What are Functional GI disorders?
- Defined by symptoms
- Biochemical, radiologic and endoscopic tests cannot identify an organic cause of symptoms
Prevalence of Functional GI disorders?
- Adult vs. pediatric
- __% of adult Americans
- __% of office visits in GIM
- __% of referrals to GI
- 28 adult and 17 pediatric
- Highly prevalent
- 40% of adult Americans
- 20% of office visits in GIM
- 40-50% of referrals to GI
What are some of the classes of Functional GI Disorders?
- Functional Esophageal (4)
- Functional Gastroduodenal (7)
- Functional Bowel (5)
- Functional Abdominal Pain
- Functional Gallbladder and Sphincter of Oddi (3)
- Functional Anorectal Disorders (8)
What are the ROME III Criteria for IBS? (Exam Question!)
Recurrent abdominal pain or discomfort at least 3 days/mo in the last 3 mo associated with 2+ of the following:
- Improvement with defecation
- Onset associated with change in stool frequency
- Onset associated with change in form of stool
Criteria fulfilled for last 3 mo with symptom onset at least 6 mo prior to diagnosis
(Essential combo = abdominal discomfort + changes in bowel habits)
What is the most common FGID?
Irritable Bowel Syndrome
- 12% in US (but not all seek healthcare)
- Women 1.5x more likely (to present, not to be affected)
- Significant impact on Quality of Life
- Significant economic impact
When is the typical onset of IBS?
- Typical onset in 20s-30s
- There is a childhood variant
- Onset decreases with age
Pathophysiology of Functional GI Disorders?
- Genetic factors
- Acute gastroenteritis
- Other precipitating factors (stress, anxiety, depression, Abx use)
- Enteric Neuropathy (inflammation of nerve endings and disruption of conduction)
- GI motor disturbances
- Visceral hypersensitivity
- Abnormal central processing of sensations
- Psychological disturbances
- Stress Result = symptoms -> consultation
Describe the brain-gut axis and the control of GI function
- Brain activation pattern (disordered in FGIDs)
- Parasympathetic and sympathetic nervous systems (PNS and SNS)
- Serotonin signaling
- Activation of mast cells
- Altered cytokine levels
- Changes in GI motility
- Changes in GI secretion
- Visceral hypersensitivity
T/F: Irritable bowel syndrome and ulcerative colitis are FGIDs?
- IBS is a FGID, but ulcerative colitis is not
How are IBS and ulcerative colitis similar?
They have an abnormal response to normal GI stimulus
- IBS pts activated limbic and paralimbic regions; may facilitate perceptual response to the stimulus
- Pts with IBS have increased response to stress/unpleasantness than control; cannot return to same degree of relaxation even with removal of stressful stimuli
T/F: A significant number of IBS pts have anxiety or depressive disorder, but it is unlikely that IBS is secondary to these
Is there a degree of genetics behind IBS? (monozygotic vs. dizogytic twin studies)
Stronger association for monozygotic twins; thus, there is some genetic component
- May be mediated by hereditability of anxiety and depression
- 38 yo ME man c/o intermittent "diarrhea" and "constipation" for past 2 yrs
- Cramps, post-cibal and morning episodes
- No weight loss, fever, GI bleeding
- No family h/o GI cancer
- Diabetes on glipizide
- Normal CBC, CMP, TSH Diagnosis?
This man fulfills criteria for GFID (pain + bowel habit symptoms for > 3 mo)
- This is irritable bowel syndrome (IBS)
What are the different patient groups with IBS/constipation?
- IBS-C: IBS with constipation
- CC: chronic constipation
- IBS-M: mixed/alternating symptoms of constipation and diarrhea
What history and physical exam findings are expected in IBS?
- Site and radiation of pain
- Relief with BM
- Onset and duration: typically subacute onset
- Nocturnal symptoms
- Organic bowel disease (e.g. cancer) may produce pain that wake people from sleep
- FGID/IBS do NOT typically have nocturnal symptoms; absence of Sx that wake from sleep (sign of impaired brain-gut axis)
- Association with meals, medications
- Often the pain results from overactive gastric reflexes
- Blood from up or down
- Weight loss
- Family history
T/F: IBS commonly occurs with co-morbidities
- Depression (39%)
- Migraine (37%)
- Anxiety (35%)
- Chronic fatigue
- Chronic pain
What signs/symptoms are NOT typical of a functional GI disorder?
- Unexplained weight loss (>10% body wt)
- Nocturnal symptoms
- Progressive dysphagia, odynophagia
- Persistent vomiting
- Abdominal mass
T/F: Organic diseases are found with increased prevalence in pt with IBS
- These (colorectal cancer, lactose malabsorption, thyroid dysfunction...) do not occur more with IBS
- Exception: celiac disease may be over-represented in pts with IBS who have diarrhea
IBS pharmacologic therapies are organized by symptoms. What symptoms are treated?
- Abdominal pain/discomfort
- Altered bowel function
What is the emerging consensus concerning the microbiota in IBS?
- Decreased proportions of the genera Bifidobacterium and Lactobacillus
- Increased ratios of Firmicutes:Bacteroidetes, at the phylum level (Some problems with studies: small, heterogeneous samples, not controlled for age/sex/meds/diet...)
What is the most extensively studied antibiotic for IBS?
- Gut-directed antibiotic; functions on the assumption that the microbiota plays a role in IBS
- Pretty broad spectrum
- Not systemically absorbed
- Generally well-tolerated
- Abdominal pain
- 40% with antibiotic vs. 32% describe adequate relief of global symptoms
What are probiotics?
Microorganisms that are believed to provide health benefits
What are some probiotics used for IBS?
- Lactobacilli (anaerobic gm + rods)
- Bifidobacteria (anaerobic gm + rods)
- VSL #3 (8 organisms: 3 bifido, 1 streptococcus, 4 lactobacilli)
- Streptococcus salivarius
What is the mechanism of action of probiotics?
- Competitive inhibition
- Barrier protection
- Immune effects
- Anti-inflammatory effects
- Production of various substances (enzymes, SCFA, bacteriocidal agents)
- Ability to alter local pH and physiology
- Provides nutrition to colonocytes
What is Lubiprostone?
- Mechanism of action
- Fatty acid derived from prostaglandin E1
- Acts by activating CIC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion
What is Linaclotide? - Mechanism of action
- Peptide agonist of the guanylate cyclase 2 C.
- Reduces activation of colonic sensory neurons, reducing pain; and activates colonic motor neurons --> increases smooth muscle contraction and thus promotes bowel movements
- Most common ASE = diarrhea
T/F: Diet affects IBS
What is the difference between a food allergy and a food intolerance? Aversion?
- Allergy- immunologic
- Intolerance- adverse reaction; non-immunologic
- Aversion: psychological avoidance to a specific food or foods
Characteristics of food allergy
- More common in
- Common food allergies
- 30-50% of GI clinic pts believe their symptoms to be related to food allergy/intolerance but true food allergies are uncommon (1-3%)
- More common in atopic individuals
- Symptoms develop after eating
- IgE mediated (type 1) – rapid in onset
- Cell mediated (type 4) – delayed hypersensitivity
- Peanuts, tree nuts
- Cow’s milk
- Soy, wheat
- Fish, shellfish
Characteristics of food intolerance?
- 20% complain of intolerance
- More women report symptoms
- Prevalence in IBS ranges from 20-67%
Why might food cause GI symptoms?
- Stimulation of mechanoreceptors
- Stimulation of chemoreceptors
- Release of hormones/peptides
- Alterations in secretion
- Changes in osmolarity
- Fermentation of foods
- Subsequent luminal distention
What foods commonly cause/exacerbate IBS?
- Non-absorbable sugars
- Other fermentable foods
What is lactose?
- Lactose = disaccharide
- Broken down into glucose and galactose
- Lactase deficiency leads to fermentation in the colon
- Excess hydrogen, CO2, methane
__% of US adults are lactose intolerant
__% worldwide prevalence
- Prevalence in IBS pts is ___ (higher/lower)
30-35% of US adults are lactose intolerant
70% worldwide prevalence
- Prevalence in IBS pts is higher
What is the Goal in lactose-free diet?
Treatment options for lactose intolerance?
- Maintain calcium
- Vitamin D
- Rice, Almond, Coconut, Hemp, Soy, Quinoa, Oat, Hazelnut
How is lactose intolerance diagnosed?
- Breath test
- Challenge (e.g. 3 big glasses of milk)
What is fructose?
- Present in what foods
Fructose = monosaccharide
- Exists as free hexose or after sucrose hydrolysis
- No enzyme present in human small intestine
- Very poorly absorbed by itself (GLUT5)
- Efficiently absorbed in conjunction with glucose (GLUT2)
- Table sugar
- High fructose corn syrup
Describe fructose intolerance
- Association with IBS
- Treatment strategies
- 11-70% fructose intolerance
- 40% of IBS pts may be fructose intolerance
- Ingest with glucose
- (no high fructose corn syrup!)
What is gluten?
- Association with IBS
Gluten = storage protein in wheat, barley, rye
- Genetically susceptible individuals (HLA-DQ2 and HLA-DQ8) develop an immune response
- Worldwide prevalence of celiac disease in IBS patients = 4% (US = 0.4%)
- KEY POINT: The vast majority of IBS patients don’t have celiac disease.
What were the effects of a low gluten diet on IBS?
- Prior symptom improvement on gluten-free diet
- Primary endpoint = adequate symptom relief
- Gluten group had less improvement in symptoms than those on gluten free (pain, bloating, satisfaction with stool consistency, tiredness)
What are FODMAPs?
Fermentable Oligo, Di, Monosaccharides and Polys
- Excess fructose (honey, apples, pears...)
- Fructans (wheat, rye, onions, leeks, zucchini)
- Sorbitol (apricots peaches, artificial sweeteners, gums)
- Raffinose (lentils, cabbage, Brussel sprouts, asparagus, green beans, legumes)
What can be eaten in a FODMAP diet?
- Lean proteins
- Gluten-free breads, rolls, pasts
- Rice, corn, and oat products
- Safe fruits and veggies: snow peas, bok choy, carrots, mandarin
What were the effects of FODMAP diet on IBS? (test question)
- FODMOP diet compared to typical Australian diet; measured stool frequency and water content
- Low FODMOP diet -> lower global GI symptom scores
- Symptoms of bloating, gas, and abdominal pain were all improved on FODMAP
What is the mechanism of action of antidepressents?
How does this relate to GI function?
- Antidepressent action works in CNS
- May have visceral analgesia
- Changes in GI motility; smooth muscle relaxation
What is a prediction error about expected interoceptive state?
Worrying about pain (worried it will be unbearable)
- Cognitive behavioral therapy functions on the relationship that thoughts -> feelings (manage thoughts to help)
What are psychological therapies?
- Cognitive behavioral therapy
- Relaxation training
- Dynamic psychotherapy