Coeliac disease Flashcards
(26 cards)
Define coeliac disease
A common, chronic, immune-mediated, enteropathy that is triggered and maintained by ingestion of gluten in genetically-predisposed individuals
what is enteropathy?
disease of the small intestine
Histologically, what features are found in individual with Coeliac disease?
Duodenum has cracked appearance Intestinal inflammation: intraepithelial lymphocyte infiltration total villous atrophy (flattened appearance) - no villi crypt hyperplasia
what is crypt hyperplasia?
Grooves between villi are elongated
what is total villous atrophy ?
erosion of intestinal villi
List the gastrointestinal clinical symptoms of an individual with CD
Indigestion (dyspepsia) Constipation Diarrhoea Vomiting Bloating + flatulence Abdominal pain Anorexia/weight loss
List other extra intestinal symptoms sometimes found in those with CD
Anaemia Bone weakness - osteoporosis, arthritis, fractures Dermatitis herpetiformis - itchy skin Delayed puberty Short stature - growth issues
Discuss the aetiology of CD ****
Genetic susceptibility
trigger: Exposure to gluten peptides from grains including wheat, rye, and barley
* *******
Gluten: a subtype of _____
prolamins
What are prolamins and what type of amino acid do they have high levels of?
Prolamins = a group of plant storage proteins that have a high proline amino acid content
what are the 2 components of gluten?
Gliadin (peptide component) and Glutenin
Describe the pathophysiology of Coeliac disease (stage of gliadin moving into the lamina propria)
- High proline content of gluten makes it resistant to intestinal proteases.
- Undigested peptides can disrupt intestinal microbiota.
- When gliadin reaches the lumen of the small intestine, it binds to secretory IgA in mucosal membrane
- Usually substances bound to IgA are subject to immune destruction but in CD, Gliadin-IgA complex binds to transferrin receptor (overexpressed in CD)
- Once bound, it moves through enterocytes and into lamina propria.
Describe the pathophysiology of Coeliac disease (“initiating inflammation” stage)
Once in the lamina propria: Tissue Transglutaminase (tTG) deamidates Gliadin (cuts off Amide) to Glutamate • Deamidated gliadin is engulfed by macrophages (type of APC) and presented on MHC class II molecules to helper T cells
- MHC II “serving complexes” are coated in HLA genes (determines what thing to present)
- In those with CD, the MHC II complexes are coated in HLA-DQ2/8
• Helper T cells recognise the gliadin and release inflammatory cytokines to initiate inflammation. This causes destruction of enterocytes and villi
- T helper cells also recruit helper B cells to release Anti-Gliadin, anti-endomysial (EMA) and anti-tTG antibodies
- Killer T cells are also recruited which cause cell death and tissue remodelling with villous atrophy and crypt hyperplasia
what is the main role of MHC class II molecules?
To present antigens to helper (CD4 )T lymphocytes
What does the de-amidation of Gliadin peptide allow?
1) high-affinity binding to the coeliac-associated HLA peptides (DQ2 or DQ8) found on APCs
2) activation of helper T cells
What HLA gene must be carried to develop coeliac disease?
Either HLA DQ2 (most common) or DQ8
Describe the effect which coeliac disease has on iron haemostasis on the body
Those with CD have impaired duodenal mucosal uptake of iron since the surface absorptive area in the duodenum is reduced. This can cause iron deficiency and anaemia
Describe the diagnosis of Coeliac disease
Serological test for: Anti-tTG antibodies (first line – high specificity and sensitivity) IgA antibodies (first line) Anti-gliadin antibodies Anti-endomysial antibodies
Duodenal biopsy: obtained via endoscopy
Human Leucocyte Antigen (only undertaken in specialist settings)
Can someone with an absence of HLA DQ2/8 have coeliac disease?
No
If someone presents with CD symptoms and after conducting diagnostic tests their results come back positive for TTG and HLA DQ2/8 but not for the biopsy - what could be the possible reason for this?
Possible that biopsy result was incorrect/insufficient as the inflamed area could have been missed
If someone presents with CD symptoms and after conducting diagnostic tests their results come back positive for biopsy and HLA DQ2/8 but not for the TTG - what could be the possible reason for this?
Patient could already be on a GF diet (TTG could be detected in blood by GP but there is a 6 month wait for the biopsy, so patient may get fed up and put themselves on a GF diet so TTG no longer positive)
How is Coeliac Disease managed?
Gluten free diet (dietician review, free prescription for GF items in Scotland)
Nutritional assessment
Possibly: Bone health assessed via DEXA scan
Those with CD should have a Vaccination:
— Pneumococcus
— Meningococcus
(as they’re more at risk)
25% of Coeliac patients are at risk of ____?
Osteoporosis
What other health consequences does coeliac disease pose?
Hyposplenism (reduced spleen function) – risk of sepsis
Risk of Infection - reduced immunity
Increased risk of Non-Hodgkin’s Lymphoma (NHL) and small bowel adenocarcinoma
Increased overall mortality in adult life
