T1 L11 Coeliac disease & IBD Flashcards
What is coeliac disease?
A gluten sensitive enteropathy or coeliac sprue
Autoimmune mediated disease of the small intestine that is triggered by the ingestion of glucose which leads to malabsorption
What is gluten?
Protein component of wheat, rye and barley which is left behind after washing off starch
Consists of gliadin & glutenin
There is a high prevalence of coeliac disease in what groups of patients?
Down’s syndrome
Type I diabetes mellitus
Auto-immune hepatitis
Thyroid gland abnormalities
What is the mechanism for coeliac disease?
1) Gluten in wheat plus small bowel mucosa
2) Tissue transglutaminase produced
3) Diamidates glutamine in gliadin
4) Negatively charged protein
5) IL-15
6) Natural killer cells & intraepithelial T lymphocytes
7) Tissue destruction & villous atrophy
How does coeliac disease present?
The hallmark is the malabsorption of nutrients
Short stature & failure to thrive in children
Diarrhoea & steatorrhoea
Weight loss & fatigue
Anaemia
Osteopenia & osteoporosis
What are the classifications of coeliac disease?
Classical - malabsorption symptoms
Non-classical including symptoms outside GI tract
Subclinical - detected with blood tests
What symptoms are there for non-classical coeliac disease?
Constipation, bloating, alternate bowel habits Heartburn Nausea Vomiting Dyspepsia Recurrent miscarriages / infertility
What investigations are done for coeliac disease?
General investigations - FBC, urea & electrolytes, LFT
Serology for diagnosis
HLA DQ2 & HLA DQ8 in children with positive TTGA & symptoms to avoid doing a biopsy
Duodenal biopsies
What does serology look for in coeliac disease?
Tissue transglutaminase IgA (TTGA)
Endomysial IgA - connective tissue covering smooth muscle fibres
Deamidated gliadin peptide IgA & IgG
Also used to monitor adherence to gluten free diet
Sero-negative coeliac disease reported
What routine coeliac disease tests are carried out?
Tissue damage tests
When the small bowel is exposed to gluten there is an overreaction of the immune system to produce antibodies to proteins involved in the tissue damage: tissue transglutaminase, endomysium, deaminated gliadin peptide
What are the microscopic features of coeliac disease?
At least 4 biopsies have to be sampled from the duodenum via an upper GI endoscopy as the changes can be patchy
Villous atrophy
Crypt hyperplasia
Increase in lymphocytes in lamina propria / chronic inflammation
Increase in intraepithelial lymphocytes
Recovery of villous abnormality on a gluten-free diet
What are the complications associated with coeliac disease?
Enteropathy associated T cell lymphoma
High risk of adenocarcinoma of the small bowel & other organs such as large bowel, oesophagus, pancreas
May be associated with dermatitis herpetiformis
Infertility & miscarriage
Refractory coeliac disease despite strict adherence to gluten free diet
What does inflammatory bowel disease constitute?
Crohn's disease Ulcerative colitis Diverticular disease Ischaemic colitis Drug-induced colitis Infective colitis
What is Crohn’s disease?
Idiopathic, chronic inflammatory bowel disease that is often complicated by fibrosis & obstructive symptoms.
It can affect any part of the GI tract from the mouth to the anus
What is the cause of Crohn’s disease?
Exact causes are unknown Genetic Infectious Immunologic Environmental Dietary Vascular Smoking NSAIDs Psychological factors Defects in mucosal barrier
What are the genetics of Crohn’s disease?
Evidence for a genetic predisposition
No classical mendelian inheritance but it is polygenic
NOD2
What is NOD2?
Nucleotide binding domain
Also known as IBD1 gene on chromosome 16
Encodes a protein that binds to intercellular bacterial peptidoglycans to activate nuclear factor kappa B. This inhibits the normal immune response to luminal microbes leading to uncontrolled inflammation
What is the infectious cause of Crohn’s disease?
Granulomas present in 60-65% of patients
Mycobacterium paratuberculosis extensively investigated
Other infectious organisms: measles virus, pseudomonas, listeria
What are the environmental factors that may cause Crohn’s disease?
Improved hygiene hypothesis
Reduces enteric infections & reduces ability of GI tract mucosa to develop regulatory processes that normally limit immune response to pathogens which cause self-limiting infections
Migration from a low to high risk population increases risk
Smoking doubles risk
What are the clinical features of Crohn’s disease?
Chronic, indolent course punctuated by periods of remission & relapses
Abdominal pain relieved by opening bowels
Prolonged, non-bloody diarrhoea
Blood may be present if colon is involved
Loss of weight, low grade fever
What is the distribution of Crohn’s disease?
Any part of GI tract from mouth to anus
Small bowel only - 40%
Large bowel only - 30%
Small & large bowel - 30%
What are the morphological features of Crohn’s disease?
Fat wrapping of serosa
Typically segmented morphology
Ulceration with cobblestone pattern
Strictures due to fibrosis
What is the microscopic appearance of Crohn’s disease?
Transmural or full thickness inflammation of bowel wall Mixed acute & chronic inflammation Preserved crypt architecture Mucosal ulceration Fissuring ulcers Granulomas Fibrosis of the wall
What are the complications of Crohn’s disease?
Intra-abdominal abscesses Deep ulcers lead to fistula Sinus tract Obstruction due to adhesion Obstruction due to strictures caused by increased fibrosis Perianal fistula & sinuses Risk of adenocarcinoma
What is ulcerative colitis?
Chronic inflammatory bowel disease that only affects large bowel from rectum to caecum
Inflammatory process is confined to mucosa & submucosa except in severe cases
What is the cause of ulcerative colitis?
Cause is unknown
Multiple factors are implicated
Genetics are not as well defined
What are the environmental factors of UC?
Smoking is protective
NSAID exacerbate UC
Antioxidants vitamin A & E found in low levels
What are the clinical features of UC?
Intermittent attacks of bloody diarrhoea Mucoid diarrhoea Abdominal pain Low grade fever Weight loss
What are the macroscopic features of UC?
Affects large bowel from rectum to caecum
Can affect rectum only (proctitis), left side (splenic flexure to rectum) or whole large bowel (total colitis)
No ulcers on endoscopic examination in early disease
Diffuse mucosal involvement which appears haemorrhagic
In chronic case the mucosa becomes flat with shortening of the bowel
What are the microscopic features of UC?
Inflammation confined to mucosa
Diffuse mixed acute & chronic inflammation
Crypt architecture distortion
In inactive UC the mucosa may be atrophic with little or few inflammatory cells in lamina propria
What are the complications of UC?
Leads to surgery Refractory to medical treatment Toxic megacolon Refractory bleeding Dysplasia or adenocarcinoma
What is toxic megacolon?
Bowel is grossly dilated & haemorrhage
Patient is very ill
Bloody diarrhoea
Abdominal distention
Electrolyte imbalance with hypoproteinaemia
What are the extra-intestinal manifestations of CD & UC?
Ocular - uveitis, iritis, episcleritis
Cutaneous - erythema nodosum, pyoderma gangrenosum
Arthropathies - ankylosing spondylitis
Hepatic - screlosing cholangitis
What investigations are done in UC?
FBC
Urea & electrolytes
Liver function tests
Inflammatory markers - C reactive protein
Endoscopy & biopsies
Radiological imaging - barium studies, MRI, U/S, CT
Why is it important to differentiate CD from UC?
A patient may have a pouch after surgery in UC but not in CD because of the risk of recurrence
A pouch is created from the small bowel as stool reservoir following removal of large bowel.
