Lecture 29 - Megaloblastic anemia

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Lecture 29
Lesley Howard
FlashCards por Lesley Howard, atualizado more than 1 year ago
Lesley Howard
Criado por Lesley Howard mais de 8 anos atrás
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Macrocytic anemia Characterized by larger than normal RBCs MCV > 100 Can be megaloblastic or not
Macrocytic anemia labs MCHC WNL MCH elevated due to large cytosol HBC decreased due to less RBCs
Non-megaloblastic anemia Milder form No DNA synthesis impairment MCV up to 110 fL
Megaloblastic anemia MCV = 110 - 160 fL DNA synthesis impaired B12 or folate deficiency Large cytoplasm / normal protein synthesis Megaloblast cells in bone marrow Hypersegmented neutrophils
Folate deficiency Usually dietary Body doesn't store much folate
Methotrexate Used to treat cancer Structural analog of folate Inhibits DHFR Strongly affects rapidly dividing cells Side effect of MB anemia
Dihydrofolate reductase Repeat reactions with folate produces tetrahydrofolate NADPH dependent Uses folate as a substrate
Tetrahydrofolate Carbon carrier for metabolic reactions Supplies carbon for nucleotide synthesis Cannot be synthesized without folate
Homocystiene methyltransferase Transfers the methyl group from N5 methyl THF to methionine Requires B12 as cofactor B12 deficiency means THF is not recycled and SAMe is not created
Pernicious anemia Autoimmune mediated by T cells Destruction of parietal cells reduces IF secretion and stomach acidity Inhibits ability of body to absorb B12
MB anemia blood smear Low RBC Oval macrocytes Anisocytosis Poikilocytosis Large hypersegmented neutrophils Low/normal reticulocytes Thrombocytopenia Leukocytopenia
MB anemia bone marrow Megaloblastic changes in all stages of development due to impairment of DNA synthesis Increased destruction of platelet precursors Increased destruction of granulocytes
Methylation Stabilizes myelin Without B12 there is no SAMe Without SAMe there is no methylation Without methylation myelin is destabilized Neuropathy results in B12 deficiency
Folate trap Result of B12 deficiency Homocystiene methyltransferase inactive N5 methyl THF cannot be recycled back to THF and is trapped Becomes a functional folate deficiency
Methylmalonyl CoA mutase Requires B12 as a cofactor Used to determine whether MB anemia is from folate or B12 If B12, will result in a buildup of substrate If folate, will be ineffective
R Binder Secreted in mouth Binds to B12 released from protein in the stomach Facilitated by pepsin and low pH from parietal cells Degraded in duodenum at neutral pH
Intrinsic factor Secreted in stomach by parietal cells Binds B12 in duodenum Binds with B12 to IF receptors in the ileum
Intrinsic factor receptors Present on the apical membrane of ileal cells Binds to IF2/B12 complex and promotes endocytosis and absorption Once inside IF will release B12
Transcobalamin II Binds B12 within ileal cells and transports it to tissues B12/TCII complex exits the basal side of the ileal cell and goes into portal circulation
Folate deficiency symptoms MB anemia Glossitis
B12 deficiency symptoms MB anemia Glossitis Peripheral neuropathy

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