IRON—DEFICIENCY ANEMIA
Anemia occurs when there’s a decreased level of hemoglobin in your red blood
cells (RBCs). Hemoglobin is the protein in RBCs that is responsible for carrying oxygen
to tissues. Iron deficiency anemia is the most common type of anemia, and it occurs
when the body doesn’t have enough of the mineral iron (Fe). The body needs iron to
make hemoglobin. When there isn’t enough iron in the blood stream, the rest of the
body can’t get the amount of oxygen it needs. When iron intake is chronically low,
stores can become depleted, decreasing hemoglobin levels. There are three
stages to iron deficiency: pre-latent, latent, and IDA
When iron stores are exhausted, the condition is called Iron Depletion (Pre-latent).
Further decreases may be called iron-deficient Erythropoiesis (Latent) and still further
decreases produce Iron-Deficiency Anemia (IDA)
NORMAL PHYSIOLOGY
FUNCTIONS OF IRON
Iron is very important in maintaining many body functions, including the
production of hemoglobin, the molecule in your blood that carries oxygen. A
normal iron concentration is required for maintaining healthy epidermis, dermis,
hair and nails. Fe (II) and Fe (III) dimers, such as ferrous ferric chloride, are very
important for regulating proliferation and differentiation of human skin cells.
Ferrous ferric chloride is involved in regulating skin homeostasis through the
regulation of the skin-cell turnover (skin cells production and shedding). Iron is a
component of certain proteins, essential for respiration and energy metabolism,
and as a component of enzymes involved in the synthesis of collagen and some
neurotransmitters.
IRON ABSORPTION AND STORAGE
Iron absorption occurs
predominantly in the duodenum and upper
jejunum. Iron enters the stomach from the
esophagus. Iron is oxidized to the
Fe3+ state no matter its original form when
taken in orally. Gastric acidity as well as
solubilizing agents such as ascorbate
prevent precipitation(solidifying) of the
normally insoluble Fe3+. Intestinal mucosal
cells in the duodenum and upper jejunum
absorb the iron. The iron is coupled to
transferrin (an iron-carrier produced by the liver) in the circulation.
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About 70 percent of your body's iron is found in the red blood cells of the
blood called hemoglobin and in muscle cells called myoglobin. Hemoglobin is
essential for transferring oxygen in your blood from the lungs to the tissues.
Myoglobin, in muscle cells, accepts, stores, transports and releases oxygen.
About 6 percent of body iron is a component of certain proteins, essential for
respiration and energy metabolism, and as a component of enzymes involved in
the synthesis of collagen and some neurotransmitters. Iron also is needed for
proper immune function. About 25 percent of the iron in the body is stored as
ferritin, found in cells and circulates in the blood.
The average adult stores about 1 to 3 grams of iron in his or her body. An
exquisite balance between dietary uptake and loss maintains this balance. About
1 mg of iron is lost each day through sloughing of cells from skin and mucosal
surfaces, including the lining of the gastrointestinal tract. Menstruation increases
the average daily iron loss to about 2 mg per day in premenopausal female
adult). No physiologic mechanism of iron excretion exists. Consequently,
absorption alone regulates body iron stores. The augmentation of body mass
during neonatal and childhood growth spurts transiently boosts iron requirements
INTERNAL STRUCTURE OF RBC
Although RBCs are considered
cells, they lack a nucleus, nuclear
DNA, and most organelles, including
the endoplasmic reticulum and
mitochondria. RBCs therefore cannot
divide or replicate like other labile cells
of the body. They also lack the
components to express genes and
synthesize proteins. Hemoglobin
molecules are the most important
component of RBCs. Hemoglobin is a
specialized protein that contains a
binding site for the transport of oxygen
and other molecules. The RBCs’
distinctive red color is due to the spectral properties of the binding of hemic iron
ions in hemoglobin, each carrying four heme groups (individual proteins). This
protein is responsible for the transport of more than 98% of the oxygen, while the
rest travels as dissolved molecules through the plasma.
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RBC PHYSIOLOGY
The primary functions of red blood cells (RBCs) include carrying oxygen to
all parts of the body, binding to hemoglobin, and removing carbon dioxide. The
main RBC functions are facilitating gas exchange and regulating blood pH.
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Red blood cells contain hemoglobin, which contains four iron-binding
heme groups.
Oxygen binds the heme groups of hemoglobin. Each hemoglobin
molecule can bind four oxygen molecules.
The binding affinity of hemoglobin for oxygen is cooperative. It is
increased by the oxygen saturation of the molecule. Binding of an
initial oxygen molecule influences the shape of the other binding sites.
This makes binding more favorable for additional oxygen molecules.
Each hemoglobin molecule contains four iron-binding heme groups
which are the site of oxygen binding. Oxygen-bound hemoglobin is
called oxyhemoglobin.
Red blood cells alter blood pH by catalyzing the reversible carbon
dioxide to carbonic acid reaction through the enzyme carbonic
anhydrase.
pH is also controlled by carbon dioxide binding to hemoglobin instead
of being converted to carbonic acid.
RED BLOOD CELLS DEATH AND PRODUCTION (simultaneous)
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After about 100-120 days, RBCs are removed from circulation through
a process called eryptosis (programmed death of RBC).
Erythropoiesis is the process by which erythrocytes are produced. It is
triggered by erythropoietin, a kidney hormone produced during
hypoxia.
Erythropoiesis takes place in the bone marrow, where hemopoietic
stem cells differentiate and eventually shed their nuclei to become
reticulocytes. Iron, vitamin B12, and folic acid are required for
hemoglobin synthesis and normal RBC maturation.
Reticulocytes (Late erythroblast with nucleus extruded) mature into
normal, functional RBCs after 24 hours in the bloodstream.
Following eryptosis, the liver breaks down old hemoglobin into heme
and globin portion. The globin (protein portion) is used for synthesis of
amino acids. The iron from heme is taken back to the bone marrow for
reuse IN RBC production by transferrin, while heme without iron,
(biliverdin) is broken down into bilirubin and excreted through digestive
system bile.
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ETIOLOGY OF IDA
The cause of iron-deficiency anemia varies based on age, gender, and
socioeconomic status. Iron deficiency may result from insufficient iron intake,
decreased absorption, or blood loss. Iron-deficiency anemia is most often from blood
loss, especially in older patients. It may also be seen with low dietary intake, increased
systemic requirements for iron such as in pregnancy, and decreased iron absorption
such as in celiac disease. In neonates, breastfeeding is protective against iron
deficiency due to the higher bioavailability of iron in breast milk compared to cow's milk;
iron deficiency anemia is the most common form of anemia in young children on cow's
milk. In developing countries, a parasitic infestation is also a significant cause of irondeficiency anemia.
RISK FACTORS
These groups of people may have an increased risk of iron deficiency anemia:
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Women. Because women lose blood during menstruation, women in general
are at greater risk of iron deficiency anemia.
Infants and children. Infants, especially those who were low birth weight or
born prematurely, who don't get enough iron from breast milk or formula may
be at risk of iron deficiency. Children need extra iron during growth spurts
Vegetarians. People who don't eat meat may have a greater risk of iron
deficiency anemia if they don't eat other iron-rich foods.
Frequent blood donors. People who routinely donate blood may have an
increased risk of iron deficiency anemia since blood donation can deplete iron
stores. Low hemoglobin related to blood donation may be a temporary
problem remedied by eating more iron-rich foods.
PATHOPHYSIOLOGY
Insufficient Iron
intake.
Decreased
Absorption of Iron
Blood
Loss/Bleeding
Depletion of Iron stores.
Impaired hemoglobin (Hb)
synthesis due to reduced
Iron supply.
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Decreased O2 transport to
organs and tissues due to
limited oxygen-binding iron
in the heme group of
hemoglobin.
Manifestation of Signs and
symptoms depending on the
degree of severity of IDA.
SIGNS AND SYMPTOMS
The signs and symptoms of moderate to severe iron deficiency anemia include:
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general fatigue
weakness
pale skin
shortness of breath
dizziness
a tingling or crawling feeling in the legs
tongue swelling or soreness
cold hands and feet
fast or irregular heartbeat
brittle nails
headaches
COMPLICATIONS
Mild iron deficiency anemia usually doesn't cause complications. However,
left untreated, iron deficiency anemia can become severe and lead to health
problems, including the following:
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Heart problems. Iron deficiency anemia may lead to a rapid or irregular
heartbeat. The heart must pump more blood to compensate for the lack of
oxygen carried in the blood when the person is anemic. This can lead to an
enlarged heart or heart failure.
Problems during pregnancy. In pregnant women, severe iron deficiency
anemia has been linked to premature births and low birth weight babies. But the
condition is preventable in pregnant women who receive iron supplements as
part of their prenatal care.
Growth problems. In infants and children, severe iron deficiency can lead to
anemia as well as delayed growth and development. Additionally, iron deficiency
anemia is associated with an increased susceptibility to infections.
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DIAGNOSTIC EXAM
COMPLETE BLOOD COUNT The CBC documents the severity of the anemia. In
chronic iron deficiency anemia, the cellular indices show a microcytic and hypochromic
erythropoiesis—that is, both the mean corpuscular volume (MCV) and the mean
corpuscular hemoglobin concentration (MCHC) have values below the normal range for
the laboratory performing the test.
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Red blood cell size and color. With iron deficiency anemia, red blood cells are
smaller and paler in color than normal.
Hematocrit. A hematocrit level below the normal range. Normal levels are
generally between 35.5 and 44.9 percent for adult women and 38.3 to 48.6
percent for adult men. These values may change depending on your age.
Hemoglobin. Lower than normal hemoglobin levels indicate anemia. The normal
hemoglobin range is generally defined as 13.2 to 16.6 grams (g) of hemoglobin
per deciliter (dL) of blood for men and 11.6 to 15. g/dL for women.
Peripheral smear. Examination of the erythrocytes shows microcytic and
hypochromic red blood cells in chronic iron deficiency anemia; the microcytosis is
apparent in the smear long before the MCV is decreased after an event producing iron
deficiency.
Total Iron-Binding Capacity (TIBC) & Serum Ferritin
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Ferritin. This protein helps store iron in your body, and a low level of ferritin
usually indicates a low level of stored iron.
Amount of Transferrin. Transferrin is an iron-carrier protein.
Stool testing. Testing stool for the presence of hemoglobin is useful in establishing
gastrointestinal (GI) bleeding as the etiology of iron deficiency anemia.
Bone marrow aspiration. A bone marrow aspirate can be diagnostic of iron deficiency;
the absence of stainable iron in a bone marrow aspirate that contains spicules and a
simultaneous control specimen containing stainable iron permit establishment of a
diagnosis of iron deficiency without other laboratory tests.
Ultrasound. Women may also have a pelvic ultrasound to look for the cause of excess
menstrual bleeding, such as uterine fibroids.
Additional Diagnostic tests
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If the bloodwork indicates iron deficiency anemia, the physician may order
additional tests to identify the location of bleeding as an underlying cause, such as:
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Endoscopy. Doctors often check for bleeding from a hiatal hernia, an ulcer or
the stomach with the aid of endoscopy. In this procedure, a thin, lighted tube
equipped with a video camera is passed down your throat to your stomach. This
the physician allows to view the tube that runs from mouth to stomach
(esophagus) and stomach to look for sources of bleeding.
Colonoscopy. To rule out lower intestinal sources of bleeding, the physician
may recommend a procedure called a colonoscopy. A thin, flexible tube
equipped with a video camera is inserted into the rectum and guided to the colon.
The patient is usually sedated during this test. A colonoscopy allows the
physician to view inside some or all of the colon and rectum to look for internal
bleeding.
TREATMENT/MANAGEMENT
Medical Management
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Iron therapy. Oral ferrous iron salts are the most economical and
effective medication for the treatment of iron deficiency anemia; of the
various iron salts available, ferrous sulfate is the one most commonly
used.
Management of hemorrhage. Surgical treatment consists of stopping
hemorrhage and correcting the underlying defect so that it does not recur;
this may involve surgery for treatment of either neoplastic or nonneoplastic
disease of the gastrointestinal (GI) tract, the genitourinary (GU) tract, the
uterus, and the lungs.
Diet. The addition of nonheme iron to national diets has been initiated in
some areas of the world.
Pharmacologic Management
Medications for iron deficiency anemia include:
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Iron products. These agents are used to provide adequate iron for
hemoglobin synthesis and to replenish body stores of iron.
Parenteral iron. Reserve parenteral iron for patients who are either
unable to absorb oral iron or who have increasing anemia despite
adequate doses of oral iron; it is expensive and has greater morbidity than
oral preparations of iron.
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