Iron-deficiency anemia, also spelled iron-deficiency anaemia, is anemia caused by a lack of iron. Anemia is defined as a decrease in the amount of red blood cells (RBCs) or hemoglobin in the blood. When anemia comes on slowly, the symptoms are often vague and may include feeling tired, weakness, shortness of breath or poor ability to exercise. Anemia that comes on quickly often has greater symptoms which may include: confusion, feeling like one is going to pass out, and increased thirst. There needs to be significant anemia before a person becomes noticeably pale. There may be additional symptoms depending on the underlying cause. It is caused by insufficient dietary intake and absorption of iron, or iron loss from bleeding. Bleeding can be from a range of sources such as the intestinal, uterine or urinary tract. The most common cause of iron-deficiency anemia in children in developing countries is parasitic worms.Worms cause intestinal bleeding, which is not always noticeable in feces, and is especially damaging to children. Malaria, hookworms and vitamin A deficiency contribute to anemia during pregnancy in most underdeveloped countries. In women over 50 years old, the most common cause of iron-deficiency anemia is chronic gastrointestinal bleeding from nonparasitic causes, such as gastric ulcers, duodenal ulcers or gastrointestinal cancer. Iron deficiency causes approximately half of all anemia cases worldwide, and affects women more often than men. Iron-deficiency anemia affected 1.2 billion people in 2013. In 2013 anemia due to iron deficiency resulted in about 183,000 deaths – down from 213,000 deaths in 1990. Signs and symptoms Iron-deficiency anemia is characterized by the sign of pallor (reduced oxyhemoglobin in skin or mucous membranes), and the symptoms of fatigue, lightheadedness, and weakness. None of the symptoms (or any of the others below) are sensitive or specific. Pallor of mucous membranes (primarily the conjunctiva) in children indicates anemia with the best correlation to the actual disease, but in a large study was found to be only 28% sensitive and 87% specific (with high predictive value) in distinguishing children with anemia and 49% sensitive and 79% specific in distinguishing severe anemia (Hb < 7.0 g/dl). Thus, this sign is reasonably predictive when present, but not helpful when absent, as only one-third to one-half of children who are anemic (depending on severity) will show pallor. Iron-deficiency must be diagnosed by laboratory testing. Because iron deficiency tends to develop slowly, adaptation occurs and the disease often goes unrecognized for some time, even years; patients often adapt to the systemic effects that anemia causes. In severe cases, dyspnea (trouble breathing) can occur. Unusual obsessive food cravings, known as pica, may develop. Pagophagia or pica for ice has been suggested to be specific, but is actually neither a specific or sensitive symptom, and is not helpful in diagnosis. When present, it may (or may not) disappear with correction of iron-deficiency anemia. Other symptoms and signs of iron-deficiency anemia include: Anxiety often resulting in OCD-type compulsions and obsessions Irritability or a low feeling Angina Constipation Sleepiness/Hypersomnia Tinnitus Mouth ulcers Palpitations Hair loss Fainting or feeling faint Depression Breathlessness Twitching muscles Pale yellow skin Tingling, numbness, or burning sensations Missed menstrual cycle Slow social development Glossitis (inflammation or infection of the tongue) Angular cheilitis (inflammatory lesions at the mouth's corners) Koilonychia (spoon-shaped nails) or nails that are weak or brittle Poor appetite Pruritus (itchiness) Dysphagia due to formation of esophageal webs (Plummer-Vinson syndrome) Insomnia Restless legs syndrome Infant development Iron-deficiency anemia for infants in their earlier stages of development may have greater consequences than it does for adults. An infant made severely iron-deficient during its earlier life cannot recover to normal iron levels even with iron therapy. In contrast, iron deficiency during later stages of development can be compensated with sufficient iron supplements. Iron-deficiency anemia affects neurological development by decreasing learning ability, altering motor functions, and permanently reducing the number of dopamine receptors and serotonin levels. Iron deficiency during development can lead to reduced myelination of the spinal cord, as well as a change in myelin composition. Additionally, iron-deficiency anemia has a negative effect on physical growth. Growth hormone secretion is related to serum transferrin levels, suggesting a positive correlation between iron-transferrin levels and an increase in height and weight. This is also linked to pica, as it can be a cause. Cause A diagnosis of iron-deficiency anemia then requires further investigation as to its cause. It can be caused by increased iron demand / loss or decreased iron intake, and can occur in both children and adults. The cause of chronic blood loss should all be considered, according to the patient's sex, age, and history, and anemia without an attributable underlying cause is sufficient for an urgent referral to exclude underlying malignancy. In babies and adolescents, rapid growth may outpace dietary intake of iron, and result in deficiency without disease or grossly abnormal diet. In women of childbearing age, heavy or long menstrual periods can also cause mild iron-deficiency anemia. Parasitic disease The leading cause of iron deficiency worldwide is a parasitic disease known as a helminthiasis caused by infestation with parasitic worms (helminths) such as tapeworms, flukes, and roundworms). 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. Blood loss Blood contains iron within red blood cells, so blood loss leads to a loss of iron. There are several common causes of blood loss: Women with menorrhagia (heavy menstrual periods) are at risk of iron-deficiency anemia because they are at higher-than-normal risk of losing a larger amount blood during menstruation than is replaced in their diet. Slow, chronic blood loss within the body — such as from a peptic ulcer, angiodysplasia, a colon polyp or gastrointestinal cancer, excessively heavy periods — can cause iron-deficiency anemia. Gastrointestinal bleeding can result from regular use of some groups of medication, such as NSAIDs (e.g. aspirin), anticoagulants such as clopidogrel and warfarin, although these are required in some patients, especially those with states causing thrombophilia. Diet The body normally gets the iron it requires from foods. 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 iron from their diet, too. A high intake of cow’s milk is associated with an increased risk of iron deficiency anemia.Other risk factors for iron deficiency include low meat intake and low intake of iron-fortified products. Iron absorption Iron from food is absorbed into the bloodstream in the small intestine, especially the duodenum and proximal ileum. Many intestinal disorders can reduce the body's ability to absorb iron. There are different mechanisms that may be present. In cases where there has been a reduction in surface area of the bowel, such as in celiac disease, inflammatory bowel disease or post surgical resection, the body can absorb iron, but there is simply insufficient surface area. If there is an 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). Ferrous and Ferric iron salts will precipitate out of solution in the bowel which are poorly absorbed. In cases where systemic inflammation is present, iron will be absorbed into enterocytes, but due to the reduction in basolateral ferroportin molecules which allow iron to pass into the systemic circulation, iron is trapped in the enterocytes and is lost from the body when the enterocytes are sloughed off.Depending on the disease state, one or more mechanisms may occur. Pregnancy Without iron supplementation, iron deficiency anemia occurs in many pregnant women because their iron stores need to serve their own increased blood volume as well as be a source of hemoglobin for the growing fetus, and for placental development. Other less common causes are intravascular hemolysis and hemoglobinuria.