10/13- Inflammatory Bowel Disease Flashcards Preview

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Flashcards in 10/13- Inflammatory Bowel Disease Deck (50)
1

Inflammatory Bowel Disease encompasses what other conditions?

- Ulcerative colitis: mucosal ulceration in colon

- Crohn's disease: transmural inflammation

  • Ileitis
  • Ileocolitis
  • Colitis

2

What are the supposed components of pathogenesis of IBD?

- Genetic susceptibility

- Environmental triggers

- Luminal agents/Immune System

3

What are supposed environmental triggers for IBD?

- Stress

- Infections

- Antibiotics

  • Especially early in life, may increase the risk for IBD

- Diet

- NSAIDs

- Smoking

4

What is the hygiene hypothesis in relation to IBD?

Limited antigenic exposure in infancy may lead to later hyper-responsiveness

- Linked to asthma, multiple sclerosis, other “auto-immune diseases”

- “Let the kids play in the dirt”

5

How does smoking relate to IBD?

- Ulcerative colitis

- Crohn's disease

Ulcerative colitis

- Smoking can protect against UC

- Ex-smokers are more likely to develop UC

Crohn's disease

- 2x risk in current smokers

- Smokers are less responsive to treatment

- Smokers are more likely to develop recurrence of disease after surgery

6

What is the role of bacteria in IBD

- Infectious etiologies

- Experimental models

- Other factors

Infectious etiology:

- Mycobacteria paratuberculosis (Johne’s d)

- Enteroadherent E. coli

- Cold chain hypothesis (Listeria)

Experimental models:

- Sterile gut -> No IBD

- Bypassed segment -> No IBD

Probiotics

Microbiome

7

What supports genetic influence of IBD?

- Are genetics more significant in UC or CD?

- Chromosomes involved

- Mutations

- More significant in Crohn's disease (50% of identical twins will be singularly affected; 50% will both half it)

- Familial occurrence

- Clinical pattern of Crohn's disease in families

- Polygenic susceptibility

Chrom/Mutations:

- Chromosomes 12 > 12, 6, 5

- NOD-2 mutations on chrom 16 in Crohn's

- Cytokine cluster region on chrom 5 in Crohn's

- Genotype/phenotype correlations

8

What is the first gene associated with Crohn's disease?

- Chromosome

- Function

- Molecules involves

NOD2

- Chrom 16q12

- Similar to plant disease resistant proteins

- Part of the innate immune system

Function

- Related to immune response to bacteria

- Activates "down stream" inflammatory cell signals

- Innate immune system:

  • Sampling of luminal antigens
  • Recognition of commensals/pathogens

NOD(CARD)/TLR Molecules:

- Pattern recognition receptors (PRP)

- Pathogen-assoc Molecular Pattern (PAMP)

- Muramyl dipeptide in cell walls

Paneth cells

Not sure if gain or loss of function

9

What is the risk of developing Crohn's disease with NOD2?

1 copy: 1.5-4x risk

2 copies: 15-40x risk

- 10% of CD pts have 2 copies

- 28% of CD pts have 1 copy

- Actual disease presence with 1-2 gene copies is still < 10%

10

What mutation may be protective for IBD?

- More in CD or UC

- Cells involved/function

IL-23 receptor

- Protective gene mutation

- (1.9% in ileal non-Jewish CD vx. 7% in controls)

- Protective in both CD and UC

- Other IL-23 mutations increase risk of CD

- Th17 immune response

11

What are other genetic components expected to play a role in IBD?

MDR-1 (UC)

- P-glycoprotein efflux pump

- Mucosal integrity

TNFSF 15

ATG16L1

- Autophagy pathway

  • Cellular adaptation to starvation
  • Inhibits TB survival in macrophages

12

Is the knowledge of a pt's genetics helpful in diagnosing/treating IBD?

- Commercially available but NOT recommended in clinical practice

- NOD2 phenotype: ileal disease

- Predictor perhaps for need for surgery but not of response to therapy

13

New genes: - ___ may be found in 20% of _____

- > ___ genes linked to IBD

- NOD2(CARD15) may be found in 20% of Crohn's disease

- > 150 genes linked to IBD

14

What are the changes in epidemiology (unexplained by genetics)?

- Increase in Crohn’s in US

- Rapid changes in Japan, Middle East, India

- Racial differences (e.g.no NOD2 in Blacks)

15

It is thought that the pathogenesis of IBD may involve an imbalance between pro and anti-inflammatory components.

What are some pro-inflammatory factors (loss of tolerance)?

What about anti-inflammatory (tolerance)?

Pro-inflammatory (loss of tolerance):

- TNF

- IL-1B

- IL-4, 6, 12, 18

- IFN-y

Anti-inflammatory (tolerance)

- IL-1Ra, 10, 13

- TGF-B

- PGE2 , PGJ2

16

Describe the macrophage/DC inflammatory pathway

- Memory CD4 cell path

Macrophages and DCs:

- IL-12 -> Th1 -> IFN-y/TNF/IL2

- IL-23 -> ThIL17 -> IL17, 17F, TNF, IL6

Memory CD4 cells, NKT, mast cells, and eos:

- IL-4 -> Th2 -> IL4, 5, 10, 13 

17

Etiologic Hypothesis of IBD?

- Persistent Infection

- Defective mucosal integrity

- Dysbiosis

- Dysregulated immune response

18

Age and sex incidence of IBD?

Ulcerative colitis:

- More in females

- Peak onset at age 20

Crohn's disease:

- More in males

- Peak onset at age 20

19

What races are most affected in IBD?

White > Black > Asian > Hispanic

- Crohn's typically more common than UC (exception = Hispanics; more affected by UC)

20

Worldwide distribution of IBD?

- US, Scandinavia, UK

- N/S America, China, India, Australia, W Europe, S Africa

21

What are common "imposters" in DDx of IBD?

- Infectious colitis (incl C. dificile)

- Ischemic colitis

- Drug-induced (NSAID) enterocolitis

- Solitary rectal ulcer syndrome

- Radiation enterocolitis

- Diversion colitis

- Endometriosis

- Malignancy

- Functional: IBS

- Diverticular disease

22

How do the following clinical features differ between UC and CD?

- Abdominal pain

- Bloody diarrhea

- Abdominal mass

- Intestinal obstruction

- Perianal disease

- Fistulae

- Effect of smoking

- Systemic symptoms: EIMs

23

T/F: The severity of UC is based upon its distribution?

False

- Based on stools/day and presence of blood

24

Distribution patterns of UC?

- Distal UC: inflammation limited to area below the splenic flexure

- Extensive UC: inflammation extends proximal to splenic flexure

25

What is a truism of UC?

Always involves the distal colon (?)

26

Describe the severity classes of UC

- Mild

- Moderate

- Severe

- Fulminant

Mild:

- Under 4 stools/day +/- blood

- Normal ESR

- No signs of toxicity

Moderate:

- 4+ stools/day

- Minimal signs of toxicity

Severe

- 6+ stools/day

- Fever, tachycardia, anemia, increased ESR

Fulminant

- 10+ stools/day with continuous bleeding

- Toxicity, abdominal tenderness/distension

- Transfusion requirement

- Colonic dilation on xray

27

What is the role of endoscopy in IBD?

- Confirm diagnosis

- Differentiate UC from CD

- Obtain histologic confirmation (severity and extent) and exclude other etiologies

- Surveillance for neoplasia

28

Describe the features of UC and CD in terms of:

- Mucosal involvement

- Strictures

- Rectal involvement

29

What is seen here?

Ulcerative colitis (spectrum of disease)

- Normal -> Mild -> Moderate -> Severe

30

What is seen here? 

Crohn's disease

Top left: discrete "punched out" aphthae

Top right: Irregular stellate ulcer (looks as though punched out by cookie cutter)

Bottom left: longitudinal ulcer

Bottom right: macroulecerations and pseudopolyps (occur in both UC and CD)

31

What are components of the NonInvasive Assessment of IBD?

Radiologic

- Barium contrast

- Abdominal US

- CT

- MRI

Nonspecific inflammation markers

- ESR

- CRP

- Platelet count

Serologic (disease specific)

- ASCA

- pANCA

- ompC

Fecal

- Lactoferrin

- Calprotectin

32

What is seen here?

Sever ulcerative colitis

33

What are some intestinal complications of ulcerative colitis?

- Bleeding

- Toxicity

  • Dilation (megacolon)

Systemic complications: related to inflammatory activity

34

Describe systemic complications in IBD?

- Extra-intestinal manifestations common but not predictable

- Sometimes more symptomatic than bowel disease

Symptoms:

- Aphthous stomatitis

- Episcleritis and uveitis

- Arthritis

- Vascular complications

- E. Nodosum

- P. gangrenosum

35

Describe epidemiology of EIMs (extra-intestinal manifestations)?

- How common

- Relation to IBD activity

- More in UC or CD?

- Occurs in up to 1/3 of IBD pts

- May parallel or be independent of IBD activity (may herald relapse)

More common associations:

- UC: PSC, pydoerma ganrenosum

- CD: Ankylosing spondylitis, erythema nodosum

36

What is aphthous stomatitis?

EIM (CD > UC)

- Occurs in under 5% of UC and 20% of CD pts

- Usually presages or follows course of IBD

- Optimal maintenance therapy to prevent occurrence is crucial 

37

What are eye-related EIMs of IBD?

Ulcerative colitis:

- Episcleritis

- Uveitis 

38

What are some skin-related EIMs of IBD?

Ulcerative colitis:

- Erythemia nodosum

- Pyoderma gangrenosum 

39

Joint related EIM of IBD?

- Characteristics

Ulcerative colitis:

Peripheral arthritis

- Monarticular

- Asymmetrical

- Large > small joint

- No synovial destruction

- No subcutaneous nodules

- Seronegative

Central (axial) arthritis

- Ankylosing spondylitis

- Sacro-iliitis 

40

Bile duct EIMs of IBD?

Ulcerative colitis:

- Sclerosing cholangitis

- Cholangiocarcinoma 

41

What are some thromboembolic complications in IBD?

(incidence of 0.5%)

- Usually occur with severe disease activity

(result of hypercoagubility associated with altered levels of clotting factors and platelet abnormalities)

- Other risk factors for thrombosis often present

42

Connection between inflammation and cancer- give examples of this in the GIT

- Gastric cancer, MALT : H. Pylori

- Liver Cancer : Chronic Hepatitis, both viral and non-viral etiologies

- Pancreatic Ca : Chronic pancreatitis

- Lymphoma : Celiac disease

43

Mechanism behind tie between inflammation and cancer?

44

Is cancer risk increased with IBD? How?

40x increased risk of colorectal cancer in ulcerative colitis (although, very low rates in normal population)

- Inflammatory change -> dysplasia

45

What is the anatomic distribution of Crohn's disease?

- Small bowel alone (33%)

- Ileocolic (45%)

- Colon alone (20%)

46

What are the clinical presentations of Crohn's disease?

- Chronic pain and diarrhea

- Intestinal obstruction

- Acute inflammation ("appendicitis-like")

47

Crohn's disease is a ___ process (histologically)?

Crohn's disease is a transmural process

- May involve granulomas (although not necessarily) 

48

Radiologic features of Crohn's disease?

- Ileitis

- "String sign" 

49

What is an intestinal complication of Crohn's disease?

Fistula

- Mesenteric

- Enter-enteric

- Entero-vesicular

- Retroperitoneal

- Entero-cutaneous

Small bowel related:

- Gallstones

- Malabsorption

Renal:

- Stones

- Fistulae

- Hydronephrosis

- Amyloidosis

50

Does UC vs. CD diagnosis make a difference in regard to:

- Meds

- Complications

- Nutrition

- Surgery

- Meds: no

- Complications: maybe

- Nutrition: yes

- Surgery: yes!!