Ch. 19 - Disorders of Iron and Heme Metabolism Flashcards
The anemias associated with iron and heme typically
are categorized as anemias of ________ _______ resulting
from the lack of raw materials for hemoglobin assembly.
impaired production
Inadequate production of ____________ leads to diminished
production of heme and thus hemoglobin, but with a relative
excess of iron.
protoporphyrin
The result of inadequate production of protoporphyrin
sideroblastic anemia
functional molecules
heme-based cytochrome,
muscle myoglobin,
hemoglobin
Iron may be unavailable for incorporation into
heme because of _____________ or __________
inadequate stores of body iron
impaired
mobilization.
The anemia associated with inadequate stores is
termed:
iron deficiency anemia
the anemia resulting
from impaired iron mobilization is known as
anemia of chronic
inflammation
an example of a chronic inflammation condition
rheumatoid arthritis
the iron
supply is adequate and mobilization is unimpaired but an
intrinsic RBC defect prevents production of protoporphyrin or
incorporation of iron into it, the resulting anemia is called:
sideroblastic anemia
refers to the presence of nonheme iron in
the developing RBCs
sideroblastic
develops when the INTAKE OF IRON IS INADEQUATE to meet a standard level of demand, when the NEED FOR IRON EXPANDS, when there is IMPAIRED ABSORPTION, when
there is CHRONIC LOSS OF HEMOGLOBIN from the body
iron deficiency anemia
Approximately how much of iron is lost from the body each day?
1 mg of iron
Iron is lost from the body mainly in the _____________________ and __________.
mitochondria of desquamated skin and sloughed intestinal epithelium
Causes of iron deficiency when the level of iron intake
is inadequate to meet the needs of an expanding erythron
-infancy
(especially in prematurity), childhood, and adolescence
-pregnancy and nursing
Causes of impaired absorption
- celiac disease
- diseases that decrease stomach acidity
- gastrectomy or bariatric surgeries
- medications such as antacids
hemolysis that results in the loss of small amounts of
heme iron from the body over a prolonged period of time
chronic hemorrhage
Excessive
heme iron can be lost through?
-chronic gastrointestinal bleeding from ulcers
-gastritis due to alcohol or aspirin ingestion,
-tumors
parasitosis
-diverticulitis
-ulcerative colitis
-hemorrhoids
In women, what conditions such as can also lead to heme iron loss?
-prolonged menorrhagia (heavy menstrual
bleeding)
-fibroid tumors
-uterine
malignancies
Individuals with chronic
intravascular hemolytic processes, such as ________________, can develop iron deficiency due to the
loss of iron in hemoglobin passed into the urine.
paroxysmal nocturnal
hemoglobinuria
iron is distributed among three compartments, what are these?
(1) the storage compartment, principally as ferritin in
the bone marrow macrophages and liver cells; (2) the transport
compartment of serum transferrin; and (3) the functional
compartment of hemoglobin, myoglobin, and cytochromes.
(1) the storage compartment, principally as ferritin in
the bone marrow macrophages and liver cells
(2) the transport
compartment of serum transferrin
(3) the functional
compartment of hemoglobin, myoglobin, and cytochromes.
True or false. Hemoglobin and intracellular ferritin constitute nearly 85% of
the total distribution of iron.
False. *95%
The body strives to maintain iron balance by accelerating
absorption of iron from the intestine through a decrease
in the production of ________ in the liver.
hepcidin
What stage of iron deficiency is defined by the exhaustion of the
storage pool of iron?
Stage 2
What stage of iron deficiency is characterized by a progressive loss
of storage iron?
Stage 1
(Stage 2) The serum iron and serum ferritin levels
decrease, whereas ______________, an indirect
measure of transferrin, increases
total iron-binding capacity (TIBC)
(Stage 2) ___________________, the porphyrin
into which iron is inserted to form heme, begins to accumulate.
Free erythrocyte protoporphyrin (FEP
(Stage 2) ____________ stain of the
bone marrow in stage 2 shows essentially no stored iron
Prussian blue
True or false. Iron deficiency in stage 2 is subclinical, and
testing is not likely to be undertaken.
True
What stage of iron deficiency is frank anemia?
Stage 3
(Stage 3) True or false. The hemoglobin
concentration and hematocrit are high relative to the reference
ranges.
False. *low :))
(Stage 3) True or false. FEP and transferrin receptor levels continue to decrease.
False *increase
Nonspecific symptoms of anemia
fatigue and weakness
A severe sign due to due to iron deficiency in the rapidly proliferating
cells of the alimentary tract
sore
tongue (glossitis)
A severe sign characterized by inflamed cracks at
the corners of the mouth
angular cheilosis
may be seen if the deficiency
is long-standing
Koilonychia
spooning of the fingernails
cravings for
nonfood items
pica
Craving for ICE
pagophagia
_______________________
can lead to a loss of nearly 900 mg of iron,
pregnancy and nursing
Growth requires
a. _____ for the cytochromes of all new cells, b. ________for new
muscle cells, and c. __________ in the additional RBCs needed
to supply oxygen for a larger body.
a. iron
b. myoglobin
c. hemoglobin
True or false. Cow’s milk
is a good source of iron
False
iron supplementation is also
recommended for breastfed infants after how many months of age?
6 months
___________ and __________ can lead to gastritis and
chronic bleeding.
-Regular aspirin
ingestion
-alcohol consumption
Iron deficiency is associated with infection by hookworms. Give two examples.
Necator americanus and Ancylostoma duodenale
Iron deficiency is also associated with infection
with other parasites, such as: __________, ___________, and __________ in which the heme iron
is lost from the body due to intestinal or urinary bleeding.
Trichuris trichiura, Schistosoma
mansoni, and Schistosoma haematobium
___________ develops when RBCs are hemolyzed
by foot-pounding trauma and iron is lost as hemoglobin
in the urine
“Marching anemia”
The tests for iron deficiency can
be grouped into three general categories:
- screening
- diagnostic,
- specialized.
When iron deficient erythropoiesis is under way, the CBC
results begin to show evidence of ________, ________ and, _________
anisocytosis, microcytosis,
and hypochromia
The classic picture of iron
deficiency anemia in stage 3 includes a decreased _________
level.
hemoglobin
An RDW greater than ___ is expected and may precede
the decrease in hemoglobin.
15%
As the hemoglobin level continues to fall, microcytosis and hypochromia become more prominent, with
progressively declining values for ____, _____, and _____
MCV, MCH, and MCHC
A low
________________ confirms a diminished rate of effective
erythropoiesis, because this is a nonregenerative anemia
absolute reticulocyte count
_____________ may be present,
particularly if the iron deficiency results from chronic bleeding,
but this is not a diagnostic parameter.
Thrombocytosis
True or false. White blood cells
(WBCs) are typically normal in number and appearance.
True
Iron
deficiency should be suspected when the CBC findings show a
hypochromic, microcytic anemia with an (a. elevated b. decreased) RDW but no
consistent shape changes to the RBCs.
a. elevated
____________ remain the backbone for diagnosis of iron deficiency
Iron studies
______________ is
a measure of the amount of iron bound to transferrin in the serum.
Serum iron
______ is an indirect measure of
transferrin and the available binding sites for iron in the
plasma.
TIBC
True or false. Ferritin is not truly an extracellular protein.
True *because it provides an intracellular storage repository for metabolically active iron
_____________ is an
easily accessible surrogate for stainable bone marrow iron
Serum ferritin
Serum ferritin
and serum iron values are (a. increased b.decreased) in iron deficiency anemia
b. decreased
Transferrin levels (a. increase b. decrease) when the hepatocytes detect low
iron levels, and research shows that this is a transcriptional and
posttranslational response to low iron levels.12
a. increase
It is important that specimens for iron studies are drawn
while ______ and when levels are highest.
fasting
early in the morning
Iron absorbed from a meal can falsely
(a.elevate b. decrease) levels
a. elevate
The reticulocyte
hemoglobin value is analogous to the ___, but for reticulocytes.
MCH
The ___ is the average weight of hemoglobin per cell
across the entire RBC population
MCH
The ________________ is able to assess iron deficient erythropoiesis within days
as the first iron deficient cells leave the bone marrow.
reticulocyte hemoglobin value
Even in stage 2 of iron deficiency, before anemia is apparent, the reticulocyte hemoglobin will be (a. low b. high)
a. low
Test results for
the accumulated porphyrin precursors to heme are (a. elevated b. decreased)
a. elevated
In
the absence of iron, FEP may be preferentially chelated with
zinc to form __________________
zinc protoporphyrin (ZPP)
The FEP and zinc
chelate can be assayed ____________
fluorometrically
A __________________ provides a less invasive and less expensive
diagnostic assessment.
therapeutic trial of iron
With routine stains, the iron deficient
bone marrow appears a. ___________ early in the progression of
the disease, with a decreased b. ________________ ratio as a
result of increased erythropoiesis.
a. hyperplastic
b. myeloid-to-erythroid
As the disease progresses,
__________ subsides, and the profound deficiency of iron leads
to slowed RBC production.
hyperplasia
_________________ (i.e.,
rubricytes) show the most dramatic morphologic changes
Polychromatic normoblasts
Without the pink provided by hemoglobin, the cytoplasm
remains ____ after the nucleus has begun to condense.
bluish
The
cell membranes appear irregular and are usually described as
_______
shaggy
The first therapy for iron deficiency is to treat any underlying
contributing cause, such as?
hookworms, tumors, or ulcers.
As
in the treatment of simple nutritional deficiencies or increased
need, dietary supplementation is necessary to replenish the
body’s iron stores. Oral supplements of _______________________________are the standard
prescription.3
ferrous sulfate (3 tablets/day containing 60 mg of elemental iron)
The supplements should be taken on an
(a. empty b. full) stomach to maximize absorption
a. empty
What can be used in rare cases in which intestinal absorption
of iron is impaired, as with gastric achlorhydria?
parenteral
administration of iron dextrans
(Response to Treatment) The reticulocyte hemoglobin will correct within how many days?
2 days
(Response to Treatment) The reticulocyte counts (relative and absolute) begin to
increase within how many days?
5 to 10 days
The anticipated rise in hemoglobin
appears in a. ______ (how many weeks), and levels should return to
normal for the individual by about b. ______ (how many months) after the initiation
of adequate treatment
a. 2 to 3 weeks
b. 2 months
The peripheral blood film and
indices still reflect the microcytic RBC population for several
months, but the _________ population eventually predominates.
normocytic
Iron therapy must continue for another ____________ (how many months)
to replenish the storage pool and prevent a relapse.
3 to 4 months
This anemia represents the most common
anemia among hospitalized patients
Anemia of Chronic Inflammation
Who was the first to suggest that although the underlying
diseases seem quite disparate, the associated anemia may be
from a single cause, proposing the concept of anemia of
chronic disease
Cartwright
True or false. Chronic
blood loss is not among the conditions leading to the anemia
of chronic disease.
True
The central feature
of anemia of chronic inflammation
sideropenia
The cause of anemia of chrosnic inflammation is now understood to be
largely what?
impaired ferrokinetics
hormone produced by
hepatocytes to regulate body iron levels, particularly absorption
of iron in the intestine and release of iron from macrophages
Hepcidin
exports iron from enterocytes into the plasma, reducing
the amount of iron absorbed into the blood from the intestine
Transmembrane protein: Ferroportin
When body iron
levels a. _______, hepcidin production by hepatocytes decreases,
and b. ________ export more iron into the plasma
a. decrease
b. enterocytes
When iron levels
are high, hepcidin increases, enterocytes export (a. more b. less) iron into
the plasma, and macrophages and hepatocytes retain iron.
b. less
an iron-binding protein in
the granules of neutrophils
Lactoferrin
Acute phase reactants
hepcidin, lactoferrin, ferritin
The peripheral blood picture in anemia of chronic inflammation
is that of a mild anemia with hemoglobin concentration
usually ______ g/dL and without reticulocytosis.
9 to 11
Because hepatocyte production
of transferrin is regulated by iron levels, the low TIBC
(an indirect measure of transferrin) reflects the (a.abundant b. diminished) iron
stores in the body.
a. abundant
Iron deficiency
anemia and anemia of chronic inflammation can be distinguished
in such situations by measuring _______________.
serum (soluble) transferrin
receptors
Therapeutic administration of ____________ can correct
anemia of chronic inflammation
erythropoietin
Trulaloo or false. The best course of treatment in anemia of chronic inflammation is effective control or
alleviation of the underlying condition.
True
True or false. As in iron deficiency, the anemia of chronic inflamm may be microcytic and hypochromic.
True
True or false. In contrast to iron deficiency, however, iron is abundant
in the bone marrow in the anemia of chronic inflamm.
True
a cofactor
in the first step of porphyrin synthesis which glycine is condensed with succinyl coenzyme A to form
aminolevulinic acid
Pyridoxine
Certain drugs that can induce sideroblastic
anemia
chloramphenicol or isoniazid
A toxin that interferes with porphyrin synthesis
Lead
The most critical steps when lead interferes with porphyrin synthesis
- The conversion of aminolevulinic acid to porphobilinogen;
the result is the accumulation of aminolevulinic acid. - The incorporation of iron into protoporphyrin IX by ferrochelatase
(also called heme synthetase); the result is accumulation
of iron and protoporphyrin.
Accumulated aminolevulinic acid is measurable in the (a. stool b. blood c. urine)
c. urine
protoporphyrin is measurable in an
extract of RBCs as___ or ___.
FEP or ZPP
Anemia, when present in lead poisoning, is most often
normocytic and normochromic; however, with chronic exposure
to lead, a ________, _________clinical picture may be
seen.
microcytic, hypochromic
Hereditary Disorders Included in Sideroblastic Anemias
X-linked
Autosomal
The presence of a
hemolytic component is supported by studies showing impairment
of the _______________by lead, which makes
the cells sensitive to oxidant stress as in glucose-6-phosphate
dehydrogenase deficiency
pentose-phosphate shunt
chronic
poisoning results in ______ of the marrow
hypoplasia
a classic finding associated with lead toxicity
Basophilic
stippling
Lead
inhibits _______________, an enzyme involved in the
breakdown of ribosomal ribonucleic acid (RNA) in reticulocytes
pyrimidine 5′-nucleotidase
In the case of lead,
___________________________are often used to
chelate the lead present in the body so that it can be excreted
in the urine
salts of ethylenediaminetetraacetic acid
The term ________ is most often
used to refer to the hereditary conditions
porphyria
The fluorescence of
the accumulated compounds can be used diagnostically as
described earlier for FEP. In a sample of bone marrow, the
erythroblasts will be _______ under a fluorescent microscope.
bright red
It occurs when there is a need for repeated transfusions, as in
the treatment of anemias such as thalassemia.
Accumulation of excess iron
It is when the iron present
in the transfused RBCs exceeds the usual 1 mg/day of iron
typically added to the body’s stores by a healthy diet.
transfusion-related hemosiderosis
may develop as a result of mutations
affecting the proteins of iron metabolism
Hemochromatosis
a gene on the short arm of chromosome 6 that encodes an HLA class I–like molecule that is closely linked to HLA-A
HFE
The most common of the two
mutations substitutes tyrosine for ________ at position 282
(Cys282Tyr)
cysteine
the other mutation substitutes _________ for histidine
at position 63 (His63Asp).
aspartate
The normal ____ protein binds
β2-microglobulin intracellularly.
HFE
Interaction of HFE with _____________ reduces transferrin binding to the receptor, inhibiting
cellular iron absorption
transferrin
receptor 1
The _______________
either does not bind β2-microglobulin and thus does not reach
the cell surface, or does not bind the transferrin receptor 1 if
it does reach the cell surface
mutated HFE molecule
The (a. active b. passive) transport of iron into the
plasma seems to be crucial in the pathophysiology of hereditary
hemochromatosis.
a. active
the gene that codes
for hemojuvelin
HJV (HFE2)
In hepatocytes, what substances regulate hepcidin expression
-iron-bound transferrin
-HFE
-transferrin
receptor 2
-hemojuvelin
The first
cellular reaction to excess iron is?
form hemosiderin
essentially a degenerate and non–metabolically active form of
ferritin
hemosiderin
the traditional characterization
of hemochromatosis
“bronzed diabetes”
occurs more frequently in patients with hemochromatosis.
Hepatocellular carcinoma
The phenotypic expression of the tissue damage
in hereditary hemochromatosis is more
common in (a.men b. women)
a. men
In classic hereditary hemochromatosis,
individuals usually harbor ______ g of iron by the time their
disease becomes clinically evident at the age of 40 to 60 years
20 to 30 g
Withdrawal of blood
by phlebotomy provides a simple, inexpensive, and effective
means of removing iron from the body. The regimen calls
for weekly phlebotomy early in treatment to remove about
___ mL of blood per treatment
500
iron-chelating drug that is a classic treatment for people who cannot be treated by phlebotomy
Desferrioxamine
When stained using Prussian blue, the iron appears in
deposits around the nucleus of the developing cells. These cells
are called?
ringed sideroblasts
In the pathogenesis of the anemia of chronic inflammation,
hepcidin levels:
Increase during inflammation and reduce iron
absorption from enterocytes
Sideroblastic anemias are anemias that result from:
Failure to incorporate iron into protoporphyrin IX
