268 II b Megaloblastic anemia Flashcards Preview

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Flashcards in 268 II b Megaloblastic anemia Deck (13):
1

haptoglobin - low?

means that it is binding hemoglobin released from lysed RBCs

2

Megaloblastic anemia and PMNs? BM appearance?

hypersegmented

hypercellular with large blasts in BM (megaloblastosis)

3

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)

4

causes of megaloblastic anemia?

Folate deficiency

B12 deficiency

orotic aciduria

5

Orotic aciduria

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

6

B12 and folate relation and methyl

M-THF --> M to B12 --> M to homocysteine --> Methionine

if either are low --> increased homocysteine

7

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

8

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

9

B12 deficiency presentation, symptoms?

macro-ovalocytes

hypersegmented PMN

Neuro symptoms - degeneration
-dorsal (vibration/proprioception)
-lateral (spasticity)
-peripheral neuropathy with sensorimotor dysfxn
-dementia

10

Schilling test

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

11

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)

12

what drugs are dihydrofolate reductase inhibitors?

methotrexate
trimethoprim

13

folate deficiency symptoms/clinical features?

glossitis
megaloblastic anemia (hypersegmented PMNs)
NTD

No CNS issues (as opposed to B12)

increased homocysteine, normal methylmalonic acid