GIT - IBD Flashcards
What is inflammatory bowel disease? What are the types?
is an inflammatory disorder of the
gastrointestinal tract
- characterized by chronic and spontaneously relapsing inflammation
Crohn’s disease
Ulcerative colitis
What are the factors involved in pathogenesis of IBD?
IBD is multifactorial
- no known cause
genetic susceptibility
- NOD2, DLG5, IL23R
immune response
gut/microbiota alterations
environmental factors
- diet, smoking, medical history, hygiene
How does genetic susceptibility affect IBD?
defects in certain genes have been found to be associated with IBD
- lead to the defects in protective mechanisms
defects in mucosal barrier
- MUC19, OCTN, DLG5
detects in bacterial sampling
- NOD2 (CARD15), TLR4
defects in immune response
- IL23R, IL10, INF gamma, autophagy genes (ATG16L1)
What is bacterial sampling? How do defects in genes associated lead to IBD?
bacterial sampling
- cells pick up antigens from the lumen and present them to the lamina proprietor
- immune cells in the lamina propria decide whether to induce an immune response or tolerate them
in IBD, mutations promote sustained release of inflammatory cytokines
How does immune response affect IBD? What types of response is it characterised by?
IBD is characterised by a defective immune response
- hyper-reactive
- insufficient
- dysregulated
What is the intestinal inflammatory process associated with IBD?
breakdown in mucosal barrier function
- exposure of the laminal propria to antigens
infiltration of immune cells (neutrophils, macrophages, dendritic cells)
local elevation of TNF alpha, IL-1 beta and IFN gamma
T effectors differentiation
- local elevation of Th17 cells (produce inflammatory cytokines)
defective regulation of immunosuppression
- T regs (typically inhibit cell proliferation)
chronic inflammation occurs
- activated T cells activate other inflammatory cells
Which T effectors are associated with Crohn’s disease and Ulcerative colitis?
Crohn’s disease
- excess Th1 and Th17 cytokines
Th1 = produce IL-12, IFN gamma and TNF alpha
Th17 = produce IL17 and IL23
- defect in T regs
Ulcerative colitis
- excess Th2 and Th17 cytokines
Th2 = produce IL5, IL13, IFN gamma and TNF alpha
Th17 = produce IL17 and IL23
= typically have excess Th2 cytokines but can have Th1 cytokines (atypical)
- defect in T regs
How do gut/microbiota alterations affect IBD?
microbiota - group of microbes reside in a previously established environment
dysbiosis - an unhealthy change in the normal microbiota
defective mucosal integrity leads to IBD
- physical barrier
= mucus layer, tight junctions
- specialised epithelial cells
= goblet cells (mucus. repair & inflammation modulatory factors)
= paneth cells (anti-microbial peptides like alpha defensins) - mucosal innate immune function
= pattern recognition receptors
What is the overview of IBD initiation?
genetic factors and environmental factors are the initiating triggers
- autophagy, chemokines, smoking, infections, NSAIDs
impaired barrier function
translocation of microbial peptides
immune cell activation
- production of pro-inflammatory mediators, failure of regulatory mechanisms
chronic inflammation
- fibrosis, stenosis, abscess, fistula, cancer, extra intestinal manisfestations
How can IBD be diagnosed?
laboratory tests
- hematography = C-reactive protein is increased, erythrocyte sedimentation rate is increased, increased platelet count, reduced haemoglobin, leukocytosis
- IBD antibodies
- fecal calponectin
sigmoidoscopy and colonoscopy
- loss of vascular patterns, granularity, friability, ulceration
radiography using barium enema
- ulcerative colitis = shows a shortened colon and destruction of mucosal pattern
- Crohn’s disease = skip pattern
What are the difference between clinical signs seen in Crohn’s disease and Ulcerative colitis?
Crohn’s disease AND Ulcerative colitis
- abdominal pain, bloody diarrhoea
Crohn’s disease
- anorexia/weight loss, growth failure, perianal disease
Ulcerative colitis
- passage of mucus (faeces)
Where do Crohn’s disease and Ulcerative colitis affect in the body?
Crohn’s disease
- any part of the GIT
- lesions are discontinuous = skip pattern
Ulcerative colitis
- always begins in the rectum but can involve the large intestine and terminal ileum (SI)
- spreads proximally in continuity
What are the characteristic features of Crohn’s disease and Ulcerative colitis?
Crohn’s disease
- transmural inflammation = extends into the deeper layers of the intestinal wall, bowel wall is thickened, lumen is narrowed
- mucosa = fissuring ulcers
- serosa = granular and fibrotic fat
Ulcerative colitis
- ulceration and inflammation of the inner lining of the colon and rectum
- characteristic ulcers and/or open sores
- active phase = red mucosa, friable friable, oedematouse
- quiescent phase = mucosa atrophic, featureless
What are extra intestinal manisfestations that occur as a result of IBD?
uveitis -inflamamtion of the middle layer of the eye
ankylosing spondylitis - inflamed spine
erythema nodosum - swollen red bumps on the skin
pyoderma gangrenous - ulcers on the skin
osteoporosis
vasculitis, thrombosis
arthritis
- most common comorbidity
