Iron deficiency anemia
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.
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.
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.
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 B 12 , 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.
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.
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.
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.
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.
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.
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.
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.
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.
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National Heart, Lung, and Blood Institute (NHLBI). 6701 Rockledge Drive, PO Box 30105, Bethesda, MD 20824–0105. Web site: http://www.nhlbi.nih.gov.
L. Lee Culvert Tom Brody, PhD