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

B5.044 Inflammatory Bowel Disease Flashcards

1
Q

symptoms of dehydration that may accompany IBD

A

orthostatic hypotension

tachycardia

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2
Q

differential diagnosis for IBD

A 
infectious diarrhea
autoimmune disease
gynecological condition
irritable bowel syndrome
inflammatory bowel disease
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3
Q

red flags that support an IBD diagnosis

A

blood in stool
nocturnal diarrhea
young age

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4
Q

lab test results of IBD

A

leukocytosis
low hemoglobin
intermediate ESR

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5
Q

important negative finding of IBD on stool culture

A

negative bacterial culture

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6
Q

CT abdomen findings in IBD

A

thickening of the sigmoid colon and descending colon

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7
Q

colonoscopy findings in IBD

A

diffuse mucosal granularity, erythema, exudate

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8
Q

ulcerative colitis histology findings

A 
distortion of crypt architecture
crypt abscesses (inflammatory cells in crypts)
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9
Q

what are some indications to consider 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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10
Q

what parts of the colon are supplied by the SMA

A

terminal ileum

right side of the colon

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11
Q

what parts of the colon are supplied by the IMA

A

left side of the colon

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12
Q

what is CMV colitis and how do you tell it from UC?

A

looks the same as UC on colonoscopy
found only in immunocompromised patients
biopsy is diagnostics

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13
Q

symptoms of UC

A 
bloody diarrhea
abdominal pain
fecal urgency
disease is limited to the colon
rectum is involved
inflammation is limited to mucosa and submucosa
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14
Q

what is the pathogenesis of IBD

A

complex immunological disorder with complex pathogenesis

chronic idiopathic intestinal inflammation

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15
Q

2 main types of IBD

A

crohn’s disease

ulcerative colitis

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16
Q

epidemiology of IBD

A

bimodal peak- 15-25 or 50-70
more common among Ashkenazi Jews
overlap with autoimmune conditions

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17
Q

environmental influences associated with IBD

A

UC- nonsmokers
crohn’s disease- smokers
more common in colder climates and in developed countries
“hygiene hypothesis”

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18
Q

how much water gets reabsorbed from the small intestine

A

6 L per day

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19
Q

how does colonic reabsorption of water vary

A

1.8 L with maximal absorptive capacity of 4.5-5 L per day

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20
Q

how much water is lost in the stool

A

<0.2 L per day

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21
Q

normal intestinal electrolyte absorption

A

sodium absorption( electrogenic or electroneutral NaCl absorption)
potassium secretion and absorption
chloride secretion
short chain fatty acid absorption

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22
Q

what is secretory diarrhea

A

excess input of NaCl into bowel lumen with water following

massive volume of plasma like fluid

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23
Q

what is inflammatory diarrhea

A

Na absorption is diminished
Cl secretion is increased
inflammatory mediators affect apical membrane transport proteins causing water to flow into lumen

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24
Q

why does defective Na transport occur in inflammatory diarrhea

A

change in properties of inflamed colonocytes
reduced Na pump activity
high concentrations of inflammatory cytokines (TNF) result in gene depression of enterocyte cellular transport function

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25
Q

things that can cause diarrhea in IBD that are NOT inflammation of the mucosa

A 
bile induces
fatty diarrhea
short bowel syndrome
concurrent c-diff
CMV
small intestinal bacterial overgrowth
celiac sprue
untreated lactose intolerance
NSAID associated enteropathy
IBS
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26
Q

progression of inflammatory diarrhea

A

minimal or severe inflammation > enterocyte damage or death > malabsorption and secretion

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27
Q

proposed pathogenesis of IBD

A

host genetics + immune system + gut microbes all play a role

possible excessive immune reactivity or inadequate immune responses to intestinal microbiota

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28
Q

microbiome

A

ecological community of pathogenic microorganisms and us

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29
Q

microbiota

A

microorganisms alone

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30
Q

discuss the human gut flora

A

largest number of bacteria and greatest # of species compared to other areas of the body
established at 1-2 years of age
150 species of bacteria in the colon

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31
Q

why can bacterial species in the gut change over time

A

mode of delivery
environment
illness and antibiotic exposures

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32
Q

what organisms dominated the microbiota of the gut

A

bacteriodetes

firmicutes

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33
Q

positive role of microbes

A

nutrition
energy metabolism
proper conditioning of the intestinal peripheral immune systems

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34
Q

negative role of microbes

A

microbial derived factors may promote IBD in the context of underlying genetic immune defect

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35
Q

what can happen as a result of changes in communities of intestinal bacteria

A

can dysregulate talk between host and microbes
inappropriate response to microbes by immune system
can contribute to development of inflammation

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36
Q

what are components of the mucosal immune system

A

intact intestinal epithelium
secretion of protective factors
innate immune system
acquired immune system

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37
Q

what are some ways that the epithelial barrier can be dysregulated

A

alteration in intestinal mucus
high numbers of bacteria within mucus
increased intestinal permeability (enhanced exposure to intestinal bacteria)
abnormalities in paneth cells

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38
Q

discuss the process of homing

A

recruitment of neutrophils from the blood vessels to the mucosa
leukocytes “roll” along endothelium
chemokines secreted from the tissue activate adhesion molecules, resulting in firm adhesion

39
Q

discuss diapedesis

A

leukocytes transverse the endothelium after adhering

40
Q

IBD dysregulation of immune cells

A

enhanced expression of adhesion molecules on leukocytes and endothelial cells, increased chemokines, and increased leukocytes binding to vascular endothelial cells

41
Q

alpha 4 beta 7 integrin heterodimer function

A

important for mediating lymphocyte trafficking to the lamina propria

42
Q

IBD dysregulation in secreted mediators

A

abnormal levels of immunoregulatory and inflammatory cytokines correlate with active IBD
CD4+ lymphocytes secrete large amounts of IFNy and TNF

43
Q

therapeutic strategies targeting secreted mediators

A

anti-TNF alpha in Crohns

44
Q

discuss the genetic susceptibility in IBD

A

more than 100 genes
NOD2 found in 17% of Crohns
70% of genes are shared between Crohn and UC

45
Q

what is NOD2

A

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

46
Q

discuss the relationship between NOD2 and Crohns

A

first susceptibility gene identified, greatest risk of developing Crohns with this gene
earlier age of development
ileal and fibrostenosing Crohns
worse outcomes for UC

47
Q

what is autophagy

A

process that mediates resistance to intracellular pathogens

48
Q

autophagy mutations in Crohns

A

mutation in ATG16L1

  • changes in Paneth cells and goblet cells
  • decreased ability to clear bacteria
  • increased secretion of cytokines
49
Q

examples of IBD imitators

A 
infections affecting the terminal ileum
-tuberculosis
-Yersinia
vasculitides
-bechet's disease
-churg strauss syndrome
ischemic colitis
solitary rectal ulcer syndrome
colitis cystica profunda
colonic endometriosis
infectious proctitis
segmental colitis associated with diverticulosis
50
Q

clinical picture of Yersinia enterocolitica

A 
weeks of diarrhea 
sore throat
may have reactive arthritis
involved terminal ileum and cecum
mesenteric adenopathy
51
Q

clinical picture of bechet’s disease

A

systemic vasculitis

Asian ancestry

52
Q

colonoscopy findings in Crohns

A

deep ulcers

skip lesions

53
Q

Crohn’s distribution

A

50% ileocolic
30% ileal
20% colic

54
Q

orofacial crohns

A

granulomatous cheilitis and glossitis
furrows on tongue
aphthous ulcers in the oral cavity

55
Q

Crohns histology

A 
granulomas in mucosa
deeper inflammation (sometimes not seen if biopsy is too shallow)
56
Q

what is CDAI

A

crohns disease activity index
combo of objective and subjective measurements
>150 active disease
>450 severe disease

57
Q

difference between crohns and UC on colonoscopy/histo

A 
Crohns
-cobblestoning
-fat wrapping
-thickened wall
-fissures
UC
-crypt distortion
-loss of haustra
-pseudopolyps of surviving mucosa
-ulceration
58
Q

complications of crohns

A 
transmural inflammation
strictures
fistulas
abscess
anal fissures
59
Q

symptoms of Crohns

A 
abdominal pain
diarrhea
weight loss
transmural inflammation
symptoms depend on location of disease
skipped lesions
granulomas
60
Q

skin manifestations in IBD

A

erythema nodosum

pyoderma gangrenosum

61
Q

erythema nodosum

A

more common in women
painful nodular lesions on the trunk and anterior shins
improves with disease treatment
usually lower extremities

62
Q

pyoderma gangrenosum

A

nectrotizing, painful lesion
can be anywhere on the body including the face
pathergy- avoid surgical debridement
independent of intestinal disease progression

63
Q

extraintestinal manifestations of IBD (independent course)

A

uveitis
axial arthropathy
pyoderma gangrenosum
PSC

64
Q

extraintestinal manifestations of IBD ( during active IBD)

A

episcleritis
peripheral arthropathy
erythema nodosum

65
Q

relationship between pancreatitis and IBD

A

medications related
IgG-4 related autoimmune pancreatitis
duodenal Crohns affecting pancreatic duct

66
Q

medications related to development of pancreatitis

A

mesalamine

AZA

67
Q

thromboembolic risk in IBD

A

increased 3 times

likely due to cytokines

68
Q

nutritional issues related to IBD

A 
can be due to small bowel disease or diminished absorptive area due to surgeries
vit B12 def
bile acid absorption
vit D def
zinc def
69
Q

symptoms of zinc def

A

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

70
Q

short bowel syndrome

A

<200 cm of small bowel
decreased absorptive surface
due to repeated surgeries

71
Q

possible outcome of transmural crohns disease

A

penetration or fistula formation

72
Q

treatment for mild IBD

A

topical corticosteroids
antibiotics
aminosalicylates (5-ASA_

73
Q

treatment for moderate IBD

A

immunomodulators

oral corticosteroids

74
Q

treatment for severe IBD

A

surgery

biologics

75
Q

anti-TNF biologics

A

adalimumab
certolizumab
infliximab

76
Q

anti integrin biologics

A

natalizumab

77
Q

immunomodulator agents

A

azathioprine
cyclosporine
methotrexate

78
Q

corticosteroids

A

budesonide
hydrocortisone
prednisone

79
Q

antibiotics for IBD

A

ciprofloxacin

metronidazole

80
Q

aminosalicylates

A

mesalamine

sulfasalazine

81
Q

optimal location of aminosalicylate action

A

large intestine

82
Q

adverse effects of aminosalicylates

A 
occur in 10-45% of patients
some are dose related (headache, nausea, fatigue, bone marrow suppression)
allergic reactions
inhibits folate absorption
olsalazine- diarrhea
mesalamine- interstitial nephritis
83
Q

serious side effects of anti-TNF therapy

A 
T cell lymphoma, hepatosplenic lymphoma
-absolute risk very low
-more likely with concurrent thiopurins
-young male
NHL is rare: 4 in 10,000
opportunistic infections
infusion reaction/serum sickness
84
Q

what is PML

A

Progressive multifocal leukoencephalopathy
demyelinating disease, leads to severe disability or death
associated with Natalizumab

85
Q

what is a way to give drugs gut selective effects

A

target the alpha 4 beta 7 integrin

86
Q

goals of surgery in UC

A

cure disease

prevent cancer

87
Q

indications for surgery in UC

A

toxic megacolon
hemorrhage
medical intractability
malignant degeneration

88
Q

options for surgery in UC

A

colectomy

ileal pouch anal anastomosis

89
Q

surgery in Crohns

A

75% of crohns patients require surgical intervention

fistula or structures

90
Q

colon cancer screening and surveillance in IBD

A

18 colon cancer risk after 30 years

91
Q

risk factors for colon cancer in IBD

A 
age of onset < 15
disease extent
duration (>8 years)
severity (strictures)
inflammatory complications
PSC
familial history of CRC
92
Q

colitis associated neoplasms

A

proto-oncogenes: activation of k-ras, c-src
tumor suppressor genes: loss or mutation p53, APC
DNA repair genes
cell cycle related genes
chromosomal instability and microsatellite instability

93
Q

special characteristic of colitis associated neoplasms

A

inflammation > multifocal dysplasia > cancer

94
Q

what is a chromoendoscopy

A

used for surveillance in IBD
every year for 8-9 years after diagnosis
dye on colonic wall helps illuminate dysplasia

GIR Test 3 (19 decks)

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