Cards (38)

  • What is Coeliac disease?
    • Gluten sensitive enteropathy or coeliac sprue
    • 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
    • Gluten is a protein compound of wheat, rye and barley which is left after washing off the starch
    • Gluten consists of gliadin and glutenins
  • What are the genetic abnormalities of coeliac disease?
    • Has a strong hereditary predisposition affecting around 10% of first-degree relatives
    • associated with HLA-DQ2 (95%) and HLA-DQ8 (5%)
    • genes located on Chr 6p21
  • Who gets coeliac disease?
    Most prevalent in Western Europe and USA esp patients of Irish and Scandinavian descent
    Increasing incidence in Africa and Asia though numbers underestimated
    Symptoms of coeliac disease may be attributed to infections
    A lot of patients in the community have undiagnosed coeliac disease - requires high index of suspicion
    High prevalence in patients with Down's, Type I diabetes, auto-immune hepatitis and thyroid gland abnormalities
    Bimodal presentation in childhood and late thirties
    Approx. 20% patients with coeliac disease older than 60
  • How does gluten cause coeliac disease?
    1. small bowel mucosa
    2. Tissue transglutaminase
    3. diamidates glutamine in gliadin
    4. negatively charged protein
    5. IL-15
    6. Natural killer cells +
    7. Intraepithelial T lymphocytes
    8. Tissue destruction + villous atrophy
  • Small bowel lining with coeliac disease
    inflammation + flat lining
  • Why do the symptoms of coeliac disease present?
    flat mucosa does not absorb nutrients and leads to symptoms
  • Types of coeliac disease
    1. Asymptomatic - detected by blood test
    2. Classical - gastrointestinal symptoms
    3. Atypical - extra-intestinal symptoms
  • Classical Coeliac Disease with Gastrointestinal symptoms
    45-85% of patients:
    • diarrhoea: smelly & bulky stool, rich in fat (steatorrhoea)
    • Flatulence 28% of patients
    • Borborygmus (gurgling noise of movement of fluid/gas in intestines)
    • Weight loss 45% of patients
    • In children failure to thrive
    • Weakness & fatigue
    • Severe abdominal pain 34-64% of patients
    • Irritable bowel syndrome like symptoms
  • Classical presentation of coeliac disease: steatorrhoea
    bulky, pale offensive stool rich in fat
  • Atypical Coeliac disease due to extra-intestinal symptoms
    • Anaemia 10-15% of patients
    • Osteopenia and osteoporosis (fragile bones)
    • Muscle weakness, pins and needles, loss of balance, fits 8-14% of patients
    • Itchy skin conditions such as dermatitis herpetiformis 10-20% of people
    • Lack of periods, delated periods in teenagers, infertility in women and impotence & infertility in men
    • Bleeding disorders due to Vitamin K deficiency
  • Atypical presentation of Coeliac disease
    • emaciation (state of being abnormally thin/weak)
    • Pot belly due to gaseous distention
    • Muscle wasting
    • Osteoporosis
  • What are the investigations for coeliac disease?
    General investigations:
    • Full blood count FBC
    • Urea & Electrolytes U&Es
    • Liver function tests LFTs
    Serology (antibody):
    • Tissue transglutaminase IgA TTGA (98% sensitive, 96% specific)
    • Endomysial IgA - connective tissue covering smooth muscle fibres; 100% specificity 90% sensitivity; not used often as very expensive
    • Deamidated gliadin peptide IgA & IgG
    + duodenal biopsy in adult to confirm diagnosis
    In children with positive TTGA + symptoms: HLA DQ2 & HLA DQ8 to avoid biopsies
  • How do routine coeliac disease tests work // coeliac disease antibodies to?
    Assess tissue damage:
    when small bowel is exposed to gluten, there is overreaction of immune system to produce antibodies to the proteins involved in tissue damage, ie antibodies to:
    • Tissue transglutaminase
    • Endomysium
    • Deamidated gliadin peptide
  • What are the microscopic features of coeliac disease?
    at least 4 biopsies should 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)
    • Recovery of villous atrophy on gluten-free diet
  • What are the complications of coeliac disease?
    • Enteropathy associated T-cell lymphoma (DNA damage if they continue to multiply)
    • High risk of adenocarcinoma of small bowel and other organs, eg 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
  • Coeliac disease: summary
    • caused by gluten found in wheat, barley and rye
    • gluten induces inflammation of small bowel mucosa leading to villous atrophy
    • Iron deficient anaemia may be subtle symptom of coeliac disease
    • Gluten free diet may reduce risk of complications such as T cell lymphoma
  • What is Crohn's Disease
    • idiopathic (arises spontaneously, cause unknown), chronic inflammatory bowel disease
    • often complicated by fibrosis and obstructive symptoms
    • can affect any part of the GIT from mouth to anus
  • What is the epidemiology of Crohn's disease?
    • high prevalence in Western world with increased incidence in patients of Jewish origin
    • Bimodal presentation with peaks in teens-20s and 60-70 year olds
  • What causes Crohn's disease?
    • exact cause unknown (idiopathic)
    • genetic, infectious, immunological, environmental, dietary, vascular, smoking, NSAIDs and psychological factors
    • Defects in mucosal barriers which allow pathogens and other antigens to induce an unregulated inflammatory reaction
  • What are the genetics of Crohn's disease?
    • strong scientific evidence for genetic predisposition to 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 gene (CARD15) on Chr16 encodes protein associated with uncontrolled inflammatory response to luminal contents and microbes
  • Environmental factors implicated in Crohn's disease - Improved Hygiene Hypothesis
    because of improved hygiene, mucosa is not immunised to microbes and when exposed to whatever pathogen that causes CD there is exaggerated immune response resulting in mucosal damage and related symptoms
  • Other environmental factors implicated in Crohn's disease
    • improved hygiene hypothesis
    • cigarette smoking doubles risk
    • migration from a low-risk population to high-risk population
  • What is the distribution of Crohn's disease?
    affects any part of GIT from mouth to anus
    • small bowel alone - 40%
    • large bowel alone - 30%
    • small and large bowel - 30%
  • What are the morphological features of Crohn's disease?
    • fat wrapping of serosa (on anterior surface)
    • involves the bowel in a segmental manner where normal bowel is separated by abnormal bowel to give rise to skip lesions
    • ulceration of the mucosa to give rise to a cobblestone pattern
    • strictures due to fibrosis
  • Morphological features of Crohn's disease - fat deposition
    fat wrapping of serosa
    at the time of surgery can assist surgeon to demarcate the extent of disease
  • Morphological features of Crohn's disease - cobblestone pattern
    ulceration of the mucosa gives rise to this pattern
  • Morphological features of Crohn's disease - strictures & skip lesions
    constriction of lumen due to fibrosis
  • Cobblestone pattern in colonic Crohn's disease - histology image

    due to ulceration
  • What are the microscopic appearances of Crohn's disease?
    • transmural or full thickness inflammation of the bowel wall
    • mixed acute and chronic inflammation, eg polymorphs and lymphocytes
    • preserved crypt architecture
    • mucosal ulceration
    • fissuring ulcers (deep crevices)
    • granulomas (collection of macrophages)
    • fibrosis of the wall which causes strictures
  • What is Ulcerative Colitis (UC)?
    chronic inflammatory bowel disease which only affects the large bowel from rectum to caecum
    unlike Crohn's disease, inflammation is confined to mucosa and sub-mucosa (except in severe cases)
  • What is the epidemiology of Ulcerative Colitis?
    • more common in Western countries with higher prevalence in patients of Jewish descent
    • Can arise at any age but rare before age of 10
    • Bimodal presentation; peaks between 20-25 years with smaller peak in 55-65 year olds
  • What causes Ulcerative colitis?
    • idiopathic (cause unknown)
    • similar to Crohn's disease multiple factors are implicated
    • Genetic predisposition not as well defined as in Crohn's disease
    • high incidence in first degree relatives and high concordance in twins
    • HLA-B27 identified in most patients with UC,
    • No specific infective agent has been identified
    • Environmental factors:
    • Smoking is protective of ulcerative colitis; cessation of smoking may trigger UC
    • NSAIDs worsen UC
    • Antioxidants vitamins A & E found in low levels in UC
  • What are the clinical features of Ulcerative Colitis?
    • intermittent attacks of bloody diarrhoea
    • mucoid diarrhoea
    • abdominal pain
    • low grade fever
    • loss of weight
  • What are the macroscopic features of Ulcerative Colitis?
    affects large bowel from rectum to caecum. can affect:
    • rectum only (proctitis)
    • left sided bowel only (splenic flexure to rectum)
    • whole large bowel (total colitis)
    despite name, no ulcers on endoscopic examination at onset of disease
    • diffuse mucosal involvement which appears haemorrhagic
    • when chronic: mucosa becomes flat with loss of mucosal folds
    Colectomy for UC not responding to treatment. Mucosa looks red and flat.
  • What are the microscopic features of Ulcerative Colitis?
    • Inflammation confined to mucosa
    • Diffuse mixed acute & chronic inflammation
    • Crypt architecture distortion
    • In quiescent (inactive) UC, mucosa may be atrophic with little or no inflammatory cells in lamina propria
  • What are the complications of Ulcerative Colitis?
    1. Toxic megacolon: bowel grossly dilated
    2. patient very ill, bloody diarrhoea, abdominal distention, electrolyte imbalance with hypoproteinaemia
    3. Refractory bleeding
    4. Dysplasia or adenocarcinoma in patients at risk:
    5. UC at an early age
    6. total unremitting UC
    7. Complications invariably lead to surgery; refractory to medical treatment. After 8-10 years of UC, annual screening colonoscopy required.
  • What are the extra-intestinal manifestations of Crohn's Disease and Ulcerative Colitis?
    Ocular: Uveitis, iritis, episcleritis
    Cutaneous: erythema nodosum, pyoderma gangrenosum
    Arthropathies: ankylosing spondylitis
    Hepatic: screlosing cholangitis
  • What are the investigations in Crohn's disease and Ulcerative colitis?
    Full blood counts FBCs
    Urea and electrolytes U&Es
    Inflammatory markers - C reactive protein CRP
    Faecal calprotectin
    Endoscopy and biopsies
    Radiological imaging
    • Barium studies
    • MRI
    • USS
    • CT scan