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Questions and Answers
What is the primary cause of an increased need for folate?
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 the rate-limiting step in DNA synthesis inhibited by folate deficiency?
What is required for the demethylation of methyl THF?
What is required for the demethylation of methyl THF?
What is the result of a lack of B12 in the conversion 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?
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?
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?
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?
What is the laboratory diagnosis of megaloblastic anaemia?
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What is a characteristic feature of the anaemia in vitamin B12 deficiency?
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?
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?
What is a laboratory finding that suggests vitamin B12 deficiency?
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What is the term for disorders of abnormal haemoglobin synthesis?
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?
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?
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?
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?
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?
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?
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?
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?
What is the primary function of transcobalamin in the body?
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What is the most common cause of vitamin B12 deficiency?
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?
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?
What is the difference between folate deficiency and vitamin B12 deficiency?
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What is the laboratory diagnosis of megaloblastic anaemia?
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.