268 II b Megaloblastic anemia

Question 1

haptoglobin - low?

Answer 1

means that it is binding hemoglobin released from lysed RBCs

Question 2

Megaloblastic anemia and PMNs? BM appearance?

Answer 2

hypersegmented

hypercellular with large blasts in BM (megaloblastosis)

Question 3

megaloblastic anemia cause?

Answer 3

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)

Question 4

causes of megaloblastic anemia?

Answer 4

Folate deficiency

B12 deficiency

orotic aciduria

Question 5

Orotic aciduria

Answer 5

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

Question 6

B12 and folate relation and methyl

Answer 6

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

if either are low –> increased homocysteine

Question 7

B12 fxns, deficiency?

Answer 7

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

Question 8

B12 absorption? what can cause it?

Answer 8

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

Question 9

B12 deficiency presentation, symptoms?

Answer 9

macro-ovalocytes

hypersegmented PMN

Neuro symptoms - degeneration

• dorsal (vibration/proprioception)
• lateral (spasticity)
• peripheral neuropathy with sensorimotor dysfxn
• dementia

Question 10

Schilling test

Answer 10

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

Question 11

folic acid metabolism and source

Answer 11

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)

Question 12

what drugs are dihydrofolate reductase inhibitors?

Answer 12

methotrexate

trimethoprim

Question 13

folate deficiency symptoms/clinical features?

Answer 13

glossitis
megaloblastic anemia (hypersegmented PMNs)
NTD

No CNS issues (as opposed to B12)

increased homocysteine, normal methylmalonic acid