Diarrheal Diseases Presenter Dr. Kapil Dhingra Moderators Dr. D Das Dr. N Goswami Dr. N Momin
Diarrhea• Diarrhea is defined as passage of abnormally liquid or unformed stools at an increased frequency.• For adults on a typical Western diet, stool weight >200 g/d can generally be considered diarrheal.• Diarrhea may be further defined – acute if <2 weeks, – persistent if 2–4 weeks, – chronic if >4 weeks
Infectious Agents – feco-oral transmission – five high-risk groups 1. Travelers - enterotoxigenic or enteroaggregative Escherichia coli, Campylobacter, Shigella, Giardia 2. Consumers of certain foods - – Salmonella, Campylobacter, or Shigella from chicken – enterohemorrhagic E. coli (O157:H7) from undercooked hamburger – Bacillus cereus from fried rice or other reheated food – Staphylococcus aureus or Salmonella from mayonnaise or creams – Salmonella from eggs – Listeria from uncooked foods or soft cheeses – Vibrio species, Salmonella, or acute hepatitis A from seafood, especially if raw.
3. Immunodeficient persons – primary immunodeficiency (e.g., IgA deficiency, common variable hypogammaglobulinemia, chronic granulomatous disease) – secondary immunodeficiency states (e.g., AIDS, senescence, pharmacologic suppression)4. Daycare attendees and their family members5. Institutionalized persons
Pathogen Incubation PeriodBacillus cereus, Staphylococcus aureus 1-8 hrClostridium perfringens 8-24 hrVibrio cholerae, enterotoxigenic 8–72 hEscherichia coli, Klebsiella pneumoniae,Aeromonas speciesEnteropathogenic and enteroadherent E. 1-8 dayscoli, Giardia organismsC. difficile 1–3 dHemorrhagic E. coli 12–72 hRotavirus and norovirus 1–3 dSalmonella, Campylobacter, and 12 h–11 dAeromonas species, Vibrioparahaemolyticus, Yersinia
• Infectious diarrhea may be associated with systemic manifestations – Reiters syndrome - arthritis, urethritis, and conjunctivitis may accompany or follow infections by Salmonella, Campylobacter, Shigella, and Yersinia. – Hemolytic-uremic syndrome - enterohemorrhagic E. coli (O157:H7) and Shigella
• Ischemic colitis – – acute lower abdominal pain preceding watery, then bloody diarrhea; – acute inflammatory changes in the sigmoid or left colon while sparing the rectum• Toxins – – organophosphate insecticides – amanita and other mushrooms; – arsenic
• Most episodes of acute diarrhea are mild and self-limited and do not justify the cost and potential morbidity rate of diagnostic or pharmacologic interventions.• 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, – elderly (70 years) – immunocompromised patients.
Investigations• The cornerstone of diagnosis in those suspected of severe acute infectious diarrhea is microbiologic analysis of the stool.• Workup includes a) cultures for bacterial and viral pathogens, b) direct inspection for ova and parasites c) immunoassays for certain bacterial toxins (C. difficile), viral antigens (rotavirus), and protozoal antigens (Giardia, E. histolytica).
• If stool studies are unrevealing, flexible sigmoidoscopy with biopsies and upper endoscopy with duodenal aspirates and biopsies may be indicated.• Structural examination by sigmoidoscopy, colonoscopy, or abdominal CT scanning (or other imaging approaches) may be appropriate in patients with uncharacterized persistent diarrhea to exclude IBD or as an initial approach in patients with suspected noninfectious acute diarrhea caused by ischemic colitis, diverticulitis, or partial bowel obstruction.
Treatment: Acute Diarrhea• Fluid and electrolyte replacement are of central importance to all forms of acute diarrhea.• Profoundly dehydrated patients, especially infants and the elderly, require IV rehydration.
Antibiotics• Reduce severity and duration of diarrhea. – Treat empirically without diagnostic evaluation using a quinolone, such as ciprofloxacin (500 mg bid for 3–5 d). – Empirical treatment can also be considered for suspected giardiasis with metronidazole (250 mg qid for 7 d).
• Antibiotic coverage is indicated, whether or not a causative organism is discovered, in patients who are immunocompromised, have mechanical heart valves or recent vascular grafts, or are elderly.
• In moderately severe nonfebrile and nonbloody diarrhea, antimotility and antisecretory agents such as loperamide can be useful adjuncts to control symptoms.• Such agents should be avoided with febrile dysentery, which may be exacerbated or prolonged by them.
Chronic Diarrhea• Diarrhea lasting >4 weeks• In contrast to acute diarrhea, most of the causes of chronic diarrhea are noninfectious.
• Secretory Causes – due to derangements in fluid and electrolyte transport across the enterocolonic mucosa. – characterized clinically by watery, large-volume fecal outputs – typically painless – persist with fasting
2. Bowel Resection, Mucosal Disease, or Enterocolic Fistula – inadequate surface for reabsorption of secreted fluids and electrolytes. – tends to worsen with eating. – With disease (e.g., Crohns ileitis) or resection of <100 cm of terminal ileum, dihydroxy bile acids may escape absorption and stimulate colonic secretion (cholorrheic diarrhea). – may contribute to so-called idiopathic secretory diarrhea, in which bile acids are functionally malabsorbed from a normal-appearing terminal ileum.
3. Hormones – Metastatic gastrointestinal carcinoid tumors • watery diarrhea ,episodic flushing, wheezing, dyspnea, and right-sided valvular heart disease. • Diarrhea is due to the release into the circulation of potent intestinal secretagogues serotonin, histamine, prostaglandins, and various kinins. – Gastrinoma • diarrhea due to fat maldigestion owing to pancreatic enzyme inactivation by low intraduodenal pH
– VIPoma • watery diarrhea hypokalemia achlorhydria syndrome, also called pancreatic cholera, • due to a non b- cell pancreatic adenoma, referred to as a VIPoma, • secretes VIP and a host of other peptide hormones pancreatic polypeptide, secretin, gastrin, gastrin- inhibitory polypeptide ,neurotensin, calcitonin, and prostaglandins
– Medullary carcinoma of the thyroid • watery diarrhea caused by calcitonin, other secretory peptides, or prostaglandins– colorectal villous adenomas
4. Congenital Defects in Ion Absorption• defects in specific carriers associated with ion absorption• defective Cl–/HCO3– exchange (congenital chloridorrhea) with alkalosis (which results from a mutated DRA [down-regulated in adenoma] gene) and• defective Na+/H+ exchange (congential sodium diarrhea), which results from a mutation in the NHE3 (sodium-hydrogen exchanger) gene and results in acidosis.• hormone deficiencies such as occurs with adrenocortical insufficiency (Addisons disease) that may be accompanied by skin hyperpigmentation.
• Osmotic Causes – ingested, poorly absorbable, osmotically active solutes draw enough fluid into the lumen to exceed the reabsorptive capacity of the colon. – characteristically ceases with fasting or with discontinuation of the causative agent.
1. Osmotic Laxatives – Ingestion of magnesium-containing antacids, health supplements, or laxatives2. Carbohydrate Malabsorption – acquired or congenital defects in brush-border disaccharidases and other enzymes – Ex. lactase deficiency • sugars, such as sorbitol, lactulose, or fructose, are malabsorbed, and diarrhea ensues with ingestion of medications, gum, or candies sweetened with these poorly or incompletely absorbed sugars
• Steatorrheal Causes – Fat malabsorption – greasy, foul-smelling, difficult-to-flush diarrhea often associated with weight loss and nutritional deficiencies due to concomitant malabsorption of amino acids and vitamins – Quantitatively, defined as stool fat exceeding the normal 7 g/d
Causes of steatorrhea1. Intraluminal Maldigestion – most commonly results from pancreatic exocrine insufficiency – Other causes include • cystic fibrosis; • pancreatic duct obstruction; • somatostatinoma. – Bacterial overgrowth in the small intestine may deconjugate bile acids and alter micelle formation, impairing fat digestion • occurs with stasis from a blind-loop, • small-bowel diverticulum or • dysmotility
2. Mucosal Malabsorption – most commonly occurs from celiac disease • characterized by villous atrophy and crypt hyperplasia • proximal small bowel • fatty diarrhea associated with multiple nutritional deficiencies – Tropical sprue • a similar histologic and clinical syndrome • occurs in residents of or travelers to tropical climates
– Whipples disease, • due to the bacillus Tropheryma whipplei • histiocytic infiltration of the small-bowel mucosa, • typically occurs in young or middle-aged men; • frequently associated with arthralgias, fever, lymphadenopathy, and extreme fatigue, and it may affect the CNS and endocardium
3. Postmucosal Lymphatic Obstruction – congenital intestinal lymphangiectasia – acquired lymphatic obstruction secondary to trauma, tumor, cardiac disease or infection – unique constellation of fat malabsorption with enteric losses of protein (often causing edema) and lymphocytopenia.
• Inflammatory Causes – accompanied by pain, fever, bleeding, or other manifestations of inflammation – The unifying feature on stool analysis is the presence of leukocytes or leukocyte-derived proteins such as calprotectin – Any middle-aged or older person with chronic inflammatory-type diarrhea, especially with blood, should be carefully evaluated to exclude a colorectal tumor.
Distinguishing characteristics of CD and UC Feature CD UC Location SB or colon Only colon Anatomic Skip lesions Continuous, distribution begins distally Rectal Rectal spare Involved in >90% involvementGross bleeding Only 25% UniversalPeri-anal disease 75% Rare Fistulization Yes No Granulomas 50-75% No
Endoscopic features of CD and UC Feature CD UC Mucosal Discontinuous Continuous involvement Aphthous ulcers Common Rare Surrounding Relatively Abnormal mucosa normalLongitudinal ulcer Common RareCobble stoning In severe cases NoMucosal friability Uncommon CommonVascular pattern Normal distorted
Pathologic features of CD and UC Feature CD UCTransmural inflammation Yes Uncommon Granulomas 50-75% No Fissures Common Rare Fibrosis Common NoSubmucosal inflammation Common Uncommon
Radiologic features of CD and UC CD UC Nodularity Collar button granularity ulcers cobble stoning string sign of SB
Primary or Secondary Forms of Immunodeficiency Eosinophilic Gastroenteritis o Eosinophil infiltration of the mucosa, muscularis, or serosa at any level of the GI tract may cause diarrhea, pain, vomiting, or ascites. o atopic history, o Charcot-Leyden crystals due to extruded eosinophil contents may be seen on microscopic inspection of stool, and o peripheral eosinophilia
• Dysmotility Causes – Hyperthyroidism, – carcinoid syndrome, – drugs (e.g., prostaglandins, prokinetic agents) – Primary visceral neuromyopathies or idiopathic acquired intestinal pseudoobstruction may lead to stasis with secondary bacterial overgrowth causing diarrhea. – Diabetic diarrhea, often accompanied by peripheral and generalized autonomic neuropathies, may occur in part because of intestinal dysmotility. – The exceedingly common IBS characterized by disturbed intestinal and colonic motor and sensory responses to various stimuli. Symptoms of • stool frequency cease at night, • alternate with periods of constipation • accompanied by abdominal pain relieved with defecation, • rarely result in weight loss.
• Factitial Causes – accounts for up to 15% of unexplained diarrheas referred to tertiary care centers – Hypotension and hypokalemia are common co- presenting features
• Peripheral blood leukocytosis, elevated sedimentation rate, or C-reactive protein suggests inflammation;• anemia reflects blood loss or nutritional deficiencies;• eosinophilia may occur with parasitoses, neoplasia, collagen-vascular disease, allergy, or eosinophilic gastroenteritis.• Blood chemistries may demonstrate electrolyte, hepatic, or other metabolic disturbances.• Measuring tissue transglutaminase antibodies may help detect celiac disease.
• Patients suspected of having IBS should be initially evaluated with flexible sigmoidoscopy with colorectal biopsies
• For secretory diarrheas medication-related side effects or laxative use should be reconsidered.• Microbiologic studies should be done including – fecal bacterial cultures – inspection for ova and parasites, and – Giardia antigen assay (the most sensitive test for giardiasis).• Small-bowel bacterial overgrowth can be excluded by intestinal aspirates with quantitative cultures or with glucose or lactulose breath tests
• Upper endoscopy and colonoscopy with biopsies and small-bowel barium x-rays are helpful to rule out structural or occult inflammatory disease.• When suggested by history or other findings, screens for peptide hormones should be pursued (e.g., serum gastrin, VIP, calcitonin, and thyroid hormone/thyroid-stimulating hormone, or urinary 5-hydroxyindolacetic acid, and histamine).
• osmotic diarrhea should include tests for lactose intolerance and magnesium ingestion, the two most common causes.• Low fecal pH suggests carbohydrate malabsorption;• lactose malabsorption can be confirmed by lactose breath testing or by a therapeutic trial with lactose exclusion and observation of the effect of lactose challenge (e.g., a liter of milk).
• For those with fatty diarrhea, endoscopy with small-bowel biopsy (including aspiration for Giardia and quantitative cultures) should be performed
Tests for steatorrhea• Quantitative test – 72hr stool fat collection – gold standard • > 7gm/day – pathologic• Qualitative tests – Sudan lll stain • Detect clinically significant steatorrhea in >90% of cases – Acid steatocrit – a gravimetric assay • Sensitivity – 100%, specificity – 95% , PPV – 90% – NIRA (near infra reflectance analysis) • Equally accurate with 72hr stool fat test • Allows simultaneous measurement of fecal fat, nitrogen, CHO
• Chronic inflammatory-type diarrheas should be suspected by the presence of blood or leukocytes in the stool.• Such findings warrant stool cultures; inspection for ova and parasites; C. difficile toxin assay; colonoscopy with biopsies.
Treatment: Chronic Diarrhea• depends on the specific etiology• If the cause can be eradicated, treatment is curative as with resection of a colorectal cancer, antibiotic administration for Whipples disease or tropical sprue, or discontinuation of a drug
• Suppression of the underlying mechanism elimination of dietary lactose for lactase deficiency or gluten for celiac sprue, use of glucocorticoids or other anti-inflammatory agents for idiopathic IBDs, adsorptive agents such as cholestyramine for ileal bile acid malabsorption, proton pump inhibitors for the gastric hypersecretion of gastrinomas,
somatostatin analogues such as octreotide for malignantcarcinoid syndrome, prostaglandin inhibitors such as indomethacin for medullary carcinoma of the thyroid, and pancreatic enzyme replacement for pancreatic insufficiency• Replacement of fat-soluble vitamins may also be necessary in patients with chronic steatorrhea.