Coeliac Disease and Inflammatory Bowel Disease Flashcards
What is Coeliac disease?
- immune-mediated small intestinal (SI) enteropathy (intestinal disease)
- triggered by exposure to dietary gluten in genetically predisposed individuals, leading to malabsorption
Coeliac disease is caused by a protein called gluten, what common products is gluten found in?
- wheat, barley and rye
- oats can be contaminated
Coeliac disease is caused by a protein called gluten, what specific part of gluten is associated with coeliac disease?
- gliadin
- component of gluten
How common is coeliac disease and does it affect men or women more?
- affects 1% of the population
- women are more susceptible and can occur at any age
Where in the world is coeliac disease most common?
- USA and western world
- very common in Ireland and Scandanavia
What diseases does tend to have a higher prevalence of coeliac disease
- down’s syndrome
- Type I diabetes mellitus
- auto-immune hepatitis
- thyroid gland abnormalities.
In family members who have coeliac disease, which members of their offspring are most likley to inherit coeliac disease?
- 1st degree relatives of patients
- greater concordance in monozygotic (identical) twins (75%)
What are the 2 genes that have been shown to correlate with coeliac disease?
- human Leukocyte Antigen (HLA) DQ2 genes
- human Leukocyte Antigen (HLA) DQ8 genes
What are the most common symptoms that patients with coeliac disease present with?
- diarrhoea
- steatorrhea (fatty floating stools)
- weight loss.
- anaemia, vague abdominal pains
The most common symptoms that patients with coeliac disease present with include diarrhoea, steatorrhea (fatty floating stools), weight loss, anaemia, vague abdominal pains. What is the most common cause of these symptoms?
- small intestinal villus atrophy
In addition to the symptoms patients experience, clinicians can look for physical signs of coeliac disease. What are the most common?
- anaemia causing glossitis (B12 and iron deficiency)
- mouth ulcers
- rash called dermatitis herpetiformis (skin rash similiar to herpes)
Do all patients with coeliac disease present with symptoms?
- no
- 1/3 of patients with coeliac disease are asymptomatic
What is the name of the rash in the image below that patients with coeliac disease present with?
- dermatitis Herpetiformis
- an itchy, vesicular rash on extensor surfaces
In the image below are 3 signs of coeliac disease. From left to right match the labels with the symptoms?
- angular stomatitis (iron/vit B12 deficiency)
- glosittis (iron deficiency)
- pallor (anaemia)
- far left = pallor (anaemia)
- middle = angular stomatitis (iron/vit B12 deficiency)
- far right = glosittis (iron deficiency)
What is gliadin?
- umbrella term for a group of gluten peptides
- all share 33 amino acid sequence triggering immune response
Gliadin is able to be absorbed by the small intestines and enter the lamina propria, what are the 2 ways gliadin is able to cross epithelial cells in the small intestines?
- paracellular (between cells and tigh junctions)
- transcellular (through cells)
Gliadin is able to be absorbed by the small intestines and enter the lamina propria. Once into the lamina propria what happens to the gliadin?
- enzyme tissue transglutaminase (tTG) removes amide group
- this leaves a deaminated gluten protein
Gliadin is able to be absorbed by the small intestines and enter the lamina propria. Once into the lamina propria the enzyme tissue transglutaminase (tTG) removes amide group producing deaminated gluten protein. What happens to the deaminated gluten proteins?
- macrophages phagocytose them and present on MHC-II
Gliadin is able to be absorbed by the small intestines and enter the lamina propria. Once into the lamina propria the enzyme tissue transglutaminase (tTG) removes amide group producing deaminated gluten protein. The deaminated gluten proteins is phagocytosed by macrophages and presented on its MHC-II. What genes encode the MHC-II that determine what the MHC-II present to the immune system?
- human leukocyte antigen genes
Human leukocyte antigen (HLA) genes are responsible for coding MHC-II and determine what the MHC-II present to the immune system. What are the 2 HLA genes that are most commonly associated with coeliac disease?
- DQ2 and DQ8 genes
- deaminated gluten proteins are presented on the MHC-II
Once deaminated gluten proteins have been phagocytosed by macrophages and presented on MHC-II. What immune cells bind to MHC-II?
- CD4 T helper cells
Once deaminated gluten proteins have been phagocytosed by macrophages and presented on MHC-II CD4 T helper cells bind to the MHC-II. What happens after this?
- T helper cells secrete inflammatory cytokines
- inflammatory cytokines can damage intestinal lumen
Once deaminated gluten proteins have been phagocytosed by macrophages and presented on MHC-II CD4 T helper cells bind to the MHC-II and secrete inflammatory cytokines that can damage intestinal lumen. What 2 other cells are activated by T-helper cells?
- B cells
- Natural killer cells
Once natural killer (NK) cells have been activated by T-helper cells in coeliac disease, what do the NK cells go on to do?
- attack and try to initiate cell lysis in the inflammed intestinal lumen
Once B cells have been activated by CD4 T helper cells, what 3 things can they then produce?
1 - anti-tissue transglutaminase (tTG) IgA
2 - anti-gliadin IgA
3 - anti-endomysial (smooth muscle bundles of many tissue)
In coeliac disease what cross contamination can cause dermatitis herpetiformis?
- IgA antibodies bind to tissue transglutaminase (tTG) in skin
- attract neutrophils and initiate an inflammatory reaction
When looking at histology of a GIT sample from a patient with coeliac disease, what are the 3 key aspects that are visible?
1 - villus atrophy
2 - infiltration of inflammatory cells
3 - crypt hyperplasia
When diagnosing coeliac disease we are able to measure antibodies in the plasma, what are these antibodies?
- anti-endomysial (tissue surrounding smooth muscle) IgA
- anti-tissue transglutaminase (IgG anti tTG in patients with IgA deficiency)
- anti-gliadin antibodies
- 6-22% of patients have serology negative CD (no detection of antibodies)
If you have measured the anti-bodies (anti-endomysial, IgA anti-tissue transglutaminase (IgG anti tTG in patients with IgA deficiency) and anti-gliadin antibodies), what is the gold standard to diagnose a patient with suspected celiac disease?
- histology of a small bowel biopsy
- look for raised intraepithelial lymphocytes, crypt hyperplasia and villous atrophy (Marsh Criteria)
Is diagnosing a patient with suspected celiac disease through antibodies in the blood 100% accurate?
- no
- •6-22% of patients with celiac disease are serology negative
How do we treat coeliac disease?
- remove gluten from the diet (barley and rye)
When treating patients with coeliac disease why is it important to provide supplement vitamins and minerals?
- increased risk of malabsorption
- B12 (intrinsic factor), folate and calcium are often taken
- annual bloods to monitor levels
What is inflammatoruy bowel disease and what are the 2 main types?
- chronic inflammation of the GIT
1 - Crohn’s disease
2 - Ulcerative Colitis