IBD pathogenesis and treatment

Question 1

what is the definition of IBD

Answer 1

chronic relapsing and remitting inflammatory disorders of unknown aetiology

Question 2

what are two types of IBD

Answer 2

crohns and ulcerative colitis

Question 3

what is the difference between crohns disease and UC

Answer 3

crohns can affect any part of the GIT although most cases start in the terminal ileum
UC is restricted to the colon and the rectum

Question 4

what is IBD caused by

Answer 4

failure to maintain oral tolerance

Question 5

what is the genetic predisposition of IBD

Answer 5

increased susceptibility associate with mutations in genes NOD2 (CD)
also with polymorphisms in IL23-R (CD and UC)
positive family history is the largest independent risk factor for IBD

Question 6

what is NOD2 and IL23-R

Answer 6

nucleotide binding oligomerisation domain containing 2 - activates NF kB in response to bacterial LPS

IL-23 produced by DC nd functions as a regulator of chronic inflammation

Question 7

what are the symptoms of UC

Answer 7

diarrhoea with blood and mucus, weight loss, abdominal pain, nocturnal symptoms

Question 8

what are the clinical signs of UC

Answer 8

tender abdomen
tachycardia
pyrexial
extra intestinal manifestations

Question 9

describe the pathogenesis of crohns

Answer 9

cam affect any part of GI but most commonly affect the ileum and colon
typically discontinuous, transmural and with granulomas

Question 10

what is the current concept and association with why we have IBD

Answer 10

results from a lack of abrogation of oral tolerance to commensal bacterial Ag’s
CD associated with Th1 response
UC associated with Th2 response

Question 11

what is the medical treatment of mild proctitis

Answer 11

5 ASA/steroid

topical

Question 12

what is the medical management of left sided UC

Answer 12

5 ASA steroid

topical

Question 13

what is the medical management of pan colitis

Answer 13

5 ASA - systemic

Question 14

how do you treatment moderate UC

Answer 14

5ASA steroid topical
systemic steroid
immunomodulator
surgery

Question 15

how do you treat severe UC

Answer 15

parenteral steroids
ciclosporin
surgery

Question 16

what are the complications of crohns disease which require surgery

Answer 16

abscess, fistula, perforation stricture cancer

Question 17

what is sulphasalazine

Answer 17

sulphapyridine diazo bounded with 5 ASA showed to improve symptoms of UC
azo bond prevents proximal absorption and colonic bacteria splits the molecule

Question 18

how does azathioprine work

Answer 18

Aza - 6-MP - 6-thioguanine
6-thioguanine - thioinosinic acid & thioguanylic acid (conj. with ribose)
Incorporated into DNA (halt replication)
Inhibit purine biosynthesis (via GPAT)
Phosphorylated to triphosphate forms -block Rac1 - increased apoptosis (of mononuclear cells)

Question 19

what is the mechanism of action of methotrexate

Answer 19

inhibits folate metabolism
cytotoxic effects via DHFR inhibition
anti-inflammatory effects via inhibition of other enzymes

leads to IL-1 receptor blockade
increased IL-2 production
decreased IL-6 and 8 production
impaired neutrophil chemotaxis

Question 20

what do these drugs do in IBD
natalizumab
vedolizumab
vercimon

Answer 20

blocks a4b1 - but receptor found elsewhere in the body and be a problem
blocks a4b7 which is more specific to he gut
withdrawn after phase 3 trials but stopped adhesion for inflammation

Question 21

when do we need to operate on patients with IBD

Answer 21

emergency such as bowel obstruction/perforation, abscess, severe bleeding

elective (planned) - cancer, patient choice

Question 22

what are the pros and cons of laparoscopic surgery

Answer 22

pros - less pain after surgery, smaller scars, faster recovery, reduced risk of infection
cons - not available in all surgeries and may not be appropriate if already had abdominal surgery

Question 23

name other potential forms of therapy for IBD

Answer 23

inhibitors of inductive cytokines 
cytokines to induce Treg cells 
genetically engineered probiotics 
attenuated helminths
faecal transplantation 
manipulation of flora

Question 24

what are the benefits of probiotic therapy / vaccination

Answer 24

targeted delivery to site
protection against disease and infection
easy administration
cheap
systemic and mucosal responses are stimulated
increased compliance

Question 25

how do you treat murine IBD

Answer 25

lactoccoucus lactis secreting IL-10

this however is non-commensal bacteria and cannot be regulated

Question 26

describe how helminths are used treat crohns disease

Answer 26

limited infection in humans

80% response with ingestion of ova