Overview
What is iron deficiency anemia?
What are the signs and symptoms of iron deficiency anemia?
Which physical findings suggest iron deficiency anemia?
Which tests are performed in the diagnosis of iron deficiency anemia?
Which tests are performed to establish the etiology of iron deficiency anemia?
Which CBC count results suggest iron deficiency anemia?
Which peripheral smear results suggest iron deficiency anemia?
Which iron study findings suggest iron deficiency anemia?
What is the treatment for iron deficiency anemia?
How is iron deficiency anemia defined and how does it occur?
Which groups are at an increased risk for iron deficiency anemia?
What is the role of GI bleeding in the development of iron deficiency anemia?
What is the role of iron in healthy individuals?
What causes an iron deficiency?
What are the pathways for iron uptake in the proximal small bowel?
What is the difference between heme and nonheme iron?
How does heme iron enter cells?
How does ferric iron enter cells?
Which cell pathway transports nonheme iron?
What are stimulators of iron transport (SFT)?
How much iron is concentrated within enterocytes?
What is enhanced erythropoiesis?
What is transferrin iron and how does it enter cells?
What is the role of nonintestinal cells in iron uptake?
Which dietary factors affect the etiology of iron deficiency anemia?
Can hemorrhaging cause iron deficiency anemia?
Which urine tests are performed to confirm hemoglobinuria in patients with iron deficiency anemia?
Which tests are performed to confirm renal loss of iron?
What is the role of prolonged achlorhydria in the etiology of iron deficiency anemia?
What is the role of starch and clay ingestion in the etiology of iron deficiency anemia?
When is iron deficiency anemia a complication of surgery?
Which tests are performed to confirm iron malabsorption?
What is iron-refractory iron deficiency anemia (IRIDA)?
What is the treatment for iron-refractory iron deficiency anemia (IRIDA)?
What is the prevalence of iron deficiency anemia in the US?
What is the global prevalence of iron deficiency anemia?
Why is the incidence of iron deficiency anemia higher in infants who drink cow’s milk?
Why are children at higher risk than adults for developing iron deficiency anemia?
Why are women of childbearing age at increased risk for iron deficiency anemia?
How do GI neoplasms cause iron deficiency anemia?
How does the pathogenesis of iron deficiency anemia differ between men and women?
Why is iron deficiency anemia more common in women than in men?
Are there differences in the prevalence of iron deficiency anemia among racial groups?
What is the prognosis of iron deficiency anemia?
What is the prognosis of chronic iron deficiency anemia?
What is the prognosis of iron deficiency anemia in children?
Presentation
What is the role of medical history in the diagnosis of iron deficiency anemia?
What history findings are characteristic of moderate iron deficiency?
Can patients with iron deficiency anemia identify the onset of symptoms?
What are the effects of a nonhemoglobin deficiency in iron deficiency anemia?
What is the purpose of dietary history in suspected iron deficiency anemia?
Can dietary iron deficiency alone cause iron deficiency anemia?
What is the role of pica in iron deficiency anemia?
How much iron is in hemoglobin?
What is the most common cause of iron deficiency anemia?
Can excessive menstrual bleeding (menorrhagia) cause iron deficiency anemia?
Which epithelial abnormalities suggest iron deficiency anemia?
Is there a relationship between epithelial abnormalities and iron deficiency anemia?
Is splenomegaly a symptom of iron deficiency anemia?
Why does iron deficiency anemia diminish work performance?
What are the effects of severe iron deficiency anemia?
How are defects in epithelial tissues related to iron deficiency anemia?
Is cold intolerance a possible complication of iron deficiency anemia?
Is papilledema a possible complication of iron deficiency anemia?
Is impaired immune function a possible complication of iron deficiency anemia?
DDX
Which disorders should be included in the differential diagnoses of iron deficiency anemia?
What are the differential diagnoses for Iron Deficiency Anemia?
Workup
How is iron deficiency anemia diagnosed?
Which tests are performed in the diagnosis of iron deficiency anemia?
What is the role of CBC count in the diagnosis of iron deficiency anemia?
What is the role of peripheral smear findings in the diagnosis of iron deficiency anemia?
What is the role of serum iron and ferritin testing in the diagnosis of iron deficiency anemia?
Does a finding of hemoglobinuria suggest iron deficiency anemia?
How is renal loss of iron detected in iron deficiency anemia?
What is the role of hemoglobin electrophoresis testing in the diagnosis of iron deficiency anemia?
What is the role of stool testing in the diagnosis of iron deficiency anemia?
What is the role of osmotic fragility testing (OFT) in the diagnosis of iron deficiency anemia?
What is the role of lead (poisoning) testing in the diagnosis of iron deficiency anemia?
What is the role of bone marrow aspiration (BMA) in the diagnosis of iron deficiency anemia?
Which histological findings suggest iron deficiency anemia?
Treatment
What is the standard treatment for iron deficiency anemia?
When is transfer for specialized treatment necessary for patients with iron deficiency anemia?
What are the BSG guidelines for treating iron deficiency anemia?
What are ACP guidelines for treating iron deficiency anemia?
Are oral ferrous iron salts effective in the treatment of iron deficiency anemia?
Which dosage of ferrous sulfate is effective in the treatment of iron deficiency anemia?
Is ferrous gluconate effective in the treatment of iron deficiency anemia?
What is the role of ferric citrate (Auryxia) in the treatment of iron deficiency anemia?
Is carbonyl iron effective in the treatment of iron deficiency anemia?
What is the usual benchmark for successful iron supplementation in iron deficiency anemia?
When is parental iron indicated in the treatment of iron deficiency anemia?
What is the role of ferumoxytol injection (Feraheme) in the treatment of iron deficiency anemia?
When is surgical intervention indicated in the treatment of iron deficiency anemia?
When is transfusion of packed RBCs indicated in the treatment of iron deficiency anemia?
Does diet affect iron deficiency?
How effective is adding nonheme iron to national diets for prevention of iron deficiency anemia?
What education should be given to patients with an iron-poor diet?
Should physical activity be restricted in patients with iron deficiency anemia?
What populations are at high risk for iron deficiency anemia?
How is iron deficiency anemia prevented in pregnant women?
What iron supplementation should be given to infants?
Should vegetarians be given iron supplementation to prevent iron deficiency anemia?
When is surgical consultation needed in the treatment of iron deficiency anemia?
Is long-term monitoring required in the treatment of iron deficiency anemia?
Medications
What is the most economical and effective medical treatment for iron deficiency anemia?
Is ferric citrate effective as a treatment for iron deficiency anemia?
Is carbonyl iron an effective treatment for iron deficiency anemia in children?
When is parenteral iron used to treat iron deficiency anemia?
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The sequence of events (left to right) that occur with gradual depletion of body stores of iron. Serum ferritin and stainable iron in tissue stores are the most sensitive laboratory indicators of mild iron deficiency and are particularly useful in differentiating iron deficiency from the anemia of chronic disorders. The percentage saturation of transferrin with iron and free erythrocyte protoporphyrin values do not become abnormal until tissue stores are depleted of iron. Subsequently, a decrease in the hemoglobin concentration occurs because iron is unavailable for heme synthesis. Red blood cell indices do not become abnormal for several months after tissue stores are depleted of iron.
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Sequential changes in laboratory values following blood loss are depicted. A healthy human was bled 5 L in 500-mL increments over 45 days. A moderate anemia ensued, initially with normal cellular indices and serum iron. Subsequently, the mean corpuscular volume (MCV) increased as iron was mobilized from body stores and reticulocytosis occurred. The serum iron decreased, followed by an increase in the total iron-binding capacity. Gradual decreases in the red blood cell indices occurred, with maximal microcytosis and hypochromia present 120 days after bleeding. Values returned to normal approximately 250 days after blood loss. At the end of the experiment, iron was absent from body stores (marrow) because hemoglobin has a first priority for iron. Iron-59 absorption was increased after all values returned to normal in order to replenish the body store with iron. This suggests that the serum iron, total iron-binding capacity, hemoglobin concentration, and indices were not the primary regulators of iron absorption.
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The total body iron in a 70-kg man is about 4 g. This is maintained by a balance between absorption and body losses. Although the body only absorbs 1 mg daily to maintain equilibrium, the internal requirement for iron is greater (20-25 mg). An erythrocyte has a lifespan of 120 days so that 0.8% of red blood cells are destroyed and replaced each day. A man with 5 L of blood volume has 2.5 g of iron incorporated into the hemoglobin, with a daily turnover of 20 mg for hemoglobin synthesis and degradation and another 5 mg for other requirements. Most of this iron passes through the plasma for reutilization. Iron in excess of these requirements is deposited in body stores as ferritin or hemosiderin.
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Dietary iron contains both heme and nonheme iron. Both chemical forms are absorbed noncompetitively into duodenal and jejunal mucosal cells. Many of the factors that alter the absorption of nonheme iron have little effect upon the absorption of heme iron because of the differences in their chemical structures. Iron is released from heme within the intestinal absorptive cell by heme oxygenase and then transferred into the body as nonheme iron. Factors affecting various stages of iron absorption are shown in this diagram. The simplest model of iron absorption must consider intraluminal, mucosal, and corporeal factors.
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Ultrastructural studies of the rat duodenum from iron-deficient (top), healthy (middle), and iron-loaded (bottom) animals are shown. They were stained with acid ferrocyanide for iron, which is seen as black dots in the specimens. No staining was seen with acid ferricyanide. This indicates that iron was in the ferric redox state. Respectively, the specimens showed no iron, moderate deposits, and increased deposits with ferritin (arrow).Incubation of the specimens with iron-nitrilotriacetic acid to satiate iron-binding proteins with iron provided specimens with equal iron staining, except that the iron-loaded specimens contained ferritin. The quantity of iron in the cell is derived from both the diet and body stores. It probably is important in the regulation of the quantity of iron accepted by the absorptive cell from the gut lumen. The authors postulate that the iron either satiates iron-binding proteins with iron, up-regulates iron regulatory protein, or does both to diminish iron uptake by the absorptive cell. The consequences of these findings are depicted in the flow charts.
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Mucosal cells in the proximal small intestine mediate iron absorption. Intestinal cells are born in the crypts of Lieberkuhn and migrate to the tips of the villi. The cells are sloughed into the intestinal lumen at the end of their 2- to 3-day lifespan. Absorptive cells remain attuned to the body requirement for iron by incorporating proportionate quantities of body iron into the absorptive cells. This iron and recently absorbed iron decrease uptake of iron from the gut lumen by satiation of iron-binding proteins with iron, by stimulating an iron regulatory element, or both. The incorporation of iron into these cells in quantities proportional to body stores of iron also provides a limited method of increasing iron excretion in individuals replete in iron.
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Both nonheme iron and heme iron have 6 coordinating bonds; however, 4 of the bonds in heme bind pyrroles, making them unavailable for chelation by other compounds. Therefore, ascorbic acid chelates nonheme iron to enhance absorption but has no effect upon heme iron. Many dietary components, such as phytates, phosphates, oxalates, and tannates, bind nonheme iron to decrease nonheme iron absorption. They do not affect heme. This explains why heme is so effectively absorbed with foods containing these chelators. Iron hemoglobin structure.
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Three pathways exist in enterocytes for uptake of food iron. In the United States and Europe, most absorbed iron is derived from heme. Heme is digested enzymatically free of globin and enters the enterocyte as a metalloporphyrin. Within the cell iron is released from heme by heme oxygenase to pass into the body as inorganic iron. Most dietary inorganic iron is ferric iron. This can enter the absorptive cell via the integrin-mobilferrin pathway (IMP).Some dietary iron is reduced in the gut lumen and enters the absorptive cell via the divalent metal transporter-1 (DMT-1/DCT-1/Nramp-2). The proteins of both pathways interact within the enterocyte with paraferritin, a large protein complex capable of ferrireduction. Excess iron is stored as ferritin to protect the cell from oxidative damage. Iron leaves the cell to enter plasma facilitated by ferroportin and hephaestin, which associate with an apotransferrin receptor. The enterocyte is informed of body requirements for iron by transporting iron from plasma into the cell using a holotransferrin receptor.
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A 70-year-old man who is 4 years post-Whipple surgery for pancreatic adenocarcinoma had been in good health with no evidence of recurrence until he had a maroon-colored stool that was heme positive. Physical examination was unrevealing. Laboratory study values showed a WBC of 9000 cells/µL, a hemoglobin of 11.5 g/dL, a mean corpuscular volume (MCV) of 95 fL, a mean corpuscular hemoglobin concentration (MCHC) of 34 g/dL, a platelet count of 250,000 cells/µL, a creatinine level of 0.9 mg/dL, a BUN level of 27 mg/dL, a total bilirubin level of 0.4 mg/dL, a serum iron level of 160 µg/dL, a total iron-binding capacity (TIBC) of 280 µg/dL, and a ferritin level of 85 ng/mL. A peripheral smear is shown.
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A 26-year-old white man was referred with a microcytic anemia that failed to respond to treatment with ferrous sulfate over 6 months. Physical examination showed only mild pallor of mucous membranes. His stool was dark but heme negative. The CBC count showed a WBC of 6000 cells/µL, a hemoglobin level of 11 g/dL, a mean corpuscular volume (MCV) of 70 fL, a mean corpuscular hemoglobin concentration (MCHC) of 33 g/dL, a platelet count of 234,000 cells/µL, a hemoglobin electrophoresis AA, a hemoglobin A2 value of 3.8%, and a fetal hemoglobin value of 2.0%.
