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

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

Question 3

What are tear drop cells and elliptocytes associated with?

Answer 3

• Tear drop cell (darcocyte) - myelofibrosis
• Elliptocyte - hereditary elliptocytosis, iron deficiency anaemia

Question 4

What is basophilic stippling? List some causes.

Answer 4

Basophilic appearance of red blood cells caused by the presence of aggregated ribosomal material

• Lead poisoning
• Beta-thalassaemia trait
• Alcoholism
• Sidroblastic anaemia

Question 5

Which condition do hypersegmented neutrophils tend to be present in?

Answer 5

Megaloblastic anaemia - reflects impaired DNA synthesis

Hypersegmented is >5 segments

Question 6

List some causes of megaloblastic anaemia.

Answer 6

• B12 deficiency
• Folate deficiency
• Drugs (nitrous oxide, valproate, chemotherapy)

Question 7

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

Answer 7

• Iron deficiency
• Thalassaemia
• Hyposplenism
• Liver disease

NOTE: target cells have a high SA: V ratio

Question 8

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

Answer 8

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

Target cells and Howell-Jolly bodies = hyposplenism

Question 9

List some causes of iron deficiency.

Answer 9

• Blood loss (major cause)
• Dietary deficiency
• Malabsorption

Can occur in combination

Question 10

List some causes of B12 and folate deficiency.

Answer 10

• Dietary deficiency
• Malabsorption
• Pernicious anaemia (B12 only)

Question 11

List some causes of hyposplenism.

Answer 11

Absent spleen

• Therapeutic
• Trauma

Poorly-functioning spleen

• Inflammatory bowel disease
• Coeliac disease
• Sickle cell disease
• SLE

Question 12

Why ALP is raised in bone turnover?

Answer 12

Released by active osteoblasts

Question 13

What are some causes of vitamin D deficiency?

Answer 13

• Lack of sunlight
• Dietary deficiency
• Malabsorption

Question 14

Which deficiencies are typically seen in Coeliac disease?

Answer 14

• Iron
• B12
• Folate
• Fat
• Calcium

Question 15

Which deficiencies are typically seen in Crohn’s disease?

Answer 15

• B12
• Bile salts
• Iron (from bleeding rather than malabsorption)

Affecting absorption in the terminal ileum

Question 16

Which deficiencies are typically seen in pancreatic disease?

Answer 16

• Fat
• Calcium
• B12

Question 17

Which investigations are typically performed in Coeliac disease?

Answer 17

• CRP and ESR
• Serological tests - anti-tTg
• Upper GI endoscopy and duodenal biopsy (GOLD STANDARD)

Question 18

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

Answer 18

• HLA-DQ2 (90%)
• HLA-DQ8

Question 19

Describe the T cell response to gluten in coeliac disease.

Answer 19

• Peptides from gluten (gliadin) are deamidated by tissue transglutaminase
• Deaminated gliadin is taken up by antigen-presenting cells and presented to CD4+ T cells via HLA DQ2 or DQ8
• 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 20

Describe the B cell response to gluten in coeliac disease.

Answer 20

• B cells will process gluten antigens and present it to CD4+ T cells
• CD4+ T cells activated these B-cells whose surface receptors recognise gliadin
• These B-cells become plasma cells that secrete anti-gliadin antibodies
• These CD4+ T cells can also active B-cells whose surface receptors recognise tTg as part of the tTg/gliadin complex
• These B-cells then become plasma cells that secrete anti-tTg antibodies

Question 21

What are the 2 most sensitive and specific antibodies used to test for coeliac disease?

Answer 21

• Anti-tTg antibodies
• Anti-endomysial antibodies

Anti-gliadin antibodies are not very sensitive nor specific

Question 22

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

Answer 22

IgA levels - IgA deficiency can produce false-negative results

Question 23

Should you do endoscopy with duodenal biopsy even if coeliac serology is positive?

Answer 23

Yes - need to confirm diagnosis & take histological baseline

Question 24

What are the characteristic histological features of coeliac disease?

Answer 24

• Villous atrophy
• Crypt hyperplasia
• Intra-epithelial lymphocytes (>25 lymphocytes per 100 epithelial cells)

Question 25

Describe the villous atrophy seen in coeliac disease.

Answer 25

* Normal villous: crypt ratio is about 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 26

List some other causes of villous atrophy. ## Footnote Don't learn - just know there are many causes

Answer 26

* Giardiasis * Tropical sprue - v.rare * Crohn's disease * Radiation/chemotherapy * Nutritional deficiencies * Graft-versus-host disease * Microvillous inclusion disease * Common variable immunodeficiency

Question 27

List some other causes of high intraepithelial lymphocytes. ## Footnote Don't learn - just know there are many causes

Answer 27

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

Question 28

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

Answer 28

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

Question 29

How is coeliac disease managed?

Answer 29

Strict adherence to a gluten-free diet Avoid: wheat, barley, rye, oats ## Footnote Support: coeliac society, dieticians, family

Question 30

List some complications of coeliac disease.

Answer 30

* Malabsorption * Osteomalacia and osteoporosis * Neurological disease (epilepsy and cerebral calcification) * Lymphoma (EATL) * Hyposplenism

Question 31

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

Answer 31

- Poor adherence with the diet - Complications (e.g. small bowel lymphoma)

Question 32

Describe the follow up investigation used for patient with coeliac

Answer 32

Question 33

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

Answer 33

DEXA of spine and hip every 3-5 years

Question 34

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

Answer 34

Mortality rate of untreated coeliacs is x 2-3 of general population * Malignancy (lymphoma) * Infection ## Footnote The excess mortality returns to normal after 3-5 years on gluten free diet

Question 35

List some conditions that are frequently associated with coeliac disease.

Answer 35

Coeliac disease is associated with auto-immune and other disorders * Dermatitis herptiformis (100% prevalence) * Type 1 diabetes mellitus (7% prevalence) * Autoimmune thyroid disease (Hashimoto's) * Down's syndrome * SLE and other connective tissue disease * Autoimmune hepatitis

Question 36

Describe the diagnostic workup for coeliac

Answer 36