Western Med School - Clinical Intestines - Part 2 2025 PDF

Clinical Intestines – Part 2 Leonard Mankin, MD, FACP Associate Program Director Legacy Health, Portland, OR Associate Professor of Medicine Oregon Health & Science University Assistant Professor of Medicine Western COMP-NW...

Clinical Intestines – Part 2 Leonard Mankin, MD, FACP Associate Program Director Legacy Health, Portland, OR Associate Professor of Medicine Oregon Health & Science University Assistant Professor of Medicine Western COMP-NW [email protected]  Objectives Understand how the body absorbs fats, carbohydrates, proteins and essential nutrients Recognize common causes of malabsorption, including exocrine pancreatic insufficiency, celiac sprue, tropical sprue, small intestinal bacterial overgrowth and Whipple’s disease Know the major risk factors, clinical manifestations and potential treatments of IBS Identify the potential causes, workup and treatment of acute and chronic diarrhea Identify the potential causes, workup and treatment of chronic constipation  Outline Malabsorption - Fat, carbohydrate, and protein - Exocrine pancreatic insufficiency - Celiac disease - Tropical sprue - Small intestinal bacterial overgrowth (SIBO) - Whipple’s disease Irritable Bowel Syndrome (IBS) Acute Diarrhea Chronic Diarrhea Constipation  Malabsorption Definition - impaired transport of nutrients across the apical membrane of intestinal cells Global malabsorption - Widespread mucosal diseases (e.g. celiac sprue, Crohn’s disease) or loss of absorptive surface (surgical resection or intestinal bypass) Selective malabsorption - inability to absorb a single nutrient (e.g. pernicious anemia) or a limited number of nutrients (fat soluble vitamins) Malabsorption - pathogenesis 3 Steps for normal nutrient absorption: 1. Luminal processing 2. Absorption into enterocyte 3. Transport into the circulation Malabsorption results from impairment of one or more of these steps Fat Absorption  Fat Absorption Most dietary fat absorbed in proximal two-thirds of jejunum Normally > 94% dietary fat absorbed Fat absorption is essential for intake of fat-soluble vitamins (A,D,E & K)  Fat Absorption 1. Fats emulsified by mastication and gastric mixing 2. Emulsion is then hydrolyzed by lipases from tongue, stomach and pancreas 3. Bile salts stabilize the emulsion of mono- and di- glycerides and fatty acids (micelles), making it easy to absorb by jejunal cells 4. Lipid components are repackaged within the enterocyte into chylomicrons, which are released into circulation 5. Bile salts are reabsorbed in terminal ileum and sent to gall bladder for reuse (enterohepatic circulation)  Fat absorption is such a beautiful process! What could possibly go wrong? Fat Malabsorption History of oil droplets in toilet bowl highly suggestive of steatorrhea Stool tests such as fecal fat or Sudan III stain may help in diagnosis Carbohydrate Absorption Starch, sucrose and lactose are the most common digestible CHOs Broken down by amylases (pancreas and salivary) and intestinal disaccharidases into monosaccharides for absorption Carbohydrate Absorption Cellulose, a plant disaccharide, cannot be digested in the small intestine, and is fermented by bacteria in the colon, releasing methane and hydrogen gases Excessive colonic fermentation produces acidic stools, flatulence, bloating and abdominal discomfort characteristic of CHO malabsorption syndromes  Carbohydrate Malabsorption 1. Pancreatic amylase deficiency 2. Reduced disaccharidases in small intestine 3. Decreased absorptive surface (eg. celiac disease, Crohn’s, small bowel resection) 4. Unabsorbable CHOs (eg. sorbitol)  Carbohydrate Malabsorption Patients often complain of watery diarrhea, excessive gas and bloating Breath tests (hydrogen, methane or CO2) may be helpful at establishing dx Protein Absorption Initial digestion by gastric pepsins Pancreatic peptidases secreted into the duodenum break down protein to AAs and dipeptides/tripeptides, which are then absorbed in intestinal brush border  Protein Malabsorption 1. Deficiency of pancreatic bicarbonate and proteases (e.g. chronic pancreatitis, cystic fibrosis) 2. Loss of intestinal absorptive surface (e.g. celiac disease, small bowel resection, Crohn’s disease)  Protein Malabsorption Low protein states are typically due to malnutrition, liver disease, or proteinuria, and are rarely a result of malabsorption Stool alpha-1 antitrypsin can be quantified if protein malabsorption from the gut is suspected  Vitamin, Mineral and Trace Element Absorption Most vitamins and minerals (iron, calcium) absorbed in proximal half of small intestine Vit B-12 and Mg are notable exceptions, being absorbed in terminal ileum Nutritional status often determines amount absorbed. Examples include calcium (regulated by Vit D) and iron (regulated by hepcidin) Malabsorption work up Suspect malabsorption in pts with weight loss and/or nutritional deficiencies What to look for on history: - Chronic intestinal diseases - Prior bowel surgery or radiation - Prior ETOH abuse or pancreatitis Exocrine Pancreatic Insufficiency (EPI) Exocrine Pancreatic Insufficiency (EPI) Exocrine pancreas produces multiple enzymes that aid in the digestion of fats, proteins and starches Chronic damage to the pancreas or the pancreatic outlet results in diminished delivery of enzymes to the duodenum and altered digestion, known as EPI  EPI - Clinical Manifestations Early: Chronic abdominal pains, bloating Late: - Maldigestion of proteins and fats leading to weight loss and chronic diarrhea with high fecal fat content (steatorrhea) - Steatorrhea does not come about until loss of 90% of pancreatic exocrine function - Malabsorption of vitamins (A,D,E, K and B12) JOP 2019;20:121-125  EPI – common causes 1. Chronic pancreatitis from alcohol in adults. Up to 85% of chronic pancreatitis patients have EPI 2. Pancreatic cancer 3. Cystic fibrosis in children – Most common GI manifestation of CF, affecting up to 80% JOP 2019;20:121-125 JOP 2019;20:121-125  EPI - Dx Presumptive dx in patients with chronic pancreatitis, diabetes, abdominal pains, diarrhea and weight loss with suggestive radiographic findings (pancreatic atrophy, scattered calcifications, ductal changes) Important to rule out cancer of pancreas or ducts with advanced imaging if never done  CT scan – normal pancreas http://radiologic-technology.blogspot.com/ Microcalcifications in chronic pancreatitis  EPI - Dx Indirect tests*: fecal elastase-1, an enzyme found in pancreatic secretions that is not degraded in the gut. Low levels in stool very sensitive for mod to severe disease Direct tests: Secretin test. Invasive! Inject secretin and then measure bicarb levels in duodenal secretions (requires EGD) * Preferred method  EPI - Rx Dietary fat reduction Avoidance of alcohol Vitamin supplements Oral replacement of pancreatic enzymes - Given with each meal and snack - Expensive! Lactose Intolerance Lactose Intolerance Abdominal pains, diarrhea, bloating and flatulence brought on by lactose ingestion Lactase present in high levels at birth, but then wanes with age  Lactose Intolerance - Prevalence Estimated 30-50 million Americans Strong genetic predisposition: - 95% of Asians - 80-100% Native Americans - 60-80% of African Americans, Ashkenazi Jews - 50-80% Hispanics - Only 2% of Northern Europeans National Institutes of Health US National Library of Medicine “Lactose Intolerance” ghr.nlm.nih.gov accessed Sep 21, 2021 Lactose Content of Dairy Products Food Lactose per 8 oz serving Regular Milk 12 g Wendy’s Frosty 8.1 g Low-fat Yogurt 13-17 g Greek Yogurt 8-9 g American Cheese 6.11 g Kefir 2g Butter 0.01 g Sour Cream 0.7 g Whipped Cream 0.07 g Source: USDA Database  Lactose Intolerance - mechanism Lactose converted to glucose and galactose and then absorbed in small intestine In lactase-deficient individuals, up to 75% of lactose is passed undigested to the colon Colonic bacteria ferment lactose, producing short-chain fatty acids and gas (hydrogen, CO2 and methane) Bacteria still consume breakdown products, but what’s left over can cause symptoms  Lactose Intolerance - Dx Lactose-hydrogen breath test - measuring levels of hydrogen gas at baseline and a couple hours after ingestion of lactose (sens 78%, spec 98%) Alternately, assessing symptoms after an oral lactose load gives more clinically relevant information, but more subjective  Lactose Intolerance – Significance? RCT with crossover design in 30 subjects with self-reported severe lactose intolerance: - 21/30 were lactose intolerant by hydrogen testing - Consuming 8 oz. of regular milk daily caused mild GI symptoms that did not differ when switched to lactose-free milk Additional 2.5 episodes of flatus per day with lactose exposure (95% CI: 0.2-4.8) N Engl J Med 1995;333:1-4  Celiac Disease (gluten-sensitive enteropathy or sprue) Celiac Disease Inappropriate T-cell reactivity to ingested gluten causing inflammatory changes to small intestinal mucosa in genetically susceptible individuals1 Affects 1.4% of individuals globally, with highest rates in Europeans2 1. Ann Intern Med 2020; Jan 7:ITC 1-16 2. Clin Gastroenterol Hepatol 2018;16:823-836  Gluten is the trigger Protein found in wheat, rye, barley, and some oat cultivars that gives dough an elastic quality, helps it to rise, and gives the final baked product a chewy texture  Celiac Disease Multisystem disorder – inflammation in small intestines triggers malabsorption, leading to diarrhea, vitamin deficiencies, chronic abdominal pains, and weight loss Increased risk for premature death and malignancy (lymphoma) in those who do not adhere to a gluten-free diet1 1. BMJ 2004;329:716-719 Celiac Disease and Malabsorption Iron iron-deficiency anemia Vit D osteopenia B vitamins neurologic disorders such as peripheral neuropathy or dementia  Celiac Disease - Genetics Familial – risk for 1st degree relatives1 - Siblings (8.9%) - Parents (3.0%) - Offspring (7.9%) Increased risk in autoimmune conditions such as type 1 DM and autoimmune thyroiditis 1. Am J Gastroenterol 2015;110:1539-1548  Celiac Disease - Genetics 99% of celiac patients have HLA-DQ2 and/or HLA-DQ8 as compared to 40% of population. Thus, haplotype testing only helpful to rule out the disease 1. N Engl J Med 2021;385:35-45 When to test for Celiac Disease No screening recs for general population Consider genetic screen for 10 relatives Serology testing for ≥ 1 of the following: - Chronic or recurrent diarrhea or constipation - Malabsorption, esp. vitamin deficiencies - Unexplained weight loss - Chronic abdominal pains  Celiac Disease – Antibody tests Anti-tissue transglutaminase (tTG-IgA) is test of choice due to accuracy (Sn 92.5%, Sp 97.9%), low cost and high availability Others: endomysial (EMA-IgA), anti-gliadin ab, and anti-deaminated gliadin peptide Pts must be consuming gluten (>6 wks) in their diet for tests to be accurate! Ann Intern Med 2020; Jan 7:ITC 1-16  Celiac Disease - Dx If antibody testing is positive, patient must undergo EGD with small bowel biopsy to confirm the diagnosis Gross: scalloping of mucosal folds Histology: flattening/loss of crypts and intraepithelial lymphocyte infiltration Ann Intern Med 2020; Jan 7:ITC 1-16 Mucosal scalloping  Celiac Disease - Rx Treatment is focused on adopting a gluten- free diet for life Monitor regularly for symptoms Yearly anti-tTG antibodies (should decrease over 6-12 months to new baseline) No need for repeat small bowel bx if asx Monitor labs (e.g. CBC, iron, vit D, B12) Ann Intern Med 2020; Jan 7:ITC 1-16 Other sources: Artificial color Ground spices Natural Flavorings Malt Malt vinegar Food starch Dextrin Soy sauce Apps for identifying gluten products Celiac Disease and the Skin Dermatitis Herpetiformis is a vesicular pruritic skin eruption that is primarily seen in patients with gluten sensitivity Yearly incidence of ≈1 out of 100,000 75-90% of DH patients have small bowel gluten enteropathy on endoscopy Treatment involves dapsone therapy and adopting a gluten-free diet Dermatitis Herpetiformis Do patients without celiac disease benefit from a gluten-free diet? Non-celiac Gluten Sensitivity Consumption of gluten leading to symptoms similar to patients with celiac disease, without elevated immune markers or pathologic changes Avoidance of gluten resolves the symptoms, which recur when gluten is reintroduced into the diet Estimated 0.6% to 6% of US population World J Gastroenterol 2017;23:7201-7210  Celiac Disease – future directions An oral inhibitor of transglutaminase 2 appears to attenuate mucosal injury when given to celiac patients during a daily gluten challenge More studies underway, but may allow some laxity in dietary restrictions New grain cultivars are being investigated N Engl J Med 2021;385:35-45 Tropical Sprue  Tropical Sprue Malabsorption syndrome believed to be caused by proximal small bowel bacterial overgrowth in people living in tropical countries, or travelers staying > 1 month Western hemisphere: Cuba, Haiti, Dominican Republic and Puerto Rico Eastern hemisphere: India and Pakistan, to a lesser degree, SE Asian nations Distribution of Tropical Sprue  Tropical Sprue Begins with infectious enteritis that evolves to chronic diarrhea and weight loss Toxigenic coliform organisms in duodenum Causes folic acid deficiency, sometimes followed by B12 deficiency as disease spreads distally megaloblastic anemia Huge differential dx including parasites, HIV, celiac disease, intestinal lymphoma  Tropical Sprue – Dx and Rx Exclude other causes, esp. parasites (Giardia, Entamoeba, Strongyloides, Cryptosporidia, Isospora, Cyclospora), HIV, and celiac disease (anti-tTG IgA) Duodenal biopsy with gross appearance and histology very similar to celiac disease Rx: Oral tetracycline + Folic acid/B12 replacement for 3-6 months Small Intestine Bacterial Overgrowth (SIBO)  SIBO Small bowel becomes colonized with excessive colonic organisms, disrupting normal absorption (CHO, protein and fat) Risk factors: - Intestinal hypomotility 90% of cases - Chronic pancreatitis - Anatomic disorders - Immune disorders - Gastric hypochlorhydria SIBO – clinical presentation and Dx Pts report excess bloating, flatulence, abdominal pains and watery diarrhea Difficult to diagnose, as symptoms are non-specific and overlap with IBS, celiac disease, EPI and IBD In individuals with persistent sx, diagnosis is made by either a timed carbohydrate breath test or jejunal aspirate  SIBO - Dx Carbohydrate breath test – lactulose, a non-absorbable sugar, is administered orally and then hydrogen and methane are measured in the breath at 90 minutes - Sens (20-93%) & Spec (45-86%) Jejunal aspirate – bacteria concentration > 103 CFU/ml. Aspirate via EGD with sterile catheter, hard to perform with accuracy  SIBO - Rx Antibiotics are given for confirmed cases Rifaximin is antibiotic of choice Up to 40% of treated pts report persistent sx Recurrence is also common, and additional antibiotic courses may become necessary Elemental diets (diet made up of building block nutrients (AAs, glucose, simple fats) have shown promise for treatment of SIBO Whipple’s Disease Whipple’s Disease A multisystem disease manifesting with joint symptoms, chronic diarrhea, malabsorption and weight loss caused by infection with Tropheryma whipplei, a common soil bacteria Rare disease, est. 30 people/year in US Dx with +PAS stain and PCR Rx with IV followed by PO abx x 1 year  Review of tests for malabsorption Condition Test(s) Fat malabsorption Fecal fat; Sudan III Stain CHO malabsorption/lactose Breath tests intolerance (hydrogen, methane, CO2) Protein malabsorption Stool for alpha-1 antitrypsin EPI Fecal elastase-1; Secretin test Celiac Disease Anti-tTG IgA + small bowel bx Tropical Sprue Neg Anti-tTG IgA + small bowel bx SIBO Timed lactulose breath test Whipple’s Disease PAS + stain/PCR for T. whipplei on small bowel sample Irritable Bowel Syndrome (IBS)  Irritable Bowel Syndrome (IBS) Functional bowel disease marked by chronic abdominal pains and altered bowel habits Very common! Affects about 9% of men and 14% of women in US Onset in 2nd or 3rd decade, more common in age < 50 Increased health care costs - #2 reason for work absenteeism - 25-50% of all referrals to gastroenterologists IBS – Associated Conditions Fibromyalgia Chronic fatigue syndrome GERD and dyspepsia Psychiatric disorders - Depression - Anxiety - Somatization IBS – Clinical Features Crampy abdominal pains - intermittent and of variable location and severity Stress worsens symptoms Altered bowel habits – diarrhea (often with mucus), constipation (often with tenesmus), or diarrhea alternating with constipation  IBS - pathophysiology Uncertain. No consistent pathophysiologic mechanism has been identified 10-20% of pts with infectious gastroenteritis will develop post-infectious IBS1 Eur J Clin Invest 2015;45:1350-1359  Proposed Mechanisms for IBS Tyemedical.com  Rome IV Criteria for Dx of IBS Recurrent abdominal pains, occurring at least 1 day per week in past 3 months, with ≥ 2 of the following: - Pain brought on by or relieved by defecation - Associated with change in stool frequency - Associated with change in stool form IBS Subtypes 1. IBS-Constipation predominant 2. IBS-Diarrhea predominant 3. IBS-Mixed bowel habits 4. IBS-Unclassified  Must exclude other diagnoses if red flags are present! Red Flags: - Onset after age 50 - Hematochezia or melena - Unexplained weight loss - Nocturnal diarrhea - Lab abnormalities (e.g. iron deficiency, elevated ESR, CRP, fecal calprotectin) - Family hx of IBD, celiac or GI cancer  IBS Diagnosis No specific diagnostic test(s) for IBS Age-appropriate screening for colon cancer CBC & CRP reasonable For IBS with diarrhea, consider: - fecal calprotectin - anti-tTG IgA - stool test for Giardia N Engl J Med 2017;376:2566-2578  IBS Diagnosis Formerly a “diagnosis of exclusion” Clinicians who believe that IBS is a diagnosis of exclusion order 1.6 times more tests and spend $396 more per patient1 In absence of red flags, pts who meet the ROME IV criteria should be given a dx of IBS Am J Gastroenterol 2010;105:848-858  IBS - Treatment Reassurance and education Heterogeneous disease, so there is no “one size fits all” approach Dietary approach is first-line: - Daily soluble fiber (psyllium) is helpful - Low FODMAP diet showed reduction in IBS global sx, pain and bloating - Consider lactose and gluten avoidance Physical activity and stress reduction, CBT N Engl J Med 2017;376:2566-2578  What are FODMAPs? FODMAP = Fermentable Oligosaccharides, Disaccharides, Monosaccharides, And Polyols FODMAPs are short chain carbohydrates that are osmotically active, easily fermentable and may precipitate IBS symptoms IBS – Pharmacotherapy  IBS Pharmacotherapy Drugs for IBS - D Drugs for IBS - C Peppermint Oil Intestinal secretagogues Tricyclic antidepressants - Linaclotide - Plecanatide Opioid receptor agonists - lubiprostone Serotonin antagonists Histamine antagonists Antibiotics (rifaximin) 1. J Clin Med 2017;6:101 2. N Engl J Med 2017;376:2566-2578 Diarrhea Diarrhea - definitions Diarrhea defined as ≥ 3 watery BMs/day - Acute < 2 weeks - Persistent = 2 – 4 weeks - Chronic > 4 weeks Dysentery is diarrhea with visible blood or mucus, often associated with fever and abdominal pains  Acute Diarrhea Worldwide, in top 10 causes of death for all persons, and top 5 for infants < 5 years 1 Majority due to infections, including viruses, bacteria and parasites In resource-rich countries, a “nuisance disease” that generally self-resolves with supportive care 1. Lancet Infect Dis 2018;18:1211-1228  Acute Diarrhea - Evaluation Hx and PE to rule out inflammatory conditions or severe dehydration (dark or scant urine, low skin turgor, dry mucus membranes, orthostatic hypotension) Most patients do not require a lab workup Consider workup for persistent fevers, bloody stools, severely ill or dehydrated, immunocompromise, or suspected outbreak  Historical Features Organism Recent antibiotics or hospital stay Clostridium difficile Immunocompromise Cryptosporidia, Cyclospora, Isospora Consumption of raw milk, unpasteurized Listeria cheeses, uncured meats; pregnancy Camping; drinking untreated water Giardia Seafood; esp raw shellfish Vibrio cholera or V. parahemolyticus Bloody stools Shigella, Campylobacter, Salmonella, STEC, C difficile, Entamoeba,Yersinia Consumption of fried rice Bacillus cereus Renal failure due to hemolytic uremic STEC syndrome (HUS) “rice water” stools Vibrio cholerae Travel to developing countries ETEC, Campylobacter, Shigella, Norovirus STEC = Shiga-toxin producing E. coli Am Fam Physician 2014;89:180-189 ETEC = Enterotoxigenic E. coli  Acute Diarrhea - Evaluation Microbiology workup for patients with severe illness, immuno-compromise, bloody diarrhea, advanced age, sx lasting > 1 week - Stool cultures (very low sensitivity test!) - Fecal occult blood testing - Fecal lactoferrin - Multi-pathogen molecular panel - C difficile testing if high-risk Am Fam Physician 2014;89:180-189  Acute Diarrhea - Rx Primary focus is preventing or treating dehydration with oral rehydration solutions containing water, salt and sugar IV hydration for severe illness Early refeeding beneficial. Avoid fatty foods and dairy during early recovery Probiotics may be helpful, but little evidence Am Fam Physician 2014;89:180-189  Acute Diarrhea – Antibiotics? Antibiotics may shorten the course of acute bacterial diarrhea Why antibiotics are generally not indicated: - Most diarrhea is viral and resolves without rx - Potential side effects - Promotion of antibacterial resistance - Replacement of normal flora and potential for C. difficile superinfection - Cost Am Fam Physician 2014;89:180-189  Diarrhea – Anti-Motility Agents Anti-motility agents (e.g. loperamide, diphenoxylate) are generally safe and reduce frequency and duration of symptoms These agents may prolong illness in inflammatory diarrhea by causing retention of infectious organisms – avoid in patients with fevers, bloody or mucoid stools! Bismuth appears to be a safe alternative in inflammatory states Am Fam Physician 2014;89:180-189 Chronic Diarrhea Loose stools, increased frequency of stools, or urgency lasting for > 28 days Affects ≈ 3-5% of US adults Clin Gastroenterol Hepatol 2017;15:182-193  Chronic Diarrhea – how to distinguish functional (IBS) from organic disorders For IBS: - Pains that peak prior to defecation - Pains relieved by defecation - Associated changes in stool caliber and frequency - Often accompanied by psychogenic stress - Absence of alarm features Clin Gastroenterol Hepatol 2017;15:182-193 Chronic Diarrhea – Alarm Features Onset > age 50 Hematochezia or melena Unexplained weight loss, fevers Immunocompromise Progressive abdominal pain Nocturnal diarrhea Family hx of IBD or CRC Clin Gastroenterol Hepatol 2017;15:182-193  Chronic Diarrhea – Organic Causes Inflammatory (IBD, CRC, C difficile) Malabsorption (EPI, celiac, SIBO, Whipple’s) Secretory (mastocytosis, carcinoid, VIPoma, bile salts in colon, hyperthyroidism) Infectious (esp. immunocompromised) Osmotic (non-absorbable sugars, laxatives) Medications Clin Gastroenterol Hepatol 2017;15:182-193 Chronic Diarrhea - Infections Immunocompetent Immunocompromised C difficile Isospora Giardiasis Cryptosporidia Amoebiasis Cyclospora T whipplei Common Drugs that cause diarrhea Metformin Magnesium antacids Antibiotics Colchicine Lactulose and sorbitol Caffeine Alcohol  Chronic Diarrhea – Sx Inflammatory - fevers, severe abdominal pains, blood in stool CHO malabsorption – gas and bloating Fat malabsorption – steatorrhea CRC – fatigue, anemia, change in stool caliber Clin Gastroenterol Hepatol 2017;15:182-193  Chronic Diarrhea - Evaluation Hx (diet, prior gut surgery or radiation, alcohol use) and PE Rule out alarm features Initial labs: CBC, CMP, CRP, anti-tTG IgA If ROME IV criteria met, diagnose IBS If still no answer, stool studies to identify watery, fatty, infectious or inflammatory stools; Consider CT, EGD, colonoscopy Constipation  Constipation < 3 stools/week for > 3 months Pts often describe difficulty defecating, straining, hard or small stools and feelings of incomplete evacuation Lack of loose stools unless using laxatives Lack of chronic abdominal pains is key component to distinguishing from IBS Constipation – prevalence and risks US prevalence: - 14% for age > 18 - 33% for age > 60 - 80% for elderly nursing home residents! Risk factors: age, female sex, African- American race, low fluid intake, low fiber intake, and sedentary lifestyle Am J Gastroenterol 2011;106:1582-1591 Ann Intern Med 2015;ITC1-17  10 Constipation - etiology Disordered movement of stool through the colon and rectum - transit through proximal GI tract is usually preserved Causes1: - Slow transit = enteric nerve hypofunction - Dyssynergistic defecation = dyscoordinated pelvic floor contraction and relaxation of puborectalis and anal sphincter muscles - IBS-C = most common etiology 1. Dis Colon Rectum 1997;40:273-279  20 Constipation - etiologies Category Condition Neurologic MS, Parkinson’s Disease, Hirschsprung’s, spinal cord injury Endocrine Diabetes Mellitus, hypothyroidism, hyperparathyroidism, pregnancy Obstructing Lesions Colon cancer or polyps Medications Opioids, antihistamines, antidepressants, antipsychotics, antispasmodics, iron, aluminum- containing antacids, calcium channel blockers, diuretics  Constipation - Evaluation Start with careful hx, esp. meds Most patients do not require labs, endoscopy or radiographic studies Red flag sx should prompt further evaluation Red Flags = Blood in stool, weight loss, family hx of colon cancer or IBD, anemia or acute onset of constipation at a late age Tests for Constipation Plain film showing severe constipation stoolsbar.blogspot.com  Constipation - Management Minimize constipating medications Education – don’t obsess about frequency of BMs! dietary fiber (recommended 25 g/day) exercise fluid intake  Laxatives – 3 types 1. Bulk-forming - increase fecal mass and stool water absorption - Examples: psyllium, methyl-cellulose, polycarbophil 2. Osmotic* - non-absorbable sugars or salts that increase intestinal water secretion - Examples: polyethylene glycol, lactulose, sorbitol, Magnesium citrate 3. Stimulant** – increase intestinal motor activity - Examples: bisacodyl, senna * May cause diarrhea with regular use ** Avoid chronic use of stimulants – may cause hypokalemia Go Natural Both prunes and kiwi fruit performed similar to or better than daily psyllium for patients with chronic constipation Aliment Pharmacol Ther 2011;33:822-828 Am J Gastroenterol 2020;115:S229  Stool Softeners Surfactant agents – lower surface tension of stool, allowing more water to penetrate - Example: docusate (colace) Studies have not shown much benefit for constipation, but may be helpful for patients complaining of very hard stools  Severe Constipation Suppositories – Liquify stool to overcome distal obstruction - Examples: bisacodyl, glycerin Enemas – Liquify stools for more proximal impaction. Safe to use in patients with suspected or known bowel obstruction - Examples: warm water, soapy water, sodium phosphate*, coca-cola * Avoid use in elderly – may cause severe hypotension and electrolyte disturbances Severe Constipation - Secretagogues Guanylate Cyclase-c receptor agonists* – stimulate intestinal secretion and motility - Examples: linaclotide, plecanatide Very expensive ($475/month)1 Chloride-channel activators – stimulates intestinal fluid secretion - Example: lubiprostone 1. Goodrx.com – price at Costco pharmacy on 12/18/2021 (good reason to save up for retirement!)  Opioid-induced Constipation (OIC) Constipation affects 50-80% of patients taking chronic opioids. Opioids stimulate mu receptors in the gut that increase segmental contraction and inhibit peristalsis1 Pts prescribed chronic opioids should be prescribed preventive measures with osmotic and/or stimulant laxatives 1. Therap Adv Gastroenterol 2015;8:360-372  Opioid-Induced Constipation - Rx Peripherally-Acting Mu Receptor Antagonists (PAMORAs) – block peripheral opioid activity without reducing central analgesia - Examples: methylnaltrexone, naldemedine, naloxone, alvimopan PAMORAs indicated for refractory constipation despite aggressive preventive measures in pts on longterm opioids (hospice, chronic cancer) Very expensive! ($327-$2,022/month)1 1. Goodrx.com – price at Costco pharmacy on 12/18/2021