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Questions and Answers
What is the primary cause of an increased need for folate?
What is the rate-limiting step in DNA synthesis inhibited by folate deficiency?
What is required for the demethylation of methyl THF?
What is the result of a lack of B12 in the conversion of methyl THF?
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What is the result of impaired DNA synthesis in megaloblastic anaemia?
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What is the difference between folate deficiency and B12 deficiency?
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What is the role of folate binding proteins in the absorption of folates?
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What is the laboratory diagnosis of megaloblastic anaemia?
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What is a characteristic feature of the anaemia in vitamin B12 deficiency?
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What is a distinguishing feature of megaloblastic anaemia caused by folate deficiency?
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What is a laboratory finding that suggests vitamin B12 deficiency?
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What is the term for disorders of abnormal haemoglobin synthesis?
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What is a characteristic feature of the bone marrow in megaloblastic anaemia?
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What is a characteristic feature of the reticulocyte count in megaloblastic anaemia?
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What is a distinguishing feature of megaloblastic anaemia caused by vitamin B12 deficiency?
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What is the term for a genetic disorder characterized by abnormal haemoglobin synthesis?
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What is the characteristic abnormality of erythroblasts in the bone marrow in megaloblastic anaemia?
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What is the primary cause of abnormal maturation of the nucleus in megaloblastic anaemia?
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What is the role of intrinsic factor in the absorption of vitamin B12?
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What is the primary function of transcobalamin in the body?
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What is the most common cause of vitamin B12 deficiency?
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How long does it take for vitamin B12 deficiency to develop due to severe malabsorption?
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What is the difference between folate deficiency and vitamin B12 deficiency?
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What is the laboratory diagnosis of megaloblastic anaemia?
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Study Notes
Folate
- Folate is a parent compound of folates, derived from pteroylglutamic acid.
- Dietary folates are converted to methyl tetrahydrofolate (THF) during absorption in the upper small intestine.
- Folate binding proteins on cell surfaces facilitate entry of reduced folates into cells.
Folate Deficiency
- Folate deficiency is often caused by poor dietary intake of folate or increased folate utilization.
- Excess cell turnover, including pregnancy, increases the need for folate, as folate molecule degrades with increased DNA synthesis.
Biochemical Basis for Megaloblastic Anaemia
- Folate deficiency inhibits thymidylate synthesis, a rate-limiting step in DNA synthesis.
- The reaction needs 5,10-methylene THF polyglutamate as a coenzyme.
- Lack of vitamin B12 prevents demethylation of methyl THF, depriving cells of THF, and resulting in impaired DNA synthesis.
Clinical Features of Megaloblastic Anaemia
- Symptoms and signs of anaemia are gradually progressive.
- Patients may be mildly jaundiced due to excess haemoglobin breakdown.
Megaloblastic Anaemia
- This is a group of anaemias with characteristic abnormality – delayed maturation of the nucleus relative to the cytoplasm.
- The cause of abnormal maturation is defective DNA synthesis, usually due to vitamin B12 or folate deficiency.
Vitamin B12 (Cobalamin)
- Vitamin B12 is synthesized by microorganisms and found in foods of animal origin.
- Absorption occurs in the distal ileum where B12 is released from protein-binding in food and combined with intrinsic factor (IF).
- The IF–B12 complex binds to a specific surface receptor, cubilin, which directs endocytosis of the complex.
Vitamin B12 Deficiency
- Causes include pernicious anaemia, veganism, gastrectomy, or small intestinal lesions.
- Vitamin B12 deficiency takes at least 2 years to develop due to depletion of body stores.
Laboratory Findings
- Anaemia is macrocytic (MCV > 98 fL) with oval-shaped macrocytes.
- The reticulocyte count is low, and the total white cell and platelet counts may be moderately reduced.
Diagnosis of Vitamin B12 or Folate Deficiency
- Serum B12 and folate are assayed to diagnose megaloblastic anaemia.
- Serum B12 is low in megaloblastic anaemia.
- The serum and red cell folate are both low in megaloblastic anaemia caused by folate deficiency.
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Description
Learn about the process of folate absorption and conversion into methyl tetrahydrofolate and folate polyglutamates in the small intestine.
