Coeliac Disease Flashcards

1
Q

What is coeliac disease

A

An inflammatory disorder, primarily affecting the small intestine, caused by exposure to gluten

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2
Q

What is another name for coeliac disease

A
  • Gluten-sensitive enteropathy
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3
Q

What are the clinical features of coeliac disease

A
  • steatorrhoea
  • bloating
  • malabsorption
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4
Q

what are the histological features of coeliac disease

A
  • chronic inflammatory cell infiltrate in lamina propria
  • increased intra-epithelial lymphocytes
  • subtotal villous atrophy
  • deepening of crypts
  • can cause small intestinal ulcers
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5
Q

What are the autoantibodies involved in coeliac disease

A
  • Anti transglutaminase antibodies
  • Anti- endomysial antibodies
  • anti-reticulin antibodies
  • anti-gliadin antibodies.

these are all IgA

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6
Q

What is gluten

A
  • Gluten is the name of a group of storage proteins that are found in various cereal grains
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7
Q

What is glutens made out of

A
  • prolamins

- glutelins

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8
Q

What do prolamins include

A
  • gliadins in wheat
  • hordeins in barley
  • secalins in rye
  • avenins in oats
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9
Q

what is true gluten limited to

A
Proteins from these four grains 
- gliadins
- hordeins 
- secalins 
- avenins 
these are collectively called gluten
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10
Q

What gluten protein is resistant to digestion in the lumen of the bowel

A
  • alpha gliadin - rich in proline and glutamine
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11
Q

What is tissue transglutaminase

A
  • This is an enzyme that is active both intracellularly and extracellularly
  • it is produced by a variety of cells including those in the bowel wall
  • it mediates deamidation and transamidation
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12
Q

What is deamidation

A

Deamidation is the removal of the side chain amino group from glutamines, converting them to glutamate.

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13
Q

What is transamidation

A

Transamidation is the cross-linking of a glutamine from the gliadin peptide to a lysine on the transglutaminase itself.

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14
Q

what is endomysium

A

Endomysium is the fine connective tissue just outside a muscle cell.

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15
Q

tissue transglutaminase is ….

A

Tissue transglutaminase is associated with the endomysium. - it gets stuck on to the endomysium

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16
Q

What is the structure of reticulin

A
  • Reticulin is a fine meshwork of fibres within the lamina propria.
  • Collagen type III is the structural protein
17
Q

What happens in coeliac disease

A
  • peptides from gliadins are difficult to digest in the lumen of the bowel
  • if they leak into the lamina propria they engage the tTG
  • therefore they become deamidated
  • the deamidated version binds strongly into the groove of certain class II HLA molecules (DQ2 and DQ8).
  • this presentation activates T lymphocytes which secrete cytokines and initiate the changes
  • villous atrophy and crypt enlargement may be a response to infection medicated by cytokines
18
Q

who is coeliac present in

A
  • white people of european origin

- twice as common in females as males

19
Q

when does coeliac disease tend to present

A
  • presents in infancy following introduction of gluten
20
Q

What two HLA classes are associated with coeliac disease

A

DQ2 and DQ8

21
Q

What can be used a diagnostic test for coeliacs disease

A
  • antibodies in the blood

- Anti tTG is detected by ELISA = this is the standard test

22
Q

what are the features of coeliac disease

A
  • Growth failure in children
  • Weight loss
  • Anaemia (iron deficiency and folate deficiency)
  • Other vitamin deficiencies, giving osteopenia (vit D) and neurological symptoms (vitamin B)
  • Hyposplenism
  • IgA deficiency
23
Q

What are the neurological symptoms in coeliac disease

A
  • Headache
  • peripheral neuropathy
  • ataxia
  • depression
  • dysthymia
  • anxiety
  • epilepsy
  • abnormalities on MRI scan

can be due to vitamin deficiency

24
Q

Why do you get sore mouth and mouth ulcers in coeliac disease

A
  • gluten on the mucus membrane
25
What is the gold standard for diagnosis of coeliac disease
endoscopy and looking at the histology
26
why are type 1 diabetes and autoimmune thyroid disease associated with coeliac disease
- they are also associated DQ2 and DQ8
27
what is dermatitis herpetiformis
- this may occur as part of typical coeliac disease or it may be prominent with less obvious bowel symptoms - get multiple intensely pruritic papules and vesicles that occur in grouped arrangements - IgA immune complexes are found at dermo-epidermal junction probably bound to gliadin
28
where is dermatitis herpetiformis found
- elbows - dorsal forearms - knees - scalp - back - buttocks
29
What malignancy is coeliac disease released to
- T cell non-hodgkin lymphoma and carcinomas
30
What are the other possible reasons for wheat intolerance
- Wheat amylase-tryptase inhibitors may excite TLRs these may be a cause of low level inflammation and malaise - non coeliac gluten sensitivity - possible by activation of TLRs - true wheat allergy caused by IgE - FODMAPS - these are short chain carbohydrates, poorly absorbed which may be fermented in the bowel and cause discomfort in bloating
31
What does FODMAPs stand for
- fermentable oligosaccharides, disaccharides, monosaccharides and polyols
32
How do you diagnose coeliac disease
- History. - Antibodies (especially anti-transglutaminase IgA antibodies). - Biopsy of bowel wall via endoscopy. These tests should be done when the patient is consuming gluten etc, because autoantibodies and histological changes may disappear while on gluten-free diet.
33
What is the treatment for coeliac disease
- Gluten-free diet. This is difficult because wheat flour is used in many foods. - Non-compliance is the most likely reason for failure of treatment
34
Do autoantibodies contribute to the damage that happens in coeliac disease
They are IgA, so do not activate complement or opsonise for phagocytosis, but may contribute by trapping antigen, or blocking actions of transglutaminase.