Describe how iron is absorbed, transported and stored in our body. Give the different tests done to assess status of iron in the body.

Iron Absorption

Iron absorption primarily occurs in the duodenum and proximal jejunum. It exists in two forms in food: heme iron (found in animal products) and non-heme iron (found in plant-based foods). Heme iron is absorbed more efficiently (15-35%) than non-heme iron (2-20%).

• Heme Iron Absorption: Heme is taken up by enterocytes via heme carrier protein 1 (HCP1). Inside the cell, heme oxygenase breaks down heme, releasing iron.
• Non-Heme Iron Absorption: Non-heme iron (Fe³⁺) is first reduced to Fe²⁺ by duodenal cytochrome b reductase (Dcytb). Fe²⁺ is then transported across the apical membrane of enterocytes by divalent metal transporter 1 (DMT1), also known as SLC11A2.
• Regulation of Absorption: Hepcidin, a peptide hormone produced by the liver, plays a central role in regulating iron absorption. It binds to ferroportin, the only known iron exporter in cells, causing its internalization and degradation, thereby reducing iron absorption and release from stores. Factors increasing hepcidin levels (inflammation, high iron stores) decrease absorption, while factors decreasing hepcidin (hypoxia, anemia) increase absorption.

Iron Transport

Once absorbed, iron enters the circulation bound to transferrin, a glycoprotein synthesized in the liver. Each transferrin molecule can bind two Fe³⁺ ions.

• Transferrin-Iron Complex: The transferrin-iron complex delivers iron to cells throughout the body via transferrin receptors (TfR1 and TfR2).
• TfR1: Primarily responsible for delivering iron to rapidly dividing cells, such as erythroid precursors in the bone marrow.
• TfR2: Plays a role in regulating hepcidin expression.

Iron Storage

The primary storage forms of iron are ferritin and hemosiderin.

• Ferritin: A soluble protein complex that stores iron in a non-toxic, readily available form. It is found in most tissues, but predominantly in the liver, spleen, and bone marrow. Ferritin levels reflect the body’s iron stores.
• Hemosiderin: An insoluble, partially degraded form of ferritin. It accumulates in tissues when iron overload occurs. It is a less readily available source of iron than ferritin.

Tests to Assess Iron Status

Several laboratory tests are used to evaluate iron status. These tests provide information about iron stores, transport, and utilization.

Test	Normal Range	Interpretation
Serum Iron	60-170 µg/dL	Measures the amount of iron bound to transferrin. Affected by diurnal variation and recent iron intake.
Total Iron Binding Capacity (TIBC)	250-450 µg/dL	Measures the blood’s capacity to bind iron with transferrin. Increases in iron deficiency.
Transferrin Saturation	20-50%	Percentage of transferrin saturated with iron. Decreases in iron deficiency.
Serum Ferritin	12-300 ng/mL (men), 12-150 ng/mL (women)	Reflects iron stores. Low levels indicate iron deficiency. Can be falsely elevated by inflammation.
Soluble Transferrin Receptor (sTfR)	1.5-3.0 mg/L	Increases in iron deficiency as cells upregulate TfR expression to increase iron uptake.
Complete Blood Count (CBC)	Varies	Evaluates red blood cell indices (MCV, MCH, MCHC) which can be altered in iron deficiency anemia.