GI MOTILITY
Educational Objectives
| The goal of this program is to improve the management of fecal incontinence, infectious diarrhea, and gastric function in diabetes.
After hearing and assimilating this program, the clinician will be better able to:
|
 | 1. Discuss the management of fecal incontinence.
|
| 2. Utilize the appropriate treatment option for the patient with fecal incontinence.
|
| 3. Explain the correlation between the pathophysiologic changes seen in the gastrointestinal tract in diabetes and the
symptoms manifested.
|
| 4. Review the major bacterial and viral pathogens causing diarrhea.
|
| 5. Summarize the diagnosis and treatment of diarrhea.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee 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. Soffer is
a consultant and researcher for Metacure. Dr. Engel and the planning committee reported nothing to disclose.
Acknowledgements
Dr. Soffer was recorded at the 8th Annual Update in Gastroenterology, held October 26-28, 2007, in La Quinta, CA, and
sponsored by the Cedars-Sinai Medical Center, Division of Gastroenterology. Dr. Engel was recorded at 29th Annual
Advances in Infectious Diseases: New Directions for Primary Care, held May 14-16, 2008, in San Francisco, CA, and
sponsored by the University of California, San Francisco, School of Medicine, Division of Infectious Diseases. The
Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
| FECAL INCONTINENCE —Edy E. Soffer, MD, Co-Director, GI Motility Program, Cedars-Sinai Medical Center, Los Angeles,
CA
|
| Sphincter mechanisms: internal anal sphincter—smooth muscle; innervation autonomic; maintains tone; responsible
for 70% of tone at rest; external anal sphincter—augments internal sphincter; striated muscle; innervation somatic via
pudendal nerve; augmented by puborectalis; rectum—other sphincter mechanism; reservoir organ; relaxes when stool
present; healthy compliant rectum important; compliance lost with, eg, radiation therapy, infection due to toxin
|
| Incontinence: colon and small bowel—diarrhea overwhelms mechanism; inability to control quick distention from gush
of liquid; rectal impairment— sensory (due to inflammation); compliance (due to disease, eg, inflammatory bowel disease
[IBD], radiation therapy); neurologic deficit (major problem in nursing home patients); sphincter weakness— etiology
obstetric, surgical (eg, hemorrhoidectomy), neuropathic, or myopathic
|
| Evaluation: history—determine whether air, fluid, or solid lost and whether urge (better prognosis) or passive incontinence
(problem with perception and lack of tone in anal canal); bowel habits; sexual habits (anal intercourse results in
trauma that damages sphincter over time); obstetric history—ask about, eg, vaginal delivery, weight of baby, length of
labor, episiotomy, tears; physical examination—perianal appearance, eg, presence of excoriations, skin damage, gaping
anus (bad prognostic sign); sensation in perianal area (pudendal nerve); prolapse; digital examination for tone; impaction
result of overflow incontinence; impaction at level of sigmoid not detected digitally (if suspected, obtain kidneys, ureter,
bladder [KUB] x-ray); in most patients, perform flexible sigmoidoscopy and colonoscopy with biopsies in those with diarrhea,
even if mucosa normal
|
| Obstetric trauma: damage to sphincters and pudendal nerve or both, even after uncomplicated vaginal delivery (occurs
in approximately one-third of primiparous patients with no symptoms and normal anatomy and physiology); use
of forceps increases rate of sphincter disruption; disruption persists over time; sphincter damage associated with fecal
incontinence; in symptomatic women, second vaginal delivery worsens symptoms
|
| Tests: anorectal manometry—looks at internal and external sphincter pressure and rectal sensation; helps with biofeedback;
endoanal ultrasonography (US)—integrity of anal sphincter; pudendal nerve terminal motor latency—not commonly
used; detects neuropathy of distal pudendal nerve (last 10 cm); prognostic factor for overlapping sphincter repair
|
| Medical treatment: perianal hygiene—keep area clean and dry; if excoriations present, use zinc lotion or calamine lotion;
excoriated skin possibly infected with Candida (anti-Candida creams provide relief); treatment of impaction—if
overflow incontinence present, induce bowel movement to clear problem; control of diarrhea; manipulation of bowel
movements; anorectal manometry—able to determine pressure, sensation, and whether coordination present between
bearing down and relaxation; if isthmus or pelvic floor dyssynergia present, proceed with biofeedback
|
| Biofeedback: increases sphincter strength and rectal sensation; manometry, electromyography (EMG), or both (4-6 sessions);
severe incontinence, neuropathy, and passive incontinence not likely to respond; variable success (50%-80%);
speaker’s opinion that surgery not solution and biofeedback safe but takes time
|
| Surgery: depends on whether sphincter defect present; if defect present, chance for sphincter repair; if no defect, interventions
include sphincter replacement or stoma
|
| Sphincter repair: almost always performed for postobstetric injury; scar tissue in sphincter cut, overlapped, and sutured to
normal tissue; most beneficial for women with anterior obstetric defect; obesity and duration of incontinence negatively
affect outcome; most successful surgical therapy currently available; 50% to 80% success rate but deteriorates
over time
|
| Bulking agents: not approved or not effective
|
| Artificial-bowel sphincter: used when patient’s sphincter thin and ineffective; high morbidity; revision commonly
needed; improves incontinence and quality of life (QOL) but at high price; prophylactic antibiotics reduce infection;
approved for use in United States; seldom used
|
| Sphincter overlap or transposition: for patients without sphincter defect; somatic muscle (gluteus or gracilis) wrapped
around anal canal and hooked into ischial spine on other side; neurostimulator delivers pulses constantly, causing
muscle to maintain tone; magnet placed when muscle relaxation desired for bowel movement; no longer manufactured
|
| Sacral nerve stimulation: best option; not yet approved in United States; used in Europe; started as intervention for urinary
incontinence; first used temporarily (inserting electrodes into S2 and S3 for 1 to 2 wk, then delivering stimulation
by external electrodes); response assessed by manometry of external sphincter; patients who respond to temporary
measure go on to permanent implantation; approved only for urinary incontinence in United States
|
| DIABETES AND GASTRIC FUNCTION —Dr. Soffer
|
| Physiology: stomach—not single organ; segments function differently; fundus—reservoir; able to relax due to vagus
nerve and inhibitory neurotransmitters (primarily nitric oxide); antrum—contains pacemaker cells (interstitial cells of
Cajal [ICCs]); ICCs form networks in myenteric plexus in between nerves and muscle and serve as pacemaker cells and
help in neurotransmission; spread of electrical activity determines organization of contractions in stomach; if disrupted,
contractions also disrupted; antrum pump grinds food; gastric emptying takes hours; food leaves stomach in particles not
>2 mm and crosses pylorus into small bowel
|
| Gastric reflexes: cause stomach segments to work in unison; modulated mostly by mechanoreceptors; positive and negative
feedback flow between segments; depend on enteric and autonomic nerves; control gastric motor function and emptying;
when individual eats, fundus relaxes; first reflex to make antrum stop pumping in anticipation of food coming; as
food moves down, it hits pump and grinding starts; with normal pump and pacemaker activity, grinding continues; inhibition
ensures delivery to small bowel at steady pace; small bowel unable to take large volumes; lag phase in gastric emptying
curve due to time required for food to move from fundus to pylorus; steady state ensures that food not dumped too
fast into small bowel (blocks stomach if too much food comes out); relationship reversed with liquids (come out quickly
since no grinding needed)
|
| Changes in diabetes: vagus and sympathetic nerves possibly affected; reduction in formation of nitric oxide, leading to
loss of accommodation reflex (fundus does not relax); pacemaker cells disrupted or markedly reduced, leading to abnormal
rhythm (tachygastria, bradygastria, or irregular rhythm); antral pump slows, with inefficient contractions and grinding;
pylorus spastic; typically, most segments affected
|
| Correlation between pathophysiology and symptoms in diabetes: dysrhythmia, antral hypomotility, or
pylorospasm—present as delayed gastric emptying manifesting as early satiety, nausea and vomiting, bezoar formation,
or unpredictable glycemic control; reduced nitric oxide—impaired fundic relaxation and potentially rapid emptying; in
10% to 50% of diabetics (particularly type 2), rapid emptying present, particularly of liquids; translates into symptoms of
early satiety and dumping; vagal spinal neuropathies—gastric hypersensitivity if performing balloon studies; clinically
manifests as pain; caveat—most data from animal models
|
| Pathophysiology: effect of hyperglycemia—raising blood glucose (BG) reduces motility of antrum, induces spasm of
pylorus, disrupts electrical rhythm, delays gastric emptying, and increases sensitivity to gastric and intestinal stimulation;
usually seen with BG 160 to 180 mg/dL or higher; inducing hypoglycemia reverses effects, eg, gastric emptying speeds
up; what happens to glucose when stomach impaired important for BG control; postprandial BG depends, in part, on rate
of delivery of nutrients to small bowel; gastric emptying accounts for ≈35% of variance in peak BG (other factors include
glycemic index of food); postprandial BG, compared to fasting BG, possibly more important in overall glycemic control
and effects of elevated BG; slowing of gastric emptying in type 2 diabetics by glucagon-like peptide (GLP)-1 improves
glycemic control (more time for insulin to work); little data from humans about effect on vagus and sympathetic nerves;
reduced ICCs in stomach of diabetic animal models and patients associated with disrupted electrical rhythm
|
| Therapy for diabetic gastroparesis: gastric electrical stimulation—2 multicenter studies showed improvement in
symptoms and QOL, allowing discontinuation of alternative nutrition in some patients; further studies showed no effect on
rhythm, and effect on gastric emptying inconsistent; data show possible effect on nausea center but unproven;
nitroglycerin—donor of nitric oxide; inhibits gastric emptying; clonidine—α-adrenergic agonist; slows gastric emptying;
cyclic guanosine monophosphate (cGMP)—effector molecule of nitric oxide and drives smooth muscle relaxation; hydrolyzed
by phosphodiesterase; sildenafil (Viagra)—blocks phosphodiesterase, leading to increased cGMP and more smooth
muscle relaxation; small study showed no effect on gastric emptying; overall effect unpredictable; botulinum toxin type A
(Botox)—binds to presynaptic acetylcholine terminals and blocks neurotransmission, reducing excitation and promoting
muscle relaxation; open-label trials in which Botox injected into prepyloric area noted improvement in symptoms but inconsistent
effect on gastric emptying; may be helpful in selected patients
|
| INFECTIOUS DISEASE APPROACH TO DIARRHEA —Joanne Engel, MD, PhD, Professor of Medicine, Microbiology,
and Immunology; Chief, Division of Infectious Diseases; Director, Microbial Pathogenesis and Host Defense Program,
University of California, San Francisco, School of Medicine
|
| Differential diagnosis: infection; ischemic damage to bowel; inflammatory bowel disease; iatrogenic or osmotic
causes; malabsorption; infectious—viral, bacterial, and protozoal; prime viral candidates include caliciviruses (Norwalk
and norovirus), and rotavirus; major bacterial pathogens in United States include Salmonella, Campylobacter, and Shigella,
enterohemorrhagic Escherichia coli, and Clostridium difficile; protozoan causes include Giardia, Entamoeba histolytica
, Cryptosporidium, Microsporidium, and Cyclospora; inflammatory diarrhea—clues include when and how illness
began, stool characteristics, frequency, presence of dysenteric symptoms, other associated symptoms, and epidemiology
|
| History: includes whether patient traveled to developing area; day care center contact or attendance; employment; consumption
of unusual foods, raw meats, eggs, or unpasteurized milk or cheese; swimming in or drinking from untreated
fresh water; visit to farm or exposure to zoo animals or pet reptiles; exposure to other ill persons; medications, especially
antibiotics (C difficile diarrhea); underlying medical conditions; sexually transmitted diseases (STDs); whether patient
food handler or caregiver
|
| Viral diarrhea: resolves on its own within 3 days (distinguishes it from bacterial diarrhea); exception rotavirus in young
children
|
| Rotavirus: usually affects children 6 to 24 mo of age; infants protected up to 3 mo of age by maternal antibodies; children
usually have 1 episode before 5 yr of age; multiple serotypes; leading cause of disease in developing nations; most disease
caused by 4 main serotypes
|
| Vaccines: 2 new live oral vaccines; given to infants at same time as diphtheria, pertussis, and tetanus (DPT) vaccine; extensive
studies show both safe and efficacious; neither vaccine showed increased risk for intussusception; side effect
profile similar to placebo; Rotarix—85% effective against severe disease; 75% effective against other serotypes
(cross-protection); 42% decrease in all diarrhea-associated hospitalizations in children <1 yr of age; Rotateq—almost
100% efficacy against severe disease; ≈60% decrease in hospitalizations in children <1 yr of age; caveat—efficacy of
oral vaccine in malnourished infants and in nonvaccine strains unknown
|
| Norovirus: came into prominence due to outbreaks on ships; reasons for increase in outbreaks—multifactorial; large
number of susceptible individuals; multiple strains, with new strains appearing; immunity strain-specific and short-lived;
spread by multiple routes (eg, person-to-person, vomitus, diarrhea, food, contact with contaminated surfaces); low infectious
dose; environmentally stable (resistant to commonly used disinfectants, heat, and freezing); accounts for >50% of
all foodborne outbreaks; risk in general population 1 in 12 (1 in 1200 on ships); direct contamination from food handler;
hand washing important
|
| Major pathogens for bacterial diarrhea (United States): Campylobacter, Salmonella, Shigella, and E coli
0157:H7 (Shiga toxin-producing E coli [STEC]; associated with hemolytic-uremic syndrome); consider if diarrhea lasts
>3 days
|
| Bacterial stool cultures: most sensitive early in illness (first 3 days); up to 2 cultures cost-effective; diagnostic yield
1.5% to 5.5%; cost savings ≈$1000/positive culture; current guidelines suggest performing only if duration of symptoms
≥24 hr; reasonable in presence of inflammatory diarrhea (eg, blood and/or pus in stool, high fever); send stool sample to
laboratory promptly to prevent overgrowth of normal flora; negligible yield if patient hospitalized >3 days; study suggested
stool cultures possibly helpful in HIV patient hospitalized >3 days, immunocompromised patients, elderly, and
those with comorbid illness; special requests to laboratory necessary for cultures of Vibrio cholerae, Yersinia, STEC, Aeromonas
, and Plesiomonas
|
| Tests for parasites: not useful in patients with hospital-acquired diarrhea; consider if patient has symptoms for >1 wk,
history of camping, or has exposure history; direct fluorescent antigen (DFA) assay for Giardia and Cryptosporidium
faster and more sensitive, but misses other pathogens seen by ova and parasites (O and P) test; O and P test—3 specimens;
first specimen has 70% sensitivity (second and third have combined sensitivity of 10%); consider if patient HIV-
positive, broader range of parasitic diseases suspected, or if symptoms persist and DFA negative
|
| Treatment: fluids primary treatment for any diarrhea; antibiotics adjunctive and used only under special circumstances;
most diarrheas resolve on their own; symptomatic relief with antimotility agents; bismuth subsalicylate (Pepto-Bismol)
for enterotoxigenic E coli; bland diet; role of antibiotics—decrease fecal excretion (important with Shigella and Salmonella
, in which only few bacteria sufficient to transmit infection); resolve persistent or life-threatening infections (eg, Giardia
, amoebiasis, cholera); hasten recovery by 1 to 2 days in traveler’s diarrhea and domestically acquired diarrhea;
weigh benefits of giving antibiotic in setting where infection resolves on its own against development of antibiotic resistance;
antibiotic options—include fluoroquinolones (effective against most bacterial pathogens); azithromycin for traveler’s
diarrhea; trimethoprim-sulfamethoxazole (TMP-SMZ) used in children but resistance significant; metronidazole
for diarrhea caused by C difficile, persistent Giardia infection, and E histolytica; treat STD if associated with diarrhea
|
Suggested Reading
Bharucha AE et al: Recent advances in assessing anorectal structure and functions. Gastroenterology 133:1069, 2007;
Brandt LJ: Bloody diarrhea in an elderly patient. Gastroenterology 128:157, 2005; Camilleri M: Clinical practice. Diabetic
gastroparesis. N Engl J Med 356:820, 2007; Casburn-Jones AC et al: Management of infectious diarrhoea. Gut
53:296, 2004; Dudding TC et al: Obstetric anal sphincter injury: incidence, risk factors, and management. Ann Surg
247:224, 2008; Featherstone PJ et al: Images in clinical medicine. Gastric dilatation secondary to diabetic autonomic
neuropathy. N Engl J Med 353:2696, 2005; Frudinger A et al: The natural history of clinically unrecognized anal
sphincter tears over 10 years after first vaginal delivery. Obstet Gynecol 111:1058, 2008; Glasheen JJ et al: Value of repeat
stool testing for Clostridium difficile. Am J Med 120:e11; author reply e13, 2007; Gonlachanvit S et al: Effect of
altering gastric emptying on postprandial plasma glucose concentrations following a physiologic meal in type-II diabetic
patients. Dig Dis Sci 48:488, 2003; Gregory WT et al: Quantitative anal sphincter electromyography in primiparous
women with anal incontinence. Am J Obstet Gynecol 198:550, 2008; Grimwood K et al: Rotavirus vaccines must perform
in low-income countries too. Lancet 370:1739, 2007; in: N Engl J Med. 2007 Jul 26;357(4):427. Marignani M et
al: Acute infectious diarrhea. N Engl J Med 350:1576, 2004; Michelsen HB et al: Sacral nerve stimulation for faecal
incontinence alters colorectal transport. Br J Surg 95:779, 2008; Norton C et al: Management of faecal incontinence in
adults: summary of NICE guidance. BMJ 334:1370, 2007; Probert CS et al: A novel method for rapidly diagnosing the
causes of diarrhoea. Gut 53:58, 2004; Roach M et al: Fecal incontinence in the elderly. Geriatrics 63:13, 2008; Russo
A et al: Insulin-induced hypoglycemia accelerates gastric emptying of solids and liquids in long-standing type 1 diabetes.
J Clin Endocrinol Metab 90:4489, 2005; Ryan ET et al: Illness after international travel. N Engl J Med 347:505, 2002;
Stacher G et al: Impaired gastric emptying and altered intragastric meal distribution in diabetes mellitus related to autonomic
neuropathy? Dig Dis Sci 48:1027, 2003.
|
