coeliac disease and inflammatory bowel disease Flashcards
1
Q
what is coeliac disease? 4
A
- 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 a gluten free diet
- Gluten is a protein compound of wheat, rye and barley which is left behind after washing off the starch
- Gluten consists of gliadin and glutenin’s
2
Q
what are the genetic abnormalities of coeliac disease? 4
A
- Associated with HLA-DQ-2 in 95% of patients and HLA-DQ8 in 5%
- The genes are located on chromosome 6p21
- Other coeliac disease genes are under investigation
- Coeliac disease has strong hereditary predisposition affecting 10% of first-degree relatives
3
Q
who gets coeliac disease? 6
A
- Most prevalent in western Europe and USA especially patients with Irish or Scandinavian descent
- Increasing incidence in Africa and Asia
- A lot of patients in the community have undiagnosed coeliac disease- it requires a high index of suspicion
- High prevalence in patients with down’s syndrome, type 1 diabetes mellitus, auto immune hepatitis and thyroid gland abnormalities
- Bimodal presentation in childhood and late thirties
- 20% of patients with coeliac disease are older than 60
4
Q
how does gluten cause coeliac disease? 7
A
- gluten in wheat + small bowel mucosa
- tissue transglutaminase
- diamidates glutamine in gliadin
- negatively charged protein
- IL-15
- natural killer cells + intraepithelial T lymphocytes
- tissue destruction + villous atrophy
5
Q
what happens to the bowel lining when people with coeliac disease eat gluten?
A
Normal small bowel lining has finger-like villi which are destroyed when people with coeliac disease eat gluten
6
Q
What are the symptoms of coeliac disease? 4
A
- Flat mucosa does not absorb nutrients and leads to the symptoms of coeliac disease
- Asymptomatic coeliac disease- detected by a blood test
- Classic coeliac disease
- Atypical coeliac disease
7
Q
Classic coeliac disease with gastrointestinal symptoms? 8
A
- Diarrhoea (smelly, pale and bulky stool but rich in fat- steatorrhea) 45-85%
- Flatulence 28%
- Borborygmus 35-72%
- Weight loss 45% of patients
- In children- failure to thrive
- Weakness and fatigue 78-80%
- Severe abdominal pain 34-64%
- Irritable bowel syndrome
8
Q
Atypical coeliac disease due to extra-interstitial symptoms? 10
A
- Anaemia 10-15%
- Osteopenia and osteoporosis
- Muscle weakness, pins and needles, loss of balance 8-14%
- Itchy skin conditions such as dermatitis hepeitformis 10-20%
- Lack of periods, delayed periods in teenagers, infertility in women and impotence and infertility in men
- Bleeding disorders due to vitamin K deficiency
- Emaciation (being abnormally thin or weak)
- Pot belly due to gaseous distention
- Muscle wasting
- Osteoporosis
9
Q
What are the investigations for coeliac disease? 4
A
- General investigations: FBC U&E, LFTs
- Serology for diagnosis of coeliac disease: tissue transglutaminase IgA, endomysial IgA (connective tissue covering the smooth muscle fibres), deamidated gliadin peptide IgA and IgG, for monitoring compliance to gluten free diet, sero-negative coeliac disease reported in 9% of patients
- HLA-DQ2 and HLA-DQ8 in children with positive TTGA and symptoms to avoid biopsies
- Duodenal biopsies
10
Q
How do routine coeliac disease tests work? 3
A
- They assess tissue damage
- When the small bowel is exposed to gluten there is an over production of the immune system to produce antibodies to the proteins involved in tissue damage
- Antibodies to tissue transglutaminase, endomysium and deamidated gliadin peptide
11
Q
What are the microscopic features of coeliac disease? 7
A
- At least 4 biopsies should be sampled from the duodenum at the upper GIT endoscopy as changes can be patchy
- On microscopy there is:
- Villous atrophy
- Crypt hyperplasia
- Increase in lymphocytes in the lamina propria/ chronic inflammation
- Increase in intraepithelial lymphocytes (IEL)
- Recovery of villous atrophy on gluten free diet
12
Q
What are the complications of coeliac disease? 6
A
- 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
13
Q
What constitutes inflammatory bowel disease? 8
A
- Chron’s disease
- Ulcerative colitis
- Diverticular disease
- Ischaemic colitis
- Drug induced colitis NSAIDS
infective colitis - CD and UC= collectively known as idiopathic inflammatory disease
- Some overlap in aetiology, clinical presentation, morphological features and treatment
- important to distinguish CD from UC because of different complications and different surgical procedures
14
Q
what is Crohn’s disease? 4
A
- an idiopathic chronic inflammatory bowel disease often caused by fibrosis and obstructive symptoms
- can affect any part of the GIT from mouth to anus
- high prevalence in the western world, increased incidence in patients with Jewish origin
- bimodal presentation with peaks in the teens-20s and 60–70-year-olds
15
Q
what causes CD? 3
A
- Exact cause is unknown
- Genetic, infectious, immunologic, environmental, dietary, vascular, smoking, NSAIDs and psychological factors are all implicated
- Defects in mucosal barriers which allow pathogens and other antigens to induce an unregulated inflammatory reaction
16
Q
what are the genetics of CD? 4
A
- Strong scientific evidence for the genetic predisposition to CD
- First degree relatives have a 18% increased risk
- No classical menelian inheritance but polygenic
- NOD2 gene also CARD15 on Chr16 encodes a protein associated with uncontrolled inflammatory response to luminal contents and microbes
17
Q
Is there a possible infectious cause of CD? 2
A
- Because granulomas are present in 65%, mycobacterium paratuberculosis was investigated but never proven
- Other infectious organisms implicated include measles virus, pseudomonas, listeria
18
Q
What environmental factors are implicated in CD? 5
A
- Improved hygiene hypothesis:
- Reduced enteric infections and the ability of the GIT mucosa to develop regulatory responses that would normally limit immune response to pathogens which cause self-limiting infections
- Because of the good hygiene, the mucosa is not immunised to microbes and when exposed to whatever pathogen causes CD is exaggerated in immune response leading to mucosal damage
- Migration from a low-risk population to a high-risk population increases the risk of developing CD
- Cigarette smoke doubles the risk
19
Q
What are the clinical features of CD? 5
A
- Chronic, indolent course punctuated by periods of remission and relapses
- Abdominal pain, relived by opening bowels
- Prolonged non bloody diarrhoea
- Blood may be present if colon is involved
- Loss of weight, low grade fever
20
Q
What is the distribution of CD? 4
A
- Affects any part of the GIT from mouth to anus
- Small bowel alone 40%
- Large bowel alone 30%
- Small and large bowel 30%
21
Q
What are the morphological features of CD? 4
A
- Fat wrapping of the serosa (fat disposition on the anterior surface which is usually fat free)
- Involves the bowel in a segmental manner where the normal bowel is separated from the abnormal bowel to give rise to skip lesions
- Ulceration of the mucosa to give rise to a cobblestone pattern
- Strictures due to fibrosis
22
Q
What are the microscopic appearances of CD? 7
A
- Transmural of full thickness inflammation of bowel wall
- Mixed acute and chronic inflammation (polymorphs and lymphocytes)
- Preserved crypt architecture
- Mucosal ulceration
- Fissuring ulcers (deep crevices)
- Granulomas (collection of macrophages) present in 60-65%
- Fibrosis of the wall
23
Q
what are the complications of CD? 7
A
- Intra-abdominal abscesses
- Deep ulcers lead to fistula= communication between two mucosal surfaces
- Sinus tract- blind ended tracts 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
24
Q
What is ulcerative colitis? 5
A
- Chronic inflammatory bowel disease which only affects the large bowel from the rectum to the caecum
- Inflammatory process is confined to the mucosa and sub-mucosa except in severe cases
- More common in western countries with a higher prevalence in patients of Jewish descent
- Can arise in any age but rare before 10
- Peaks between 20-25 years with smaller peak in 55-65-year-olds
25
Q
what causes UC? 7
A
- Unknown
- Similar to CD, multiple factors are implicated
- Genetic prevalence is not as well defined
- High incidence in first degree relatives
- HLA-B27 identified in most patients
- Similar to CD as no specific infective agent has been identified
- Environmental factors: smoking is protective, NSAIDs exacerbates UC, antioxidants vitamins A and E are found in low levels in UC
26
Q
what are the clinical features of UC? 5
A
- Intermittent attacks of bloody diarrhoea
- Mucoid diarrhoea
- Abdominal pain
- low grade fever
- Loss of weight
27
Q
What are the macroscopic features of UC? 5
A
- Affects the large bowel from the rectum to the caecum
- Can affect the rectum only (proctitis), left sided bowel only (splenic flexure of rectum) or whole large bowel (total colitis)
- 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 and appears red
28
Q
What are the microscopic features of UC? 4
A
- Inflammation confined to the mucosa (black bar)
- Diffuse mixed acute and chronic inflammation
- Crypt architecture distortion
- In quiescent (inactive) UC, the mucosa may be atrophic with little or few inflammatory cells in the lamina propria
29
Q
What are the complications of UC? 6
A
- Invariably lead to surgery
- Refractory to medical treatment
- Toxic megacolon= bowel grossly dilated- patient very ill, bloody diarrhoea, abdominal distention, electrolyte imbalance and hypoproteinaemia
- Refractory bleeding
- Dysplasia or adenocarcinoma in patients at risk (UC at early age, toral unremitting UC)
- After 9-10 years of UC, patients require annual screening colonoscopy
30
Q
What are the extra-intestinal manifestations of CD and UC? 4
A
- Ocular- uveitis, iritis, episcleritis
- Cutaneous- erythema nodosum, pyoderma gangernosum
- Arthropathies- ankylosing spondylitis
- Hepatic- sclerosing cholangitis
31
Q
What are the investigations in CD and UC? 7
A
- FBC
- U and Es
- LFTs
- Inflammatory markers (C reactive protein)
- Faecal Cal protein
- Endoscopy and biopsies
- Radiological imaging- barium studies, MRI, USS, CT
32
Q
Is it important to differentiate UC from CD? 3
A
- Whenever possible yes
- A patient may have a pouch after surgery in UC but not in CD because of risk of reoccurrence
- A pouch is created from the small bowel as a stool reservoir following surgical removal of the large bowel
