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Questions and Answers
What is the characteristic abnormality of erythroblasts in the bone marrow in megaloblastic anemias?
What is the characteristic abnormality of erythroblasts in the bone marrow in megaloblastic anemias?
What is the underlying defect that accounts for the asynchronous maturation of the nucleus in megaloblastic anemias?
What is the underlying defect that accounts for the asynchronous maturation of the nucleus in megaloblastic anemias?
What is the source of vitamin B12 in nature?
What is the source of vitamin B12 in nature?
How do animals acquire vitamin B12?
How do animals acquire vitamin B12?
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What is the structure of vitamin B12?
What is the structure of vitamin B12?
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What is the definition of macrocytic anemia?
What is the definition of macrocytic anemia?
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What is the primary function of vitamin B12 in the body?
What is the primary function of vitamin B12 in the body?
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What is a common characteristic of the anaemia seen in pernicious anaemia?
What is a common characteristic of the anaemia seen in pernicious anaemia?
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What is the autoimmune target in pernicious anaemia?
What is the autoimmune target in pernicious anaemia?
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What is a diagnostic marker for pernicious anaemia?
What is a diagnostic marker for pernicious anaemia?
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What is a potential initiating factor for pernicious anaemia?
What is a potential initiating factor for pernicious anaemia?
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What is a characteristic of the stomach in pernicious anaemia?
What is a characteristic of the stomach in pernicious anaemia?
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Which of the following food sources does not contain vitamin B12?
Which of the following food sources does not contain vitamin B12?
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What is the role of vitamin B12 in DNA synthesis?
What is the role of vitamin B12 in DNA synthesis?
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What is the consequence of folate deficiency on DNA synthesis?
What is the consequence of folate deficiency on DNA synthesis?
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What is the substrate for folate polyglutamate synthesis?
What is the substrate for folate polyglutamate synthesis?
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What is the function of 5,10-methylene THF polyglutamate in DNA synthesis?
What is the function of 5,10-methylene THF polyglutamate in DNA synthesis?
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What is the term for both natural folates in food and folic acid, the synthetic form used in supplements and fortified food?
What is the term for both natural folates in food and folic acid, the synthetic form used in supplements and fortified food?
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What is the effect of iron deficiency on MCV in megaloblastic anemia?
What is the effect of iron deficiency on MCV in megaloblastic anemia?
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What is characteristic of neutrophils in megaloblastic anemia?
What is characteristic of neutrophils in megaloblastic anemia?
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What is the typical appearance of erythroblasts in the bone marrow of megaloblastic anemia?
What is the typical appearance of erythroblasts in the bone marrow of megaloblastic anemia?
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What is the expected response to correct vitamin therapy in megaloblastic anemia?
What is the expected response to correct vitamin therapy in megaloblastic anemia?
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What is the expected timeframe for normalization of white cell and platelet counts after correct vitamin therapy?
What is the expected timeframe for normalization of white cell and platelet counts after correct vitamin therapy?
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What is the characteristic feature of metamyelocytes in megaloblastic anemia?
What is the characteristic feature of metamyelocytes in megaloblastic anemia?
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Study Notes
Introduction to Macrocytic Anemia
- Macrocytic anemia is characterized by abnormally large red blood cells, with a mean corpuscular volume (MCV) greater than 98 fL.
Megaloblastic Anemias
- A group of anemias where erythroblasts in bone marrow show delayed nuclear maturation compared to cytoplasm.
- Defective DNA synthesis is the primary underlying cause, commonly due to vitamin B12 or folate deficiency.
- Rarely, other metabolic abnormalities or lesions in DNA synthesis may present similar hematological features.
Vitamin B12
- Synthesized by microorganisms; animals obtain it from food, particularly animal-origin sources.
- Composed of cobalamins, which include a cobalt atom at the center of a corrin ring and a nucleotide portion.
- Essential for converting methyl THF to THF, leading to the synthesis of polyglutamate forms of folate.
Folate
- Dietary folates are converted to methyl THF in the small intestine.
- Folate is vital for the metabolism of nucleic acid precursors and methylation reactions.
Pernicious Anemia (PA)
- Caused by autoimmune attack on the gastric mucosa, resulting in atrophy and decreased secretion of intrinsic factor (IF).
- Associated with thin gastric walls, achlorhydria, raised serum gastrin levels, and possible intestinal metaplasia.
- 90% of patients exhibit parietal cell antibodies; 50% show anti-IF antibodies inhibiting B12 binding.
- Diagnosis relies on the detection of anti-IF autoantibodies.
Laboratory Findings
- Macrocytic anemia typically presents with MCV > 98 fL, often reaching 120-140 fL in severe cases.
- Macrocytes are generally oval.
- Serum levels of vitamin B12 are higher in foods of animal origin, while absent in fruits, cereals, or vegetables.
Biochemical Basis for Megaloblastic Anemia
- DNA synthesis requires four deoxyribonucleoside triphosphates; folate plays a crucial role in thymidylate synthesis.
- Vitamin B12 indirectly facilitates DNA synthesis by converting methyl THF to THF, the substrate for folate polyglutamate synthesis.
- Folate is necessary for the conversion of deoxyuridine monophosphate to thymidine monophosphate, crucial for DNA replication.
Clinical Features
- In cases of concurrent iron deficiency, MCV may appear normal.
- Low reticulocyte counts may be observed, with total white cell and platelet counts potentially reduced.
- Neutrophils may show hypersegmented nuclei (≥ six lobes).
Bone Marrow Findings
- Typically hypercellular with large erythroblasts exhibiting an open, fine chromatin pattern.
- Normal cytoplasmic hemoglobinization observed, with the presence of giant and abnormally shaped metamyelocytes.
Response to Therapy
- Patients report improvement within 24-48 hours of appropriate vitamin therapy, experiencing increased appetite and well-being.
- Hemoglobin levels should rise by 20-30 g/L every fortnight; white cell and platelet counts normalize within 7-10 days.
- Bone marrow returns to a normoblastic state within approximately 48 hours, though giant metamyelocytes may persist for up to 12 days.
Other Macrocytic Anemias
- Includes various non-megaloblastic causes of macrocytic anemia, indicating a broader spectrum of conditions that can affect red blood cell size.
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Description
Test your knowledge on megaloblastic anemias, including vitamin B12 and folate deficiencies, clinical features, diagnosis, and other macrocytic anemias. Learn about the characteristics and treatment of these blood disorders.
