Flashcards in 268 II b Megaloblastic anemia Deck (13):
haptoglobin - low?
means that it is binding hemoglobin released from lysed RBCs
Megaloblastic anemia and PMNs? BM appearance?
hypercellular with large blasts in BM (megaloblastosis)
megaloblastic anemia cause?
shitty DNA synthesis --> BM precursor nucleus lags behind cytoplasm --> abnormal cells that lyse in BM/can't mature --> pancytopenia
hypercellular marrow, increased bilirubin, LDH, decreased haptoglobin (binds free hemoglobin)
causes of megaloblastic anemia?
can't convert orotic acid --> UMP (de novo pyrimidine synthesis) because bad UMP synthase
kids get megalobllstic anemia that isn't fixed with folate or B12
No hyperammonemia (vice ornithine transcarbamylase deficiency)
Rx - uridine monophosphate
B12 and folate relation and methyl
M-THF --> M to B12 --> M to homocysteine --> Methionine
if either are low --> increased homocysteine
B12 fxns, deficiency?
M transfer with THF --I DNA synthesis
Converts methylmalonyl CoA --> Succinyl CoA
**causes CNS symptoms if deficient because methylmaloyl CoA is toxic to myelin**
deficiency = increased homocysteine AND increased methylmalonic acid
B12 absorption? what can cause it?
gastric acid liberates B12 from protein --> R factors bind B12 --> duodenum: pancreatic proteases release R protein --> IF binds B12 --> terminal ileum takes up complex
diet - extremely rare
malabsorption --> PPI, low IF (pernicious anemia), gastrectomy, pancreatic insufficiency
B12 deficiency presentation, symptoms?
Neuro symptoms - degeneration
-peripheral neuropathy with sensorimotor dysfxn
oral radiolabeled B12 + IM B12 injection --> radio B12 should be excreted in urine if absorbed (thus malabsorption isn't an issue)
Next give radio B12 w/ IF + IM B12 --> increased urine amount if pernicious anemia
folic acid metabolism and source
THG-M --> M to B12 leave THF
THF involved in purine and pyrimidine synthesis - requires dihydrofolate reductase
source: leafy green veggies, low body stores (months)
what drugs are dihydrofolate reductase inhibitors?