Iron Deficiency Anemia manifested by behavioral changes such as

fatigue, anorexia, and pica, especially

Pathophysiology pagophagia (ice eating). Abnormal cognitive
development in children suggests iron
Iron deficiency anemia is characterized by the deficiency before it has developed into overt
production of (microcytic) erythrocytes and a anemia. Growth abnormalities, epithelial
diminished level of circulating hemoglobin. disorders, and a reduction in gastric acidity
This microcytic anemia is the last stage of iron are also common. A possible sign of early iron
deficiency, and it represents the end point of deficiency is reduced immunocompetence,
a long period of iron deprivation. There are particularly defects in cell-mediated immunity
many causes of iron deficiency anemia as and the phagocytic activity of neutrophils,
discussed in Box 32-1. which may lead to frequent infections.
Causes of Iron Deficiency Anemia Restless legs syndrome (RLS) with leg pain or
1. Inadequate dietary intake secondary to a discomfort may result from a lack of iron in
poor diet without supplementation the brain; this alters dopamine production
2. Inadequate absorption resulting from and movement. Besides iron deficiency,
diarrhea, achlorhydria, intestinal disease such kidney failure, Parkinson’s disease, diabetes,
as celiac disease, atrophic gastritis, partial or rheumatoid arthritis, and pregnancy can
total gastrectomy, or drug interference
aggravate RLS (Allen et al, 2013; National
3. Inadequate utilization secondary to chronic
gastrointestinal disturbances Institutes of Health [NIH], National Heart
4. Increased iron requirement for growth of Blood and Lung Institute [NHBLI], 2010). As
blood volume, which occurs during infancy, iron deficiency anemia becomes more severe,
adolescence, pregnancy, and lactation and defects arise in the structure and function of
which is not being matched with intake the epithelial tissues, especially of the tongue,
5. Increased excretion because of excessive nails, mouth, and stomach. The skin may
menstrual blood (in females); hemorrhage
appear pale, and the inside of the lower eyelid
from injury; or chronic blood loss from a
bleeding ulcer, bleeding hemorrhoids, may be light pink instead of red. Mouth
esophageal varices, regional enteritis, celiac changes include atrophy of the lingual
disease, Crohn’s disease, ulcerative colitis, papillae, burning, redness, and in severe cases
parasitic or malignant disease a completely smooth, waxy, and glistening
6. “Increased destruction” of iron from iron appearance of the tongue (glossitis). Angular
stores into the plasma and defective iron use
stomatitis also may occur, as may a form of
caused by a chronic inflammation or other
dysphagia. Gastritis occurs frequently and
chronic disorder
With few exceptions, iron deficiency anemia may result in achlorhydria. Fingernails can
in adult men is the result of blood loss. Large become thin and flat, and eventually
losses of menstrual blood can cause iron koilonychia (spoon-shaped nails) may be
deficiency in women, many of whom are noted (see Figure 32-2). Progressive,
unaware that their menses are unusually untreated anemia results in cardiovascular
heavy. Because anemia is the last and respiratory changes that can eventually
manifestation of chronic, long-term iron lead to cardiac failure. Some behavioral
deficiency, the symptoms reflect a symptoms respond to iron therapy before the
malfunction of a variety of body systems. anemia is cured, suggesting they may be the
Inadequate muscle function is reflected in result of tissue depletion of iron-containing
decreased work performance and exercise enzymes rather than from a decreased level
tolerance. Neurologic involvement is of hemoglobin (see Pathophysiology and Care
Management Algorithm: Iron Deficiency individuals vary widely. After absorption, iron
Anemia). is transported by plasma transferrin— a beta
1 globulin (protein) that binds iron derived
PATHOPHYSIOLOGY AND CARE from the gastrointestinal tract, iron storage
MANAGEMENT ALGORITHM
sites, or hemoglobin breakdown—to the bone
ET I O L O G Y
Iron Deficiency : Inadequate ingestion, marrow (hemoglobin synthesis), endothelial
Increased destruction resulting in decreased cells (storage), or placenta (fetal needs).
release from stores, Increased blood loss or Transferrin molecules are generated on the
excretion, Inadequate absorption, Inadequate surface of RBCs in response to the need for
utilization, Increased requirement iron. With iron deficiency, so many transferrin
PAT H OPH Y S I O L O G Y receptors are on the cell surface looking for
Stages of Deficiency
iron that some of them break off and float in
Stage 1: Moderate depletion of iron stores No
dysfunction Stage the serum. Their presence is an early
2: Severe depletion of iron stores No measurement of developing iron deficiency; a
dysfunction Stage higher quantity of soluble serum transferrin
3: Iron deficiency Dysfunction Stage receptors (STFRs) means greater deficiency of
4: Iron deficiency Dysfunction and anemia iron. Progressive stages of iron deficiency can
Clinical Findings
be evaluated by measurements, as shown in
Early :• Inadequate muscle function • Growth
Table 32-2. Protoporphyrin is the iron
abnormalities • Epithelial disorders • Reduced
immunocompetence • Fatigue containing portion of the respiratory pigments
Late :• Defects in epithelial tissues • Gastritis that combines with protein to form
• Cardiac failure hemoglobin or myoglobin. The zinc
MA N A G EMENT protoporphyrin (ZnPP)/heme ratio is
Medical Management : • Assess for and treat measured to assess iron deficiency. However,
underlying disease • Oral iron salts • Oral
both this ZnPP/ heme ratio and hemoglobin
iron, chelated with amino acids • Oral
sustained-release iron • Iron-dextran by levels are affected by chronic infection and
parenteral administration other factors that can produce a condition
Nutrition Management : • Increase that mimics iron deficiency anemia when, in
absorbable iron in diet • Include vitamin C at fact, iron is adequate. With higher altitudes,
every meal • Include meat, fish, or poultry at where there is a lower availability of oxygen,
every meal • Decrease tea and coffee hematocrit and hemoglobin levels increase to
consumption
adapt. This must be considered in any anemia
Assessment
assessment strategies (Zubieta-Calleja et al,
A definitive diagnosis of iron deficiency 2007). High altitude is 4900 to 11,500 feet;
anemia requires more than one method of very high altitude is 11,500 to 18,000 feet;
iron evaluation; serum ferritin, iron and extreme altitude is above 18,000 feet.
transferrin are the most useful. The
Medical Management
evaluation also should include an assessment
of cell morphology. By itself, hemoglobin Treatment of iron deficiency anemia should
concentration is unsuitable as a diagnostic focus primarily on the underlying cause,
tool in cases of suspected iron deficiency although this is often difficult to determine.
anemia for three reasons: (1) it is affected The goal is repletion of iron stores. Oral
only late in the disease, (2) it cannot Supplementation. The chief treatment for iron
distinguish iron deficiency from other deficiency anemia involves oral administration
anemias, and (3) hemoglobin values in normal of inorganic iron in the ferrous form. Although
the body uses ferric and ferrous iron, the report subjective improvements in mood and
reduced ferrous is easier on the gut and appetite sooner. The hemoglobin level will
better absorbed. At a dose of 30 mg, begin to increase by day 4. Iron therapy
absorption of ferrous iron is three times should be continued for 4 to 5 months, even
greater than if the same amount were given in after restoration of normal hemoglobin levels,
the ferric form. Iron is best absorbed when to allow for repletion of body iron reserves.
the stomach is empty; however, under these Parenteral Iron-Dextran. If iron
conditions it tends to cause gastric irritation. supplementation fails to correct the anemia,
Gastrointestinal side effects can include (1) the patient may not be taking the
nausea, epigastric discomfort and distention, medication as prescribed due to gastric
heartburn, diarrhea, or constipation. If these distress; (2) bleeding may be continuing at a
side effects occur, the patient is told to take rate faster than the erythroid marrow can
the iron with meals instead of on an empty replace blood cells; or (3) the supplemental
stomach; however, this sharply reduces the iron is not being absorbed, possibly as a result
absorbability of the iron. Gastric irritation is a of malabsorption secondary to steatorrhea,
direct result of the high quantity of free celiac disease, or hemodialysis. In these
ferrous iron in the stomach. Chelated forms of circumstances parenteral administration of
iron (combined with amino acids) are more iron in the form of iron dextran may be
bioavailable than nonchelated iron. Chelated necessary. Although replenishment of iron
iron is less affected by phytate, oxalate, stores by this route is faster, it is more
phosphate, and calcium (all iron absorption expensive than, and not as safe as, oral
inhibitors). Chelated iron causes less administration. Medical Nutrition Therapy In
gastrointestinal disturbances than elemental addition to iron supplementation and its
iron because it is needed in lower doses when dosage adjustment depending on patient
it is absorbed into mucosal cells (Ashmead, tolerance, attention should be given to the
2001). Health professionals usually prescribe amount of absorbable dietary iron consumed.
oral iron three times daily for 3 months to A good source of iron contains a substantial
treat iron deficiency. Depending on the amount of iron in relation to its calorie
severity of the anemia and the patient’s content and contributes at least 10% of the
tolerance, the daily dose of elemental iron recommended dietary allowance (RDA) for
recommended is 50-100 mg three times daily iron. Liver; kidney; beef; dried fruits; dried
for adults and 4-6 mg/kg of body weight peas and beans; nuts; dark green leafy
divided into three doses per day for children. vegetables; and fortified whole-grain breads,
Vitamin C greatly increases iron absorption muffins, cereals, and nutrition bars are among
and gastric irritation somewhat through its the foods that rank highest in iron content
capacity to maintain iron in the reduced state (see Appendix 49). It is estimated that 1.8 mg
(Aditi and Graham, 2012). Absorption of 10 to of iron must be absorbed daily to meet the
20 mg of iron per day permits RBC production needs of 80% to 90% of adult women and
to increase to approximately three times the adolescent boys and girls. Bioavailability of
normal rate and, in the absence of blood loss, Dietary Iron. Because typical Western diets
hemoglobin concentration to rise at a rate of generally contain 6 mg/1000 kcal of iron, the
0.2 g/dl daily. Increased reticulocytosis (an bioavailability of iron in the diet is more
increase in the number of young RBCs) is seen important in correcting or preventing iron
within 2 to 3 days after iron deficiency than the total amount of dietary
administration,but affected persons may iron consumed. The rate of absorption
depends on the iron status of the individual,
as reflected in the level of iron stores. The
lower the iron stores, the greater the rate of
iron absorption. Individuals with iron
deficiency anemia absorb approximately 20%
to 30% of dietary iron compared with the 5%
to 10% absorbed by those without iron
deficiency. Form of Iron. Heme iron
(approximately 15% of which is absorbable) is
the organic form in meat, fish, and poultry,
and is known as the meat-fish-poultry (MFP)
factor. It is much better absorbed than
nonheme iron. Nonheme iron can also be
found in MFP, as well as in eggs, grains,
vegetables, and fruits, but it is not part of the
heme molecule. The absorption rate of
nonheme iron varies between 3% and 8%,
depending on the presence of dietary
enhancing factors, specifically vitamin C and
meat, fish, and poultry. Vitamin C not only is a
powerful reducing agent, but also binds iron
to form a readily absorbed complex. The
mechanism by which the MFP factor
potentiates the absorption of nonheme iron
in other foodstuffs is unknown. Inhibitors.
Iron absorption can be inhibited to varying
degrees by factors that chelate iron, including
carbonates, oxalates, phosphates,
andphytates (unleavened bread, unrefined
cer als, and soybeans). Factors in vegetable fib
r may inhibit nonheme iron absorption. If
taken with meals, tea and coffee can reduce
iron absorption by 50% through the formation
of insoluble iron compounds with tannin. Iron
in egg yolk is poorly absorbed because of the
presence of phosvitin.