iron metab

Question 1

describe properties of iron

Answer 1

• very useful for binding oxygen and transferring electrons
• But it Rusts
  
  • meaning: oxygen can remove an electron and transform it from the useful Fe2+ to rather useless Fe 3+
    
    • doesn’t hold onto its electrons well
  • transfer of electron to oxygen causes reduced oxygen which poses a problem (Reactive oxygen species)
• iron needs to be controlled at all times: NO FREE Fe2+/3+ allowed

Question 2

describe the ROS production by iron and copper

Answer 2

oxygen wants to become water

• so it pulls electron from other sources
• O2- and HO- are both radicals (HO- is really bad)

Question 3

Dietary sources of iron

Answer 3

• Need about 10-20 mg/day in normal diet
  
  • todays diet is usually sufficient (exception: growth, blood loss)
    
    • no way of excreting iron through feces or urine
  • plant iron is mostly Fe3+ (only 5% taken up)
  • Animal iron is mostly heme-bound (about 25% taken up)

Question 4

Excretion of iron

Answer 4

• No regulated loss through urine
  
  • iron should be bound to protein all the time
  • iron homeostasis regulated through UPTAKE ONLY
• Blood loss
  
  • can occur in intestine
  • intravascular hemolysis (hemoglobin in urine)
• Sloughing off of iron-containing cells in the intestine and kidney
  
  • continue iron loss…

Question 5

iron distribution in body

Answer 5

• 80% in active forms
  
  • hemoglobin, myoglobin, cytochromes
  • Transport: Transferrin (in transit)
• 20% is in inactive form
  
  • dynamic storage: ferritin
  • Degenerated, long-term storage: HEMOSIDERIN

Question 6

describe the flow of iron through body

Answer 6

1. Iron is taken up in diet (heme, Fe3+) by Enterocytes
2. Iron in plasma bound to transferrin
   
   1. can be transported and stored iin the liber
3. can be bound to erythroid precurors to make RBC iron (heme)
   
   1. iron can be shedded or blood loss can occur
4. Mononucleaur phagocytes can degrade the RBC and take up iron to become phagocyte iron (ferritin)
   
   1. stored and recycled

Question 7

describe the regulation of the uptake of iron in enterocyte

Answer 7

• enterocyte has 3 systems on luminal side
  
  • cytochrome B –> reduces things
  • DMT1 –> takes up metals with 2+ charge (Fe2+)
  • heme transporter
• Iron Fe2+ can directly pass through DMT1
• Iron Fe3+ must be reduced by Cytochrome B first and then through DMT1
• Both iron coming in from heme and DMT1 is stored within Ferritin (keeps iron on the inside)
  
  • if no need for iron then ferritin granules build up in enterocytes
  • Ferroportin 1 exports from enterocyte into the circulation (decides how much iron is available)
• Fe2+ must be oxidized to Fe3+ to make sure it doesnt do any damage and bound to Transferrin to be transported

Question 8

role of Ferroportin 1

Answer 8

• regulates how much iron is available in the body by regulating the release of iron from enterocyte ferritin granules into circulation

- IRON EXPORT inhibited by HEPCIDIN

• once Ferroportin 1 releases Fe2+ it must be oxidized to Fe3+ to prevent oxidized radicals and bound to TRANSFERRIN to be transported around body.

Question 9

Describe the generals of iron inside the cell

Answer 9

• Iron binds to ferritin
  
  • water soluble
  • easy to mobilize
  • high conc in liver, spleen and bone marrow
• ferritin particles slowly denature to hemosiderin granules
  
  • water insoluble
  • hard to movilize
  • sign of iron overload (lots of granules is bad)

Question 10

describe the role macrophages play in iron metabolism

Answer 10

• the life of red blood cells usuall ends in splenic macrophages (extravascular)
  
  • macrophages take up the iron
  • a hemolytic disorder leads to accumulation of ferritin and hemosiderin in macrophages

Question 11

describe the regulation of iron uptake**

Answer 11

• Iron uptake into body is regulated by RELEASE OF IRON FROM ENTEROCYTES
• MAIN REGULATORS: The INHIBITOR HEPCIDIN
  
  • low hepcidin = HIGH UPTAKE
  • Hepcidin also regulates IRON RELEASE FROM MACROPHAGES
• upstream regulator, often defective: HFE
  
  • mutation in HFE cause LOW HEPCIDIN EXPRESSION
    
    • causes IRON OVERLOAD

Question 12

describe laboratory tests (TIBC)

Answer 12

• Serum iron conc
  
  • no information about body iron stores
• Total iron binding capacity (TIBC) or transferrin saturation
  
  • TIBC measures UNOCCUPIED TRANSFERRIN (the higher the TIBC, the lower the iron stores)
  • Transferrin saturation measures OCCUPIED transferrin (the higher the saturation, the high the iron stores

Question 13

describe laboratory tests (serum ferritin, red cell protoporphytrin)

Answer 13

• Serum ferritin
  
  • fraction of ferritin is present in serum - BEST MEASURE for body iron stores
• Red cell protoporphyrin
  
  • protoporphyrin is IRON-free precursor of heme
  • the lower the iron stores, the higher the protoporphyrin

Question 14

causes of iron deficiency

Answer 14

chronic blood loss

chronic disease (hepcidin production)

poor dietary intake (limited absopriton of plant iron)

intestinal parasites (compete for iron)

malabsorptive disease (celiac)

Question 15

Iron deficiency develops into anemia via STAGES

Answer 15

• Iron depletion –> serum ferritin falls
• Deficient erythropoiesis –> hemoglobin still normal, but protoporphyrin levels up, transferring saturation falls
• Iron deficiency anemia –> HYPOCHROMIC (low hemoglovin), microcytosis
  
  • look for size differences in erythocytes

Question 16

describe iron overload

Answer 16

• CAUSES
  
  • blood transusion for tx of hemolytic disease (iron accumulates in macrophages)
  • slow erythropoiesis (renal failure)
  • hereditary hemochromatosis type I (HFE mutation, up to 10% of population are carriers)
• LAB RESULTS SHOW
  
  • HIGH TRANSFERRIN SATURATION
  • Hemosiderin deposits (in liver) (mostly ASYMPTOMATIC)