8. Nutritional Deficiency Anemias Flashcards
which 3 nutrients are relevant to anemias, and general type?
Iron defic: microcytic anemia (affects hemoglobin synth)
Folate and B12 defic: macrocytic and megaloblastic anemia (affects DNA synth)
total iron pool for men vs women
3540 mg vs 2450 mg
iron cycle
- Fe recycled b/w functional and storage pools
- Some shedding each day, but balance maintained by regulating absorption of dietary Fe in proximal duodenum
○ Balance thanks to loss in keratinocytes, enterocytes, and endometrium shedding - Absorbed iron (gut) bound to transferrin for transport to marrow
○ Delivered to developing RBCs & incorporated into Hb
○ Erythroid precursors in marrow w/ high affinity receptors for transferrin
§ Fe import through receptor-mediated endocytosis - Mature RBCs rel. into circulation
- Life of 120 days
- Post ^ ingested by macrophages in spleen, liver, and bone marrow
- Fe extracted from Hb and recycled to plasma transferrin (synth in liver)
- Some shedding each day, but balance maintained by regulating absorption of dietary Fe in proximal duodenum
regulation of Fe absorption
- Hepcidin = circlulating small peptide
○ Synth and released from liver re: increase in intrahepatic Fe levels- Q storage sites replete w/Fe and erythropoietic activity is normal, hepcidin is high
○ Downregulation of ferroportin and trapping of most of the absorbed iron
○ Lost duodenal epith cells are shed into gut - Q storage sites have no Fe or w/ stimulated erythropoietic activity, hepcidin levels fall
○ Ferroportin activity increases
○ Greater fraction of absorbed iron transferred to plasma transferrin - Non-heme iron (Fe3+ ferric form) is reduced to Fe++ ferrous state by brush border ferrireductase pre abosrption
○ Transported in thanks to DMT1
○ Variable, affected by diet - The mucosal “barrier” is insufficient to prevent the inappropriate absorption of supraphysiologic amounts of iron, e.g. accidental ingestion of medicinal iron.
- Q storage sites replete w/Fe and erythropoietic activity is normal, hepcidin is high
heme vs nonheme iron
20-25% absorbable vs 1-5% absorbable
Fe absorption vs requirements
- Daily requirement: absorbed from 10-20 mg dietary Fe
○ Men and postmenopausal women: 8 mg/d RDA
○ Premenopausal women: 18 mg/d RDA
○ Pregnant women: 27 mg/d RDA- Absorption varies inversely w/stores
○ Iron sufficiency: absorb ~5% from diet
○ Iron deficiency: absorb >10% from diet
- Absorption varies inversely w/stores
groups at increased risk for iron deficiency
Groups at ^ Risk for Fe deficiency
- Women of childbearing age, esp w/lots of menstrual loss - Pregnant women - Teenage girls - Preterm and LBW infants - GI disease and malabsorption - Renal failure, esp on dialysis (platelet dysfunction and occult GI bleeding) - Regular blood donors
markers of Fe deficiency
- Decreased serum iron
- Increased serum transferrin (TIBC)
- Decreased transferrin saturation
○ % sat = Fe/TIBC X100% - Increased soluble transferrin receptor
- Decreased ferritin (reflects low storage iron)
○ Acute phase reactant**
w/prolonged inflammation, may have it increased
lab findings of iron deficiency anemia (peripheral blood smear)
decreased MCV, decreased MCHC
clinical manifestations of Fe deficiency anemia
○ Sx of anemia
§ Fatigue, headache, irritibility
○ Pica
○ Epithelial changes (uncommon) (angular stromatitis, koilonychia, mucosal web)
○ Children
§ Retarded growth, impaired cognitive development
○ Pregnancy
Increased risk of preterm birth and LBW
Tx iron deficiency anemia
○ Oral iron salts = effective and cheap
§ Dose: 150-200 mg/day elemental iron in in 3 divided doses
□ FeSO4 300 mg provides 60 mg of elemental iron. 60 x 3 = 180 mg/day. The absorbed amount at this dose (assuming 10% absorption) is only 18 mg.
§ Adverse effects: GI irritation
□ Nausea
□ Constipation
□ Diarrhea
○ Parenteral iron
§ Selected pts
□ Dialysis dependent renal failure treated w/ EPO
Hematopoietic response no faster than w/ oral iron and oral iron is safer (less risk of anaphylaxis)
treatment response to tx for Fe deficient anemia
○ Hematopoietic response § ^ retic. □ Starts 3-4 days □ Peaks 5-10 days § ^ Hb □ Starts 2 weeks □ Takes 2-3 months ○ Rx after anemia is corrected to replenish iron stores § Monitor serum ferritin
Treat underlying cause
pathophys of anemia of chronic disease
cytokine mediated induction of hepcidin and inhibition of erythropoiesis (not responsive to supplemental iron)
iron deficiency vs anemia of chronic disease: iron, ferritin, cytokine levels
iron: reduced in both
ferritin: normal to increased in chronic, reduced in iron deficiency
cytokine: increased in chronic, normal in iron defic
macrocytic vs megaloblastic anemia
Not ALL macrocytic anemias are megaloblastic (but all megaloblastic anemias are macrocytic)
- Macrocytic: big cells - Reticulocytosis, liver disease, other conditions can also cause big cells that are not megaloblastic
Megaloblastic cell shave a characteristic nuclear maturation defect
