Immuno: Malabsorption CPC Flashcards
List three causes of microcytic anaemia.
- Iron deficiency
- Thalassaemia trait
- Anaemia of a chronic disease
What is anisopoikilocytosis and which type of anaemia is it associated with?
- Variations in size (aniso-) and shape (poikilo-) of cells
- Associated with iron deficiency anaemia (and thalassaemia trait to a lesser degree)
What are tear drop cells and elliptocytes associated with?
- Tear drop cell (darcocyte) - myelofibrosis
- Elliptocyte - hereditary elliptocytosis, iron deficiency anaemia
What is basophilic stippling? List some causes.
Basophilic appearance of red blood cells caused by the presence of aggregated ribosomal material
- Lead poisoning
- Beta-thalassaemia trait
- Alcoholism
- Sidroblastic anaemia
Which condition do hypersegmented neutrophils tend to be present in?
Megaloblastic anaemia - reflects impaired DNA synthesis
Hypersegmented is >5 segments
List some causes of megaloblastic anaemia.
- B12 deficiency
- Folate deficiency
- Drugs (nitrous oxide, valproate, chemotherapy)
In which conditions might you see target cells (codocytes)?
- Iron deficiency
- Thalassaemia
- Hyposplenism
- Liver disease
NOTE: target cells have a high SA: V ratio
What are Howell-Jolly bodies? Which condition are they associated with?
- Nuclear remnants present within red blood cells
- Present in hyposplenism
Target cells and Howell-Jolly bodies = hyposplenism
List some causes of iron deficiency.
- Blood loss (major cause)
- Dietary deficiency
- Malabsorption
Can occur in combination
List some causes of B12 and folate deficiency.
- Dietary deficiency
- Malabsorption
- Pernicious anaemia (B12 only)
List some causes of hyposplenism.
Absent spleen
- Therapeutic
- Trauma
Poorly-functioning spleen
- Inflammatory bowel disease
- Coeliac disease
- Sickle cell disease
- SLE
Why ALP is raised in bone turnover?
Released by active osteoblasts
What are some causes of vitamin D deficiency?
- Lack of sunlight
- Dietary deficiency
- Malabsorption
Which deficiencies are typically seen in Coeliac disease?
- Iron
- B12
- Folate
- Fat
- Calcium
Which deficiencies are typically seen in Crohn’s disease?
- B12
- Bile salts
- Iron (from bleeding rather than malabsorption)
Affecting absorption in the terminal ileum
Which deficiencies are typically seen in pancreatic disease?
- Fat
- Calcium
- B12
Which investigations are typically performed in Coeliac disease?
- CRP and ESR
- Serological tests - anti-tTg
- Upper GI endoscopy and duodenal biopsy (GOLD STANDARD)
Which HLA alleles are particularly common in patients with coeliac disease?
- HLA-DQ2 (90%)
- HLA-DQ8
Describe the T cell response to gluten in coeliac disease.
- 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)
Describe the B cell response to gluten in coeliac disease.
- 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
What are the 2 most sensitive and specific antibodies used to test for coeliac disease?
- Anti-tTg antibodies
- Anti-endomysial antibodies
Anti-gliadin antibodies are not very sensitive nor specific
What important test should be performed before checking anti-tTg and anti-endomysial antibody levels?
IgA levels - IgA deficiency can produce false-negative results
Should you do endoscopy with duodenal biopsy even if coeliac serology is positive?
Yes - need to confirm diagnosis & take histological baseline
What are the characteristic histological features of coeliac disease?
- Villous atrophy
- Crypt hyperplasia
- Intra-epithelial lymphocytes (>25 lymphocytes per 100 epithelial cells)
