Bowel Stop and Go

Educational Objectives

The goal of this program is to improve the management of constipation and diarrhea. After hearing and assimilating this program, the clinician will be better able to:

1.   Employ the Rome III criteria for diagnosis of chronic constipation.

2.   Describe and utilize the treatment options for chronic constipation.

3.   Describe and utilize the treatment options for chronic diarrhea.

4.   Review the commonly used drugs that can causediarrhea.

5.   Discuss the infectious and noninfectious causes of diarrhea.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committe to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Peura is a consul­tant and speaker for Takeda Pharmaceutical. In his lecture, Dr. Peura discusses the off-label or investigational use of a ther­apy, product, or device. Dr. Weisiger and the planning committee reported nothing to disclose.

Acknowledgements

Dr. Peura was recorded at the 18th Annual GI Symposium, held November 1, 2008, in New Brunswick, NJ, and sponsored by the University of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School, Department of Medicine, Division of Gastroenterology and Hepatology. Dr. Weisiger was recorded at the 37th Annual Advances in Internal Medi­cine, held May 18-22, 2009, in San Francisco, CA, and sponsored by the University of California, San Francisco, School of Medicine. The Audio-Digest Foundation thanks Drs. Peura and Weisiger and the sponsors for their cooperation in the pro­duction of this program.

The Constipation Conundrum: What to Do

David A. Peura, MD, Professor, Department of Medicine, Division of Gastroenterology and Hepatology, University of Vir­ginia Health Sciences Center, Charlottesville

Prevalence: affects all ages and all sexes; more prevalent in women and increases with age (irritable bowel syndrome [IBS] seen in younger women and decreases with age); as population ages, sex difference disappears; constipation associated with decreased quality of life (QOL; improves with treatment), depression, immobility, and psychologic distress; laxatives third and fourth most frequently used medications in elderly population; stimulants and bulking laxatives most common

Racial and ethnic incidence: more common in nonwhite than white patients; significant economic impact seen

Perceptions of chronic constipation: physician  — frequency-based;  £1 bowel movement (BM) every 3 to 4 days; patient  —symptom-based; quality of defecation, eg, straining, hard stools, incomplete evacuation

Definition: Rome III criteria  —  chronic constipation must include ³2 of following, ie, straining, lumpy or hard stools, incomplete evacuation, sensation of obstructive blockage, manual maneuvers to assist defecation, or infrequent def­ecation; quality as important as quantity in diagnosis; loose stools unusual in chronic constipation, unless patient on laxatives

Differentiating chronic constipation from IBS: abdominal pain  —  necessary for diagnosis of IBS; IBS shares sev­eral symptoms with constipation, eg, straining, lumpy hard stools; reduced number of BMs not seen in most pa­tients with IBS; other differentiating symptom visceral hypersensitivity or abdominal bloating (excessive bloating or distention not really present); having patient lie on table eliminates accentuated lumbar lordosis (position as­sumed to offset visceral hypersensitivity)

Clinical evaluation and diagnostic approach: extensive testing nor needed; ask patient key questions and to de­scribe stool; perform abdominal and digital rectal examinations; evaluation of sphincter  —  have patient strain on finger and, if contracting (rather than relaxing), disordered defecation present; key questions  —  what patient means by constipation; presence of abdominal pain (to differentiate from IBS); what medications patient taking; presence of alarm signs or symptoms

Possible secondary causes of constipation: medications; neurologic disorders; endocrine disorders (constipation most common gastrointestinal [GI] manifestation of diabetes); stool form  —  basis for categorizing IBS and for treatment

American College of Gastroenterology (ACG) Task Force: no action necessary, other than empiric treatment, if alarm signs or features absent; diagnostic studies indicated in patients with alarm signs or symptoms or those >50 yr of age who require colorectal cancer screening; alarm signs and symptoms  —  bleeding; family history; anemia; persistent condition unresponsive to treatment; new-onset symptoms in elderly patient; unexplained systemic symptoms

Specialized diagnostic tests: colonoscopy; colonic transit studies; marker studies; balloon expulsion test as part of anorectal manometry; if balloon expelled in 3 min, mechanism functioning; if not expelled, disordered defecation probable; colonic manometry; defecography to look for structural disorders

Treatment: no evidence to support hydration, increased intake of fiber, and exercise, although lifestyle measures ef­fective; dedicated bathroom time important; probiotics  —Align, Activa yogurt, and DanActive shown effective in randomized trials; suppositories and enemas  —  stimulate rectum; bulking agents  —  only psyllium studied; stool softeners  —  widely prescribed; not effective; osmotic laxatives  —  polyethylene glycol (PEG); lactulose actually prebiotic; stimulant laxatives  —  for patients on long-term opiates; psyllium  —  effective, compared to placebo; stud­ied only in short-term trials; lactulose  —  effective, but leads to bloating and gas; PEG  —  effective; approved only for short-term use; over-the-counter if used for 1 wk (prescription required if used for 2 wk); data show long-term efficacy in adults (off-label use); effective for £1 yr; tegaserod  —  off market; available only for life-threatening condition; lubiprostone  —  only drug approved for chronic constipation; when type 2 chloride channels in intestine open, exit of chloride with sodium and water seen; presence of isotonic fluid distends intestine, causing BM; dose for chronic constipation 24 µg bid (for IBS-constipation predominant [IBS-C], one-third of dose or 8 µg bid); 50% to 80% of time, BM occurs within first 2 days of starting drug; generally taken on as-needed basis by patients; long-term efficacy shown

Special patient populations: institutionalized patients  —  >50% of patients residing in institutions or geriatric hospi­tals expected to have constipation and require laxation; fiber problematic due to possibility of impaction; disor­dered defecation  —   screened with balloon expulsion test (high sensitivity and positive predictive value); benefit from biofeedback therapy; patients who require surgery  —  rare; realistic expectations necessary; surgery offered by speaker only in patients with documented slow transit by marker study; disordered defecation excluded; anorectal manometry performed before surgery; must also  rule out generalized intestinal dysmotility; psychologic screening for all patients; total colectomy  —procedure of choice; unacceptable result if anything less performed; persistent abdominal pain, diarrhea, and incontinence seen in small number of patients

Evaluation and Management of Diarrhea

Richard A. Weisiger, MD, PhD, Clinical Professor of Medicine, and Chief, Gastrointestinal Faculty Practice, University of California, San Francisco, School of Medicine

Definition: stool volume >200 g daily; for patient, loose or watery stools, urgent stools, or incontinence

Approach: duration  —  acute (first 2 wk); chronic (>1 mo); character  —  watery; bloody (likely inflammatory or in­fectious); fatty (likely malabsorption); timing  —  frequency; relation to meals; nocturnal; associated symptoms  —  if flu-like or with fever, likely infectious; weight loss suggests malabsorption; tenesmus suggests inflammatory dis­ease involving rectum; inciting factors  —  whether other people infected; milk ingestion

Laboratory studies: if diarrhea <24 hr, reasonable to provide fluid replacement and adopt watchful waiting; if diar­rhea severe, bloody, accompanied by fever, or persistent, reasonable to perform stool studies; chronic diarrhea  —  stress most common reason in patients with previously undiagnosed IBS; obtain social history; if diarrhea severe, appropriate to send patient to emergency department (ED)

Treatment of severe acute diarrhea: intravenous (IV) fluid replacement effective; if IV fluid replacement not avail­able, World Health Organization (WHO) recommends oral replacement therapy, with electrolytes (sodium and po­tassium) and glucose; absorption of fluid by small intestine involves sodium-dependent glucose cotransporter; once stool studies performed, acceptable to treat empirically for presumed infection

Treatment of chronic diarrhea: fiber  —  recommended for functional diarrhea; attapulgite (eg, Kaopectate)  —  effective at binding irritating components in stool; not used as much as formerly; effective; use with care in elderly (can cause bowel obstruction if too much given); bismuth subsalicylate (eg, Pepto Bismol)  —  highly effective; cyto­protective and antibacterial (in stomach and small intestine; used to treat Helicobacter pylori); anti-inflammatory due to salicylate component and tends to block secretion of fluid; linked to Reye’s syndrome (severe, potentially fa­tal liver abnormality that occurs when children or teenagers treated with aspirin-like drug after influenza-type in­fection); use only in adults; loperamide (eg, Imodium)  —  over-the-counter; no risk for dependency; alosetron (Lotronex)  —  for treatment of IBS, but later withdrawn from market (caused severe constipation requiring surgery); back on market on limited prescribing protocol; although targeted for diarrhea-predominant IBS (IBS-D), also ef­fective for other forms of chronic diarrhea; diphenoxylate and atropine (Lomotil)  —  some narcotic dependency risks; octreotide  —somatostatin analog; long-acting; effective at turning off all secretions from pancreas and parts of GI tract; given parenterally only; tincture of opium (paregoric and laudanum)  —  laudanum 25 times more con­centrated than paregoric; most effective, especially in HIV patients with chronic cryptosporidiosis; should not pre­scribe as tincture of opium (ambiguous)

Commonly used drugs that cause diarrhea: sorbitol  —marketed as laxative; main component in sugar-free gum and diabetic candies; lactose  —  major filler ingredient in many medications (pills); antibiotics  —  diarrhea can oc­cur while patient on antibiotics (not just after completing course); any antibiotic can cause diarrhea; antidiabetics  —metformin major culprit; acarbose inhibits certain polysaccharide-degrading enzymes in brush bor­der of small intestine; other drugs  —  proton pump inhibitors (PPIs);  psychotropic drugs (cause diarrhea and consti­pation); cardiac drugs

Functional diarrhea: not all patients with functional diarrhea have full-blown IBS (possibly just stress-related); typ­ically chronic or intermittent; correlates with stress; soft nonbloody stools typical, usually with mucus; may alter­nate with constipation; rarely nocturnal; patient may have formed stool in morning, with subsequent stools progressively looser; postinfectious diarrhea or IBS may develop after resolved infection (enteritis); more common after childhood abuse or neglect; should exclude celiac sprue and thyroid disorders before making diagnosis of functional diarrhea; treatment often symptomatic with antidiarrheal drugs

Malabsorption: 3 categories; pancreatic  —  chronic pancreatitis (secretory capacity of gland lost); Whipple proce­dure for pancreatic tumor; inadequate production of digestive enzymes, typically lipase; with inadequate lipase, tri­glycerides present in large intestine and broken down by bacteria into free fatty acids (irritating to colon; act as stimulant laxative); abnormalities of mucosal surface  —  abnormally small surface area (eg, short bowel syndrome, bypass surgery); celiac sprue (disruption of normal microvillous pattern of bowel); inborn errors of metabolism that present with diarrhea; brush border is carbohydrate matrix, extracellular, and loaded with enzymes for digesting peptides and oligosaccharides for absorption; disruption of brush border or microvilli causes malabsorption; abnor­malities in liquid phase  —  lack of bile acids due to inadequate production, malabsorption, or deconjugation from bacterial overgrowth; improper pH (enzymes require neutral pH) as in Zollinger-Ellison syndrome (too much acid) and pancreatic insufficiency (inadequate bicarbonate); diabetic enteropathy allows for bacterial overgrowth due to insufficient contractions; diagnosis  —  stain for undigested food); absorption tests

Celiac sprue: relatively common cause of mild diarrhea with no weight loss; can present as iron deficiency without diarrhea; damages upper intestine, particularly duodenum (responsible for iron absorption); tests  —  none standard­ized; gluten-elimination diet difficult; antigliadin antibodies relatively nonspecific and insensitive; antiendomysial antibody; tissue transglutaminase best; small bowel biopsy to confirm

Bile salt malabsorption: diagnosed with good history; any patient with ileal disease at risk; bile salts reabsorbed at terminal ileum; seen with bacterial overgrowth; treated with bile acid binders, eg, cholestyramine

Neoplasms: <1% of diarrhea caused by neoplasms secreting compounds that cause diarrhea (eg, vasoactive intestinal peptide, gastrin, glucagon); most pancreatic endocrine neoplasms; medullary thyroid cancer, carcinoid syndrome, and systemic mastocytosis all have circulating humoral factor that causes diarrhea

Infectious causes

Traveler’s diarrhea: more common in those traveling to underdeveloped countries, younger travelers, PPI users, and those with concurrent illness; most common causative agent enterotoxigenic Escherichia coli (ETEC); also vi­ruses and parasites; prevention from careful selection of food and water; prophylactic antibiotics no longer rec­ommended by Centers for Disease Control and Prevention (promotes resistance and provides false sense of security); treatment fluid replacement in mild cases and bismuth or fluoroquinolone in severe cases

Clostridium difficile: increasingly difficult to control as nosocomial problem; several strains, but not all produce cy­totoxins; somatic assay screens for antigen (proves that C difficile present, but not presence of toxin); cytotoxin assay more expensive; hand washing with alcohol gels not effective (does not kill spores); drug resistance emerg­ing; human and animal strains identical

Food poisoning: generally bacterial; enterotoxins  —  eg, ETEC, Vibrio cholera; “rice water” diarrhea; cytotoxins  —eg, C difficile, enterohemorrhagic E coli, Shigella, Vibrio parahaemolyticus; diarrhea likely bloody, inflammatory, and associated with systemic signs; enteroinvasive  —diarrhea inflammatory

Norwalk virus: now termed norovirus;  no assay available;  outbreaks in cruise ships seen; spread by food, water, and fomites; incubation period 1 to 2 days; characterized by nausea, vomiting, cramps, and watery diarrhea; usually self-limited and does not require hospitalization (just fluid replacement); treatment bismuth (antibiotics ineffec­tive); prevented by hand washing and not touching hands to mouth

Adenovirus: causes upper respiratory infection with severe diarrhea, typically in children <2 yr of age; self-limited; treatment hydration

Rotavirus: usually seen in day care centers and during winter months; no specific treatment; serious sequelae rare

Entamoeba histolytica: invasive (once in gut, migrates through blood to other organs and cause abscesses, most com­monly in liver); symptomatically similar to bacterial abscess; eventually form cysts which pass from body to infect others

Giardiasis: more common in day care centers; organism motile and flagellated; sucker on ventral surface used to ad­here to lining of small intestine; typically colonizes upper intestine and causes diarrhea through different mecha­nisms (interferes with absorption of food nutrients, causes inflammation, covers up surface area, and causes flattening of villi); cyst extraordinarily stable at cold temperatures

Cryptosporidiosis: no treatment; cleared by body; typically transmitted in drinking water; standard method of disin­fecting drinking water not always effective (chlorine ineffective for killing cysts); cysts lodge in small intestine; generally, immune system clears organism; sometimes fatal; most common cause of chronic diarrhea in HIV-posi­tive patients

Microsporidiosis: spread by spores, either swallowed or inhaled; spore has polar tubule that injects infectious mate­rial into cytoplasm of enterocyte; reproduction of spores occurs in cytoplasm or inside vacuole; cell eventually rup­tures, releasing spores

Cyclospora: seen only in tropics; single-celled parasite; causes cyclical diarrhea, typically lasting »6 wk; self-limited

Suggested Reading

Adams BD et al: The law of unintended consequences: The Joint Commission regulations and the digital rectal examination. Ann Emerg Med. 51:197, 2008; Bleser SD: Practical symptom-based evaluation of chronic constipation. J Fam Pract. 55:580, 2006; Boujaoude J et al: When does severe diarrhoea disclose a hereditary disease? Gut. 56:342, 2007; Carpenter LR: Stool cultures and antimicrobial prescriptions related to infectious diarrhea. J Infect Dis. 197:1709, 2008; DiPalma JA et al: A com­parison of polyethylene glycol laxative and placebo for relief of constipation from constipating medications. South Med J. 100:1085, 2007; Kalish VB et al: Clinical inquiries. What is the best treatment for chronic constipation in the elderly? J Fam Pract.56:1050, 2007; Konfortov MB: Probiotics and diarrhea: No proton pump inhibitors? BMJ. 335:171, 2007; Krier MJ et al: Management of severe Clostridium difficile-associated diarrhea. Dig Dis Sci. 54:1199, 2009; Nair P et al: Epidemiology of cryptosporidiosis in North American travelers to Mexico. Am J Trop Med Hyg. 79:210, 2008; Ripetti V et al: Is total colectomy the right choice in intractable slow-transit constipation? Surgery. 140:435, 2006; Stebbins S: Rotavirus: disease and vaccine up­date, 2007. J Fam Pract. 56(2 Suppl):S6-11, 2007; Talley NJ: Managing chronic constipation from constipating medicines. South Med J. 100:1070, 2007; Troeger H et al: Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum. Gut. 56:328, 2007; Wichro E et al: Microsporidiosis in travel-associated chronic diarrhea in im­mune-competent patients. Am J Trop Med Hyg. 73:285, 2005.