Iron
Iron:
First let’s break down the players
Fe2+: ferrous iron, the form of iron used in heme synthesis
Fe3+: ferric iron
Transferrin: a beta globulin that carries iron in the blood
Ferritin: iron storage in the gastrointestinal mucosa, liver, spleen, bone marrow, and reticuloendothelial cells.
Hemosiderin: intracellular form of iron storage
Iron transport and metabolism is a complex process. We’ll break down the basics here, and give a general understanding of the major players.
Most dietary iron is in the form of Fe3+ (ferric iron). Iron is absorbed into intestinal cells through a series of complex reactions, and it either stays there as storage in the form of ferritin or is released into the plasma. Since iron can be toxic to cells and biomolecules when it’s in the plasma, it’s got a chauffeur. Transferrin transports iron (Fe3+) in the blood, each transferrin molecule has two binding sites for Fe3+ that range from 20-50% saturation (more on transferrin saturation later). Another series of complex reactions takes place, and iron is transported into the cell, and during this process is converted into ferrous iron (Fe2+) which can be used in heme synthesis. Woohoo!
About 2/3 of iron is used in hemoglobin, another 10% is found in myoglobin and other processes, and the remaining 20-25% is storage iron.
Lab measurements of iron:
There’s a lot of ways to measure iron.
Total iron binding capacity (TIBC):
Measures the amount of total iron transferrin is able to bind. Think of TIBC as seats in a stadium. The TIBC test is run by adding excess Fe3+ to the sample, equilibrating, and then washing away excess Fe3+. The Fe3+ is then measured and you have your TIBC.
Serum iron:
Serum iron represents the amount of iron currently bound to transferrin. Serum iron is how many people are in the stadium. Serum iron can be falsely elevated in hemolysis and has a diurnal pattern where it is higher in the morning than at night. Serum iron results need to be used with other results.
Transferrin % saturation:
Transferrin % saturation can be calculated using the formula serum iron/TIBC x 100. Think of this as the percent capacity of the stadium. Is it sold out? Is it half full? Is barely anyone there? Serum iron tells you the attendance, TIBC tells you the stadium capacity. Multiply by 100 to get the percent.
Ferritin:
Ferritin is a protein that stores iron. A small amount of ferritin can be found in the serum and is indicative of current iron levels. Serum ferritin can be one of the first indicators that there is an iron deficiency (or iron deficiency anemia). Why is this? Let’s say there’s a messy eater in your house who is always leaving chip crumbs on the ground. One day you notice there’s no chip crumbs. Then you look in the pantry and there’s no chips. The chip bags are representative of storage iron, and the crumbs serum ferritin. Another important term is apoferritin. The prefix apo- means apart from or away from, so apoferritin is ferritin without iron. Is that possible? Yes! Most of the serum ferritin is in the apo form. One precaution, ferritin is an acute phase reactant, meaning it can fluctuate quickly due to an underlying condition. Ferritin can be falsely elevated in liver disease and hyperthyroidism. Ferritin is commonly measured using a serum immunoassay.
Things that can go wrong with iron:
Iron deficient anemia:
This is the most common nutritional cause of anemia in the world. If a person becomes deficient in iron, their iron stores will be used up, and that’s the point when chemistry iron tests will look abnormal. For example serum ferritin could be low and an elevated TIBC could be observed. If the iron deficiency continues it will be seen in hematology tests. All departments are connected! We’re coming full circle here! Hemoglobin will be decreased due to the lack of heme synthesis and microcytic hypochromic RBCs will be present.
Hemochromatosis:
Iron overload! There is a hereditary and acquired version on this condition. Both store too much iron in various organs including the liver and heart amongst others depending on the condition. The iron overload eventually leads to organ failure.
Study Tip
Most questions about iron will revolve around four parameters: serum iron, TIBC, serum ferritin, and % transferrin saturation. These parameters tend to be intuitive. Just go back to the analogies drawn above. Serum iron is people in the stadium; TIBC is the amount of seats; % transferrin saturation is the amount of seats that are filled as a percentage of the whole stadium, and serum ferritin is chip crumbs! Here’s a chart of common iron related conditions where you can practice thinking through the results. The more concepts you can understand and think through the better.
| Condition | Serum iron | TIBC | % Transferrin saturation | Serum ferritin |
| Normal range | 50-165 ug/dL | 250-425 ug/dL | 20-55% | 12-125 ng/mL female 25-250 ng/mL male |
| Iron deficient anemia | ↓ | ↑ | ↓ | ↓ |
| Hemochromatosis | ↑ | ↓ | ↑ | ↑ |
| Anemia of chronic infection | ↓ | ↓ | ↓ | ↑ |
| Storage iron depletion | N | N | N | ↓ (no chip crumbs!) |
| Beta-Thalassemia | ↑ | ↓ | ↑ | ↑ |
| Beta Thalassemia minor | N | N | N | N |
Beta thalassemia results are based off of the patients need for regular blood transfusions. The iron accumulates. In beta thalassemia minor, iron levels are normal.