Inflammatory Bowel Disease (IBD) Flashcards
What is irritable bowel disease?
chronic, relapsing idiopathic inflammation of the GI tract
Broken down in to two diseases:
- ulcerative colitis (UC)
- crohns disease (CD)
What factors are associated in IBD development?
Alterations to:
- gut microbiota (dysbiosis)
- intestinal epithelium/barrier function (increased permeability)
- immune cells within GI tract (dyfunction and loss of regulation)
Caused by:
- environmental factors (IBD triggered by inappropriate response to environmment that self-perpetuate
- multiple genetic factors (increases susceptibility)
Compare the parts of the GI tract affected by CD and UC.
CD:
- any part of GI tract
- most commonly terminal ileum and colon
- lesions are discontinuous (skip lesions)
- typically spares rectum
UC:
- limited to colon
- begins distally and spreads proximally (favors left/distal colon)
- lesions are continuous
- ALWAYS involves rectum
Compare the typical symptoms of CD and UC.
CD:
- abdominal pain (RLQ, mimics appendicitis)
- nonbloody diarrhea
- intermittent fever
UC:
- bloody diarrhea
- tenesumus/fecal urgency
Compare pathologic features of CD and UC.
CD:
- transmural inflammation
- non-continuous lesions (skip lesions/cobblestoning)
- abscesses
- fissures/fistulas
- strictures
- granulomas
- creeping fat
UC:
- limited mucosal/submucosal inflammation
- pseudopolyps (continuous, ulcerated lesion interrupted by sparse normal tissue -> appears like a polyp)
- toxic megacolon
Compare diagnostic features of CD and UC.
(serology and barium studies)
CD:
- Anti-Sacchromyces cervisiae Ab (ASCA)
- “string sign”/obstruction due to inflammation (barium XR)
UC:
- peripheral anti-neutrophil antibody (pANCA)
- “lead pipe” sign from loss of haustra
Compare and contrast extraintestinal manifestations of CD and UC.
CD:
- cholelithiasis
- calcium oxolate stones
- IDA
UC:
-sclerosing cholangitis
both:
- eyes: uveitis
- skin: erythema nodosum and pyroderma gangrenosum
- skeletal: migratory polyarthritits, sacroilitis, ankylosing spondylitis
Compare complications of CD and UC.
CD:
- fistula
- abscess
- stricture -> obstruction
- bile acid malabsorption (distal ileum) -> steatorrhea
- IDA
UC:
- hemorrhage
- toxic megacolon -> perforation
Both:
-colorectal cancer
Which IBD can be cured by surgery?
UC, it is limited to the colon and rectum so proctocolectomy is curative
What main groups of oranisms are present in a healthy large intestine microbiota? (Which predominate)
Compare the shifts in CD and UC.
Normal:
- Bacteroidetes (~70%)
- Firmicutes (~25%)
- Proteobacteria
- Actinobacteria
CD:
- increased Firmicutes (~70%) > Actinobacteria
- drastically reduced Bacteroidetes
UC:
- increased Proteobacteria (PUC)
- reduced Bacteroidetes
What diet promotes normal large intestinal microbiota?
high fiber diet
What is a common trait in all genes that have been associated with IBD?
immune/inflammation related
What gene is most associated with a form of IBD and what gene is it?
IBD-1 gene on chromosome 16
- associated with CD
- encodes CARD15/NOD2
What is the function of CARD15/NOD2?
PRR found in MΦ and DCs that recognizes muramyl dipeptide (MDP), a peptidoglycan common to many bacteria
CARD15/NOD2 phosphorylates IκB -> activating NF-κB (proinflammatory gene regulator)
How might a CARD15 mutation contribute to CD?
no CARD15 -> no proinflammatory gene transcription:
- defective MΦ killing -> prolonged stimulation of T cells
- defective epithelial barrier responses
- defective APC conditioning
What immune cell types play a large role in maintaining homeostais through anti-inflammatory responses and maintenance of epithelial integrity?
Treg: anti-inflammatory IL-10 and
Basal Th17 activation: Treg like variant that produces IL-17 and IL-10
Plasma cells: IgA
What gut microbial factors promote Treg differentiation?
Specific bacteria:
- segement filamentous bacteria (SFB)
- Bacteroides fragilis
- Clostridium spp.
Factors:
- bacterial polysaccharides
- short chain fatty acids (SCFA)
What gut microbial factors promote basal Th17 activation?
segement filamentous bacteria (SFB)
By what mechanims do commensal organisms stimulate immune tolerance?
Commensal organisms activate PPAR, a molecule that transports NF-κB out of the nucleus -> downregulates inflammatory signaling
What immune state is typical of CD?
(cytokines, active cell types)
Th1/Th17 type responses:
IL-12 -> Th1 -> IFN-γ
IL-23/IL-6/TGF-β -> Th17 -> IL-17/IL-22
-IFN-γ -> M1 macrophage -> TNF-α
What immune state is typical of UC?
(cytokines, active cell types)
Th2 type and NKT responses:
IL-4 -> Th2 -> IL-4/IL-5/IL-13
NKT -> IL-13
