Inflammatory bowel disease Flashcards
what are the two major forms of IBD?
ulcerative colitis
Crohn’s disease
what are the genetic risk factors of IBD
people of white european origin most susceptible
201 loci
what are the risk factors of IBD
diet medication smoking sleep stress air pollution microbiome appendectomy
describe the pathophysiology of IBD
autoimmune disease
defective interaction between mucosal immune system and gut flora
pro inflammatory compensatory response
leading to physical damage and chronic inflammation
compare chrons and ulcerative colitis
crohns-
Th1 mediated
lots of T cell expansion and defective T cell apoptosis
all layers of gut affected and all regions of gut
patchy inflamed areas (which makes surgery more difficult)
UC Th2 mediated limited T cell expansion normal T cell apoptosis mucosa/submucosa affected rectum region, spreading proximally usually continuous
what are the clinical features of IBD?
abdominal pain and cramping diarrhoea bloody faeces (particularly with Crohns) anaemia fever weight loss skin rashes
what are the types of therapies for IBD?
supportive therapies
fluid/electrolyte replacement
blood transfusion/oral iron
nutritional support
symptomatic treatments (for flair ups)
aminosalicylates
glucocorticoids
immunosuppressives
what are aminosalicylates?
anti-inflammatory treatment for IBD
which IBD is aminosalicylates more effective for?
ulcerative colitis
aminosalicylates are ineffective in inducing remission in crohns
how do glucocorticoids treat IBD?
steroids are powerful anti inflammatory and immunosuppressants
down reg T cell and macrophage activity
however- unwanted side effects
which IBD is gulucocorticoid treatment more effective for
GC induce remission in crohns
not reccomended for UC
what is azathioprine
immuno suppressant
pro drug, activated by gut flora
purine antagonist
what are the effects of azathioprine on the immune system?
impairs: cell and antibody mediated immune response lymphocyte proliferation mononuclear cell inflitration synthesis of antibodies
and enhances T cell apoptosis
what are the unwanted effects of azathioprine?
pancreatitis
bone marrow suppression
hepatotoxicity
increased risk of lymphoma and skin cancer
what are the strategies for minimising unwanted effects of drugs?
administer topically
use low dose u combination with another drug
use drug with high hepatic first pass metabolism so little escapes the systemic circulation
what are the potentially curative therapies?
manipulation of the microbiome:
- exclusive enteral nutrition. liquid diet, allows resting of mucosa and recovery of gut flora
hard to maintain and unpalatable
- probiotic therapies (no evidence that useful in crohns)
- faecal microbiota replacement
-antibiotic treatement. interferes with bacterial transcriptionby binding to RNA polymerase
(some evidence for sustained remission in CD but not UC)
biologic therapies -anti TNF alpha antibodies. eg- infliximab works by binding to TNFa and stop it from binding to the receptors and reduces downstream inflammatory events (only CD not UC)
what is the MOA of infliximab?
works by binding to TNFa and stop it from binding to the receptors and reduces downstream inflammatory events
given intravenously
what are the problems with anti TNFa therapy?
loss of responsiveness within 3 years due to production of antibodies against the drug and increasing the drug clearance
increased risk of TB
inc risk of septicaemia
worsening HF
inc risk of demyelinating diseases
inc risk of malignancy