Reduced ability of the blood to carry oxygen due to a lack of iron
Medical condition
Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, short of breath, or having decreased ability to exercise. Anemia that comes on quickly often has more severe symptoms, including confusion, feeling like one is going to pass out or increased thirst. Anemia is typically significant before a person becomes noticeably pale. Children with iron deficiency anemia may have problems with growth and development. There may be additional symptoms depending on the underlying cause.
Iron-deficiency anemia is caused by blood loss, insufficient dietary intake, or poor absorption of iron from food. Sources of blood loss can include heavy periods, childbirth, uterine fibroids, stomach ulcers, colon cancer, and urinary tract bleeding. Poor absorption of iron from food may occur as a result of an intestinal disorder such as inflammatory bowel disease or celiac disease, or surgery such as a gastric bypass. In the developing world, parasitic worms, malaria, and HIV/AIDS increase the risk of iron deficiency anemia. Diagnosis is confirmed by blood tests.
Iron deficiency anemia can be prevented by eating a diet containing sufficient amounts of iron or by iron supplementation. Foods high in iron include meat, nuts, and foods made with iron-fortified flour. Treatment may include dietary changes, iron supplements, and dealing with underlying causes, for example medical treatment for parasites or surgery for ulcers. Supplementation with vitamin C may be recommended due to its potential to aid iron absorption. Severe cases may be treated with blood transfusions or iron infusions.
Iron-deficiency anemia affected about 1.48 billion people in 2015. A lack of dietary iron is estimated to cause approximately half of all anemia cases globally. Women and young children are most commonly affected. In 2015, anemia due to iron deficiency resulted in about 54,000 deaths – down from 213,000 deaths in 1990.
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Signs and symptoms.
Iron-deficiency anemia may be present without a person experiencing symptoms. It tends to develop slowly; therefore the body has time to adapt, and the disease often goes unrecognized for some time. If symptoms present, patients may present with the sign of pallor (reduced oxyhemoglobin in skin or mucous membranes), and the symptoms of feeling tired, weak, dizziness, lightheadedness, poor physical exertion, headaches, decreased ability to concentrate, cold hands and feet, cold sensitivity, increased thirst and confusion. None of these symptoms (or any of the others below) are sensitive or specific. 
In severe cases, shortness of breath can occur. Pica may also develop; of which consumption of ice, known as pagophagia, has been suggested to be the most specific for iron deficiency anemia.
Other possible symptoms and signs of iron-deficiency anemia include:
Child development.
Iron-deficiency anemia is associated with poor neurological development, including decreased learning ability and altered motor functions. This is because iron deficiency impacts the development of the cells of the brain called neurons. When the body is low on iron, the red blood cells get priority on iron, and it is shifted away from the neurons of the brain. Exact causation has not been established, but there is a possible long-term impact from these neurological issues.
Cause.
A diagnosis of iron-deficiency anemia requires further investigation into its cause. It can be caused by increased iron demand, increased iron loss, or decreased iron intake. Increased iron demand often occurs during periods of growth, such as in children and pregnant women. For example, during stages of rapid growth, babies and adolescents may outpace their dietary intake of iron which can result in deficiency in the absence of disease or a grossly abnormal diet. Iron loss is typically from blood loss. One example of blood loss is by chronic gastrointestinal blood loss, which could be linked to a possible cancer. In women of childbearing age, heavy menstrual periods can be a source of blood loss causing iron-deficiency anemia. People who do not consume much iron in their diet, such as vegans or vegetarians, are also at increased risk of developing iron deficiency anemia.
Parasitic disease.
The leading cause of iron-deficiency anemia worldwide is a parasitic disease known as a helminthiasis caused by infestation with parasitic worms (helminths); specifically, hookworms. The hookworms most commonly responsible for causing iron-deficiency anemia include "Ancylostoma duodenale", "Ancylostoma ceylanicum", and "Necator americanus". The World Health Organization estimates that approximately two billion people are infected with soil-transmitted helminths worldwide. Parasitic worms cause both inflammation and chronic blood loss by binding to a human's small-intestinal mucosa, and through their means of feeding and degradation, they can ultimately cause iron-deficiency anemia.
Blood loss.
Red blood cells contain iron, so blood loss also leads to iron loss. There are several causes of blood loss, including menstrual bleeding, gastrointestinal bleeding, stomach ulcers, and bleeding disorders. The bleeding may occur quickly or slowly. Slow, chronic blood loss within the body – such as from a peptic ulcer, angiodysplasia, inflammatory bowel disease, a colon polyp or gastrointestinal cancer (e.g., colon cancer) – can cause iron-deficiency anemia.
Menstrual bleeding.
Menstrual bleeding is a common cause of iron deficiency anemia in women of childbearing age. Women with menorrhagia (heavy menstrual periods) are at risk of iron deficiency anemia because they are at higher than normal risk of losing more iron during menstruation than is replaced in their diet. Most women lose about 40 mL of blood per cycle. Some birth control methods, such as pills and IUDs, may decrease the amount of blood and therefore iron lost during a menstrual cycle. Intermittent iron supplementation may be as effective a treatment in these cases as daily supplements and reduce some of the adverse effects of long-term daily supplements.
Gastrointestinal bleeding.
The most common cause of iron deficiency anemia in men and post-menopausal women is gastrointestinal bleeding. There are many sources of gastrointestinal tract bleeding, including the stomach, esophagus, small intestine, and the large intestine (colon). Gastrointestinal bleeding can result from regular use of some medications, such as non-steroidal anti-inflammatory drugs (e.g. aspirin), as well as antiplatelets such as clopidogrel and anticoagulants such as warfarin; however, these are required in some patients, especially those with states causing a tendency to form blood clots. Colon cancer, which typically occurs in older individuals, is another potential cause of gastrointestinal bleeding. In addition, some bleeding disorders, such as von Willebrand disease and polycythemia vera, can cause gastrointestinal bleeding.
Blood donation.
Frequent blood donors are also at risk for developing iron deficiency anemia. When whole blood is donated, approximately 200 mg of iron is lost from the body. The blood bank screens people for anemia before drawing blood for donation. If the patient has anemia, blood is not drawn. Less iron is lost if the person is donating platelets or white blood cells.
Diet.
The body normally gets the iron it requires from food. If a person consumes too little iron, or iron that is poorly absorbed (non-heme iron), they can become iron deficient over time. Examples of iron-rich foods include meat, eggs, leafy green vegetables and iron-fortified foods. For proper growth and development, infants and children need dietary iron. For children, a high intake of cow's milk is associated with an increased risk of iron-deficiency anemia. Other risk factors include low meat intake and low intake of iron-fortified products.
The National Academy of Medicine updated Estimated Average Requirements (EAR) and Recommended Dietary Allowances (RDA) in 2001. The current EAR for iron for women ages 14–18 is 7.9 mg/day, 8.1 for ages 19–50, and 5.0 thereafter (post menopause). For men the EAR is 6.0 mg/day for ages 19 and up. The RDA is 15.0 mg/day for women ages 15–18, 18.0 for 19–50, and 8.0 thereafter; for men, 8.0 mg/day for ages 19 and up. (Recommended Dietary Allowances are higher than Estimated Average Requirements so as to cover people with higher than average requirements.) The RDA for pregnancy is 27 mg/day, and during lactation, 9 mg/day. For children ages 1–3 years it is 7 mg/day, 10 for ages 4–8 and 8 for ages 9–13. The European Food Safety Authority refers to the collective set of information as Dietary Reference Values, with Population Reference Intakes instead of RDAs, and Average Requirements instead of EARs. For women the Population Reference Intake is 13 mg/day ages 15–17 years, 16 mg/day for women ages 18 and up who are premenopausal, and 11 mg/day postmenopausal; for pregnancy and lactation, 16 mg/day. For men the Population Reference Intake is 11 mg/day ages 15 and older. For children ages 1 to 14 the Population Reference Intake increases from 7 to 11 mg/day. The Population Reference Intakes are higher than the US RDAs, with the exception of pregnancy.
Iron malabsorption.
Iron from food is absorbed into the bloodstream in the small intestine, primarily in the duodenum. Iron malabsorption is a less common cause of iron-deficiency anemia, but many gastrointestinal disorders can reduce the body's ability to absorb iron. There are different mechanisms that may be present.
In coeliac disease, abnormal changes in the structure of the duodenum can decrease iron absorption. Abnormalities or surgical removal of the stomach can also lead to malabsorption by altering the acidic environment needed for iron to be converted into its absorbable form. If there is insufficient production of hydrochloric acid in the stomach, hypochlorhydria/achlorhydria can occur (often due to chronic H. pylori infections or long-term proton-pump inhibitor therapy), inhibiting the conversion of ferric iron to the absorbable ferrous iron.
Bariatric surgery is associated with an increased risk of iron deficiency anemia due to malabsorption of iron. During a Roux-en-Y anastamosis, which is commonly performed for weight management and diabetes control, the stomach is made into a small pouch and this is connected directly to the small intestines further downstream (bypassing the duodenum as a site of digestion). About 17–45% of people develop iron deficiency after a Roux-en-Y gastric bypass.
Pregnant women.
Without iron supplementation, iron-deficiency anemia occurs in many pregnant women because their iron stores need to serve their own increased blood volume and be a source of hemoglobin for the growing baby and placental development. Other less common causes are intravascular hemolysis and hemoglobinuria. Iron deficiency in pregnancy appears to cause long-term and irreversible cognitive problems in the baby.
Iron deficiency affects maternal well-being by increasing risks for infections and complications during pregnancy. Some of these complications include pre-eclampsia, bleeding problems, and perinatal infections. Iron deficiency can lead to improper development of fetal tissues. Oral iron supplementation during the early stages of pregnancy, specifically the first trimester, is suggested to decrease the adverse effects of iron-deficiency anemia throughout pregnancy and to decrease the negative impact that iron deficiency has on fetal growth. Iron supplements may lead to a risk for gestational diabetes, so pregnant women with adequate hemoglobin levels are recommended not to take iron supplements. Iron deficiency can lead to premature labor and to problems with neural functioning, including delays in language and motor development in the infant.
Some studies show that women pregnant during their teenage years can be at greater risk of iron-deficiency anemia due to an already increased need for iron and other nutrients during adolescent growth spurts.
Children.
Babies are at increased risk of developing iron deficiency anemia due to their rapid growth. Their need for iron is greater than they are getting in their diet. Babies are born with iron stores; however, these iron stores typically run out by 4–6 months of age. In addition, infants who are given cow's milk too early can develop anemia due to gastrointestinal blood loss.
Children who are at risk for iron-deficiency anemia include:
Hepcidin.
Decreased levels of serum and urine hepcidin are early indicators of iron deficiency. Hepcidin concentrations are also connected to the complex relationship between malaria and iron deficiency.
Mechanism.
Anemia can result from significant iron deficiency. When the body has sufficient iron to meet its needs (functional iron), the remainder is stored for later use in cells, mostly in the bone marrow and liver. These stores are called ferritin complexes and are part of the human (and other animals) iron metabolism systems. Men store about 3.5 g of iron in their body, and women store about 2.5 g.
Hepcidin is a peptide hormone produced in the liver that is responsible for regulating iron levels in the body. Hepcidin decreases the amount of iron available for erythropoesis (red blood cell production). Hepcidin binds to and induces the degradation of ferroportin, which is responsible for exporting iron from cells and mobilizing