Coeliac Disease Flashcards
What is coeliac disease?
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
What is the prevalence of coeliac disease?
1/100
What genes are associated with coeliac disease?
HLA DQ2 and DG8
What is the treatment for coeliac disease?
gluten free diet
Which part of the GIT is most effected in coeliac disease?
The small intestine
What nutrients are absorbed in the duodenum?
protein, fat, fat soluble vitamins, glucose, iron, water soluble vitamins
Where is vitamin B12 absorbed?
In the ileum
What are the valves of kerkring?
semicircular folds in the duodenum - to increase the surface area
Where is the proliferative zone of the epithelium?
Below the vili, in the crypts
How often to epithelial cells in the small intestine regenerate?
Every 2-3 days
What type of cells make up the villus of the epithelium?
Mature cells
What is the ratio of mature to immature cells in the epithelium?
4:1
Why are there lots of lymphocytes present in the lamina propria of the duodenal epithelium?
It has mild chronic inflammation to keep the microbiota in check
What increases the surface area of the small intestine?
The valves of kerkring, the villi and the microvilli
What is the reduction in surface area with a loss of villi?
60 fold reduction
What is stage 1 of coeliac disease?
Where there are more than 30 intraepithelial lymphocytes per 100 enterocytes
What is stage 2 of coeliac disease?
There is additional elongation of the crypts
What is stage 3 of coeliac disease?
Villi are blunted and the villous to crypt ratio is less than 1:4 - villous atrophy
What type of lymphocytes are the intraepithelial lymphocytes in coeliac disease?
CD8 cells
Where are the CD4 cells located?
In the lamina propria
What happens to the microvilli of the remaining enterocytes in coeliac disease?
Loss, distortion and stunting
What is present at increased levels in the lamina propria in coeliac disease?
Plasma cells
What are some other causes of intraepithelial lymphocytosis and villous atrophy?
tropical sprue, small bowel bacterial overgrowth, common variable immunodeficiency, autoimmune enteropathy, drugs
What is the clinical presentation of coeliac disease?
diarrhoea, bloating, abdominal cramps, flatulence, anemia, vitamin deficiencies, osteoporosis, lethargy, migraines, infertility, mouth ulcers, steatorrhea
When can coeliac disease present?
At any stage in life - most common at 0-9 and 30-39
What percentage of patients have HLA-DQ8 or DQ2?
99.6%
What percentage of the population have HLA-DQ8 or DQ2 and don’t have coeliac disease?
20-30%
What is the impact of breast feeding on coeliac disease?
It is protective
How does timing of introduction of gluten into diet impact on coeliac disease?
Too much gluten too soon may increase risk
How do infections impact on coeliac disease?
May trigger it
How do CD4 T cells cause damage to the small bowel?
By producing harmful cytokines such as IFN-gamma, IL-4 and TNF alpha
What is gluten?
The protein component of wheat and other grains
What are gluten peptides made up of?
Glutamine and proline
What makes gluten resistant to digestion by proteases?
The high proline content
What is the action of tissue transglutaminase?
converts glutamine residues to glutamate
What binds to HLA-DQ2 and DQ8?
deamidated gluten peptides - (the negatively charged glutamate binds selectively to the groove) and a complex of gluten and tTG
What antibodies are produced in coeliac disease?
anti-tTG and anti-AGA
How are enterocytes killed by the immune system in coeliac disease?
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.
How is coeliac disease diagnosed?
serological testing (tTG or deamidated gliadin peptide) or HLA-DQ haplotyping or bowel biopsy
What are the long term risks of undiagnosed coeliac disease?
osteoporosis, autoimmune diseases, increased risk of cancer
