Coeliac disease

Annotations:

• https://en.wikipedia.org/wiki/Coeliac_disease#Cause 

1. Epidemiology
   1. Prevelance of 1/100
   2. 9/10 of people are adults
   3. Mot common cause of diarrhoea in the western world
2. What is it?
   1. 'gluten sensitive enteropathy'
   2. Gluten
      1. Found in...
         1. Oats
         2. Rye
         3. Wheat
         4. Barley
      2. Broken down into gliadin peptides
      3. Prolamin (protin found in gluten)
   3. Autoimmune disease
      1. Autoimmune response --> GLIADIN

         Annotations:

         • NORMAL PHYSIOLOGY --> gliaidin should be broken down when it is in the small bowel by IgA, which mark it for breakdown by the immune system. HOWEVER, in coeliacs, there is an increased expression of the transferrin receptor, allowing gliadin to cross the enterocyte barrier -> creates an immune response.
         1. HLA DQ2/8

            Annotations:

            • Genes that are found in patients with coeliac disease, that code for specific MHC receptors on macrophages that bind to gliadin fragments, and thus create an immune response to gliadin. T helper cells (CD4+) bind to the gliadin fragments expressed on the macrophages and cause a subsequent inflammatory response - secrete inflammatory cytokines that can directly destroy cells in the intestine.  B cells also produce antibodies against trangultaminases (enzymes that break down the gliadin into fragments), and also against gliadin -- good for making a diagnosis. Killer T cells are drawn to the area, kill cells that have been afffected by the inflammation.
         2. Inflammation and cellular destruction

            Annotations:

            • Results from the Killer T cells (CD8) and from inflammatory cytokines released by T helper cells (CDT4+), in response to gliadin. 
         3. Flattened crypts lead to maladsorption
   4. Lifelong
3. Causes
   1. Genetics
      1. 10% chance if first relative with coeliac's
      2. 75% chance with an identical twin
   2. Environment
      1. Intorducing gluten before a child is 3 months
      2. Not breastfeeding the child
      3. Having a digestive infection at a young age
4. Treatment
   1. Gluten free diet

      Annotations:

      • Only proven treatment. *Still a chance of relapse/refractory. Doesn't eliminate the chance of developing bowel cancers, lymphoma - but reduces the risk and improves the symptoms. 
      1. If this is not successful...
         1. FODMAP

            Annotations:

            • FermentableOligosaccharidesDisaccharidesMonosaccharidesAndPolyols FODMAPs are short chain carbohydrates that may be poorly absorbed in the small intestine.  This can cause more water to be pulled into the colon and can also rapidly ferment, or be broken down, by bacteria in the bowel. This can cause symptoms like increased gas, bloating, constipation/diarrhea and pain.   May help for indiviuals who's bowels do not resolve from gluten free diet. 
   2. DEXA scan

      Annotations:

      • Assesses risk of osteoparosis --> poor adsorption of calcium and vitamin D - flattened villi 
5. Diagnosis
   1. Duodenal biopsy

      Annotations:

      • Villi are flattened (villus atrophy), and the epithelial cells are damaged.  Looks at the duodenum as this is the most affected part of the small bowel --> is the first part of the small bowel, therefore most of the gliadin 'attacks' here first.
      1. Endoscopy
   2. Blood test
      1. Anti-DGP antibodies deaminated gliadin peptides)
      2. Anti-transglutaminase antibodies (Anti tTG)

         Annotations:

         • Break down gliadin into smaller molecules - processed by the macrophages, cause the ummune response.
      3. False negatives - lack of IgA

         Annotations:

         • For some, the blood tests may be negaitve - dont produce IgA.However, may have IgG anti - antibodies, would need to check this by doing further blood test with IgG
         1. IgG anti-trasglutaminases
      4. Anti-endomysium antibodies

         Annotations:

         • IgA. A molecule exists within the muscle cells with a similar structure and properties to gliadin fragments - even though not harmful, antibodies are made against it.
   3. Hard to do
      1. Gluten free diet can reduce signs and symptoms
         1. 'Gluten challenge'

            Annotations:

            • People with suspected coeliac/gluten sesntivities will need to be put back onto a gluten diet for 6 weeks, and then tested again for signs (as symptoms improv with gluten free diet)
6. Symptoms
   1. Weight loss
   2. Bloating
   3. Abdominal pain
   4. Diarrhoea
   5. Flatulence (wind)
   6. Constipation
   7. Dermititis herpeformis
7. Complications
   1. Bowel cancer
   2. Maladsorption associated
      1. Osteoparosis

         Annotations:

         • Vit D and calcium maladsorption
      2. Iron deficiency anemia

         Annotations:

         • Low iron absorption, usually done in the DUODENUM 
      3. Macrocytic anemia

         Annotations:

         • As a result of B12 and folate deficiency, caused by maladsorption
      4. Weight loss and fatigue

         Annotations:

         • Maladsorption of fats and carbohydrates 
8. Complications
   1. Cancer

      Annotations:

      • 2 x increase the risk of cancer, treated less likely to lead to it
   2. Osteoparosis