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Gastrointestinal System > 89-92. Coeliac disease > Flashcards

89-92. Coeliac disease Flashcards

1
Q

What is coeliac disease? What are the features of the disease?

A

Gluten sensitive enteropathy
Small intestinal villous atrophy that resolves when gluten is withdrawn from the diet
Inappropriate T cell response in genetically susceptible individuals

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2
Q

What is the most toxic moiety of gliadin (present in wheat)?

A

alpha-gliadin

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3
Q

What is the gene which genetically predisposes people to coeliac disease?

A

HLA-DQ2 (95%)

The rest are HLA-DQ8

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4
Q

What causes coeliac disease?

A

Infection with adenovirus 12 in genetically susceptible individuals

Peptide on alpha-gliadin is similar to that within the Eb1 portion of the virus

This leads to cross reactivity with alpha-gliadin and development of coeliac disease

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5
Q

How does alpha-gliadin produce an inflammatory response in coeliac patients?

A

Digestion of alpha-gliadin produces a stable peptide, which is absorbed intact to the lamina propria

Exposure to TTG (an autoantibody) from damaged epithelium leads to deamination of glutamine residues

This enables bonding to HLA-DQ2 and the activation of pro-inflammatory T cell responses

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6
Q

What are the 7 main presentations associated with coeliac disease?

A
  1. Symptomatic (may be provoked by infection, pregnancy or surgery)
    - diarrhoea, bloating, flatulence, abdominal discomfort
  2. Chronic or recurrent iron deficiency anaemia (50% of coeliacs present with this)
  3. Nutritional deficiency (i.e. vit B12, folate)
  4. Reduced fertility/amenorrhoea
  5. Osteoporosis
  6. Unexplained raised AST/ALT
  7. Neurological/psychiatric symptoms
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7
Q

How many litres of fluid does the small intestine absorb daily?

A

6 litres

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8
Q

What is the surface area of the small intestine?

A

200m^2

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9
Q

What are the pathological changes of the small intestine in coeliac disease?

A

Mucosal inflammation - can vary based on severity & extent
Mild proximal disease typically occurs
Mucosal damage may be patchy
Loss of villous height
- villi may be completely flat or short and broad (sub total villous atrophy)

No change in total mucosal thickness as crypts become elongated (hypertrophy)

Increased plasma cells and intraepithelial lymphocytes (IELs)

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10
Q

Describe the clinical features related to the small bowel in coeliac disease

A

Diarrhoea - steatorrhoea, watery and high volume, rarely bloody
Weight loss
Malabsorption
abnormal pain/vomiting

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11
Q

What are the indicators of small bowel disease?

A

Malabsorption/electrolyte imbalances

  • folate
  • vit D/ calcium —–> osteoporosis
  • Vit K/ coagulopathy
  • magnesium
  • vit B12

Chronic/recurrent IDA

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12
Q

What 80% of iron is incorporated into red cell haemoglobin?

A

80%

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13
Q

How many mg of iron is required daily for the rate of renewal of RBCs?

A

20mg

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14
Q

What is the RDA of iron, including pregnant women?

A

8-18mg

27 in pregnancy

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15
Q

How many mg of iron is lost per day and what causes this loss?

A

1mg lost through sloughing of cells from skin and mucosal surfaces, including the lining of the GI tract

In menstruation, this increases to 2mg per day

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16
Q

Where is iron absorption most predominant?

A

Duodenum and proximal jejunum

17
Q

Why is more iron absorbed in the duodenum and upper jejunum than other areas?

A

At physiological pH, iron is rapidly oxidised from the ferrous iron into insoluble ferric iron

Gastric acid lowers the pH, and when present in the duodenum this increases the solubility of iron for enhanced uptake

18
Q

What enhances uptake of iron?

A

Vitamin C and citric acid

19
Q

What inhibits the uptake of iron?

A

Phytates and tannins (tea)

20
Q

What are tested in serology for the diagnosis of coeliac disease?

A 
IgA tTG (tissue transglutaminase antibody)
IgA EMA (antiendomysial Ab)

TTG more sensitive in adults, with EMA more specific

21
Q

What can be used to monitor patient compliance?

A

Seroconversion (the length of time it takes for an antibody to develop) with gluten free diet

22
Q

What may appear on endoscopy of a patient with coeliac disease?

A 
Scalloping of the folds
Insufficient amount of folds
Music pattern "cracked mud"
Prominent submucosal blood vessels
Nodular pattern to the mucosa

May also appear NORMAL

23
Q

How are biopsies used to diagnose coeliac disease?

A

Taken from distal duodenum
Minimum of 4 biopsies
Biopsies from duodenal bulb may improve diagnosis
Must be on gluten rich diet

24
Q

If there is villous atrophy with no coeliac serology, what do you check for?

A

IgA selective deficiency (in 2-5%)

25
Q

What are rarer causes of villous atrophy without coeliac serology?

A 
Giardiasis (parasitic disease) - most common parasite infection in humans
CVID (common variable immune deficiency)
Radiation enteritis
Crohn's disease
lymphoma
Whipple's disease
Tropical Sprue
HIV enteropathy
Chronic ischaemia
NSAIDs
26
Q

What are the coeliac related diseases?

A

Dermatitis herpetiformis
T1DM - NICE advise to screen all patients
Thyrotoxicosis (hyperthyroidism)
Addison’s disease (not enough cortisol)

27
Q

What are features of dermatitis herpetiformis?

A

Itchy rash on exterior surfaces
90% villous atrophy
Gluten sensitive/dapsone

28
Q

What foods should coeliacs avoid and what foods can they eat?

A

Avoid: wheat, barley, rhye

Can eat: Oats*, rice and maize
Should continue to eat dairy to avoid hypolactasia (50%)

*Debate as to whether or not coeliacs can eat oats

29
Q

What % show symptomatic improvement within 2-52 weeks?

A

70%

30
Q

How long does it take to show improvement in histology?

A

3-12 months

31
Q

What are the 4 main complications of coeliac disease?

A

Osteoporosis
Malignancy
Recurrent coeliac disease
Infection

32
Q

What may cause infection in coeliacs?

A 
Functional hyposplenism - defective immune responses to:
Encapsulated organisms
Pneumococcal
Haemophilus influenzae
Meningococcus
Vaccinations
33
Q

What % of coeliacs develop osteoporosis and why?

A

25%
Low BMI
Calcium and vitamin D deficiency

(consider DEXA at diagnosis and supplementation)

34
Q

What is refractory coeliac disease?

A

Recurrent malabsorptive symptoms and villous atrophy despite strict adherence to a gluten free diet for at least 6-12 months in the absence of other causes of non-responsive treated coeliac disease and overt malignancy.

35
Q

What are the outcomes and treatment for patients with refractory coeliac disease 1 (RCD1) - villous atrophy with normal immunophenotype?

A

96% 5 year survival rate

Treated with steroids/azathiopine (over 75% response)

36
Q

What are the outcomes for RCD2 - villous atrophy with abnormal immunophenotype?

A

58% 5 year survival rate

60-80% progression onto EATL (enteropathy associated T cell lymphoma) at 5 years

37
Q

What are the clinical features of EATL, the treatment and survival rate?

A

Weight loss, night sweats, itch, overt/occult GI bleeding, venous thromboembolism
Often advanced and incurable
Chemotherapy and autologous stem cell Tx
Poor response, 8-20% 5 year survival

38
Q

What are the main features of small bowel adenocarcinoma?

A 
Rare -13% coeliac, 7% Crohns
58% survival at 30 months
Male more than female
55% present with obstruction
Mean time from symptoms to diagnosis - 14 months

Gastrointestinal System (29 decks)

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