L20-21 Gastrointestinal Disorders Flashcards
What is a peptic ulcer?
A break in the mucus lining of the stomach or duodenum causes stomach acid to damage the epithelial lining
What are the main causes of peptic ulcers?
Helicobacter pylori infection (most common) and non-steroidal anti-inflammatory drugs (NSAIDS) or aspirin
How does Helicobacter pylori cause peptic ulcers?
Breaks down mucus layer and colonises stomach mucosa - allows acid to cause damage
How do NSAIDS (non-steroidal anti-inflammatory drugs) cause peptic ulcers?
They block cox-1, which is involved in prostaglandin and mucus production in stomach - cant form lining
What are the two main ways of diagnosing peptic ulcers?
Endoscopy or H. pylori testing
How can testing for H. pylori in relation to peptic ulcers be carried out?
(3)
Faecal antigen testing
Serum antibody quantitation
Carbon-13 urea breath test
What does the carbon-13 urea breath test test for?
How does this work?
H. pylori infection as a cause for peptic ulcers
Patient is given carbon-13 urea, H. pylori splits it into H2O and CO2, labeled CO2 in breath confirms infection
What is the recommended treatment for peptic ulcers?
Triple therapy regimen: - Proton pump inhibitor (reduces HCl production) - One pair of antibiotics - Amoxicillin and clarithromycin OR Metronidazole and clarithromycin
What is a gastrinoma?
A gastrin secreting tumour of the pancreas or duodenum that promotes gastric acid production
How is a gastrinoma diagnosed?
Fasting serum gastrin (FSG) levels - elevated
What is the treatment for a gastrinoma?
Surgery or proton-pump inhibitors
What is oral tolerance?
Suppression of immune response against antigens that have previously been eaten as they are seen as harmless
What role does the small intestine have in oral tolerance?
It must tolerate ingested food and microbiota, and recognise and control potential pathogens
What is Coeliac disease (CD)?
No oral tolerance to gluten
What is gluten?
Substance found in endosperm of wheat grains
What is the composition of gluten?
Composed of two proteins: gliadin and glutenin
What are the three major diseases caused by wheat?
Coeliac disease
Non-Coeliac gluten sensitivity
Wheat allergy
What is the difference between Coeliac disease and other conditions caused by wheat in terms of disease mechanism?
CD - autoimmune reaction causes oral intolerance of gluten
Others - hypersensitivity reaction mediated by IgE mechanism
Why is there an increased incidence of Coeliac disease (CD)?
4
Greater awareness, testing frequency, gluten exposure, and due to population’s underlying genetics
What are the four major symptoms of coeliac disease?
Malabsorption (weight loss)
Diarrhoea
Steatorrhea (fat secretion)
Abdominal distention
What is dermatitis herpetiformis?
What GI condition is this sometimes seen in?
Small groups of blisters on red plaques on knees, elbows, forearms and buttocks; can burst making them itch and sting
Coeliac disease
What biological sex has a higher risk of developing coeliac disease? How much higher?
Females (XX) - 1.5-2 times higher risk
What conditions can a first degree relative have that puts someone at higher risk of coeliac disease?
(4)
Autoimmune diseases (T1 diabetes, Hashimoto’s thyroiditis etc.)
Down’s syndrome
Turner’s syndrome
IgA deficiency
What has been identified in coeliac disease that makes it unique among autoimmune diseases?
(3)
Environmental trigger - gluten
Genetic contribution needed for disease to occur - HLA-DQ2 or HLA-DQ8 haplotype
Autoantibodies - against transglutaminase in 95% of patients
What is the association between HLA and coeliac disease?
What other disease has these associations?
Most patients with coeliac disease have HLA-DQ2 haplotype and the rest have HLA-DQ8
T1 diabetes is associated with the same DQ molecules
What does tTG stand for? What is its relation to coeliac disease?
Tissue transglutaminase - body creates autoantibodies (IgA) against this enzyme
What effect does tissue transglutaminase (tTG) have on gluten?
Gives it a more negative charge - HLA-DQ2 and DWQ8 preferentially bind negatively charged peptides, giving more stable binding
Give three signs and symptoms that could call for screening the individual for coeliac disease
Chronic diarrhoea, gastrointestinal symptoms (e.g. vomiting, nausea), abdominal pain, sudden weight loss, fatigue, anaemia, faltering growth in children
What should be done by the patient before serological testing for coeliac disease?
Eat gluten in at least one meal per day for 6 weeks
In children, only test after being exposed to gluten
When should a patient with possible coeliac disease stop eating gluten?
Only after diagnosis is confirmed by biopsy
What serological tests can be carried out to screen for coeliac disease?
What is the preferred test?
Tissue transglutaminase (tTG) Endomysial antibody (EMA)
tTG is prefered
What is endomysial antibody (EMA) and its relation to coeliac disease?
Anti-EMA is produced in response to muscle damage from intestinal lining (seen in coeliac disease)
What is test is required to diagnose coeliac disease?
Biopsy and histological test
What is seen in histological examination of a biopsy obtained from someone with coeliac disease?
(4)
Atrophied villi
Enlarged crypts
Infiltrated lymphoid cells
Degeneration of surface epithelium
What is the cause of the gastrointestinal symptoms of coeliac disease?
Intestinal villi - can’t function efficiently due to reduced surface area etc.
What system is used to stage coeliac disease?
Why is a grading system needed?
MARSH system
Symptoms can be variable with some patients only displaying increased infiltrated lymphocytes
What is the MARSH grading system used for?
How many stages are there?
Grading coeliac disease
5 grades - 1, 2, 3a, 3b, and 3c
What is the treatment for coeliac disease?
Gluten free diet
How is the treatment of coeliac disease monitored?
Regular serological testing of tissue transglutaminase (tTG) - determines effectiveness of therapy and compliance to diet
