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review Im > 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
  • Variations in size (aniso-) and shape (poikilo-) of cells
  • Associated with iron deficiency anaemia (and thalassaemia trait to a lesser degree)
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3
Q

What are tear drop cells and elliptocytes associated with?

A
  • Tear drop cell (darcocyte) - myelofibrosis
  • Elliptocyte - hereditary elliptocytosis, iron deficiency anaemia
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4
Q

What is basophilic stippling? List some causes.

A

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

  • Lead poisoning
  • Beta-thalassaemia trait
  • Alcoholism
  • Sidroblastic anaemia
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5
Q

Which condition do hypersegmented neutrophils tend to be present in?

A

Megaloblastic anaemia - reflects impaired DNA synthesis

Hypersegmented is >5 segments

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6
Q

List some causes of megaloblastic anaemia.

A
  • B12 deficiency
  • Folate deficiency
  • Drugs (nitrous oxide, valproate, chemotherapy)
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7
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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8
Q

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

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

Target cells and Howell-Jolly bodies = hyposplenism

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9
Q

List some causes of iron deficiency.

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

Can occur in combination

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10
Q

List some causes of B12 and folate deficiency.

A
  • Dietary deficiency
  • Malabsorption
  • Pernicious anaemia (B12 only)
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11
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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12
Q

Why ALP is raised in bone turnover?

A

Released by active osteoblasts

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13
Q

What are some causes of vitamin D deficiency?

A
  • Lack of sunlight
  • Dietary deficiency
  • Malabsorption
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14
Q

Which deficiencies are typically seen in Coeliac disease?

A
  • Iron
  • B12
  • Folate
  • Fat
  • Calcium
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15
Q

Which deficiencies are typically seen in Crohn’s disease?

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

Affecting absorption in the terminal ileum

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16
Q

Which deficiencies are typically seen in pancreatic disease?

A
  • Fat
  • Calcium
  • B12
17
Q

Which investigations are typically performed in Coeliac disease?

A
  • CRP and ESR
  • Serological tests - anti-tTg
  • Upper GI endoscopy and duodenal biopsy (GOLD STANDARD)
18
Q

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

A
  • HLA-DQ2 (90%)
  • HLA-DQ8
19
Q

Describe the T cell response to gluten in coeliac disease.

A
  • 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)
20
Q

Describe the B cell response to gluten in coeliac disease.

A
  • 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
21
Q

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

A
  • Anti-tTg antibodies
  • Anti-endomysial antibodies

Anti-gliadin antibodies are not very sensitive nor specific

22
Q

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

A

IgA levels - IgA deficiency can produce false-negative results

23
Q

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

A

Yes - need to confirm diagnosis & take histological baseline

24
Q

What are the characteristic histological features of coeliac disease?

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

Describe the villous atrophy seen in coeliac disease.

A
  • 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
26
Q

List some other causes of villous atrophy.

Don’t learn - just know there are many causes

A
  • Giardiasis
  • Tropical sprue - v.rare
  • Crohn’s disease
  • Radiation/chemotherapy
  • Nutritional deficiencies
  • Graft-versus-host disease
  • Microvillous inclusion disease
  • Common variable immunodeficiency
27
Q

List some other causes of high intraepithelial lymphocytes.

Don’t learn - just know there are many causes

A
  • Dematitis herpetiformis
  • Giardiasis
  • Cows’ milk protein sensitivity
  • IgA deficiency
  • Tropical sprue
  • Post-infective malabsorption
  • Drugs (NSAIDs)
  • Lymphoma
28
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)

29
Q

How is coeliac disease managed?

A

Strict adherence to a gluten-free diet
Avoid: wheat, barley, rye, oats

Support: coeliac society, dieticians, family

30
Q

List some complications of coeliac disease.

A
  • Malabsorption
  • Osteomalacia and osteoporosis
  • Neurological disease (epilepsy and cerebral calcification)
  • Lymphoma (EATL)
  • Hyposplenism
31
Q

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

A
  • Poor adherence with the diet
  • Complications (e.g. small bowel lymphoma)
32
Q

Describe the follow up investigation used for patient with coeliac

A
33
Q

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

A

DEXA of spine and hip every 3-5 years

34
Q

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

A

Mortality rate of untreated coeliacs is x 2-3 of general population

  • Malignancy (lymphoma)
  • Infection

The excess mortality returns to normal after 3-5 years on gluten free diet

35
Q

List some conditions that are frequently associated with coeliac disease.

A

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
36
Q

Describe the diagnostic workup for coeliac

A

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