Iron enters the body through the diet in two forms, heme and non-heme iron. Both forms are found in foods of both plant and animal origin. Not much is known about the absorption of heme iron, which is mostly consumed through foods of animal origin. Non-heme iron enters the proximal part of the small intestine, called the duodenum, and is absorbed by mature duodenal enterocytes. If iron is not immediately needed by the body, it is stored within the cells by ferritin, the major iron-storing protein. If the body does not end up needing this iron, it is lost through the death of the enterocyte. If the iron is immediately needed, it needs to move from the intestinal lumen into the bloodstream. This is accomplished by dietary iron (Fe3+) first being reduced to ferrous iron (Fe2+) by duodenal cytochrome B. Next, divalent metal transporters (DMT1) help the Fe2+ cross the apical brush-border of the enterocyte. Ferroportin (FPN1) then steps in to export the iron across the enterocyte basolateral membrane, where it is then converted back into iron (Fe3+) to be used in the body. Newly absorbed or released iron binds to plasma transferrin which distributes the iron around the body. The place of most need is erythroid marrow where iron is utilized for hemoglobin synthesis in the making of new RBCs. Recycling of iron occurs when macrophages eat up RBCs, releasing the iron back into circulation either to be stored or used again. Iron homeostasis is controlled by Hepcidin which is released by the liver. If iron requirements increase, hepcidin levels decrease and more iron is mobilized from storage or absorbed in the duodenum. Alternatively, if there are adequate levels of iron hepcidin levels increase to downregulate these processes. Iron is utilized in the body for many things including RBC formation, immune function, brain function, muscle function, and energy production. (Anderson & Frazer, 2017)
Iron deficiency anemia (IDA) is a hypochromic-microcytic anemia characterized by abnormally small erythrocytes that contain reduced amounts of hemoglobin. Anemia is the direct result of iron store depletion due to inadequate dietary intake, blood loss, or metabolic dysfunction. Regardless of the cause of depletion, the main outcome of IDA is a reduction in hemoglobin synthesis. IDA occurs when the demand for iron by the body exceeds the supply. There are several stages that lead to this supply-demand imbalance which are explained below. Metabolic IDA is caused by various metabolic disorders that lead to either insufficient iron delivery to bone marrow or impaired iron use by the bone marrow. There may be sufficient iron stores in the body, but a functional issue leads to inadequate delivery or use for heme synthesis, therefore producing relative iron deficiency. Blood loss creates a need for more iron, which leads to iron store depletion as the body rapidly uses stored iron to replace what is being lost. Inadequate dietary intake of iron leads to store depletion as the body uses up iron without it being replaced. (McCance & Rote, 2019)
Stages of Development:
- Body’s iron stores are depleted, RBC production proceeds normally with hemoglobin content remaining normal
- Reduction in iron transport to bone marrow, causing iron-deficient RBC production (hemoglobin content of RBC is reduced)
- Small, hemoglobin-deficient cells enter circulation, replacing normal RBC
Early symptoms of IDA include fatigue, weakness, shortness of breath, and pallor. These symptoms start to develop in stage three of development due to the reduction in hemoglobin leading to hypoxemia. As hemoglobin levels continue to drop, epithelial tissue begin to express structural and functional changes such as finger nails becoming brittle, thin, ridged and spoon-shaped (figure 1). These changes are caused by impaired capillary circulation. Glossitis, caused by tongue papillae atrophy, causes soreness and redness of the tongue (figure 2). Additionally, individuals with IDA experience angular stomatitis, a dry soreness in the epithelial tissues at the corners of the mouth. Iron is an essential component of many enzymes in the body (cytochromes, myoglobin, catalases, peroxidases). Individuals with IDA can also experience gastritis, neuromuscular changes, irritability, headaches, numbness, tingling, and vasomotor disturbances due to deficiencies in these iron-dependent enzymes. (McCance & Rote, 2019)
Evaluation of IDA is based on clinical symptoms and blood tests. Decreased levels of hemoglobin are caused by the direct reduction of hemoglobin synthesis caused by low levels of iron. Lower than normal serum iron, ferritin, and transferrin saturation levels will also be seen. Low levels of ferritin, the iron-storing protein, and transferring, the iron transporter are seen when iron levels are low because their functions are not in high demand (McCance & Rote, 2019).