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Chapter 10
Iron Deficiency Anemia and
Anemia of Chronic Inflammation
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Iron Deficiency Anemia and
Anemia of Chronic Inflammation
• Scope of the problem
– A common false assumption is that iron deficiency
anemia (IDA) due to inadequate nutrition is confined
to developing or underdeveloped countries.
– It is not.
– Worldwide, more than 40% of children have an IDA
that is frequently associated with infections.
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Iron Deficiency Anemia
• Early diagnosis of iron deficiency is essential in
nonanemic infants and toddlers (under 2 years of age).
• Early diagnosis of iron deficiency is equally important in
pregnant women to reduce maternal–fetal morbidity.
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Factors in Iron Deficiency Anemia
Figure 10.1 Factors in iron deficiency.
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Iron Deficiency Anemia (cont.)
Etiology
1. Decreased iron intake, for example, meat-poor diets
2. Faulty or incomplete iron absorption, for example,
resection of small bowel, celiac disease
3. Increased iron utilization, for example, growth spurt
4. Iron loss (pathological), for example, GI bleeding,
malignancy
5. Iron loss (physiological), for example, pregnancy,
menstruation
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Iron Deficiency Anemia (cont.)
Epidemiology
– Although a high prevalence of iron deficiency existed in
the 1960s in the US population, intensified efforts to
combat iron deficiency in this country appear to have
successfully reduced anemia in some vulnerable age
subgroups, such as infants.
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Iron Deficiency Anemia (cont.)
– In the United States, iron deficiency continues to be
common in
• Toddlers
• Adolescent girls
• Women of childbearing age
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Iron Deficiency Anemia (cont.)
• Physiology
– Humans have 35 to 50 mg of iron per kilogram of
body weight.
– The average adult has 3.5 to 5.0 g of total iron.
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Iron Deficiency Anemia (cont.)
• Physiology
– Normal iron loss is very small, amounting to less than
1 mg/day.
– Iron is lost from the body through exfoliation of
intestinal epithelial and skin cells, the bile, and
through urinary excretion.
– To compensate for this loss, the adult male has a
replacement iron need of 1 mg/day.
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Iron Deficiency Anemia (cont.)
• Physiology
– Operational iron consists of iron used for oxygen
binding and biochemical reactions.
– In humans, most operational iron is found in the
heme portion of hemoglobin or myoglobin.
– Most operational iron is incorporated into the
hemoglobin molecules of erythrocytes and is recycled.
– In normal adults, hemoglobin contains two thirds of
the iron present in the body.
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Iron Deficiency Anemia (cont.)
Figure 10.2 Iron physiology.
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Iron Deficiency Anemia (cont.)
• Iron needs in infants and children
– In the normal infant at term, iron stores are adequate
to maintain iron sufficiency for approximately 4
months of postnatal growth.
– In premature infants, total body iron is lower than in
the full-term newborn. They have a faster rate of
postnatal growth than infants born at term, so unless
the diet is supplemented with iron, they become irondepleted more rapidly than full-term infants. Iron
deficiency can develop by 2 to 3 months of age in
premature infants.
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Iron Deficiency Anemia (cont.)
• Breast milk and cow’s milk both contain about 0.5 to 1.0
mg of iron per liter, but its bioavailability differs
significantly.
• The absorption of iron from breast milk is uniquely high,
about 50% on average, and tends to compensate for its
low concentration.
• By contrast, only about 10% of iron in whole cow’s milk
is absorbed. About 4% of iron is absorbed from ironfortified cow’s milk formulas that contain 12 mg of iron
per liter. Reasons for high bioavailability of iron in breast
milk are unknown.
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Iron Deficiency Anemia (cont.)
• Dietary iron
– There are two broad types of dietary iron:
• Approximately 90% of iron from food is in the form
of iron salts and is referred to as nonheme iron.
• The other 10% of dietary iron is in the form of
heme iron, which is derived primarily from the
hemoglobin and myoglobin of meat.
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Iron Deficiency Anemia (cont.)
• Sequential phases of iron deficiency:
– Stage 1 (Prelatent)
• Decrease in storage iron
– Stage 2 (Latent)
• Decrease in iron for erythropoiesis
– Stage 3 (Anemia)
• Decrease in circulating red blood cell parameters &
• Decrease in oxygen delivery to peripheral tissues
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Iron Deficiency Anemia (cont.)
• Clinical signs and symptoms
– The history and physical presentation are the typical
initial observations in the diagnostic workup of a
patient with symptoms of paleness, fatigue, and/or
weakness.
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Iron Deficiency Anemia (cont.)
• Clinical signs and symptoms
– Iron deficiency anemia in children is associated with
psychomotor and mental impairment in the first 2
years of life.
– Currently, more than one third of children in the
United States demonstrate evidence of iron
insufficiency,
• 7% have iron deficiency without anemia, and
• 10% have iron deficiency anemia.
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Iron Deficiency Anemia (cont.)
• Laboratory characteristicshematology studies
– Complete blood count including observation of the
peripheral blood smear and a platelet count
– Platelet count and white blood cell count should be noted.
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Iron Deficiency Anemia (cont.)
• Laboratory characteristicshematology studies
– Essential red blood cell parameters:
• Hemoglobin
• Microhematocrit
• Red blood cell count
• Calculation of the red blood cell indices (MCV=mean
corpuscular volume, MCH=mean corpuscular
hemoglobin, and MCHC=mean corpuscular hemoglobin
concentration)
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Iron Deficiency Anemia (cont.)
• The MCV can separate macrocytic, normocytic, and
microcytic red blood cells.
• Approximately one third of patients with iron deficiency
will present with normal red blood cell morphology
because they are in an early phase of iron depletion.
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Iron Deficiency Anemia (cont.)
• Another evaluation of mature erythrocyte indices as a
new marker of iron status is the percentage of
hypochromic red blood cells (% HYPO). This marker has
been demonstrated to be the most sensitive and specific
parameter of functional iron deficiency.
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Iron Deficiency Anemia (cont.)
• A reticulocyte count is additionally helpful. A reticulocyte
count equal to or greater than 2.5% demonstrates
increased erythropoiesis.
• In the presence of a reticulocyte count of less than 2.5%,
the red blood cell indices can form the algorithmic basis
for separating anemias into categories.
• Reticulocyte hemoglobin content (CHr) is an effective
early indicator of iron deficiency. Early alert is particularly
important in infants and toddlers, who can suffer
cognitive and psychomotor developmental problems as a
result of inadequate iron in the synthesis of hemoglobin.
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Iron Deficiency Anemia (cont.)
Figure 10.3 Iron deficiency maturation drawing. (Reprinted with permission from Anderson SC, Poulsen
KBV. Anderson's Atlas of Hematology, Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams &
Wilkins, Copyright 2003.)
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Iron Deficiency Anemia (cont.)
Figure 10.4 The blood in iron deficiency anemia. A: Normal blood smear. B: Blood smear in iron deficiency
anemia. The red cells are small (microcytic) and pale (hypochromic). (Reprinted with permission from
McConnell TH. The Nature Of Disease: Pathology for the Health Professions. Philadelphia, PA: Lippincott
Williams & Wilkins, 2007.)
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Iron Deficiency Anemia (cont.)
Figure 10.5 A blood smear showing normal erythrocytes (A) compared with a blood smear revealing
microcytic, hypochromic erythrocytes in a patient with iron deficiency anemia (B). (Reprinted with
permission from Willis MC. Medical Terminology: A Programmed Learning Approach to the Language of
Health Care. Baltimore, MD: Lippincott Williams & Wilkins, 2002.)
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Iron Deficiency Anemia (cont.)
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Iron Deficiency Anemia (cont.)
• Clinical chemistry studies
– Serum iron
– Transferrin saturation
– Serum ferritin
– Soluble transferrin receptor (sTfR)
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Iron Deficiency Anemia (cont.)
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD)
• Etiology
– Anemia of chronic diseases or disorder (ACD) or
anemia of inflammation is another common form of
anemia.
– Anemia results in illnesses as diverse as
inflammation, infection, malignancy, or various
systemic diseases.
– Approximately half of AOI/ACD cases are caused by
subacute or chronic infections.
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
• Microbial agents associated with anemia of
inflammation
– Bacterial, for example, M. tuberculosis
– Fungal, for example, C. neoformans
– Viral, for example, HIV, Cytomegalovirus
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
• Other cases may be caused by the following:
– Neoplasms
– Rheumatoid arthritis
– Rheumatic fever
– Systemic lupus erythematosus (SLE)
– Uremia
– Chronic liver disease
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
• Pathophysiology
– AOI/ACD is a hypoproliferative defect not related to
any nutritional deficiency.
– The principal pathogenesis of ACD is believed to be
related to hepcidin, a small plasma protein, that is a
key molecule in controlling iron absorption and
recycling.
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
• Characteristics of AOI associated with malignancy can be as follows:
– Decreased erythrocyte production because of direct bone marrow
infiltration by malignant tumor cells or by primary marrow cell
malignancies
– Production and release of TNF-α and IL-1 by macrophages
– Increased erythrocyte destruction present in immune or
microangiopathic hemolytic anemia
– Acute and chronic blood loss
– Toxic effects of invasive therapy (e.g., chemotherapy or radiation
therapy)
– Indirect multiple causes such as anemia associated with
malignant disease, anemia associated with major organ failure,
and various hemolytic anemias
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
• The systemic diseases that produce AOI are accompanied
by the release of acute-phase reactants in the blood.
– Elevated C-reactive protein (CRP)
– Fibrinogen
– Haptoglobin
– Ceruloplasmin
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
• This response becomes unified in a common pathway of
metabolic events initiated by interleukin-1 (IL-1-) from
activated macrophages.
• IL-1- then initiates a cascade of events mediated by the
cytokines released from macrophages, lymphocytes, and
other numerous cells within the body.
• IL-1- is specifically responsible for production of fever,
neutrophilia, leukocytosis, acute-phase protein synthesis,
stimulation of production of lymphokines, and the release
of lactoferrin from granulocytes.
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
• Laboratory characteristics
– Laboratory assays that suggest inflammation or
infection include the following:
• Elevated platelet counts
• Elevated total leukocyte counts
• Evidence of acute-phase reactants. C-reactive
protein (CRP), an acute-phase protein, is
frequently a surrogate marker that may or may not
correlate with hepcidin levels.
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
• Hematology studies
– This form of anemia is usually a mild hypoprolific
anemia
• hematocrit usually fixed in the 28% to 32% range,
• in some cases (e.g., uremia), the hemoglobin may
be as low as 5 g/dL.
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
• The peripheral blood smears usually show normochromic
and normocytic erythrocytes, but one fourth to one third
of patients display hypochromic and microcytic
erythrocytes.
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
Figure 10.6 Anemia of chronic diseases. (Reprinted with permission from Armitage JO. Atlas of Clinical
Hematology, Philadelphia, PA: Lippincott Williams & Wilkins, 2004.)
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Anemia of Inflammation (AOI) or Anemia
of Chronic Disorders (ACD) (cont.)
• Clinical chemistry studies
– Serum iron
– Transferrin (iron-binding capacity)
– Total iron-binding capacity
– Transferrin saturation levels
– Serum ferritin
– Soluble transferrin receptor (sTfR)
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Iron Deficiency Anemia and Anemia of
Inflammation or Chronic Disorders
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Iron Deficiency Anemia and Anemia of
Inflammation or Chronic Disorders (cont.)
• Treatment of the underlying cause of anemia is the most
direct approach.
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