Met1

Question 1

1. Give three histologic features of a biopsy of the small intestine from a coeliac patient? (3 mark)

Answer 1

• Flattened mucosa / absence of villi (1 mark)*
• Crypt hyperplasia (1 mark)*
• Increased* intraepithelial lymphocytes (1 mark)

Question 2

1. Cécile is taking Ferrograd, yet her ferritin is low, explain why? (1 mark)

Answer 2

She has malabsorption (in particular iron malabsorption due to flattened mucosa and blockade of iron uptake by hepcidin**), so she is unable to absorb iron supplements such as Ferrograd.

Question 3

1. What is the main gluten component destructive to the small intestinal mucosa? Which cells of the immune system recognise this component? (2 marks)

Answer 3

Gliadin (1 mark) recognised by CD4 T cells (1 mark)

Question 4

1. Explain why total IgA is measured in the blood test. (1 mark)

Answer 4

To exclude IgA deficiency (which would give a false negative result to IgA anti-tTG test, as IgA deficient patients produce IgG anti-tTG).

Question 5

1. Approximately 95% of people with coeliac disease carry one particular MHC molecule. What is this? (1 mark)

Answer 5

HLA-DQ2

Question 6

1. Give one example of a condition leading to (I) secretory diarrhoea and (ii) one for osmotic diarrhoea (2 marks)

Answer 6

(I) Cholera / laxative abuse / bacterial infection (E. Coli)

(ii) lactose intolerance / Ingestion of a poorly absorbed substrate / malabsorption

Question 7

what is Mean Corpuscular volume (MCV)?

Answer 7

• Mean Corpuscular volume (MCV)- a measure of the average volume of a red blood cell.

Question 8

explain mechanism of gluten causing :( in people with CD

Answer 8

• Gliadin resists being broken down by any sorts of enzyme in the small intestine
• When it gets to small intestine, it binds on secretory IgA in mucosal membrane which helps protect enterocytes from toxins and pathogens

•IN COELIAC DISEASED PATIENTS:
- the IgA along with gliadin do not get broken down and are transferred from the apical membrane of the enterocytes down to the basolateral membrane

• This is done because on the apical membrane there is overexpression off Transferrin receptor (TFR) which is usually used to transport iron
• Now the gliadin molecule is in lamina propria
• Here enzyme called tissue transglutaminase (tTG) remove amide group from gliadin to form DEAMIDATED GLIADIN
• Then this deamidated gliadin is taken up by macrophages
• The gliadin is presented on the cell surface membrane by MHC
• Coeliac diseased patients have 1 of 2 types of MHC (because of their alleles). They either have HLA-DQ2 or HLA-DQ8
• The macrophages present gliadin via MHC to CD4 T cells which in turn release inflammatory cytokines like IFN-γ which destroys epithelia of small intestine
• CD4 T cells also activate B cells to produce IgA anti-gliadin, anti-tTG and anti-endomysial* (EMAs)

•CD4 T cells also recruit CD8 T cells which further destroys epithelia of small intestine

Question 9

what can result from CD?

Answer 9

1. As a result:
   
   1. malabsorption -> anaemia & osteomalacia (softening of the bones)
   2. Diarrhoea: caused by unabsorbed chyme sitting in lumen – osmotic effect & draws water into lumen = d

Question 10

explain how you can diagnose CD

Answer 10

1. Duodenal biopsy:
   
   1. Patient must eat gluten for 6 weeks prior to ensure that immune reaction is triggered
2. Blood tests:
   
   1. Anti-tissue transglutaminase Antibody (tTG), IgA: Gliadin, peptide derivative of gluten triggers the development of tTG autoantibodies
   2. Anti-Endomysial Antibodies (EMA), IgA:
      
      1. Almost 100% of patients with active CD have anti-EMA, IgA antibodies
3. Histological samples:
   
   1. Crypt hyperplasia
   2. Villus atrophy
   3. Intraepithelial lymphocytosis

Question 11

why is CD poorly diagnosed?

Answer 11

1. can suffer from latent CD, which can be triggered by activation of genes for CD

Question 12

how can u treat CD?

Answer 12

1. Gluten free diet (no wheat, barley, rye)
2. Fe & Folic acid given for 1^st three months
3. Reassess symptoms after 8-12 weeks

Question 13

symptons and signs of CD?

Answer 13

Symptoms

Weight loss
Fatigue
Weakness
Abdominal pain
Bloating
Flatulence
Loose stools
Steatorrhoea
Failure to thrive (babies and young children)

Signs

Mouth ulcers
Angular stomatitis
Abdominal distension
Ecchymosis
Muscle wasting
Neuropathy

Question 14

What are extra intestinal mainfestations of CD? [1]

Name 3 extra intestinal mainfestations of CD [3]

Answer 14

Extra-intestinal manifestations of coeliac disease occur as a secondary consequence of malabsorption.

Anaemia

Anaemia occurs in 10-15% of patients. Typically this is due to malabsorption of iron and folate. A such a mixed megaloblastic/microcytic picture may be seen. In severe disease affecting the ileum, B12 malabsorption may occur.

Osteoporosis

Multiple mechanisms are responsible for the osteoporosis seen in coeliac disease. Malabsorption of calcium and vitamin D deficiency contribute. Calcium may also be sequestered to poorly absorbed fatty acids.

Dermatitis herpetiformis

Dermatitis herpetiformis is a blistering skin condition that is strongly associated with coeliac disease. The rash is intensely pruritic. It may be managed with dapsone and a gluten free diet.

Question 15

what are the two anitbody tests do for test for CD?

Answer 15

IgA Anti-tissue transglutaminase (tTGA)

IgA Anti-endomysial (EMA)

Question 16

An estimated 5% of patients with coeliac disease will not respond to a Gluten-free diet. In the majority of cases (>90%), this is due to WHAT? [1]

Answer 16

An estimated 5% of patients with coeliac disease will not respond to a Gluten-free diet. In the majority of cases (>90%), this is due to inadvertant gluten ingestion.

Question 17

what is refractory coeliac disease?

Answer 17

Refractory coeliac

Refractory coeliac disease is defined an persistent or recurrent malabsorptive symptoms and villous atrophy (on duodenal biopsies) despite adherence to a gluten free diet for at least 6-12 months.

Question 18

why does gluten cause CD?

Answer 18

gluten broken down into prolamins (gliadin, secalin, hordein) which are resistant to breakdown by pepsin/chymotrypsin

Question 19

coeliac’s disease and anaemia?

• malabsorption of what causes microcytic and macrocytic anaemia? [2]

Answer 19

microcytic anaemia caused by Fe malabsorption

macrocytic anaemia caused by folate malabsorption

in PBL1 pt has microcytic anaemia (MCV 76.4 fL) altho she is also folate deficient

Question 20

how is a duodenal biopsy taken for CD?

Answer 20

pt sedated and examined in a post absorptive state

fibre optic tube used to visualise GIT mucosa

biopsy then taken for analysis

Question 21

implications for acid/base homeostasis with severe diarrhoea ?

Answer 21

metabolic acidosis brought about by HCO3- loss (therefore included in ORT) thru stools