Iron deficiency

• Morphologic classification of anemia uses erythrocyte indices (MCV).
• Macrocytic, Normochromic anemia is caused by Folate or B12 deficiency, liver disease, and alcoholism.
• Normocytic, Normochromic anemiais caused by bone marrow failure, haemolytic anaemia, chronic renal failure, leukaemia, and metastatic malignancy.
• Microcytic, Hypochromic anemia is the most common type of anemia.
• Microcytic, Hypochromic anemia is caused by iron deficiency, sideroblastic anemia, thalassemia, and chronic diseases.

Diagnosing Anemia

• Diagnosing anemia starts with the patient's clinical history.
• Physical presentations can include pallor, fatigue, weakness, dizziness, and dyspnea (shortness of breath).
• Laboratory tests are used in diagnosis such as:
  • CBC (complete blood count)
  • Examination of the blood smear
  • Reticulocyte count to measure effectiveness of erythropoiesis
  • Iron studies measuring iron, total iron-binding capacity (TIBC), and ferritin
  • Vitamin B12 and folate levels
  • Erythropoietin level
  • Bone marrow examination via smear and trephine biopsy

Iron Metabolism

• Primary function of iron is oxygen transport and storage.
• Iron-containing compounds assist in enzymatic and metabolic functions.
• They're also used for transportation or storage.
• Iron is located predominantly in RBCs.
• Macrophages of the spleen and liver are where RBC destruction occurs, liberating iron.
• Iron is stored in hepatocytes and enterocytes.
• Iron is lost through secretions of urine, bile, sweat, and exfoliation of intestinal epithelial cells of the GI tract.
• Iron regulation maintains a balance between loss and absorption.

Iron Regulation

• Human iron levels are regulated at two levels.
• Systemic iron is balanced by controlled dietary iron absorption in the intestines.
• Iron loss occurs through epithelial sloughing, sweat, injuries, and blood loss.
• A male adult needs ~1mg/day of iron absorbed from their diet.
• Iron levels are regulated through systemic iron recycling and loss processes.

Iron Re-Cycling

• Most of the body's iron is hoarded and recycled by the reticuloendothelial (RE) system.
• The Reticuloendothelial system breaks down aged red blood cells.
• Red cells are broken down in the macrophages of the RE system, subsequently releasing iron into the plasma.
• Iron is stored in RE cells as hemosiderin and ferritin in the ferric form.
• Stored iron is mobilized after reduction to the ferrous form using vitamin C.

Iron Absorption

• Only 5-10% of iron is normally absorbed and can increase to 20-30% in iron deficiency or pregnancy cases.
• Even with higher rate of absorbtion, most dietary iron remains unabsorbed.
• The body's iron absorption rate depends on:
  • Total iron stores
  • Bone marrow activity in producing new red blood cells
  • Concentration of hemoglobin in the blood
  • Oxygen content of the blood
• The body absorbs less iron during inflammation to deprive bacteria of it.
• About 1/3 of iron is stored in the liver and spleen.
• A transferrin is synthesized in the liver that transports iron in plasma and has a half-life of 8-10 days.
• Transferrin can bind two atoms of iron per molecule and is re-utilized after it has given up its iron.
• Approximately 95% of iron is complexed with transferrin.
• Once iron needs are met in the bone marrow, it is deposited in tissues, like the liver, for storage.
• Ferritin and hemosiderin are the largest non-heme iron stores in the body.
• Storage iron serves as a quick supply in cases of increased iron loss through bleeding.
• Iron is transported from the duodenum into mucosal cells in the ferrous form, where it is converted to the ferric form.
• Iron may combine with apoferritin to form ferritin or cross into the plasma.
• The majority of transferrin-bound iron is delivered to the bone marrow, binding to transferrin receptors on the normoblasts as ferrous form.
• If there is excess iron absorbed as ferritin, it is deposited as hemosiderin.

Iron Deficiency Anemia (IDA)

• Iron Deficiency Anemia is the most common form of anemia.
• A normal adult male needs ~1.0 mg/day of iron.
• IDA occurs when iron stores in the body are inadequate to preserve homeostasis, leading to fatigue, lethargy, and dizziness.
• Symptoms also include pallor of mucous membranes, koilonychias (spooning of nails).
• Causes of IDA include dietary deficiency, blood loss, hemodialysis, and malabsorption.
• Non-heme iron (Ferric) is found in vegetables and grains but is not easily absorbed.
• Heme iron (ferrous) is found in red meat and is readily absorbed.
• IDA involves three stages:
  • Stage 1: Decrease in storage iron (ferritin decrease) with no anemia and normal RBC morphology, RDW may be elevated
  • Stage 2: Decrease in iron for erythropoiesis with no anemia or hypochromia, RBC slightly microcytic
  • Stage 3: Decrease in Blood Hb causes decreased oxygen to peripheral tissue resulting in microcytic, hypochromic anemia
• Laboratory findings for IDA include:
  • Increased RDW
  • Decreased RBC, Hb, Hct, MCV, MCH, and MCHC
  • Normal to decreased reticulocyte count.
• Chemistry results also show decreases in serum iron and ferritin, and increased TIBC.
• Peripheral blood smear findings:
  • Anisocytosis, microcytic-hypochromic cells in late stage.
  • Poikilocytosis (e.g., elliptocytes, teardrops), presence of nRBC.
  • If IDA is from bleeding, leukocytosis and thrombocytosis are possible.
• Bone marrow findings include absent or reduced sideroblasts and mild to moderate erythroid hyperplasia.
• IDA is a type of ineffective erythropoiesis due to decreased ability of erythrocytes to make hemoglobin

Anemia's Associated with Abnormal Heme Synthesis

• Sideroblastic Anemia
• Lead Poisoning
• Porphyrias

Sideroblastic Anemia

• Sideroblastic Anemia affects the first step in heme synthesis, the formation of ALA (amino levuilinate synthase).
• It is characterized by increased total body iron, ringed sideroblasts in bone marrow, and hypochromic anemia.
• Sideroblastic Anemia Mechanisms include:
  • Adequate iron can not be incorporated into hemoglobin synthesis
  • Iron enters mitochondria, accumulates, and leads to formation of ringed sideroblasts.
  • Eventually, the mitochondria rupture due to excess iron.
• Sideroblastic Anemia can also result in classification from
• Hereditary via X-linked recessive gene defect.
• Acquired anemia consists if 2 forms
  • Idiopathic anemia
  • Secondary type anemia with underlying causes for therapeutic drugs (eg TB drug), chronic transfusions (for aplastic anemia, leukemia, thalassemia), alcoholism and food fads, use of iron utensils or increased iron in water

Lead Poisoning

• Lead poisoning is a common cause of sideroblastic anemia.
• Lead interferes with iron storage in the mitochondria and damages the activity of enzymes used for heme synthesis.
• Basophilic stippling is pronounced.
• Laboratory findings:
  • Peripheral blood shows Pappenheimer bodies, hypochromic or normochromic RBCs, and normal to increased platelets.
  • Chemistry displays increased serum iron and ferritin, and decreased TIBC.