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Gastrointestinal > Coeliac Disease > Flashcards

Coeliac Disease Flashcards

1
Q

What is coeliac disease?

A

Immunologically mediated disease in genetically susceptible individuals, driven by an environmental antigen, gluten, found in wheat, rye and barley, which results in chronic inflammation of the small bowel mucosa

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2
Q

What is the prevalence of coeliac disease?

A

1/100

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3
Q

What genes are associated with coeliac disease?

A

HLA DQ2 and DG8

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4
Q

What is the treatment for coeliac disease?

A

gluten free diet

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5
Q

Which part of the GIT is most effected in coeliac disease?

A

The small intestine

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6
Q

What nutrients are absorbed in the duodenum?

A

protein, fat, fat soluble vitamins, glucose, iron, water soluble vitamins

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7
Q

Where is vitamin B12 absorbed?

A

In the ileum

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8
Q

What are the valves of kerkring?

A

semicircular folds in the duodenum - to increase the surface area

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9
Q

Where is the proliferative zone of the epithelium?

A

Below the vili, in the crypts

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10
Q

How often to epithelial cells in the small intestine regenerate?

A

Every 2-3 days

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11
Q

What type of cells make up the villus of the epithelium?

A

Mature cells

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12
Q

What is the ratio of mature to immature cells in the epithelium?

A

4:1

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13
Q

Why are there lots of lymphocytes present in the lamina propria of the duodenal epithelium?

A

It has mild chronic inflammation to keep the microbiota in check

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14
Q

What increases the surface area of the small intestine?

A

The valves of kerkring, the villi and the microvilli

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15
Q

What is the reduction in surface area with a loss of villi?

A

60 fold reduction

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16
Q

What is stage 1 of coeliac disease?

A

Where there are more than 30 intraepithelial lymphocytes per 100 enterocytes

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17
Q

What is stage 2 of coeliac disease?

A

There is additional elongation of the crypts

18
Q

What is stage 3 of coeliac disease?

A

Villi are blunted and the villous to crypt ratio is less than 1:4 - villous atrophy

19
Q

What type of lymphocytes are the intraepithelial lymphocytes in coeliac disease?

A

CD8 cells

20
Q

Where are the CD4 cells located?

A

In the lamina propria

21
Q

What happens to the microvilli of the remaining enterocytes in coeliac disease?

A

Loss, distortion and stunting

22
Q

What is present at increased levels in the lamina propria in coeliac disease?

A

Plasma cells

23
Q

What are some other causes of intraepithelial lymphocytosis and villous atrophy?

A

tropical sprue, small bowel bacterial overgrowth, common variable immunodeficiency, autoimmune enteropathy, drugs

24
Q

What is the clinical presentation of coeliac disease?

A

diarrhoea, bloating, abdominal cramps, flatulence, anemia, vitamin deficiencies, osteoporosis, lethargy, migraines, infertility, mouth ulcers, steatorrhea

25
Q

When can coeliac disease present?

A

At any stage in life - most common at 0-9 and 30-39

26
Q

What percentage of patients have HLA-DQ8 or DQ2?

A

99.6%

27
Q

What percentage of the population have HLA-DQ8 or DQ2 and don’t have coeliac disease?

A

20-30%

28
Q

What is the impact of breast feeding on coeliac disease?

A

It is protective

29
Q

How does timing of introduction of gluten into diet impact on coeliac disease?

A

Too much gluten too soon may increase risk

30
Q

How do infections impact on coeliac disease?

A

May trigger it

31
Q

How do CD4 T cells cause damage to the small bowel?

A

By producing harmful cytokines such as IFN-gamma, IL-4 and TNF alpha

32
Q

What is gluten?

A

The protein component of wheat and other grains

33
Q

What are gluten peptides made up of?

A

Glutamine and proline

34
Q

What makes gluten resistant to digestion by proteases?

A

The high proline content

35
Q

What is the action of tissue transglutaminase?

A

converts glutamine residues to glutamate

36
Q

What binds to HLA-DQ2 and DQ8?

A

deamidated gluten peptides - (the negatively charged glutamate binds selectively to the groove) and a complex of gluten and tTG

37
Q

What antibodies are produced in coeliac disease?

A

anti-tTG and anti-AGA

38
Q

How are enterocytes killed by the immune system in coeliac disease?

A

The IFN-gamma released causes increased cytotoxicity of IELs. The IELs cause apoptotic death of enterocytes via fas/fas ligand or via perforin granzyme. IFN-gamma also activates matrix metalloproteases which break down enterocytes and lead to apoptosis.

39
Q

How is coeliac disease diagnosed?

A

serological testing (tTG or deamidated gliadin peptide) or HLA-DQ haplotyping or bowel biopsy

40
Q

What are the long term risks of undiagnosed coeliac disease?

A

osteoporosis, autoimmune diseases, increased risk of cancer

Gastrointestinal (40 decks)

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