An 18-year-old woman presents to your clinic for a third opinion regarding her chronic constipation. This has been present since she was a young child. She has tried multiple over-the-counter (OTC) therapies including soluble and insoluble fiber, polyethylene glycol 3350, senna, bisacodyl suppositories, and enemas. She has also tried and failed lubiprostone, linaclotide, and plecanatide. Many of these treatments have been tried in combination and were ineffective. She has undergone 2 colonoscopies (both normal) and serologies including CBC, TSH, and basic metabolic panel have been unrevealing. She has been told that she should see a surgeon for a colectomy. Currently, she is having 1 bowel movement per week. These range from Bristol 1-6 in texture, and she reports sensations of incomplete evacuation. She is concerned because she never feels like she has an urge to defecate. She does not perform manual disimpaction. She denies a history of abuse. Her physical exam including digital rectal exam is normal. Prior to addressing the need for a colectomy, an anorectal manometry is performed revealing the results shown in figures A and B. Which of the following would be the next most appropriate step in her care?
- This young patient has failed to respond to multiple classes of therapeutics and reports experiencing symptoms since childhood. In these instances, the probability of dyssynergic defecation increases and laxatives are ineffective in most cases for treating individuals with this disorder. However, the anorectal manometry (ARM) results reveal a normal bear-down pattern. As seen in FIGURE B, there is an appropriate increase in intra-rectal pressure (>45 mm Hg) and relaxation of the pelvic floor. FIGURE A represents testing for the recto-anal inhibitory reflex (RAIR). When the rectum is distended with a balloon at the end of the ARM catheter, there should be reflexive relaxation of the internal anal sphincter. However, this is not identified in this patient. A failure to identify sphincter relaxation (especially in young individuals without a neuropathic disorder) is concerning for potential Hirschsprung’s disease. While Hirschsprung’s is usually identified in infancy and childhood, some cases escape diagnosis until late adolescence/early adulthood. Consequently, further testing via double-contrast barium enema (DCBE) or deep rectal tissue biopsy would be the next most prudent course of action.
A 35-year-old woman reports chronic heartburn and water brash symptoms an average of 4 days a week. She also notes epigastric burning and nausea, and some early satiety postprandially, and waking from sleep with these symptoms. Her weight has been stable, and she denies any family history of GI malignancy. Her past medical history is notable for IBS with diarrhea. Her current medications include pantoprazole 40 mg twice daily and loperamide as needed for diarrhea. In the past year, she had an EGD with no evidence of esophagitis or gastritis, and no hiatal hernia. She undergoes a 72-hour capsule pH test after discontinuing her proton pump inhibitor for 5 days [figure]. The patient noted that her symptoms were “terrible” off her PPI, and she reported 168 symptom experiences (heartburn and epigastric pain) during the course of the study. Based on these results, which of the following is the most appropriate treatment?
A. Increase pantoprazole to 40 mg in the morning and 80 mg at bedtime.
B. Add an evening dose of ranitidine 150 mg at bedtime.
C. Add baclofen 10 mg 3 times daily.
D. Refer for anti-reflux surgical procedure.
E. Add amitriptyline 25 mg at bedtime.
This patient has a multitude of GI symptoms, including heartburn and dyspepsia, as well as IBS. This constellation of sensory GI symptoms increases the likelihood that she has a functional GI disorder. Her capsule pH study demonstrated minimal acid exposure, with the exception of the third night of the study, when she experienced a prolonged period of acid exposure (around 12 hours at a pH <4). It is important to recognize that this observation reflects dislodgement of the capsule from the distal esophagus, with passage into the stomach (followed by an increase in pH as the capsule migrates from the stomach into the small bowel). This segment of the study should be excluded from analysis in order to avoid a false positive interpretation. Treatment efforts to further suppress acid production thus are unlikely to improve her symptoms. Baclofen can be used to decrease transient lower esophageal sphincter relaxations and thus improve reflux, and anti-reflux surgery can be an effective definitive treatment for reflux. However, neither would be indicated in view of the low degree of reflux evident on this pH test. Given the high degree of perceptive GI symptoms in this patient, she would be a reasonable candidate for a trial of tricyclic antidepressant, with the potential to improve all of her sensory symptoms.
A 25-year-old woman presents to your clinic for further evaluation of her constipation that has been present for the past 8 months. Initially, she increased both soluble fiber and water consumption without improvement. Subsequent use of PEG 3350 17 grams on a daily basis and milk of magnesia were also ineffective. She is currently using bisacodyl suppositories every 3 days which produce small, soft, loose stools with persistent sensations of incomplete evacuation. Without the suppositories, she can go 5-6 days before passing hard stools with straining and sensations of incomplete evacuation.
Upon review of her medication list, you identify that she is currently taking hydrocodone twice a day. She notes that she was involved in a motor vehicle collision 8 months earlier which was complicated by chronic lower back pain. When asked, she denies any constipation-related symptoms prior to the accident and initiation of hydrocodone. She denies any alarm signs or symptoms. A quick bowel function index (BFI) score is obtained and she scores 65. Which of the following would be the next most appropriate course of action?
A. Discontinue the use of bisacodyl and begin treatment with senna and docusate.
B. Discontinue the use of bisacodyl and begin treatment with naloxegol 25 mg daily.
C. Continue use of the bisacodyl suppositories and initiate concurrent treatment with plecanatide for the constipation.
D. Order radio-opaque marker testing to evaluate for new onset slow transit constipation.
E. Continue the use of bisacodyl suppositories and initiate a low-FODMAP diet.
This patient has developed and meets Rome IV criteria for opioid-induced constipation (OIC). She denies any constipation-related symptoms prior to initiation of opioid therapy. She also denies the development of any subsequent alarm signs or symptoms. She has attempted to modify her diet and used multiple over-the-counter (OTC) therapies without improvement. Her symptoms began immediately after beginning opioid therapy and have persisted. Constipation is the most common adverse event associated with opioid use and people do not develop tolerance to this side effect. Approximately 50% of individuals who experience OIC will respond to OTCs but for the other 50%, treatment escalation is necessary. The bowel function index (BFI) is a validated 3-item survey which can identify those with OIC who are more likely to require escalation to prescription therapy and a cut-off score of >30 identifies >93% of these individuals. This patient has a BFI of 65. Discontinuing the bisacodyl and starting other OTC therapies would not be recommended at this time.
Tx CVS
. prophylaxis : Prescribe amitriptyline 25 mg orally every night at bedtime
A 32-year-old woman with a history of supraventricular tachycardia was seen in the outpatient GI clinic for bloating and postprandial abdominal pain with nausea. She denies weight loss, vomiting, or bleeding. She notes symptoms have been worsening over the last 6 months. A recent H. pylori breath test was negative. She has had a negative HIDA scan. She endorses regular bowel movements. An EGD was performed with small bowel aspirate revealing >100,000 CFU/mL streptococcus mitis/oralis. What is the next best step in treatment for this patient?
A. Antibiotics for small intestinal bacterial overgrowth (SIBO)
B. Probiotics for SIBO
C. High-FODMAP diet for SIBO
D. Consider other causes than SIBO
SIBO can be most inclusively defined as a clinical syndrome of GI symptoms caused by the presence of excessive numbers of bacteria within the small intestine. The most recent North American consensus found that a bacterial colony count of ≥103 colony-forming units per milliliter (CFU/mL) in a duodenal/jejunal aspirate as diagnostic of SIBO. Evidence suggests that abdominal pain, bloating, gas, distension, flatulence, and diarrhea are the most common symptoms described in patients with SIBO and prevalent in more than two-thirds of patients. In general, during an upper endoscopy, a deep duodenal intubation can be achieved while minimizing suction during the insertion of the scope through the mouth and stomach and preventing cross-contamination of secretions from outside the duodenum. Care is taken not to aspirate oral secretions or stomach juices before securing the scope in the duodenum and passing the catheter. The limitations of small bowel culture include its potential for sample contamination. Strep mitis/oralis is a common oral flora and likely represents cross-contamination rather than true small intestinal bacterial overgrowth. Data do support that a low-FODMAP diet is associated with fewer fermentation products, as assessed by the breath test. Probiotics studies in SIBO are mostly small and of poor quality and probiotics may inadvertently colonize the small bowel, causing both SIBO and D lactic acidosis.
Patients with constipation with which of the following conditions are most likely to benefit from biofeedback therapy?
A. Slow transit constipation
B. Functional fecal incontinence (encopresis)
C. Solitary rectal ulcer syndrome
D. Dyssynergic defecation and rectal prolapse
E. Dyssynergic defecation and IBS
E. Dyssynergic defecation and IBS
Which of the following is an alarm symptom or sign for chronic abdominal pain? - anemia
Alarm features include but are not limited to, symptom onset after the age of 50 years, severe or progressive symptoms, unexplained weight loss, nocturnal pain, anemia, family history of GI malignancy or inflammatory bowel diease, or rectal bleeding.
Goal of biofeedback therapy
Therefore, the goal of biofeedback therapy is to: (1) correct the dyssynergia in coordination of abdominal, rectal, and anal sphincter muscles in order to achieve normal and complete evacuation; and (2) enhance rectal sensory perception in patients with impaired rectal sensation.
38-year-old woman reports a 12-year history of crampy, lower abdominal pain with associated loose, watery stools (Bristol 6-7), and some relief following bowel movements. Her symptoms are worse postprandially. Over the past several years, she has seen 3 different gastroenterologists, and was ultimately given a diagnosis of “irritable bowel syndrome with diarrhea” (IBS-D). She read recently about bile acid malabsorption as an etiology of IBS-D, and is interested in being evaluated for bile acid diarrhea (BAD). Which of the following test results would be consistent with BAD?
A. Elevated 7-alpha-hydroxy-4-cholesten-3-one (C4)
B. Elevated fibroblast growth factor-19 (FGF-19)
C. Decreased stool chenodeoxycholic acid
D. Decreased stool cholic acid
E. Elevated 75-selenium homotaurocholic acid taurine (Se-HCAT) retention
- Bile acid diarrhea (BAD) is recognized to be a relevant mechanism of IBS-D symptoms in perhaps as many as 30% of cases.
- Clinically, 3 different subtypes.
- Type 1 is related to ileal dysfunction/resection (e.g., Crohn’s disease).
- Type 2 is the primary or idiopathic subtype, as in IBS-D or functional diarrhea (e.g., this patient).
- Type 3 is associated with other gastrointestinal disorders such as celiac disease, small intestinal bacterial overgrowth, and chronic pancreatitis.
- The gold standard test for BAD in the United Kingdom is the 75-selenium homotaurocholic acid (Se-HCAT) retention test, with BAD defined by decreased retention (<10%) and severe disease characterized by <5% retention. Se-HCAT is a modified bile acid (BA) that mirrors the enterohepatic circulation of taurocholic acid. Se-HCAT testing requires oral administration of a radiolabeled synthetic bile acid followed by gamma camera measurement of retention (baseline and 7 days post administration). As Se-HCAT testing is not available in the United States, 48-hour fecal BA excretion is the gold standard test. Fecal BA testing measures the total mass of bile acids excreted per day as a measure of increased BA production. Elevations in both fecal primary bile acids - chenodeoxycholic acid and cholic acid - would be expected with BAD. Challenges of fecal bile acid testing are that it requires a 48-hour stool collection, and adherence to a high dietary fat intake (100 g per day) for 4 days. Pathophysiological links between IBS-D and altered BA metabolism include decreased signaling via the ileal enterokine, fibroblast growth factor 19 (FGF19), as well as increased circulating levels of 7-alpha-hydroxy-4-cholesten-3-one (C4), a surrogate for 7-alpha-hydroxylase activity, the first and rate-limiting enzyme in BA production from cholesterol.
A 29-year-old woman is referred to you from her gynecologist for chronic nausea, vomiting, and abdominal pain. She is followed by her gynecologist for chronic pelvic pain and interstitial cystitis. She describes chronic daily nausea that is worse in the morning when she wakes up. She is unable to eat breakfast due to nausea and abdominal pain that occurs even with a half a cup of oatmeal. While eating, she experiences worsening of the nausea, epigastric pain, palpitations, and flushing. She also frequently feels lightheaded and dizzy upon standing as well as frequent daily headaches that impact her ability to work. She has had a history of migraines since her teenage years, but they have become more frequent in her 20s. She has had an upper GI endoscopy and abdominal ultrasound which were normal. A gastric emptying scintigraphy was done which demonstrated 80% emptying of the radioactive meal at 1 hour. Which of the following tests will most likely identify the cause of this patient’s symptoms?
A. MRI brain
B. CT abdomen and pelvis
C. Fat pad biopsy
D. Autonomic function testing
E. Holter monitor
POTS
- rapid gastric emptying
- chronic nausea
- dizziness etc
Autonomic function testing can determine if patients have an exaggerated HR response to being upright. Postural orthostatic tachycardia syndrome (POTS) is defined as a sustained HR increase >30 bpm or HR >120 bpm within 10 minutes of standing. The quantitative sudomotor axon reflex test (QSART) is a test that measures autonomic control of sweating. It is a test to help diagnose peripheral or painful, small fiber neuropathy. Patients with POTS frequently experience chronic gastrointestinal symptoms with nausea, vomiting and abdominal pain present in approximately 70% of patients. Those with POTS and small fiber neuropathy are more likely to experience GI symptoms than those with POTS and no small fiber neuropathy (68% vs 26%). The most common motility abnormality found in patients with POTS is rapid gastric emptying (24-48% of patients). Rapid gastric emptying is defined as <30% retained at 1 hour.
Which of the following is a risk factor for the development of post-infection irritable bowel syndrome?
A. Age over 60 years
B. Male gender
C. Stressful life events at the time of the gastroenteritis
D. Diarrhea less than 7 days
Multiple studies and systematic reviews have found that
- age less than 60 years,
- female gender,
- stressful life events,
- anxiety and depression at the time of the gastroenteritis,
- smoking, and
- diarrhea lasting more than 7 days,
- increase the risk of developing post-infection irritable bowel syndrome.
Diagnosis of centrally mediated abdominal pain syndrome
- Continuous or nearly continuous abdominal pain
- None or only occasional relationship of pain with physiological events (e.g., eating, defecation, or menses)
- Pain limits some aspect of daily functioning.
- The pain is not feigned.
- Pain is not explained by another structural or functional GI disorder or other medical condition.
Microscopic colitis causes what kind of diarrhea?
secretory
can give you stool electrolytes and recommend colonoscopy with biopsy in 60yo F with diarrhea
HIGH FODMAP Fruits?
LOW FODMAP fruits?
- High FODMAP foods include apples, cherries, mango, pears, peaches, and watermelon.
- Low-FODMAP fruits include cantaloupes, grapes, oranges, pineapples, and strawberries.
IBS D drugs, drugs approved?
Alosetron indication? Other side effect?
TCA/Antidep like Amitrytyline, contra I when?
- Rifaxamin, Alosetron, Eluxodoline
- Alosetron is a 5-HT3 antagonist currently approved for IBS-D in women only
- severe constipation
- bipolar disorder, antidepressants could precipitate a manic episode and should likely be avoided unless prescribed with psychiatry coordination
young patient with normal colon, hx of cholecystectomy, no other hx
trial of cholestyramine 4 g every morning and evening
Other things being equal, the most likely cause of chronic diarrhea in this patient is post-cholecystectomy diarrhea due to bile acid malabsorption. This is thought to occur when the bile acid pool that normally resides in the gallbladder at night is swept from the small bowel into the colon by interdigestive motility, producing colonic secretion and motility. In the absence of a high-reliability diagnostic test, an empiric trial of a bile acid-sequestrant is the most direct way to make a diagnosis. Dosing at bedtime and in the morning is sufficient to optimize delivery of the bile acid binder to the colon in most patients. A 2-week empiric trial is sufficient to see if cholestyramine or other binding agents will control diarrhea
wireless motility capsule (WMC) study normal and abnormal
GET - gastric emptying time
SBTT - SB
CTT - colon
WGTT - whole gut transit time
- normal GET is <5 hours
- After residing in the small bowel for about 6 hours, the pH abruptly drops around 27 hours indicating that the capsule has moved into the cecum and thereafter is gradually propelled in the colon and eventually exits the body at 145 hours (normal WGTT <73 hours).
- The colonic transit time was 118 hours. Thus, the patient has delayed GET, slow CTT, and slow WGTT.
treatment to dec attacks in CVS
amitrityline
This patient meets the updated Rome IV criteria for cyclic vomiting syndrome (CVS):
•At least 5 attacks in any interval, or a minimum of 3 attacks during a 6-month period
•Episodic attacks of intense nausea and vomiting lasting 1 hour to 10 days and occurring at least 1 week apart
•Stereotypical pattern and symptoms in the individual patient
•Vomiting during attacks occurs at least 4 times per hour for at least 1 hour
•Return to baseline health between episodes
•Not attributed to another disorder
•History or family history of migraine headaches (supportive of CVS)
A 48-year-old woman presents with 8 months of postprandial fullness and upper abdominal bloating that begins within a few minutes of eating a meal. She is only able to finish about half of her regular sized meals before she is too full to eat any more. She denies vomiting or dysphagia. Over this time, she has lost 18 lb, and her BMI is now 19. She has no response to a trial of a proton pump inhibitor. She has also tried metoclopramide 10 mg before meals without response.
Upper endoscopy is performed and is notable for mild erythema of the gastric mucosa, with normal esophagus and duodenum. Biopsies of the stomach and duodenum are performed which reveal reactive gastropathy, and normal duodenal mucosa. Gastric emptying scan (after stopping metoclopramide) is performed with 20% of the standardized meal remaining after 1 hour, and 5% remaining at 2 hours. The patient’s primary concern is her weight loss due to poor oral intake. Which of the following treatment options may help her symptoms?
A. Erythromycin 250 mg before meals
B. Citalopram 20 mg daily
C. Lubiprostone 24 mcg twice a day
D. Mirtazapine 15 mg every night at bedtime
- In those with predominantly postprandial distress symptoms, prokinetics or medications that relax the fundus (buspirone or mirtazapine) can help alleviate symptoms. Tricyclic antidepressants - epigastric pain
- The patient complains of 8 months of dyspeptic symptoms, specifically postprandial distress subtype (PDS). As the patient has had negative upper endoscopy with biopsies, she fits Rome IV criteria for functional dyspepsia (PDS subtype). Of note, she has rapid gastric emptying on her gastric emptying scan, as less than 30% of a standardized meal remains after 1 hour.
- Of the choices listed, only mirtazapine has been shown to be beneficial in functional dyspepsia. In a randomized controlled trial, mirtazapine significantly improved weight loss, nutrient tolerance, early satiety, and quality of life in patients with functional dyspepsia and weight loss. Erythromycin is often used as off-label treatment for gastroparesis, but this patient has rapid gastric emptying as noted above. Given the poor response to another prokinetic (metoclopramide), off-label use of erythromycin would not be the optimal choice.
- SSRIs like citalopram have not been shown to be efficacious in randomized controlled trials for functional dyspepsia.
“Brainerd diarrhea”
“Brainerd diarrhea” after a notable outbreak in Minnesota.
Patients with this syndrome always have the sudden onset of voluminous diarrhea, often associated with weight loss.
Diagnostic tests are negative (answer C is incorrect). Patients who present with this picture eventually get better, typically after 7-31 months of illness (answer B is correct; answer A is incorrect).
The offset of illness occurs over a few months and has not been shown to be altered by medication or dietary interventions
Most common causes of IBS
IBS account for most cases:
dietary intolerances (40%)
bile acid malabsorption (30%), and
small intestinal bacterial overgrowth (SIBO) (20%)
In the absence of accurate and widely available diagnostic tests for these entities, empiric therapeutic trials are the most direct way to make a more specific diagnosis.
Dx CIPO
Tx CIPO
A 38-year-old woman presents with over 10 years of daily bloating and abdominal distention. She also has intermittent episodes of severe vomiting that persist for 2-4 days and have required hospital admission 3 times in the past year. Despite these symptoms, she has daily bowel movements. She has a remote history of cholecystectomy over 5 years ago. Within the past year, she has undergone the following tests:
- -Upper endoscopy and colonoscopy were normal, with normal biopsies of the stomach and duodenum.
- -Two separate CT scans of the abdomen over the past year demonstrate diffusely dilated small bowel up to 5 cm in diameter, without transition point.
- -Diagnostic laparoscopy was negative for any evidence of an obstructive lesion.
Which of the following therapies may help with the patient’s symptoms?
A. Octreotide 50 mcg subcutaneously every night at bedtime
B. Dicyclomine 20 mg 4 times daily
C. Eluxadoline 75 mg twice daily
D. Simethicone 180 mg 3 times daily as needed
Dx: dilated small bowel
Tx: Octreotide 50mcg subQ qhs
The patient has chronic intestinal pseudo-obstruction (CIPO). Octreotide 50 mcg subcutaneous at night has been shown to induce migrating motor complexes in CIPO, and reduce nausea, bloating, and abdominal pain in patients with CIPO (answer A is correct). While dicyclomine may help abdominal cramping, it has not been shown to improve symptoms in CIPO, and indeed may worsen CIPO by further slowing intestinal transit (answer B is incorrect). Eluxadoline is approved by the FDA for irritable bowel syndrome with diarrhea but might exacerbate CIPO and further is contraindicated in patients with history of cholecystectomy due to increased risk of pancreatitis (answer D is incorrect). There is no data to support the use of simethicone for chronic bloating/distention, nor in the setting of CIPO (answer E is incorrect).
A 34-year-old man presents with chronic diarrhea. He has had insulin-dependent diabetes since age 20 with hemoglobin A1c in the range of 7.5-9.0% over the last 3 years. Diarrhea began gradually 2 years ago and was intermittent until 3 months ago. Now he has 4-5 daily loose stools accompanied by increased flatus and weight loss of 10 lb. Stools are brown, watery, and malodorous. He takes no medications other than insulin.
Physical examination shows a thin young man in no distress. He is afebrile, blood pressure 120/80, pulse 80 and regular, and normal respiratory rate. His height is 68 inches and weight is 140 lb (body mass index of 21). Abdomen is soft, slightly distended, and bowel sounds are active. Knee jerks are absent. Physical examination is otherwise normal.
Laboratory tests results include:
Serum glucose 125 mg/dL
Serum sodium 140 mmol/L
Serum potassium 5.0 mmol/L
Blood urea nitrogen 12 mg/dL
Serum creatinine 1.2 mg/dL
What is the next step in his evaluation?
A. Colonoscopy with biopsies
B. Upper gastrointestinal endoscopy with biopsies
C. CT scan of abdomen and pelvis with contrast
D. Serum B12 level
E. Qualitative stool fat
- Up to 25% of patients with diabetes mellitus develop diarrhea as a complication of their disease or its treatment. The key to discovering the underlying cause of diarrhea in diabetics is to determine whether steatorrhea is present or not.
- Qualitative stool fat is a quick, inexpensive screening test (answer E is correct). If steatorrhea is present, 3 causes of diarrhea which occur more often in diabetics should be sought:
- small intestinal bacterial overgrowth (SIBO), pancreatic exocrine insufficiency, and celiac disease.
- The common causes of diarrhea in diabetics if steatorrhea is not present are:
- drug side effects (e.g., metformin, GLP-1 agonists such as exenatide or liraglutide, sitagliptin and other dipeptidyl peptidase-4 [DPP-4] inhibitors), non-nutritive sweeteners (e.g., mannitol, sorbitol), and diabetic autonomic neuropathy.
- The other tests listed might be needed later in the evaluation, but the sequencing of tests depends on the presence or absence of steatorrhea (answers A-D are incorrect)
