What is Iron deficiency anemia (A common type of anemia)?
Anemia is defined as the decrease in the normal level of hemoglobin. As hemoglobin is composed of heme and the globin chain, and Iron is present in the heme. So, when the iron decrease in the body, it leads to the decreased synthesis of heme, ultimately the hemoglobin synthesis is reduced, which leads to anemia.
Iron deficiency anemia is the most common nutritional disorder that occurs in developing countries mostly like the USA. Normally 3-5g of iron is present in the body, in males, the amount is 3.5g, while in females it is 2.5g. The normal dietary intake of iron is10-20mg per day, while the excretion is 2.5g.
Sources of Iron
There are two types of sources, which are Heme and Non-heme sources. Heme sources include Meat, Kidney, Liver, etc. While the non-heme sources include Fruits, Leafy vegetables. The factors that facilitate the absorption of iron are called Facilitatory Ligands, they include Aminoacids, Ascorbic acid, Citric acid, Meat, Sugar, etc. As the factors that inhibit the absorption of iron are called Inhibitory Ligands, these include Tannic acid, Phosphate, Phytic acid, etc.
Iron distribution
The iron in the body is distributed in three categories, that are in Hemoglobin, Iron stores, and Plasma. 80% of body iron is present in the hemoglobin. While the iron stores are of two types namely Available and Non-available. Available iron stores are ferritin and hemosiderin, Iron stored in both proteins can be used when needed by the body. And the Non-available iron stores are myoglobin and enzymes whose iron can not be used if needed by the body. Last is the plasma, where Iron is bonded with transferrin, about 500mg of iron is present in the plasma.
Metabolism of Iron
The iron is absorbed in the Proximal duodenum in ferrous form. First, the iron in the ferric form reaches the proximal duodenum, where with the help of the enzyme Ferric reductase, Fe+3 (ferric form) is reduced to Fe+2 (ferrous form), which is the absorbable form. The ferrous iron is transported into mucosal cells through DM-T1 (Divalent Metal Transporter-1), where its small amount is stored via binding with Ferritin, and the remaining is transported through basolateral enterocyte membrane by Ferroportin into the blood plasma. As iron reaches the plasma, converted to a ferric state again and binds with transferrin.
Less than 5% of Non-heme iron is absorbed, while about 25% of heme iron is derived from hemoglobin, myoglobin, and other animal proteins.
Free iron is highly toxic, so stored by binding with ferritin and hemosiderin. Ferritin is a ubiquitous protein-iron complex found at high levels in the liver, bone marrow, spleen, and skeletal muscles. Most of the ferritin present in the liver is stored within the parenchymal cells. Iron in the hepatocyte is derived from plasma transferrin, whereas Storage iron in macrophages is derived from the breakdown o red blood cells. Hemosiderin will be present in traces if the iron level is normal. But if the Iron is overloaded, then most iron will be stored in hemosiderin form.
Iron balance is maintained largely by regulating the absorption of dietary iron in the proximal duodenum. As there is no regulated pathway for the excretion of iron. So, daily 1-2mg of iron is excreted by shedding of mucosal and skin epithelial cells.
Role of Hepcidin
Hepcidin is a small circulating peptide that regulates how much iron should be absorbed or excreted. As the iron level increases in the plasma, the synthesis of hepcidin increases in the liver. Then hepcidin causes the internalization or endocytosis of the ferroportin, which leads to the inhibition of iron absorption. Hepcidin not only inhibits ferroportin but also suppresses iron release from macrophages, that iron is the important source of hemoglobin synthesis.
Increased level of hepcidin occurs when the increase in the concentration of intracellular iron, increases the concentration of extracellular iron, increases iron requirements, and also in inflammation. If the inflammation is chronic, then leads to Anemia.
Causes of Iron deficiency anemia
Following are the factors that lead to a decrease of the iron level in the body,
- Blood loss: The most common cause of iron deficiency is chronic blood loss, as it leads to the increase in hematopoiesis, that requires iron for erythropoiesis(RBC formation).
- Malnutrition: The decrease iron intake that leads to the decrease iron level in the body.
- Increase demand: As in children or infants, or pregnant women, the iron demand is increased, that may lead to iron-deficiency anemia.
- Malabsorption: If an individual has good amount of iron intake, but have impaired absorption, then it may leads to iron-deficiency anemia.
Pathophysiology of Iron-deficiency anemia
As the iron level decreases due to any cause, the iron stores like ferritin and hemociderin may be adequate to maintain the normal hemoglobin and hematocrit level as well as serum iron level and transferrin saturation. But the progressive depletion of iron reserves first cause decrease serum iron level, decrease in transferrin saturation without producing Anemia, also increased erythroid precursors activity in bone marrow. Anemia appears when iron stores are completely depleted, low serum iron, low ferritin, and low transferrin saturation.
Morphology
Bone marrow of Iron deficiency anemia patient reveals mild to moderate increase in erythroid precursors. The diagnostic finding of Iron-deficiency anemia is the disappearance of stainable iron from macrophages in bone marrow, the best assessed by performing pruassion blue stains on smear of aspirated marrow. In peripheral smear of blood, microcytic(small) and hypchromic (pale) RBCs are present. Poikilocytosis in the form of small, elongated (Pencil like) RBC is also characteristically seen.
Symptoms of Iron-Deficiency Anemia
Following are the Symptoms of Iron-Deficiency Anemia:
- Lassitude
- Weakness
- Fatigue
- Dyspnea (shortness of breath)
- Palpitation
- Angina
- Pallor
- Brittle Nails
- Pica (Eating non-food stuff like soil)
Diagnosis of Iron-deficiency Anemia
Iron-deficiency anemia is diagnosed by the blood tests like Complete blood count test. Other tests are done to check the levels of ferritin, serum iron, total iron binding capacity, and transferrin saturation levels. If a patient is diagnosed with this anemia, then the results will be:
- low hemoglobin
- low hematocrit
- low ferritin
- low serum iron
- increased total iron binding capacity
- low iron saturation
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