Iron Metabolism Flashcards
Ferrous and ferric forms are components of …
hemoglobin, myoglobin, and mitochondrial cytochromes
- involved in reduction and oxidation rxns
T or F. Iron has no mechanism for active excretion
T; most is bound to protein
Iron Sources
10-20 mg/day is ingested from food sources
- only 1-2 mg absorbed (~10%)
Heme iron
most bioavailable form Fe 2+; from meat sources
Non-heme iron
Fe 3+
- legumes
- leafy green vegetables
- cereals
Absorption of non-heme iron
- enhanced by ascorbic acid and citric acid
- inhibited by polyphenols, phylates, and calcium
How much iron is lost daily through sweat and cell sloughing
1-2 mg
How much iron is released through hemolysis of senescent RBCs?
20 mg; reused by bone marrow
How much iron is lost through menstruation
0.8 mg/day
Iron and pregnancy
can require up to 1000 mg of iron
Approximately how much iron is in the body
~3500-4000 mg
List the progress of Iron as it is absorbed in the body
- ingested as either Fe 2+ or Fe 3+
- gastric acid reduces Fe 3+ to 2+
- absorbed in duodenum and upper jejunum
- converted back to Fe 3+ to bind to transferrin
- gets into cells via receptor-mediated endocytosis
- placed into protoporphyrin IX as 2+
Difference in absorption bw Fe 2+ and 3+
2+:
- enters enterocytes through heme transporter (heme oxygenase separates iron from heme)
3+:
- 3+ reduced to 2+ before enterocytes
- Ferrireductase: Dcytb
- now 2+, transported into enterocytes via divalent metal transporter 1 (DMT1)
How does iron get out of enterocytes?
- Ferroportin exports iron to the circulation
- Hephaestin oxidizes Fe
- transferrin carries 3+ to tissues
What is hepcidin?
- hormone made by hepatocytes
- negative regulator of iron absorption
- binds to ferroportin to prevent iron export
- limits absorption in gut and prevents release from storage
Hepcidin is an acute phase reactant
- upreg by inflammation and iron overload
- downreg in response to anemia and hypoxia
2/3 of the body’s iron is in
Hb
Storage forms of iron
- ferritin
- hemosiderin
Ferritin
- apofer. + Fe 3+ = ferritin
- globular protein cage w iron inside (M&M’s!)
- readily accessible!
- stored in macs, hepatocytes, and developing normoblasts
- water soluble
- not visible w light microscopy
Hemosiderin
- precipitated aggregates of ferritin
- fer cage is partially degraded; portion aggregate to form hemosiderin
- stable but less available
- not water soluble
0 visualized w light microscopy using Perls’ Prussian Blue Stain
Measures iron in the blood (only transferrin bound)
Serum iron
Total Iron Binding Capacity (TIBC)
indirect measure of the amount of transferrin available to carry iron
Transferrin saturation
calc of the % of transferrin bound to iron
- serum iron/TIBC x 100
Serum Ferritin
- reflects amount of stored iron
- also an acute phase reactant
Prussian Blue Stain
stains for stored iron (hemosiderin) in bone marrow smears or tissue biopsies
Hemochromatosis
- genetic condition that causes increased iron absorption (HFE gene)
- increased iron and hemosiderin in tissues = organ damage = organ failure
- treated by regular phlebotomy
Hemosiderosis
- iron overload secondary to repeated blood transfusions
- localized hemosiderosis from tissue hemorrhage or increased hemolysis
Sideroblastic anemia
- due to inability to produce heme
- increased or normal iron supply
- examples: lead poisoning, porphyrias
Pappenheimer Bodies
- clusters of blue inclusions in RBCs
- composed of precipitated hemosiderin, protein, and RNA
- seen in sideroblastic anemia (and others)
- not reported in the Edmonton zone
decrease in oxygen-carrying capacity of the blood
Anemia
This arises if there is insufficient Hb or the Hb has impaired function
Anemia
- decreased Hb conctn
- decreased RBC count
- decreased hematocrit
Causes of anemia
- decreased production
- increased destruction (immune + non-immune causes of hemolysis, hereditary or acquired RBC defect)
- increased loss (hemorrhage, etc.)
Laboratory diagnosis of anemia
- complete blood cell count
- RBC indices
- peripheral blood smear
- reticulocyte count
- bone marrow smear and biopsy