44 Iron Deficiency and Overload

Question 1

The earliest stage of iron deficiency, in which storage iron is decreased or absent but serum iron concentration, transferrin saturation, and blood hemoglobin levels are normal

Answer 1

Iron depletion

Question 2

Characterized by absent storage iron, usually low serum iron concentration and transferrin saturation, but without frank anemia

Answer 2

Iron deficiency without anemia

Question 3

Most advanced stage of iron deficiency, is characterized by absent iron stores, low serum iron concentration, low transferrin saturation, and low blood hemoglobin concentration

Answer 3

Iron-deficiency anemia

Question 4

The most common anemia worldwide and is especially prevalent in women and children in regions where meat intake is low, food is not fortified with iron, and malaria, intestinal infections, and parasitic worms are common

Answer 4

Iron-deficiency anemia

Question 5

Most common cause of iron deficiency

Answer 5

Gastrointestinal or menstrual blood loss

Question 6

Most common cause of iron deficiency among men and in postmenopausal women

Answer 6

Gastrointestinal Blood Loss

Question 7

The average menstrual blood loss is approximately

Answer 7

40 mL per cycle

Question 8

Iatrogenic anemia is particularly prevalent in intensive care units, where repetitive blood sampling may result in removal of ______mL of blood daily

Answer 8

40–70 mL

Question 9

• Each whole-blood donation removes approximately ______mg of iron from the body.

Answer 9

200 mg

Question 10

In pregnancy, the average iron loss resulting from diversion of iron to the fetus, blood loss at delivery (equivalent to an average of 150–200 mg of iron), and lactation is altogether approximately 900 mg; in terms of iron content, this is equivalent to the loss of more than _____ L of blood

Answer 10

2 L

Question 11

Approximately _____ mg of iron may be expended monthly in lactation.

Answer 11

30 mg of iron

Question 12

TRUE OR FALSE

Gastric secretion of hydrochloric acid is often reduced in iron deficiency.

Answer 12

TRUE

Gastric secretion of hydrochloric acid is often reduced in iron deficiency.

Question 13

TRUE OR FALSE

Intestinal malabsorption of iron is quite an uncommon cause of iron deficiency except after gastrointestinal surgery and in malabsorption syndromes.

Answer 13

TRUE

Intestinal malabsorption of iron is quite an uncommon cause of iron deficiency except after gastrointestinal surgery and in malabsorption syndromes.

Question 14

Identified in genome-wide association studies as genetic factors that cause or predispose to iron deficiency

Associated with the the genetic syndrome of iron-refractory iron-deficiency anemia

Answer 14

Tmprss667

Question 15

TRUE OR FALSE

Iron deficiency decreases the risk and severity of malaria, and iron supplementation may have the opposite effect, especially when not targeted to patients with iron deficiency.

Answer 15

TRUE

Iron deficiency decreases the risk and severity of malaria, and iron supplementation may have the opposite effect, especially when not targeted to patients with iron deficiency.

Question 16

TRUE OR FALSE

The rapidly proliferating cells of the upper part of the alimentary tract seem particularly susceptible to the effect of iron deficiency.

Answer 16

TRUE

The rapidly proliferating cells of the upper part of the alimentary tract seem particularly susceptible to the effect of iron deficiency.

Question 17

Condition wherein in the laryngopharynx, mucosal atrophy may lead to web formation in the postcricoid region, thereby giving rise to dysphagia

Answer 17

Paterson-Kelly or Plummer-Vinson syndrome

Question 18

The craving to eat unusual substances, for example, dirt, clay, ice, laundry starch, salt, cardboard, and hair, is a well-documented manifestation of iron deficiency

Answer 18

Pica

Question 19

INCREASE OR DECREASE (IDA)

Plasma iron concentration
Iron-binding capacity
Serum ferritin
Serum transferrin receptor (sTfR)
Erythrocyte zinc protoporphyrin
Marrow stainable iron

Answer 19

Plasma iron concentration: DECREASE
Iron-binding capacity: INCREASE
Serum ferritin: DECREASE
Serum transferrin receptor (sTfR): INCREASE
Erythrocyte zinc protoporphyrin: INCREASE
Marrow stainable iron: DECREASE

Question 20

The earliest recognizable morphologic change of erythrocytes in iron-deficiency anemia

Answer 20

Anisocytosis

Question 21

TRUE OR FALSE

Both thrombocytopenia and thrombocytosis have been associated with iron deficiency.

Answer 21

TRUE

Both thrombocytopenia and thrombocytosis have been associated with iron deficiency.

Question 22

TRUE OR FALSE

Thus, evaluation of iron stores should be a sensitive and usually reliable means for the differentiation between iron-deficiency anemia and all other anemias.

Answer 22

TRUE

Thus, evaluation of iron stores should be a sensitive and usually reliable means for the differentiation between iron-deficiency anemia and all other anemias.

Question 23

Decreased or absent hemosiderin in the marrow is characteristic of iron deficiency and is readily evaluated after staining by the

Answer 23

Prussian blue method

Question 24

Physiologically, the serum iron concentration has a diurnal rhythm; it decreases in late afternoon and evening, reaching a nadir near ______ and increases to its maximum between _______

Answer 24

9 pm

7 am and 10 am

Question 25

During chemotherapy of malignancy, the serum iron concentration may be quite elevated, because cytotoxic effects of the drugs on erythroblasts inhibit erythropoiesis and related iron consumption

This effect is observed from the ____________ day after inception of chemotherapy

Answer 25

Third to the seventh day

Question 26

Oral iron medication should be withheld for_____hours before blood samples are obtained for serum iron levels

Answer 26

24 hours

Question 27

A measure of the amount of transferrin in circulating blood

Answer 27

Iron-binding capacity

Question 28

The sum of the ______ and the _______represents total iron-binding capacity (TIBC).

Answer 28

UIBC and the plasma iron

Question 29

Serum ferritin, secreted mainly by

Answer 29

Macrophages and hepatocytes

Question 30

Conditions wherein the serum ferritin concentration is commonly in the range of thousands of micrograms per liter

Answer 30

Gaucher disease, juvenile rheumatoid arthritis and various macrophage activation syndromes, and in ferroportin disease

Question 31

Conditions wherein zinc protoporphyrin is increased

Answer 31

Iron deficiency, lead poisoning, and sideroblastic anemias

Question 32

Sensitive in the diagnosis of iron deficiency and practical for large-scale screening programs designed to identify children with either iron deficiency or lead poisoning

Answer 32

Erythrocyte Zinc Protoporphyrin

Question 33

TRUE OR FALSE

Erythrocyte Zinc Protoporphyrin can differentiate between iron deficiency and anemia that accompanies inflammatory or malignant processes.

Answer 33

FALSE

Erythrocyte Zinc Protoporphyrin does not differentiate between iron deficiency and anemia that accompanies inflammatory or malignant processes.

Question 34

Transports transferrin iron into cells

Mirror the amount of cellular receptor, and therefore are proportional to the number of erythroblasts expressing the receptor and the number of receptors per erythroblast

Answer 34

Serum Transferrin Receptor

Question 35

Calculation for soluble transferrin index

Answer 35

Ratio of sTfR/log ferritin (TfR-F Index)

Question 36

An indicator of iron restriction of hemoglobin synthesis during 3–4 days before the test

Answer 36

Reticulocyte Hemoglobin Content

Question 37

Offers a longer-term assessment of iron restriction during the preceding few months

Answer 37

Percentage of hypochromic erythrocytes

Question 38

TRUE OR FALSE

Erythrocyte counts of 5 × 1012/L (5,000,000/μL) or higher are common among adults with iron-deficiency anemia than in thalassemia

Answer 38

FALSE

Erythrocyte counts of 5 × 1012/L (5,000,000/μL) or higher are relatively uncommon among adults with iron-deficiency anemia than in thalassemia

Question 39

Exceptions among hemolytic disorders that show pronounced erythrocytic hypochromia

Answer 39

Hemoglobin H disease or hemoglobin Köln disease

Question 40

TRUE OR FALSE

In the patient with pernicious anemia or folic acid deficiency, early after starting treatment, the serum iron concentration decreases markedly as iron is utilized rapidly for hemoglobin synthesis.

Answer 40

TRUE

In the patient with pernicious anemia or folic acid deficiency, early after starting treatment, the serum iron concentration decreases markedly as iron is utilized rapidly for hemoglobin synthesis.

Question 41

Hyperthyroidism or Hypothyroidism

Causes normochromic and normocytic and may be accompanied by mild to moderate depression of serum iron concentration

Answer 41

Hypothyroidism

Question 42

Large doses of IV iron may increase hemoglobin not only in iron-deficiency anemia but, by overwhelming the sequestration of iron in reticuloendothelial macrophages, also in conditions where total body iron is maldistributed, as in :

Answer 42

Anemia of inflammation or anemia associated with chronic renal disease

Question 43

If the cause of anemia is iron deficiency, adequate iron therapy should result in reticulocytosis, with a peak occurring after_______weeks of therapy

Answer 43

1–2 weeks

Question 44

A significant increase in the hemoglobin concentration of the blood should be evident ______ weeks later

Answer 44

3–4 weeks

Question 45

Hemoglobin concentration should attain a normal value within _____months

Answer 45

2–4 months

Question 46

TRUE OR FALSE

In general, the oral route is preferred but the IV route is increasingly used because of the improved safety and convenience of new parenteral iron preparations.

Answer 46

TRUE

In general, the oral route is preferred but the IV route is increasingly used because of the improved safety and convenience of new parenteral iron preparations.

Question 47

Each dose of an inorganic iron preparation for an adult should contain between __________ mg of ferrous iron

Answer 47

30 and 100 mg

Question 48

Form of iron that in the chronic renal disease setting has the potential benefit of acting as a phosphate binder

Answer 48

Ferric iron as citrate

Question 49

Substances that enhance iron absorption

Answer 49

Ascorbic acid, succinate, and fructose

Question 50

For therapy of iron deficiency in adults, the dosage should be sufficient to provide between _______ mg of elemental iron daily.

Answer 50

150 mg and 200 mg of elemental iron daily.

Question 51

Traditionally, the iron is taken orally in __________ doses __________ before meals.

Answer 51

Three or four doses one hour before meals

Question 52

Mild gastrointestinal side effects of oral iron

Answer 52

Nausea, heartburn, constipation, or changes in stool consistency and color

Question 53

Proposed as an alternative to iron salts, on the assertion that it can be given in large doses with minimal side effects

Answer 53

Carbonyl iron

Question 54

Formulated to enhance solubility and containing 210 mg of ferric iron in each tablet has been approved for the treatment of iron deficiency in the setting of chronic kidney disease, and it appears to be effective and well tolerated at doses of 3–12 tablets per day

Answer 54

Oral ferric citrate

Question 55

The earliest manifestation of iron poisoning is

Answer 55

Vomiting

Question 56

The initial treatment of iron poisoning is

Answer 56

Prompt evacuation of the stomach

Question 57

The agent of choice for specific therapy of hyperferremia/ acute iron poisoning

Answer 57

Intravenous desferrioxamine

Maximum rate of 15 mg/kg per hour for one hour, then lowered to 125 mg/h

Question 58

Established indications for the use of parenteral rather than oral iron

Answer 58

Malabsorption, either because of systemic inflammation or gastrointestinal pathology
Intolerance to iron taken orally
Iron need in excess of an amount that can be absorbed in the intestine
Noncompliance

Question 59

TRUE OR FALSE

Parenteral iron administration has an erythropoietin-sparing effect in anemic patients on long-term hemodialysis for chronic renal disease.

Answer 59

TRUE

Parenteral iron administration has an erythropoietin-sparing effect in anemic patients on long-term hemodialysis for chronic renal disease.

Question 60

1 mL of red cells contains approximately ______ mg of iron.

Answer 60

1 mg of iron

Question 61

Formula for calculating dosage of iron

Answer 61

The dose of iron (mg) = whole-blood hemoglobin deficit (g/dL) × body weight (lbs) + iron stores*

• 1000 mg for men
• 600 mg for women

Question 62

Form of parenteral iron that was associated with anaphylactoid adverse events

Answer 62

High-molecular-weight dextran

Question 63

Form of parenteral iron that may cause clinically important phosphate wasting and hypophosphatemia which can result in osteomalacia after chronic repeated use

Answer 63

Ferric carboxymaltose
Iron polymaltose
Saccharated ferric oxide

*it is important to check serum phosphate levels before repeat administration of ferric carboxymaltose, iron polymaltose, or saccharated ferric oxide.

Question 64

The mechanism involved in hypophosphatemia with Ferric carboxymaltose is increased plasma concentrations of the active form of this phosphaturic hormone

Answer 64

Fibroblast growth factor 23

Question 65

IV iron preparation that doesn’t require processing by reticuloendothelial macrophages

It transfers iron directly to transferrin and has been approved for iron supplementation during hemodialysis.

Answer 65

Ferric pyrophosphate citrate

Question 66

Used to designate an increase of tissue iron resulting in a disease state

Answer 66

Iron storage disease and hemochromatosis

Question 67

Denotes an increase of tissue iron stores with or without tissue damage

Answer 67

Hemosiderosis

Question 68

Occurs in patients who receive multiple blood transfusions, particularly when they have ineffective erythropoiesis and hence hyperabsorb dietary iron

Answer 68

Secondary hemochromatosis

Question 69

Characterized by increased quantities of brain iron

Found in Alzheimer disease, parkinsonism, Friedreich ataxia, Hallervorden-Spatz disease, and multiple-system atrophy.

Answer 69

Aceruloplasminemia

Question 70

Characterized by hepatic and extrahepatic iron deposition and fulminant hepatitis caused by the maternal immune response to fetal antigens.

Answer 70

Neonatal hemochromatosis

Question 71

Hereditary hemochromatosis usually is applied to the common genetic form of the disorder, found principally in those of northern European ancestry, and as a result of mutation of this gene

Answer 71

HFE gene

Question 72

The most important HFE gene mutation

Gene frequency of approximately 0.07 in the northern European population, approximately 5 in 1000 northern Europeans are homozygous for the mutation.

Answer 72

c.845 A→G (C282Y) mutation

Question 73

Haber-Weiss reaction

Answer 73

Fe++ + H2O2 → Fe+++ + OH– + HO∙
O2− + Fe+++ → O2 + Fe++

Question 74

Fenton reaction:

Answer 74

O2− + H2O2 → O2 + OH− + HO∙

Question 75

Subunit of ferritin that exerts most of its ferroxidase activity in the cytosol

Answer 75

H-ferritin (heavy)

Question 76

The common pathway that causes hyperabsorption of iron is

Answer 76

Deficiency of hepcidin

Question 77

The erythroid suppressors of hepcidin

Answer 77

GDF-15 and erythroferrone

Question 78

In the liver of patients with classical hemochromatosis, TfR2 mutations and in juvenile hemochromatosis, hemosiderin is found primarily in____________. Kupffer cells are relatively spared.

Answer 78

Hepatocytes

Question 79

In the case of patients with ferroportin mutations that prevent transport of iron, storage of iron takes place mostly in the _________ and fibrosis seems to be absent

Answer 79

Kupffer cells

Question 80

Ferroportin mutations that prevent interaction with hepcidin, on the other hand, are associated with_________ iron overload, as is seen in classical hemochromatosis.

Answer 80

Hepatocyte

Question 81

○ An iron concentration of more than________ μmol/g dry weight (or about _______μmol/g wet weight) is considered strong evidence for hemochromatosis when factors such as transfusions are eliminated as the cause.

Answer 81

300 μmol/g dry weight (or about 50 μmol/g wet weight)

Question 82

TRUE OR FALSE

Iron accumulates more slowly in the myocardium than in the liver but the heart is less sensitive to its toxic effects.

Answer 82

FALSE

Iron accumulates more slowly in the myocardium than in the liver but the heart is more sensitive to its toxic effects.

Question 83

The leading cause of death in transfused patients with β-thalassemia major.

Answer 83

Accumulation of cardiac iron

Question 84

Direct cardiac iron measurement using _______________ predicts cardiac complications and can stratify the risk of subsequent cardiac dysfunction.

Answer 84

Magnetic resonance imaging

Measures the half-life, T2*, of cardiac muscle darkening (with respect to echo time) produced by magnetically active stored cardiac iron

Question 85

Iron overload in the marrow is characteristically distributed into small, equal-size granules located in ___________ rather than in macrophages.

Answer 85

Endothelial lining cells

Question 86

The most common cause of hereditary hemochromatosis

Answer 86

Mutation of the HFE gene

Question 87

The HFE gene, an HLA-like gene, resides on chromosome ______.

Answer 87

Chromosome 6.

Question 88

Three polymorphic HFE mutations have been identified

Answer 88

These are located at nucleotides 187, 193, and 845 of the complementary DNA and at the protein level encode the H63D, S65C, and C282Y mutations, respectively.

Question 89

The phenotypic severity of HFE mutations on iron homeostasis is manifested in the following order:

Answer 89

C282Y > H63D > S65C

Question 90

Mode of inheritance of Hereditary hemochromatosis

Answer 90

Autosomal recessive

Question 91

Rare mutation associated with severe juvenile hemochromatosis

Answer 91

Hamp (Hepcidin)

Question 92

Mode of inheritance of SLC40A1 (Ferroportin) Mutations

Answer 92

Autosomal dominant

Question 93

Two types of SLC40A1 (Ferroportin) Mutations

Answer 93

Gain of function mutations: C326S mutation, interfere with hepcidin binding to ferroportin or with the resulting ferroportin endocytosis

Loss-of-function mutations: (more common); ferroportin mutations that do not localize to the cell surface, or prevent transport of iron

Question 94

Mode of inheritance of TfR2 Mutations

Answer 94

Autosomal recessive

Question 95

Mutation that cause juvenile hemochromatosis

Answer 95

Hemojuvelin Mutations

Question 96

Now known to be a key regulator of hepcidin transcription.

Answer 96

Bone morphogenetic protein receptor

Question 97

Mutation associated with hepatic hemosiderosis and most with abnormal liver function tests in addition to microcytic hypochromic anemia

Answer 97

DMT-1 Human Mutations

Question 98

The clinical features of the most common form of hereditary hemochromatosis

Answer 98

Cirrhosis of the liver, darkening of the skin, cardiomyopathies, and diabetes

Question 99

Onset of Juvenile Hemochromatosis

Answer 99

Second or third decade of life

Question 100

Onset of classical hereditary hemochromatosis

Answer 100

Fifth or sixth decade of life

Question 101

Characteristic features of the arthropathy of patients with hemochromatosis

Answer 101

Begin at the small joints of the hands, especially the second and third metacarpal joints, and in some cases, episodes of acute synovitis

Question 102

Features considered distinctive to arthropathy of patients with hemochromatosis

Answer 102

Joint distribution, the presence of shape osteophytes emerging from the radial sides of the metacarpal distal epiphysis, and the presence of radiolucent zones in the subchondral area of the femoral head

Question 103

Major clinical features of Juvenile Hemochromatosis

Answer 103

Cardiomyopathies and endocrine deficiencies

Question 104

The main laboratory features of hereditary hemochromatosis

Answer 104

High transferrin saturation, and increased serum ferritin level

Question 105

An uncommon autosomal dominant defect in which a mutation in the 5′ iron-responsive element of the ferritin light chain prevents binding of the iron-regulatory proteins, resulting in unrestrained constitutive production of the ferritin chains

Answer 105

Hyperferritinemia-cataract syndrome

Question 106

“gold standard” for the diagnosis of iron overload

No longer required for the diagnosis of hemochromatosis

Answer 106

Liver biopsy

Question 107

Formula for iron index

Answer 107

Dividing the iron content by the patient’s age

*liver biopsy

Question 108

An iron index of greater than_______ implies the presence of hemochromatosis.

Answer 108

2

Question 109

Can detect and reliably quantify increased amounts of iron in the liver

Answer 109

Magnetic resonance imaging

Question 110

Treatment of choice for iron overload in patients who are able to mount an erythropoietin response

Answer 110

Phlebotomy

Question 111

Treatment for patient that has marked impairment of erythropoiesis, as in thalassemia and dyserythropoietic anemia,

Answer 111

Chelating agents

**Occasionally serial phlebotomy will stimulate sufficient erythropoiesis to make it a viable therapy

Question 112

End point of the initial part of the phlebotomy program

Answer 112

Signs of iron deficiency

Question 113

The frequency of phlebotomies tailored to maintain the serum ferritin level, the best indicator of body stores, below _______ ng/m

Answer 113

100 ng/m

Question 114

TRUE OR FALSE

The hematocrit or hemoglobin and the MCV of the red cells should be measured before each phlebotomy is undertaken. If there has been a substantial decrease in the hematocrit or hemoglobin, the phlebotomy should be deferred.

Answer 114

TRUE

The hematocrit or hemoglobin and the MCV of the red cells should be measured before each phlebotomy is undertaken. If there has been a substantial decrease in the hematocrit or hemoglobin, the phlebotomy should be deferred.

Question 115

During phlebotomy, the transferrin saturation and serum ferritin level should be measured every _______months

Answer 115

Two or three months

When the transferrin saturation is less than 10% and the serum ferritin less than 10 ng/mL, phlebotomy should be discontinued and the patient monitored every 3–6 months so that the rate of ferritin rise can be estimated.

When the serum ferritin is in the 50–100 ng/mL range, the maintenance phase should be initiated.

Question 116

A naturally occurring iron-chelating compound synthesized by the microorganism Streptomyces pilosus, having evolved to enable the microbe to obtain iron from its environment

Answer 116

Desferrioxamine

Question 117

Rapid IV or intramuscular injection results in relatively little iron mobilization; instead, it is necessary to administer desferrioxamine by

Answer 117

Slow IV or subcutaneous infusion over a period of 8–10 hours

Question 118

Usual recommended dose of desferrioxamine

Answer 118

30–50 mL/kg

Question 119

Large doses of desferrioxamine are associated with

Answer 119

Hearing loss, night blindness and other visual abnormalities, growth retardation, and skeletal changes

Question 120

Usual recommended dose of deferiprone

Answer 120

75 mg/kg per day divided into three doses

Question 121

Toxic effects of deferiprone

Answer 121

Gastrointestinal disturbances, arthropathy, transient increases in the serum levels of liver enzymes, and zinc deficiency

Question 122

Oral chelating agent excreted almost entirely in the urine

Answer 122

Deferiprone

Question 123

Oral chelating agent that has propensity to produce neutropenia and agranulocytosis

Answer 123

Deferiprone

Question 124

More effective in removing iron from the heart

Answer 124

Deferiprone

Question 125

More effective with respect to liver iron accumulations

Answer 125

Desferrioxamine

Question 126

Usual recommended dose of Deferasirox

Answer 126

30 mg/kg per day

Question 127

Toxic effects of Deferasirox

Answer 127

Renal and hepatic, but it may also cause gastrointestinal hemorrhage