Iron Deficiency AnemiaMedicine

Abbas A. A. Shawka

Introduction• hypoproliferative anemias : Anemias associated with

normocytic and normochromic red cells and an inappropriately low reticulocyte response (reticulocyte index <2–2.5)

• This category includes early iron deficiency (before hypochromic microcytic red cells develop), acute and chronic inflammation (including many malignancies), renal disease, hypometabolic states such as protein malnutrition and endocrine deficiencies, and anemias from marrow damage

Introduction• Hypoproliferative anemias are the most common anemias.• In the clinic, iron deficiency anemia is the most common

of these followed by the anemia of inflammation. The anemia of inflammation, similar to iron deficiency, is related in part to abnormal iron metabolism.

• The anemias associated with renal disease, inflammation, cancer, and hypometabolic states are characterized by a suboptimal erythropoietin response to the anemia.

Questions ? 1. What is the common point between iron

deficiency anemia and anemia after inflammation ?

2. What is the characteristics of The anemias associated with renal disease, inflammation, cancer, and hypometabolic states ?

Iron metabolism• the body must protect itself from free iron, which is highly

toxic.

• Elaborate mechanisms have evolved that allow iron to be made available for physiologic functions while at the same time conserving this element and handling it in such a way that toxicity is avoided.

Why Iron is very important for body ? 1. to carry O2 as part of hemoglobin.2. O2 is also found in myoglobin. 3. critical element in iron-containing enzymes, including the

cytochrome system in mitochondria. Without iron, cells lose their capacity for electron transport and energy metabolism.

4. In erythroid cells, hemoglobin synthesis is impaired, resulting in anemia and reduced O2 delivery to tissue.

High or low plasma Transferrin ?• When erythropoiesis is markedly stimulated, the pool of

erythroid cells requiring iron increases and the clearance time of iron from the circulation decreases. The half-clearance time of iron In the presence of iron deficiency is as short as 10–15 min.

• With suppression of erythropoiesis, the plasma iron level typically increases and the half-clearance time may be prolonged to several hours.

• The major requirement of Iron is supplied from aged RBCs.• Normally, an adult male will need to absorb at least 1 mg of elemental

iron daily to meet needs, while females in the childbearing years will need to absorb an average of 1.4 mg/d .

• However, to achieve a maximum proliferative erythroid marrow response to anemia, additional iron must be available. With markedly stimulated erythropoiesis, demands for iron are increased by as much as six to eightfold

Extravascular VS. Intravascular Hemolytic Anemias

• With extravascular hemolytic anemia ( RBCS phagocytic by macrophage ), the rate of red cell destruction is increased, but the iron recovered from the red cells is efficiently reutilized for hemoglobin synthesis.

• In contrast, with intravascular hemolysis ( release Hb to blood ) or blood loss anemia, the rate of red cell production is limited by the amount of iron that can be mobilized from stores.

Way to lo

• There is no regulated excretory pathway for iron, and the only mechanisms by which iron is lost are blood loss (via gastrointestinal bleeding, menses, or other forms of bleeding) and the loss of epithelial cells from the skin, gut, and genitourinary tract.

Questions ? 1. A patient with IV hemolysis anemia what

do you expect for these values ? ( serum iron , ferritin , TIBC )

2. A patient with damaged bone marrow what will you expect for his serum iron value ?

Iron deficiency anemia

• Iron deficiency is one of the most prevalent forms of malnutrition.

• Many causes!

STAGES OF IRON DEFICIENCY

Measurements of marrow iron stores, serum ferritin, and total iron-binding capacity (TIBC) are sensitive to early iron-store depletion.

Iron-deficient erythropoiesis is recognized from additional abnormalities in the serum iron (SI), percent transferrin saturation, the pattern of marrow sideroblasts, and the red blood cell (RBC) protoporphyrin level.

Patients with iron-deficiency anemia demonstrate all the same abnormalities plus hypochromic microcytic anemia

Laboratory Iron Studies• The serum iron level represents the amount of circulating iron bound

to transferrin.• The TIBC is an indirect measure of the circulating transferrin.

• Iron deficiency states are associated with saturation levels below 20%• A transferrin saturation % >50% indicates that a disproportionate

amount of the iron bound to transferrin is being delivered to nonerythroid tissues. If this persists for an extended time, tissue iron overload may occur

SI 50–150 μg/dL

TIBC 300–360 μg/dL

• Serum Ferritin level is the most convenient laboratory test to estimate iron stores. The normal value for ferritin varies according to the age and gender of the individual

Iron store depletion and iron deficiency are accompanied by a decrease in serum ferritin level below 20 μg/L

• The serum ferritin level is a better indicator of iron overload than the marrow iron stain. However, in addition to storage iron, the marrow iron stain provides information about the effective delivery of iron to developing erythroblasts.

• Under conditions in which heme synthesis is impaired, protoporphyrin ( Not occupied Iron Heme ) accumulates within the red cell. Normal values are <30 μg/dL of red cells. In iron deficiency, values in excess of 100 μg/dL are seen. The most common causes of increased red cell protoporphyrin levels are absolute or relative iron deficiency and lead poisoning.

• Serum Levels of Transferrin Receptor Protein Because erythroid cells have the highest numbers of transferrin receptors of any cell in the body, and because transferrin receptor protein (TRP) is released by cells into the circulation, serum levels of TRP reflect the total erythroid marrow mass.

• This laboratory test is becoming increasingly available and, along with the serum ferritin, has been proposed to distinguish between iron deficiency and the anemia of inflammation.

Differential diagnosing

• Other than iron deficiency, only three conditions need to be considered in the differential diagnosis of a hypochromic microcytic anemia.

1. Thalassemia's. These are differentiated from iron deficiency most readily by serum iron values; normal or increased serum iron levels and transferrin saturation are characteristic of the thalassemia's. In addition, the red blood cell distribution width (RDW) index is generally normal in thalassemia and elevated in iron deficiency.

2. The second condition is the anemia of inflammation (AI; also referred to as the anemia of chronic disease) with inadequate iron supply to the erythroid marrow. The distinction between true iron deficiency anemia and AI is among the most common diagnostic problems encountered by clinicians (see below). Usually, AI is normocytic and normochromic. The iron values usually make the differential diagnosis clear, as the ferritin level is normal or increased and the percent transferrin saturation and TIBC are typically below normal.

3. Occasionally, patients with myelodysplasia have impaired hemoglobin synthesis with mitochondrial dysfunction, resulting in impaired iron incorporation into heme. The iron values again reveal normal stores and more than an adequate supply to the marrow

despite the microcytosis and hypochromia.

Treatement1- Blood transfusion2- Oral Iron Therapy3- Parenteral Iron Therapy

Note!

Questions ?A patient with early stage of Iron defeiciency anemia what will you expect for these valuse ? ( SI , Serum ferritin , TIBC , Trans. Saturation )