Malabsorption Flashcards
What are the causes of a low MCV?
- Iron deficiency
- Thalassemia trait
- Anaemia of chronic disease
Describe what the following will be in Iron deficiency anemia:
- Hb
- Serum iron
- TIBC or transferrin
- Transferrin saturation
- Ferritin
- Hb - LOW
- Serum iron - LOW
- TIBC or transferri - RAISED
- Transferrin saturation - LOW
- Ferritin - LOW
What will be following be in Anemia of chronic disease?
- Hb
- Serum iron
- TIBC or transferrin
- Transferrin saturation
- Ferritin
- Hb - LOW
- Serum iron - LOW
- TIBC or transferrin - NORMAL/LOW
- Transferrin saturation - NORMAL
- Ferritin - NORMAL (high in acute phase)
Describe what the following would be like in Thalassemia trait:
- Hb
- Serum iron
- TIBC or transferrin
- Transferrin saturation
- Ferritin
- Hb - NORMAL/LOW
- Serum iron - NORMAL
- TIBC or transferrin - NORMAL
- Transferrin saturation - NORMAL
- Ferritin - NORMAL
What does this image show? What could this be?
- Hypochromic RBC
- Pale
- Microcytic RBC
Iron deficiency anemia
Thalassemia trait
What are the irregular shaped cells in this blood film called?
What are they a sign of?
- Poikilocytes - abnormally shaped red blood cells - ‘tear drop’ cell
- Also a sign of hypochromic red cells
- Signs of Iron deficiency anemia
What is anisopoikilocytosis? What can it be a sign of?
Anisopoikilocytosis
- Variations in size (aniso)
- and shape (poikilo)
- of cells (cytosis)
Sign of iron deficiency
- What does the image show?
- What could this be a sign of?
- Basophillic stippling - aggregated ribosomal material
- Can be a sign of:
- Beta thalassemia trait
- Lead poisoning
- Alcoholism
- Sideroblastic anemia - form of anemia where the bone marrow produces ringed sideroblasts rather than normal erythrocytes
- What does this image show?
- What is the caused/what is it a sign of?
- What could this be a sign of?
- Hypersegmented neutrophil
- This is megaloblastic anemia, which reflects impaired DNA synthesis
- Can be a sign of B12 deficiency, Folate deficiency and Drugs
- What does this image show?
- What are they?
- What can they be a sign of?
- Target cells/Codocytes
- Codocytes have a relatively high surface area:volume ratio
- Can be a sign of:
- Iron deficiency
- Thalassemia
- Hyposplenism
- Liver disease
- What does this image show/what is the abnormality?
- What is this abnormality a sign of?
- Howell-Jolly bodies - signs of nuclear remnants visible in red cells
- Hyposplenism
EMQ
Which are the following features of iron deficiency anemia?
A. Howell Jolly bodies and codocytes (target cells)
B. Macrocytosis and hypersegmented neutrophils
C. Microcytic hpochromic red cells with anisopoikilocytosis
C- microcytic hypochromic red cells with anisopoikilocytosis
What are the causes of iron deficiency?
- MAJOR CAUSE - blood loss
- Poor diet
- Malabsorption
- Combinations of the above
What are the causes of a megaloblastic change?
- B12 or folate deficiency
- Poor diet
- Malabsorption
- Pernicious anemia
What are the causes of hyposplenism?
- Absent spleen - theraputic or trauma
- Poorly-functioning spleen
- Inflammatory bowel disease
- Coeliac disease
- Sickle cell disease
- SLE
EMQ
Blood results show:
Ca 2.00 (2.15-2.65umol/l)
Alk phos 400 (30-130 U/l)
Vitamin D 18 (70-150nmol/l)
PTH 14 (1.1-6.8pmol/l)
What is the diagnosis?
A. Primary hyperparathyroidism
B. Vitamin D deficiency and secondary hyperparathyroidism
C. Vitamin D deficiency and tertiary hyperparathyroidism
D. Hypoparathyroidism
E. Osteoporosis
B - Vitamin D deficiency and secondary hyperparathyroidism
What deficiences will be seen with the following conditions?
- Coeliac disease
- Crohn’s disease
- Pancreatic disease
- Infective/post-infective
- Coeliac disease - Iron, B12, Folate, Fat and calcium
- Crohn’s disease - B12, bile salts
- Pancreatic disease - Fat, Ca, B12
- Infective/post-infective - Fat, Folate
What investigations should be done if suspecting a GI malabsorption issue?
- Inflammatory markers - CRP and ESR
- Serological tests
- Upper GI endocscopy and distal duodenal biopsies
- Faecal elastase, pancreolauryl test, CT scanning
- MRI of small bowel
- What is coeliac disease?
- What is the form of inheritance?
- Which HLA is it associated with?
- Coeliac disease is a polygenic auto-immune disease, causing an intolerance to gluten
- 75% concordanxe in monozygotic twins. 40% heritability maps to MHC complex gene loci
- 90% patients carry HLA DQ2
What happens during coeliac disease when gluten is present?
- Coeliac disease is T cell response to gluten
- Peptides from gliadin are demaidated by tissue transglutaminase and presented by APCs
- CD4 T cells recognise deamidated peptides presented by HLA DQ2 or DQ8
- T cell activation leads to the secretion of IFN-gamma and may indirectly increased the release of IL-15
- Cytokines produced promotes activation of the intra-epithelial lymphocytes
- Intra-epithelial lymphocytes kill epithelial cells in a NKG2D dependent manner. Therefore damage in coeliac is mediated by gamma and delta T cell receptors expressing IEL (intra-epithelial lymphocytes)
What are the antibodies in coeliac disease
- Anti- Tissue transglutaminase
- Endomysial antibodies
- Deamidated gliadin peptide antibodies
What does tissue transglutaminase do?
Tissue transglutaminase deamidates gliadin. Gliadin is component of gluten
Describe how the body can produce anti-gliadin antibodies and their role in the pathophysiology of coeliac disease
- Stimulation of T cells specific for gliadin peptides - APC presents a gliadin peptide complex (HLA DQ2 or 8)
- T cells specific for gliafin provide help for B cells whose surface receptors recognise gliadin
- B cells specific for gliadin mature to form plasma cells secreting antibodies specific for gliadin
- antibodies for anti-gliadin attack gliadin produced when gluten is broken down and cause an immune response in the body when gluten is ingested
Describe the production of antibodies against transglutaminase
- T cells specific for gliadin can also provide help for B cells whose surface receptors recognise the transglutaminase part of the transglutaminase/gliadin complex
- B cells for transglutaminase mature to for plasma cells secreting antibodies specific for transglutaminase
- antibodies recognise surface tissue transglutaminase on the endomysial cells
Describe the different serological tests for coeliac disease including sensitivity and specificity and when they appear
- IgA anti-transglutaminase antobody - sensitivity = 90-94%, specificity =95%. Antibody appears within several months after insitution of gluten free diet
- IgA anti-endomysial antibody - sensitivity 85-94%, specificity = 95%. Antibody disappears within several months after insitution of gluten free diet
- IgA or IgG anti-gliadin antibody - sensitivity = 57-80%, specificity =30-50%. Most persistent, may be detectable up to 12 months after institution of a gluten-free diet. Not used often as a poor test
What is the gold-standard for diagnosis of coeliac disease and why?
- duodenal biospy and histology is gold standard
- otherwise, there is major implications of the diagnosis including having to follow a gluten-free diet and complications of having coeliac disease
What is the histopathology of coeliac disease from a duodenal biopsy?
- Villous atrophy
- Normal villous:crypt ratio is 2-4:1. In coeliac disease, the villous height is reduced and crypts become hyperplastic, resulting in reduced villous:crypts ratio
- mucosal thickness remains the dame due to crypt hyperplasia
- villous atrophy results in decreased surface area leading to malabsorption
- What are intraepithelial lymphocytes?
- How many are there in people with coeliac disease?
- What else can cause an increase in IELs?
- Normal duodenal villi contain less than 20 IELs per 100 epithelial cells. These lymphocytes are 𝛄ƍ T cells
- In coeliac disease, this is increased to more than 20 IELs oer 100 epithelial cells
- Other causes include: dermatitis herpetiformis, giardiasis, cows milk protein sensitivity, IgA deficiency etc.
Apart from coeliac disease, what are other causes of villous atrophy?
- Giardiasis - parasitic infection
- tropical sprue
- Crohn’s disease
- Radiation/chemotherapy
- Bacterial overgrowth
- Nutritional deficiencies
- Graft vs host disease
- Microvillous inclusion disease
- Common variable immunodeficiency
A diagnosis of coeliac disease was made in someone, what needs to be done now?
- Dietary management - avoidance of gluten
- Advice long term about complications
- Implications for family
- Sources of patient information
- Ongoing monitoring
What are the complications of coeliac disease?
- Malabsorption
- Osteomalacia and osteoporosis
- Neurological disease - epilepsy and cerebral calcification
- Lymphoma - EATL
- Hyposplenism
What are the possible complications of undiagnosed coeliac disease?
- Undiagnosed deficiencies - iron, folate, B12, Vitamin D and K
- Dietary compliance protects against malignancy
- Often feel better physically and psychologically when treated
- mortality rate of untreated coeliacs is x2-3 of general popultion - lymphomas and infection
What other automimmune conditions is coeliac disease associated with?
- Dermatitis herpetiformis = 100%
- Type 1 diabetes mellitus = 7%
- Autoimmune thyroid disease
- Down’s syndrome
In which patients is it useless in looking for antibodies for coeliac disease?
Patients who are IgA deficient
