Definition: groups of anemias characterized by macrocytosis (in the peripheral blood) and megaloblastic changes in the bone marrow. The megaloblasts are large blasts – bone marrow.
In periphery= macrocytosis= macrocytic anemia
Cause: IMPAIRED DNA SYNTHESIS due to folate/ B12 deficiency Vitamin B12 is involved in the synthesis of methionine from homocysteine;methionine is necessary for the synthesis of myeline; B12 deficiency will explain the neurological manifestation, because of demyelination. Also B12 is involved in the reaction that transforms folic acid from inactive form (methyl TH4) in the active form (TH4). Folic acid is involved in biosynthesis of nucleic acids (DNA) DNA synthesis impairment:
Affects tissues with rapid turnover: hematopoietic precursors, gastrointestinal epithelial cell
Takes longer for nucleus to mature, but cytoplamic synthesis is not affected => Larger cells => megaloblastic haematopoiesis Megaloblastic changes in the bone marrow (BM):
On the erythroid line: abnormal precursors of erythrocytes called megaloblasts (large cells)
On the granulocytic line: gigantic metamyelocytes
On the megacariocytic line: large megacariocytes, with polilobulated nucleus. Because of the destruction of the abnormal precursors in the BM (ineffective erythropoiesis, granulopoiesis, megacariopoiesis) on the hemogram we have macrocytic anemia/ leucopenia/trombocytopenia. On the peripheral blood smear: macrocytes, hypersegmented neutrophils. Source for both B12 and folate: exogenous.
Source: animal (meat, dairy products); usually dietary intake far exceeds needs => a deficiency is almost always due to malabsorbtion (exception: true vegetarians and their breast-fed infants). 1 μg is necessary every day.
Liver deposits last about 3-5 years.
Serum level: 200-600pg/ml.
Absorption takes place in the terminal ileonum and is dependant of intrinsic factor (IF, Castle’s) secreted by parietal cells of...
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