Immuno: Malabsorption CPC

Question 1

List three causes of microcytic anaemia.

Answer 1

• Iron deficiency
• Thalassaemia trait
• Anaemia of a chronic disease

Question 2

What is anisopoikilocytosis and which type of anaemia is it associated with?

Answer 2

• Variatios in size and shape of cells
• Associated with iron deficiency anaemia (and thalassaemia trait to a lesser degree)

Question 3

What is basophilic stippling? List some causes.

Answer 3

• Basophilic appearance of red blood cells caused by the presence of aggregated ribosomal material
• Causes: beta-thalassaemia trait, lead poisoning, alcoholism, sidroblastic anaemia

Question 4

Which condition do hypersegmented neutrophils tend to be present in?

Answer 4

Megaloblastic anaemia

Question 5

List some causes of megaloblastic anaemia.

Answer 5

• B12 deficiency
• Folate deficiency
• Drugs

Question 6

In which conditions might you see target cells (codocytes)?

Answer 6

• Iron deficiency
• Thalassaemia
• Hyposplenism
• Liver disease

NOTE: target cells have a high SA: V ratio

Question 7

What are Howell-Jolly bodies? Which condition are they associated with?

Answer 7

• Nuclear remnants present within red blood cells
• Present in hyposplenism

Question 8

List some causes of iron deficiency.

Answer 8

• Blood loss (major cause)
• Poor diet
• Malabsorption
• Combinations of the above

Question 9

List some causes of B12 and folate deficiency.

Answer 9

• Poor diet
• Malabsorption
• Pernicious anaemia

Question 10

List some causes of hyposplenism.

Answer 10

• Absent spleen: therapeutic, trauma
• Poorly-functioning spleen: inflammatory bowel disease, Coeliac disease, sickle cell disease, SLE

Question 11

Which deficienceies are typically seen in Coeliac disease?

Answer 11

• Iron
• B12
• Folate
• Fat
• Calcium

Question 12

Which deficiencies are typically seen in Crohn’s disease?

Answer 12

• B12
• Bile salts

Question 13

Which deficiencies are typically seen in pancreatic disease?

Answer 13

• Fat
• Calcium
• B12

Question 14

Which investigatio are typically performed in Coeliac disease?

Answer 14

• CRP and ESR
• Serological tests
• Upper GI endoscopy and distal duodenal biopsy (GOLD STANDARD)

Question 15

Which gene locus does the heritability of coeliac disease tend to frequently map to?

Answer 15

MHC complex gene loci

Question 16

Which HLA alleles are particularly common in patients with coeliac disease?

Answer 16

• HLA-DQ2 (80%) - DQA1*0501 and DQB1*02 alleles
• HLA-DQ8

Question 17

Describe the T cell response to gluten in coeliac disease.

Answer 17

• Peptides from gluten (gliadin) are deamidated by tissue transglutaminase
• Deamidated gliadin is taken up by antigen-presenting cells and presented via HLA molecules to CD4+ T cells
• CD4+ T cell activation results in secretion of IFN-gamma and may increase IL-15 secretion
• These cytokines promote activation of intra-epithelial lymphocytes (gamma-delta T cells)
• The intraepithelial lymphocytes will kill epithelial cells via the NKG2D receptor (normally recognises the stress protein MICA)

Question 18

Describe the B cell response to gluten in coeliac disease.

Answer 18

• B cells will process gluten antigens and present it via HLA molecules to CD4+ T cells
• The primed T cells will provide help to the B cells via CD40L: CD20 to allow B cells to undergo germinal centre reactions
• B cells undergo isotype switching and affinity maturation to become memory cells and plasma cells which produce antibodies against gliadin

Question 19

Which type of anti-gliadin antibodies may be tested when investigating coeliac disease?

Answer 19

IgA antibodies

NOTE: it is not a very sensitive test and is outdated

Question 20

B cells produce antibodies against tissue transglutaminase. Where is tTG expressed?

Answer 20

On endomysial cells

So, antibodies can be detected as anti-endomysial cell antibodies

Question 21

What important test should be performed before checking anti-tTG and anti-endomysial antibody levels?

Answer 21

• IgA levels
• IgA deficiency can produce false-negative results

Question 22

What are the characteristic histological features of coeliac disease?

Answer 22

• Subtotal villous atrophy with crypt hyperplasia
• Intra-epithelial lymphocytes

Question 23

Describe the villous atrophy seen in coeliac disease.

Answer 23

• Normal villous: crypt ratio is about 2-4: 1
• In coeliac disease, villous height is reduced and crypts become hyperplastic
• This leads to a reduced or reversed villous: crypt ratio
• The mucosa remains the same thickness due to crypt hyperplasia
• However, decreased surface area (due to villous atrophy) leads to malabsorption

Question 24

List some other causes of villous atrophy.

Answer 24

• Giardiasis
• Tropical sprue
• Crohn’s disease
• Radiation/chemotherapy
• Nutritional deficiencies
• Graft-versus-host disease
• Microvillous inclusion disease
• Common variable immunodeficiency

Question 25

How many intraepithelial lymphocytes would you expect to see in coeliac disease?

Answer 25

More than 20 IELs/100 epithelial cells NOTE: normal would be \< 20

Question 26

List some other causes of high intraepithelial lymphocytes.

Answer 26

* Dematitis herpetiformis * Giardiasis * Cows' milk protein sensitivity * IgA deficiency * Tropical sprue * Post-infective malabsorption * Drugs (NSAIDs) * Lymphoma

Question 27

What does the interpretation of the histological report in suspected coeliac disease depend on?

Answer 27

Dietary history (e.g. if the patient has been avoiding gluten then they may have normal histology)

Question 28

How is coeliac disease managed?

Answer 28

Strict adherence to a gluten-free diet

Question 29

List some complications of coeliac disease.

Answer 29

* Malabsorption * Osteomalacia and osteoporosis * Neurological disease (epilepsy and cerebral calcification) * Lymphoma (causes multi-focal T cell lymphoma) * Hyposplenism

Question 30

What does a high anti-tTG antibody level in a patient with previously diagnosed coeliac disease suggest?

Answer 30

Poor compliance with the diet Complications (e.g. lymphoma)

Question 31

How often should a DEXA scan be performed in coeliac patients?

Answer 31

Every 3-5 years

Question 32

What does mortality in untreated coeliac disease tend to be due to?

Answer 32

* Malignancy (lymphoma) * Infection

Question 33

List some conditions that are frequently associated with coeliac disease.

Answer 33

* Dermatitis herptiformis * Type 1 diabetes mellitus * Autoimmune thyroid disease * Down syndrome * SLE * Autoimmune hepatitis