Coeliac Disease Flashcards
What is Coeliac Disease?
Immune-mediated systemic disorder (autoimmune)
- Triggered by gluten
- May have no gastrointestinal symptoms
- Protein malabsorption disorder –> CD is activated by proteins in the dietary cereal grains wheat, rye and barley. Gluten is a wheat protein.
Only people who are a carrier of certain genes can develop coeliac disease, but not all who express these genes develop coeliac disease.
When there is an inherent in the family there is a 1 in 10 chance the baby will develop the condition.
In the UK it affects 1 in 500 people
- more prevalent in higher-income conditions
- most cases are not clinically apparent, and the condition is so mild that medical intervention is not sought.
Some people are gluten intolerant, this is not the same as coeliac disease.
Occurs in the duodenum
What are the two types of gluten proteins?
Gliadin and Glutenin
Both 50%.
Pathogenesis of coeliac disease is associated with both proteins
They have a high proline and glutamine content.
- High proline content of these proteins render them resistant to the complete proteolytic digestion by gastric, pancreatic and brush border enzymes
- This is because these enzymes lack prolyl endopeptidase activity.
The lack of complete digestion of gliadin leads to the accumulation of relatively large peptide fragments in the lumen of the small intestine –> occurs in all humans
What factors can make an individual susceptible to Coeliac Disease?
Genetic factors –> high rate in monozygotes (70-75%)
- the main factor, people can do tests to see if they are carriers of the disease or not. Those who are carriers do not always present with the disease.
Immunological factors –> can be related to other immunological disorders, such as type 1 diabetes
Environmental factors –> some medications, those that affect epithelial cells in the gut and microbiome. Change the state of immune cells.
Medical treatments such as chemotherapy can change the structure of the gut.
What genes are affected?
HLA genes - code for immune proteins
Human Lymphocyte Antigen
Coeliac disease does not develop unless a person has alleles that code for HLA-DQ2 or HLA-DQ8.
A lot of people carry these alleles and do not develop the disease.
Their presence is necessary but not sufficient for the development of the disease.
Sibling studies and monozygotes suggest that the HLA gene is only responsible for 50% of the genetic compound.
These genes are encoding for proteins that are located on the cell membrane of immune cells. These are important proteins to recognise antigens.
Explain the genetics behind Coeliac Disease
HLA-DQA1 and HLA DQB1
When gluten enters the interstitial space it can be identified by an antigen (foreign particle) by the proteins that recognise gluten fragments, causing activation of immune cells.
When the protein isn’t present, gluten isn’t recognised as an antigen so no inflammatory response is stimulated.
The presence of these proteins triggers an immune response when gluten is detected. This immune response is only found in those with coeliac disease, as gluten is being treated as an antigen.
Why is coeliac disease associated with some other conditions?
Coeliac disease can occur after an immune challenge causes a change in gut structure, allowing gluten into the interstitial space allowing the cells to be in contact with gluten fragments and stimulating an immune response.
- type 1 diabetes
- autoimmune thyroid disease –> Hashimoto’s disease
Stimulating of pro-inflammatory cells can cause gluten to go to the interstitial space.
What are the three stages of coeliac disease?
- Luminal and early mucosal events
Gluten entry to interstitial space
In healthy individuals, gluten fragments should not enter the interstitial space. When is damage to the endothelial cells, gaps occur and gluten can move into the spaces. - Events that occur following the entry of proteins into the submucosal areas
- The release of inflammatory cytokines from invading macrophages, e.g TNFa. Production of antibodies (can be detected in blood, common coeliac diagnostic test)
Occurs in the duodenum
What happens in Stage 1 on Coeliac Disease?
Luminal and early mucosal events
- gluten digested to form gluten peptides rich in proline and glutamine which remain in the lumen
- 99% of those with the alleles do not present problems
- with additional genetic and or environmental factors, gluten peptides can initiate a series of events
What happens in Stage 2 of Coeliac Disease?
Events occur following the entry of proteins into the submucosal areas
- only patients with susceptible alleles develop the condition
- HLA-DQ2 or HLA-DQ8
- gluten is recognised as an antigen/ foreign body that triggers an immune response
- gluten peptides activate CDT4 cell response which initiates a B cell response to produce antibodies against the gluten peptides
What happens in Stage 3 of Coeliac Disease?
CD4+ cell produces and releases pro-inflammatory cytokines e.g TNFa which cause inflammation and alter key mucosal functions
- activation and release of enzymes that can damage the mucosa
- loss of villus structure –> villus atrophy, can effect electrolyte absorption (and iron), the ability to absorb these minerals (calcium, iron, B12) and electrolytes is compromised
- crypt hypertrophy
B cells produce antibodies to amplify the immune response
- tissue tranglutamine antibodies produced which are only present in coeliacs –> used in diagnostic blood tests –> can last in blood for several years (memory cells), speed up immune response when in contact again with antigen
What are some classic childhood symptoms?
Gastrointestinal disorders
- diarrhoea
- constipation
- abdominal pain
- blood in stools –> hard to tell due to CD affecting duodenum so once the blood reaches stools, it is a dark colour, so can go undetected
Extraintestinal symptoms
- anaemia
- raised transaminases –> found in liver, usually indicate inflammation to liver (link unknown)
- weight loss –> feel better/ less symptoms when they don’t eat
- failure to thrive
Occurs post-prandial after gluten intake
Why can anaemia occur in coeliacs?
Loss of villus structure can alter the absorption of nutrients, minerals and electrolytes in the duodenum. Iron is a mineral that is absorbed here, with comprised absorption from villus atrophy, people with coeliac disease can become deficient in iron despite having a sufficient oral intake.
Also puts them at risk of osteoporosis (age dependent)
When is it usually diagnosed?
Most of the time it is diagnosed in early life and can be as early as 2 years old. Used to be known as a paediatric disease.
It can occur later in life
What is the clinical presentation of an adult with undiagnosed/ recently diagnosed coeliac disease?
- Chronic diarrhoea
- Weight loss
- Malabsorption –> especially electrolyte - measure hydration levels (urine/ blood) as dehydration can be common
- Iron deficiency anaemia
- Low plasma albumin (main protein in blood, general nutritional status marker) and ferritin –> malabsorption and lack of food intake
- Osteoporosis
Occurs when struggling with the condition for several weeks/ months.
Can occur at around 40 years old
What are some consequences of leaving Coeliac disease untreated?
Consequences of the disordered absorption can lead to
- Tetany –> due to electrolyte imbalance
- Oedema –> due to disordered protein absorption and metabolism
- Intestinal bleeding
In many cases, affected people only have mild symptoms and may not seek help.
