MET 1 - Mother Losing Weight

Question 1

Getting familiar with the scenario

Answer 1

Mrs Cécile Hilliac is a 26-year-old female who has presented to her GP with aches and pains, particularly in her legs, tiredness, irritability, and weight loss. She has a 6-month-old daughter and had been anaemic through pregnancy. She is currently taking Ferrograd, 1 tablet daily. She recalled she had loose stools during her childhood, but other than this, there is little else in her past medical history to explain her condition. Dietary intake is satisfactory. Her BMI is 24. She read some articles on the Internet and thinks she must have IBS. The GP requests some blood tests, which are showed below:

After reviewing the blood results, her doctor refers Cécile to a gastroenterologist at Royal London Hospital. The consultant then performs an upper GI endoscopy to obtain duodenal biopsies. These are fixed in formalin and processed in the pathology laboratory. The histology shows very characteristic features and, together with the IgA antibodies results, confirm the diagnosis. Cécile is then referred to a dietician who recommends a specific diet. Although she finds adhering to the diet difficult, after a few weeks, Cécile starts to feel better and reports increased energy levels, no further pain and her weight has improved. Her mood has also improved dramatically. Six months later she goes back to the GP who takes a blood sample and her bloods have normalised. To understand more about her disease, Cécile is searching the Internet for information about absorption of gluten and gut immunology. She wonders why it is possible that she was not diagnosed before.

Question 2

Where is the biopsy taken from in the scenario (duodenal biopsy)?

Answer 2

Duodenum

Mucosal layer

Question 3

Name 3 features for coelic disease seen in histology

Answer 3

• Flattened villi
• Crypt hyperplasia
• Lymphocyte infiltration in lamina propria

Question 4

Why is she still tired after taking Ferrograd?

Answer 4

Common symptom of anaemia
She has microcytic anaemia as the Hb is low and MCV is less than 80
She has anaemia due to malabsorption

Question 5

What MHC molecule doe 95% of CD patients have?

Answer 5

HLA DQ2

Question 6

What is the main component that is destructive to the small intestinal mucosa? What cells recognise this component?

Answer 6

Alpha gliadine

CD4 +ve T cells

Question 7

Why is IgA measured in the blood test?

Answer 7

Some patients have generalised IgA deficiency

If IgA tTG is not high it can be a false positive as some patients may not produce any IgA at all let alone IgA tTG

Question 8

Why was she not diagnosed earlier?

Answer 8

• amount of gluten previously eaten
• time for atrophy
• variety of symptoms

Question 9

Give three histologic features of a biopsy of the small intestine from a coeliac patient?

(3 mark)

Answer 9

Flattened mucosa with absence of villi (1 mark)

Crypt hyperplasia (1 mark)

Increased intraepithelial lymphocytes (1 mark)

Question 10

Testing for what two antibodies gives a high sensitivity and specificity for the diagnosis of untreated coeliac disease?

1 mark

Answer 10

Endomysial (EMA) (1/2)
Tissue transglutaminase (tTG) antibodies (1/2) 

Both are IgA

Question 11

Cécile is taking Ferrograd, yet her ferritin is low, explain why?

1 mark

Answer 11

She has malabsorption (in particular iron malabsorption), so she is unable to absorb iron supplements such as Ferrograd.

Question 12

What is the main gluten component destructive to the small intestinal mucosa? Which cells of the immune system recognise this component?

2 marks

Answer 12

α –Gliadin recognised by CD4 T cells.

Question 13

Explain why total IgA is measured in the blood test.

1 mark

Answer 13

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

Question 14

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

(1 mark)

Answer 14

HLA-DQ2

Question 15

What is the general structure of the gut wall? (enterocytes/villi etc)

Answer 15

Small intestine
Villi
Villi are lined with enterocytes

Enterocytes are lined with microvilli on the apical surface which create the brush border

Question 16

What happens with carbohydrate digestion?

Answer 16

Broken down by the brush border enzymes into glucose, lactose and galactose

Question 17

Where is iron absorbed?

Answer 17

Iron is predominantly absorbed in the duodenum at the start of the small intestine

DNT1 = membrane protein in the brush border

Question 18

How is iron stored? What happens if it isn’t stored?

Answer 18

Stored as Ferritin and stays in the cell until the cell dies

If not stored, it is converted into Fe3+ and bound to transferrin

Question 19

What is the pathophysiology of Coelic’s Disease?

Answer 19

1. Gliadin peptides are resistant to absorption so remains in lumen
2. In CD patients gliadin is bound to IgA and crosses the enterocytes from the apical to basolateral membrane into the lamina propria
3. The gliadin is deamidated by tTG
4. Deamidated gliadin is engulfed by macrophages and binds to the APC MHC Class II molecules (linked to HLA DQ2/8)
5. Cytotoxic T cells are activated and activate B cells
6. CD4 T cells produce cytokines that cause villous destruction, Killer CD8 T cells kill the epithelial cells and B cells produce antibodies (Anti tTG, Anti EMA, anti gliadine)

Question 20

Name 5 signs and symptoms of Coelic’s Disease?

Answer 20

Diarrhoea
Failure to thrive
Unexplained nausea and vomitting
Prolonged fatigue
Recurrent abdominal pain, cramping, distension
Sudden unexpected weight loss
Unexplained iron deficiency anaemia

Osteoporosis
Dermatitis herpetiformis (skin condition linked to coelics disease)

Question 21

What is formalin?

Answer 21

Helps fix the specimen to slides (solution of aldehyde and water)

Question 22

What is the formula to calculate the MCV?

Answer 22

HCT X10 / estimated RBCs

Question 23

What does a low MCV indicate?

Answer 23

Small RBCs

Microcytic anaemia

Question 24

What is the structure of enterocytes? What type of cells are they?

Answer 24

Enterocytes are the most abundant epithelial cells in the SI
They are simple columnar cells
They have microvilli on the apical surface

Question 25

What happens at the brush border? What helps this process? How are they structured?

Answer 25

Place of terminal digestion
The microvilli have enzymes called brush border enzymes

The brush border enzymes are anchored to the plasma membrane as integral membrane proteins

Question 26

What happens at fat digestion?

Answer 26

Emulsified by bile

Broken down further by lipases

Hydrolysis forms micelles of fatty acids and glycerol

Question 27

What happens at protein digestion?

Answer 27

Broken down by pepsin and trypsin and other proteases

Forms amino acids at the brush border

Question 28

What is the component of gluten that is immunogenic?

Answer 28

Gliadine

33 amino acid peptide

Question 29

What is ferritin?

Answer 29

Blood cell protein that produces iron

Question 30

What is Coelic’s Disease?

Answer 30

Coelic’s Disease is an autoimmune disorder when the immune system mistakenly thinks gluten as a foreign invader and begins to break down the microvilli enterocyte wall

Question 31

What is alkaline phosphatase a marker of?

Answer 31

Marker for bone tissue production

Question 32

Why is alkaline phosphatase increased in Coelic’s Disease?

Answer 32

Due to bone softening due to Calcium and Vit D deficiency due to poor absorption

Indicative of osteomalasia

Question 33

What HLA molecule is Coelic’s commonly associated with?

Answer 33

HLA DQ2

HLA DQ8

Question 34

Which 2 antibodies do you test for in Coelic’s Disease?

Answer 34

• Anti tTG

- Anti EMA

Question 35

Where is gluten found?

Answer 35

Wheat, barley, rye, oats

Question 36

What is the Mean Corpuscular Volume?

Answer 36

Average volume of RBC

Question 37

How common is Coelic’s Disease?

Answer 37

1% of the population