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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
negative role of microbes
microbial derived factors may promote inflammatory bowel disease in the context of an underlying **genetic immune defect**
26
what are factors that can change intestinal bacteria
dietary helminths antibiotics
27
what are ways the epithelial barrier can be dysregulated
alterations in intestinal mucus high numbers of bacteria within mucus increased intestinal permeability "**leaky gut**" enhanced exposure to intetsinal bacteria abnormalities in paneth cells
28
ways that dysregulation of immune cells can happen
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
29
what is alpha 4 beta 7 integrin heterodimer
important for mediating lymphocyte trafficking to lamina propria, blocks adhesion of leukocytes
30
describe dysregulation in secreted mediators seen in IBD
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
31
describe the genetic susceptibility in IBD
NOD2 - stenotic ds 70% of the genes are shared between crohns and UC
32
what is NOD2
greatest risk of developign crohns responds to bacterial peptidoglycan which then activates signaling pathways that lead to cytokine production and clearance of bacteria
33
what is NOD2 associated with
**ileal and fibrostenosing crohn disease** worse outcomes following ileal pouche anal anastemosis for UC
34
what is autophagy
a process that mediates resistance to intracellular pathogens
35
what mutation is associated with
crohns changes in paneth cells and goblet cells decreased ability to clear bacteria increased secretion of cytokines
36
what are common infections affecting terminal ileum
TB yersinisa
37
describe symptoms of yersinia enterocolitica
weeks of diarrhea, sore throat, may have reactive arthritis, involves TI and cecum, mesenteric adenopathy
38
describe the clinical picture of behcets disease
systemic vasculitis, asian, apthous mouth ulcers, RLQ pain, diarrhea, genital ulcers
39
crohns distribution
50% ileocolic 30% ileal 20% colic
40
crohns note the granuloma
41
CDAI
crohns disease activity index 0-600 \>150 active disease \>450 severe disease
42
crohns
43
ulcerative colitis
44
crohns complications
transmural inflammation stricutres fistulas abscesses anal fissure
45
describe symptoms of crohns
abdominal pain weight loss transmural inflammation symptoms depend on location of disease colonoscopy shows skipped lesions histo - granuloma
46
what is erythema nodosum
painful nodular lesions on the trunk and anterior shins improves with disease treatment
47
erythema nodosum
48
pyoderma gangrenosum
necrotizing painful lesion can be anywhere including face pathergy - avoid surgical debridement!!
49
pyoderma gangrenosum
50
active IBD extraintestinal manifestations
episcleritis peripheral arthropathy erythema nodosum
51
PSC features
beads on a string, chain of lakes independent risk factor for colon cancer start colonoscopic surveillance when found 10% lifetime risk of cholangiocarcinoma
52
describe pancreatitis and IBD
medications related (mesalamine and AZA) IgG-4 related autoimmune pancreatitis associated with IBD **thromboembolic risk in IBD increased 3 x**
53
what are nutritional issues that can arise from IBD
small bowel disaese or diminished absorptive area due to surgeries ileal resection: \* vit B12 deficiency \* bile acid absorption \* vit D deficiency \* zinc deficiency
54
describe zinc deficiency
seborrheic rash on legs and face, scaling around the nose and mouth + diarrhea
55
left - ulcerative colitis right - crohns
56
anti-TNF drugs
adalimumab certolizumab infliximab
57
anti integrin drug
natalizumub
58
immunomodulator drugs for IBD
azathoprine cyclosporine methotrexate
59
corticosteroids for IBD
budesonide hydrocortisone prednisone
60
antibiotics for IBD
ciprofloxacin metronidazole
61
aminosalicylates
mesalamine sulfasalazine
62
describe the treatment of IBD
mild - corticosteroids, antibiotics, aminosaicylates moderate - immunomodulators, oral corticosteroids severe - surgery biologics
63
what are aminosalicylates used for and what do they do
UC inhibit IL1, TNF, arachadonic acid metabolites, NFkB, leukocyte chemotaxins, PG and LT produciton Induce - apoptosis, activation of PPAR-g , ROS scavenger
64
5-ASA release sites
pentasa - stomach, SI, LI apriso - SI, LI
65
AEs of aminosalicylates
sulfa moiety headache, nausea, fatigue, bone marrow suppression allergic rxns also inhibits intestinal folate absorption olsalazine diarrhoea mesalamine - interstitial nephritis
66
corticosteroids side effects
HTN Hypokalemia adrenal suppression cushings retionapthy osteoporosis diabetes avascular necrosis
67
serious side effects of anti TNF therapy
T cell lymphoma, hepatosplenic lymphoma absolute risk is VERY low young male concurrent with thiopurins infusion reactions/serum sickness
68
what is PML
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
what is vedolizumab
alpha 4 beta 7 specific drug, specific for gut
70
goals of surgery for UC
cure the disease prevent cancer
71
indications for surgery for UC
toxic megacolon hemorrhage medical intractability malignant degeneration
72
toxic megacolon
73
discuss surgery in crohns
75% of crohns patients require some surgical intervention fistula in crohns disease strictures
74
discuss colon cancer risk
in general IBD patients live as long as others except cancer and thromboembolic event 18% colon cancer risk after 30 years
75
risk factors for colon cancer in IBD
age of colitis onset \<15 duration disease extent severity, inflammatory complications, PSC, familial hx of CRC
76
proto oncogenes colitis associated neoplasm
k-ras, c-src
77
tumor suppressor genes associated with colitis neoplasm
loss of mutation of p53, APC
78
describe instability types in colitis associated neoplasm
CIN - chromosomal instability microsatellite instability - MSI
79
what is aneuploidy
a difference in chromosome number in neoplastic lesions **AND** in flat nondysplastic colonic mucosa
80
describe carcinogenesis in UC
normal -aneuploidy, p53 --\> low grade dysplasia --\> k-ras, c-src --\> microsat instab --\> APC, Rb, other TSG --\> malignant cell
81
sporadic carcinogenesis
normal colonic cell --\> APC, DNA hypomethylation, aneuploidy --\> early adenoma --\> k-ras --\> intermediate adenoma --\> DCC --\> microsat --\> late adenoma --\> p53 --\> maignant cell
82
special characteristics of colitis associated neoplasm
inflammation - **multifocal dysplasia** - cancer

GIR Test 3 (6 decks)

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