Coeliac Disease Flashcards

(54 cards)

0
Q

What is a hallmark of coeliac disease?

A

remission on a gluten free diet

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1
Q

Where do you mainly find gluten?

A

wheat
barley
rye

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2
Q

Coeliac disease definition?

A

immunologically mediated disease in genetically susceptible people driven by gluten antigen

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3
Q

Prevalence of Coeliac disease?

A

1:100

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4
Q

Coeliac disease has strong association with which genes?

A

HLA-DQ2

HLA-DQ8

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5
Q

When does Coeliac disease manifest?

A

anytime from infancy to late adulthood

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6
Q

what’s the treatment for Coeliac disease?

A

gluten-free diet only

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7
Q

what mainly gets absorbed in the ileum?

A

Vitamin B12 and bile acids

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8
Q

what are valves of Kerkring?

A

found in duodenum

circumferential rings to increase surface area

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9
Q

how many cells (kgs) do we lose every 2-3 days ?

A

1kg

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10
Q

crypts produce how many cell per day?

A

200-300 cells and climb the villus

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11
Q

how are chylomicrons absorbed?

A

via lymphatics

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12
Q

what is the ratio for mature to crypt cells?

A

4:1

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13
Q

what are Paneth cells for?

A

secrete natural defensins (antibiotics) to ward off pathogens

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14
Q

What is IELs?

A

intraepethelial lymphocytes

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15
Q

how does the small bowel keep bacteria undercontrol overall?

A

by being in a constant state of controlled mild inflammation

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16
Q

normally how many CD3/CD8 cells per enterocytes?

A

<25/100

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17
Q

what do you see in advanced Coeliac disease histologically? 3 things

A

total villous atrophy
crypt hyperplasia
intraepithelial lymphocytosis

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18
Q

what is the ratio of IELs per enterocytes in Coeliac disease?

A

2-3 per enterocyte! More plasma cells

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19
Q

what do the microvilli in Coeliac disease look like?

A

distorted

stunted

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20
Q

What do you find in Marsh Type I?

A

more than 30 IELs per 100 enterocyte

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21
Q

What do you find in Marsh Type II?

A

elongation and branching of crypts

22
Q

What do you find in Marsh Type III?

A

villi shortened and blunted

villous to crypt ratio is less than 1:4

23
Q

In Marsh Type III what is there a marked increase in?

A

CD8 and T-cells

24
other causes of villous atrophy?
tropical sprue other immunodeficiency autoimmune enteropathy drugs: mycophenolate mofetil (used in transplants)
25
Gastro clinical presentations of Coeliac disease?
``` fatty diarrhea bloating cramps flatulence malabsorption of nutrients ```
26
nutrients affected by Coeliac disease?
anaemia | vitamin deficiencies
27
bones and general disposition of Coeliac disease?
osteoporosis risk lethargic migraines
28
people with Coeliac disease have increased prevalence of what else?
autoimmune diseases type I diabetes thyroiditis
29
Coeliac disease in babies consequences?
failure to thrive
30
does Coeliac disease have to be symptomatic?
could be asymptomatic
31
age of many new Coeliac disease diagnosis?
0-9 | 30-59
32
4 elements in pathogenesis of Coeliac disease?
genetics environment T-cells Gluten
33
what % of people have this gene in Coeliac disease?
99.6% have the HLA-DQ2/DQ8
34
how many people who have HLA-DQ2.DQ8 don't have Coeliac disease?
20-30%
35
what does HLA-DQ2/DQ8 do?
helps with antigen presentation to T-Cells
36
infant environment for Coeliac disease is avoided how? 3 ways
breast feeding timing of gluten introduction prevention of infections
37
Where are the CD4 cells that react to gluten?
in the small bowel mucosa
38
how do CD4s cause damage in Coeliac disease?
IFN-y
39
how is the innate immune response in Coeliac disease?
CD8+ and NK cells accumulate in epethelium
40
What proteins from wheat are the culprits for Coeliac disease?
Gliadins (alcohol soluble) | Glutenins
41
What does proline do to toxic gluten peptides?
proline resists digestion by proteases and increases toxicity
42
so what? high glutamine and proline and resists digestion?
it allow to pass through intestinal epithelium intact
43
what happens after intact peptides pass through intestinal epithelium?
convert glutamine to negatively charged glutamate
44
what converts glutamine to negatively charged glutamate?
tTG | tissue transglutaminase
45
so big deal, there's negatively charged glutamate?
they can bind to HLA-DQ2 T-cell receptor on an APC. effectively making the glutamate an antigen
46
what happens after peptides bound to receptor on APCs??
bound to MHCII and start making cytokines
47
what antibodies are made by plasma cells in Coeliac disease?
anti-tTG | anti AGA
48
how do the enterocytes apoptose?
gliadin activated perforins are released
49
can Coeliac disease give you cancer?
T-cell malignancy is possible | get autoreactive IEL
50
Serological dx of Coeliac disease?
tTG antibody | deaminated gliadin peptide ( DGP-IgG)
51
what is gold standard for dx of Coeliac disease?
small bowel biopsy during gluten exposure
52
how soon to get the diagnosis of Coeliac disease?
the earlier the better | long term risks are bad
53
long term risks of undiagnosed Coeliac disease?
osteoporosis autoimmune diseases cancer