Download Treatment of Severe Steroid-refractory Ulcerative Colitis: Medical

Pathophysiology
GI Pathophysiology
2016. 11. 01.
Jaeyoung Chun, M.D.
1
IBD
IBS
IBD : inflammatory bowel disease
IBS : irritable bowel syndrome
Introduction : IBD
• Inflammatory bowel disease (IBD)
– Chronic relapsing inflammation of the digestive tract
– Rare
• Two major forms
– Crohn’s disease (CD)
– Ulcerative colitis (UC)
IBD : CD vs. UC
Superficial inflammation
Involved in any part of the GI tract
Associated with complications such as strictures,
fistulas and abscesses
At a higher risk of colorectal cancer
Introduction : IBS
• Irritable bowel syndrome (IBS)
– Functional gastrointestinal disease
– Very common
– Change in bowel habits : diarrhea, constipation
– Abdominal pain or discomfort relieved with bowel
movement
IBD
IBS
Incidence
Rare
5~20 / 100,000
Very common
67 / 1,000 person years
(20% prevalence)
Peak age of onset
20-30 & 60-70 years
NA
Sex (male : female)
1:1
1:2
Symptoms
Chronic relapsing GI symptoms
(abdominal pain, bowel habit change, etc)
Radiologic findings
Abnormal
Normal
Histologic findings
Chronic inflammation
Normal
Treatment
Anti-inflammatory drugs
Immunomodulatory drugs
Steroids
Biologic agents
Dietary modification
Probiotics
Anti-spasmodics
Anti-depressants
Prognosis
Lifelong disease
Complications (stricture,
perforation, infection, or
colorectal cancer)
Affect quality of life,
but not life threatening
Crohn’s Disease
Ulcerative Colitis
Gastroenterology 2012;142:46-54
Incidence of IBD in Korea
6.0
5.0
Incidence (/105)
4.2
4.0
UC
3.0
3.1
CD
2.0
1.0
0.0
06
07
08
09
10
11
12
Year of diagnosis
Population-based Cohort in the Songpa-Kangdong
District, Seoul, Korea, 1986-2005
Database from the Health Insurance and
Review Agency, 2006-2012
Yang SK, Kim JS et al. Inflamm Bowel Dis 2008;14:542–549
Kim HJ et al. Inflamm Bowel Dis 2015;21:623-630
IBD - Etiology
Inflamm Bowel Dis 2015;21:912–922
IBD – Genetics
163 IBD risk loci
Ann Gastroenterol 2014;27:294-303
Gut Microbiome
• We are more “bacteria” than “human”
– 10x the No. of human cells
– 150x the No. of human genome
• Microbiome as “human organ”
– Weighs ~1kg
– Is more akin to immune system than liver
Gut Microbiome: Implication for Clinical Practice
• Disease associated with dysregulated gut microbiome
–
–
–
–
–
–
–
–
DM
Obesity
Metabolic syndrome
Stress/anxiety
Heart disease
Allergic disorders
Cancer
IBD & IBS
IBD & Gut Microbiota
• Evidence for role of microbiota in IBD
– Patients with IBD have less diverse microbiome.
– Antibiotics improve disease course in some IBD patients.
– Animal models of IBD require presence of microbiota for
inflammation.
– Many genetic risk loci for IBD involve pathways for protection of
host against gut microbiota.
– Established association of diet, which impacts microbiome, and
risk for IBD
Pharmacol Ther 2015;149:191-212
IBS Pathophysiology
Am J Med 2015;128:817-827
IBS & Gut Microbiota
• Evidence for role of microbiota in IBS
– Small intestinal bacterial overgrowth (SIBO) may initiate IBS
symptoms.
– Infectious gastroenteritis may trigger microinflammation
(“postinfectious IBS”)
Am J Med 2015;128:817-827
Brain-Gut-Enteric Microbiota Axis
EMS : emotional motor system
ANS : autonomic nervous system
Nat Rev Gastroenterol Hepatol 2009;6:306-314
Brain-Gut-Enteric Microbiota Axis
Ann Gastroenterol 2015;28:203-209.
Summary : IBD vs. IBS
• IBD is rare, but chronic relapsing GI inflammation
• IBS is very common, functional GI disorder
• IBD & IBS are multifactorial disease
– Genetic factor
– Environmental factor : diet
– Gut microbiota
– Brain-gut-microbiota axis