Iron Metabolism and Hypochromic Anemias

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Chapter 6

• Iron Metabolism and Hypochromic Anemias

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1. Study Questions2. Homework Assignment3.
Exam for Unit III
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Iron Metabolism and Hypochromic Anemias

• In Chapter 6, you will learn about iron
  deficiency anemia and other microcytic,
  hypochromic anemias.  Anemia of chronic disease,
  sideroblastic anemia, and thalassemia will also
  be discussed.   
• It is important that you pay close attention to
  the morphological changes that occur in each of
  these anemias. 

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Introduction 1 of 2

• Hemoglobin synthesis requires production and
  assembly of three key components iron,
  protoporphyrin and globin chains.
• Deficiency in any component is deficiency in
  entire hemoglobin molecule and results in
  microcytic, hypochromic erythrocytes.
• Primary function of Hgb is oxygen transport.  

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Introduction 2 of 2

• Despite the excess of iron in the western diet,
  iron deficiency continues to be a significant
  cause of morbidity in North America and
  throughout the world.
• Most common causes of iron deficiency
• Child-bearing women Menstrual bleeding
• Adult men GI bleeding

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NORMAL IRON METABOLISM
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Iron Requirements and Distribution 1 of 3

• Average adult has 3500 mg iron in body. About
  2/3 found in hemoglobin and 1/3 as tissue iron
  which is in storage, primarily in the form of
  ferritin or hemosiderin.
• Iron metabolism and maintenance of body stores is
  a tightly regulated process Daily iron intake,
  absorption, and losses are usually very small

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Iron Requirements and Distribution 2 of 3

• Body iron is repeatedly recycled, and the small
  amount of iron each day that is lost is replaced
  by diet.
• Normal life span of a RBC is 120 days 1 of the
  RBCs are replaced each day in the healthy adult.
• The iron from senescent RBCs is recycled.

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Iron Requirements and Distribution 3 of 3

• Approximately 1 mg/day of iron is lost through
  cellular shedding and sweating, and it is
  typically replaced through diet.
• Minimum Daily Requirement (MDR) of iron is 1
  mg/day Increased iron requirements during
  infancy, adolescence, menstruation, pregnancy,
  and lactation.

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Absorption, Storage, and Reutilization 1 of 6

• Of the iron ingested in the diet, 5 - 10 is
  absorbed.
• Vast majority is absorbed in the duodenum and
  first portion of the jejunum.
• Ferric iron (Fe3) is the most common dietary
  form of iron.
• It is typically converted into the ferrous (Fe2)
  state by the acid of the stomach.

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Absorption, Storage, and Reutilization 2 of 6

• Ferrous iron within the intestinal lumen readily
  enters the mucosal cells.
• Within the mucosal cells ferrous iron is
  reoxidized to ferric iron, some of which creates
  complexes with the protein apoferritin to form
  ferritin.
• Ferritin is the primary storage compound for iron
  and is commonly found within the liver, spleen,
  and bone marrow.

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Absorption, Storage, and Reutilization 3 of 6

• Ferritin iron is easily mobilized by the body for
  utilization.
• Serum ferritin levels can be measured and used as
  an indirect measure of iron stores.
• Hemosiderin, another form of storage iron, is
  made up of precipated aggregates of ferritin.
• The iron in hemosiderin is released more slowly
  than that from ferritin and is less readily
  available for utilization.

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Absorption, Storage, and Reutilization 4 of 5

• The remainder of the ferric iron from within the
  mucosal cells combines with apotransferrin to
  form transferrin.
• Transferrin is a protein responsible for
  transporting iron through the bloodstream to the
  various organs of the body.

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Absorption, Storage, and Reutilization 5 of 6

• Ferrous iron combines with protoporphyrin in the
  mitochondria of the RBC to form heme.
• Protoporphyrin is produced through a sequence of
  steps that starts with aminolevulinic acid (ALA)
  formation from glycine and succinyl coenzyme A
  (CoA) This is the rate-limiting step in heme
  synthesis.

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Absorption, Storage, and Reutilization 6 of 6

• Within the cytoplasm of the RBC, alpha (a) and
  beta (ß) globin protein chains are synthesized.
• Two a and two ß chains combine with four heme
  groups and four oxygen molecules to form an
  intact functional hemoglobin molecule.

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Definitions

• Ferritin
• The storage form of iron in the tissues, found
  principally in the reticuloendothelial cells of
  the liver, spleen, and bone marrow
• Ferritin levels are easily measured as a serum
  value in the laboratory
• Transferrin
• A glycoprotein synthesized in the liver, with the
  primary function of iron transport

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Definitions

• Sideroblast
• A ferritin-containing normoblast in the bone
  marrow Makes up from 20 - 90 of normoblasts
  in the marrow
• Siderocyte
• A nonnucleated red blood cell containing iron in
  a form other than hematin and confirmed by a
  specific iron stain such as the Prussian blue
  reaction

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Definitions

• Pappenheimer bodies
• Basophilic inclusions in the red blood cell that
  are cluster-like
• They are believed to be iron particles
  Confirmation is made by Prussian blue stain
• Hemosiderin
• An iron-containing pigment derived from
  hemoglobin on disintegration of red cells one
  method whereby iron is stored until needed for
  making hemoglobin

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Hypochromic Anemias
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Introduction

• Hypochromic anemias represent a related group of
  disorders in which there is a quantitative defect
  in hemoglobin synthesis.
• Lack of Hgb results in hypochromic RBCs that are
  usually smaller than normal.
• Etiology of hypochromic anemias includes
  disorders that affect iron metabolism and
  utilization, heme synthesis, and globin protein
  chain synthesis.

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Introduction

• Iron deficiency and chronic disease states are
  the most common causes of hypochromic anemia.
• Sideroblastic anemia is a disorder of heme
  synthesis, which can be inherited or acquired
  from toxins such as lead, alcohol, and various
  other drugs.
• Thallasemia is a disorder of globin protein chain
  synthesis (a or ß chains).

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Iron Deficiency Anemia(IDA)
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IDA

• Most commonly recognized cause of hypochromic
  anemia.
• Characterized by a decrease in Hgb concentration,
  Hct, and MCV.
• Results after there is total or near total
  depletion of the body iron stores.

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Development of IDA

• Sequential steps in the development of IDA
• 1. Depletion of iron stores. Decrease or
  absence of stainable bone marrow iron, decreased
  serum ferritin level, increased TIBC.
• 2. Iron-deficient erythropoiesis. Decreased
  hemoglobin in developing RBCs without frank
  anemia, early microcytosis, decreased trnasferrin
  saturation.
• 3. Iron-deficiency anemia. Decreased hemoglobin
  synthesis with anemia and significant
  microcytosis (decreased MCV), anisocytosis of the
  RBCs, increased serum soluble transferring
  receptor levels.

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Clinical Findings in IDA

• Clinical findings depend on severity of the
  anemia.
• Severe anemias may be associated with pallor,
  weakness, and dyspnea.

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Morphological Features of IDA

• Usually hypochromic, microcytic RBCs
• Mild to moderate anisopoikilocytosis
• Decreased storage iron
• Decreased sideroblasts
• Absent ringed sideroblasts

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Laboratory Tests for IDA

• Serum Fe
• Fe circulates bound to transferrin
• Normal ranges for men is 50-160 µg/dL and women
  is 40-150 µg/dL
• Decreased serum iron in IDA
• Total Iron-Binding Capacity (TIBC)
• Indirect measure of transferrin Equals sum of
  the serum iron plus additional Fe that serum
  transferrin can bind.
• Normal range is 250-400 µg/dL
• Increased TIBC in IDA

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Laboratory Tests for IDA

• Saturation of Transferrin
• How much of the transferrin is transporting iron
• Normal range is 20-50
• Decreased transferrin saturation in IDA
• Serum Ferritin
• Correlates with Fe stores
• Ranges
• Iron deficiency 0-12 ng/mL
• Borderline 13-20 ng/mL
• Iron excess gt 400 ng/L
• Decreased serum ferritin in IDA

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Anemia of Chronic Disease(ACD)
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ACD

• Anemia present for several months following
  development of a chronic disease state
• Commonly associated with infections, malignant
  neoplasms, and autoimmune disorders.
• Defined by an aggregate of clinical,
  morphological and laboratory findings.

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Morphological Features of ACD

• Usually normocytic RBCs with normal MCV
• May be hypochromic or normochromic
• Normal number of bone marrow erythrocytic
  precursors
• Increased storage iron
• Decreased sideroblasts
• Rare to absent ringed sideroblasts

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Laboratory Results in ACD

• Decreased serum iron
• Decreased TIBC
• Decreased transferrin saturation
• Normal to increased serum ferritin levels
• Normal serum soluble transferrin receptor levels

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SideroblasticAnemias
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Sideroblastic Anemias

• A heterogenous group of disorders that are
  characterized by ineffective erythropoiesis.
• Inherited or acquired.
• Heriditary sideroblastic anemias are rare, and
  usually appear within the first few months or
  years of life.
• Acquired sideroblastic anemias can be primary or
  secondary

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Sideroblastic Anemias

• The primary or idiopathic sideroblastic anemias
  are exemplified by refractory anemia with ringed
  sideroblasts (RARS)
• The secondary sideroblastic anemias are the
  result of ingestion of alcohol, lead, and various
  medications.
• Coarse basophilic stippling of the RBCs is also a
  common feature of lead poisoning.

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Thallasemia
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Thallasemia

• The thalassemic syndromes are a group of
  disorders that result in variable impairment of
  the synthesis of globin protein chains.