Iron Deficiency Anemia PDF

**[IRON DEFICIENCY ANEMIA]** - Common form of anemia - Iron is an essential element in the synthesis of hemoglobin - Early diagnosis - essential to non-anemic infants and toddlers to prevent decline cognitive and psychomotor skills - Important in proper treatment...

**[IRON DEFICIENCY ANEMIA]** - Common form of anemia - Iron is an essential element in the synthesis of hemoglobin - Early diagnosis - essential to non-anemic infants and toddlers to prevent decline cognitive and psychomotor skills - Important in proper treatment - Equally important in pregnant women to reduce maternal-fetal morbidity - Etiology - Decrease iron intake -- when not enough iron is consumed to meet the normal, daily required amount of iron - Increase iron utilization -- during pregnancy, growth years, or periods of increased blood regeneration - Excessive loss of iron -- occur on acute or chronic hemorrhage or heavy menstruation - Faulty or incomplete iron absorption -- caused by **achlorhydria** (absence of or reduction in hydrochloric acid in gastric juice) in certain disorders or following gastric resection; or chronic diarrhea - Pathological iron loss in adult males and postmenopausal females with iron deficiency - Physiology - Humans have 35 to 50 mg of iron per kilogram of body weight. - Average adult has 3.5 to 5.0 g of total iron - Average loss of iron is 1 mg/day -- need to be replace - Iron excretion -- exfoliation of intestinal epithelial and skin cells, the bile , and urinary excretion - Operational iron -- use for oxygen binding and biochemical reactions; - in humans found in heme portion of hgb or myoglobin and is recycled - normal adults hgb has the 2/3 of the iron present in the body - Iron needs in infants and children - Iron stores are adequate to maintain iron sufficiency for approximately 4 months of postnatal growth - Approximately two thirds of iron losses in infancy occur when cells are extruded from the intestinal mucosa and the remainder when cells are shed from the skin and urinary tract - Infants aged 7 to 12 months need 11 mg of iron a day. - Babies younger than 1 year should be given iron-fortified cereal in addition to breast milk or an infant formula supplemented with iron - Absorption of iron from breast milk is uniquely high, about 50% on average, and tends to compensate for its low concentration; In contrast, only about 10% of iron in whole cow's milk is absorbed - Dietary iron - Two broad types of dietary iron; - Non-heme iron -- in the form of iron salt, 90% iron from food - Ascorbic acid enhances absorption of non-heme iron - Inhibitors for the absorption: bran, polyphenols, oxalates, phytates, vegetable fiber, the tannin in tea, and phosphates - Heme iron -10% of dietary iron derived from hgb and myoglobin of meat - Following oral intake of iron in ferric (Fe^3+^), stomach secretions reduce iron to the ferrous (Fe^2+^) - **Reducing agents**, include glutathione, ascorbic acid, and sulfhydryl groups of proteins and digestion products. - **Absorption** by the GI epithelial cells is finely tuned to admit just enough iron to cover losses, without permitting either excess or deficiency of body iron to develop. - Most absorbed iron becomes attached to the **plasma protein transferrin**, which is formed in the liver. - **Transferrin**, a beta globulin, is a glycoprotein. Transferrin chelates iron within the intestinal lumen and shuttles it into the mucosal cells of the small intestine - **Cellular uptake** of iron begins with the binding of the transferrin-iron complex to a specific receptor. - Cells of different organ systems show considerable differences in the concentration of cellular **transferrin receptors,** - The highest concentrations being found in cells of organs with the highest requirements, such as the hemoglobin synthesizing erythroid bone marrow cells and placental trophoblasts. - **Circulating transferrin receptor** concentrations increase in tissue iron deficiency, reflecting the degree of iron deficiency in the erythroid precursors of the marrow. - The **ratio** of transferrin receptor to ferritin displays an **inverse linear** relationship to iron status - Any remaining iron is retained in the cells, where it combines with the protein **apoferritin** to form **ferritin** - **Storage iron** is the second largest iron compartment in the body. - Most storage iron is found in hepatocytes and macrophages, where it is sequestered in ferritin - The first line of iron supply is the mononuclear phagocyte system - Pathophysiology - Three sequential phase - Stage 1 Prelatent -- decrease in storage iron - Stage 2 Latent -- decrease in iron available for erythrophoiesis - Stage 3 Anemia -- decrease in circulating RBC parameters and decrease in oxygen delivery to peripheral tissue - Clinical signs and symptoms - Paleness, fatigue, and/or weakness - Papilledema -- related to abnormal hemodynamics, as in the state of increased blood flow to the brain; lead to visual loss if untreated - Anemia may lead to reversible bulging of the fontanels in infants - Psychomotor and mental impairment in the first 2 yrs of life - Pica -- a consequence of IDA - Laboratory Characteristics - Hematology studies - CBC - platelet count & WBC count must be noted - Platelets usually normal but may increase following acute blood loss - WBC count is normal - Hgb and hct are decreased - PBS -- N/N or micro/hypo; percentage of hypochromic RBC (%HYPO), this marker has been demonstrated to be the most sensitive and specific parameter of functional iron deficiency - RBC Indices -- MCV can separate macro/normo or microcytic rbc presentations - Decreased RBC indices - Reticulocyte count -- usually normal to decreased - equal to or greater than 2.5% demonstrates increased erythropoiesis; - **Reticulocyte hgb content** (CHr)is an effective early indicator of IDA - Done with fully automated hematology analyzers (Sysmex XE2100, Bayer ADVIA 2120) - Cut off level of 27.2 pg, IDA can be diagnosed with a sensitivity of 93.3% and a specificity of 83.2% - Bone marrow smear -- reveals marked decrease in stainable iron and erythroid hyperplasia - Clinical Chemistry - Iron studies -- used to establish a differential diagnosis of microcytic/hypochromic anemia because micro/hypo rbc can be associated with thalassemias or sideroblastic anemias - Tests total body iron, transferrin, serum iron levels - Low total body iron = increase transferrin = decline serum iron - Serum iron level of 10-15 g/dL is a characteristic of IDA - Serum ferritin -- currently accepted as lab assay for IDA diagnosis - Value of 12 ug/L or less is a highly specific indicator of iron deficiency - Soluble transferrin receptor (sTfR) - complete transferrin receptor is a membrane-bound protein that captures transferrin - As the supply of transferrin-bound iron declines, hungry cells produce more TfR, which results in a higher serum concentration of the fragment - An apparent, and potentially major, advantage is the ability of sTfR to provide differentiation of IDA from anemia of chronic inflammation disorders (ACDs) **[ANEMIA OF INFLAMMATION (AOI) OR ANEMIA OF CHRONIC DISORDERS (ACD)]** - Etiology - second most prevalent anemia after IDA - This form of anemia is a common complication in patients with disorders as diverse as inflammation, infection, malignancy, or various systemic diseases. - Pathophysiology - AOI/ACD is a hypoproliferative anemia resulting from underproduction of red cells. - not related to any nutritional deficiency - The main defect is related to hepcidin. - HEPCIDIN -- a small 25-amino acid polypeptide hormone, is a key molecule in controlling iron absorption and recycling. - Released by the liver and circulates to interact with its cellular receptor; also produced in human monocytes - Laboratory characteristics - Elevated platelet count - Elevated total WBC count - Positive CRP test - Hematology studies - mild hypoprolific anemia with a hematocrit usually fixed in the 28% to 32% range - hemoglobin may be as low as 5 g/dL - PBS is usually N/N; but1/4 to 1/3 of the patients display hypo/micro - Reticulocytosis is not present - Leukoerythroblastosis in AOI cause by malignancy - Abnormal RBC morphology -- teardrop rbc, schistocytes, helmet cells, fibrosis, hypochromia - Platelets are normal - In bone marrow, hemosiderin is increased or normal - Sideroblasts are decreased - Reticulocyte count is usually less than 2% - Clinical chemistry - Abnormalities in iron metabolism are associated with this disorder - Serum iron levels and transferrin are decreased - Serum iron level is low because recycling of iron from macrophages are impaired - TIBC and transferrin saturation level is decreased or normal - Serum level ferritin are variable - combination of low serum iron and iron-binding capacity combined with stainable iron in the bone marrow is virtually diagnostic of ACD - In women of childbearing age, both characteristics of IDA and ACD coexist. - Treatment - If anemia is severe, blood transfusion may be considered. - Recombinant human erythropoietin, rHu-EPO (Procrit, epoetin alfa), is a newer treatment alternative. **[MEGALOBLASTIC ANEMIA]** - Term **megaloblastic** refers to the abnormal marrow erythrocyte precursor seen in processes, such as pernicious anemia, associated with altered DNA synthesis. - Megaloblastic anemias can be classified into two major categories based on etiology - Vitamin B12 (cobalamin, Cbl) deficiency - Folic acid deficiency - Etiology - Megaloblastic anemia caused by vitamin B12 deficiency is associated with - Increased utilization of vitamin B12 - Due to parasitic infections such as *D. latum* (tapeworm) and pathogenic bacteria in disorders such as diverticulitis and small bowel stricture. - Malabsorption syndrome - caused by gastric resection, gastric carcinoma, and some forms of celiac disease or sprue. - Nutritional deficiency or diminished supply of vitamin B~12~. - Cobalamin is synthesized by bacteria and is found in soil and in contaminated water. - Foods of animal origin (e.g., meat, eggs, and milk) are the primary dietary sources. - Pernicious anemia - the condition associated with chronic atrophic gastritis. - Megaloblastic anemia caused by folic acid deficiency is associated with - Abnormal absorption caused by celiac disease or sprue - Increased utilization caused by pregnancy or some acute leukemias - Treatment with antimetabolites that act as folic acid antagonists - Physiology - Normal red cell maturation is dependent on many hematological factors, two of which are the vitamin B12 coenzymes (also called cobalamin) and folates. - Megaloblastic **dyspoiesis** occurs when one of these factors is absent. - Vitamin B~12~ - Vitamin B~12~ and a variety of structurally similar compounds, known as **cobalamin analogues** becomes available to humans through the food chain. - Cobalamin analogues are that lack the functional coenzyme activity of the vitamin occur in nature as a product of certain microorganisms. - Adults has 5,000 ug of Vit B~12~ and 1/3 of it is stored at the liver. - Daily requirement of Vit B~12~ is 5 ug/day - Cobalamin transport is mediated by three different binding proteins - intrinsic factor (IF), - transcobalamin II (TC II), and - R proteins. - Folic acid - Folates are abundant in yeast, many leafy vegetables, and organ meats such as liver and kidneys. - **Alcohol** is the most common pharmacological cause of folic acid deficiency. - Folic acid antagonists, such as certain drugs used to treat leukemias and oral contraceptives, appear to reduce the absorption of folic acid. ***[Pernicious Anemia]*** - the most common megaloblastic anemia - deficiency is caused by reduced IF (intrinsic factor) secondary to gastric atrophy - majority of cases of pernicious anemia, anti-IFs or antibodies to parietal cells (large cells on the margin of the peptic glands of the stomach) have been reported. - Most authorities consider the demonstration of these antibodies to support the theory that pernicious anemia is an **autoimmune disorder**. - The presence of **IF-blocking antibodies** is diagnostic of pernicious anemia. - Pathophysiology: - Pernicious anemia applies only to the condition associated with chronic atrophic gastritis. - Clinical signs & symptoms: - Because of the pivotal role of cobalamin in metabolism, multiple organ systems can be affected in pernicious anemia. - Patients may note changes in their skin color to a lemon-yellow appearance. - The nail beds, skin creases, and periorbital areas may become hyperpigmented owing to melanin deposition. - Angular cheilitis (cracking at the corners of the mouth), dyspepsia, and diarrhea can occur. - Glossitis and a painful tongue are frequently observed. - Early graying of the hair can be seen - Patients may complain of tiredness, dyspnea on exertion, vertigo, or tinnitus secondary to anemia - Congestive heart failure, angina, or palpitations may be noted. Neurological and cognitive abnormalities may be seen in cobalamin deficiency - Laboratory Findings: - hemoglobin and red cell counts are usually **extremely low** - increase in red cell size is typically reflected in the **mean corpuscular volume** (**MCV**), which may be as **high** as 130 fL. - **mean corpuscular hemoglobin** (**MCH**) varies but is usually increased in 90% of cases - **mean corpuscular hemoglobin concentration** (**MCHC**) is usually normal - **platelet** counts are usually moderately decreased. - The total white **WBC** will classically demonstrate a leukopenia, particularly a neutropenia - PBS reveals a moderate to significant anisocytosis and poikilocytosis with many macrocytic, ovalocytic red cells - **metarubricytes**, may also be observed. - **Promegaloblasts** and **nucleated erythrocytes** may be seen In severe anemia with a hematocrit of less than 20% - Red cell inclusions such as **basophilic stippling, Howell-Jolly bodies,** and **Cabot rings** may be observed. - Abnormalities in leukocytes may include **hypersegmented** (more than four lobes) **neutrophils** and an increase in the percentage of **eosinophils** (eosinophilia). - **reticulocyte** count is less than 1% if untreated - **Pancytopenia** may be seen in advanced cases - **RDW** is high - Clinical chemistry and Immunology assays: - serum vitamin B12, - serum folate - serum methylmalonic acid, - total homocysteine, - intrinsic factor blocking antibody (IF-antibody), - parietal cell antibody (IgG), - gastrin levels. - Ancilllary findings include increase LDH and bilirubin levels. - absence of free HCl in gastric fluid/ achlorhydria is a universal feature of this form of megaloblastic anemia - Treatment - standard treatment for vitamin B12 deficiency is regular monthly intramuscular injections of at least 100 mg of vitamin B12 to correct the vitamin deficiency.