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YEAR 5: Immunopathology AS > Immuno: Malabsorption CPC > Flashcards

Immuno: Malabsorption CPC Flashcards

1
Q

List three causes of microcytic anaemia.

A
  • Iron deficiency
  • Thalassaemia trait
  • Anaemia of a chronic disease
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2
Q

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

A
  • Variatios in size and shape of cells
  • Associated with iron deficiency anaemia (and thalassaemia trait to a lesser degree)
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3
Q

What is basophilic stippling? List some causes.

A
  • Basophilic appearance of red blood cells caused by the presence of aggregated ribosomal material
  • Causes: beta-thalassaemia trait, lead poisoning, alcoholism, sidroblastic anaemia
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4
Q

Which condition do hypersegmented neutrophils tend to be present in?

A

Megaloblastic anaemia

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5
Q

List some causes of megaloblastic anaemia.

A
  • B12 deficiency
  • Folate deficiency
  • Drugs
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6
Q

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

A
  • Iron deficiency
  • Thalassaemia
  • Hyposplenism
  • Liver disease

NOTE: target cells have a high SA: V ratio

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7
Q

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

A
  • Nuclear remnants present within red blood cells
  • Present in hyposplenism
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8
Q

List some causes of iron deficiency.

A
  • Blood loss (major cause)
  • Poor diet
  • Malabsorption
  • Combinations of the above
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9
Q

List some causes of B12 and folate deficiency.

A
  • Poor diet
  • Malabsorption
  • Pernicious anaemia
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10
Q

List some causes of hyposplenism.

A
  • Absent spleen: therapeutic, trauma
  • Poorly-functioning spleen: inflammatory bowel disease, Coeliac disease, sickle cell disease, SLE
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11
Q

differentials

A

coeliac
crohn’s
stress+/-
menorrhagia
pancreatic disease
bacterial overgrowth, topical sprue, thyrotoxicosis, post-surgery, lymphoma, zollinger-ellison

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12
Q

Which deficiencies are typically seen in Coeliac disease?

A
  • Iron
  • B12
  • Folate
  • Fat
  • Calcium
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13
Q

Which deficiencies are typically seen in Crohn’s disease?

A
  • B12
  • Bile salts
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14
Q

Which deficiencies are typically seen in pancreatic disease?

A
  • Fat
  • Calcium
  • B12
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15
Q

deficiency seen in infective/ post-infective

A

fat, folate

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16
Q

Which investigatio are typically performed in Coeliac disease?

A
  • CRP and ESR and faecal calprotectin
  • Serological tests
  • Upper GI endoscopy and distal duodenal biopsy (GOLD STANDARD)
  • faecal elastase, pancreaolauryl test, CT scanning, small bowel MRI
17
Q

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

A

MHC complex gene loci

18
Q

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

A
  • HLA-DQ2 (80%) - DQA1*0501 and DQB1*02 alleles
  • HLA-DQ8
19
Q

Describe the T cell response to gluten in coeliac disease.

A
  • 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)
20
Q

Describe the B cell response to gluten in coeliac disease.

A
  • 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
21
Q

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

A

IgA antibodies

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

22
Q

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

A

On endomysial cells

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

23
Q

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

A
  • IgA levels
  • IgA deficiency <0.3g/L can produce false-negative results= do a biopsy
24
Q

why do a biopsy in patients with antibody confirmation

A

gold standard duodenal histology and baseline needed

scalloping of ridges in the duodenum- loss of villi to form lumps

25
Q

What are the characteristic histological features of coeliac disease?

A
  • Subtotal villous atrophy with crypt hyperplasia
  • Intra-epithelial lymphocytes
26
Q

Describe the villous atrophy seen in coeliac disease.

A
  • Normal villous: crypt ratio is about 3-5: 1 + less than 20intrepithelial lymphocytes/100 epithelial cells
  • 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 (thickness increases)
  • However, decreased surface area (due to villous atrophy) leads to malabsorption
  • brunner’s glands in first part of duodenum may distort villous architecture
27
Q

List some other causes of villous atrophy.

A
  • Giardiasis
  • Tropical sprue
  • Crohn’s disease
  • Radiation/chemotherapy
  • Nutritional deficiencies
  • Graft-versus-host disease
  • Microvillous inclusion disease
  • Common variable immunodeficiency
28
Q

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

A

More than 25 IELs/100 epithelial cells

NOTE: normal would be < 20

29
Q

what receptors may be seen with immunohistochemistry staining

A

CD3 immunohistochemistry (normally CD8+ t cells)

30
Q

List some other causes of high intraepithelial lymphocytes.

A
  • Dematitis herpetiformis
  • Giardiasis
  • Cows’ milk protein sensitivity
  • IgA deficiency
  • Tropical sprue
  • Post-infective malabsorption
  • Drugs (NSAIDs)
  • Lymphoma
31
Q

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

A

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

32
Q

How is coeliac disease managed?

A

Strict adherence to a gluten-free diet- wheat, barley rye, some oats
implications for family
refer to dietician
sources of patient information
ongoing monitoring

33
Q

List some complications of coeliac disease.

A
  • Malabsorption
  • Osteomalacia and osteoporosis
  • Neurological disease (epilepsy and cerebral calcification)
  • Lymphoma (causes multi-focal T cell lymphoma)
  • Hyposplenism
34
Q

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

A

Poor compliance with the diet

Complications (e.g. lymphoma)

35
Q

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

A

Every 3-5 years

36
Q

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

A
  • Malignancy (lymphoma)
  • Infection
37
Q

List some conditions that are frequently associated with coeliac disease.

A
  • Dermatitis herptiformis: 100% prevalence, extensor surfaces of arms
  • Type 1 diabetes mellitus: 7%
  • Autoimmune thyroid disease
  • Down syndrome
  • SLE
  • Autoimmune hepatitis
  • recurrent aphthous ulceration
  • sjogren’s
  • sarcoidosis
  • vitiligo/ alopecia areata
  • IgA deficiency

YEAR 5: Immunopathology AS (12 decks)

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