Page 566 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 36 Disorders of Iron Homeostasis 481

TABLE Causes of Iron Deficiency of menstruation usually is delayed for months. If the infant is breast-
36.1 fed, lactation necessitates an intake of about 0.5 to 1.0 mg of
Increased Iron Requirements iron daily.
In some instances, an insufficient supply of iron may contribute
Blood loss to the development of iron deficiency. In infants or in women who
6
Gastrointestinal tract have experienced heavy menstrual losses or multiple pregnancies, the
Genitourinary tract risk of iron deficiency may be further increased by diets with insuf-
Respiratory tract ficient amounts of bioavailable iron, such as those with little or no
Blood donation heme iron and with small amounts of enhancers or large amounts of
Growth inhibitors of nonheme iron absorption. For older children, men, and
Pregnancy and lactation postmenopausal women, the restricted availability of dietary iron is
Inadequate Iron Supply almost never the sole explanation for iron deficiency, and other
Dietary insufficiency of bioavailable iron causes, especially blood loss, must be considered.
Impaired absorption of iron Impaired absorption of iron in itself infrequently is the sole source
Intestinal malabsorption of iron deficiency. Nonetheless, in patients in whom evaluation fails
Gastric surgery to identify a source of blood loss, as well as in those unresponsive to
Iron-refractory iron-deficiency anemia oral iron therapy, celiac disease, autoimmune, atrophic, or H. pylori
6
gastritis may be responsible. Iron deficiency frequently complicates
gastric surgery, such as partial or total gastric resection, gastroenter-
ostomy for bypass of the duodenum, and bariatric surgery.
Etiology and Pathogenesis Increased iron requirements and an inadequate supply of iron
often work in concert to produce iron deficiency. Infants fed cow’s
The foremost task in the evaluation of patients with iron deficiency milk receive a diet that not only contains small amounts of iron of
is identifying and treating the underlying cause of the imbalance low bioavailability but also increases iron losses by causing gastro-
7
between iron requirements and supply that is responsible for the lack intestinal bleeding. Patients with ulcer disease and increased gastro-
of iron (Table 36.1). Overall, the iron requirement for an individual intestinal blood loss may habitually take antacids or proton pump
includes not only the iron needed to replenish physiologic losses and inhibitors, which diminish dietary iron absorption.
meet the demands of growth and pregnancy but also any additional An uncommon heritable cause of iron deficiency is iron-refractory
amounts needed to replace pathologic losses. Physiologic iron losses iron-deficiency anemia (IRIDA), an autosomal recessive disorder
generally are restricted to the small amounts of iron contained in the with severe iron-deficiency anemia and increased concentrations of
urine, bile, and sweat; shedding of iron-containing cells from the plasma hepcidin. The anemia is unresponsive to orally administered
8
intestine, urinary tract, and skin; occult gastrointestinal blood loss; iron and incompletely responsive to parenteral iron. Mutations in
and, in women, uterine losses during menstruation and pregnancy. TMPRSS6, a gene that normally inhibits hepcidin production, are
In normal men, the daily basal iron loss is slightly less than 1.0 mg/d. responsible (see Chapter 35).
In normal menstruating women, the daily basal iron loss is approxi-
mately 1.5 mg/d. The median total iron loss with pregnancy is
approximately 600 mg, or almost 2 mg/d over the 280 days of Clinical Presentation
gestation.
The most common pathologic cause of increased iron requirements Patients with iron deficiency may present with (1) no signs or symp-
6
leading to iron deficiency is blood loss. In men and postmenopausal toms, coming to medical attention only because of abnormalities
women, iron deficiency almost inevitably signifies gastrointestinal noted on laboratory tests; (2) features of the underlying disorder
blood loss. Within the gastrointestinal tract, any hemorrhagic responsible for the development of iron deficiency; (3) manifesta-
lesion may result in blood loss, and the responsible lesion may be tions common to all anemias; or (4) one or more of the few signs
asymptomatic. Iron deficiency often is the first sign of an occult and symptoms considered highly specific for iron deficiency, namely,
6
gastrointestinal malignancy or other unrecognized conditions such as pagophagia, koilonychia, and blue sclerae. In addition, a high
coeliac disease, or autoimmune, atrophic, or Helicobacter pylori gas- prevalence of iron deficiency with or without anemia has been
tritis. Chronic ingestion of drugs such as alcohol, salicylates, steroids, reported among patients with restless legs syndrome, a neurologic
and nonsteroidal antiinflammatory drugs may cause or contribute to disorder characterized by a distressing need or urge to move the legs
blood loss. Worldwide, the most frequent cause of gastrointestinal (akathisia).
6
blood loss is hookworm infection, but other helminthic infections, An uncomplicated depletion of storage iron generally is not associ-
such as Schistosoma mansoni and Schistosoma japonicum, and severe ated with signs or symptoms, although patients without iron reserves
Trichuris trichiura infection also may be responsible. will not respond as rapidly to an increased need for iron resulting
In women of childbearing age, genitourinary blood loss with from blood loss, growth, or pregnancy. Iron-deficiency anemia pro-
6
menstruation adds to iron requirements. Other, less frequent causes duces the signs and symptoms common to all anemias, which are
of genitourinary bleeding may be involved, including chronic hemo- pallor, palpitations, tinnitus, headache, irritability, weakness, dizzi-
globinuria and hemosiderinuria resulting from paroxysmal nocturnal ness, easy fatigability, and other vague and nonspecific complaints.
hemoglobinuria or from chronic intravascular hemolysis. Uncom- The prominence of these signs depends on the degree and rate of
monly, respiratory tract blood loss resulting from chronic recurrent development of the anemia. With greater severity, anemia becomes
hemoptysis of any cause produces iron deficiency. increasingly debilitating as work capacity and tolerance of physical
In infants, children, and adolescents, the need for iron for growth exertion are restricted and eventually can produce cardiorespiratory
7
may exceed the supply available from diet and stores. Premature failure and even death.
infants, who have a lower birth weight and a more rapid postnatal Iron deficiency may produce clinical manifestations independent
rate of growth, are at high risk for iron deficiency unless given iron of anemia. Epithelial tissues have high iron requirements because of
supplements. With rapid growth during the first year of life, the body rapid rates of growth and turnover and thus are affected in many
weights of term infants normally triple, and iron requirements are at patients with chronic iron deficiency. Glossitis, angular stomatitis,
high levels. Iron requirements decline as growth slows during the postcricoid esophageal stricture or web (which may become malig-
second year of life and into childhood but rise again with the ado- nant), and gastric atrophy may develop. Pagophagia, a variant of pica
lescent growth spurt. in which ice is the substance obsessively consumed, is a behavioral
Without supplemental iron, pregnancy entails the net loss of the abnormality that is considered to be a highly specific symptom of
equivalent of 1200 to 1500 mL of blood. After delivery, resumption iron deficiency, resolving within a few days to 2 weeks after beginning