TAILIEUCHUNG - Chapter 100. Megaloblastic Anemias

The megaloblastic anemias are a group of disorders characterized by the presence of distinctive morphologic appearances of the developing red cells in the bone marrow. The cause is usually deficiency of either cobalamin (vitamin B12) or folate, but megaloblastic anemia may arise because of genetic or acquired abnormalities affecting the metabolism of these vitamins or because of defects in DNA synthesis not related to cobalamin or folate (Table 100-1). Cobalamin and folate absorption and metabolism are described next and then the biochemical basis, clinical and laboratory features, causes, and treatment of megaloblastic anemia. The marrow is usually cellular, and. | Chapter 100. Megaloblastic Anemias The megaloblastic anemias are a group of disorders characterized by the presence of distinctive morphologic appearances of the developing red cells in the bone marrow. The cause is usually deficiency of either cobalamin vitamin B12 or folate but megaloblastic anemia may arise because of genetic or acquired abnormalities affecting the metabolism of these vitamins or because of defects in DNA synthesis not related to cobalamin or folate Table 100-1 . Cobalamin and folate absorption and metabolism are described next and then the biochemical basis clinical and laboratory features causes and treatment of megaloblastic anemia. The marrow is usually cellular and the anemia is based on ineffective erythropoiesis. Table 100-1 Causes of Megaloblastic Anemia Cobalamin deficiency or abnormalities of cobalamin metabolism see Tables 100-3 100-4 Folate deficiency or abnormalities of folate metabolism see Table 100-5 Therapy with antifolate drugs . methotrexate Independent of either cobalamin or folate deficiency and refractory to cobalamin and folate therapy Some cases of acute myeloid leukemia myelodysplasia Therapy with drugs interfering with synthesis of DNA . cytosine arabinoside hydroxyurea 6-mercaptopurine azidothymidine AZT Orotic aciduria responds to uridine Thiamine-responsive Cobalamin Cobalamin vitamin B12 exists in a number of different chemical forms. All have a cobalt atom at the center of a corrin ring. In nature the vitamin is mainly in the 2-deoxyadenosyl ado form which is located in mitochondria. It is the cofactor for the enzyme methylmalonyl CoA mutase. The other major natural cobalamin is methylcobalamin the form in human plasma and in cell cytoplasm. It is the cofactor for methionine synthase. There are also minor amounts of hydroxocobalamin to which methyl- and adocobalamin are rapidly converted by exposure to light. Dietary Sources and Requirements Cobalamin is synthesized solely by microorganisms. Ruminants obtain

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