44 Iron Deficiency and Overload Flashcards
(129 cards)
1
Q
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
A
Iron depletion
2
Q
Characterized by absent storage iron, usually low serum iron concentration and transferrin saturation, but without frank anemia
A
Iron deficiency without anemia
3
Q
Most advanced stage of iron deficiency, is characterized by absent iron stores, low serum iron concentration, low transferrin saturation, and low blood hemoglobin concentration
A
Iron-deficiency anemia
4
Q
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
A
Iron-deficiency anemia
5
Q
Most common cause of iron deficiency
A
Gastrointestinal or menstrual blood loss
6
Q
Most common cause of iron deficiency among men and in postmenopausal women
A
Gastrointestinal Blood Loss
7
Q
The average menstrual blood loss is approximately
A
40 mL per cycle
8
Q
Iatrogenic anemia is particularly prevalent in intensive care units, where repetitive blood sampling may result in removal of ______mL of blood daily
A
40–70 mL
9
Q
Each whole-blood donation removes approximately ______mg of iron from the body.
A
200 mg
10
Q
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
A
2 L
11
Q
Approximately _____ mg of iron may be expended monthly in lactation.
A
30 mg of iron
12
Q
In infants, iron deficiency is most often a result of
A
Use of unsupplemented milk diets, which contain an inadequate amount of iron
13
Q
TRUE OR FALSE
Gastric secretion of hydrochloric acid is often reduced in iron deficiency.
A
TRUE
Gastric secretion of hydrochloric acid is often reduced in iron deficiency.
14
Q
TRUE OR FALSE
Intestinal malabsorption of iron is quite an uncommon cause of iron deficiency except after gastrointestinal surgery and in malabsorption syndromes.
A
TRUE
Intestinal malabsorption of iron is quite an uncommon cause of iron deficiency except after gastrointestinal surgery and in malabsorption syndromes.
15
Q
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
A
Tmprss667
Time-pers sa iron! Ayaw gumana
16
Q
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.
A
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.
17
Q
A particularly iron-rich region of the brain and contains dopaminergic neurons that are suspected of involvement in restless leg syndrome
A
Substantia nigra
18
Q
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.
A
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.
19
Q
TRUE OR FALSE
The rapidly proliferating cells of the upper part of the alimentary tract seem particularly susceptible to the effect of iron deficiency.
A
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.
20
Q
Bone changes in IDA
A
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.
21
Q
Condition wherein in the laryngopharynx, mucosal atrophy may lead to web formation in the postcricoid region, thereby giving rise to dysphagia + IDA
A
Paterson-Kelly or Plummer-Vinson syndrome
22
Q
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
A
Pica
23
Q
INCREASE OR DECREASE (IDA)
Plasma iron concentration
Iron-binding capacity
Serum ferritin
Serum transferrin receptor (sTfR)
Erythrocyte zinc protoporphyrin
Marrow stainable iron
A
Plasma iron concentration: DECREASE
Iron-binding capacity: INCREASE
Serum ferritin: DECREASE
Serum transferrin receptor (sTfR): INCREASE
Erythrocyte zinc protoporphyrin: INCREASE
Marrow stainable iron: DECREASE
24
Q
The earliest recognizable morphologic change of erythrocytes in iron-deficiency anemia
A
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
25
# TRUE OR FALSE
Both thrombocytopenia and thrombocytosis have been associated with iron deficiency.
TRUE
Both **thrombocytopenia** and **thrombocytosis** have been associated with iron deficiency.
26
# 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.
27
Decreased or absent hemosiderin in the marrow is characteristic of iron deficiency and is readily evaluated after staining by
Prussian blue
28
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
29
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
30
Oral iron medication should be withheld for_____hours before blood samples are obtained for serum iron levels
24 hours
31
A measure of the amount of **transferrin** in circulating blood
Iron-binding capacity
32
The sum of the ______ and the _______represents **total iron-binding capacity (TIBC).**
UIBC and the plasma iron
## Footnote
Noermally, transferrin may be found to be approximately **one-third saturated** with iron.
33
Serum ferritin, secreted mainly by
Macrophages and hepatocytes
34
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
35
Conditions wherein **zinc protoporphyrin** is **increased**
Iron deficiency, lead poisoning, and sideroblastic anemias
36
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
37
# 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.
38
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
## Footnote
Increased in IDA
39
Calculation for soluble transferrin index
Ratio of sTfR/log ferritin (TfR-F Index)
40
An indicator of iron restriction of hemoglobin synthesis during 3–4 days before the test
Reticulocyte Hemoglobin Content
41
Offers a longer-term assessment of iron restriction during the preceding few months
Percentage of hypochromic erythrocytes
42
# 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
43
Exceptions among hemolytic disorders that show pronounced erythrocytic **hypochromia**
Hemoglobin H disease or hemoglobin Köln disease
## Footnote
* In these disorders, there is moderate reticulocytosis, which helps to differentiate them from iron-deficiency anemia.
* The serum iron concentration is normal or increased.
44
# 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.
45
# Hyperthyroidism or Hypothyroidism
Causes normochromic and normocytic and may be accompanied by mild to moderate depression of serum iron concentration
Hypothyroidism
## Footnote
Iron deficiency often complicates myxedema because of menorrhagia, which is common in this disorder.
46
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
47
A significant **increase in the hemoglobin** concentration of the blood should be evident ______ weeks later
3–4 weeks
48
Hemoglobin concentration should attain a **normal value** within _____months
2–4 months
49
# 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.
## Footnote
**Medicinal iron is superior to dietary iron in the therapy of iron deficiency.**
50
Each dose of an inorganic iron preparation for an adult should contain between __________ mg of ferrous iron
30 and 100 mg
51
Form of iron that in the **chronic renal disease** setting has the potential benefit of acting as a **phosphate binder**
Ferric iron as citrate
52
Substances that **enhance iron absorption**
Ascorbic acid, succinate, and fructose
53
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
54
Traditionally, the iron is taken orally in __________ doses __________ **before meals**.
Three or four doses
One hour before meals
55
Mild **gastrointestinal** side effects of oral iron
Nausea, heartburn, constipation, or changes in stool consistency and color
56
Proposed as an alternative to iron salts, on the assertion that it can be given in **large doses with minimal side effects**
Carbonyl iron
57
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
58
The earliest manifestation of iron poisoning is
Vomiting
59
The initial treatment of iron poisoning is
Prompt evacuation of the stomach
## Footnote
* Gastric intubation and lavage
* Whole-bowel irrigation
60
The agent of choice for specific therapy of hyperferremia/ acute iron poisoning
**Intravenous desferrioxamine**
## Footnote
Maximum rate of **15 mg/kg per hour** for one hour, then lowered to 125 mg/h
61
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
62
# 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.
63
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
64
Form of parenteral iron that was associated with **anaphylactoid** adverse events
High-molecular-weight dextran
65
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
.
## Footnote
It is important to check serum phosphate levels before repeat administration of ferric carboxymaltose, iron polymaltose, or saccharated ferric oxide
66
The mechanism involved in hypophosphatemia with Ferric carboxymaltose is increased plasma concentrations of the active form of this phosphaturic hormone
Fibroblast growth factor 23
67
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
68
The **reticulocyte count** begins to increase after a few days, usually reaches a maximum at about _______ days
7–12 days
69
Used to designate an increase of tissue iron resulting in a disease state
Iron storage disease and hemochromatosis
## Footnote
The hemoglobin concentration in the blood may be halfway back to normal after 4–5 weeks of therapy.
70
Denotes an increase of tissue iron stores with or without tissue damage
Hemosiderosis
71
Occurs in patients who receive **multiple blood transfusions,** particularly when they have ineffective erythropoiesis and hence hyperabsorb dietary iron
Secondary hemochromatosis
72
Characterized by increased quantities of **brain iron**
Found in Alzheimer disease, parkinsonism, Friedreich ataxia, Hallervorden-Spatz disease, and multiple-system atrophy.
Aceruloplasminemia
73
Characterized by hepatic and extrahepatic iron deposition and fulminant hepatitis caused by the maternal immune response to fetal antigens.
Neonatal hemochromatosis
74
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
75
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
## Footnote
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.
76
**The most important HFE gene mutation**
c.845 A→G (C282Y) mutation
## Footnote
Gene frequency of approximately 0.07 in the northern European population, approximately 5 in 1000 northern Europeans are homozygous for the mutation.
77
Haber-Weiss reaction
Fe++ + H2O2 → Fe+++ + OH– + HO∙
O2− + Fe+++ → O2 + Fe++
78
Fenton reaction:
O2− + H2O2 → O2 + OH− + HO∙
79
Subunit of ferritin that exerts most of its ferroxidase activity in the cytosol
H-ferritin (heavy)
80
The common pathway that causes hyperabsorption of iron is
Deficiency of hepcidin
81
The erythroid suppressors of hepcidin
GDF-15 and erythroferrone
82
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
83
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
## Footnote
**Ferroportin mutations that prevent interaction with hepcidin**, on the other hand, are associated with **hepatocyte** iron overload, as is seen in classical hemochromatosis.
84
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)
85
# 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**.
86
The leading cause of death in transfused patients with β-thalassemia major.
Accumulation of cardiac iron
87
Direct cardiac iron measurement using _______________ predicts cardiac complications and can stratify the risk of subsequent cardiac dysfunction.
Magnetic resonance imaging
## Footnote
Measures the half-life, **T2***, of cardiac muscle darkening (with respect to echo time) produced by magnetically active stored cardiac iron
88
Iron overload in the marrow is characteristically distributed into small, equal-size granules located in ___________ rather than in macrophages.
## Footnote
*The quantity of iron in the marrow of patients with classical hereditary hemochromatosis is only modestly increased, if at all.*
Endothelial lining cells
89
The most common cause of hereditary hemochromatosis
Mutation of the HFE gene
90
The HFE gene, an HLA-like gene, resides on chromosome ______.
Chromosome 6
91
Three polymorphic HFE mutations have been identified
* 187- H63D
* 193 - S65C
* 845- C282Y
92
The phenotypic severity of HFE mutations on iron homeostasis is manifested in the following order:
**C282Y** > H63D > S65C
93
Mode of inheritance of Hereditary hemochromatosis
Autosomal recessive
94
Rare mutation of **hepcidin** associated with severe juvenile hemochromatosis
Hamp (Hepcidin)
95
Mode of inheritance of **SLC40A1** (**Ferroportin**) Mutations
Autosomal dominant
96
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
97
Mode of inheritance of TfR2 Mutations
Autosomal recessive
98
Known to be a key regulator of hepcidin transcription
Bone morphogenetic protein receptor
| BMP
99
Mutation associated with hepatic hemosiderosis and most with **abnormal liver function tests** in addition to **microcytic hypochromic anemia**
DMT-1 Human Mutations
100
The clinical features of the most common form of hereditary hemochromatosis
Cirrhosis of the liver, darkening of the skin, cardiomyopathies, and diabetes
## Footnote
"Bronze diabetes"
101
Onset of Juvenile Hemochromatosis
Second or third decade of life
102
Onset of classical hereditary hemochromatosis
Fifth or sixth decade of life
103
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
104
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
## Footnote
**Arthritis does not respond to phlebotomy therapy**
105
Major clinical features of Juvenile Hemochromatosis
Cardiomyopathies and endocrine deficiencies
106
The main laboratory features of hereditary hemochromatosis
High transferrin saturation, and increased serum ferritin level
107
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
108
“Gold standard” for the diagnosis of iron overload
No longer required for the diagnosis of hemochromatosis
Liver biopsy
109
Formula for **iron index**
Dividing the iron content by the patient’s age
| *liver biopsy
110
An iron index of greater than_______ implies the presence of hemochromatosis.
2
111
Can detect and reliably quantify increased amounts of iron in the liver
Magnetic resonance imaging
112
Treatment of choice for iron overload in patients who are *able to mount an erythropoietin response*
Phlebotomy
113
Treatment for patient that has marked *impairment of erythropoiesis*, as in thalassemia and dyserythropoietic anemia
Chelating agents
## Footnote
Occasionally serial phlebotomy will stimulate sufficient erythropoiesis to make it a viable therapy
114
End point of the initial part of the phlebotomy program
Signs of iron deficiency
115
The frequency of phlebotomies tailored to maintain the serum ferritin level, the best indicator of body stores, below _______ ng/m
100 ng/m
116
# 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**.
117
During phlebotomy, the transferrin saturation and serum ferritin level should be measured every _______months
Two or three months
## Footnote
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.
118
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
119
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
## Footnote
Poorly absorbed from the gastrointestinal tract
120
Usual recommended dose of desferrioxamine
30–50 mL/kg
## Footnote
**Vitamin C (up to 200 mg daily)** may be given to enhance iron excretion.
121
Large doses of desferrioxamine are associated with
Hearing loss, night blindness and other visual abnormalities, growth retardation, and skeletal changes
122
Usual recommended dose of **deferiprone**
75 mg/kg per day divided into three doses
123
Toxic effects of deferiprone
Gastrointestinal disturbances, arthropathy, transient increases in the serum levels of liver enzymes, and zinc deficiency
124
Oral chelating agent excreted almost entirely in the urine
Deferiprone
125
Oral chelating agent that has propensity to produce **neutropenia and agranulocytosis**
Deferiprone
126
More effective in removing iron from the **heart**
Deferiprone
127
More effective with respect to **liver** iron accumulations
Desferrioxamine
128
Usual recommended dose of Deferasirox
30 mg/kg per day
129
Toxic effects of Deferasirox
Renal and hepatic, but it may also cause gastrointestinal hemorrhage
