9 Osmotic Diarrhoea Mechanism : Causes : -retention of water in the bowel as a result of an accumulation of non‐absorbable water‐soluble compounds-cease with fasting, discontinue oral agentsCauses :-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 : Causes : Active intestinal secretion of fluid and electrolytes as well as decreased absorption.Large volume, painless, persist with fastingCauses :Cholera enterotoxin, heat labile E.coli enterotoxinVasoactive Intestinal Peptide hormone in Verner-Morrison syndromeBile salts in colon following ileal resectionLaxatives like docusate sodiumCarcinoid tumours
11 Inflammatory Diarrhoea Mechanism :-damage to the intestinal mucosal cell leading to a loss of fluid and blood-pain, fever, bleeding, inflammatory manifestationsCauses :-- Immunodeficiency patientInfective conditions like Shigella dysentaryInflammatory conditionsUlcerative 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 neuropathyPost vagotomyHyperthyroid diarrhoeaIrritable Bowel Syndrome
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 Infectious Agents Acquired by fecal-oral route via direct personal contactingestion of food or water contaminated with pathogens from human or animal fecesAcute 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.
20 High Risk Groups Travelers Consumers of certain foods Immunodeficient personDaycare participantsInstitutionalized person
21 1. TravelersTourists 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 withSalmonella or Campylobacter from chicken;Enterohemorrhagic Escherichia coli (O157:H7) from undercooked hamburgerBacillus aureus from fried riceS. aureus from mayonnaise or creamsSalmonella from eggsVibro species, acute hepatitis A or B from (raw) seafood
24 4. Daycare ParticipantsInfections 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 facilitiesThe causes are a variety of microorganisms but most commonly Clostridium difficile.
26 PathophysiologyInfectious agents cause diarrhoea in 3 different ways as follows:Mucosal adherenceMucosa InvasionToxin Production
27 Mucosal adherenceBacteria adhere to specific receptors on the mucosa, e.g. adhesions at the tip of the pili or fimbriaeMode of action: effacement of intestinal mucosa causing lesions, produce secretory diarrhoea as a result of adherenceCausing moderate watery diarrhoeae.g. enteropathogenic E.coli
28 Mucosa InvasionThe bacteria penetrate into the intestinal mucosa, destroying the epithelial cells and causing dysenterye.g. Shigella spp.Enteroinvasive E.coliCampylobacter 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 vomitinge.g Staph.aureus (enterotoxin B)Bacillus cereusVibrio choleraeCytotoxins- 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
31 Clinical Features Diarrhoea Cramping abdominal pain WateryBloodyCramping abdominal painNausea, +/- VomitingFeverLoss of appetiteLethargyShock
32 Investigations FBC U&E, BUN Stool culture Stool examination, microscopy for ova, cysts, parasites and fecal WBCELISA 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 dehydrationEradicate causative pathogensTetracycline, CiprofloxacinPrevent spread by early recognition and institution of infection-control measuresimmunization, chemoprophylaxis, good hygiene, improve sanitation
34 Prevent, Identify & Treat Dehydration Moderate to severe dehydration need referral to hospitalOral Rehydration Solution (ORS)Glucose, Na, Cl, K, bicarbonate or citrateencourage 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.
40 Differentiating small bowel from large bowel Small intestine or proximal colon involvedLarge stool DiarrheaAbdominal cramping persists after DefecationDistal colon involvedSmall stool DiarrheaAbdominal cramping relieved by Defecation
41 Stool characteristics Water: Chronic Watery DiarrheaBlood, pus or mucus: Chronic Inflammatory DiarrheaFoul, bulky, greasy stools: Chronic Fatty Diarrhea
42 Diurnal variation No relationship to time of day: Infectious Diarrhea Morning Diarrhea and after mealsGastric causeFunctional bowel disorder (e.g. irritable bowel)Inflammatory Bowel DiseaseNocturnal Diarrhea (always organic)Diabetic Neuropathy
43 Weight Loss Despite normal appetite Associated with fever HyperthyroidismMalabsorptionAssociated with feverInflammatory Bowel DiseaseWeight loss prior to Diarrhea onsetPancreatic CancerTuberculosisDiabetes Mellitus
44 Medication and dietary intakes Drug-Induced DiarrheaFood borne IllnessWaterborne IllnessHigh fructose corn syrupExcessive Sorbitol or mannitolExcessive coffee or other caffeine
45 Recent travel to undeveloped areas Traveler's DiarrheaInfectious Diarrhea
46 Colorectal Carcinoma Colorectal carcinoma Adenoma - carcinoma sequence Colorectal cancer is second commonest cancer causing death in the UK20,000 new cases per year in UK - 40% rectal and 60% colonic3% 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 hereditaryMost related to environmental factors - dietary red fat and animal fatAdenoma - carcinoma sequenceOf all adenomas - 70% tubular, 10% villous and 20% tubulovillousMost cancers believed to arise within pre-existing adenomasRisk of cancer greatest in villous adenomaSeries of mutations results in epithelial changes from normality, through dysplasia to invasionImportant genes - APC, DCC, k-ras, p53.
47 Colorectal Carcinoma Clinical presentation Right-sided lesions present withIron deficiency anaemia due occult GI Blood lossWeight lossRight iliac fossa massLeft-sided lesions present withAbdominal painAlteration in bowel habitRectal bleeding40% of cancers present as a surgical emergency with either obstruction or perforation
48 Colorectal CarcinomaDeveloped by Cuthbert Duke in 1932 for rectal cancersDukes staging of colorectal cancerStage A - Tumour confined to the mucosaStage B - Tumour infiltrating through muscleStage C - Lymph node metastases presentFive year survival - 90%, 70% and 30% for Stages A, B and C respectively
49 Chronic Inflammatory Diarrhea Inflammatory Bowel DiseaseUlcerative Colitisis a form of colitis, a disease of the intestine, specifically the large intestine or colonusually present with diarrhea mixed with blood and mucus, of gradual onsetalso may have signs of weight loss, and blood on rectal examinationCrohn's Diseaseis 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 eyeDiverticulitis
54 MedicationMechanismAntineoplasticsExudative diarrhea (protein losing enteropathy)NSAIDSLymphocytic or collagenous colitisAlpha-glucosidase inhibitorMalabsorption of carbohydrates (osmotic diarrhea)Lipase inhibitors (Orlistat)Malabsorption of fat (steatorrhea)
55 Antibiotic-induced diarrhea unexplained onset of diarrhea that occurs with the administration of any antibioticdue to disruption of normal intestinal flora, which leads toeither proliferation of pathogenic microorganisms or impairment of the metabolic functions of the microflora
57 Simple antibiotic associated diarrhea disturbance in the normal colonic flora, leading to impaired fermentation of carbohydrates and osmotic diarrheareduced production of short-chain fatty acids which by reducing colonic absorption of fluid causes secretory diarrheareduced digestion of bile salts by normal colonic flora and the resultant increased colonic concentration can stimulate secretion of fluid by the colon and cause a secretory diarrhea
58 Occurs in dose-related fashion more common in drugs given orally rather than parenterally, except with drugs excreted in the bilegenerally resolves within days of discontinuing the offending antibiotictypically have a larger impact on anaerobic bacteria in the normal fecal flora
59 Common antibiotics involved ClindamycinAmpicillinAmoxicillin-clavulanateCefiximeCephalosporinsFluoroquinolonesAzithromycinClarithromycin,ErythromycinTetracyclines
60 Erythromycin induced diarrhea Caused by erythromycinIncreased motility through stimulation of motilin receptors
61 Clostridium difficile associated diarrhea (CDAD) not dose relatedsymptoms can last weeks to months after the offending antibiotic has been discontinued,often until treatment for the infection is administered
62 disturbance in the normal flora of the colon antibiotic therapydisturbance in the normal flora of the coloncolonization of the individual by theorganism (faecal-oral route)majorityasymptomaticSymptomatic(1st day of antibiotic to 6 weeks after stopping the drug)
63 Common antibiotics involved ClindamycinAmpicillinAmoxicillinQuinolonesCephalosporins
64 Clostridium difficile gram-positive bacillusspore-former, allowing it to survive under harsh conditions and during antibiotic therapydevelopment of infection caused by Clostridium difficile involves several steps
65 Clostridium difficile demonstrate production of 2 toxins Toxin A – bind to specific receptors in the brush border of the intestinal epitheliumToxin B – site of binding has not yet been described
66 Release of inflammatory mediators & cytokines Toxin A & BRelease of inflammatory mediators & cytokinesChemotaxis of inflammatory cellsIncreased fluid secretion by the epitheliumPatchy necrosis with production of an exudate composed fibrin and neutrophilsPseudomembrane fomation(necrotic cellular debris, fibrin, mucin & leucocytes)
67 Contributing factors to CDAD Host susceptibility to infectionVirulence of the infecting strainType of antibiotic usedTiming of exposure
69 Clinical features Lethargy Abdominal pain Nausea Anorexia Water diarrheaLow-grade feverPeripheral leucocytosisPseudomembranous colitis – more profuse diarrhea, occult bleeding, high fever.
70 Fulminant colitis1-3% of patients with Clostridium difficile infectionPresentation –severe abdominal pain, distension, high fever, marked leucocytosisComplications – colonic perforation, toxic megacolon
71 Diagnosis of Clostridium difficile infection Tissue culture assay for toxin BELISA for toxin A/BLatex agglutination assays (detect enzyme glutamate dehydrogenase)
72 Treatment of CDAD Discontinuation of the offending antibiotic Supportive fluids and electrolytes replacementEnteric isolation precautionsAviod antiperistaltic agents and opiates
73 Antibiotic is indicated for moderate to severe cases 1st line : Vancomycin 125mg qds andmetronidazole 250mg tds orbacitracin 25,000 units qdsParenteral metronidazole 500mg qds may be used if oral agents are not tolerated
74 Used of probiotics in recurrent relapses of Clostridium difficile infection Saccharomyces boulardii 1g od during concurrent antibiotic treatment
83 Neuroendocrine tumours of pancreas Zollinger Ellison syndromeSevere peptic ulcerationGastric acid hypersecretionNon beta cell islet tumour of pancreas (gastrinoma)
84 Gastrinoma Increase gastrin levels Increase acid production by parietal cells of stomachSmall intestine pH low &acidicPancreatic lipase inactivated, bile acids precipitatedDiarrhoea & steatorrhoeaTreatment: High dose proton pump inhibitors
85 VIPoma Vasoactive intestinal peptide (VIP) Stimulate adenyl cyclase in enterocytes (stimulate secretion of water and electrolytes)Secretory diarrhoeaClinical syndrome: watery diarrhoea, hypokalemia, metabolic acidosis
86 SomatostatinomaFunction of somatostatin: suppress GI hormones, pancreatic hormones, pancreatic enzymesIncrease levels of somatostatinDiabetes mellitus and diarrhoea/steatorrhoea
87 Investigations Treatment Fasting blood sample for: ~ Chromogranin A ~ Hormones ( gastrin, VIP, somatostatin)Ultrasound scan, CT, MRI to look for tumoursTreatmentSurgically resect solitary tumoursSomatostatin analogue (Octreotide)
88 Carcinoid tumour Most commonly found in small bowel Local mass effect (obstruction, appendicitis) orHormone excess~ ectopic ACTH or 5-HT (serotonin)Carcinoid syndrome- when vasoactive hormones reach systemic circulation
97 Acute-self limiting diarrhoea- No investigations are necessary Investigations are indicated when:-Signs of Dehydration (electrolytes imbalances)-Chronic or persistent diarrhoea-Bloody Diarrhoea-Anemia, Weight loss, abdominal mass orsuspicion of neoplasia-Patients with IBS with significant change ofsymptoms
101 Clinical Features Abdominal pain or discomfort Abdominal bloating/ distensionChange in bowel habits (constipation alternating with diarrhoea)Urgency of bowel movementsTenesmus
102 Diagnosis no specific laboratory or imaging test Diagnosis of exclusionRome Criteria
103 Rome III Criteria (2006)Recurrent abdominal pain or discomfort at least 3 days per month during the previous 3 months that is associated with 2 or more of the following:Relieved by defecationOnset associated with a change in stool frequencyOnset associated with a change in stool form or apperance.
104 Cont. Supporting symptoms: Altered stool frequency Altered stool form Altered stool passage (straining and/or urgency)MucorrhoeaAbdominal bloating or subjective distention
105 Etiology Currently unknown. Thought to result from an interplay of abnormal gastrointestinal(GI) tract movementsIncreased awareness of normal bodily functionsChange in the nervous system communication between the brain and the GI tract,
106 Cont. Has also developed after episodes of gastroenteritis Dietary allergies or food sensitivities (not yet proven)Symptoms worsen during periods of stress or mensesFOODS. MANY PEOPLE FIND THAT THEIR SIGNS AND SYMPTOMS WORSEN WHEN THEY EAT CERTAIN FOODS. FOR INSTANCE, CHOCOLATE, MILK AND ALCOHOL MIGHT CAUSE CONSTIPATION OR DIARRHEA. CARBONATED BEVERAGES AND SOME FRUITS AND VEGETABLES MAY LEAD TO MORE BLOATING AND DISCOMFORT IN SOME PEOPLE WITH IBS. THE ROLE OF FOOD ALLERGY OR INTOLERANCE IN IRRITABLE BOWEL SYNDROME HASN'T BEEN WELL STUDIED.IF YOU EXPERIENCE CRAMPING AND BLOATING MAINLY AFTER EATING DAIRY PRODUCTS, FOOD WITH CAFFEINE, OR SUGAR-FREE GUM OR CANDIES, THE PROBLEM MAY NOT BE IRRITABLE BOWEL SYNDROME. INSTEAD, YOUR BODY MAY NOT BE ABLE TO TOLERATE THE SUGAR (LACTOSE) IN DAIRY PRODUCTS, CAFFEINE OR THE ARTIFICIAL SWEETENER SORBITOL.Stress. If you're like most people with IBS, you probably find that your signs and symptoms are worse or more frequent during stressful events, such as a change in your daily routine or family arguments. But while stress may aggravate symptoms, it doesn't cause them.Other illnesses. Sometimes another illness, such as an acute episode of infectious diarrhea (gastroenteritis), can trigger IBS.
107 Management Exclusion diet Fiber supplements Laxatives Anti-diarrhoea medicationAntispasmodicAntidepressantsExclusion diet for example for lactose intolerance pt.Fiber supplements and laxatives can relieve the constipation-predominant irritable bowel.Antidiarrhoeals such as loperamide can relieve diarrhoeaAntispasmodic for colic and bloating.Antidepressants such as amitryptiline if the patient has pain ass wif depression.
108 Blood Tests1. Full Blood Count - Anemia? MCH? (iron deficiency? Anemia of chronic illness?) - MCV (inc in Crohn’s, celiac disease; dec in iron defi anemia)
109 2. Renal Profile - Electrolyte imbalances (dec K) 3 2. Renal Profile - Electrolyte imbalances (dec K) 3. Arterial Blood Gas - Acid-Base balance (loss of alkali in diarrhoea)
110 4. HIV serology (opportunistic infection of the gutchronic diarrhoea) 5. ESR (cancer, IBD) 6. CRP (IBD) 7. Thyroid function test (hyperthyroidism) 8. Celiac Serology 9. Tumor Markers (eg: CEA) …… Depends on your differential diagnosis~
111 Stool ( must be collected fresh on three occasions) Microscopy for parasites and red and white cells ( warm specimen for amoebiasis)Cultures: Pathogens, Campylobacter sp., C.difficile (pseudomembranous colitis, Yersinia, sp
112 StoolFor occult bloodFor ova and cyst (eg: Cryptosporidiosis, Blastocystis)For fat excretion (steatorrhoea)
114 Imaging and Scope:Small Bowel Endoscopy (for malabsorption disorders) and Capsule EndoscopyColonoscopy/ Barium enemaTo exclude malignancy and in colitisRigid / Flexible sigmoidoscopyBiopsy of normal and abnormal looking mucosa
118 Acute Diarrhoea : Management Access Hydration StatusEncourage fluids intakeConsider antibiotics if ill or frailConsider referring if very ill, diabetic on insulin or metformin
119 Symptomatic relief with antimotility drugs Advice on how to reduce spread by hand washing.Food-handlers and staff in health care services should be symptom free for 48 hours before return.
120 Drink glucose containing liquids and soups Carbohydrates e.g. pasta and bread, assist the co-transport of glucose and sodium, so the amount of diarrhoea lost will be less than if water is used alone
121 Particular care should be taken when dealing with the following patients: The very young or elderlyThose with co-morbidity e.g.diabetes, immunodeficiency, inflammatory bowel disorder or gastric hypochlorhydriaPatients taking systemic corticosteroids, ACE-inhibitors, diuretics or acid suppressants
122 Antibiotic therapy is usually only indicated for patients with positive stool cultures, who are systemically unwell and whose condition fails to improve within a few days.
123 Dehydration: Management Children and Elderly are especially prone to dehydration.A child should be encouraged by their preferred diet.Breastfeeding should be continued and alternate with ORS
124 Oral Rehydration Therapy The use of Oral Rehydration Therapy (ORT) is advisable for all cases with dehydration seen.Oral Rehydration Salt –standard or reduced osmolarityHome solutions
125 Oral Rehydration Therapy Sodium chloride gTrisodium citrate dehydrate 2.9 g(or sodium bicarbonate 2.5g)Potassium chloride 1.5gGlucose gTo be dissolved in one litre of clean drinking waterencourage 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.
126 Adults should receive 2 litres of ORT in the first 24 hours, followed by unrestricted normal fluids with 200 ml of ORT for every loose stool or vomit.Mild dehydration (<5%) can be treated in a primary care, by giving ORS.Moderate (5-10%) or severe (greater than 10%)dehydration is an indication for admission.
127 Fluid management of Moderate to Severe Dehydration Treat ShockRehydrateMaintainanceOngoing Losses
128 Treat Shock:20 ml /kg 0.9% saline over 10 to 15 minsRehydrationfluid deficit: % of dehydration X body weight0.45% saline/2.5 % dextroseover 24 hours-low or normal plasma sodiumover 48 hours-high plasma sodium
129 Maintenance :First 10 kg : ml/kg/24 hoursSecond 10 kg : 50 ml/kg/24 hoursSubsequent kg : 20 ml/kg/24 hoursClose monitoring : clinical condition (vomiting, diarrhoea), plasma creatinine, and electrolytes.