Inflammatory bowel disease

Question 1

what are the two major forms of IBD?

Answer 1

ulcerative colitis

Crohn’s disease

Question 2

what are the genetic risk factors of IBD

Answer 2

people of white european origin most susceptible

201 loci

Question 3

what are the risk factors of IBD

Answer 3

diet 
medication
smoking 
sleep
stress
air pollution
microbiome 
appendectomy

Question 4

describe the pathophysiology of IBD

Answer 4

autoimmune disease
defective interaction between mucosal immune system and gut flora

pro inflammatory compensatory response
leading to physical damage and chronic inflammation

Question 5

compare chrons and ulcerative colitis

Answer 5

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

Question 6

what are the clinical features of IBD?

Answer 6

abdominal pain and cramping 
diarrhoea
bloody faeces 
(particularly with Crohns)
anaemia 
fever 
weight loss 
skin rashes

Question 7

what are the types of therapies for IBD?

Answer 7

supportive therapies
fluid/electrolyte replacement
blood transfusion/oral iron
nutritional support

symptomatic treatments (for flair ups)
aminosalicylates
glucocorticoids
immunosuppressives

Question 8

what are aminosalicylates?

Answer 8

anti-inflammatory treatment for IBD

Question 9

which IBD is aminosalicylates more effective for?

Answer 9

ulcerative colitis

aminosalicylates are ineffective in inducing remission in crohns

Question 10

how do glucocorticoids treat IBD?

Answer 10

steroids are powerful anti inflammatory and immunosuppressants

down reg T cell and macrophage activity

however- unwanted side effects

Question 11

which IBD is gulucocorticoid treatment more effective for

Answer 11

GC induce remission in crohns

not reccomended for UC

Question 12

what is azathioprine

Answer 12

immuno suppressant
pro drug, activated by gut flora
purine antagonist

Question 13

what are the effects of azathioprine on the immune system?

Answer 13

impairs: 
cell and antibody mediated immune response 
lymphocyte proliferation 
mononuclear cell inflitration 
synthesis of antibodies 

and enhances T cell apoptosis

Question 14

what are the unwanted effects of azathioprine?

Answer 14

pancreatitis
bone marrow suppression
hepatotoxicity
increased risk of lymphoma and skin cancer

Question 15

what are the strategies for minimising unwanted effects of drugs?

Answer 15

administer topically

use low dose u combination with another drug

use drug with high hepatic first pass metabolism so little escapes the systemic circulation

Question 16

what are the potentially curative therapies?

Answer 16

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)

Question 17

what is the MOA of infliximab?

Answer 17

works by binding to TNFa and stop it from binding to the receptors and reduces downstream inflammatory events

given intravenously

Question 18

what are the problems with anti TNFa therapy?

Answer 18

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