Etiology
IDA has many causes and is not an end diagnosis in and of itself. Diagnosis of IDA should prompt further investigation to determine the cause, and to correct if possible.
Inadequate dietary iron intake
Impaired iron absorption (e.g., due to achlorhydria, gastric surgery, or celiac disease)
Increased iron loss because of bleeding, usually in the gastrointestinal tract (e.g., hemorrhoids, salicylate ingestion, peptic ulcer disease, hiatal hernia, diverticulosis, neoplasm, ulcerative colitis, hookworm, milk allergy in infants, Meckel diverticulum). Other causes of iron loss include menorrhagia, blood loss from hemodialysis, runner's anemia, schistosomiasis, trichuriasis, blood donation, hemoglobinuria, self-induced bleeding, idiopathic pulmonary hemosiderosis, Goodpasture syndrome, hereditary hemorrhagic telangiectasia, angiodysplasia, and disorders of hemostasis
Increased iron requirements of young children (e.g., due to growth, and inadequate dietary iron intake), pregnancy, or lactation
Unknown cause.
Blood loss is the principal cause of IDA. Rarely, in specific disorders (e.g., idiopathic pulmonary hemosiderosis or paroxysmal nocturnal hemoglobinuria), the iron is deposited in tissues where it is unavailable for hemoglobin production; however, total body iron stores may not be decreased.[11]
Pathophysiology
Iron is required for the formation of hemoglobin, myoglobin, and heme enzymes (cytochromes), and is therefore essential for red blood cell (RBC) production and cellular processes (e.g., cell metabolism, DNA replication/repair, and cell cycle regulation).[12]
The body does not have a regulatory pathway for iron excretion.[13] Physiologic iron loss occurs through menstrual bleeding, sweating, skin desquamation, and urinary/fecal excretion.[13] Men and postmenopausal women lose approximately 1 mg of iron daily, and menstruating women lose approximately 2 mg of iron daily.[14] Pregnancy results in a net loss of approximately 580 mg of iron during the gestation period due to expansion of maternal RBC mass and growth of the fetus and placenta, with the highest loss occurring in the third trimester.[9][15][16]
The body replenishes iron stores and maintains iron homeostasis by recycling iron from destroyed or senescent RBCs, and regulating dietary iron intake and absorption.[8] Dietary iron is absorbed mostly in the duodenum and jejunum, where it is transported by transferrin and stored in either ferritin or hemosiderin forms.[17]
The peptide hormone hepcidin decreases intestinal iron absorption and prevents recycling of iron by reticuloendothelial cells, leading to decreased circulating iron levels. It does this by binding and degrading the cellular iron exporter, ferroportin, which is found in reticuloendothelial cells, hepatocytes, and the basement membrane of enterocytes. Hepcidin transcription is depressed in iron deficiency, which results in increased intestinal iron absorption and release of iron from bodily stores in the bone marrow, liver, and spleen. Hepcidin expression is increased in systemic inflammatory or infectious states, and in chronic kidney disease.[18][19]
If iron stores are depleted because more iron is lost or used than can be absorbed, then hemoglobin formation and RBC production are impaired. This results in IDA, which is characterized by hypochromic and microcytic RBCs. Symptoms of IDA, such as fatigue, low energy level, and dyspnea on exertion, occur due to impaired RBC production and decreased oxygen-carrying capacity.[12]
Classification
Iron deficiency and related disorders[4]
The causes of iron deficiency can be categorized as:
Inadequate dietary iron intake
Impaired absorption (e.g., due to achlorhydria, gastric surgery, or celiac disease)
Increased iron loss because of bleeding, usually from the gastrointestinal tract
Increased iron requirements because of infancy, pregnancy, or lactation
Unknown cause.
Use of this content is subject to our disclaimer