Pathophys & Pharm: IBD

Question 0

Why is it believed that the enteric flora plays a role in the development of IBD?

Answer 0

(1) Mouse models have shown that colitis will not develop in a germ-free environment.
(2) Some patients with Crohn’s develop antibodies to proteins of certain enteric bacteria.
(3) The most common location for Crohn’s is the ileum and colon, where enteric flora is most prevalent.

Question 1

Which gene pathways are involved in both Crohn’s disease and ulcerative colitis?

Answer 1

The IL-23 and IL-12 gene pathways, which are both involved in Th17 regulation.

Question 2

What are functions of Th17 cells?

Answer 2

(1) Regulate Th1 and Th2 cells.

2) Produce cytokines that activate a number of cell lineages (epithelial cells, macrophages, fibroblasts

Question 3

What environmental factors affect the risk of IBD?

Answer 3

(1) Higher socioeconomic status
(2) Stress
(3) Smoking in Crohn’s disease (protective for ulcerative colitis)

Question 4

J: In Crohn’s disease, this refers to an area of inflammation with surrounding normal mucosa.

Answer 4

What is a skip lesion?

Question 5

J: In Crohn’s disease, this refers to a coalescence of ulceration with deep, serpiginous ulceration and heaped, edematous mucosa adjacent.

Answer 5

What is cobblestoning?

Question 6

In Crohn’s disease, to where can a fistula form?

Answer 6

Bladder, skin, elsewhere in bowel, genitourinary organs.

Perianal fistulae are frequently seen (along with skin tags, abscesses).

Question 7

Describe the formation of a stricture in Crohn’s disease.

Answer 7

(1) Chronic inflammation results in a TGF-B-driven attempt to heal.
(2) This results in a deposition of type 3 collagen.
(3) Fibrosis can lead to a stricture.

Question 8

What is the gross appearance of ulcerative colitis?

Answer 8

Hyperemia, edema and a granular appearance. The disease extends only into the mucosa.

Question 9

What is the clinical presentation of IBD?

Answer 9

(1) abdominal pain
(2) RLQ tenderness
(3) urgent diarrhea
(4) hematochezia
(5) constitutional symptoms
(6) weight loss, malabsorption

Question 10

What are the noted extraintestinal manifestations of IBD?

Answer 10

(1) erythema nodosum
(2) pyoderma gangrenosum
(3) primary sclerosing cholangitis

Question 11

What is primary sclerosing cholangitis?

Answer 11

Chronic inflammation of intra- and extrahepatic ducts of the biliary tree with beading irregularity and stricturing of the ducts. It is frequently associated with ulcerative colitis and increases risk of colorectal cancer and cholangiocarcinoma.

Question 12

Is Crohn’s disease curable? Is ulcerative colitis?

Answer 12

No. Yes.

Question 13

What is the medical therapy for mild IBD?

Answer 13

(1) short course of glucocorticoids for remission induction
(2) 5-ASAs for ulcerative colitis
(3) budesonide for Crohn’s disease
(4) topical steroids for distal disease

Question 14

What is the medical therapy for severe IBD?

Answer 14

(1) immunomodulators
(2) anti-TNF agents
(3) anti-a4 inhibitors

Question 15

What is the mechanism of action of aminosalicylates?

Answer 15

(1) inhibition of T cell activation
(2) inhibition of antigen presentation
(3) inhibition of adhesion
(4) decreased TNF production

Question 16

What are adverse effects of aminosalicylates?

Answer 16

(1) paradoxical diarrhea

(2) interstitial nephritis

Question 17

Are aminosalicylates used for Crohn’s disease? Ulcerative colitis?

Answer 17

No. Yes.

Question 18

What is the mechanism of action of glucocorticoids as a therapy for IBD?

Answer 18

(1) Inhibition of pro-inflammatory cytokines and adhesion molecules
(2) Inhibition of proteases, like elastase, collagenase
(3) Regulation of NF-kB
(4) Decreased phagocytosis by neutrophils
(5) Apoptosis of lymphocytes

Question 19

J: This steroid is used to treat IBD and is noted for its high first-pass metabolism in the liver.

Answer 19

What is budesonide?

Question 20

What are the thiopurines used in IBD therapy? What is the mechanism of action?

Answer 20

Azathioprine, 6MP.

(1) Inhibition of DNA synthesis
(2) Inhibition of purine synthesis
(3) Induction of apoptosis

Question 21

What are adverse effects of thiopurines?

Answer 21

(1) leukopenia, marrow suppression
(2) pancreatitis
(3) hepatitis
(4) infection
(5) 3-5 fold increased risk of non-Hodgkin lymphoma

Question 22

What is the mechanism of action of methotrexate?

Answer 22

(1) Folate antagonist

(2) Inhibition of some interleukins, anti-inflammatory

Question 23

What are adverse effects of methotrexate?

Answer 23

(1) nausea
(2) hepatic fibrosis
(3) teratogen
(4) mild leukopenia
(5) pneumonitis

Question 24

How is cyclosporin A used in treatment of IBD?

Answer 24

In fulminant cases of ulcerative colitis, it is used as a bridge until thiopurines kick in.

Question 25

What anti-TNF agents are used to treat IBD?

Answer 25

(1) infliximab
(2) adalimumab
(3) certolizumab

Question 26

What is the mechanism of action of anti-TNF agents?

Answer 26

(1) Bind and inhibit free and cell-bound TNF-a.
(2) Induction of apoptosis of lymphocytes in the lamina propia.
(3) Decrease secretion of IL-1, IL-6, IL-18 and INF-y.

Question 27

What are the adverse effects of anti-TNF agents?

Answer 27

(1) transfusion reactions
(2) drug-induced lupus
(3) infection
(4) malignancies (lymphoma, hepatosplenic T cell lymphoma, non-melanomatous skin cancer

Question 28

What is the mechanism of action of anti-a4 inhibitors (natalizumab)?

Answer 28

Binds to the a4 subunit of surface integrins on leukocytes, inhibiting adhesion

Question 29

In what setting are antibiotics like fluoroquinolones and imidazoles used to treat IBD?

Answer 29

When there are penetrating complications of Crohn’s disease.