44 Iron Deficiency and Overload Flashcards
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
Iron depletion
Characterized by absent storage iron, usually low serum iron concentration and transferrin saturation, but without frank anemia
Iron deficiency without anemia
Most advanced stage of iron deficiency, is characterized by absent iron stores, low serum iron concentration, low transferrin saturation, and low blood hemoglobin concentration
Iron-deficiency anemia
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
Iron-deficiency anemia
Most common cause of iron deficiency
Gastrointestinal or menstrual blood loss
Most common cause of iron deficiency among men and in postmenopausal women
Gastrointestinal Blood Loss
The average menstrual blood loss is approximately
40 mL per cycle
Iatrogenic anemia is particularly prevalent in intensive care units, where repetitive blood sampling may result in removal of ______mL of blood daily
40–70 mL
Each whole-blood donation removes approximately ______mg of iron from the body.
200 mg
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
2 L
Approximately _____ mg of iron may be expended monthly in lactation.
30 mg of iron
In infants, iron deficiency is most often a result of
Use of unsupplemented milk diets, which contain an inadequate amount of iron
TRUE OR FALSE
Gastric secretion of hydrochloric acid is often reduced in iron deficiency.
TRUE
Gastric secretion of hydrochloric acid is often reduced in iron deficiency.
TRUE OR FALSE
Intestinal malabsorption of iron is quite an uncommon cause of iron deficiency except after gastrointestinal surgery and in malabsorption syndromes.
TRUE
Intestinal malabsorption of iron is quite an uncommon cause of iron deficiency except after gastrointestinal surgery and in malabsorption syndromes.
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 mediated by inappropriately increased hepcidin
Tmprss667
Time-pers sa iron! Ayaw gumana
TRUE OR FALSE
The concentration of many other iron-containing proteins is affected, often in an organ-specific manner.
Skeletal and cardiac muscle myoglobin is mildly depleted.
FALSE
The concentration of many other iron-containing proteins is affected, often in an organ-specific manner.
Skeletal muscle myoglobin is mildly depleted but cardiac myoglobin is not.
A particularly iron-rich region of the brain and contains dopaminergic neurons that are suspected of involvement in restless leg syndrome
Substantia nigra
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.
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.
TRUE OR FALSE
The rapidly proliferating cells of the upper part of the alimentary tract seem particularly susceptible to the effect of iron deficiency.
TRUE
The rapidly proliferating cells of the upper part of the alimentary tract seem particularly susceptible to the effect of iron deficiency.
- There may be atrophy of the mucosa of the tongue and esophagus, stomach, and small intestine.
- The epithelium of the lateral margins of the tongue is reduced in thickness despite an increase in the progenitor compartment.
Bone changes in IDA
Widening of diploic spaces of bones, particularly those of the skull and hands
In the skull, this is of the same character as in thalassemia, except that in β-thalassemia major there is maxillary hypertrophy, whereas in severe iron-deficiency anemia, maxillary growth and pneumatization are normal.
Condition wherein in the laryngopharynx, mucosal atrophy may lead to web formation in the postcricoid region, thereby giving rise to dysphagia + IDA
Paterson-Kelly or Plummer-Vinson syndrome
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
Pica
INCREASE OR DECREASE (IDA)
Plasma iron concentration
Iron-binding capacity
Serum ferritin
Serum transferrin receptor (sTfR)
Erythrocyte zinc protoporphyrin
Marrow stainable iron
Plasma iron concentration: DECREASE
Iron-binding capacity: INCREASE
Serum ferritin: DECREASE
Serum transferrin receptor (sTfR): INCREASE
Erythrocyte zinc protoporphyrin: INCREASE
Marrow stainable iron: DECREASE
The earliest recognizable morphologic change of erythrocytes in iron-deficiency anemia
Anisocytosis
- With further progression, hemoglobin concentration, erythrocyte count, mean corpuscular volume (MCV), and mean erythrocyte hemoglobin content all decline together
- The distribution of erythrocyte volume (eg, red cell distribution width [RDW]) is usually increased
TRUE OR FALSE
Both thrombocytopenia and thrombocytosis have been associated with iron deficiency.
TRUE
Both thrombocytopenia and thrombocytosis have been associated with iron deficiency.
TRUE OR FALSE
Evaluation of iron stores should be a sensitive and usually reliable means for the differentiation between iron-deficiency anemia and all other anemias.
TRUE
Evaluation of iron stores should be a sensitive and usually reliable means for the differentiation between iron-deficiency anemia and all other anemias.
Decreased or absent hemosiderin in the marrow is characteristic of iron deficiency and is readily evaluated after staining by
Prussian blue
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 _______
9 pm
7 am and 10 am
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
Third to the seventh day
Oral iron medication should be withheld for_____hours before blood samples are obtained for serum iron levels
24 hours
A measure of the amount of transferrin in circulating blood
Iron-binding capacity
The sum of the ______ and the _______represents total iron-binding capacity (TIBC).
UIBC and the plasma iron
Noermally, transferrin may be found to be approximately one-third saturated with iron.
Serum ferritin, secreted mainly by
Macrophages and hepatocytes
Conditions wherein the serum ferritin concentration is commonly in the range of thousands of micrograms per liter
Gaucher disease, juvenile rheumatoid arthritis and various macrophage activation syndromes, and in ferroportin disease
Conditions wherein zinc protoporphyrin is increased
Iron deficiency, lead poisoning, and sideroblastic anemias
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
Erythrocyte Zinc Protoporphyrin
TRUE OR FALSE
Erythrocyte Zinc Protoporphyrin can differentiate between iron deficiency and anemia that accompanies inflammatory or malignant processes.
FALSE
Erythrocyte Zinc Protoporphyrin does not differentiate between iron deficiency and anemia that accompanies inflammatory or malignant processes.
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
Serum Transferrin Receptor
Increased in IDA
Calculation for soluble transferrin index
Ratio of sTfR/log ferritin (TfR-F Index)
An indicator of iron restriction of hemoglobin synthesis during 3–4 days before the test
Reticulocyte Hemoglobin Content
Offers a longer-term assessment of iron restriction during the preceding few months
Percentage of hypochromic erythrocytes
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
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
Exceptions among hemolytic disorders that show pronounced erythrocytic hypochromia
Hemoglobin H disease or hemoglobin Köln disease
- In these disorders, there is moderate reticulocytosis, which helps to differentiate them from iron-deficiency anemia.
- The serum iron concentration is normal or increased.
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.
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.
Hyperthyroidism or Hypothyroidism
Causes normochromic and normocytic and may be accompanied by mild to moderate depression of serum iron concentration
Hypothyroidism
Iron deficiency often complicates myxedema because of menorrhagia, which is common in this disorder.
If the cause of anemia is iron deficiency, adequate iron therapy should result in reticulocytosis, with a peak occurring after_______weeks of therapy
1–2 weeks
A significant increase in the hemoglobin concentration of the blood should be evident ______ weeks later
3–4 weeks
Hemoglobin concentration should attain a normal value within _____months
2–4 months
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.
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.
Medicinal iron is superior to dietary iron in the therapy of iron deficiency.
Each dose of an inorganic iron preparation for an adult should contain between __________ mg of ferrous iron
30 and 100 mg
Form of iron that in the chronic renal disease setting has the potential benefit of acting as a phosphate binder
Ferric iron as citrate
Substances that enhance iron absorption
Ascorbic acid, succinate, and fructose
For therapy of iron deficiency in adults, the dosage should be sufficient to provide between _______ mg of elemental iron daily.
150 mg and 200 mg of elemental iron daily
Traditionally, the iron is taken orally in __________ doses __________ before meals.
Three or four doses
One hour before meals
Mild gastrointestinal side effects of oral iron
Nausea, heartburn, constipation, or changes in stool consistency and color
Proposed as an alternative to iron salts, on the assertion that it can be given in large doses with minimal side effects
Carbonyl iron
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
Oral ferric citrate
The earliest manifestation of iron poisoning is
Vomiting
The initial treatment of iron poisoning is
Prompt evacuation of the stomach
- Gastric intubation and lavage
- Whole-bowel irrigation
The agent of choice for specific therapy of hyperferremia/ acute iron poisoning
Intravenous desferrioxamine
Maximum rate of 15 mg/kg per hour for one hour, then lowered to 125 mg/h
Established indications for the use of parenteral rather than oral iron
- 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
TRUE OR FALSE
Parenteral iron administration has an erythropoietin-sparing effect in anemic patients on long-term hemodialysis for chronic renal disease.
TRUE
Parenteral iron administration has an erythropoietin-sparing effect in anemic patients on long-term hemodialysis for chronic renal disease.
Formula for calculating dosage of iron
The dose of iron (mg) = whole-blood hemoglobin deficit (g/dL) × body weight (lbs) + iron stores*
- 1000 mg for men
- 600 mg for women
Form of parenteral iron that was associated with anaphylactoid adverse events
High-molecular-weight dextran
Form of parenteral iron that may cause clinically important phosphate wasting and hypophosphatemia which can result in osteomalacia after chronic repeated use
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
The mechanism involved in hypophosphatemia with Ferric carboxymaltose is increased plasma concentrations of the active form of this phosphaturic hormone
Fibroblast growth factor 23
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.
Ferric pyrophosphate citrate
The reticulocyte count begins to increase after a few days, usually reaches a maximum at about _______ days
7–12 days
Used to designate an increase of tissue iron resulting in a disease state
Iron storage disease and hemochromatosis
The hemoglobin concentration in the blood may be halfway back to normal after 4–5 weeks of therapy.
Denotes an increase of tissue iron stores with or without tissue damage
Hemosiderosis
Occurs in patients who receive multiple blood transfusions, particularly when they have ineffective erythropoiesis and hence hyperabsorb dietary iron
Secondary hemochromatosis
Characterized by increased quantities of brain iron
Found in Alzheimer disease, parkinsonism, Friedreich ataxia, Hallervorden-Spatz disease, and multiple-system atrophy.
Aceruloplasminemia
Characterized by hepatic and extrahepatic iron deposition and fulminant hepatitis caused by the maternal immune response to fetal antigens.
Neonatal hemochromatosis
Types of Hereditary Hemochromatosis
- Classical hemochromatosis (HFE hemochromatosis) (type 1)- most common
-
Juvenile hemochromatosis (type 2)
Abnormality in hemojuvelin (HFE2, HJV)
Abnormality of hepcidin (Hamp) - Transferrin receptor-2 deficiency (type 3)
-
Ferroportin abnormalities (type 4)- (SLC40A1)
Gain of function (systemic iron overload)
Loss of function (macrophage iron overload) - Ferritin H-chain iron-responsive element mutation
- African iron overload
Classic Young TransFeree
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
HFE gene
The patient’s gender is clearly a modifying factor, with more severe manifestations observed in males, because pregnancy and menstrual iron losses tend to ameliorate the disease in women.
The most important HFE gene mutation
c.845 A→G (C282Y) mutation
Gene frequency of approximately 0.07 in the northern European population, approximately 5 in 1000 northern Europeans are homozygous for the mutation.
Haber-Weiss reaction
Fe++ + H2O2 → Fe+++ + OH– + HO∙
O2− + Fe+++ → O2 + Fe++
Fenton reaction:
O2− + H2O2 → O2 + OH− + HO∙
Subunit of ferritin that exerts most of its ferroxidase activity in the cytosol
H-ferritin (heavy)
The common pathway that causes hyperabsorption of iron is
Deficiency of hepcidin
The erythroid suppressors of hepcidin
GDF-15 and erythroferrone
In the liver of patients with classical hemochromatosis, TfR2 mutations and in juvenile hemochromatosis, hemosiderin is found primarily in____________. Kupffer cells are relatively spared.
Hepatocytes
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
Kupffer cells
Ferroportin mutations that prevent interaction with hepcidin, on the other hand, are associated with hepatocyte iron overload, as is seen in classical hemochromatosis.
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.
300 μmol/g dry weight (or about 50 μmol/g wet weight)
TRUE OR FALSE
Iron accumulates more slowly in the myocardium than in the liver but the heart is less sensitive to its toxic effects.
FALSE
Iron accumulates more slowly in the myocardium than in the liver but the heart is more sensitive to its toxic effects.
The leading cause of death in transfused patients with β-thalassemia major.
Accumulation of cardiac iron
Direct cardiac iron measurement using _______________ predicts cardiac complications and can stratify the risk of subsequent cardiac dysfunction.
Magnetic resonance imaging
Measures the half-life, T2*, of cardiac muscle darkening (with respect to echo time) produced by magnetically active stored cardiac iron
Iron overload in the marrow is characteristically distributed into small, equal-size granules located in ___________ rather than in macrophages.
The quantity of iron in the marrow of patients with classical hereditary hemochromatosis is only modestly increased, if at all.
Endothelial lining cells
The most common cause of hereditary hemochromatosis
Mutation of the HFE gene
The HFE gene, an HLA-like gene, resides on chromosome ______.
Chromosome 6
Three polymorphic HFE mutations have been identified
- 187- H63D
- 193 - S65C
- 845- C282Y
The phenotypic severity of HFE mutations on iron homeostasis is manifested in the following order:
C282Y > H63D > S65C
Mode of inheritance of Hereditary hemochromatosis
Autosomal recessive
Rare mutation of hepcidin associated with severe juvenile hemochromatosis
Hamp (Hepcidin)
Mode of inheritance of SLC40A1 (Ferroportin) Mutations
Autosomal dominant
Two types of SLC40A1 (Ferroportin) Mutations
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
Mode of inheritance of TfR2 Mutations
Autosomal recessive
Known to be a key regulator of hepcidin transcription
Bone morphogenetic protein receptor
BMP
Mutation associated with hepatic hemosiderosis and most with abnormal liver function tests in addition to microcytic hypochromic anemia
DMT-1 Human Mutations
The clinical features of the most common form of hereditary hemochromatosis
Cirrhosis of the liver, darkening of the skin, cardiomyopathies, and diabetes
“Bronze diabetes”
Onset of Juvenile Hemochromatosis
Second or third decade of life
Onset of classical hereditary hemochromatosis
Fifth or sixth decade of life
Characteristic features of the arthropathy of patients with hemochromatosis
Begin at the small joints of the hands, especially the second and third metacarpal joints, and in some cases, episodes of acute synovitis
Features considered distinctive to arthropathy of patients with hemochromatosis
- Joint distribution
- The presence of shape osteophytes emerging from the radial sides of the metacarpal distal epiphysis
- Presence of radiolucent zones in the subchondral area of the femoral head
Arthritis does not respond to phlebotomy therapy
Major clinical features of Juvenile Hemochromatosis
Cardiomyopathies and endocrine deficiencies
The main laboratory features of hereditary hemochromatosis
High transferrin saturation, and increased serum ferritin level
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
Hyperferritinemia-cataract syndrome
“Gold standard” for the diagnosis of iron overload
No longer required for the diagnosis of hemochromatosis
Liver biopsy
Formula for iron index
Dividing the iron content by the patient’s age
*liver biopsy
An iron index of greater than_______ implies the presence of hemochromatosis.
2
Can detect and reliably quantify increased amounts of iron in the liver
Magnetic resonance imaging
Treatment of choice for iron overload in patients who are able to mount an erythropoietin response
Phlebotomy
Treatment for patient that has marked impairment of erythropoiesis, as in thalassemia and dyserythropoietic anemia
Chelating agents
Occasionally serial phlebotomy will stimulate sufficient erythropoiesis to make it a viable therapy
End point of the initial part of the phlebotomy program
Signs of iron deficiency
The frequency of phlebotomies tailored to maintain the serum ferritin level, the best indicator of body stores, below _______ ng/m
100 ng/m
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.
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.
During phlebotomy, the transferrin saturation and serum ferritin level should be measured every _______months
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.
A naturally occurring iron-chelating compound synthesized by the microorganism Streptomyces pilosus, having evolved to enable the microbe to obtain iron from its environment
Desferrioxamine
Rapid IV or intramuscular injection results in relatively little iron mobilization; instead, it is necessary to administer desferrioxamine by
Slow IV or subcutaneous infusion over a period of 8–10 hours
Poorly absorbed from the gastrointestinal tract
Usual recommended dose of desferrioxamine
30–50 mL/kg
Vitamin C (up to 200 mg daily) may be given to enhance iron excretion.
Large doses of desferrioxamine are associated with
Hearing loss, night blindness and other visual abnormalities, growth retardation, and skeletal changes
Usual recommended dose of deferiprone
75 mg/kg per day divided into three doses
Toxic effects of deferiprone
Gastrointestinal disturbances, arthropathy, transient increases in the serum levels of liver enzymes, and zinc deficiency
Oral chelating agent excreted almost entirely in the urine
Deferiprone
Oral chelating agent that has propensity to produce neutropenia and agranulocytosis
Deferiprone
More effective in removing iron from the heart
Deferiprone
More effective with respect to liver iron accumulations
Desferrioxamine
Usual recommended dose of Deferasirox
30 mg/kg per day
Toxic effects of Deferasirox
Renal and hepatic, but it may also cause gastrointestinal hemorrhage
