MEH 7 - Anaemia, Vit B12 & Folate Deficiency Flashcards
What is anaemia?
What are the clinical symptoms and signs?
Is anaemia a diagnosis?
- Anaemia is a Hb concentration lower than the normal range for a certain individual.
- Symptoms (related to insufficient O2 delivery to tissues) … shortness of breath, palpitations, headaches, angina etc
- Signs = pallor, tachycardia, hypotension, tachypnoea
- Anaemia is a manifestation of an underlying disease state, not an official diagnosis.
How might anaemia arise in the following stages of a RBC lifecycle?
1) In the bone marrow/synthesis (3 factors)
2) In circulation (4 factors)
3) During removal (1 factor)
1) Reduced or dysfunctional erythropoiesis, abnormal haem synthesis + abnormal globin chain synthesis.
2) Abnormal structure of RBC’s, mechanical damage to RBC’s, abnormal metabolism of RBC’s or excessive bleeding.
3) Increased removal via the RES
How might anaemia arise as a result of reduced/dysfunctional erythropoiesis?
- Usually, kidney senses hypoxia and releases EPO, which binds to bone marrow receptors stimulating RBC production.
1) In chronic kidney disease the kidney may stop producing EPO
2) Marrow may be unable to respond to EPO, e.g.: after chemotherapy
3) Marrow can be infiltrated by cancer cells or fibrous tissue reducing the number of normal haemopoietic cells.
How might defects in haemoglobin synthesis result in anaemia? (3)
- Mutations in a or b globin chains can result in thalassaemia or sickle cell disease.
- Defects in haem synthetic pathway can lead to sideroblastic anaemia.
- Insufficient dietary iron can lead to iron deficiency anaemia.
What are the 2 ways in which abnormal structure or mechanical damage of Hb can cause haemolytic anaemia?
1) Inherited - mutations in genes coding for proteins involved in plasma membrane + cytoskeleton interactions cause cells to become less flexible and easily damaged. Quickly removed by RES - e.g.: hereditary spherocytosis.
2) Acquired - Microangiopathic haemolytic anaemias can result from shear stress (RBC’s passing through defective heart valve) or cells snagging on fibrin strands. Results in fragments called schistocytes (good indicator of pathology)
How might defects in red cell metabolism cause anaemia? (2)
1) G6PDH deficiency - reduces amount of glutathione (GSH), leading to oxidative stress. Aggregates of cross-linked Hb form (Heinz bodies) which are removed by RES
2) Pyruvate kinase deficiency - Final enzyme in glycolysis, RBC’s lack mitochondria so rely on glycolysis for energy. Causes deficiency in ATP and they undergo haemolysis.
How may excessive bleeding arise leading to anaemia? (2)
1) Chronic bleeding - e.g.: heavy menstrual bleeding, regular nosebleeds or GI bleeding.
2) Chronic NSAID use - Induce GI bleeding via inhibition of COX activity.
How might the RES be affected to an extent that anaemia occur?
- In haemolytic anaemias, RBC’s are destroyed rapidly as they are abnormal. Can be intra or extravascular. Splenomegaly occurs as a result as spleen is doing extra work.
- Alternatively autoimmune haemolytic anaemias causes autoantibodies to bind to RBC membrane proteins causing macrophages in the spleen to destroy them.
What 2 factors are key in evaluating the cause of anaemia in a patient?
1) Presence or absence of reticulocytes - this shows whether the bone marrow is working or not. (if absent, problem in bone marrow)
2) RBC size - e.g.: macro, micro or normocytic.
See flow chart for anaemia evaluation on slide 13.
What are macrocytic anaemias?
Name 3 kinds of macrocytic anaemias and their causes.
- Anaemias where the average RBC size is increased (high MCV)
1) Megaloblastic anaemias - Interference w/DNA synthesis, retarded nucleus synthesis, cell division delayed + megaloblasts formed - e.g.: VitB12/folate deficiency.
2) Macronormoblastic erythropoiesis - Erythroblasts are larger than normal giving rise to large RBC’s, e.g.: liver disease or alcohol toxicity.
3) Stress erythropoiesis - Conditions associated with high reticulocyte count, high EPO leads lead to expanded and accelerated erythropoiesis - e.g.: after haemorrhage.
What is folate?
What happens to it after absorption by the duodenum + jejunum?
What is it required for?
- Synthesised by bacteria + plants, abundant in green leafy veg’s.
- Converted to THF by intestinal cells, taken up by liver (stores enough for 3-4 months)
- Provides carbons for other reactions, and required for synthesis of nucleotide bases in DNA synthesis.
Describe some causes of folate deficiency?
What symptoms are associated with folate deficiency?
Why should folic acid be taken during the 1st 12 weeks of pregnancy?
- Dietary deficiency, increased requirement in pregnancy, diseases of the duodenum/jejunum (e.g.: coeliacs), urinary loss of folate in liver/heart failure.
- Those related to anaemia, reduced taste, diarrhoea, muscle weakness, numbness/tinging in feet + hands.
- Prevents majority of neural tube defects in babies.
What is Vit B12 (cyanocobalamin)?
What is it required for?
How is it obtained?
- Water soluble vitamin
- Essential co-factor for DNA synthesis, required for erythropoiesis, essential for normal function + development of CNS
- Produced by bacteria, obtained from foods of animal origin. Vegans need to get food fortified w/B12.
Describe the entire process of Vit B12 absorption.
- B12 released from proteins via proteolysis in stomach, binds to haptocorrin.
- Hatpocorrin/B12 complex digested by pancreatic proteases in SI, B12 binds to intrinsic factor.
- Instrinic factor/b12 complex binds to cubam receptor, mediates receptor mediated endocytosis into enterocytes.
- Undergoes lysosomal release in enterocytes, leaves via BL membrane through MDR1.
- Binds to transcobalamin, transported around bloodstream, majority stored in liver.
Name some causes of Vit B12 deficiency.
What are the symptoms?
- Dietary deficiency (particularly vegans), lack of intrinsic factor (pernicious anaemia), diseases of the ileum, lack of transcobalamin, chemical inactivation of B12.
- Those related to anaemia, glossitis/mouth ulcers, diarrhoea, paraesthesia, irritability etc.
