Iron Flashcards
distribution
1800 mg RBC 1000 mg liver 600 mg macrophages 300 mg bones 300 mg muscle 3 mg transferrin
iron containing heme proteins
hemoglobin (for O2– Fe containing porphyrin ring)
myoglobin (O2 in cytoplasm of muscle cells)
cytochromes (electron carriers)
Fe- S enzymes
aconitase
iron storage and transfer proteins
transferrin (Fe carrying in plasma)
lactoferrin (Fe binding in milk)
ferritin and hemosiderin (storage form of Fe in cells)
Functions
transport O2 in body, normal cell function, synthesis of hormones, connective tissue
Absorption– Heme
heme iron- meats. 5-10% of dietary iron in western countries
bioavailability is 20-30%
binds to HCP1 –> intestinal cell
Absorption– nonheme
plants (Fe3+)
(+) absorption:
(+) solubilization of Fe in food (stomach acid)
(+) reduction of Fe2+ (by VitC, Dcyt b- Fe3+ reductase) at mucosal surface of duodenum
(-) absorption:
phytates, polyphenols
transport into intestinal cell
Heme: HCP1
nonheme: DMT1
Storage
either stored as ferritin or transported across basolateral membrane –> circulation.
Export
If Fe needed, passes into labile iron pool, processed for export by ferroportin (transport protein, IREG1). efflux of iron across basolateral surface of enterocytes to blood is achieved through coordinated action of ferroportin
Ferroportin
transport Fe from inside cell–> out.
in enterocytes, hepatocytes, macrophages
hepcidin
(-) ferroportin, traps iron inside intestinal cell
hephaestin
(alpha ferroxidase) converts Fe2+ –> Fe3+, delivers iron to plasma transferrin
Fe into Hgb by erythrocyte precursor cells: mechanism
- transferrin in plasma can bind 2 atoms of iron as Fe3+
- diferric transferrin– transferrin receptors (TfR) in cell surface
- TfR + transferrin –> cell, acidification –> Fe + transferrin (separated)
- Fe3+ –> Fe2+ –> out of endosome (DMT1)
- Fe2+ –> mitochondria –> Fe-Hgb + Fe-S proteins
iron balance and excretion
fecal loss from shed enterocytes, extravasated RBCs, biliary heme breakdown products.
menstrual loss ~1.5 mg/d
clinical outcomes of deficiency
low work performance, cognitive development, adverse pregnancy outcomes, difficulty maintaining body temp, low immune function, glossitis
at risk
pregnant, infants, young children, heavy periods, freq blood donors, cancer, GI disease, heart failure, anemia of chronic dz
Fe and heart disease
60% of patients w CHF have Fe deficiency, 17% IDA –> inc risk of death
Fe and intense exercise
inc exercise –> inc RBC turnover, inc whole body Fe turnover
Fe/Ca supplements
inc Ca –> low bioavailability of heme/ nonheme iron
Stages of Fe depletion
mild deficiency/ storage iron depletion: low ferritin, low Fe in bone barrow
marginal deficiency/ mild functional deficiency/ iron deficient erythropoiesis: low iron stores, low plasma iron, low transferrin, inc STfR
Iron deficient anemia: (iron stores exhausted) low Hct, low Hgb, microcytic, hypochromic anemia
3 types of anemias
microcytic: MCV <80, low Fe, Low Cu, low B6
normocytic MCV 80-100, protein calorie malnutrition
macrocytic MCV >100, low B12, folate