Karteikarten
Lecture 29 - Megaloblastic anemia
Karten in diesem Stapel (21)
- 1Macrocytic anemiaCharacterized by larger than normal RBCs
MCV > 100
Can be megaloblastic or not - 2Macrocytic anemia labsMCHC WNL
MCH elevated due to large cytosol
HBC decreased due to less RBCs - 3Non-megaloblastic anemiaMilder form
No DNA synthesis impairment
MCV up to 110 fL - 4Megaloblastic anemiaMCV = 110 - 160 fL
DNA synthesis impaired
B12 or folate deficiency
Large cytoplasm / normal protein synthesis
Megaloblast cells in bone marrow
Hypersegmented neutrophils - 5Folate deficiencyUsually dietary
Body doesn't store much folate - 6MethotrexateUsed to treat cancer
Structural analog of folate
Inhibits DHFR
Strongly affects rapidly dividing cells
Side effect of MB anemia - 7Dihydrofolate reductaseRepeat reactions with folate produces tetrahydrofolate
NADPH dependent
Uses folate as a substrate - 8TetrahydrofolateCarbon carrier for metabolic reactions
Supplies carbon for nucleotide synthesis
Cannot be synthesized without folate - 9Homocystiene methyltransferaseTransfers 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 - 10Pernicious anemiaAutoimmune mediated by T cells
Destruction of parietal cells reduces IF secretion and stomach acidity
Inhibits ability of body to absorb B12 - 11MB anemia blood smearLow RBC
Oval macrocytes
Anisocytosis
Poikilocytosis
Large hypersegmented neutrophils
Low/normal reticulocytes
Thrombocytopenia
Leukocytopenia - 12MB anemia bone marrowMegaloblastic changes in all stages of development due to impairment of DNA synthesis
Increased destruction of platelet precursors
Increased destruction of granulocytes - 13MethylationStabilizes myelin
Without B12 there is no SAMe
Without SAMe there is no methylation
Without methylation myelin is destabilized
Neuropathy results in B12 deficiency - 14Folate trapResult of B12 deficiency
Homocystiene methyltransferase inactive
N5 methyl THF cannot be recycled back to THF and is trapped
Becomes a functional folate deficiency - 15Methylmalonyl CoA mutaseRequires 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 - 16R BinderSecreted 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 - 17Intrinsic factorSecreted in stomach by parietal cells
Binds B12 in duodenum
Binds with B12 to IF receptors in the ileum - 18Intrinsic factor receptorsPresent on the apical membrane of ileal cells
Binds to IF2/B12 complex and promotes endocytosis and absorption
Once inside IF will release B12 - 19Transcobalamin IIBinds 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 - 20Folate deficiency symptomsMB anemia
Glossitis - 21B12 deficiency symptomsMB anemia
Glossitis
Peripheral neuropathy