Hematology
Anemia
Iron deficiency anemia

Author: R. Amita, M.D., D.N.B (see Authors page)

Revised: 24 August 2016, last major update May 2016

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Iron deficiency anemia [title]

Cite this page: Iron deficiency anemia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/hematologyirondefanemia.html. Accessed October 20th, 2017.
Definition / general
  • Develops when iron stores are too low to support normal red blood cell (RBC) production
Essential features
  • Occurs when iron deficiency is severe enough to diminish erythropoiesis and cause development of anemia
Terminology
  • Also called nutritional anemia
Epidemiology
  • Single most prevalent deficiency state on worldwide basis
Pathophysiology
  • Infants:
    • Total body iron decreases from 250 mg (80 parts per million/ppm) to 60 ppm in first 6 months of life, due to consumption of iron deficient milk diet
    • Cow milk consumption results in greater incidence of iron deficiency, due to higher concentration of calcium, which competes with iron for absorption
    • Growing children must obtain approximately 0.5 mg more iron daily than is lost to maintain a normal body concentration of 60 ppm

  • Adult males:
    • Absorb and lose about 1 mg of iron from a diet containing 10 - 20 mg daily
    • Lose body iron in sloughed epithelium, in secretions from the skin and gut lining, and from small daily losses of blood from the GI tract (0.7 mL daily)
    • Those with severe siderosis from blood transfusions can lose a maximum of 4 mg daily via these routes without additional blood loss

  • Adult females:
    • Lose an average of 2 mg of iron daily during childbearing years; must absorb a similar quantity to maintain equilibrium
    • Lose about 500 mg of iron with each pregnancy
    • Menstrual losses are highly variable; range from 10 - 250 mL (4 - 100 mg) per period

  • Iron absorption:
    • 3 pathways, but most absorbed iron is derived from heme
      • Digested enzymatically free of globin; enters enterocytes as a metalloporphyrin; released from heme within the cell by heme oxygenase to pass into the body as inorganic iron
      • Most dietary inorganic iron is ferric; enters absorptive cell via integrin-mobilferrin pathway (IMP)
      • Some dietary iron is reduced in gut lumen and enters absorptive cell via the divalent metal transporter-1 (DMT 1 / DCT 1 / Nramp 2)
    • Proteins of both pathways interact within enterocyte with paraferritin (large protein complex capable of ferric reduction)
    • Excess iron is stored as ferritin to protect cell from oxidative damage
    • Iron leaves cell to enter plasma, facilitated by ferroportin and hephaestin (associates with an apotransferrin receptor)
    • Enterocyte is informed of body requirements by transporting iron from plasma into cell using holotransferrin receptor
Etiology
  • Dietary deficiency: substances that diminish absorption of ferrous and ferric iron include phytates, oxalates, phosphates, carbonates and tannates
  • Malabsorption of iron:
    • Prolonged achlorhydria may produce iron deficiency because acidic conditions are required to release ferric iron from food
    • Starch and clay eating produce malabsorption of iron and iron deficiency anemia
    • Extensive surgical removal of proximal small bowel or chronic diseases (e.g., untreated sprue or celiac syndrome) can diminish iron absorption
  • Bleeding for any reason produces iron depletion
  • Hemosiderinuria, hemoglobinuria (paroxysmal nocturnal hemoglobinuria, brisk intravascular hemolytic anemia associated with implantation of artificial valves)
  • Pulmonary hemosiderosis
Diagrams / tables

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Iron equilibrium in the body

Clinical features
  • Fatigue and diminished capability to perform hard labor
  • Leg cramps on climbing stairs
  • Craving ice (in some cases, cold celery or other cold vegetables) to suck or chew
  • Poor scholastic performance
  • Cold intolerance
  • Reduced resistance to infection
  • Altered behavior (e.g., attention deficit disorder)
  • Dysphagia with solid foods (from esophageal webbing)
  • Worsened symptoms of comorbid cardiac or pulmonary disease
Diagnosis
  • Low serum iron and ferritin levels with an elevated total iron binding capacity / TIBC are diagnostic of iron deficiency
  • A normal serum ferritin can be seen in patients with iron deficiency plus either hepatitis or anemia of chronic disorders
Laboratory
  • Complete blood count shows low mean corpuscular volume (MCV) and low mean corpuscular hemoglobin concentration (MCHC)
  • Reticulocyte hemoglobin content (CHr) value is a strong predictor of iron deficiency and iron deficiency anemia

  • Peripheral blood smear:
    • Microcytic and hypochromic RBCs with marked anisopoikilocytosis in chronic cases
    • Platelets usually are increased
    • In contrast to thalassemia, target cells are usually not present

  • Testing includes:
    • Serum iron, total iron binding capacity (TIBC) and serum ferritin
    • Evaluation for hemosiderinuria, hemoglobinuria and pulmonary hemosiderosis
    • Hemoglobin electrophoresis and measurement of hemoglobin A2 and fetal hemoglobin
    • Reticulocyte hemoglobin content


    RBC indices and biochemical markers
    of microcytic anemia (Medscape)

Case reports
Treatment
  • Correct the etiology and replenish iron stores

  • Iron therapy:
    • Oral ferrous (sulphate) iron salts
    • Reserve parenteral iron for those unable to absorb oral iron or with increasing anemia despite adequate doses of oral iron
    • Reserve transfusion of packed RBCs for those experiencing significant acute bleeding or in danger of hypoxia or coronary insufficiency
Clinical images

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Koilonychia: abnormal
fingernail shape

Atrophic glossitis

Peripheral smear description
  • For anemia due to hemorrhage, maximal changes in RBC cellular indices occur by 120 days, when all normal erythrocytes produced prior to hemorrhage are replaced by microcytes
  • Before this, the peripheral smear shows a dimorphic population of erythrocytes: normocytic cells produced before bleeding and microcytic cells produced after bleeding - this is reflected in the red blood cell distribution width (RDW)
  • Earliest evidence of iron deficient erythropoiesis is reflected by increased RDW
Microscopic (histologic) images
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Prussian blue stain: normal (left), anemia (right)

Negative stains
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Slide 38: Prussian blue staining of bone
marrow aspirate shows absence of iron

Additional references