Coeliac Disease & IBD Flashcards
Coeliac disease definition
Gluten sensitive enteropathy or coeliac sprue
leading to malabsorption with cessation of symptoms on gluten-free diet
Gluten definition
A protein compound of wheat, rye and barley which is left behind after washing off the starch
Gluten consists of gliadin and glutenins
Genetic abnormalities in Coeliac Disease
Associated with HLA – DQ2 and HLA - DQ8 in 95% and 5% of the patients respectively
The genes are located on Chr 6p21
High coeliac disease prevalence in patients with
Down’s syndrome, Type I diabetes mellitus, auto-immune hepatitis and thyroid gland abnormalities
Abnormal liver function tests
Process
Gluten + Small bowel mucosa
Tissue transglutaminase ↓ diamidates glutamine in gliadin ↓ Negatively charged protein ↓ IL – 15 ↓ Natural killer cells + Intraepithelial T lymphocytes ↓ Tissue destruction + villous atrophy
Hallmarks of coeliac disease [6]
Malabsorption of nutrients
Short stature; failure to thrive in children
Diarrhoea : smelly & bulky stool, rich in fat (steatorrhoea)
Weight loss and fatigue
Anaemia – folate and Fe deficiency
Osteopenia and osteoporosis – calcium and Vitamin D deficiency
Classification of Coeliac Disease
Classical – Malabsorption symptoms
Non-classical including symptoms outside the gastro-intestinal tract:
constipation, bloating alternate bowel habits
→ constipation/diarrhoea
Heartburn, nausea, vomiting and dyspepsia
Recurrent miscarriage/infertility
Sub-clinical – Detected with blood tests
Coeliac disease investigations
FBC, U & Es, LFTs
Deamidated gliadin peptide IgA & IgG
Endomysial IgA
Tissue transglutaminase IgA
HLA D2 & HLA DQ8 in children with positive TTGA and symptoms to avoid biopsies
Tissue transglutaminase IgA
98% sensitive, 96% specific
Endomysial IgA
100% specificity,
90% sensitivity
Macroscopic features of coeliac disease
Villous atrophy (VA)
Crypt hyperplasia
Increase in lymphocytes in the lamina propria/chronic inflammation
Increase in intraepithelial lymphocytes (IEL)
Recovery of villous abnormality on gluten-free diet
Coeliac disease complications
Enteropathy associated T-cell lymphoma
High risk of adenocarcinoma
Dermatitis hepetiformis – very itchy skin condition
Infertility and miscarriage
Refractory coeliac disease despite strict adherence to gluten free diet
Crohn’s disease definition
An idiopathic, chronic inflammatory bowel disease often complicated by fibrosis and obstructive symptoms a
Affect any part of the GIT from mouth to anus
Potential CD genetics
NOD2 (nucleotide binding domain) also known as IBD1 gene on Chr16 encodes a protein that binds to intercellular bacterial peptoglycans, activates nuclear factor kappa B (NF-KB) and inhibits normal immune response to luminal microbes leading to uncontrolled inflammation
Hint that CD could be infectious
Because granulomas are present in 60 -65% of patients, mycobacterium para-tuberculosis was extensively investigated as a possible cause but never proven
Other infectious organisms implicated – measles virus, pseudomonas, listeria, but never proven
CD environmental factors
Improved hygiene hypothesis
Migration to high risk population
Cigarette smoking
CD clinical features
Chronic, indolent course punctuated by periods of remission and relapses
Abdominal pain, relieved by opening bowels
Prolonged non-bloody diarrhoea
Blood may be present if the colon is involved
Loss of weight, low grade fever
CD morphological features
Fat wrapping of the serosa - noted during surgery
Typically segmental morphology→normal bowel separated by abnormal bowel = skip lesions
Ulceration with a cobblestone pattern
Strictures due to fibrosis
Microscopic appearance of CD
Transmural or full thickness inflammation of the bowel wall
Mixed acute and chronic inflammation i.e. polymorphs and lymphocytes
Preserved crypt architecture
Mucosal ulceration
Fissuring ulcers (deep crevices)
Granulomas ( collection of macrophages) present in 60 - 65%
Fibrosis of the wall
UC
A chronic inflammatory bowel disease which only affects the large bowel from the rectum to the caecum. Unlike CD, the inflammatory process is confined to the mucosa and sub-mucosa except in severe cases.
UC causes
High incidence of UC in first degree relatives and high concordance in twins
HLA-B27 identified in most patients with UC, but not thought to be an aetiological factor
NSAIDs exacerbates UC
Antioxidants Vitamins A & E are found in low levels in UC
UC clinical features
Intermittent attacks of bloody diarrhoea Mucoid diarrhoea Abdominal pain Low grade fever Loss of weight
UC macroscopic features
Affects the large bowel from rectum to the caecum
Can affect the rectum only (proctitis), left sided bowel only ( splenic flexure to rectum) or whole large bowel = total colitis
Despite the term ‘ulcerative’ there are no ulcers on endoscopic examination in early disease
Diffuse mucosal involvement which appears haemorrhagic
With chronicity, the mucosa becomes flat with shortening of the bowel
Microscopic features of UC
Inflammation confined to the mucosa (black bar)
Diffuse mixed acute & chronic inflammation
Crypt architecture distortion
In quiescent (inactive) UC, the mucosa may be atrophic with little or few inflammatory cells in the lamina propria
