hematology - anemias caused by defects in DNA

macrocytic anemias

defects in DNA metabolism leads to _____

megaloblastic anemia

oval macrocytes and hypersegmented neutrophils, due to deficiencies in vitamin B12 or folate

nonmegaloblastic anemia

macrocytes only and are not oval, normal in newborns, liver disease, chronic alcoholism, BM failure, reticulocytosis

folate

function is to transfer methyl groups and is important in metabolism of amino acids and nucleotides

5-methyltetrahydrofolate

folate’s main form, inactive until single methyl group is removed to form THF

nuclear cytoplasmic asynchrony

RNA processes occur at normal rates and results in unequal growth of the nucleus and cytoplasm

reverse transcriptase

one cause of these anemias could be patients taking _____ inhibitors for HIV treatment and show megaloblastic changes

glossitis

loss of epithelium of tongue, smooth surface and soreness

vitamin B12 deficiency

takes years to develop after dietary deficiency or malabsorption

folate deficiency

occurs in a few months

vitamin B12 deficiency

neurologic manifestations, memory loss, tingling and numbness, loss of balance, impairment of walking, personality changes or apoptosis, appears due to demyelination in CNS and PNS

folate deficiency

no neurologic symptoms, in pregnancy can lead to impaired formation of fetal nervous system resulting in spina bifida

folate deficiency

can be caused by inherited deficiency of PCFT transporter protein, intestinal disease, or surgical resection

vitamin B12 deficiency

can be caused by lack of intrinsic factor from inherited or acquired defect, failure to separate from food proteins (reduced acidity), failure to separate from haptocorrin (lack of trypsin), intestinal disease

pernicious anemia

caused by a lack of intrinsic factor from gastric parietal cells, these factors are required for vitB12 absorption

pernicious anemia

parietal cells are destroyed by autoimmune disorder, CD4 T lymphs mount an immune response to the gastric parietal cells

pernicious anemia

patient will have blocking antibodies to intrinsic factor and reduced acid production, gastrin levels increased, more than half of patients also have parietal cell antibodies as well

pernicious anemia

decreased H&H, may have blasts, low MCV, MCH increased due to larger cells, increased RDW