Hematology (SCIE2020) Past Paper PDF

Hematology I (SCIE2020) Harmening - Chapter 6 : Part A (5TH ED) Harmening – Chapter 7 : Part A (6TH ED) Iron Metabolism and Hypochromic Anemias OBJECTIVES 3.18  List the proteins that carry the following components in circulation: 3.18.1 : Iron 4.1...

Hematology I (SCIE2020) Harmening - Chapter 6 : Part A (5TH ED) Harmening – Chapter 7 : Part A (6TH ED) Iron Metabolism and Hypochromic Anemias OBJECTIVES 3.18  List the proteins that carry the following components in circulation: 3.18.1 : Iron 4.1  Describe clinical signs of anemia 4.2  State the laboratory criteria for the diagnosis of anemia 4.3  State the significance of red blood cell indices as related to the diagnosis of anemia 4.4  Describe the appearance of the peripheral blood smear in various anemias 4.11  Correlate red cell indices with red cell morphology and the diagnosis of anemia 4.16  Correlate pathophysiology of clinical conditions associated with abnormal appearance of red cells noted on the peripheral blood smear 4.22  Compare the categories of anemia based on morphology 4.23  Describe the clinical presentation and laboratory findings of the following pathological conditions: 4.23.1 : Iron Deficient Anemia  Morphological Classification of Anemia (by appearance/indices) Erythrocyte Size Hgb. conc. Anemia Example(s) Microcytic Below Below Microcytic Iron Deficiency Today Hypochromic normal normal Hypochromic Anemia Macrocytic Above Normal Macrocytic Megaloblastic and Normochromic normal Normochromic Non-Megaloblastic Anemia Normocytic Normal Normal Normocytic Aplastic Anemia Normochromic Normochromic 4 Introduction  The microcytic hypochromic anemias are a group of red cell disorders that involve a defect in hemoglobin synthesis due to a deficiency of iron or an abnormal utilization of iron.  These anemias include:  iron-deficiency anemia (IDA), which is the most common;  anemia of chronic disease (ACD); and  sideroblastic anemia  Microcytic hypochromic anemias also include disorders of globin chain synthesis, which comprise the thalassemias.  We will cover these globin chain defects later, in Chapter 12 Recall from Chapter 3  Erythropoiesis is a highly regulated process throughout the entire life span of each individual  Hemoglobin synthesis is an integral part of erythropoiesis and requires three compounds: iron, globin, and protoporphyrin  Each hemoglobin molecule consists of four heme groups and four globin chains.  Each heme group contains a protoporhyrin ring plus an iron molecule  Adult hemoglobin A contains two alpha and two beta polypeptide chains.  For a review of hemoglobin formation and function, refer back to Chapter 3.  This chapter reviews normal iron metabolism followed by a discussion of iron deficiency anemia (IDA), anemia of chronic disease (ACD), sideroblastic anemia, and hereditary hemochromatosis Normal Iron Metabolism  Daily iron intake, absorption, and losses are usually very small  Body iron is repeatedly recycled, and the small amount of iron that is lost each day is replaced by the diet  This small amount of iron which is lost each day through cellular shedding and sweating is approximately 1mg  In adults, for example, this 1 mg of iron = Minimum Daily Requirement (MDR)  Normally absorb 1-2 mg/day  Normal Iron Metabolism Recall:  The normal life span of the red blood cell (RBC) is approximately 120 days  Each day approximately 1% of red blood cells are taken out of circulation  Approximately 90% of these senescent RBCs are removed by extravascular hemolysis  Approximately 10% of these old RBCs are removed by intravascular hemolysis  As a result, an average of 20 mg of iron is needed each day to replace the iron lost by senescent red blood cells  The majority of this iron comes from recycling  Because nearly 100% of the iron from RBC turnover is taken up by the mononuclear phagocytic system (MPS/RES cells) and re-utilized. The daily iron turnover is illustrated in Harmening figure 6.1, p. 119. Normal Iron Metabolism Distribution and Requirements  Iron is an essential element for all living organisms!  It is the essential component of the heme complex and is required by every cell in the body  It is important for cellular growth, oxygen transport, and the proliferation of red blood cells  The average adult has a total body iron content of between 3500 - 4000 mg  Approximately two-thirds of the total body iron is found in the hemoglobin molecule and one third is found in the storage pools of the bone marrow, liver, and spleen (nearly 90% of this stored iron is in the form of ferritin or hemosiderin) Iron Storage  Iron that is not used for erythropoiesis is stored in the mononuclear phagocytic system (MPS) or reticuloendothelial (RES) cells of the bone marrow, liver, and spleen.  Iron taken in excess is stored in two forms: (1) Ferritin and (2) Hemosiderin  RES / MPS cells ingest old red cells and catabolize the hemoglobin to recycle the iron  The major form (#1) of storage iron is ferritin  Ferritin is water soluble and is easily mobilized by the body for utilization  The second storage (#2) form of iron is hemosiderin  Hemosiderin is not water soluble. The iron in hemosiderin is released more slowly than that from ferritin and is less readily available for utilization  Hemosiderin represents aggregates of iron and can be visualized in tissue with the use of a Prussian Blue blue stain for iron  Hemosiderin appears as granules and aggregates. Ferritin is seen only via electron microscopy (EM). Hemosiderin does become available in iron- deficient patients  Stored Iron Ferritin Hemosiderin Water soluble Yes No Stained by Iron Stain No Yes (such as Prussian Blue) Release of iron Readily Slowly Amt. possible stored Limited Large Where stored Iron in serum and Iron storage in mainly tissue sites RE cells in bone marrow and other tissue sites Can be measured in Serum Typically bone marrow (correlation of serum ferritin or urine and stored iron; approximately 1µg correlates with 8 mg of stored iron) 11 Normal Iron Metabolism Distribution and Requirements  Serum ferritin levels are used as a measure of the body’s iron stores  Hemosiderin, another form of storage iron, represents precipitated aggregates of ferritin and is less readily available for utilization  Ten percent of tissue iron is unavailable or elemental iron and includes the iron in myoglobin (next slide)  A very small amount of iron is also present in plasma as transport iron  Iron metabolism and maintenance of body stores is a tightly regulated process Hemoglobin vs. Myoglobin  Note: While the structures of hemoglobin and myoglobin are similar, they are different structures!  Both are made of polypeptide globin chains and heme molecules:  Hemoglobin (Hgb) molecule contains 4 globin chains and 4 heme molecules  Myoglobin is constructed with 1 globin chain and 1 heme molecule.  Myoglobin (carries/stores oxygen in muscle cells) functions differently with regards to oxygen dissociation.  Myoglobin (term) cannot be used interchangeably with hemoglobin!  BE CAREFUL WITH THIS!  Iron Transport Transferrin is a plasma protein that transports iron Normal transferrin saturation is 1/3 or 33% Transferrin delivers iron to liver, bone marrow & body tissues Iron Storage  The major sites of iron stores Macrophages in the bone marrow Reticuloendothelial cells in the liver (Kupffer’s cells)  2 main storage forms of iron: Ferritin – Free floating and water soluble in blood Hemosiderin – Found in deposits in the liver, spleen, bone marrow & skeletal muscle 14 Normal iron levels in periperhal blood: Daily Iron Requirements and Absorption Daily iron requirements are affected by a number of physiologic states, including menstruation, pregnancy, lactation, and growth  Menstruation (Menhorragia)  Can lose approximately 0.8 mg of iron per day, in addition to the 1 to 2 mg typically lost daily through cellular shedding and sweating  Aka. “One step forward, two steps back”  The extent of menstrual bleeding is extremely variable, and some women may lose up to 1.5 to 2.5 mg of iron per day as a result of menstruation (!)  Aka. “One step forward, three steps back” Daily Iron Requirements and Absorption  In pregnant and lactating individuals:  The MDR increases to 3.0 mg per day. In the second and third trimesters, the daily requirement of iron can increase to as high as 5 to 6 mg.  At delivery, there is an average loss of 600 to 700 mL of blood.  Remember: Total blood volume is often 4-5 L, so that’s 1/10 of blood volume gone!  In total, during pregnancy approximately 1000 mg of iron is utilized. This equals and at times may exceed the amount of storage iron in an average woman of childbearing age.  Lactation and breast feeding:  Because milk is not a good source of iron, many baby formulas are supplemented with iron. Infants who are exclusively breastfeed may, upon doctor’s recommendation, need to have iron drops/elixir added to their diet.  During periods of growth, such as infancy and adolescence:  Iron requirements are substantially increased!  During the first year of life, absorption of 150 to 175 mg of iron is required to maintain an appropriate hemoglobin concentration. The minimum daily requirements (MDRs) for iron for different individual groups are listed below in Table 6-1 below. Source: Harmening: p. 119  Many foods are rich in iron, including meats, legumes, green vegetables, cereals, and prunes (see Table 6-2 below). Source: Harmening: p. 120  Some Iron Rich Foods Heme sources of iron: Red meats Ostyers Egg yolk Non-Heme sources of iron: Spinach Beans Iron-enriched cereals It is recommended that infants less than 1 year not drink cow’s milk because the milk can bind to the iron which prevents absorption 19 Keep in mind that iron has 2 sources: ** Diet/ingestion ** Recycling/senescent red blood cells Summary of Multiple Forms of Iron in the Body Iron in Food Heme sources: Meat Nonheme sources: Beans, clams, vegetables Iron in Storage Ferritin: Found in liver, spleen, skeletal muscle, bone marrow Hemosiderin: Found in excreted urine or bone marrow Iron in Circulation Iron and globin are recycled as a result of red cell senescence 21  Of the iron ingested in the diet, only 5% to 10% is absorbed! The foods that increase and decrease iron absorption are listed in Table 6-3 below. Source: Harmening: p. 120  Regulation of iron absorption occurs within the intestinal mucosa of the small bowel.  The vast majority of iron is absorbed in the duodenum and the first portion of the jejunum. Iron molecules within the diet and iron complexes within the body can be present in various iron states (Table 6-4 below). Source: Harmening: p. 121  Ferric (Fe3+) Iron  Ferric iron (Fe3+) is the most common dietary form of iron  In the stomach, hydrochloric acid (with the help of vitamin C) will transform iron from the ferric to the ferrous state; the acidic pH (