Theme 1 - Part I

Question 1

Coeliac disease definition [3]

Answer 1

Autoimmune mediated disease of the SI

Ingestion of gluten in genetically predisposed individuals

Malabsorption with cessation of symptoms on gluten free diet

Question 2

Coeliac disease genetics [3]

Answer 2

HLA - DQ2 and HLA-DQ8

Chr 6p21

Question 3

Coeliac disease prevalence [4]

Answer 3

Western Europe & US = Irish/Scandinavian

Down’s syndrome, Type I diabetes mellitus, auto-immune hepatitis and thyroid gland abnormalities

Can present with abnormal liver function tests due to auto-immune hepatitis

Question 4

Coeliac disease process [6]

Answer 4

Tissue transglutaminase -> Diaminates glutamine in gliadin -> -ve charged protein -> IL-15 -> NK cells and intraepithelial T lymphocytes -> Tissue destruction and villous atrophy

Question 5

Coeliac disease presentation - SODA

Answer 5

Short stature & failure to thrive in children
Osteopenia and osteoporosis – calcium and Vitamin D deficiency
Diarrhoea : smelly & bulky stool, rich in fat (steatorrhoea)
Anaemia – folate and Fe deficiency

Weight loss and fatigue

Question 6

Coeliac disease classification [4]

Answer 6

Classical - malabsorption 
Non-classical = outside GI tract
- Constipation 
- Heartburn (Dyspepsia) & Vomiting 
- Recurrent miscarriage

Question 7

Coeliac disease investigation [5]

Answer 7

FBC, U & Es, LFTs

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

Sero-negative coeliac disease reported in 6.4-9% of patients

HLA D2 & HLA DQ8 in children with positive TTGA and symptoms to avoid biopsies

Question 8

Microscopic features of Coeliac disease [6]

Answer 8

At least 4 biopsies sampled from duodenum at upper GIT endoscopy

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

Question 9

Complications of coeliac disease - ACID-ER

Answer 9

Adenocarcinoma - high risk
Complications reduced by diet
Infertility
Dermatitis hepetiformis

Enteropathy associated T-cell lymphoma
Refractory coeliac disease despite strict adherence to gluten free diet

Question 10

Crohn’s disease definition [3]

Answer 10

Idiopathic, chronic IBD

Often complicated by fibrosis and obstructive symptoms

Can affect any part of the GIT from mouth to anus

Question 11

Epidemiology of CD [3]

Answer 11

High prevalence in the Western world with increased incidence in patients of Jewish origin

Increasing incidence in Africa, South America and Asia

Bimodal presentation with peaks in the teens-20s and 60-70 year age groups

Question 12

Genetics of CD [3]

Answer 12

First degree relatives have 13-18% increased risk of developing CD with a 50% concordance in monozygotic twins

Polygenic

NOD2 (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

Question 13

NOD2 [3]

Answer 13

(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

Question 14

Possible infectious cause of CD

Answer 14

Because granulomas are present in 60 -65% of patients, mycobacterium para-tuberculosis was extensively investigated as a possible cause but never proven

• migration
• smoking

Question 15

Clinical features of CD [5]

Answer 15

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

Question 16

Distribution of CD

Answer 16

Small bowel alone – 40%
Large bowel alone – 30%
Small and large bowel – 30%

Question 17

Morphological features of CD [4] FUST

Answer 17

Fat wrapping of the serosa - noted during surgery

Ulceration with a cobblestone pattern

Strictures due to fibrosis

Typically segmental morphology→normal bowel separated by abnormal bowel = skip lesions

Question 18

Microscopic

appearances of CD

Answer 18

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

Question 19

Complications of CD

Answer 19

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 strictures caused by increased fibrosis
Perianal fistula and sinuses
Risk of adenocarcinoma, but not as high as in UC

Question 20

Ulcerative Colitis definition [3]

Answer 20

Chronic inflammatory bowel disease

Only affects the large bowel from the rectum to the caecum

Confined to mucosa and sub-mucosa

Question 21

Epidemiology of UC [4]

Answer 21

More common in Western countries with higher prevalence in patients of Jewish descent
Less frequent in Africa, Asia and South America
Can arise at any age but rare before the age of 10
Peaks between 20-25 years with a smaller peak in 55-65 year age groups

Question 22

Causes of UC [4]

Answer 22

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

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

Question 23

Clinical Features of UC [5]

Answer 23

Intermittent attacks of bloody diarrhoea 
Mucoid diarrhoea
Abdominal pain
Low grade fever
Loss of weight

Question 24

Macroscopic features of UC [4]

Answer 24

Can affect the rectum only (proctitis), left sided bowel only ( splenic flexure to rectum) or whole large bowel = total colitis

No ulcers in early disease

Diffuse mucosal involvement which appears haemorrhagic
With chronicity, the mucosa becomes flat with shortening of the bowel

Question 25

Microscopic features of UC [4]

Answer 25

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

Question 26

Complications of UC

Answer 26

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

Question 27

Extra-intestinal manifestations of CD & UC [4]

Answer 27

Ocular - uveitis, iritis, episcleritis
Cutaneous - erythema nodosum, pyoderma gangrenosum
Arthropathies - ankylosing spondylitis and others
Hepatic - screlosing cholangitis

Question 28

Investigations in CD & UC

Answer 28

FBC
U & Es
LFTs
Inflammatory markers – C reactive protein (CRP)
Endoscopy and biopsies
Radiological imaging
Barium  studies
MRI
USS
CT Scan