IBD Flashcards
What is the most common age for the diagnosis of IBD?
20-30’s but can occur at any age
may be a second peak in 70’s - 80’s
What are the key features of Crohn’s disease?
Idiopathic, chronic inflammatory condition
Involves anywhere from mouth - anus
Relapses and remissions
What is the characteristic presentation of Crohn’s disease?
Abdominal pain and diarrhoea
often indolent onset
other symptoms include rectal bleeding, fever, weight loss, malnutrition, bone loss, and vitamin deficiencies
What is the pathophysiologiy of Crohn’s?
Defective regulation of Th1 cells causes chronic inflammation
Th1 cells release cytokines - IL12 and TNF alpha, interferon gamma which stimulate an inflammatory response
Inflammatory cells release inflammatory mediators
- arachidonic acid metabolites, proteases, platelet activating factor, and free radicals, which result in direct injury to the intestine
Increased production of TNF-α by macrophages in patients with Crohn disease results in increased concentrations of TNF-α in the stool, blood, and mucosa
What are the macroscopic findings of Crohn’s?
Initial findings of hyperaemia and oedema of mucosa
Superficial ulcers which can be serpiginous giving a cobblestone appearance
Skip lesions
Thickening of bowel and narrowing of lumen due to transmural inflammation - strictures can form
Advance disease: deep ulceration can lead to fistulas, micro perforation, abscess formation, adhesions
What are the histological findings of Crohn’s?
Inflammatory infiltrate around crypts Ulceration of superficial mucosa Non-caseating granulomas - inflammatory cells invade deeper mucosal layers forming non-caveating granulomas* Transmural inflammation Crypt abscesses - due to neutrophil invasion of crypts Villous blunting
- Although granuloma formation is pathognomonic of Crohn disease, its absence does not exclude the diagnosis
Name the genetic abnormalities associated with Crohn’s?
More than 70 genes have been found to be involved
NOD2/CARD15
- a polymorphic gene involved in the innate immune system.
- 3 single nucleotide polymorphisms (SNPs) play a role in 27% of patients with Crohns, primarily ill disease
IL23R gene
- encodes 1 subunit of IL-23 receptor protein
- 2 SNPs identified
TG16L1 gene, which encodes the autophagy-related 16-like protein involved in the autophagosome pathway that processes intracellular bacteria
IRGM gene SNP
mounting evidence that the autophagosome pathway is very important in the pathogenesis of the disease.
XBP1 gene, which is involved in the unfolded protein response pathway of the endoplasmatic reticulum.[52][53] Other well documented genes which increase the risk of developing Crohn disease are ATG16L1,[54] IL23R,[55] IRGM,[56] and SLC11A1
What are the non-genetic risk factors for Chron’s?
Infectious agents such as Mycobacterium paratuberculosis, Pseudomonas species, and Listeria species have all been implicated in the pathogenesis of Crohn disease, suggesting that the inflammation seen with the disease is the result of a dysfunctional, but appropriate, response to an infectious source
Smoking - doubles risk
What is the typical rates of involvement of parts of the large bowel in UC
Proctitis/proctosigmoiditis 30-50%
Left sided colon 20-30%
Pan-colitis 20%
What is the pathogenesis of UC?
Largely unknown
Possible abnormal induction of T2 cells to secrete various cytokines causing superficial mucosal inflammation
Possible abnormal immune response to gut flora
What are some genetic associations with UC (syndromes + specific gene mutations)
IL-23R mutation STAT 3 Jak2 Turners syndrome Hermansky-pudlack
What is the risk of a patient with UC having a first degree relative affected?
10-25%
Clinical manifestations of UC
Freq, small volume diarrhoea Blood/mucus/pus in BM Tenesmus, urgency Colicky abdo pain Fever, fatigue, weight loss Symptoms of anaemia
What is the severity classification for UC?
Mild - less then 4 BM per day, small Blood, normal ESR, no fever, normal haemodynamics
Moderate - 4-6 BM per day with moderate blood, low grade fever, mild anaemia, low grade fever
Severe - greater then 6 BM per day, large blood, febrile, tacy, ESR greater then 30
Fulminant - greater then 10 BM per day with large blood and haemodynamic instability
Extra-intestinal manifestations of UC
Enteropathic arthropathy Ankylosing spondylitis Osteopenia/osteoporosis/osteonecrosis Uveitis/episcleritis/iritis/conjunctivitis Erythema nodosum Pyoderma gangrenosm PSC Fatty liver Increased risk of arterial and venous clots Autoimmune haemolytic anaemia
- all except PSC, uveitis, ank spon correlate and flare with disease flares
