Chronic Diarrhea & Malabsorption Dr. Thant Zin Aung PG 2nd Year NORMAL PHYSIOLOGY • The main function of SI is digestion and assimilation of nutrients • The small intestine and colon together • regulate the secretion and absorption of water and electrolytes, • transport of intraluminal contents aborally, and • the salvage of some nutrients that are not absorbed in the small intestine Alterations in fluid and electrolyte handling contribute significantly to diarrhea. Alterations in motor and sensory functions of the colon result in highly prevalent syndromes s/a irritable bowel syndrome (IBS), chronic diarrhea, and chronic constipation the ascending and transverse colon function as reservoirs (average transit time, 15 h) the descending colon acts as a conduit (average transit time, 3 h). NEURAL CONTROL • intrinsic and extrinsic innervation. • The intrinsic innervation comprises • myenteric, • submucosal, and • mucosal neuronal layers. • The myenteric plexus regulates smooth-muscle function • The submucosal plexus affects secretion, absorption, and mucosal blood flow. • The extrinsic innervations are part of the autonomic nervous system • The parasympathetic nerves. • via the vagus nerve reach the small intestine and proximal colon along the branches of the superior mesenteric artery. • The distal colon is supplied by sacral nerves (S2–4) via the pelvic plexus; • The sympathetic nerve • reaches the small intestine and colon alongside their arterial vessels. • generally excitatory to sphincters and • inhibitory to non-sphincteric muscle. • Normally, 9-10 liters of fluid composed of ingested fluid and secretions from the salivary glands, stomach, pancreas, bile ducts and duodenum enter the GIT • The jejunum absorbs approximately 6L and the ileum 2.5L • ~1 L of residual fluid reaches the colon • Normally, the colon removes 90% of this load • so stool water represents only about 1% of the fluid entering the gut each day Reduction of water absorption by as little as 1% can result in diarrhea. SMALL-INTESTINAL MOTILITY • During the fasting period, the motility of the small intestine is characterized by a cyclical event called the migrating motor complex (MMC), which serves to clear nondigestible residue from the small intestine (the intestinal “housekeeper”). Rapid transit prevents adequate time for absorption: • This organized, propagated series of contractions lasts, on average, 4 Diarrhea or constipation may result from alteration in the reservoir min, occurs every 60–90 function min of the proximal colon or the propulsive function of the left colon Diarrhea results despite intact mucosal absorptive capacity. • After food ingestion, the small intestine produces irregular, mixing Intestinal hurry has been linked to post-vagotomy diarrhea, diarrhea contractions of relativelypredominant low amplitude Irritable bowel syndrome and diabetic diarrhea ILEOCOLONIC STORAGE AND SALVAGE • The distal ileum acts as a reservoir, &empty the ileum by bolus transfers. • Segmentation by haustra compartmentalizes the colon and facilitates mixing, retention of residue, and formation of solid stools. • The resident microorganisms, predominantly 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. COLONIC MOTILITY AND TONE • The small-intestinal MMC only rarely continues into the colon. • However, short duration or phasic contractions mix colonic contents and high-amplitude (>75 mmHg) propagated contractions are sometimes associated with mass movements through the colon and normally occur approximately five times per day, usually on awakening in the morning and post-prandially. • Increased frequency of HAPCs may result in diarrhea or urgency. The predominant phasic contractions in the colon are irregular and nonpropagated and serve a “mixing” function. DEFECATION What is diarrhea? Definition • Patients may describe diarrhea as bowel movements that are increased in frequency, larger in size, loose in consistency, or associated with urgency or incontinence. • The normal daily stool weight is 100-200 g, although individuals on high-fiber diet may pass 500 g/day. • In the United States, a daily stool weight of more than 200 g is considered abnormal • Diarrhea can be 1. Acute if <2 weeks 2. Persistent if 2-4 weeks 3. Chronic if > 4 weeks duration Causes of diarrheas by predominant pathophysiological mechanisms The classification of chronic diarrhea by pathophysiologic mechanism facilitates a rational approach to management, although many diseases cause diarrhea by more than one mechanism & direct the evaluations in meaningful ways Iatrogenic Causes • Cholecystectomy • Ileal resection • Bariatric surgery • Vagotomy, Factitial Causes • Munchausen • Eating disorders Dysmotile Causes • Irritable bowel syndrome (including postinfectious IBS) • Visceral neuromyopathies • Hyperthyroidism • Drugs (prokinetic agents) • Postvagotomy Secretory diarrheas • are due to derangements in fluid and electrolyte transport across the enterocolonic mucosa. • They are characterized clinically by watery, large-volume fecal outputs that are typically painless and persist with fasting. MEDICATIONS • Surreptitious or habitual use of stimulant laxatives (e.g., senna, cascara, bisacodyl, ricinoleic acid [castor oil) • Chronic ethanol consumption • Inadvertent ingestion of certain environmental toxins (e.g., arsenic) may lead to chronic diarrhea BOWEL RESECTION, MUCOSAL DISEASE, OR ENTEROCOLIC FISTULA • inadequate surface for reabsorption of secreted fluids and electrolytes. • Unlike other secretory diarrheas, it tends to worsen with eating. • Crohn’s ileitis • resection of <100 cm of terminal ileum HORMONES • The carcinoid syndrome due to the release of potent intestinal secretagogues including serotonin, histamine, prostaglandins, and various kinins. • Gastrinoma due to pancreatic enzyme inactivation by low intraduodenal pH. • Non-β cell pancreatic adenoma, a VIPoma, that secretes VIP and a host of other peptide hormones including pancreatic polypeptide, secretin, gastrin, gastrininhibitory polypeptide, neurotensin, calcitonin, and prostaglandins. • The secretory diarrhea is often massive with stool volumes >3 L/d; • daily volumes as high as 20 L have been reported. • Life- threatening dehydration; neuromuscular dysfunction from associated hypokalemia, hypomagnesemia, or hypercalcemia; flushing; and hyperglycemia may accompany a VIPoma. • Medullary carcinoma of the thyroid may present with watery diarrhea caused by calcitonin, other secretory peptides, or prostaglandins. • Systemic mastocytosis, which may be associated with the skin lesion urticaria pigmentosa, may cause diarrhea that is either secretory and mediated by histamine or inflammatory due to intestinal infiltration by mast cells. • Large colorectal villous adenomas may rarely be associated with a secretory diarrhea that may cause hypokalemia, can be inhibited by NSAIDs, and are apparently mediated by prostaglandins Osmotic Causes • 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. stool osmotic gap (>50 mosmol/L): serum osmolarity (typically 290 mosmol/kg) − (2 × [fecal sodium + potassium concentration Measurement of fecal osmolarity is no longer recommended because, even when measured immediately after evacuation, it may be erroneous because carbohydrates are metabolized by colonic bacteria, causing an increase in osmolarity. OSMOTIC LAXATIVES • Magnesium-containing antacids, • Health supplements, or • Laxatives CARBOHYDRATE MALABSORPTION • due to acquired or congenital defects in brush-border disaccharidases and other enzymes leads to osmotic diarrhea with a low pH. • lactase deficiency, • Some sugars, such as sorbitol, lactulose, or fructose, are frequently malabsorbed, and diarrhea ensues with ingestion of medications, gum, or candies sweetened with these poorly or incompletely absorbed sugars. WHEAT AND FODMAP INTOLERANCE • non-celiac gluten intolerance and • intolerance of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Steatorrheal Causes 1. Intraluminal maldigestion, 2. mucosal malabsorption, or 3. lymphatic obstruction may produce Fat malabsorption • Increased fecal output due to osmotic effects of fatty acids • greasy, foul-smelling, diicult-to-flush diarrhea • Quantitatively, steatorrhea is defined as stool fat exceeding the • normal 7 g/d; • mild steatorrhea of up to 14 g/d can be produced by maldigestion from rapid transit alone • In the presence of diarrhea, value more than 14 g/d is considered significant • daily fecal fat averages 15–20 g with small-intestinal diseases and • is often > 20 g with pancreatic exocrine insuiciency. INTRALUMINAL MALDIGESTION • Due to pancreatic exocrine insuiffciency, • Chronic pancreatitis, cystic fibrosis, pancreatic duct obstruction, somatostatinoma. • Bacterial overgrowth in the small intestine may deconjugate bile acids and alter micelle formation, impairing fat digestion; blind-loop, small-bowel diverticulum or dysmotility • cirrhosis or biliary obstruction may lead to mild steatorrhea due to deficient intraluminal bile acid concentration. MUCOSAL MALABSORPTION • Celiac disease • Tropical sprue • Whipple’s disease, • Mycobacterium avium- intracellulare infection in patients with AIDS. • Giardiasis • Abetalipoproteinemia • Medications (e.g., olmesartan, MMF, colchicine, cholestyramine, neomycin), • amyloidosis, and • chronic ischemia. POSTMUCOSAL LYMPHATIC OBSTRUCTION • congenital intestinal lymphangiectasia • acquired lymphatic obstruction secondary to trauma, tumor, cardiac disease or infection, Inflammatory Causes • generally accompanied by pain, fever, bleeding, or other manifestations of inflammation. • The mechanism of diarrhea may not only be exudation but, depending on lesion site, may include fat malabsorption, disrupted fluid/electrolyte absorption, and hypersecretion or hypermotility from release of cytokines and other inflammatory mediators. • Stool Analysis leukocytes or leukocyte-derived proteins such as calprotectin. • With severe inflammation, exudative protein loss can lead to anasarca (generalized edema).. IDIOPATHIC INFLAMMATORY BOWEL DISEASE • Crohn’s disease and ulcerative colitis • Microscopic colitis, including both lymphocytic and collagenous colitis, especially in middle-aged women and those on NSAIDs, statins, proton pump inhibitors (PPIs), and selective serotonin reuptake inhibitors (SSRIs); • It typically responds well to anti-inflammatory drugs (e.g., bismuth), the opioid agonist loperamide, or to budesonide. EOSINOPHILIC GASTROENTERITIS • Eosinophil infiltration of the mucosa, muscularis, or serosa at any level of the GI tract may cause diarrhea, pain, vomiting, • Affected patients often have an atopic history, Charcot-Leyden crystals due to extruded eosinophil contents may be seen on microscopic inspection of stool, • peripheral eosinophilia is present in 50–75% of patients. Dysmotility Causes • Rapid transit may accompany many diarrheas as a secondary or contributing phenomenon • Stool features often suggest a secretory diarrhea, • Hyperthyroidism, carcinoid syndrome, and certain 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. Factitial Causes • Factitial diarrhea accounts for up to 15% of unexplained diarrheas referred to tertiary care centers. • Either as a form of Munchausen syndrome or eating disorders, selfadminister laxatives or surreptitiously add water or urine to stool sent for analysis. How will you approach to a patient with chronic diarrhea? APPROACH TO THE PATIENT • Assess the patient’s fluid/electrolyte and nutritional status • Diagnostic evaluation must be rational • Directed by a careful history, and physical examination • When this strategy is unrevealing, simple triage tests are often warranted to direct the choice of more complex investigations Algorithm for management of chronic diarrhea. • In an estimated two-thirds of cases, the cause for chronic diarrhea remains unclear after the initial encounter, and further testing is required. TREATMENT • Fluid and electrolyte repletion • Replacement of fat-soluble vitamins may also be necessary in patients with chronic steatorrhea. • Treat specific underlying etiology • Induction and maintenance of remission is the main goal of therapy in patients with inflammatory bowel disease. This goal can be achieved by using 5-ASA (aminosalicylates) and immunosuppressant drugs • Gluten free diet is the main therapeutic measure in patients with celiac disease. • Role of long-term antibiotics in management of tropical sprue is yet not proved, but limited studies showed that 6 months treatment using doxycyclin and folic acid improved diarrhea frequency and malabsorption. • The somatostatin analogue, octreotide, is of proven effectiveness in carcinoid tumors and other peptide-secreting tumors, dumping syndrome, and chemotherapy-induced diarrhea • Patients with gastrinoma, and VIPoma can be treated by surgical removal. • Empiric therapy can be provided: a) as a temporizing measure during evaluation, b) when there is a failure to reach a diagnosis in a patient with chronic diarrhea, c) when a diagnosis is made, but is not specifically treatable. 9/11/2019 53 Thank You!