Coeliac disease week 3 gi block

Question Answer
What's coeliac disease? a common digestive condition where the small intestine becomes unable to absorb nutrients. A gluten-sensitive enteropathy
What's enteropathy? disease of the intestine, especially the small intestine
What is coeliac disease with relation to the small intestine and what does it absolve with? Small intestinal villous atrophy that resolves when gluten is withdrawn from the diet. There's an inappropriate T cell-mediated immune response in genetically susceptible individuals
What's gliadin and which is most toxic? Gliadin is a class of proteins present in meat and several other cereals – alpha gliadin is most toxic moiety (part)
Give the epidemiology of coeliac disease Affects females more than males, any age, 20% of people diagnosed are 60+, 1% prevalence in UK although not actually 1% of population have it, assumed undiagnosed cases
Where is coeliac disease rare? Africa and Asia
What percentage prevalence does coeliac disease have in 1st degree relatives? 10% prevalence in first degree relatives
What are 95% of coeliac disease sufferers and what are the rest? 95% are HLA-DQ2 (rest are HLA-DQ8)
How can infection cause you to get coeliac disease? What is the peptide on alpha gliadin similar to? Infection with adenovirus 12 in genetically susceptible individuals. Peptide on alpha gliadin similar to that within E1b portion of the virus, leads to cross reactivity with alpha gliadin and development of coeliac disease
What does digestion of alpha gliadin produce and what is this absorbed into? Digestion of alpha gliadin produces stable peptide which is absorbed into the lamina propria
What does exposure to TTG do to alpha gliadin? Exposure to TTG (from damaged epithelium) leads to deamination of glutamine residues. Enables bonding to HLADQ2 and activation of pro-inflammatory T cell response
When do infants present with coeliac disease? What can this lead to in them? Present aged 4-24 months (after cereals have been introduced). Present with impaired growth, diarrhoea, vomiting, abdominal distension
How do older children present with coeliac diseasde? Anaemia, short stature, pubertal delay, recurrent abdominal pain or behavioural disturbance
What percentage of people with iron deficiency anaemia have coealiac? 3-12% of all IDA
What percentage of people with iron deficiency anemia present with coeliac? 50%
Give adult symptoms of coeliac disease diarrhoea, bloating, flatulence, abdominal discomfort. 50% have no history of diarrhoea, may be constipated. Symptomatic disease may be provoked by infection, pregnancy or surgery
Give five other presentations of people with coeliac disease Nutritional deficiency, reduced fertility/amenorrhoea, osteoporosis, unexplained increased AST/ALT, neurological/psychiatric symptoms (e.g. epilepsy, peripheral neuropathy)
Does digestion or absorption happen more in the duodenum and proximal jejenum? Digestion happens more than absorption. Acidic pH means solubility and absorption of polyvalent cations (e.g. iron and calcium)
which part of the small intestine is responsible for the bulk of nutrient absorption? distal jejenum and ileum. terminal ileum – specialised absorption of cobalamin (vitamin B12) and bile salts
what does the colon do? salvages fluid and electrolytes not absorbed by the small intestine. absorbs short chain fatty acids produced by colonic bacteria from undigested carbs
how much fluid does the small bowel absorb daily 6 litres of lfluid daily, plus fat, protein, and electrolytes
How long is the small bowel and each of its parts? Overall approximately 3-7m in length, duodenum (26cm), jejunum (3.5m), ileum (1.5m)
Pathology of coeliac disease Mucosal inflammation can vary in severity and extent. Mild proximal disease typically occurs. Mucosal damage may be patchy. Loss of villous height
What might happen to the villi in coeliac disease? May be completely flat or short and broad (sub-total villous atrophy)
What happens to mucousal thickness in coeliac disease? No change in total mucousal thickness as crypts become elongated (hypertrophy)
What happens to plasma cells and intraepithelial lymphocytes during coeliac disease? Increased plasma cells and intraepithelial lymphocytes (IELs)
Describe diarrhoea during small bowel disease watery and high volume, rarely bloody, steatorrhoea (the excretion of abnormal quantities of fat with the faeces owing to reduced absorption of fat by the intestine
Give three signs of small bowel disease Malabsorption (Fat/Vits/Carbs/Protein), weight loss, and abdominal pain/vomiting
Give an indicator of small bowel disease malabsorption/electrolyte imbalance of folate, magnesium, vitamin B12, vitamin K, calcium and vitamin D
What can chronic or recurrent iron deficiency anaemia indicate? small bowel disease
What happens to 80% of total body iron? ultimately incorporated into red cell haemoglobin
How much RBCs does an average adult produce daily? 2 x 10 to the power of 11
What's the red cell renewal rate per day 0.8% per day – this requires 20mg elemental iron daily
What is the recommended daily iron intake? 8-18mg (27mg in pregnant women)
How much iron does an average adult store? 1-3g of iron. A balance between dietary uptake and loss maintains this balance
How much iron is lost each day and through where? About 1mg of iron is lost each day through sloughing of cells from skin and mucosal surfaces, including the lining of the gi tract
What does menstruation do to iron loss? Increases the average daily iron loss to about 2mg per day in premenopausal female adults
Where does iron absorption predominantly occur? Duodenum and upper jejunum
what happens to the ferrous iron fe2+ at physiological pH, ferrous iron Fe2+ is rapidly oxidised to the insoluble ferric Fe3+ form
What does gastric acid do to the uptake of ferric iron? Gastric acid lowers the pH in the proximal duodenum, enhancing the solubility and uptake of ferric iron
What enhances and inhibits iron absorption? enhanced by ascorbic acid (vitamin C), citric acid but inhibited by phytates and tannins (tea)
What two serology tests can you do for coeliac disease? IgA tTG (tissue transglutaminase Ab) and IgA EMA (antiendomysial Ab)
Give the sensitivity and specificity of the IgA tTG test sensitivity 93% and specificity 99%+
Give the sensitivity and specificity of the IgA EMA test Sensitivity 93% and specificity 98%+
which serum test is more sensitive and specific in coeliac disease? In adults TTG more sensitive and EMA more specific
What can you see on the endoscopy of someone with coeliac disease scalloping of the folds, paucity of folds, mosaic patter ('cracked mud), prominent submucosal blood vessels, nodular pattern to the mucosa, or could just be normal
Describe the small bowel biopsy distal duodenum, minimum 4 biopsies (patchy changes), biopsies from duodenal bulb may improve diagnosis, must be on gluten rich diet
what is the marsh classification dependent on? number of intraepithelial lymphocytes per 100 enterocytes, and number of crypts, and atrophy/absence of villi
what do you need to do if they've got villous atrophy but negative coeliac serology? check IgA – selective deficiency in 2-5%
List some rarer causes of coeliac disease Giardiasis (most common infection in humans), CVID, Crohn's disease, NSAIDs, chronic ischaemia, lymphoma
give a disease associated with coeliac disease Dermatitis Herpetiformis
Give some deets about dermatitis herpetiformis itchy rash on extensor surfaces, gluten sensitive/dapsone, 90% villous atrophy
Give some other autoimmune disorders associated with coeliac disease T1DM, thyrotoxicosis, Addison's disease
What's a solution for people with coeliac disease? put them on a gluten free diet
what do you need to avoid on a gluten free diet? wheat, barley and rye
what can you eat on a gluten free diet? oats, rice and maize
what percentage respond to a gluten free diet? 85% respond (histology takes 3-12months)
why do people on a gluten free diet continue dairy? because gluten free diet stops insult to villi so enzyme that digests milk can be upregulated again, but 50% of people with coeliac disease have secondary hypolactasia, so are lactose intolerant as a result of having coeliac disease
give four complications of coeliac disease infection, osteoporosis, refractory coeliac disease, malignancy
what's functional hyposplenism? a condition accompanying many diseases such as celiac disease. characterised by defective immune responses against infectious agents, since the spleen is thought to play an important role in the production and maturation of B-memory lymphocytes
what percentage of coeliac patients have osteoporosis? 25% – low BMI and calcium/vitamin D deficient
Define refractory coeliac disease recurrent malabsorptive symptoms and villous atrophy despite strict adherence to a gluten free diet for at least 6-12 months in the absence of other causes of non-responsive treated coeliac disease and overt malignancy
what's refractory coeliac disease type 1? Persistent villous atrophy but normal immunophenotype
what's the 5 year survival like for RCD 1? 96%
what can you use to treat RCD 1 and what is the response like? Steroids/Azathioprine – 75% + response
What's RCD type II like? persistent villous atrophy with abnormal immunophenotype (CD3/CD8 -ve)
What's the 5 year survival like for people with RCD II? 58% 5 year survival
What can RCD II cause? ulcerative jejunitis; ulceration in jejunum/ileum
What do 60-80% of people with RCD II progress to at 5 years and what is this? EATL – enteropathy-associated T-cell lymphoma (cancer). 5 year survival only 8-20%
Give symptoms of EATL weight loss, night sweats, itch, overt/occult GI bleeding, venous thromboembolism . poor response to chemotherapy and autologous stem cell treatment
give three other coeliac related malignancies small bowel adenocarcinoma, oesophageal and colonic adenocarcinoma
what reduces the risk of coeliac-related malignancy? oesophageal and colonic adenocarcinoma

Leave a Reply

Your email address will not be published. Required fields are marked *