Chapter 10

Chapter 10
Iron Deficiency Anemia and

Anemia of Chronic Inflammation
Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
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.
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 maternalfetal morbidity.
Factors in Iron Deficiency Anemia
Figure 10.1 Factors in iron deficiency.

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

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.

In the United States, iron deficiency continues to be
common in
Toddlers
Adolescent girls
Women of childbearing age

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.

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.

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.
Figure 10.2 Iron physiology.


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.

Breast milk and cows 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 cows milk
is absorbed. About 4% of iron is absorbed from ironfortified cows milk formulas that contain 12 mg of iron
per liter. Reasons for high bioavailability of iron in breast
milk are unknown.

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.

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

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.

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.

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.

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)

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.

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.

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.
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.)
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.)
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.)

Clinical chemistry studies
Serum iron
Transferrin saturation
Serum ferritin
Soluble transferrin receptor (sTfR)
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.

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

Other cases may be caused by the following:
Neoplasms
Rheumatoid arthritis
Rheumatic fever
Systemic lupus erythematosus (SLE)
Uremia
Chronic liver disease

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.


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- 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

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

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.

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.

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.

The peripheral blood smears usually show normochromic
and normocytic erythrocytes, but one fourth to one third
of patients display hypochromic and microcytic
erythrocytes.

Figure 10.6 Anemia of chronic diseases. (Reprinted with permission from Armitage JO. Atlas of Clinical
Hematology, Philadelphia, PA: Lippincott Williams & Wilkins, 2004.)

Clinical chemistry studies
Serum iron
Transferrin (iron-binding capacity)
Total iron-binding capacity
Transferrin saturation levels
Serum ferritin
Soluble transferrin receptor (sTfR)
Iron Deficiency Anemia and Anemia of

Inflammation or Chronic Disorders
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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Chapter 10

Iron Deficiency Anemia and

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia and

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Factors in Iron Deficiency Anemia

Figure 10.1 Factors in iron deficiency.

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Iron Deficiency Anemia (cont.)

Figure 10.2 Iron physiology.

Iron Deficiency Anemia (cont.)

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Iron Deficiency Anemia (cont.)

Complete blood count including observation of the

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Essential red blood cell parameters:

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Iron Deficiency Anemia (cont.)

Iron Deficiency Anemia (cont.)

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Iron Deficiency Anemia (cont.)

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Anemia of Inflammation (AOI) or Anemia

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Anemia of Inflammation (AOI) or Anemia

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Anemia of Inflammation (AOI) or Anemia

Anemia of Inflammation (AOI) or Anemia

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Anemia of Inflammation (AOI) or Anemia

Copyright 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Anemia of Inflammation (AOI) or Anemia

Anemia of Inflammation (AOI) or Anemia