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GIR Test 3 > B5.044 - Inflammatory Bowel Disease > Flashcards

B5.044 - Inflammatory Bowel Disease Flashcards

1
Q

clinical picture of IBS

A

LLQ abdominal cramping which improves with defecation, needing to use bathroom at night

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2
Q

differential for abdominal pain and BRB

A

infectious vasculitis irritable bowel IBD

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3
Q
A

diffuse mucosal granularity, erythema, exudate

UC

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4
Q

histo of UC

A

distortion of crypt architecture

crypt abscesses

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5
Q
A

crypt abscesses, UC

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6
Q

when should you think ischemic colitis

A

young female on HRT

watershed areas (limited blood supply in splenic flexure and rectosigmoid junction)

sparing of the rectum

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7
Q
A

CMV colitis

mimic for UC

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8
Q

symptoms of ulcerative colitis

A

bloody diarrhea

abdominal pain

fecal urgency

disease limited to colon

rectum involved

inflammation limited to mucosa and submucosa

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9
Q

what is inflammatory bowel disease

A

complex immunological disorder with complex pathogenesis

chronic idiopathic intestinal inflammation

2 main subtypes: UC, crohns

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10
Q

epidemiology of IBD

A

bimodal peak

15-25, 50-70

more common among ashkenazi jews

overlap with autoimmune conditions

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11
Q

environmental influences of IBD

A

UC - non smokers

crohns - smokers

impact of geographic latitude: more common in colder climates and in developed countries

Hygiene hypothesis

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12
Q

what constitutes diarrhea

A

>200 ccs / day

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13
Q

where is most water absorbed in descending order

A

jejunum, small intestine, colon, ileocecal

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14
Q

describe sodium absorption in the intestine

A

electrogenic

electroneutral NaCl

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15
Q

describe inflammatory diarrhea

A

NA absorption is diminished

Cl secretion is increased: inflammatory mediators affecting apical membrane transport proteins

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16
Q

what causes the defective NA absorption in IBD

A

change in priorties of inflamed colonocytes

reduce NA pump activity

high concentrations of inflammatory cytokines (TNF is one of them) result in gene depression of enterocyte cellular transport function

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17
Q

describe infectious inflammatory diarrhea

A

luminal or invading

viruses

bacteria

protozia

helminths

all lead to minimal or severe inflammation, enterocyte damage or death, malabsorption and secretion

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18
Q

describe inflammatory diarrhea

A

immunological mechanisms

complement

T lymphocytes

proteases

oxidants

minimal or sever inflammation, enterocyte damage, malabsorption and secretion

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19
Q

pathogenesis of IBD

A

host genetics/immune system

microbes in the lumen

excessive immune reactivity or inadequate immune responses to intestinal microbiota

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20
Q

what is the microbiome and how is it different from microbiota

A

ecological community pathogenic microorganisms (bacteria, fungus, yeast) and us

microbiota is microorganisms alone

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21
Q

what part of the body has the highest numeber of bacteria and species

A

gut flora

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22
Q

when is the gut flora established

A

1-2 years after birth

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23
Q

microbiota dominated by what

A

bacteriodetes and firmicutes

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24
Q

positive role of microbes

A

nutrition

energy metabolism

proper conditioning of the intestinal and peripheral immune systems

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25
Q

negative role of microbes

A

microbial derived factors may promote inflammatory bowel disease in the context of an underlying genetic immune defect

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26
Q

what are factors that can change intestinal bacteria

A

dietary

helminths

antibiotics

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27
Q

what are ways the epithelial barrier can be dysregulated

A

alterations in intestinal mucus

high numbers of bacteria within mucus

increased intestinal permeability “leaky gut” enhanced exposure to intetsinal bacteria

abnormalities in paneth cells

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28
Q

ways that dysregulation of immune cells can happen

A
  1. homing - recruitmen of neutrophils from the blood vessels to the mucosa, chemokines secreted from the tissues acrivate adhesion molecules
  2. diapedesis - moving through the endothelium

enhanced expression of adhesion molecules on leukocytes and endothelial cells, chemokines, leukocyte binding have been described in IBD

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29
Q

what is alpha 4 beta 7 integrin heterodimer

A

important for mediating lymphocyte trafficking to lamina propria, blocks adhesion of leukocytes

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30
Q

describe dysregulation in secreted mediators seen in IBD

A

abnormal levels of immunoregulatory and inflammatory cytokines correlate with active IBD

CD4+ T lymphocytes secrete large amounts of IFN gamma and TNF

ant TNF antibodies for crohsn sometimes helps

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31
Q

describe the genetic susceptibility in IBD

A

NOD2 - stenotic ds 70% of the genes are shared between crohns and UC

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32
Q

what is NOD2

A

greatest risk of developign crohns

responds to bacterial peptidoglycan which then activates signaling pathways that lead to cytokine production and clearance of bacteria

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33
Q

what is NOD2 associated with

A

ileal and fibrostenosing crohn disease

worse outcomes following ileal pouche anal anastemosis for UC

34
Q

what is autophagy

A

a process that mediates resistance to intracellular pathogens

35
Q

what mutation is associated with

A

crohns

changes in paneth cells and goblet cells

decreased ability to clear bacteria

increased secretion of cytokines

36
Q

what are common infections affecting terminal ileum

A

TB

yersinisa

37
Q

describe symptoms of yersinia enterocolitica

A

weeks of diarrhea, sore throat, may have reactive arthritis, involves TI and cecum, mesenteric adenopathy

38
Q

describe the clinical picture of behcets disease

A

systemic vasculitis, asian, apthous mouth ulcers, RLQ pain, diarrhea, genital ulcers

39
Q

crohns distribution

A

50% ileocolic

30% ileal

20% colic

40
Q
A

crohns

note the granuloma

41
Q

CDAI

A

crohns disease activity index

0-600

>150 active disease

>450 severe disease

42
Q
A

crohns

43
Q
A

ulcerative colitis

44
Q

crohns complications

A

transmural inflammation

stricutres

fistulas

abscesses

anal fissure

45
Q

describe symptoms of crohns

A

abdominal pain

weight loss

transmural inflammation

symptoms depend on location of disease

colonoscopy shows skipped lesions

histo - granuloma

46
Q

what is erythema nodosum

A

painful nodular lesions on the trunk and anterior shins

improves with disease treatment

47
Q
A

erythema nodosum

48
Q

pyoderma gangrenosum

A

necrotizing painful lesion

can be anywhere including face

pathergy - avoid surgical debridement!!

49
Q
A

pyoderma gangrenosum

50
Q

active IBD extraintestinal manifestations

A

episcleritis

peripheral arthropathy

erythema nodosum

51
Q

PSC features

A

beads on a string, chain of lakes

independent risk factor for colon cancer

start colonoscopic surveillance when found

10% lifetime risk of cholangiocarcinoma

52
Q

describe pancreatitis and IBD

A

medications related (mesalamine and AZA)

IgG-4 related autoimmune pancreatitis associated with IBD

thromboembolic risk in IBD increased 3 x

53
Q

what are nutritional issues that can arise from IBD

A

small bowel disaese or diminished absorptive area due to surgeries

ileal resection:

* vit B12 deficiency

* bile acid absorption

* vit D deficiency

* zinc deficiency

54
Q

describe zinc deficiency

A

seborrheic rash on legs and face, scaling around the nose and mouth + diarrhea

55
Q
A

left - ulcerative colitis

right - crohns

56
Q

anti-TNF drugs

A

adalimumab

certolizumab

infliximab

57
Q

anti integrin drug

A

natalizumub

58
Q

immunomodulator drugs for IBD

A

azathoprine

cyclosporine

methotrexate

59
Q

corticosteroids for IBD

A

budesonide

hydrocortisone

prednisone

60
Q

antibiotics for IBD

A

ciprofloxacin

metronidazole

61
Q

aminosalicylates

A

mesalamine

sulfasalazine

62
Q

describe the treatment of IBD

A

mild - corticosteroids, antibiotics, aminosaicylates

moderate - immunomodulators, oral corticosteroids

severe - surgery biologics

63
Q

what are aminosalicylates used for and what do they do

A

UC

inhibit IL1, TNF, arachadonic acid metabolites, NFkB, leukocyte chemotaxins, PG and LT produciton

Induce - apoptosis, activation of PPAR-g , ROS scavenger

64
Q

5-ASA release sites

A

pentasa - stomach, SI, LI

apriso - SI, LI

65
Q

AEs of aminosalicylates

A

sulfa moiety

headache, nausea, fatigue, bone marrow suppression

allergic rxns

also inhibits intestinal folate absorption

olsalazine diarrhoea mesalamine - interstitial nephritis

66
Q

corticosteroids side effects

A

HTN

Hypokalemia

adrenal suppression

cushings

retionapthy

osteoporosis

diabetes

avascular necrosis

67
Q

serious side effects of anti TNF therapy

A

T cell lymphoma, hepatosplenic lymphoma

absolute risk is VERY low

young male

concurrent with thiopurins

infusion reactions/serum sickness

68
Q

what is PML

A

demyelinating disease leads to severe disability or death

Natalizumab (antibody agaisnt alpha 4 integrin)

reactivation of JC virus

JVC antibodies (risk is low with negative antibodies)

69
Q

what is vedolizumab

A

alpha 4 beta 7 specific drug, specific for gut

70
Q

goals of surgery for UC

A

cure the disease

prevent cancer

71
Q

indications for surgery for UC

A

toxic megacolon

hemorrhage

medical intractability

malignant degeneration

72
Q
A

toxic megacolon

73
Q

discuss surgery in crohns

A

75% of crohns patients require some surgical intervention

fistula in crohns disease

strictures

74
Q

discuss colon cancer risk

A

in general IBD patients live as long as others except cancer and thromboembolic event

18% colon cancer risk after 30 years

75
Q

risk factors for colon cancer in IBD

A

age of colitis onset <15

duration

disease extent

severity, inflammatory complications, PSC, familial hx of CRC

76
Q

proto oncogenes colitis associated neoplasm

A

k-ras, c-src

77
Q

tumor suppressor genes associated with colitis neoplasm

A

loss of mutation of p53, APC

78
Q

describe instability types in colitis associated neoplasm

A

CIN - chromosomal instability

microsatellite instability - MSI

79
Q

what is aneuploidy

A

a difference in chromosome number in neoplastic lesions AND in flat nondysplastic colonic mucosa

80
Q

describe carcinogenesis in UC

A

normal -aneuploidy, p53 –> low grade dysplasia –> k-ras, c-src –> microsat instab –> APC, Rb, other TSG –> malignant cell

81
Q

sporadic carcinogenesis

A

normal colonic cell –> APC, DNA hypomethylation, aneuploidy –> early adenoma –> k-ras –> intermediate adenoma –> DCC –> microsat –> late adenoma –> p53 –> maignant cell

82
Q

special characteristics of colitis associated neoplasm

A

inflammation - multifocal dysplasia - cancer

GIR Test 3 (6 decks)

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