COELIAC DISEASE Flashcards
What is coeliac disease?
An autoimmune disease characterised by a permanent intolerance to gluten which results in damage to the lining of the small bowel, specifically villous atrophy. This leads to loss of surface area and malabsorption is hence the main complication.
What is precise protein, which partly makes up gluten, that is responsible for triggering the immune reaction in coeliac disease?
Gliadin
What contains gluten?
Wheat
Barley
Rye
Oats
What parts of the world are most affected by coeliac disease?
European disease
What is the prevalence of coeliac disease in the UK?
1 in 300
What is gliadin?
Important structural component of gluten which is responsible for inflammatory gut response in coeliac disease. It is a proline and glutamine-rich glycoprotein.
How is the surface area of the small bowel expanded beyond the simple surface area of a tube?
Circular folds of bowel called plicae circulares
Villi - finger-like projections
Microvilli (brush border) on each villous enterocyte.
In the villi of the small bowel where do you find the most absorptive cells?
Cells become progressively more absorptive as they climb the villous stalk. Cells at the tip express the full absorptive capacity. They survive for 72 hours before being shed into the lumen.
What is contained on the brush border which aid digestion of food?
Brush border enzymes which are necessary for absorption of disaccharides and oligopeptides.
What is the underlying pathology in coeliac disease?
Stunting and atrophy of the villi, leads to loss of mature apical cells. Overall loss of surface area and absorptive capacity by villous enterocytes as not allowed to mature before being shed.
What are the causes and risk factors for coeliac disease?
Underlying mechanism of pathology still largely unknown.
Genetic factors: HLA-DQ2/DQ8
Immunological factors: Tissue transglutaminase (tTG) and IgA Anti-tTG antibodies
Environmental factors:
Infection with rotavirus
Infection with human intestinal adenovirus
Being exposed to wheat, barley or rye in first three months of life
Factors that trigger symptoms in diagnosed patients: Pregnancy Surgery Emotional stress Infection
What proportion of coeliac patients have the HLA-DQ2 antigen?
95%
What diseases other than coeliac disease have been associated with the HLA-DQ2 antigen?
Type 1 diabetes
Addison’s disease
Sjogrens syndrome
Autoimmune thyroiditis
These are all more common in coeliac patients
What are the antibodies associated with coeliac disease?
IgA antibodies against tTG (tissue transglutaminase)
Anti-alpha-gliadin
Anti-endomysial
What is the underlying mechanism of pathology in coeliac disease?
Coeliac disease appears to be multifactorial and is not fully understood.
Gliadin stimulates both the innate and adaptive immune response leading to some damage of the small bowel. This is partly as a result of binding to HLA-DQ2, which potentiates their capacity to stimulate T-cells. Activated T-cells infiltrate the small bowel mucosa and release cytokines and other inflammatory mediators. Leads to blunting and atrophy of villi.
The tissue transglutaminase (tTG) is an intracellular enzyme found in all tissue types. Mechanical irritation or inflammation as a result of the gliadin stimulated immune response leads to tTG being released from the endothelial cells and fibroblasts. tTG cross-links glutamine-rich proteins such as gliadin. This cross-linking produces a negative charge in the gluten peptides. This increases their binding to HLA-DQ2 and further potentiates their capacity to stimulate T-cells.
How does coeliac disease lead to malabsorption? (There are 3 ways)
Reduced surface area for absorption
Reduced absorptive capacity by villous enterocytes due to blunted villi. Absorption of minerals, haematinics (folate and iron) and trace elements occurs in the cells of upper third of healthy villus.
Also, hormonal secretagogues such as secretin and cholecystokinin are derived from endocrine secreting cells of proximal small intestine. These secretagogues are responsible for stimulating biliary and pancreatic secretions. Coeliac patients have fewer small intestine endocrine secreting cells, so both pancreatic and biliary secretion is attenuated.
When do coeliac patients present?
Surveillance usually picks up childhood coeliac disease in first year.
Adult presentation is more variable.
How would someone with suspected coeliac disease present? (Name 4 symptoms)
Diarrhoea Nausea Vomiting Bulky, pale and malodorous fatty stools Abdominal bloating Flatulence Abdominal cramps Aphthous ulcers
Generalised picture of malabsorption: Weight loss (Carbohydrates) Fatigue (Anaemia) Weakness (Anaemia) History related to weak bones (Ca and vitamin D) Easy bruising (vitamin K) Intolerant to lactose Headache (Ca) Ataxia (Ca) Depression (Ca) Anxiety (Ca) Epilepsy (Ca)
