T1 L11 Coeliac disease & IBD

Question 1

What is coeliac disease?

Answer 1

A gluten sensitive enteropathy or coeliac sprue
Autoimmune mediated disease of the small intestine that is triggered by the ingestion of glucose which leads to malabsorption

Question 2

What is gluten?

Answer 2

Protein component of wheat, rye and barley which is left behind after washing off starch
Consists of gliadin & glutenin

Question 3

There is a high prevalence of coeliac disease in what groups of patients?

Answer 3

Down’s syndrome
Type I diabetes mellitus
Auto-immune hepatitis
Thyroid gland abnormalities

Question 4

What is the mechanism for coeliac disease?

Answer 4

1) Gluten in wheat plus small bowel mucosa
2) Tissue transglutaminase produced
3) Diamidates glutamine in gliadin
4) Negatively charged protein
5) IL-15
6) Natural killer cells & intraepithelial T lymphocytes
7) Tissue destruction & villous atrophy

Question 5

How does coeliac disease present?

Answer 5

The hallmark is the malabsorption of nutrients
Short stature & failure to thrive in children
Diarrhoea & steatorrhoea
Weight loss & fatigue
Anaemia
Osteopenia & osteoporosis

Question 6

What are the classifications of coeliac disease?

Answer 6

Classical - malabsorption symptoms
Non-classical including symptoms outside GI tract
Subclinical - detected with blood tests

Question 7

What symptoms are there for non-classical coeliac disease?

Answer 7

Constipation, bloating, alternate bowel habits
Heartburn
Nausea
Vomiting
Dyspepsia
Recurrent miscarriages / infertility

Question 8

What investigations are done for coeliac disease?

Answer 8

General investigations - FBC, urea & electrolytes, LFT
Serology for diagnosis
HLA DQ2 & HLA DQ8 in children with positive TTGA & symptoms to avoid doing a biopsy
Duodenal biopsies

Question 9

What does serology look for in coeliac disease?

Answer 9

Tissue transglutaminase IgA (TTGA)
Endomysial IgA - connective tissue covering smooth muscle fibres
Deamidated gliadin peptide IgA & IgG
Also used to monitor adherence to gluten free diet
Sero-negative coeliac disease reported

Question 10

What routine coeliac disease tests are carried out?

Answer 10

Tissue damage tests
When the small bowel is exposed to gluten there is an overreaction of the immune system to produce antibodies to proteins involved in the tissue damage: tissue transglutaminase, endomysium, deaminated gliadin peptide

Question 11

What are the microscopic features of coeliac disease?

Answer 11

At least 4 biopsies have to be sampled from the duodenum via an upper GI endoscopy as the changes can be patchy

Villous atrophy
Crypt hyperplasia
Increase in lymphocytes in lamina propria / chronic inflammation
Increase in intraepithelial lymphocytes
Recovery of villous abnormality on a gluten-free diet

Question 12

What are the complications associated with coeliac disease?

Answer 12

Enteropathy associated T cell lymphoma
High risk of adenocarcinoma of the small bowel & other organs such as large bowel, oesophagus, pancreas
May be associated with dermatitis herpetiformis
Infertility & miscarriage
Refractory coeliac disease despite strict adherence to gluten free diet

Question 13

What does inflammatory bowel disease constitute?

Answer 13

Crohn's disease
Ulcerative colitis
Diverticular disease
Ischaemic colitis
Drug-induced colitis
Infective colitis

Question 14

What is Crohn’s disease?

Answer 14

Idiopathic, chronic inflammatory bowel disease that is often complicated by fibrosis & obstructive symptoms.
It can affect any part of the GI tract from the mouth to the anus

Question 15

What is the cause of Crohn’s disease?

Answer 15

Exact causes are unknown
Genetic
Infectious
Immunologic
Environmental
Dietary
Vascular
Smoking 
NSAIDs
Psychological factors
Defects in mucosal barrier

Question 16

What are the genetics of Crohn’s disease?

Answer 16

Evidence for a genetic predisposition
No classical mendelian inheritance but it is polygenic
NOD2

Question 17

What is NOD2?

Answer 17

Nucleotide binding domain
Also known as IBD1 gene on chromosome 16
Encodes a protein that binds to intercellular bacterial peptidoglycans to activate nuclear factor kappa B. This inhibits the normal immune response to luminal microbes leading to uncontrolled inflammation

Question 18

What is the infectious cause of Crohn’s disease?

Answer 18

Granulomas present in 60-65% of patients
Mycobacterium paratuberculosis extensively investigated
Other infectious organisms: measles virus, pseudomonas, listeria

Question 19

What are the environmental factors that may cause Crohn’s disease?

Answer 19

Improved hygiene hypothesis
Reduces enteric infections & reduces ability of GI tract mucosa to develop regulatory processes that normally limit immune response to pathogens which cause self-limiting infections
Migration from a low to high risk population increases risk
Smoking doubles risk

Question 20

What are the clinical features of Crohn’s disease?

Answer 20

Chronic, indolent course punctuated by periods of remission & relapses
Abdominal pain relieved by opening bowels
Prolonged, non-bloody diarrhoea
Blood may be present if colon is involved
Loss of weight, low grade fever

Question 21

What is the distribution of Crohn’s disease?

Answer 21

Any part of GI tract from mouth to anus
Small bowel only - 40%
Large bowel only - 30%
Small & large bowel - 30%

Question 22

What are the morphological features of Crohn’s disease?

Answer 22

Fat wrapping of serosa
Typically segmented morphology
Ulceration with cobblestone pattern
Strictures due to fibrosis

Question 23

What is the microscopic appearance of Crohn’s disease?

Answer 23

Transmural or full thickness inflammation of bowel wall
Mixed acute & chronic inflammation
Preserved crypt architecture
Mucosal ulceration
Fissuring ulcers
Granulomas
Fibrosis of the wall

Question 24

What are the complications of Crohn’s disease?

Answer 24

Intra-abdominal abscesses
Deep ulcers lead to fistula
Sinus tract
Obstruction due to adhesion
Obstruction due to strictures caused by increased fibrosis
Perianal fistula & sinuses
Risk of adenocarcinoma

Question 25

What is ulcerative colitis?

Answer 25

Chronic inflammatory bowel disease that only affects large bowel from rectum to caecum
Inflammatory process is confined to mucosa & submucosa except in severe cases

Question 26

What is the cause of ulcerative colitis?

Answer 26

Cause is unknown
Multiple factors are implicated
Genetics are not as well defined

Question 27

What are the environmental factors of UC?

Answer 27

Smoking is protective
NSAID exacerbate UC
Antioxidants vitamin A & E found in low levels

Question 28

What are the clinical features of UC?

Answer 28

Intermittent attacks of bloody diarrhoea
Mucoid diarrhoea
Abdominal pain
Low grade fever
Weight loss

Question 29

What are the macroscopic features of UC?

Answer 29

Affects large bowel from rectum to caecum
Can affect rectum only (proctitis), left side (splenic flexure to rectum) or whole large bowel (total colitis)
No ulcers on endoscopic examination in early disease
Diffuse mucosal involvement which appears haemorrhagic
In chronic case the mucosa becomes flat with shortening of the bowel

Question 30

What are the microscopic features of UC?

Answer 30

Inflammation confined to mucosa
Diffuse mixed acute & chronic inflammation
Crypt architecture distortion
In inactive UC the mucosa may be atrophic with little or few inflammatory cells in lamina propria

Question 31

What are the complications of UC?

Answer 31

Leads to surgery
Refractory to medical treatment
Toxic megacolon 
Refractory bleeding
Dysplasia or adenocarcinoma

Question 32

What is toxic megacolon?

Answer 32

Bowel is grossly dilated & haemorrhage
Patient is very ill
Bloody diarrhoea
Abdominal distention
Electrolyte imbalance with hypoproteinaemia

Question 33

What are the extra-intestinal manifestations of CD & UC?

Answer 33

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

Question 34

What investigations are done in UC?

Answer 34

FBC
Urea & electrolytes
Liver function tests
Inflammatory markers - C reactive protein
Endoscopy & biopsies
Radiological imaging - barium studies, MRI, U/S, CT

Question 35

Why is it important to differentiate CD from UC?

Answer 35

A patient may have a pouch after surgery in UC but not in CD because of the risk of recurrence
A pouch is created from the small bowel as stool reservoir following removal of large bowel.