Iron Kinetics Flashcards
1
Q
It is critical to energy production in all cells, being at the center of the cytochrome of mitochondria
A
Iron (most important metal required for metabolic processes)
2
Q
True or False:
There is no mechanism for the active excretion of Iron in the Body
A
True (Iron is recycled to conserve as much as possible in the body, even going as far as storing iron for times when they are scarce in the diet)
3
Q
Where is the largest storage for iron in the body?
A
Hemoglobin in the RBC (70%)
(20% within hepatocytes and macrophages)
(10% divided among muscles, cytochrome, various iron-containing enzyme, and plasma)
4
Q
How much percentage of iron is stored within hepatocytes and macrophages?
A
20%
(Iron is stored within macrophages, which provides iron to immature RBCs found inside the bone marrow)
5
Q
Are redox-active proteins containing a heme, with a central iron (Fe) atom at its core, as a cofactor. They are involved in the electron transport chain and redox catalysis
A
Cytochromes
(any of a group of hemoprotein cell components that, by readily undergoing reduction and oxidation (gain and loss of electrons) with the aid of enzymes, serve a vital function in the transfer of energy within cells.)
6
Q
What are the three types of compartments used to determine the iron distribution in the body?
A
- Functional compartment
- Storage compartment
- Transport compartment
7
Q
Iron compartment that contains all iron that is functioning within cells, including iron in hemoglobin, myoglobin, and cytochrome (all cells other than mature RBCs)
A
Functional compartment
8
Q
Iron compartment in the body where iron that is not currently functioning but is available when needed is stored
A
Storage compartment
(mainly macrophages and hepatocytes, but every cell stores some iron for its own use)
9
Q
Iron compartment that contains iron that is in transit from one body site to another in the plasma
A
Transport compartment
10
Q
True or False:
The reactivity of iron ions makes them central to energy production processes without producing instability within the cells
A
False
(This reactivity makes cells unstable, posing risks to the cell)
(Thus, the body regulates iron carefully at the level of the whole body and also within individual cells, maintaining levels that are necessary for critical metabolic processes while avoiding the dangers of excess iron accumulation. )
11
Q
True or False:
The metabolic functions of iron depend on its ability to change
its valence state from reduced ferrous (Fe2+) iron to the oxidized ferric (Fe3+) state
A
True
(It is involved in oxidation and reduction reactions such as the electron transport within mitochondrial cytochrome)
12
Q
In cells, ferrous ion can react with _____ via the _____, forming highly reactive oxygen molecules
A
Peroxide; Fenton reaction
(Fenton reaction :Fe^2+ + H2O2 = Fe^3+ + HO- + OH)
13
Q
In cells, ferrous ion can react with peroxide via the Fenton reaction, forming ______
A
Highly reactive oxygen molecules
(Fenton reaction :Fe^2+ + H2O2 = Fe^3+ + HO- + OH)
14
Q
The resulting hydroxyl radical (OH) in the Fenton reaction, also known as a free radicals, is especially reactive as a short-lived but potent _____, able to damage proteins, lipids, and nucleic acids
A
Oxidizing agent
15
Q
The free radicals formed during the Fenton reaction could damage what structures in the cell?
A
- Proteins
- Lipids
- Nucleic acids
16
Q
What do you call the total amount of iron available to all body cells?
A
Systemic body iron
( Regulated by absorption into the body because there is no mechanism for excretion)
17
Q
Iron can be absorbed in the intestine as _____ from animal food sources or as _____, mostly from vegetable sources
A
Heme; Ionic iron
18
Q
True or False:
The means by which heme is absorbed by enterocytes is not entirely clear
A
True
(The primary heme carrier protein is still being sought)
19
Q
Once the heme enters the entrerocyte, likely by receptor-mediated endocytosis, the iron is freed from _____ by heme oxygenase
A
Protoporphyrin
20
Q
Once the heme enters the entrerocyte, likely by receptor-mediated endocytosis, the iron is freed from Protoporphyrin by ____
A
Heme oxygenase
21
Q
True or False;
Most dietary iron is in the ferrous form and enters the enterocyte readily through receptor-mediated endocytosis
A
False (They are usually in ferric form and require reduction by duodenal cytochrome B)
22
Q
Most dietary iron is nonheme ionic iron in the _____ and must be reduced by _____ before it can enter the enterocyte
A
Ferric form; duodenal cytochrome b (Dcytb)
23
Q
Once reduced to its ferric form, dieteary iron is carried across the luminal side of the enterocyte by ______
A
Divalent metal transporter 1 (DMT1)
24
Q
True or False:
Whether derived from heme or absorbed as an ion, the ferric iron can be stored as hemoglobin and used for enterocyte needs.
A
False
(It is stored as ferritin not Hgb)
25
True or False:
While some of the iron is stored as ferritin inside the enterocyte, most are chaperoned to the basolaminal side of the enterocyte for transport into the plasma
True
(The exact method of the chaperone is not known)
26
What is the protein that exports ferrous iron from the basolaminal side of the enterocyte to the blood?
Ferroportin
(The only known protein that exports iron across cell membranes)
27
______ is the only known protein that exports iron across the cell membrane
Ferroportin
28
During adequate stores of iron, the hepatocyte increases the production of _____, a protein that can bind to ferroportin, leading to its inactivation
Hepcidin
(results in lower absorption of iron in the body)
(Ito din ung protein that is affected by erythropoietin, which stimulates erythroid precursors to secrete erythroferrone that acts on hepatocytes to decrease hepcidin production during times of anemia)
29
What is the function of hepcidin in the body?
Inactivates ferroportin by binding to them during times of adequate stores of iron in the body
30
True or False:
When the body iron begins to drop, the liver senses that change and decreases hepcidin production. As a result, ferroportin is once again active and able to transport iron into the blood
True
31
Iron exported from the enterocyte into the blood is ______ and must be converted to the _____ for transport in the blood
Ferrous; Ferric
(Remember that iron needs to be in FERROUS form to be absorbed in the enterocyte, but it needs to be in FERRIC form to be transported in the blood)
32
A protein found on the basolaminal enterocyte membrane that can oxidize iron as it exits the enterocyte
Hephaestin
(It is then carried by apotransferrin, and once it binds to ApoTf, it is now known as transferrin)
33
Once the iron is oxidized by hephaestin in the basolaminal end, it is then transported through the plasma by _____
Apotransferrin (ApoTf)
34
How many iron molecules does Apotransferrin bind?
Two molecules of FERRIC iron
(When fully loaded, it is often referred to as diferric transferrin or holotransferrin)
35
Apotransferrin binds up to two molecules of ferric iron and thus when fully loaded is often referred to as ______ or ______
Diferric transferrin; holotransferrin
36
Proteins involved in the regulation of hepcidin
TTHH-BBdSM (the BDSM)
- Transferrin receptor 1 (TfR1)
- TfR2
- Hemochromatosis receptor (HFE)
- Hemojuvelin (HJV)
- Bone morphogenic protein (BMP)
- BMP receptor (BMPR)
- Sons of mothers against decapentaplegic (SMAD)
- Matripase-2
36
Two pathways that regulate hepcidin production
- BMP/SMAD Pathway
- Erythroferrone Pathway
(Note na hindi talaga yan ung tawag its just so i can differentiate the two)
37
Binds circulating diferric transferrin and releases hemochromatosis protein (HFE) for signaling
Transferrin receptor 1 (TfR1)
(Lahat na location is hepatocyte membrane except for BMP, ERFE, and TfR2 (BET-2))
38
With transferrin receptor 2, associates with bone morphogenetic protein receptor (BMPR) to initiate the signal to upregulate hepcidin production
Hemochromatosis protein (HFE)
39
With freed HFE, associates with BMPR to initiate the signal to upregulate hepcidin production
Transferrin receptor 2 (TfR2)
40
The ligand that initiates signal transduction when it binds to its receptor in a cell membrane
Bone morphogenetic protein (BMP)
(Found in Secreted products)
41
A common membrane receptor initiating signal transduction within a cell when its ligand (BMP) binds
Bone morphogenetic protein
receptor (BMPR)
42
A coreceptor acting with BMPR for signal transduction, leading to hepcidin production
Hemojuvelin (HJV)
43
A second messenger of signal transduction, phosphorylated by BMPR-HJV complex, and able to migrate to the nucleus and upregulate hepcidin gene expression
Sons of mothers against
decapentaplegic (SMAD)
44
Cleaves hemojuvelin to downregulate hepcidin production
Matriptase-2
45
Binds holotransferrin (Tf), which initiates a signal leading to secretion of erythroferrone
Transferrin receptor 2 (TfR2)
(Found on erythroblast membrane)
46
Able to downregulate hepcidin production in the liver; mechanism unknown
Erythroferrone (ERFE)
(Secreted by erythroblasts)
47
When body iron is replete and transferrin is well saturated, there is more ______ available to bind to the TfR1 and TfR2 on hepatocytes
diferric transferrin
(This binding contributes to a sequence of cell signaling events involving the proteins that result in the secretion of hepcidin)
48
When the body iron is replete and transferrin is saturated, hepcidin is carried in the blood to ______ and ______, where it binds to ferroportin and leads to its inactivation
Enterocytes and macrophages
(This leads to restriction of the entrance of iron into the blood)
49
When body iron is low, there is less ______ to trigger this pathway, leading to the decline of hepcidin production, and ferroportin is more active
Differic transferrin
(This leads to entry of more iron in the blood)
50
True or False:
The mutation in the proteins associated with increase and decrease in hepcidin production leads to either iron overload or deficiency
True
51
True or False:
The gene for erythroferrone (ERFE) is not erythropoietin responsive
False
(They are erythropoietin responsive)
52
Inanemias with elevated EPO levels, erythroblasts, mainly polychromatic normoblasts, secrete _____
Erythroferrone
(acts on the liver, reducing the production of hepcidin and increasing iron absorption in the intestine)
53
Protein responsible for reducing hepcidin production in the liver
Erythroferrone
54
True or False:
Through ERFE production, developing red blood cells
control the availability of iron for their hemoglobin production
True
(This explains the excess absorption of iron in anemias in which ineffective erythropoiesis increases the number of erythroblasts that secrete ERFE)
55
Hepatocytes and erythroblasts carry the ____, which acts as an iron sensor
Transferrin receptor 2 (TfR2)
56
Appears to enhance erythrocyte sensitivity to EPO by stabilizing the EPO receptor, thereby rescuing
more cells from apoptosis, and increasing the number of cells
producing ERFE
Transferrin receptor 2 (TfR2)
57
What are the two other products of erythroblasts that have been found to affect hepcidin production
growth differentiation factor-15 (GDF-15) and twisted gastrulation protein homolog 1 (TWSG1)
(In vivo effect in humans appears to be minimal)
58
True or False:
Individual cells tightly regulate the amount of iron they absorb to minimize the adverse effects of free radicals
True
59
To regulate the amount of iron absorbed, the body relies on a specific carrier to move iron into the cell through a process called _______
Receptor-mediated endocytosis
60
Cell membranes, including those of developing erythroblasts, posses a receptor for ______, which has the highest affinity for differic transferrin
TfR1 (Transferrin)
(When TfR1 molecules bind transferrin, they move within the membrane and cluster together)
61
Once a critical mass of TfR1 molecule accumulates, the membrane invaginates until it pinches off a vesicle inside the cytoplasm called ______
Endosome
62
________ are pumped inside endosomes, which results in the release of iron into the cytoplasm
Hydrogen ions
(The decrease in pH changes the affinity of transferrin for iron; Simultaneously, the affinity of TfR1 for apotransferrin also increases allowing it to remain bound to the receptor)
63
After hydrogen ions are pumped into the endosome, the iron is exported from the endosome into the cytoplasm by _____
DMT1
64
Process whereby the endosome and the mitochondria touch during iron transfer
Kiss and run
65
In the mitochondria, iron atoms are incorporated into ______, or in the case of erythroblasts, into _______ for the production of hemoglobin.
Cytochromes; erythroblasts
66
True or False:
The direct transfer of iron into the mitochondria appears to be especially important in the mitochondria
False
(It is important for ERYTHROBLASTS, as this allows them to bypass cytoplasmic systems, resulting in the acquisition of additional iron needed for Hgb production)
67
At the pH of the extracellular fluid, TfR1 has a very low affinity for _______
Apotransferrin
(It is then released into the plasma, available to bind iron once again)
68
True or False:
Although all cells, except mature erythrocytes, store iron, those cells that are central to recycling systemic body iron, macrophages and hepatocytes, contain most of the iron in the body
True
69
Ferric iron is stored in a cage-like protein called
Apotransferrin
70
Once iron binds to apoferritin, it is now known as _______
Ferritin
(Ferritin can bind to more than 4000 iron ions)
71
True or False:
Ferritin can only be found in the cytoplasm
False
(Although ferritin is typically considered a cytoplasmic protein, it has been established that mitochondria contain ferritin as well
72
Ferritin iron can be mobilized for use during times of iron need by ______ of the protein
Lysosomal degradation
73
Partially degraded ferritin is known as ______ and is considered to be less metabolically available than ferritin
Hemosiderin
74
True or False:
To regulate the amount of iron inside the cell and avoid free radicals, cells can control the amount of TfR2 on their surface
False (TfR1 dapat)
75
When iron stores inside the cell are sufficient, production of TfR1 ______ (Increase or declines)
Increases
(This results in the reduction of cellular iron absorption)(Reverse lang if kulang)
76
True or False:
When cells die, iron is excreted by the kidney into the urine
False
(It is recycled)
76
The largest percentage of recycled iron comes from _______, where they are ingested by macrophages in the spleen
RBC
77
In the spleen, senescent RBCs are ingested by macrophages, and their hemoglobin is degraded, with the iron being held by ______ as ferritin
Macrophages
78
In the spleen, senescent RBCs are ingested by macrophages, and their hemoglobin is degraded, with the iron being held by macrophages as ______
Ferritin
79
True or False:
Unlike enterocytes, macrophages do not possess ferroportin in their membrane
| Hello ngayon lang ako tinuruan ni emman nito so starting from here ganto
False
| They do have ferroportin in their membranes
## Footnote
These proteins allows for iron to be exported and salvaged by other cells
80
The exported iron that came from the macrophages are bound to ______
Plasma apotransferrin
| It is bound to apotransferrin, as if it was absorved in the intestines
81
# True or False
Because Haptoglobin and hemopecin are proteins, they pass readily through the glomerulus into the urine
False
| They do not pass readily thrugh the glomerulus
## Footnote
Hence, the bound heme iron is retained in the body
81
____ and ____ are plasma porteins that salvage plasma hemoglobin or heme, respectively
Haptoglobin and hemopexin
| These proteins salvage plasma Hgb or heme freed during hemolysis
82
Macrophages carry a receptor for the ________, whereas hepatocytes have a ________, making them both important cells in iron salvage
haptoglobin-hemoglobin complex; hemopexin-heme receptor
83
# True or False
Hepatocytes also possess ferroportin so that the salvaged iron can be exported to transferrin and ultimately to other body cell
True
84
# True or False
The body requires daily large amounts of new iron acquired from the diet
False
| We only require a small amount of new iron
## Footnote
The body stores and recycles iron in the body and is acquired through eating foods sontaining high levels of iron such as **red meats, legumes, and dark green leafy vegetables**
85
# True or False
Although some foods may be high in iron, that iron may not be readily absorbed and thus is not bioavailable
True
| Most dietary iron is **Ferric**, especially those from plant sources
85
# Identify the following
Dietary compounds that bind iron and inhibit absorption
- Oxalates
- Phylates
- Phosphates
- Calcium
## Footnote
Release from these binders and reduction to the ferrous form are enhanced by gastric acid, acidic foods (e.g., citrus), and an enterocyte luminal membrane ferrireductase, duodenal cytochrome b (Dcytb).
85
# Enumerate the following
Screening tests for iron status
- Serum iron
- Total iron-binding capacity
- percent transferrin saturation
- Serum ferritin
## Footnote
When the results of screening assays are equivocal, additional tests include Prussian blue staining of tissues, soluble transferrin receptor (sTfR), and hemoglobin content of reticulocytes
85
Iron can be absorbed as either ____ or ____ in the form of heme
Ionic iron or non-ionic iron
| Ionic iron must bein the ferrous form for absorption into enterocytes
## Footnote
This is accomplished via luminal membrane carries, DMT1
86
# True or False
Heme with its bound iron is less readily absorbed than ionic iron
False
| Heme is more readily absorbed than ionic iron
## Footnote
Thus meat, with heme in both myoglobin of muscle and hemoglobin of blood, is the **most bioavailable source of dietary iron.**
87
How much of the dietary iron is absorbed in the intestine daily
1-2 mg
| This amount is adequate for most men
## Footnote
but menstruating women, pregnant and lactating women, and growing children usually need additional iron supplementation to meet their increased need for iron
88
# Enumerate
Additional tests performed when results are equivocal
- Prussioan blue staining
- soluble transferrin receptor (sTfR)
- hemoglobin content of reticulocytes
## Footnote
results of measured parameters can be combined to calculate a sTfR/log ferritin ratio or graph a Thomas plot
89
Test assay with special application in sideroblastic anemia
Zinc protoporphyrin
90
____ can be measured colorimetrically using any of several reagents such as **ferrozine**
Serum Iron
## Footnote
The iron is first released from transferrin by acid, and then the reagent is allowed to react with the freed iron, forming a colored complex that can be detected spectrophotometrically.
91
**Serum Iron** can be measured colorimetrically using any of several reagents such as ______
Ferrozine
## Footnote
The iron is first released from transferrin by acid, and then the reagent is allowed to react with the freed iron, forming a colored complex that can be detected spectrophotometrically.
92
# True or False
The serum iron level has limited utility on its own because of its highwithin-day and between-day variability
True
| Also increases after** recent ingestion **of iron containing foods
93
To acoid the diurnal variation in serum iron, the standard practice has been to collect the specimen ______ and ______ when levels are expected to be highest
Fasting and early in the morning
94
# Reference interval
Serum iron level
50-160 ug/dl
95
Test that is limited by the amount of transferrin that is available to carry iron in plasma or serum
Toral Iron-Binding capacity
96
In order to remove unbound iron in Total Iron-Binding Capacity test, it is precipitated using what chemical powder
Mahnesoum carbonate powder
97
In order to account for the limitiations of Total Iron-binding Capacity, transferrin is macimally saturated by addition of excess ____ to the specimen
Ferric iron
| Any unbound iron is removed using magensium carbonate powder
98
# What type of test
Amount of iron detected represents all the binding sites available on transferrin
Total iron-binding capacity
## Footnote
It is expressed as an iron value, although it is actually an indirect measure of transferrin
99
# Reference interval
Total iron-binding capacity
250-400 ug/dl
100
# What type of test
Degree to which the available sites are occupied by iron
(Percent) transferrin saturation
101
# Reference interval
Transferrin saturation
20-55%
102
Formula used for percent transferrin saturation
SI/TIBC x 100% = % transferrin saturation
103
# What type of test
Considered the gold standard for assessment of body iron stores
Prussian blue staining
104
Prusian blue is actually a chemical compound with the formula _____
Fe7(CN)18
| This compound is formed during the staining process
105
Chemical used during staining procedure in Prussian Blue staining
Acidic potassium ferrocyanide
| The ferric iron reacts with acidic potassum ferrocyanide
## Footnote
This allows for the formation of the prussian blue compound that is readily seen microscopically as **dark blue granules/precipitate** (In high choncentrations, it could appear as a diffuse cytoplasmic blueness)
106
In Prussian blue staining, staining is conducted routinly when ____ or ____ is collected for other purposes
Bone marrow or liver biopsies
107
# True or False
One of the disadvantages of Prussian blue staining is the detection of ferritin
False
| ferritin is not typically detected because of the intact protein cage
108
# True or False
Although ferritin is not detected, hemosiderin is stained readily
True
| Forms distinct dark black granules
109
# Type of test
Test used to detect the iron-storage protein that functions mainly within cells through serum immunoassys
Ferritin
110
Cells known to secrete ferritin during in citro studies
Macrophages (kupffer cells) and hepatocytes
110
# True or False
The development of the serum immunoassay for ferritin has provided a convenient, minimally invasive, quantitative assessment of body iron stores.
True
| Until this was developed, need pa dati bone marrow
## Footnote
Invasive procedure
111
# True or False
The level of serum ferritin has been found to be inversely proportional to stored iron as assessed by prussian blue stains
False
| They are directly proportiona/correlated with one another
112
Significant drawback of serum ferritin
Increase during acute phase of inflammation, especially during infections
| Ferritin is an acute phase reactant (APR) produced by the liver
## Footnote
They include cytokines that are nonspecific, but also other proteins with the apparent intent to suppress bacteria.
113
Because bacteria requires iron, the body's production of ____ during an infection seems to be an attempt to sequester the iron away from the bacteria
Ferritin
| Leading to a falsely increased ferritin levels
## Footnote
These rises may not exceed the reference interval but may still be high enough to elevate a patient’s ferritin to greater than what it would otherwise be
114
Ferritin values between ____ are most equivocal, making it difficult to recognize true iron deficiency when an inflammatory condition is also present.
30-100 ng/ml
115
# What type of test
Measure of the truncated form of the TfR1 that is shed into the plasma and can be detected by immunoassay
Soluble Transferrin receptor
## Footnote
Cells regulate the amount of TfR1 on their membrane based on the amount of intracellular iron. When the intracellular iron drops, the cell expresses more TfR1 on the membrane
116
Increases in the soluble receptor, sTfR, reflect
either increases in the ____ on individual cells, as in** iron deficiency,** or an increase in the ____ each with a normal amount of TfR1
Amounts of TfR1; Number of cells
117
# Increase in # of cells or increase in the TfR1
Occurs during instances of rapid erythropoiesis, such as response to hemolytic anemia
Increase in TfR1
118
# Reference interval
Soluble Transferrin Receptor
1.15-2.75 mg/L
119
# Type of test
Detects the amount of hemoglobin in reticulocytes; analogous to the mean cell hemoglobin (MCH) but for reticulocytes
Hemoglvon content of Reticulocytes
120
# True or False
The number of circulating reticulocytes represents the status of erythropoiesis in the prior 24-hour period
True
## Footnote
the amount of hemoglobin in reticulocytes provides a near real-time assessment of iron available for hemoglobin production
121
# True or False
The Hemoglobin content of reticuloctes will Increase when iron forerythropoiesis is restricted
False
| The amount of Hgb will drop
122
# Reference interval
Hemoglobin content of reticulocytes
27-34 pg/cell
| Different in children and infants
123
# What type of test
Computes for the ration of sTfR to ferritn or sTfR ti log ferritin
Soluble transferrin Receptor/Log Ferritin
| Improves the identification of Iron deficiency
124
# True or False
Because the sTfR drops in iron deficiency and the ferritin rises, these ratios are especially useful to ampifly changes when one of the parameters has changed but is not outside the reference interval
False
| sTfR rises while ferritin drops in iron deificiency
125
# Reference Interval
Soluble Transferrin receptor/Log ferritin
0.63-1.8
126
# What type of test
sTfR/log ferritin is plotted against the hemoglobin content of reticulocytes that results in a four-quadrant plot
Thomas Plot
| improves the identification of iron deficiency
127
# What quadrant on the Thomas plot
In instances where there is true iron deficiency, the sTfR will rise and the ferritin will drop so that the sTfR/log ferritin will be high and the hemoglobin content of reticulocytes will be low
Lower Right Quadrant
128
# What quadrant of the Thomas plot
In instances where the ferritin may be falsely elevated by inflammation, the sTfR/log ferritin will be normal despite reduced availability of iron for hemoglobin production resulting in a low hemoglobin content in reticulocytes
Lower left quadrant
| Also called functional iron deficiency
## Footnote
because the systemic body stores are adequate
but not available for transport and use by cells
129
# What quadrant in the Thomas plot
As iron deficiency develops, other cells are starved for iron before erythrocytes; production of hemoglobin in reticulocytes remains at a normal level for as long as possible. However, the body’s other iron-starved cells will increase sTfR production and systemic iron stores of ferritin will be depleted, thus elevating the sTfR/log ferritin value
Upper right quadrant
| Also called latent iron deficiency
130
# What type of test
accumulates in RBCs when iron is not incorporated into heme and zinc binds instead to protoporphyric IX
Zinc Protoporphyrin (ZPP)
| Easily detected by fluorescence
130
# What quadrant in the thomas plot
Shows Normal iron status
Upper left quadrant
131
The value of ZPP is greatest when the activity of ____ is impared, as in lead poisoning
Ferrochelatase
132
# True or False
llthough ZPP will rise during iron-deficient erythropoiesis, the value of the test is greatest when the activity of the **ferrocelatas**e is impared, as in lead poisoning
True
133
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135
135
135
136
