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)
Describe the villous atrophy seen in coeliac disease.
- 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
List some other causes of villous atrophy.
Don’t learn - just know there are many causes
- Giardiasis
- Tropical sprue - v.rare
- Crohn’s disease
- Radiation/chemotherapy
- Nutritional deficiencies
- Graft-versus-host disease
- Microvillous inclusion disease
- Common variable immunodeficiency
List some other causes of high intraepithelial lymphocytes.
Don’t learn - just know there are many causes
- Dematitis herpetiformis
- Giardiasis
- Cows’ milk protein sensitivity
- IgA deficiency
- Tropical sprue
- Post-infective malabsorption
- Drugs (NSAIDs)
- Lymphoma
What does the interpretation of the histological report in suspected coeliac disease depend on?
Dietary history
(e.g. if the patient has been avoiding gluten then they may have normal histology)
How is coeliac disease managed?
Strict adherence to a gluten-free diet
Avoid: wheat, barley, rye, oats
Support: coeliac society, dieticians, family
List some complications of coeliac disease.
- Malabsorption
- Osteomalacia and osteoporosis
- Neurological disease (epilepsy and cerebral calcification)
- Lymphoma (EATL)
- Hyposplenism
What does a high anti-tTg antibody level in a patient with previously diagnosed coeliac disease suggest?
- Poor adherence with the diet
- Complications (e.g. small bowel lymphoma)
Describe the follow up investigation used for patient with coeliac
How often should a DEXA scan be performed in coeliac patients?
DEXA of spine and hip every 3-5 years
What does mortality in untreated coeliac disease tend to be due to?
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
List some conditions that are frequently associated with coeliac disease.
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
Describe the diagnostic workup for coeliac
