Harrison’s Club:Inflammatory Bowel DiseaseMarica A. Lazo
Inflammatory Bowel Disease
• Immune-mediated chronic intestinal condition
• 2 major types: Ulcerative colitis (UC) and Crohn’s disease (CD)
• Highest incidence in Europe, the United Kingdom, and North America
• Urban areas have a higher prevalence of IBD than rural areas, and high socioeconomic classes have a higher prevalence than lower socioeconomic classes
Epidemiology
Genetic Disorders Associated with IBD
Etiology and Pathogenesis
In genetically predisposed individuals, exogenous factors (e.g., composition of normal
intestinal microbiota)+
endogenous host factors (e.g., intestinal epithelial cell barrier function, innate and adaptive immune
function)
chronic state of dysregulated mucosal immune function that is further modified by specific
environmental factors (e.g., smoking, enteropathogens)
Genetic Considerations
• The diseases and the genetic risk factors that are shared with IBD include rheumatoid arthritis (TNFAIP3), psoriasis (IL23R,IL12B), ankylosing spondylitis (IL23R), type 1 diabetes mellitus (IL10,PTPN2), asthma (ORMDL3), and systemic lupus erythematosus (TNFAIP3,IL10)
Genetic Considerations
• Defective Immune regulation• Suppression of inflammation is altered
uncontrolled inflammation• Inflammatory cascade
• Cytokine activity not regulated imbalance between proinflammatory and anti-inflammatory mediators
• Exogenous factors• Normal microbiota is perceived
inappropriately as if it were a pathogen
Pathology
Ulcerative Colitis – Macroscopic Features
Crohn’s Disease – Macroscopic Features
Macroscopic Features
UC CDRectal involvement
Pseudopolyps Toxic megacolon
Skip lesions Perirectal fistulas,
fissures, abscesses, and anal stenosis
Transmural involvement
Cobblestone appearance
Ulcerative Colitis – Microscopic Features
Crohn’s Disease – Microscopic Features
Only GALS can be Crohn’s!
G – GranulomasAL – All Layers and All LevelsS – Skip lesions
Clinical Presentation
Clinical Features of UC vs CD
Endoscopic and Radiographic Features of UC vs CD
Differential Diagnosis of UC and CD
Diseases that Mimic IBD
Diseases that Mimic IBD
Extraintestinal Manifestations
• Dermatologic• Rheumatologic• Ocular• Hepatobiliary• Urologic• Metabolic bone disorders• Thromboembolic disorders• Others
Extraintestinal Manifestations:A PIE SAC
• Aphthous ulcers• Pyoderma gangrenosum• Iritis• Erythema nodosum• Sclerosing cholangitis• Arthritis• Clubbing of fingertips
Treatment of IBD
Treatment
• 5-ASA Agents• Mainstay of therapy for mild to
moderate UC is Sulfasalazine and other 5-ASA agents. Limited role in inducing remission in CD.
Treatment
• Glucocorticoids• For moderate to severe UC and CD• Prednisone 40–60 mg/d for active UC
that is unresponsive to 5-ASA therapy. • Parenteral: hydrocortisone, 300 mg/d,
or methylprednisolone, 40–60 mg/d.• No role in maintenance therapy for
both UC and CD
Treatment
• Antibiotics• Pouchitis in 1/3 of UC patients post
colectomy = responsive to metronidazole and/or ciprofloxacin
• Metronidazole • Effective in active inflammatory,
fistulous, and perianal CD and may prevent recurrence after ileal resection.
• The most effective dose is 15–20 mg/kg per day in three divided doses; it is usually continued for several months.
Treatment
• Azathioprine• 6-Mercaptopurine• Methotrexate• Cyclosporine• Tacrolimus• Biologic therapies
• Anti-TNF therapies• Natalizumab
Standard Medical Management of UC
Standard Medical Management of CD
Indications for Surgery
Harrison’s Club:Irritable Bowel SyndromeMarica A. Lazo
Irritable Bowel Syndrome
• A functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habits in the absence of detectable structural abnormalities
• 10-20% of adults and adolescents have symptoms c/w IBS, with FEMALE predominance (2-3x as often as men)
• Commonly first symptoms occur before age 45
Diagnostic Criteria for IBS(ROME II Criteria)
Clinical Features
• Abdominal pain/discomfort• Prerequisite clinical feature of IBS• Variable in intensity and location• Exacerbated by eating or emotional
stress and improved by passage of flatus or stools
• Altered bowel habits• Most consistent clinical feature in IBS• Constipation alternating with
diarrhea, usually with one symptom predominating
Clinical Features
• Gas and flatulence• Impaired transit and tolerance of
intestinal gas loads• Reflux gas from distal to proximal
intestine - flatulence• Upper GI symptoms
• 25-50% of patients complain of dyspepsia, heartburn, nausea or vomiting
Pathophysiology
1. Gastrointestinal motor abnormalities• Increased rectosigmoid motor activity
for up to 3 hours after eating• Recordings from the transverse,
descending and sigmoid colon showed that the motility index and peak amplitude of high-amplitude propagating contractions (HAPCs) in IBS-D were increased
Pathophysiology
2. Visceral hypersensitivity• Exaggerated sensory responses to
visceral stimulation• Proposed mechanisms:
• End-organ sensitivity• CNS modulation• Long-term hyperalgesia• Tonic cortical regulation• Neuroplasticity
Pathophysiology
3. Central Neural Dysregulation• Clinical association of emotional
disorders and stress with symptom exacerbation and the therapeutic response
• In response to distal colonic stimulation, the mid-cingulate cortex shows greater activation in IBS patients
• Preferential activation of the prefrontal lobe increased perception of visceral pain
Pathophysiology
4. Abnormal Psychological Features• Abnormal psychiatric features are
present in up to 80% of IBS patients• An association between prior sexual
or physical abuse and development of IBS has been reported
• Increased motor reactivity of the colon and small bowel to a variety of stimuli and altered visceral sensation associated with lowered sensation thresholds
Therapeutic Targets for IBS
Pathophysiology
5. Post-Infectious IBS• Occurs more commonly in females
and affects younger rather than older patients
• Risk factors: prolonged duration of initial illness, toxicity of bacterial strain, smoking, mucosal markers of inflammation, female gender, depression, hypochondriasis, and adverse-life events in the preceding 3 months
• Campylobacter, Salmonella and Shigella
Pathophysiology
6. Immune Activation and Mucosal Inflammation
• Activated lymphocytes, mast cells, and enhanced expression of proinflammatory cytokines abnormal epithelial secretion and visceral hypersensitivity
• Psychological stress release of proinflammatory cytokine alter intestinal permeability
Pathophysiology
7. Altered Gut Flora• High prevalence of small intestinal
bacterial overgrowth in IBS patients (positive lactulose hydrogen breath test)
• Bacterial genera with Lactobacillus sequence appear to be absent from IBS, and Collinsella sequences were reduced
Pathophysiology
8. Abnormal Serotonin Pathways• Serotonin (5HT)-containing
enterochromaffin cells in the colon are increased in a subset of IBS-D patients compared to healthy individuals or patients with ulcerative colitis
• Increased release of serotonin may contribute to postprandial symptoms and provides a rationale for the use of serotonin antagonists in the treatment of IBS
Approach to the Patient with IBS
IBS NOT IBS• recurrence of lower
abdominal pain with altered bowel habits over a period of time without progressive deterioration
• onset of symptoms during periods of stress
• absence of other systemic symptoms such as fever and weight loss
• small-volume stool without any evidence of blood
• appearance of the disorder for the first time in old age
• progressive course from time of onset, persistent diarrhea after a 48-h fast
• presence of nocturnal diarrhea or steatorrheal stools
Differentials• Lactase deficiency• Celiac sprue• Side-effects from
anticholinergic, antihypertensive, and antidepressant meds
• Biliary tract disease, intestinal ischemia, peptic ulcer disorders, and carcinoma of the stomach and pancreas
• Diverticular disease of the colon, inflammatory bowel disease
• Giardia• Laxative abuse• Hyperthyroidism
Approach to the Patient with IBS
• Young pxs with mild symptoms require minimal diagnostic evaluation, while older pxs or those with rapidly progressive symptoms should undergo a more thorough one
• CBC and sigmoidoscopic examination, stool exam
• In pxs with persistent diarrhea not responding to anti-diarrhea agents, a sigmoid colon biopsy should be performed to rule out microscopic colitis
Approach to the Patient with IBS
• In those aged >40 years, an air-contrast barium enema or colonoscopy should also be performed
• If the main symptoms are diarrhea and increased gas, the possibility of lactase deficiency should be ruled out with a hydrogen breath test or with evaluation after a 3-week lactose-free diet
• Lab features that argue against IBS include anemia, elevated ESR, presence of leukocytes or blood in stool, and stool volume >200–300 mL/d
Treatment• High-fiber diet• Anticholinergic drugs inhibit gastrocolic
reflex (ipratropium bromide)• Anti-diarrheals (loperamide)• Anti-depressants – TCAs and SSRIs
(fluoxetine)• Activated charcoal as part of anti-
flatulence therapy• Serotonin Receptor Agonist and
Antagonists – alosetron, tegaserod• Chloride Channel Activators –
lubiprostone
Thank you!
