Lecture 11 Flashcards
What is coeliac disease?
Gluten sensitive enteropathy or coeliac sprue
An auto-immune mediated disease of the small intestine triggered by the ingestion of gluten in genetically predisposed individuals leading to malabsorption with cessation of symptoms on gluten free diet
What is gluten
Gluten is a protein compound of wheat, rye and barley which is left behind after washing off the starch
Gluten consists of gliadin and glutenins
What are the genetic abnormalities of coeliac disease?
Associated with HLA – DQ2 and HLA - DQ8 in 95% and 5% of the patients respectively
The genes are located on Chr 6p21
Coeliac disease has a strong hereditary predisposition affecting around 10% of first degree relatives
How does gluten cause coeliac disease?
Gluten in wheat + small bowel mucosa->
Tissue transglutaminase->
diamidates glutamine in gliadin->
Negatively charged protein->
IL-15->
NK cells + intraepithelial T lymphocytes->
Tissue destruction + villous atrophy
How does coeliac disease present?
Hallmark of coeliac disease is the 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
Heartburn, nausea, vomiting and dyspepsia
Recurrent miscarriage/infertility
What are the investigation for coeliac disease
General investigations: FBC, U & Es, LFTs
Serology for diagnosis of coeliac disease
Tissue transglutaminase IgA (TTGA); 98% sensitive, 96% specific
Endomysial IgA – connective tissue covering the smooth muscle fibres; 100% specificity, 90% sensitivity
Deamidated gliadin peptide IgA & IgG (new)
For monitoring compliance to gluten free diet
HLA D2 & HLA DQ8 in children with positive TTGA and symptoms to avoid biopsies
Duodenal biopsies
What are the microscopic features of coeliac disease?
At least four biopsies to be sampled from the duodenum at upper GIT endoscopy as changes can be patchy
On microscopy there is: 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
What are the complications of coeliac disease?
Enteropathy associated T-cell lymphoma
High risk of adenocarcinoma of small bowel and other organs – large bowel, oesophagus, pancreas
May be associated with dermatitis hepetiformis – very itchy skin condition
Infertility and miscarriage
Refractory coeliac disease despite strict adherence to gluten free diet
Gluten free diet may reduce risk of complications
What is Crohn’s disease
An idiopathic, chronic inflammatory bowel disease often complicated by fibrosis and obstructive symptoms and can affect any part of the GIT from mouth to anus
What causes CD
The exact cause is unknown
Genetic, infectious, immunologic, environmental, dietary, vascular, smoking, NSAIDs and psychological factors – all have been implicated
Defects in mucosal barriers
What are the genetics of CD?
First degree relatives have 13-18% increased risk of developing CD with a 50% concordance in monozygotic twins
No classical Mendelian inheritance but polygenic
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
What environmental factors are implicated in Crohn’s disease
Improved Hygiene Hypothesis:
Improved hygiene in susceptible individuals reduces enteric infections and this reduces the ability of the GIT mucosa to develop regulatory processes that would normally limit immune response to pathogens which cause self-limiting infections i.e. because of the good hygiene, the mucosa is not immunised to microbes and when exposed to whatever pathogen that causes CD there is exaggerated immune response resulting in mucosal damage.
Cigarette smoking doubles the risk of developing CD
What are the clinical features of CD
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
What is the distribution of CD
Small bowel alone – 40%
Large bowel alone – 30%
Small and large bowel – 30%
What are the morphological features of CD
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
What are the microscopic appearances 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
What are the complications of CD
Intra-abdominal abscesses
Deep ulcers lead to fistula = communication between two mucosal surfaces (e.g. colo-vesical fistula leads to pneumaturia)
Sinus tract = blind ended tract ends in a “cul de sac”
Obstruction due to adhesions
Obstruction due to strictures caused by increased fibrosis
Perianal fistula and sinuses
Risk of adenocarcinoma, but not as high as in UC
What is ulcerative colitis
UC is 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.
What causes UC?
As with CD the cause of UC is unknown
Similar to CD multiple factors are implicated
Genetics not as well defined as in CD
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
Similar to CD no specific infective agent has been identified
What about environmental factors?
Smoking is protective in UC; cessation of smoking may trigger UC or activate disease in remission
NSAIDs exacerbates UC
Antioxidants Vitamins A & E are found in low levels in UC
What are the clinical features of UC?
Intermittent attacks of bloody diarrhoea Mucoid diarrhoea Abdominal pain Low grade fever Loss of weight
What are the macroscopic features of UC?
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
What are the microscopic features of UC?
Inflammation confined to the mucosa
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
What are the complications of UC
Complications invariably lead to surgery
Refractory to medical treatment
Toxic megacolon = bowel grossly dilated
Patient very ill
Bloody diarrhoea
Abdominal distention
Electrolyte imbalance with hypoproteinaemia
Refractory bleeding
Dysplasia or adenocarcinoma
UC at an early age
Total unremitting UC
After 8-10 years of UC
Patient requires annual screening colonoscopy
What is a toxic megacolon
bowel dilated and haemorrhagic
