Iron deficiency anemia

Definition

Iron deficiency anemia refers to anemia that is caused by lower than normal levels of iron. This type of anemia is caused by deficient erythropoiesis, the ongoing process of the bone marrow to produce healthy red blood cells (RBCs). It is characterized by the production of small (microcytic) RBCs. When examined under a microscope, the RBCs also appear pale or light colored from the absence of heme, the major component of hemoglobin, which is the iron-bearing protein and coloring pigment in RBCs. Anemia resulting from a deficiency of iron is also called microcytic anemia.

Description

Anemia is a blood disorder characterized by abnormally low levels of healthy RBCs or reduced levels of hemoglobin (Hgb), the iron-bearing protein in RBCs that delivers oxygen to tissues throughout the body. Blood cell volume (hematocrit) may also be reduced in some anemias , but not necessarily in iron deficiency anemia. The reduction of any or all of these blood parameters reduces the essential delivery of oxygen through the bloodstream to the organs of the body. Iron is a mineral found in the bloodstream that is essential for growth, enzyme development and function, a healthy immune system, energy levels, and muscle strength. It is an important component of hemoglobin and myoglobin, the type of hemoglobin in muscle tissue.

Iron deficiency anemia is the most common type of anemia throughout the world, although it occurs to a lesser extent in the United States because of the higher consumption of iron-rich red meat and the practice of food fortification (addition of iron to foods by manufacturers). In developing countries in tropical climates, the most common cause of iron deficiency anemia is infestation with hookworm.

The onset of iron deficiency anemia is gradual and may not have early symptoms. The deficiency begins when the body's store of iron is depleted and more iron is being lost through bleeding or malabsorption than is derived from food and other sources. Because depleted iron stores cannot meet the red blood cells' needs, fewer red blood cells develop. In this early stage of anemia, the red blood cells look normal, but they are reduced in number. Eventually the body tries to compensate for the iron deficiency by producing more red blood cells, which are characteristically small in size (spherocytosis). Symptoms of anemia, especially weakness and fatigue, develop at this stage.

Causes and symptoms

Iron is an essential component of the production of healthy RBCs, and iron stores must be maintained for the ongoing production of RBCs by the bone marrow. Iron deficiency anemia can develop as a result of depleted iron stores from chronic blood loss, increased demands for iron as seen in periods of growth (e.g., in infancy and adolescence ), or malabsorption of iron even when foods or supplements are supplying adequate amounts. It is accepted that iron is hard to absorb; this, in combination with diets that may not meet daily requirements, is a common route to iron deficiency and iron deficiency anemia. Iron can also be lost through strenuous exercise and heavy perspiration, poor digestion, frequent consumption of antacids, long-term illness, heavy menstrual cycles, and other causes.

Infancy is a period of increased risk for iron deficiency because dietary iron may not be adequate for the rapid growth of the child in the first two years of life, an example of increased demand. The human infant is born with a built-in supply of iron, which can be tapped during periods of drinking low-iron milk or formula. Both human milk and cow milk contain rather low levels of iron (0.5–1.0 mg iron/liter). However, the iron in the mother's breast milk is about 50 percent absorbed by the infant, while the iron of cow milk is only 10 percent absorbed. During the first six months of life, growth of the infant is made possible by the milk in the diet and by the infant's built-in supply of iron. However, premature infants have a lower supply of iron and, for this reason, it is recommended that pre-term infants, beginning at two months of age, be given oral supplements of 7 mg iron/day, as ferrous sulfate. Iron deficiency can be provoked where infants are fed formulas based on unfortified cow milk. For example, unfortified cow milk is given free of charge to mothers in Chile. This practice has the fortunate result of preventing general malnutrition , but the unfortunate result of allowing the development of mild iron deficiency.

Children have a great need for iron as they grow, and in most cases, the diet will provide replacement iron for the iron used in growth. Children seem to stay in balance unless a bleeding disorder of some kind exists, either hereditary (hemophilia or von Willebrand's) or related to hookworm infection or another illness. In adolescence, girls have an increased requirement for iron because of increased growth and the start of menstruation . Adolescent boys also experience a major growth spurt that demands more iron; iron stores are worn thin especially when healthy red cell function is needed for adequate oxygenation of exercising muscles and developing organs. Teenagers are also not noted for making healthy food choices; often they are losing iron stores and not replenishing iron through diet.

Iron deficiency occurs most often through chronic blood loss, more often in adults than in children, although the sources of bleeding can apply to people of all ages. Blood losses from gastrointestinal bleeding, excessive menstrual bleeding, and infection with hookworm can deplete iron and lead to iron deficiency anemia. In hookworm infection, a parasitic worm that thrives in warm climates, including in the southern United States, enters the body through the skin, such as through bare feet. The hookworm then migrates to the small intestines where it attaches itself to small sausage-shaped structures in the intestines (villi) that help with the absorption of all nutrients. The hookworm damages the villi, resulting in blood loss; they simultaneously produce anti-coagulants that promote continued bleeding. Each worm can initiate losses of up to 0.25 ml of blood per day.

Chronic blood losses through gradual bleeding in the gastrointestinal tract can be provoked by other conditions such as hemorrhoids, bleeding ulcers, anal fissures, irritable bowel syndrome , aspirin-induced bleeding, blood clotting disorders, and diverticulosis (a condition caused by an abnormal opening from the intestine or bladder). Several genetic diseases also lead to bleeding disorders. These include the coagulation disorders hemophilia A and hemophilia B, and von Willebrand's disease, a bleeding disorder caused by a deficiency in von Willebrand factor, an essential component of the coagulation system. All three genetic diseases can produce symptoms and be diagnosed in childhood.

The symptoms of iron deficiency anemia appear slowly and typically include weakness and fatigue. These symptoms result because of the reduced oxygen carrying capacity of RBCs and the reduced ability of the RBCs to carry iron to working muscles. Iron deficiency can also affect other tissues, including the tongue and fingernails. Prolonged iron deficiency can result in a smooth, shiny, and reddened tongue, a condition called glossitis. The fingernails may grow abnormally and acquire a spoon-shaped appearance.

When to call the doctor

Weakness, dizziness , listlessness, or fatigue may be the first signs of iron deficiency anemia. A compulsion to chew on ice cubes or to eat soil is also an indication of iron deficiency. The pediatrician should be consulted if the child is extremely pale, with little or no color in the gums, nail beds, creases of the palm, or lining of the eyelids.

Demographics

In the United States, iron deficiency anemia affects thousands of toddlers between one and two years of age and more than 3 million women of childbearing age. This condition is less common in older children and in adults over 50 and rarely occurs in teenage boys and young men.

Diagnosis

Diagnosing iron deficiency anemia begins with the pediatrician taking a careful history, including the child's age, symptoms, illnesses, general state of health, and a family history of anemias. Symptoms noticed in children by their parents may include fatigue, weight loss, inability to concentrate, loss of appetite, and light-headedness when standing up. The physical examination may reveal paleness, and lack of color in the creases of the palms, in gums, and in the linings of the eyelids.

Diagnostic testing starts with a complete blood count (CBC) and differential, counting RBCs, white blood cells (WBCs) and measuring hemoglobin (Hgb), hematocrit (Hct), and other factors. In iron deficiency anemia, the RBC count can be normal or elevated and hemoglobin will be abnormally low. In infants, iron deficiency anemia is defined as having a hemoglobin level below 109 mg/ml when measured in whole blood, and a hematocrit of less than 33 percent. In the microscopic examination of a stained blood smear (differential), red cells may appear smaller than normal. The mean corpuscular volume (MCV) will be measured to compare the size of RBCs with normal RBCs. A reticulocyte (young RBCs) count will help determine if anemia is caused by impaired RBC production, as in iron deficiency anemia, or increased RBC destruction as in some other types of anemia. Iron, vitamin C or vitamin B₁₂, and folate levels will be measured in blood serum to identify possible deficiencies. In addition to measuring iron itself (Fe) and total iron-binding capacity (TIBC), transferrin and transferrin saturation tests may be performed to evaluate iron metabolism. Different types of hemoglobin may be measured by a diagnostic testing method called hemoglobin electrophoresis. Protoporphyrin IX, a component of hemoglobin, may be measured to help confirm a diagnosis of iron deficiency anemia. Confirmation may also be obtained by taking a bone marrow sample (bone marrow biopsy) for microscopic examination. Kidney function tests, coagulation tests, and stool examinations for occult (hidden) blood may also be performed.

The presence of occult blood found in a stool examination may indicate gastrointestinal bleeding or other causes of bleeding such as aspirin-induced or a bleeding ulcer. The physician then needs to examine the gastrointestinal tract to determine the cause and location of bleeding. In this case, a diagnosis of iron deficiency anemia may include examination with a sigmoidoscope, a flexible, tube-like instrument with a light source that permits examination of the colon. A barium-enhanced x ray of the intestines may also be used to detect abnormalities that can cause bleeding.

The diagnosis of iron deficiency anemia may include a test for oral iron absorption, especially when evidence suggests that oral iron supplements have failed to raise hemoglobin. The oral iron absorption test is conducted by injecting 64 mg iron (325 mg ferrous sulfate) in a single dose. Blood samples are then taken after two hours and four hours. The iron content of the blood serum is then measured. The concentration of iron should rise by about 22 micromolar, when iron absorption is normal. Lesser increases in concentration mean that iron absorption is abnormal and that more effective therapy may involve injections or infusions of iron.

Treatment

The goal of treatment for iron deficiency anemia is to restore iron levels and the production of healthy RBCs and increase the essential flow of oxygen to tissues. Iron preparations may be given by injection or, in older children, as oral supplements. Taking vitamin C along with oral iron supplementation is accepted as a way to achieve better absorption of the iron. Taking iron supplements can result in constipation , diarrhea , cramps, or vomiting in sensitive individuals. Injections and infusions of iron can be given to individuals with poor iron absorption. Treatment of iron deficiency anemia sometimes requires more than iron supplementation. When iron deficiency is provoked by hemorrhoids or gastrointestinal bleeding, for example, surgery may be required to prevent recurrent iron deficiency anemia. When iron deficiency is provoked by bleeding due to aspirin ingestion, aspirin is discontinued. Iron deficiency caused by hookworm infection requires drug therapy to eliminate the parasite; prevention includes wearing shoes when walking in soil known to be infested with hookworms.

Alternative treatment

Vitamin C is noted for helping to absorb iron in the diet and iron supplements. Cooking in a cast iron skillet may leach small amounts of absorbable iron into the diet. Besides the iron found in eggs, fish, liver, meat, poultry, green leafy vegetables, whole grains, and enriched or whole grain breads and cereals, good food sources of iron include blackstrap molasses, brewer's yeast, and certain types of sea vegetable (e.g., hijiki, kelp, dulse). Herbal supplements that benefit individuals who have iron deficiency anemia include alfalfa, burdock root, dandelion, dong quai, mullein, nettle, raspberry leaf, shepherd's purse, and yellow dock. Herbs are available as tinctures and teas or in capsules.

Nutritional concerns

Decreased dietary iron intake is a contributing factor in iron deficiency and iron deficiency anemia. Deciding how to add enough iron to the diet, however, depends not just on which foods contain it, but in which foods iron is most available for absorption and use by the body. Bioavailability describes the percent of dietary iron that is successfully absorbed via the gastrointestinal tract to the bloodstream. Non-absorbed iron is lost in the feces. Generally, iron bioavailability in fruits, vegetables, and grains is lower than the iron availability of meat. The availability of iron in plants ranges from only 1 to 10 percent, with some exceptions, while that in meat, fish, chicken, and liver is consistently 20–30 percent. In the following list, the iron content is given parenthetically for each food.

• cabbage (1.6 mg/kg)
• spinach (33 mg/kg)
• lima beans (15 mg/kg)
• potatoes (14 mg/kg)
• tomatoes (3 mg/kg)
• apples (1.5 mg/kg)
• peanut butter (6.0 mg/kg)
• raisins (20 mg/kg)
• whole wheat bread (43 mg/kg)
• eggs (20 mg/kg)
• canned tuna (13 mg/kg)
• chicken (11 mg/kg)
• beef (28 mg/kg)

It is easy to see that apples, tomatoes, and peanut butter are relatively low in iron, while spinach, whole wheat bread, and beef are relatively high in iron. Red meat sources reliably replace the heme component of red blood cells, raising hemoglobin levels and helping to correct iron deficiency. For infants and toddlers, the most available source of iron is human milk (50% availability).

The assessment of whether a food is low or high in iron can also be made by comparing the amount of that food eaten per day with the recommended dietary allowance (RDA) for iron. The RDA for iron for the adult male is 10 mg/day, while that for the adult woman is 15 mg/day. The RDA during pregnancy is 30 mg/day. The RDA for infants five months of age or younger is 6 mg/day, while that for infants of five months to one year of age is 10 mg/day. RDA values are based on the assumption that people eat a mixture of plant and animal foods.

Prognosis

The prognosis for treating and curing iron deficiency anemia is excellent, particularly when those affected take iron supplements as advised and are able to assimilate the iron. A number of studies have shown that iron deficiency anemia in infancy can result in reduced intelligence , when intelligence was measured in early childhood. It is not certain if iron supplementation of children with reduced intelligence, due to iron-deficiency anemia in infancy, has any influence in allowing a "catch-up" in intellectual development.

Prevention

In the healthy population, mineral deficiencies can be prevented by the consumption of inorganic nutrients at levels defined by the RDA. Iron deficiency anemia in infants and young children can be prevented by breast-feeding, consuming good dietary sources of iron, and using fortified foods. Liquid cow milk-based infant formulas are generally supplemented with iron (12 mg/L). The iron in liquid formulas is added as ferrous sulfate or ferrous gluconate. Commercial infant cereals are also fortified with iron, adding small particles of elemental iron. The levels used are about 0.5 gram iron/kg dry cereal. This amount of iron is about 10-fold greater than that of the iron naturally present in the cereal. Iron supplementation is not recommended for all infants, and children and pediatricians should be consulted before giving supplements. Vitamin C is recommended to improve the assimilation of iron in the body, especially when iron is obtained from non-food sources.

Nutritional concerns

The average diet in the United States contains about 6 mg of iron per calorie of food, which is sufficient for maintaining iron stores. Only 1 mg of iron, however, is absorbed for every 10 mg. consumed, which mean sources of iron must be carefully chosen. The bioavailability of iron in foods varies, influencing the amounts that can be absorbed through the intestines. Absorption is best when the food contains heme, just as in human red cells. That makes meat the best choice as a source of iron and iron-rich vegetables and fruits such as spinach and apricots the next best choice. Certain other plant foods that contain fiber, such as bran, actually reduce the absorption of non-heme iron; so do antacid medications, often taken to relieve the upset stomach associated with taking oral iron supplements. Additionally, food interactions reduce bioavailability. Ascorbic acid (vitamin C) is the only food constituent known to increase the availability of non-heme iron, such as in vegetables and also in food supplements.

KEY TERMS

Erythropoiesis —The process through which new red blood cells are created; it begins in the bone marrow.

Hematocrit —A measure of the percentage of red blood cells in the total volume of blood in the human body.

Heme —The iron-containing molecule in hemoglobin that serves as the site for oxygen binding.

Hemoglobin —An iron-containing pigment of red blood cells composed of four amino acid chains (alpha, beta, gamma, delta) that delivers oxygen from the lungs to the cells of the body and carries carbon dioxide from the cells to the lungs.

Protoporphyrin IX —A protein the measurement of which is useful for the assessment of iron status. Hemoglobin consists of a complex of a protein plus heme. Heme consists of iron plus protoporphyrin IX. Normally, during the course of red blood cell formation, protoporphyrin IX acquires iron, to generate heme, and the heme becomes incorporated into hemoglobin. However, in iron deficiency, protophoryrin IX builds up.

Recommended Dietary Allowance (RDA) —The Recommended Dietary Allowances (RDAs) are quantities of nutrients in the diet that are required to maintain good health in people. RDAs are established by the Food and Nutrition Board of the National Academy of Sciences, and may be revised every few years. A separate RDA value exists for each nutrient. The RDA values refer to the amount of nutrient expected to maintain good health in people. The actual amounts of each nutrient required to maintain good health in specific individuals differ from person to person.

Parental concerns

Understanding iron metabolism and the ways to ensure that iron deficiency anemia in infants and children can be successfully treated and prevented from recurring may be concerns of parents. It is important to remember that although iron deficiency anemia is common in infants and toddlers, it is easily corrected by feeding infants mother's milk or iron-fortified formulas. In older children, the diet usually balances iron usage and replacement. In teenage years, when demands for iron increase for rapid growth and to compensate for menstruation in girls, parents will need to pay attention once again to providing adequate food sources. However, supplementation of iron should only be done with a doctor's recommendation.

Resources

BOOKS

"Blood Disorders." The Merck Manual of Medical Information, 2nd Home Edition. Edited by Mark H. Beers et al. White House Station, NJ: Merck & Co., 2003.

Floyd, B. A. Anemia. Bloomington, IN: AuthorHouse, 2002.

Lark, Susan. Heavy Menstrual Flow and Anemia Self Help Book. Berkeley, CA: Celestial Arts Publishing, 2004.

Ross, Allison J. Everything You Need to Know about Anemia. New York: Rosen Publishing Group, 2001.

ORGANIZATIONS

National Heart, Lung, and Blood Institute (NHLBI). 6701 Rockledge Drive, PO Box 30105, Bethesda, MD 20824–0105. Web site: <www.nhlbi.nih.gov>.

L. Lee Culvert Tom Brody, PhD

Iron deficiency anemia

Definition

Anemia can be caused by iron deficiency, folate deficiency, vitamin B ₁₂ deficiency, and other causes. Iron deficiency anemia is due to a shortage of iron. It is characterized by the production of red blood cells that are smaller than normal (microcytic) and appear pale or light colored (hypochromic) when viewed under a microscope . For this reason, the anemia that occurs with iron deficiency is also called hypochromic microcytic anemia.

Description

Iron deficiency anemia is the most common type of anemia throughout the world. In the United States, iron deficiency anemia occurs to a lesser extent than in developing countries because of the higher consumption of red meat and the practice of food fortification (addition of iron to foods by manufacturers). In the United States, iron deficiency anemia is caused by a variety of factors, including excessive losses of iron in menstrual fluids and excessive bleeding into the gastrointestinal tract. In developing countries located in tropical climates, the most common cause of iron deficiency anemia is infestation with hookworm.

Causes and symptoms

Infancy is a period of increased risk for iron deficiency. A human infant is born with a built-in supply of iron, which can be tapped during periods of drinking low-iron milk or formula. Both human milk and cow milk contain rather low levels of iron (0.5-1.0 mg iron/liter). However, about 50% of the iron in human milk is absorbed by an infant, while only 10% of the iron in cow milk is absorbed. During the first six months of life, growth of an infant is made possible by milk in the diet and by the infant's built-in supply. Premature infants have a lower supply of iron. For this reason, it is recommended that pre-term infants (beginning at two months of age) be given oral supplements of 7 mg iron/day, in the form of ferrous sulfate. Iron deficiency can develop when infants are fed formulas that are based on cow milk that has not been fortified. For example, unfortified cow milk is given free of charge to mothers in Chile. This practice prevents general malnutrition, but results in the development of mild iron deficiency.

The normal rate of blood loss in the feces is 0.5-1.0 ml per day. About 60% of persons with cancer of the colon and rectum experience further blood loss in the range of 10 ml/day, which can lead to iron deficiency anemia. The fecal occult blood test is widely used to screen for the presence of cancer of the colon or rectum. In the absence of testing, colorectal cancer may be first detected because of the resulting iron deficiency anemia.

Infection with hookworm can also cause iron deficiency anemia. The hookworm is a parasite that thrives in warm climates, including in the southern United States. A hookworm enters the body through the skin, very commonly through bare feet. The hookworm then migrates to the small intestines where it attaches itself to the villi (small, finger-like structures found on the walls of the intestines, which are used for the absorption of nutrients). Hookworms damage the villi, resulting in blood loss. Further, they produce anticoagulants which promote continued bleeding. Each hookworm can cause the loss of up to 0.25 ml of blood per day.

Bleeding and blood loss through the gastrointestinal tract can also be caused by hemorrhoids, anal fissures, irritable bowel syndrome, aspirin-induced bleeding, blood clotting disorders, and diverticulosis (a condition caused by an abnormal opening from the intestine). Several genetic diseases are characterized by bleeding disorders . These include hemophilia A, hemophilia B, and von Willebrand's disease. Of these, only von Willebrand's disease leads to gastrointestinal bleeding.

The symptoms of iron deficiency anemia include weakness and fatigue. These symptoms result from the lack of function of red blood cells, and the reduced ability of red blood cells to carry iron to exercising muscles. Iron deficiency can also affect other tissues, including the tongue and fingernails. Prolonged iron deficiency can result in changes of the tongue, which may become smooth, shiny, and reddened, a condition known as glossitis. Fingernails may grow abnormally and acquire a spoon-shaped appearance.

Decreased iron intake is a contributing factor in iron deficiency and the resulting iron deficiency anemia. The iron content of some common foods is:

• whole wheat bread (43 mg/kg)
• spinach (33 mg/kg)
• beef (28 mg/kg)
• raisins (20 mg/kg)
• eggs (20 mg/kg)
• lima beans (15 mg/kg)
• potatoes (14 mg/kg)
• canned tuna (13 mg/kg)
• chicken (11 mg/kg)
• peanut butter (6.0 mg/kg)
• tomatoes (3.0 mg/kg)
• cabbage (1.6 mg/kg)
• apples (1.5 mg/kg)
• corn oil (0.6 mg/kg)

It is readily apparent that apples, tomatoes, and corn oil are relatively low in iron, while whole wheat bread, spinach, and beef are relatively high in iron. The assessment of whether a food is low or high in iron can also be made by comparing the amount of that food eaten per day with the recommended dietary allowance (RDA) for iron. The RDA for iron for an adult male is 10 mg/day, while that for an adult woman is 15 mg/day. The RDA during pregnancy is 30 mg/day. The RDA for infants of 0-0.5 years of age is 6 mg/day, while that for infants of 0.5-1.0 year of age is 10 mg/day. RDA values are based on the assumption that a person eats a mixture of plant and animal foods.

The above list of iron values alone may be deceptive, because bioavailability varies. Bioavailability means the percent of iron in the food that is absorbed via the gastrointestinal tract to the bloodstream. Non-absorbed iron is lost in the feces. The bioavailability of iron in fruits, vegetables, and grains is very low, but is much higher in meats. The bioavailability of iron in plants ranges from only 1-10%, while that in meat, fish, chicken, and liver is 20-30%. The most readily absorbable source of iron is human milk, which has a 50% bioavailability.

Interactions between various foods also influence the absorption of dietary iron. Vitamin C , for example, increases the absorption of dietary iron. Thus, if rice is consumed with a vitamin C-rich food such as orange juice, then the absorption of the rice's iron is enhanced. The increased use of formulas fortified with both iron and vitamin C has led to a marked reduction in anemia in infants and young children in the United States. In contrast, if rice is consumed with tea, certain chemicals (tannins) in the tea reduce the absorption of iron. Another potent inhibitor of iron absorption is phytic acid, a chemical that occurs naturally in legumes, cereals, and nuts.

Diagnosis

Iron deficiency anemia in infants is defined as a hemoglobin level below 109 mg/ml of whole blood, and a hematocrit of under 33%. Anemia in adult males is defined as hemoglobin under 130 mg/ml and a hematocrit of under 38%. Anemia in adult females is defined as hemoglobin under 120 mg/ml and a hematocrit of under 32%. Anemia in pregnant women is defined as hemoglobin of under 110 mg/ml and a hematocrit of under 31%.

When an abnormally high presence of blood is found in feces during a fecal occult blood test, a physician needs to examine the gastrointestinal tract to determine the cause or source of bleeding. For this, a sigmoidoscope may be used. This is an instrument that consists of a flexible tube with a light at the end and allows an examiner to directly visualize and examine the interior of the large bowel or colon to a distance of 60 cm from the anus. A barium enema , with an x ray, may also be used to detect abnormalities that can cause bleeding.

KEY TERMS

Barium —An element used in liquid suspension with radiography (x rays) due to its high contrast with human tissue.

Diverticulitis —A disease caused by abnormal outpocketings in the walls of the intestines.

Ferrous —A form of iron that has two electrons available for chemical reactions and is readily absorbed by humans; ferrous iron is also referred to as reduced.

Gastroenterology —The study of the structures of the gastrointestinal tract, commonly including the stomach, small intestines and large intestines.

Glossitis —A condition of the tongue in which the tongue becomes red, smooth, and shiny.

Hematocrit —The proportion of whole blood in the body, by volume, that is composed of red blood cells.

Heme —A protein comprising most of the mass of red blood cells that transports oxygen and carbon dioxide.

Hemoglobin —An iron-containing protein within red blood cells. Hemoglobin accounts for about 95% of the protein in the red blood cell.

Hypochromic —Having less than normal color.

Microcytic —Cells that are smaller than normal size.

Occult —Hidden or difficult to observe.

Protoporphyrin IX —A protein. Measuring proporphyrin IX is useful to assess iron status. Hemoglobin consists of a complex of a protein plus heme. Heme consists of iron plus protoporphyrin IX. Normally during the course of red blood cell formation, protoporphyrin IX acquires iron to generate heme. Protoporphyrin IX builds up to abnormally high levels when iron is deficient.

Recommended Dietary Allowance (RDA) — Quantities of nutrients in the diet that are required to maintain human health. RDAs are established by the Food and Nutrition Board of the National Academy of Sciences and may be revised every few years.

Villi —Small, finger-like structures found on the walls of the intestines that are used for the absorption of nutrients.

If evidence suggests that oral iron supplements are failng in treating anemia, a test for oral iron absorption is indicated. The oral iron absorption test is conducted by ingesting 64 mg iron (325 mg ferrous sulfate) in a single dose. Blood samples are then taken after two hours and four hours. The iron content of the person's serum is then measured. If iron absorption is normal, the concentration of iron should rise by an increment of about 22 micro-moles. Smaller increases in concentration mean that iron absorption is abnormal, and that therapy should involve injections or infusions of iron.

Treatment

Oral iron supplements (pills) may contain various chemical compounds containing iron, often called iron salts. Iron salts include ferrous sulfate, ferrous gluconate, or ferrous fumarate. Injections and infusions of iron can be given using a preparation called iron dextran. In patients with poor gastrointestinal absorption of iron, therapy with injection or infusion is preferable over oral supplements. Treatment of iron deficiency anemia sometimes requires more than therapy with iron. If iron deficiency is due to bleeding from hemorrhoids, surgical correction of the hemorrhoids may be essential to prevent recurrent iron deficiency anemia. If iron deficiency is caused by bleeding due to aspirin treatment, aspirin should be discontinued. If iron deficiency is due to hookworm infestations, therapy for this parasite should be given in conjunction with protection of feet by wearing shoes whenever walking in areas that are potentially infested with hookworms.

Prognosis

The prognosis for treating and curing iron deficiency anemia is excellent. One important issue, however, is failure to take iron supplements. Pregnant women may be advised to take 100-200 mg iron/day, a dose that leads to nausea, diarrhea , or abdominal pain in 10-20% of women. Such a high dosage is recommended to rapidly cure the anemia during pregnancy. Before conception, problems associated with side effects and nonadherence may be avoided by taking iron doses (100-200 mg) only once a week. This can be continued throughout a woman's fertile period. The problem of adherence is not an issue when infusions are used, although a fraction of persons treated with iron infusions experience flushing, headache, nausea, seizures, or anaphylaxis .

A number of studies have shown that iron deficiency anemia in infancy can result in reduced intelligence in early childhood. It is not clear whether iron supplementation given to children with reduced intelligence due to iron-deficiency anemia in infancy has any influence in allowing a "catch-up" in intellectual development.

Health care team roles

Screening for iron deficiency anemia is commonly conducted by nurses and physicians. However, when professionally-trained personnel are not available, other people may be given specific training to administer the screening test. Laboratory technicians process blood samples collected by screening tests. Physicians and nurses administer iron injections or intravenous infusions. Surgeons or physicians trained in gastroentnerology perform gastroscopic examinations. Radiologists interpret the results of x rays taken after infusion of a barium enema.

Prevention

In a healthy population, all mineral deficiencies can be prevented by ingesting inorganic nutrients at levels defined by the RDA. Iron deficiency anemia in infants and young children can be prevented by consuming fortified foods. Cow milk-based infant formulas are generally supplemented with iron (12 mg/L). The iron in liquid formulas is added as ferrous sulfate or ferrous gluconate. Commercial infant cereals are also fortified with iron. In addition, small particles of elemental iron may be added to the cereal. The levels used are about 0.5 gram iron/kg dry cereal, an amount about 10-fold greater than what is naturally present.

Resources

BOOKS

Hazelwood, Loren F. Can't Live Without It: The Story ofHemoglobin in Sickness and in Health. Huntington, NY, Nova Science Publishers, 2001.

Hillman, Robert S. "Iron Deficiency and Other Hypoproliferative Anemias." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci. New York: McGraw Hill, 1998.

Ramakrishnan, U. Nutritional Anemias. Boca Raton, FL: Lewis Publishers, 2000.

Uthman, Ed. Understanding Anemias. Jackson, MS: University Press of Mississippi, 1998.

PERIODICALS

Abelson, HT. "Complexities in recognizing and treating iron deficiency anemia." Archives of Pediatric and Adolescent Medicine, 155(3):332-333, 2001.

Anonymous. "Iron deficiency anemia: reexamining the nature and magnitude of the public health problem." Journal of Nutrition 131(2S-2):563S-703S, 2001.

Couper, R.T. and K.N. Simmer. "Iron deficiency in children: food for thought." Medical Journal of Australia 174(4):162-163, 2001.

Jolobe, O. "Guidelines for the management of iron deficiency anemia." Gut 48(2):283-284, 2001.

ORGANIZATIONS

American Academy of Family Physicians, 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (913) 906-6000. <http://www.aafp.org/>. [email protected].

American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (847) 434-4000. Fax (847) 434-8000. <http://www.aap.org/default.htm>. [email protected].

American Association for Clinical Chemistry, 2101 L Street, NW - Suite 202, Washington, D.C. 20037-1558. (800) 892-1400 or (202) 857-0717. Fax: (202) 887-5093. <http://www.aacc.org>. [email protected].

American Society of Hematology, 1900 M Street NW, Suite 200, Washington, D.C. 20036. (202) 776-0544. Fax:(202) 776-0545. <http://www.hematology.org/>. [email protected].

OTHER

Centers for Disease Control and Prevention. <http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00051880.htm>.

Columbia Presbyterian Medical Center. <http://cpmcnet.columbia.edu/texts/gcps/gcps0032.html>.

Oregon Health Sciences University. <http://www.ohsu.edu/som-hemonc/handouts/deloughery/fe.shtml>.

University of Virginia Health Sciences College. <http://hsc.virginia.edu/medicine/clinical/pathology/educ/ innes/text/rcd/iron.html>.

L. Fleming Fallon, Jr., MD, PhD, DrPH

Iron Deficiency Anemia

Definition

Anemia can be caused by iron deficiency, folate deficiency, vitamin B₁₂ deficiency, and other causes. Iron deficiency anemia is due to a shortage of iron. It is characterized by the production of red blood cells that are smaller than normal (microcytic) and appear pale or light colored (hypochromic) when viewed under a microscope. For this reason, the anemia that occurs with iron deficiency is also called hypochromic microcytic anemia.

Description

Iron deficiency anemia is the most common type of anemia throughout the world. In the United States, iron deficiency anemia occurs to a lesser extent than in developing countries because of the higher consumption of red meat and the practice of food fortification (addition of iron to foods by manufacturers). In the United States, iron deficiency anemia is caused by a variety of factors, including excessive losses of iron in menstrual fluids and excessive bleeding into the gastrointestinal tract. In developing countries located in tropical climates, the most common cause of iron deficiency anemia is infestation with hookworm.

Causes and symptoms

Infancy is a period of increased risk for iron deficiency. A human infant is born with a built-in supply of iron, which can be tapped during periods of drinking low-iron milk or formula. Both human milk and cow milk contain rather low levels of iron (0.5-1.0 mg iron/liter). However, about 50% of the iron in human milk is absorbed by an infant, while only 10% of the iron in cow milk is absorbed. During the first six months of life, growth of an infant is made possible by milk in the diet and by the infant's built-in supply. Premature infants have a lower supply of iron. For this reason, it is recommended that pre-term infants (beginning at two months of age) be given oral supplements of 7 mg iron/day, in the form of ferrous sulfate. Iron deficiency can develop when infants are fed formulas that are based on cow milk that has not been fortified. For example, unfortified cow milk is given free of charge to mothers in Chile. This practice prevents general malnutrition, but results in the development of mild iron deficiency.

The normal rate of blood loss in the feces is 0.5-1.0 ml per day. About 60% of persons with cancer of the colon and rectum experience further blood loss in the range of 10 ml/day, which can lead to iron deficiency anemia. The fecal occult blood test is widely used to screen for the presence of cancer of the colon or rectum. In the absence of testing, colorectal cancer may be first detected because of the resulting iron deficiency anemia.

Infection with hookworm can also cause iron deficiency anemia. The hookworm is a parasite that thrives in warm climates, including in the southern United States. A hookworm enters the body through the skin, very commonly through bare feet. The hookworm then migrates to the small intestines where it attaches itself to the villi (small, finger-like structures found on the walls of the intestines, which are used for the absorption of nutrients). Hookworms damage the villi, resulting in blood loss. Further, they produce anticoagulants which promote continued bleeding. Each hookworm can cause the loss of up to 0.25 ml of blood per day.

Bleeding and blood loss through the gastrointestinal tract can also be caused by hemorrhoids, anal fissures, irritable bowel syndrome, aspirin-induced bleeding, blood clotting disorders, and diverticulosis (a condition caused by an abnormal opening from the intestine). Several genetic diseases are characterized by bleeding disorders. These include hemophilia A, hemophilia B, and von Willebrand's disease. Of these, only von Willebrand's disease leads to gastrointestinal bleeding.

The symptoms of iron deficiency anemia include weakness and fatigue. These symptoms result from the lack of function of red blood cells, and the reduced ability of red blood cells to carry iron to exercising muscles. Iron deficiency can also affect other tissues, including the tongue and fingernails. Prolonged iron deficiency can result in changes of the tongue, which may become smooth, shiny, and reddened, a condition known as glossitis. Fingernails may grow abnormally and acquire a spoon-shaped appearance.

Decreased iron intake is a contributing factor in iron deficiency and the resulting iron deficiency anemia. The iron content of some common foods is:

• whole wheat bread (43 mg/kg)
• spinach (33 mg/kg)
• beef (28 mg/kg)
• raisins (20 mg/kg)
• eggs (20 mg/kg)
• lima beans (15 mg/kg)
• potatoes (14 mg/kg)
• canned tuna (13 mg/kg)
• chicken (11 mg/kg)
• peanut butter (6.0 mg/kg)
• tomatoes (3.0 mg/kg)
• cabbage (1.6 mg/kg)
• apples (1.5 mg/kg)
• corn oil (0.6 mg/kg)

It is readily apparent that apples, tomatoes, and corn oil are relatively low in iron, while whole wheat bread, spinach, and beef are relatively high in iron. The assessment of whether a food is low or high in iron can also be made by comparing the amount of that food eaten per day with the recommended dietary allowance (RDA) for iron. The RDA for iron for an adult male is 10 mg/day, while that for an adult woman is 15 mg/day. The RDA during pregnancy is 30 mg/day. The RDA for infants of 0-0.5 years of age is 6 mg/day, while that for infants of 0.5-1.0 year of age is 10 mg/day. RDA values are based on the assumption that a person eats a mixture of plant and animal foods.

The above list of iron values alone may be deceptive, because bioavailability varies. Bioavailability means the percent of iron in the food that is absorbed via the gastrointestinal tract to the bloodstream. Nonabsorbed iron is lost in the feces. The bioavailability of iron in fruits, vegetables, and grains is very low, but is much higher in meats. The bioavailability of iron in plants ranges from only 1-10%, while that in meat, fish, chicken, and liver is 20-30%. The most readily absorbable source of iron is human milk, which has a 50% bioavailability.

Interactions between various foods also influence the absorption of dietary iron. Vitamin C, for example, increases the absorption of dietary iron. Thus, if rice is consumed with a vitamin C-rich food such as orange juice, then the absorption of the rice's iron is enhanced. The increased use of formulas fortified with both iron and vitamin C has led to a marked reduction in anemia in infants and young children in the United States. In contrast, if rice is consumed with tea, certain chemicals (tannins) in the tea reduce the absorption of iron. Another potent inhibitor of iron absorption is phytic acid, a chemical that occurs naturally in legumes, cereals, and nuts.

Diagnosis

Iron deficiency anemia in infants is defined as a hemoglobin level below 109 mg/ml of whole blood, and a hematocrit of under 33%. Anemia in adult males is defined as hemoglobin under 130 mg/ml and a hematocrit of under 38%. Anemia in adult females is defined as hemoglobin under 120 mg/ml and a hematocrit of under 32%. Anemia in pregnant women is defined as hemoglobin of under 110 mg/ml and a hematocrit of under 31%.

When an abnormally high presence of blood is found in feces during a fecal occult blood test, a physician needs to examine the gastrointestinal tract to determine the cause or source of bleeding. For this, a sigmoidoscope may be used. This is an instrument that consists of a flexible tube with a light at the end and allows an examiner to directly visualize and examine the interior of the large bowel or colon to a distance of 60 cm from the anus. A barium enema, with an x ray, may also be used to detect abnormalities that can cause bleeding.

If evidence suggests that oral iron supplements are failing in treating anemia, a test for oral iron absorption is indicated. The oral iron absorption test is conducted by ingesting 64 mg iron (325 mg ferrous sulfate) in a single dose. Blood samples are then taken after two hours and four hours. The iron content of the person's serum is then measured. If iron absorption is normal, the concentration of iron should rise by an increment of about 22 micromoles. Smaller increases in concentration mean that iron absorption is abnormal, and that therapy should involve injections or infusions of iron.

Treatment

Oral iron supplements (pills) may contain various chemical compounds containing iron, often called iron salts. Iron salts include ferrous sulfate, ferrous gluconate, or ferrous fumarate. Injections and infusions of iron can be given using a preparation called iron dextran. In patients with poor gastrointestinal absorption of iron, therapy with injection or infusion is preferable over oral supplements. Treatment of iron deficiency anemia sometimes requires more than therapy with iron. If iron deficiency is due to bleeding from hemorrhoids, surgical correction of the hemorrhoids may be essential to prevent recurrent iron deficiency anemia. If iron deficiency is caused by bleeding due to aspirin treatment, aspirin should be discontinued. If iron deficiency is due to hookworm infestations, therapy for this parasite should be given in conjunction with protection of feet by wearing shoes whenever walking in areas that are potentially infested with hookworms.

Prognosis

The prognosis for treating and curing iron deficiency anemia is excellent. One important issue, however, is failure to take iron supplements. Pregnant women may be advised to take 100-200 mg iron/day, a dose that leads to nausea, diarrhea, or abdominal pain in 10-20% of women. Such a high dosage is recommended to rapidly cure the anemia during pregnancy. Before conception, problems associated with side effects and nonadherence may be avoided by taking iron doses (100-200 mg) only once a week. This can be continued throughout a woman's fertile period. The problem of adherence is not an issue when infusions are used, although a fraction of persons treated with iron infusions experience flushing, headache, nausea, seizures, or anaphylaxis.

A number of studies have shown that iron deficiency anemia in infancy can result in reduced intelligence in early childhood. It is not clear whether iron supplementation given to children with reduced intelligence due to iron-deficiency anemia in infancy has any influence in allowing a "catch-up" in intellectual development.

Health care team roles

Screening for iron deficiency anemia is commonly conducted by nurses and physicians. However, when professionally trained personnel are not available, other people may be given specific training to administer the screening test. Laboratory technicians process blood samples collected by screening tests. Physicians and nurses administer iron injections or intravenous infusions. Surgeons or physicians trained in gastroentnerology perform gastroscopic examinations. Radiologists interpret the results of x rays taken after infusion of a barium enema.

Prevention

In a healthy population, all mineral deficiencies can be prevented by ingesting inorganic nutrients at levels defined by the RDA. Iron deficiency anemia in infants and young children can be prevented by consuming fortified foods. Cow milk-based infant formulas are generally supplemented with iron (12 mg/L). The iron in liquid formulas is added as ferrous sulfate or ferrous gluconate. Commercial infant cereals are also fortified with iron. In addition, small particles of elemental iron may be added to the cereal. The levels used are about 0.5 gram iron/kg dry cereal, an amount about 10-fold greater than what is naturally present.

KEY TERMS

Barium— An element used in liquid suspension with radiography (x rays) due to its high contrast with human tissue.

Diverticulitis— A disease caused by abnormal out-pocketings in the walls of the intestines.

Ferrous— A form of iron that has two electrons available for chemical reactions and is readily absorbed by humans; ferrous iron is also referred to as reduced.

Gastroenterology— The study of the structures of the gastrointestinal tract, commonly including the stomach, small intestines and large intestines.

Glossitis— A condition of the tongue in which the tongue becomes red, smooth, and shiny.

Hematocrit— The proportion of whole blood in the body, by volume, that is composed of red blood cells.

Heme— A protein comprising most of the mass of red blood cells that transports oxygen and carbon dioxide.

Hemoglobin— An iron-containing protein within red blood cells. Hemoglobin accounts for about 95% of the protein in the red blood cell.

Hypochromic— Having less than normal color.

Microcytic— Cells that are smaller than normal size.

Occult— Hidden or difficult to observe.

Protoporphyrin IX— A protein. Measuring protoporphyrin IX is useful to assess iron status. Hemoglobin consists of a complex of a protein plus heme. Heme consists of iron plus protoporphyrin IX. Normally during the course of red blood cell formation, protoporphyrin IX acquires iron to generate heme. Protoporphyrin IX builds up to abnormally high levels when iron is deficient.

Recommended Dietary Allowance (RDA)— Quantities of nutrients in the diet that are required to maintain human health. RDAs are established by the Food and Nutrition Board of the National Academy of Sciences and may be revised every few years.

Villi— Small, finger-like structures found on the walls of the intestines that are used for the absorption of nutrients.

Resources

BOOKS

Hazelwood, Loren F. Can't Live Without It: The Story of Hemoglobin in Sickness and in Health. Huntington, NY, Nova Science Publishers, 2001.

Hillman, Robert S. "Iron Deficiency and Other Hypoproliferative Anemias." In Harrison's Principals of Internal Medicine. Edited by Anthony S. Fauci. New York: McGraw Hill, 638-644, 1998.

Ramakrishnan, U. Nutritional Anemias. Boca Raton, FL: Lewis Publishers, 2000.

Uthman, Ed. Understanding Anemias. Jackson, MS: University Press of Mississippi, 1998.

PERIODICALS

Abelson, H.T. "Complexities in recognizing and treating iron deficiency anemia." Archives of Pediatric and Adolescent Medicine 155, no. 3 (2001):332-333.

Anonymous. "Iron deficiency anemia: reexamining the nature and magnitude of the public health problem." Journal of Nutrition 131, no. 2S-2 (2001):563S-703S.

Couper, R.T., and K.N. Simmer. "Iron deficiency in children: food for thought." Medical Journal of Australia 174, no. 4 (2001):162-163.

Jolobe, O. "Guidelines for the management of iron deficiency anemia." Gut 48, no. 2 (2001):283-284.

ORGANIZATIONS

American Academy of Family Physicians, 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (913) 906-6000. 〈http://www.aafp.org/〉. [email protected].

American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (847) 434-4000. Fax (847) 434-8000. 〈http://www.aap.org/default.htm〉. [email protected].

American Association for Clinical Chemistry, 2101 L Street, NW, Suite 202, Washington, D.C. 20037-1558. (800) 892-1400 or (202) 857-0717. Fax: (202) 887-5093. 〈http://www.aacc.org〉. [email protected].

American Society of Hematology, 1900 M Street NW, Suite 200, Washington, D.C. 20036. (202) 776-0544. Fax: (202) 776-0545. 〈http://www.hematology.org/〉. [email protected].

OTHER

Centers for Disease Control and Prevention. 〈http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00051880.htm〉.

Columbia Presbyterian Medical Center. 〈http://cpmcnet.columbia.edu/texts/gcps/gcps0032.html〉.

Oregon Health Sciences University. 〈http://www.ohsu.edu/som-hemonc/handouts/deloughery/fe.shtml〉.

University of Virginia Health Sciences College. 〈http://hsc.virginia.edu/medicine/clinical/pathology/educ/innes/text/rcd/iron.html〉.

Iron Deficiency Anemia

Definition

Anemia can be caused by iron deficiency, folate deficiency, vitamin B₁₂ deficiency, and other causes. The term iron deficiency anemia means anemia that is due to iron deficiency. Iron deficiency anemia is characterized by the production of small red blood cells. When examined under a microscope, the red blood cells also appear pale or light colored. For this reason, the anemia that occurs with iron deficiency is also called hypochronic microcytic anemia.

Description

Iron deficiency anemia is the most common type of anemia throughout the world. In the United States, iron deficiency anemia occurs to a lesser extent than in developing countries because of the higher consumption of red meat and the practice of food fortification (addition of iron to foods by the manufacturer). Anemia in the United States is caused by a variety of sources, including excessive losses of iron in menstrual fluids and excessive bleeding in the gastrointestinal tract. In developing countries located in tropical climates, the most common cause of iron deficiency anemia is infestation with hookworm.

Causes and symptoms

Infancy is a period of increased risk for iron deficiency. The human infant is born with a built-in supply of iron, which can be tapped during periods of drinking low-iron milk or formula. Both human milk and cow milk contain rather low levels of iron (0.5-1.0 mg iron/liter). However, the iron in human milk is about 50% absorbed by the infant, while the iron of cow milk is only 10% absorbed. During the first six months of life, growth of the infant is made possible by the milk in the diet and by the infant's built-in supply. However, premature infants have a lower supply of iron and, for this reason, it is recommended that preterm infants (beginning at 2 months of age) be given oral supplements of 7 mg iron/day, as ferrous sulfate. Iron deficiency can be provoked where infants are fed formulas that are based on unfortified cow milk. For example, unfortified cow milk is given free of charge to mothers in Chile. This practice has the fortunate result of preventing general malnutrition, but the unfortunate result of allowing the development of mild iron deficiency.

The normal rate of blood loss in the feces is 0.5-1.0 ml per day. These losses can increase with colorectal cancer. About 60% of colorectal cancers result in further blood losses, where the extent of blood loss is 2-10 ml/day. Cancer of the colon and rectum can provoke losses of blood, resulting in iron deficiency anemia. The fecal blood test is widely used to screen for the presence of cancer of the colon or rectum. In the absence of testing, colorectal cancer may be first detected because of the resulting iron deficiency anemia.

Infection with hookworm can provoke iron deficiency and iron deficiency anemia. The hookworm is a parasitic worm. It thrives in warm climates, including in the southern United States. The hookworm enters the body through the skin, as through bare feet. The hookworm then migrates to the small intestines where it attaches itself to the villi (small sausage-shaped structures in the intestines that are used for the absorption of all nutrients). The hookworm provokes damage to the villi, resulting in blood loss, and they produce anti-coagulants which promote continued bleeding. Each worm can provoke the loss of up to 0.25 ml of blood per day.

Bleeding and blood losses through gastrointestinal tract can be provoked by colorectal cancer and hookworms, as mentioned above, but also by hemorrhoids, anal fissures, irritable bowel syndrome, aspirin-induced bleeding, blood clotting disorders, and diverticulosis (a condition caused by an abnormal opening from the intestine or bladder). Several genetic diseases exist which lead to bleeding diorders, and these include hemophilia A, hemophilia B, and von Willebrand's disease. Of these, only von Willebrand's disease leads to gastrointestinal bleeding.

The symptoms of iron deficiency anemia include weakness and fatigue. These symptoms result because of the lack of function of the red blood cells, and the reduced ability of the red blood cells to carry iron to exercising muscles. Iron deficiency can also affect other tissues, including the tongue and fingernails. Prolonged iron deficiency can result in changes of the tongue, and it may become smooth, shiny, and reddened. This condition is called glossitis. The fingernails may grow abnormally, and acquire a spoon-shaped appearance.

Decreased iron intake is a contributing factor in iron deficiency and iron deficiency anemia. The iron content of cabbage, for example, is about 1.6 mg/kg food, while that of spinach (33 mg/kg), lima beans (15 mg/kg), potato (14 mg/kg), tomato (3 mg/kg), apples (1.5 mg/kg), raisins (20 mg/kg), whole wheat bread (43 mg/kg), eggs (20 mg/kg), canned tuna (13 mg/kg), chicken (11 mg/kg), beef (28 mg/kg), corn oil (0.6 mg/kg), and peanut butter (6.0 mg/kg), are indicated. One can see that apples, tomatoes, and vegetable oil are relatively low in iron, while whole wheat bread and beef are relatively high in iron. The assessment of whether a food is low or high in iron can also be made by comparing the amount of that food eaten per day with the recommended dietary allowance (RDA) for iron. The RDA for iron for the adult male is 10 mg/day, while that for the adult woman is 15 mg/day. The RDA during pregnancy is 30 mg/day. The RDA for infants of 0-0.5 years of age is 6 mg/day, while that for infants of 0.5-1.0 years of age is 10 mg/day. The RDA values are based on the assumption that the consumer eats a mixture of plant and animal foods.

The above list of iron values alone may be deceptive, since the availability of iron in fruits, vegetables, and grains is very low, while that the availability from meat is much higher. The availability of iron in plants ranges from only 1-10%, while that in meat, fish, chicken, and liver is 20-30%. The term availability means the percent of dietary iron that is absorbed via the gastrointestinal tract to the bloodstream. Nonabsorbed iron is lost in the feces.

Interactions between various foods can influence the absorption of dietary iron. Vitamin C can increase the absorption of dietary iron. Orange juice is a rich source of vitamin C. Thus, if a plant food, such as rice, is consumed with orange juice, then the orange juice can enhance the absorption of the iron of the rice. Vitamin C is also added to infant formulas, and the increased use of formulas fortified with both iron and vitamin C have led to a marked decline in anemia in infants and young children in the United States (Dallman, 1989). In contrast, if rice is consumed with tea, certain chemicals in the tea (tannins) can reduce the absorption of the iron. Phytic acid is a chemical that naturally occurs in legumes, cereals, and nuts. Phytic acid, which can account for 1-5% of the weight of these foods, is a potent inhibitor of iron absorption. The increased availability of the iron in meat products is partly due to the fact that heme-iron is absorbed to a greater extent than free iron salts, and to a greater extent than iron in the phytic acid/iron complex. Nearly all of the iron in plants is nonheme-iron. Much of the iron in meat is nonheme-iron as well. The nonheme-iron in meat, fish, chicken and liver may be about 20% available. The heme-iron of meat may be close to 30% available. The most available source of iron is human milk (50% availability).

Diagnosis

Iron deficiency anemia in infants is defined as a hemoglobin level below 109 mg/ml of whole blood, and a hematocrit of under 33%. Anemia in adult males is defined as a hemoglobin under 130 mg/ml and a hematocrit of under 38%. Anemia in adult females is defined as hemoglobin under 120 mg/ml and a hematocrit of under 32%. Anemia in pregnant women is defined as hemoglobin of under 110 mg/ml and hematocrit of under 31%.

When an abnormally high presence of blood is found in the feces during a fecal occult blood test, the physician needs to examine the gastrointestinal tract to determine the cause of bleeding. Here, the diagnosis for iron deficiency anemia includes the examination using a sigmoidoscope. The sigmoidoscope is an instrument that consists of a flexible tube that permits examination of the colon to a distance of 60 cm. A barium enema, with an x ray, may also be used to detect abnormalities that can cause bleeding.

The diagnosis of iron deficiency anemia should include a test for oral iron absorption, where evidence suggests that oral iron supplements fail in treating anemia. The oral iron absorption test is conducted by eating 64 mg iron (325 mg ferrous sulfate) in a single dose. Blood samples are then taken after 2 hours and 4 hours. The iron content of the blood serum is then measured. The concentration of iron should rise by an increment of about 22 micromolar, where iron absorption is normal. Lesser increases in concentration mean that iron absorption is abnormal, and that therapy should involve injections or infusions of iron.

Treatment

Oral iron supplements (pills) may contain various iron salts. These iron salts include ferrous sulfate, ferrous gluconate, or ferrous fumarate. Injections and infusions of iron can be carried out with a preparation called iron dextran. In patients with poor iron absorption (by the gut), therapy with injection or infusion is preferable over oral supplements. Treatment of iron deficiency anemia sometimes requires more than therapy with iron. Where iron deficiency was provoked by hemorrhoids, surgery may prove essential to prevent recurrent iron deficiency anemia. Where iron deficiency is provoked by bleeding due to aspirin treatment, aspirin should be discontinued. Where iron deficiency is provoked by hookworm infections, therapy for this parasite should be used, along with protection of the feet by wearing shoes whenever walking in hookworm-infested soil.

Prognosis

The prognosis for treating and curing iron deficiency anemia is excellent. Perhaps the main problem is failure to take iron supplements. In cases of pregnant women, the health care worker may recommend taking 100-200 mg iron/day. This dose is rather high, and can lead to nausea, diarrhea, or abdominal pain in 10-20% of women taking this dose. The reason for using this high dose is to effect a rapid cure for anemia, where the anemia is detected at a mid-point during the pregnancy. The above problems of side-effects and noncompliance can be avoided by taking iron doses (100-200 mg) only once a week, where supplements are initiated some time prior to conception, or continuously throughout the fertile period of life. The problem of compliance is not an issue where infusions are used, however a fraction of patients treated with iron infusions experience side effects, such as flushing, headache, nausea, anaphylaxis, or seizures. A number of studies have shown that iron deficiency anemia in infancy can result in reduced intelligence, where intelligence was measured in early childhood. It is not certain if iron supplementation of children with reduced intelligence, due to iron-deficiency anemia in infancy, has any influence in allowing a "catch-up" in intellectual development.

KEY TERMS

Hematocrit— The proportion of whole blood in the body, by volume, that is composed of red blood cells.

Hemoglobin— Hemoglobin is an iron-containing protein that resides within red blood cells. Hemoglobin accounts for about 95% of the protein in the red blood cell.

Protoporphyrin IX— Protoporphyrin IX is a protein. The measurement of this protein is useful for the assessment of iron status. Hemoglobin consists of a complex of a protein plus heme. Heme consists of iron plus protoporphyrin IX. Normally, during the course of red blood cell formation, protoporphyrin IX acquires iron, to generate heme, and the heme becomes incorporated into hemoglobin. However, in iron deficiency, protophoryrin IX builds up.

Recommended Dietary Allowance (RDA)— The Recommended Dietary Allowances (RDAs) are quantities of nutrients of the diet that are required to maintain human health. RDAs are established by the Food and Nutrition Board of the National Academy of Sciences and may be revised every few years.

Prevention

In the healthy population, all of the mineral deficiencies can be prevented by the consumption of inorganic nutrients at levels defined by the RDA. Iron deficiency anemia in infants and young children can be prevented by the use of fortified foods. Liquid cow milk-based infant formulas are generally supplemented with iron (12 mg/L). The iron in liquid formulas is added as ferrous sulfate or ferrous gluconate. Commercial infant cereals are also fortified with iron, and here small particles of elemental iron are added. The levels used are about 0.5 gram iron/kg dry cereal. This amount of iron is about 10-fold greater than that of the iron naturally present in the cereal.

Resources

PERIODICALS

Walter, T., P. Pino, F. Pizarro, and B. Lozoff. "Prevention of Iron-deficiency Anemia: Comparison of High- and Low-iron Formulas in Term Healthy Infants after Six Months of Life." Journal of Pediatrics 132 (1998): 635-640.

Iron deficiency anemia

Definition

Anemia is a blood disorder characterized by abnormally low levels of healthy red blood cells (RBCs) or reduced hemoglobin (Hgb), the iron-bearing protein in red blood cells that delivers oxygen to tissues throughout the body. Iron deficiency anemia describes anemia that results from low levels of iron, the mineral present in hemoglobin.

Description

Iron deficiency is the world's most common nutritional deficiency, and because this deficiency often results in anemia, iron deficiency anemia is the

most common form of anemia worldwide. In the United States alone, iron deficiency anemia affects about 250,000 young children and about 3 million women of childbearing age. Iron deficiency anemia is less common in senior adults over age 50, usually occurring in conjunction with gastrointestinal bleeding or malabsorption of iron.

Iron is the main component of hemoglobin, the oxygen-carrying substance in RBCs. Iron is distributed in storage pools within the body, including in body tissue cells and RBCs. Total body iron is about 3.5 g in men and 2.5 g in women, primarily related to differences in body size and the reduced storage pool in women due to menstruation.

Iron is poorly absorbed by the body, making it difficult for most adults to meet daily intake requirements through the diet and causing any blood loss to result in iron deficiency. Iron deficiency anemia usually stems from chronic gastrointestinal blood loss through the stool (occult blood loss), and an accompanying loss of iron. This condition may not produce noticeable symptoms and the ongoing blood loss is discovered during a routine physical examination or treatment for another condition. Deficiencies in iron can also occur when the body is using more iron than can be replaced by food or other sources, depleting iron stores. In some individuals, iron deficiency may be the result of an increased need for iron such as increased iron absorption after stomach or small bowel surgery, or the result of malabsorption of iron.

When iron stores are depleted, not enough iron-bearing hemoglobin is available to carry oxygen to body tissues. In turn, fewer RBCs are produced by the body because not enough iron is available for the production of RBCs in bone marrow (erythropoisis). Red blood cells viewed microscopically appear normal in this early stage of iron deficiency anemia, but the total RBC count is reduced. When the body tries to compensate for the iron deficiency by producing more RBCs, it produces cells that are smaller than normal (microcytic anemia), which reduces blood cell volume (hematocrit). At this stage of development, symptoms of iron deficiency anemia begin to develop. The reduction of all three blood parameters—hemoglobin, red blood cell count, and cell volume results in reduced oxygen-carrying capacity of the blood, reducing the oxygenation of body tissues, a condition called hypoxia. Oxygenated blood is needed to give the body energy and to promote effective performance of muscles and organs such as the heart, lungs, and brain.

Demographics

Iron deficiency anemia occurs in 2% of adult men and up to 20% of adult women. African-American and Hispanic-American women are affected more than Caucasian women, and the greatest percentage are between early teens and 49 years of age due to blood loss from menstruation and pregnancy. In men and women age 65 and older, 6–9% of cases of iron deficiency anemia are caused by gastrointestinal bleeding associated with gastrointestinal cancer .

Causes and symptoms

In senior adults, the first suspected cause of iron deficiency anemia is bleeding somewhere in the body, typically chronic bleeding from the gastrointestinal tract that is associated with stomach ulcers, kidney or bladder tumors, colon polyps, or colon cancer . Certain conditions of the body's vascular system (veins and arteries) may also cause regular blood loss, resulting in iron deficiency. Individuals with inflammatory diseases such as rheumatoid arthritis , and individuals with liver diseases such as cirrhosis may develop iron deficiency that can ultimately lead to anemia. Taking non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin , naproxen sodium , or prescription NSAIDs as treatment for inflammatory disease can sometimes cause gastrointestinal bleeding that leads to iron deficiency anemia.

Individuals who do not properly absorb iron from the diet (malabsorption) may develop iron deficiency anemia; this is the most common cause of iron deficiency in post-menopausal women. Poor iron absorption can also cause iron deficiency anemia in patients who have had stomach surgery or small bowel surgery. In rare cases, genitourinary bleeding results in iron deficiency anemia.

The usual signs of anemia, including iron deficiency anemia, are paleness and weakness or lack of sufficient energy for daily activities. Other symptoms include easy bruising of the skin, dizziness and fainting . Nails and hair can become brittle and break easily. Appetite may be reduced.

Diagnosis

Individuals complaining of weakness and fatigue may be evaluated for iron deficiency anemia. The physician first observes the person's skin color for noticeable pallor (pale coloring) and observes the inside of the eyelid or presses on the nail beds to evaluate blood color. Laboratory tests include a complete blood count to determine the RBC count, hemoglobin and hematocrit; all of which are indicators of possible anemia. The RBCs are also examined for size in a stained differential blood smear; smaller than normal red cells with pale centers are indicative of iron deficiency anemia, also called microcytic anemia. Iron levels are evaluated by serum iron ferritin tests, which confirm iron deficiency. Measurement of an iron-bearing protein in the blood (transferrin) may be done to evaluate cellular iron status.

Individuals older than age 65 whose blood tests confirm iron deficiency anemia must be evaluated for the presence of gastrointestinal bleeding. This is done by first testing for the presence of occult blood in a stool sample. If blood is detected, additional diagnostic procedures are done to locate the source of bleeding. Procedures may include examining the upper intestinal tract with a lighted telescopic device (endoscope) that has a tiny digital camera attached. The tube-like endoscope is passed through the nose or mouth and images can be viewed on a monitor as the procedure is performed. Examination of the lower intestinal tract may require colonoscopy , an endoscopic procedure performed with the same type of telescopic device, this time passed through the anus to examine the walls of the colon and rectum.

Treatment

Replacing lost iron stores is an essential part of treatment for iron deficiency anemia. Correcting any sources of bleeding such as gastrointestinal bleeding or certain types of vascular disorders (e.g., hereditary hemorrhagic telangiectasia) is the first concern and must be addressed while iron therapy is underway. Various iron salts (ferrous sulfate, ferrous fuconate, or ferrous fumarate) can provide sufficient iron supplementation. Absorption is enhanced by giving simultaneous vitamin C (ascorbic acid). Some individuals experience stomach upsets when taking oral iron supplements. Oral iron is considered a safer form of iron than injection, but individuals who do not tolerate oral iron may need iron by injection. Sodium ferric gluconate, is a safe form of injectable iron approved by the FDA in 1999, as is iron sucrose, which was approved in 2000.

QUESTIONS TO ASK YOUR DOCTOR

• Why have I developed iron deficiency anemia?
• How can I increase the iron in my blood?
• Will taking iron supplements be the only treatment I need?
• How soon will I begin to feel stronger?
• How can I avoid becoming anemic again?

The normal response to iron replacement typically occurs 7 to 10 days after the start of therapy when new RBCs (reticulocytes) can be seen in blood smears. Hemoglobin usually returns to normal in about two months, but iron replacement therapy may continue for six months to ensure complete replacement of iron stores. Individuals with illnesses such as infection or cancer may not respond well to iron replacement therapy and may require longer treatment or blood transfusion. Only rarely are blood transfusions needed to replace lost blood and iron, usually in patients who do not respond to other forms of iron therapy or whose bleeding is not controlled.

Nutrition/Dietetic concerns

Consumption of meat that contains haem iron (found in animal meats) is easily absorbed. Vitamin C (ascorbic acid) maintains an acidic environment in the stomach and is known to help the absorption of iron from non-meat sources the diet (such as bread, fruit, cereal, etc.) and is especially helpful when taking iron supplements to correct iron deficiency anemia. Coffee, tea, and alcoholic beverages, especially wine, interfere with absorption of iron and should be avoided while taking replacement iron. Antacids may also interfere with iron absorption by changing the acid environment of the stomach to alkaline; antacid intake should be avoided while using iron supplements. To maintain iron stores, all adults should consume a diet high in iron, including red meat, fish, eggs, beans and green leafy vegetables.

KEY TERMS

Erythropoisis —The production of red blood cells in the body.

Hematocrit —An indication of blood volume determined by the percentage of blood composed of red blood cells and hemoglobin compared to the liquid portion called plasma.

Hypoxia —Decreased levels of oxygen in the blood, blood gases, and tissues of body organs.

Malabsorption —Decreased ability to absorb nutrients through the body's normal absorption processes.

Microcytic anemia —Any type of anemia in which red blood cells are of smaller than normal size.

Reticulocytes —Young red blood cells formed in bone marrow that make up about 1% of all red blood cells circulating in the veins and arteries.

Prognosis

Iron deficiency anemia can be corrected in most individuals regardless of cause. In individuals with gastrointestinal bleeding, the underlying source of bleeding must be successfully treated to obtain a good result with iron supplementation and a return to good health. Malabsorption is more difficult to treat but iron levels can usually be restored and the individual typically resumes good health in the absence of other underlying disease. Untreated iron deficiency anemia can lead to serious problems such as heart beat irregularities (cardiac arrhythmias ) and angina , which is heart pain caused by decreased oxygen being delivered to the heart through the blood.

Prevention

Prevention of iron deficiency anemia in senior adults depends on sufficient iron intake and prevention of gastrointestinal bleeding. Iron can be obtained in the diet by consuming a variety of meats and vegetables. Foods high in iron include eggs, red meat, liver, fish, beans, green leafy vegetables, almonds, avocados, blackstrap molasses, brewer's yeast, dried plums (prunes), dates, raisins, and seaweeds such as dulse, hijiki and kelp. Iron supplements such as ferrous sulfate can be taken if recommended by the physician; iron supplements should be taken with vitamin C and absorption can be increased by consuming meat regularly.

Caregiver concerns

Individuals with iron deficiency anemia typically feel weak and fatigued. For safety reasons and to prevent falling, they should be observed for signs of weakness or dizziness such as lack of stability when walking. A healthy diet should be maintained, including a range of meats, eggs, fish, beans and vegetables. Coffee, tea and alcohol, especially wine, should be avoided because they interfere with iron absorption. Any excessive bruising should be reported to the physician.

Resources

BOOKS

“Anemias Caused by Deficient Erythropoiesis.” The Merck Manual of Diagnosis and Therapy, Section 11. Edited by R. S. Porter. White House Station, NJ: Merck Research Laboratories, 2007.

PERIODICALS

Killip, S., J. M. Bennett, and M. D. Chambers. “Iron Deficiency Anemia.” American Family Physician 75, no. 5 (2007).

OTHER

“Iron Deficiency Anemia.” Food & Nutrition Mayo Foundation for Medical Education and Research. March 7, 2007 [cited April 12, 2008]. http://www.mayoclinic.com/health/iron-deficiency-anemia/DS00323.

ORGANIZATIONS

American Academy of Family Physicians, 114 Tomahawk Creek Parkway, Leawood, KS, 66211-2672, (800) 274-2237, (913) 906-6269, [email protected], http://www.familydoctor.org.

American Dietetic Association, 120 South Riverside Plaza, Chicago, IL, 60606-6995, (800) 366-1655, http://www.eatright.org.

National Heart, Lung, and Blood Institute (NHLBI), 6701 Rockledge Drive, P.O. Box 30105, Bethesda, MD, 20824-0105, (301) 592-8573, http://www.nhlbi.nih.gov.

L. Lee Culvert