iron deficiency anemia,metabolism, cause, treatment
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IRON DEFICIENCY ANEMIA Dr Rahul Arya Assistant Professor Department of Medicine
Iron is one of the most essential trace element Total body iron content is 3 to 5 g. 75 % present in blood, the rest is in liver, bone marrow & muscles. Iron is present in almost all cells. Heme is the most predominant iron-containing substance.
Sources of iron The best sources of food iron include liver, meat , egg yolk, green leafy vegetables, dates , whole grains and cereals . In a typical Indian diet, the major quantity of iron is received from cereals because of the bulk quantity taken, although they contain iron only in moderate amounts . Jaggery is a good source of iron . Milk is a very poor source of iron, containing less than 0.1 mg/100 ml.
RDA Adult man & postmenopausal women:10 mg Premenopausal women: 15 to 20 mg Pregnant women: 30 to 60 mg Women require greater amount than men due to physiological loss during menstruation.
Biochemical functions Iron is a component of several functionally important molecules . Iron is required for the synthesis of hemoglobin , myoglobin, cytochromes, catalase and peroxidase . Iron helps mainly in the transport, storage and utilization of oxygen.
Metabolism of iron Iron is absorbed from upper small intestine. Iron is absorbed in three forms: ( 1) ferrous iron (2 ) ferric iron (3) heme iron. • Iron is absorbed mainly in the ferrous form.
Ferric ions are reduced with ascorbic acid & glutathione of food to more soluble ferrous (Fe2 +) form which is more readily absorbed than Fe3 + After taken up by the intestinal mucosa, iron is either stored in the form of ferritin in the mucosal cells or transported across the mucosal cells to the plasma in the form of transferrin.
The iron (Fe2+) entering the mucosal cells by absorption is oxidized to ferric form (Fe3+) by the enzyme ferroxidase Fe3+ combines with apoferritin to form ferritin, which the temporary storage form of iron.
Causes of Iron Deficiency Anemia 1) Increased Demand for Iron Rapid growth in infancy or adolescence Pregnancy Erythropoietin therapy 2) Increased Iron Loss Chronic blood loss Menses Acute blood loss Blood donation Phlebotomy as treatment for polycythemia vera
3) Decreased Iron Intake or Absorption Inadequate diet Malabsorption from disease (sprue, Crohn’s disease) Malabsorption from surgery (gastrectomy and some forms of bariatric surgery) Acute or chronic inflammation
STAGES OF IRON DEFICIENCY Negative iron balance :- Demands for (or losses of) iron exceed the body’s ability to absorb iron from the diet . B lood loss, pregnancy, rapid growth spurts in the adolescent, or inadequate dietary iron intake. Blood loss in excess of 10–20 mL of red cells per day is greater than the amount of iron that the gut can absorb from a normal diet. T he iron deficit must be made up by mobilization of iron from RE storage sites. At this stage, red cell morphology and indices are normal.
2) Iron-deficient erythropoiesis :- When iron stores become depleted, the serum iron begins to fall; gradually , the TIBC increases . Once the transferrin saturation falls to 15–20%, hemoglobin synthesis becomes impaired . First appearance of microcytic cells.
3) Iron deficiency anemia :- Hemoglobin and hematocrit begin to fall. The transferrin saturation at this point is 10–15%.
When moderate anemia is present (hemoglobin 10–13 g/ dL ), the bone marrow remains hypoproliferative . With more severe anemia (hemoglobin 7–8 g/ dL ), hypochromia and microcytosis become more prominent , target cells and misshapen red cells ( poikilocytes ) appear on the blood smear as cigar- or pencil-shaped forms, and the erythroid marrow becomes increasingly ineffective.
LABORATORY IRON STUDIES 1) Serum Iron and Total Iron-Binding Capacity The serum iron level represents the amount of circulating iron bound to transferrin. The TIBC is an indirect measure of the circulating transferrin . Normal value- - Serum iron is 50–150 μg / dL - TIBC is 300–360 μ g/ dL
2) Transferrin saturation = serum iron × 100 ÷ TIBC. N ormally 25–50 %. Iron deficiency states are associated with saturation levels below 20%.
3) Serum Ferritin :- Under steady-state conditions, the serum ferritin level correlates with total body iron stores . Normal values- Adult males- 100 μ g/L adult females- 30 μ g/L S erum ferritin <15 μg /L are diagnostic of absent body iron stores.
4) Evaluation of Bone Marrow Iron Stores : B one marrow aspirate or biopsy T he marrow iron stain provides information about the effective delivery of iron to developing erythroblasts.
5) Red Cell Protoporphyrin Levels- Protoporphyrin is an intermediate in the pathway to heme synthesis . Under conditions in which heme synthesis is impaired, protoporphyrin accumulates within the red cell . This reflects an inadequate iron supply to erythroid precursors to support hemoglobin synthesis. Normal values are <30 μg / dL of red cells . In iron deficiency, values in excess of 100 μg / dL are seen.
DIFFERENTIAL DIAGNOSIS Other than iron deficiency, only three conditions need to be considered in the differential diagnosis of a hypochromic microcytic anemia . Anemia of inflammation Thalassemia Sideroblastic anemia
Tests Iron Deficiency Inflammation Thalassemia Sideroblastic Anemia Smear Micro/hypo Normal micro/hypo Micro/hypo with targeting Variable Serum iron ( μ g/ dL ) <30 <50 Normal to high Normal to high TIBC ( μ g/ dL ) > 360 <300 Normal Normal Percent saturation < 15 10-20 30–80 30–80 Ferritin ( μ g/L) < 10 30-200 50–300 50–300 Hemoglobin pattern on electrophoresis Normal Normal Abnormal with β thalassemia; can be normal with α thalassemia Normal
Treatment 1) RED CELL TRANSFUSION Indications individuals who have symptoms of anemia cardiovascular instability continued and excessive blood loss from whatever source who require immediate intervention.
2) ORAL IRON THERAPY Ferrous sulfate, Ferrous fumarate, Ferrous gluconate . U p to 200 mg of elemental iron per day is given, usually as three or four iron tablets (each containing 50–65 mg elemental iron) given over the course of the day . Ideally, oral iron preparations should be taken on an empty stomach , since food may inhibit iron absorption .
The goal of therapy in individuals with iron-deficiency anemia is not only to repair the anemia, but also to provide stores of at least 0.5–1 g of iron. Sustained treatment for a period of 6–12 months after correction of the anemia will be necessary to achieve this. Side effect :- Gastrointestinal distress- abdominal pain , nausea, vomiting, or constipation.
3) PARENTERAL IRON THERAPY Indications- patients who are unable to tolerate oral iron whose needs are relatively acute who need iron on an ongoing basis.
iron dextran, sodium ferric gluconate, iron sucrose and ferric carboxymaltose . ferric gluconate delivers 125 mg per injection, ferric carboxymaltose 750 mg per injection, and iron sucrose 200 mg per injection . The amount of iron needed by an individual patient is calculated by the following formula : Body weight (kg) × 2.3 × (15 – patient’s hemoglobin, g/ dL ) + 500 or 1000 mg (for stores )
Side effect- Anaphylaxis ( most commonly with iron dextran ). Early in the infusion of iron, if chest pain , wheezing, a fall in blood pressure, or other systemic symptoms occur , the infusion of iron should be stopped immediately.