Information about iron metabolism

Normal Iron Metabolism

A well-balanced diet contains sufficient iron to meet body requirements. About 10% of the normal 10 to 20 mg of dietary iron is absorbed each day, and this is sufficient to balance the 1 to 2 mg daily losses from desquamation of epithelia. Greater iron utilization via growth in childhood, greater iron loss with minor hemorrhages, menstruation in women, and greater need for iron in pregnancy will increase the efficiency of dietary iron absorbtion to 20%.

Iron is mainly absorbed in the duodenum and upper jejunum. A transporter protein called divalent metal transporter 1 (DMT1) facilitates transfer of iron across the intestinal epithelial cells. DMT1 also facilitates uptake of other trace metals, both good (manganese, copper, cobalt, zinc) and bad (cadmium, lead). Absorbed iron is bound in the bloodstream by the glycoprotein named transferrin. Normally, about 20 to 45% of transferrin binding sites are filled (the percent saturation). About 0.1% of total body iron is circulating in bound form to transferrin. Most absorbed iron is utilized in bone marrow for erythropoiesis. Membrane receptors on erythroid precursors in the bone marrow avidly bind transferrin. About 10 to 20% of absorbed iron goes into a storage pool, which is also being recycled into erythropoiesis, so there is a balance of storage and use. The trace elements cobalt and manganese are also absorbed and transported via the same mechanisms as iron.

Iron absorbtion is regulated by three mechanisms:

· Dietary regulator: a short-term increase in dietary iron is not absorbed as the mucosal cells have accumulated iron and "block" additional uptake.

· Stores regulator: as body iron stores fall, the mucosa is signalled to moderately increase absorbtion.

· Erythropoietic regulator: in response to anemia the erythroid cells will signal the mucosa to increase iron absorbtion more significantly.

The composition of the diet may also influence iron absorbtion. Citrate and ascorbate (in citrus fruits, for example) can form complexes with iron that increase absorbtion, while tannates in tea can decrease absorbtion. The iron in heme found in meat is more readily absorbed than inorganic iron by an unknown mechanism. The ferrous form of iron is more readily absorbed than ferric iron. Duodenal microvilli contain ferric reductase to promote absorbtion of ferrous iron.

Only a small fraction of the body's iron is gained or lost each day. Most of the iron in the body is recycled when old red blood cells are taken out of circulation and destroyed, with their iron scavenged by macrophages in the mononuclear phagocyte system, and returned to the storage pool for re-use. Iron homeostasis is closely regulated via intestinal absorption. Increased absorption is signalled by decreasing iron stores, hypoxia, and erythropoietic activity.

Storage iron occurs in two forms:

· Ferritin

· Hemosiderin

Iron is initially stored as ferritin, but ferritin can be incorporated by phagolysosomes to hemosiderin. There are about 2 gm of iron in the adult female, and up to 6 gm iron in the adult male. About 1.5 to 2 gm of this total is found in red blood cells as heme in hemoglobin, and 0.5 to 1 gm occur as storage iron, with the remainder in myoglobin and in enzymes that require iron.

Laboratory testing for iron may include tests for:

· Serum iron

· Serum iron binding capacity

· Serum ferritin

· Complete blood count (CBC)

· Bone marrow biopsy

· Liver biopsy

The simplest tests that indirectly give an indication of iron stores are the serum iron and iron binding capacity, with calculation of the percent transferrin saturation. The serum ferritin correlates well with iron stores, but it can also be elevated with liver disease, inflammatory conditions, and malignant neoplasms. The CBC will also give an indirect measure of iron stores, because the mean corpuscular volume (MCV) can be decreased with iron deficiency. The amount of storage iron for erythropoiesis can be quantified by performing an iron stain on a bone marrow biopsy. Excessive iron stores can be determined by bone marrow and by liver biopsies.

Iron Deficiency Anemia

The most common dietary deficiency worldwide is iron, affecting half a billion persons. However, this problem affects women and children more. A growing child is increasing the red blood cell mass, and needs additional iron. Women of reproductive age who are menstruating require double the amount of iron that men do, but normally the efficiency of iron absorbtion from the gastrointestinal tract can increase to meet this demand. Also, a developing fetus draws iron from the mother, totaling 200 to 300 mg at term, so extra iron is needed in pregnancy. An infant requires formula with 4 - 12 mg/L of iron. Iron in breast milk is more readily absorbed.

Of course, hemorrhage will increase the iron need to replace lost RBC's. Aside from trauma, the most common form of pathologic blood loss is via the gastrointestinal tract. Gastrointestinal lesions that can bleed include: ulcers, carcinomas, hemorrhoids, and inflammatory disorders. Also, ingestion of aspirin will increase occult blood loss in the GI tract. A disease that could impair iron absorbtion would be sprue (celiac disease).

The end result of decreased dietary iron, decreased iron absorbtion, or blood loss is iron deficiency anemia. This anemia is characterized by a decreased size of red blood cells, so that the mean corpuscular volume (MCV) is lower. Also, the serum iron will be decreased, while the serum iron binding capacity is somewhat increased, so that the percent transferrin saturation is much lower than normal--perhaps only 5 to 10%.

The following images illustrate findings with iron deficiency:

1. Normal bone marrow, microscopic.

2. Normal peripheral blood smear.

3. Normal CBC, diagram.

4. Iron deficiency anemia, peripheral blood smear.

5. Iron deficiency anemia, peripheral blood smear.

6. Iron deficiency anemia, CBC, diagram.

Iron Overload

Excessive iron can accumulate acutely or chronically.

Iron Poisoning: Acute iron poisoning is mainly seen in children. A single 300 mg tablet of ferrous sulfate will contain 60 mg of elemental iron. Toxicity producing gastrointestinal symptoms, including vomiting and diarrhea, occurs with ingestion of 20 mg of elemental iron per kg of body weight. If enough iron is ingested and absorbed, about 60 mg per kg body weight, systemic toxicity occurs. Toxicity results when free iron not bound to transferrin appears in the blood. This free iron can damage blood vessels and produce vasodilation with increased vascular permeability, leading to hypotension and metabolic acidosis. In addition, excessive iron damages mitochondria and causes lipid peroxidation, manifest mainly as renal and hepatic damage.

Early signs of iron poisoning include vomiting and diarrhea, fever, hyperglycemia, and leukocytosis. Later signs include hypotension, metabolic acidosis, lethargy, seizures, and coma. Hyperbilirubinemia and elevated liver enzymes suggest liver injury, while proteinuria and appearance of tubular cells in urine suggest renal injury.

Chronic Iron Overload: This can occur in patients who receive multiple transfusions for anemias caused by anything other than blood loss. Patients with congenital anemias may require numerous transfusions for many years. Each unit of blood has 250 mg of iron.Ineffective Erythropoiesis: Increased iron absorbtion can occur in certain types of anemia in which there is destruction of erythroid cells within the marrow, not peripheral destruction. This phenomenon signals the erythroid regulator to continually call for more iron absorbtion. These conditions include: thalassemias, congenital dyserythropoietic anemias, and sideroblastic anemias

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