Coeliac Disease Flashcards
What is coeliac disease
An inflammatory disorder, primarily affecting the small intestine, caused by exposure to gluten
What is another name for coeliac disease
- Gluten-sensitive enteropathy
What are the clinical features of coeliac disease
- steatorrhoea
- bloating
- malabsorption
what are the histological features of coeliac disease
- chronic inflammatory cell infiltrate in lamina propria
- increased intra-epithelial lymphocytes
- subtotal villous atrophy
- deepening of crypts
- can cause small intestinal ulcers
What are the autoantibodies involved in coeliac disease
- Anti transglutaminase antibodies
- Anti- endomysial antibodies
- anti-reticulin antibodies
- anti-gliadin antibodies.
these are all IgA
What is gluten
- Gluten is the name of a group of storage proteins that are found in various cereal grains
What is glutens made out of
- prolamins
- glutelins
What do prolamins include
- gliadins in wheat
- hordeins in barley
- secalins in rye
- avenins in oats
what is true gluten limited to
Proteins from these four grains - gliadins - hordeins - secalins - avenins these are collectively called gluten
What gluten protein is resistant to digestion in the lumen of the bowel
- alpha gliadin - rich in proline and glutamine
What is tissue transglutaminase
- 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
What is deamidation
Deamidation is the removal of the side chain amino group from glutamines, converting them to glutamate.
What is transamidation
Transamidation is the cross-linking of a glutamine from the gliadin peptide to a lysine on the transglutaminase itself.
what is endomysium
Endomysium is the fine connective tissue just outside a muscle cell.
tissue transglutaminase is ….
Tissue transglutaminase is associated with the endomysium. - it gets stuck on to the endomysium
What is the structure of reticulin
- Reticulin is a fine meshwork of fibres within the lamina propria.
- Collagen type III is the structural protein
What happens in coeliac disease
- 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
who is coeliac present in
- white people of european origin
- twice as common in females as males
when does coeliac disease tend to present
- presents in infancy following introduction of gluten
What two HLA classes are associated with coeliac disease
DQ2 and DQ8
What can be used a diagnostic test for coeliacs disease
- antibodies in the blood
- Anti tTG is detected by ELISA = this is the standard test
what are the features of coeliac disease
- 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
What are the neurological symptoms in coeliac disease
- Headache
- peripheral neuropathy
- ataxia
- depression
- dysthymia
- anxiety
- epilepsy
- abnormalities on MRI scan
can be due to vitamin deficiency
Why do you get sore mouth and mouth ulcers in coeliac disease
- gluten on the mucus membrane