Disorders of Iron Kinetics and Heme Metabolism

What is the most critical metal in the body?

Iron

What are cytochromes and where are they found in the body?

Heme containing proteins that are found in the mitochondria and are vital to the electron transport chain (production of ATP)

What is Irons role in the body?

It is essential for oxygen transport and is attached to HGB molecules in the RBC

Where is Iron found in the body?

• 65% is housed in HGB molecules

• 25% is stored in the form of ferritin and hemosiderin

• 10% in myoglobin, cytochromes, iron-containing enzymes, plasma

The body has no mechanism for active excretion, what does this mean?

The body tightly regulates the amount of iron it takes via absorption in the intestines

What is the iron storage capacity for men?

2.5-4g

What is the iron storage capacity for women?

2-3g

Why is iron recycled in the body?

So the body can conserve as much as possible

How is iron recycled?

1. Aging RBCs are ingested by macrophages in the spleen

2. HGB is broken down and kept in the form of ferritin

3. Ferritin can be used by erythroblasts when needed

Each HGB molecule can carry how many molecules of oxygen?

4

A decrease in body iron leads to what regarding HGB?

Defective HGB synthesis resulting in a decrease in HGB levels in the body

What is the majority of iron utilized for?

Hemoglobin synthesis (65-70%)

What is ferritin?

The main storage area for body iron - found in many cells especially the liver

• metabolically active and easily accessible

What is Hemosiderin?

Partially degraded ferritin

• not metabolically active

• Intracellular storage form of iron

• Can used Prussian blue stain to ID microscopically

Where does the body get non-heme iron?

Nuts, seeds, vegetables, etc

Where does the body get heme iron?

Meat, poultry, fish, etc.

If body iron increases what happens?

1. Hepcidin will increase

2. Ferroportin door is blocked from transporting iron out

3. Decrease in iron absorption in intestines and iron release from storage

4. Decrease body iron → hepcidin

What is the serum iron study?

Testing the amount of circulating iron that is bound to plasma transferrin

How does the serum iron test work?

1. Acid causes the release of iron from the transferrin molecule

2. Free iron forms a coloured complex when mixed with the test reagent

3. Iron is limited bc of its daily fluctuation (fasting morning collection preferred)

What does the total iron binding capacity test do?

Tests the total amount of iron that can be bound to transferrin

The amount of iron in plasma/serum is limited by?

The amount of transferrin that is available

How does the TIBC test work?

1. Excess ferric iron is mixed with a specimen to saturate the transferrin sites

2. Unbound iron is removed with a magnesium carbonate powder

3. The Serum Iron test is performed and the iron release from the transferrin is measured = TIBC

• an indirect measurement of transferring concentration

What is the Percent Transferrin Saturation test (%SAT)?

It represents the degree by which the available transferrin sites are occupied by iron

• about 1/3 of transferrin is typically saturated

What is the calculation for %SAT test?

Serum Iron/Total Iron Binding Capacity x 100 = %SAT

What does a %SAT result of <16 mean you have?

Iron Deficiency Anemia

Does prussian blue staining detect Ferritin or Hemosiderin?

Hemosiderin

What is prussian blue staining made of?

It is a compound that forms during a staining process and uses acidic potassium ferrocyanide as the reagent/stain

How does prussian blue staining work?

The ferric iron in tissues reacts with the stain to form the Prussian blue compound ands the tissue can be graded based on the amount of stain seen

What is the gold standard for assessing body iron?

Prussian blue staining

What is the purpose of checking the hemoglobin content of reticulocytes?

It reflects the amount of iron available for hemoglobin production in the bone marrow

• the # of retics in the blood represents the status of the erythropoiesis in the prior 24hr period

What is ferritin?

An acute phase reactant that is produced by the liver in the initial phase of inflammation

How is ferritin measured?

Serum immunoassay techniques

Ferritin levels are directly proportional to what?

The amount of stored body iron

Cells regulate the amount of Transferrin Receptors on their membrane based on what?

The levels of intracelular iron therefore, Decreased Iron = Increased Transferrin Receptors

What is Soluble transferrin receptors?

A portion of the transferrin receptor cell membrane that has been shed into the plasma and measured using immunoassay

An increase in soluble transferrin receptors =

An increase in membrane transferrin receptors on individual cells = iron deficiency

What is Zinc Protoporphyrin?

ZPP accumulates in RBCS when iron is not incorporated into heme (free erythrocyte protoporphyrins)

How does an iron deficiency affect zinc protoporphyrins?

It leads to an increase of ZPP