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 acticvated 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
Crohns disease is one of the 2 types of inflammatory bowel disease. What and where does it affect?
- patchy with healthy and disease tissue side by side
- transmural, affecting mucosa, submucosa, muscularis propria and serous layers
- affects anywhere from mouth to anus
Ulcerative colitis disease is one of the 2 types of inflammatory bowel disease. What and where does it affect?
- continous inflammatory condition
- affects the mucosal surface only in the colon
In the image below, which is crohns disease and which is ulcerative colitis?
- left = crohns with deep but patchy inflammation
- right = ulcerative colitis with shallow systemic inflammation
What does transmural mean?
- affects all layers of GIT
When comparing crohns and ulcerative colitis, which has granulomas?
- crohns
When comparing crohns and ulcerative colitis, which has crypt ulcerations and abscesses?
- ulcerative colitis
- abscesses = pus formed from dead tissue and immune cells
What are granulomas?
- aggregates of macrophages surrounding foreign substances they want to eliminate
- hallmarks of crohns disease
In ulcerative colitis and crohns disease is there patchyness in the inflammation?
- crohns = yes
- ulcerative colitias = no
Is crohns more common in older or younger people?
- younger adults and children
What is a lifestyle factor that significantly increases the risk of crohns disease?
- smoking
Stricture are commonly seen in crohns, what are they?
- abnormal narrowing in a passage in the body
Fistula are commonly seen in crohns, what are they?
- abnormal connection between two body parts
- can be between tissues or tissue and an organ
Perianal disease is common in crohns disease, what is this?
- inflammation around the anus
Although the exact cause of crohns is unknown, what are some of the suggested causes?
- genetics / immunity
- smoking
- NSAIDs
- mucosal barriers deficiencies
What is a first degree relative?
- sharing at least 50% of genetics from mum or dad
Is there genetic risk of developing crohns?
- first degree relatives have 13-18% increased risk of developing it
- 50% concordance in monozygotic twins
Have any specific genes been associated with crohns?
- yes
- NOD2 (nucleotide binding domain) on Chr16 is the most known
- BUT over 200 other variants have been identified
What is the primary aim of treatment in crohns disease?
- to prevent excessive surgery and short bowel syndrome
- 50% of patients with crohns will need surgery and 70% of those will need a 2nd operation within 5 years of the first
- surgery may be the only treatment for drainage of abscesses or treatment of fibrostenotic strictures (causes obstruction)
What religous group are at a higher risk of developing Crohns disease?
- Ashkenazi Jewish
- the group are insular meaning they mate within the group so the genetic aspect of crohns is enhanced
In ulcerative colits are men or women more at risk, and is smoking associasted with this disease?
- women
- no, non-smokers are more likley to develop the disease
In ulcerative colits what ages are most at risk?
- biomodal
- so 20s and then 60s
In ulcerative colits is there a genetic risk of developing the disease?
- genetics are implicated but lots of genes
- concordance amongst monozygotic twins being similarly as high
What from of medication has been linked with ulcerative colitis?
- NSAIDs can cause flare ups
Ulcerative colitis only affects the colon and the mucosal layer, but why does this increase the risk of perforation (hole in tissue)?
- bowel walls become think as colon expands
- thinned walls are more likley to perforate. essentially explode
In ulcerative colitis what is the lifetime risk of a colectomy (complete removal of colon)?
- 20-30%
In patients with ulcerative colitis what % of patients will go into remission, maintain with symptoms and progress?
- 33.33% for each
How is ulcerative colitis treated?
- pyramid of drug treatments
- start at bottom and work upwards
Corticosteroids are naturally occuring hormones in the body that regulate the immune system, and are used to treat inflammation, IBD and asthma, etc… What are the 2 core corticosteroids that we need to be aware of?
1 - hydrocortisone = intravenous only
2 - prednisolone = oral only
When treating IBD, we use the pyramid which includes Mesalazines (bottom, so first line), Thiopurines (middle) and Biologics (top). Mesalazines are the first line treatment, but are they used in both ulcerative colitis and crohns disease?
- no
- ulcerative colitis only
Mesalazines are the first line of treatment for IBD. What is the core drug we need to know?
- 5 – aminosalicyclic acids ( 5-ASAs)
Mesalazines are the first line of treatment for IBD 5–aminosalicyclic acids ( 5-ASAs) is the core drug we need to know, but what is the mechanism of action?
- poorly digestion and metabolised in GIT by bacteria
- topical effects in colon only
- absorbed by epithelial cells and down regualates inflammatory genes
5–aminosalicyclic acids ( 5-ASAs) is the core Mesalazines that we need to be aware of. How can it be administered?
- oral, rectal suppositories and enemas
- delivered in pH dependent capsules
When treating acute crohns disease, are patients allows to eat?
- no
- nil by mouth
If patients with acute crohns disease, that are suspected of having abdominal abscesses should be prescribed what?
- antibiotics through IVs
- increased risk of infection with abscesses
If patients with acute crohns disease, patients are given a unique liquid nutritionally complete diet that is able to stop acute flare ups of crohns disease. What is this called?
- modulen
If patients with acute crohns disease, patients may be prescribed a corticosteroid intravenously. What is this drug called?
- hydrocortisone
In acute ulcerative colitis what drug will patients be given intravenously to help reduce inflammation?
- hydrocortisone
In acute ulcerative colitis patients they are at risk of embolus fro DVTs. What drug are they prescribed to reduce the risk of this?
- low molecular weight heparin
In acute ulcerative colitis patients some patients are at risk of colectomy. What treatment would be used here?
- surgary
What is inflammation of the rectus called?
- proctitis
- proc = greek for anus
- itis = inflammation
What is ulcerative colitis called when it affects the whole large intestines?
- pancolitis
What is the first line treatment for crohns, and is the 2nd line treatment for ulcerative colitis?
- Thiopurines
What is the second line treatment for crohns, and the final line treatment for ulcerative colitis?
- biologics
When using medication for IBD, such as Mesalazines, Thiopurines and Biologics, instead of jumping between these 3 medication types, patients can often be prescribed something in between which can help them get into remission, what is this?
- corticosteroids
Thiopurines are the first line of treatment in Crohns disease, but are the second line for ulcerative colitis. How long do these drugs take to act?
- up to 6 weeks
Thiopurines are the first line of treatment in Crohns disease, but are the second line for ulcerative colitis. They tend to take 6 weeks to act, so another drug can be prescribed alongside to help, what drug is this?
- corticosteroids
Thiopurines are the first line of treatment in Crohns disease, but are the second line for ulcerative colitis. What is the mechanism of action of this drug?
- anti-inflammatory
- Thiopurines metabolised into thioguanine nucleotides
- thioguanine nucleotides are inserted into DNA backbone
- stop DNA unwinding, which is required for inflammatory processes
Thiopurine methyl transferase (TPMT) is the enzyme that metabolises Thiopurines. Why is it important to do genetic testing on patients with IBD before prescribing them with Thiopurines?
- 1:10 patients have no thiopurine methyl transferase (TPMT)
- they are much more likely to suffer severe side effects
Thiopurines have a triomodal distribution of activity, what does this mean?
- effectiveness is divided into threes
- 1/3 will have no effect
- 1/3 will have low/moderate effect
- 1/3 will have normal/large effect
Biologics are the final drug that can be prescribed to patients with IBD if other treatments have failed. What was the first biologic used to treat IBD?
- anti TNF-a
- 60% effective helping IBD remission
