IRON Flashcards

1
Q

What is the chemical symbol for Iron?

A

Fe

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2
Q

What is the atomic number of Iron?

A

26

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3
Q

What is the molecular weight of Iron?

A

56

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4
Q

In which oxidation states can Iron exist?

A

• 2+ • 3+

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5
Q

What is Ferrous iron and what does it indicate?

A

• Ferrous (2+) “reduced” - gained an electron

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6
Q

What is Ferric iron and what does it indicate?

A

• Ferric (3+) “oxidized” - lost an electron

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7
Q

Why is a redox change required for Iron metabolism?

A

• Redox change is required for iron metabolism

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8
Q

What is the total body iron content?

A

• Body iron content: 3-4 g

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9
Q

What percentage of the body’s iron is found in hemoglobin?

A

• Hb iron: 70%

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10
Q

What percentage of the body’s iron is stored iron?

A

• Storage iron: 25%

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11
Q

What forms of storage iron exist in the body?

A
  • Ferritin
  • Hemosiderin
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12
Q

What percentage of iron is found in myoglobin?

A

• Myoglobin iron: 5%

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13
Q

What percentage of iron comes from other sources in the body?

A

• Other sources: <1%

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14
Q

What are the other sources of iron in the body?

A
  • Peroxidase
  • Catalase
  • Cytochromes
  • Fiboflavin enzymes
  • Transferrin
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15
Q

What percentage of body iron is found in serum?

A

• Serum: 0.1%

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16
Q

What are the oxygen-related functions of iron?

A

• Oxygen carriers • Hemoglobin • Oxygen storage • Myoglobin

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17
Q

What role does iron play in energy production?

A
  • Cytochromes (oxidative phosphorylation)
  • Krebs cycle enzymes
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18
Q

What is the role of iron in liver detoxification?

A

• Liver detoxification (cytochrome p450)

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19
Q

What are the potential damages caused by iron toxicity?

A
  • Iron can damage tissues
  • Catalyzes the conversion of hydrogen peroxide to free-radical ions
  • Free radicals can attack cellular membranes * Proteins * DNA
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20
Q

What health issues can result from iron excess?

A
  • Iron excess (overload) possibly related to cancers
  • Cardiac toxicity
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21
Q

What are the possible causes of iron deficiency?

A
  • Excessive bleeding
  • Inadequate intake
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22
Q

How is iron reused in the body?

A
  • Old cells broken down in macrophages in spleen and other organs
  • Iron transported to liver and other storage sites
  • Red cell iron recovered from old red cells
  • Very little iron lost in routine metabolism
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23
Q

What enzyme releases free ferrous iron from the protoporphyrin ring in hemin?

A

• Heme Oxygenase

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24
Q

How is heme transported into cells?

A

• Receptor-mediated endocytosis via Heme transporter

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25
Q

What is the role of Duodenal Cytochrome B (DCYTB) in iron metabolism?

A

• Reduce ferric iron to ferrous iron

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26
Q

What does Divalent Metal Transporter-1 (DMT-1) do?

A

• Ferrous iron enters enterocytes

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27
Q

What is the function of Ferroportin?

A

• Gateway from enterocyte to blood (ferrous)

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28
Q

How does Hepcidin regulate Ferroportin?

A

• Hepcidin regulates ferroportin

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29
Q

What is the role of Hephaestin in iron metabolism?

A

• Oxidizes ferrous to ferric iron

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30
Q

What are the mechanisms of iron scavenging in the body?

A
  • Intravascular hemolysis
  • Breakdown of red cells in the circulation
  • Free hemoglobin binds haptoglobins -> taken up by liver
  • Free heme binds hemopexin -> taken up by liver
  • Heme passing through the kidney is reabsorbed
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31
Q

Why has the body evolved to avoid iron deficiency?

A

• Historically iron deficiency is the disease we have evolved to avoid.

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32
Q

Is iron loss a regulated process?

A

• No, iron loss is an unregulated process

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33
Q

How does the body regulate iron loss?

A
  • No mechanisms to up- or down-regulate iron loss from the body
  • Over-intake cannot be matched by increased loss
  • Under intake cannot be matched by decreased loss
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34
Q

How is iron homeostasis maintained in the body?

A

• Iron homeostasis is regulated by adjusting iron intake

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35
Q

What are the physiological mechanisms of iron loss?

A
  • Cell loss: gut, desquamation
  • Menstruation (1mg/day)
  • Pregnancy
  • Lactation
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36
Q

What are the pathological mechanisms of iron loss?

A
  • Bleeding
  • Gut diseases
  • Menorrhagia
  • Surgery
  • Gross hematuria
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37
Q

What is required for iron homeostasis in a steady state?

A

• Intake of any element equals loss of that element (nitrogen, water, salt, iron)

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38
Q

How much iron is absorbed each day through the diet?

A

• 10 – 20 mg iron are absorbed each day

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39
Q

What percentage of dietary iron is absorbed?

A

• Only 10% of dietary iron absorbed

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40
Q

How much iron leaves the body each day in iron balance?

A

• 1 – 2 mg iron leaves the body each day

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41
Q

Where does iron absorption primarily occur in the digestive system?

A

• Occurs in the duodenum & upper jejunum

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42
Q

What are the two forms of dietary iron?

A

• Heme iron • Non-heme iron

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43
Q

What is Hepcidin and where is it synthesized?

A
  • 25 amino acid peptide
  • Chromosome 19
  • Hepatic bacteriocidal protein
  • Master iron regulatory hormone
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44
Q

What is the primary function of Hepcidin?

A
  • Inactivates ferroportin
  • Stops iron getting out of gut cells
  • Leads to decreased gut iron absorption
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45
Q

How does Hepcidin affect iron absorption?

A
  • Inactivates ferroportin
  • Stops iron getting out of gut cells
  • Leads to decreased gut iron absorption
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46
Q

What enzymes are required to oxidize iron for binding to transferrin during iron release from cells?

A
  • Hephaestin in gut
  • Ceruloplasmin in other cells
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47
Q

How does Hepcidin block iron release from cells?

A

• Hepcidin blocks iron release from all cells

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48
Q

What is the function of Transferrin?

A
  • Protein MW 77,000
  • Synthesized in the liver
  • Each molecule can bind two Fe3+ molecules (oxidized)
  • Contains 95% of serum Fe
  • Usually about 33% saturated with Fe * Production decreased in iron overload
  • Production increased in iron deficiency
  • Measured in blood as a marker of iron status
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49
Q

What is the molecular weight of Transferrin?

A

• Protein MW 77,000

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50
Q

Where is Transferrin synthesized?

A

• Synthesized in the liver.

51
Q

How many Fe3+ molecules can each Transferrin molecule bind?

A

• Each molecule can bind two Fe3+ molecules (oxidized)

52
Q

What percentage of serum iron is bound to Transferrin?

A

• Contains 95% of serum Fe

53
Q

What is the typical saturation percentage of Transferrin with iron?

A

• Usually about 33% saturated with Fe

54
Q

How does iron overload affect Transferrin production?

A

• Production decreased in iron overload

55
Q

How does iron deficiency affect Transferrin production?

A

• Production increased in iron deficiency

56
Q

What is the role of Transferrin Receptors in iron metabolism?

A
  • Collect iron from transferrin for uptake into cells
  • Recognizes and binds transferrin
  • Receptor + transferrin endocytosed * Iron released into the cell via Iron transporter (DMT1)
  • Receptor + transferrin return to the cell surface
  • Transferrin released
57
Q

What happens to Transferrin Receptors after binding Transferrin?

A
  • Receptor + transferrin endocytosed * Iron released into the cell via Iron transporter (DMT1)
  • Receptor + transferrin return to the cell surface
  • Transferrin released
58
Q

What are Soluble Transferrin Receptors?

A
  • Truncated form of cell surface receptors
  • Found in the circulation
  • High levels with iron deficiency
  • Low levels with iron overload
59
Q

When are Soluble Transferrin Receptor levels high?

A

• High levels with iron deficiency

60
Q

When are Soluble Transferrin Receptor levels low?

A

• Low levels with iron overload

61
Q

What is Ferritin and its molecular weight?

A

• Ferritin is an iron storage protein • Molecular weight: 460,000 Da

62
Q

Where is Ferritin primarily stored in the body?

A

• In the liver and nearly all other cells

63
Q

What percentage of body iron is stored in Ferritin?

A

• 20% iron by weight

64
Q

What is Hemosiderin?

A

• Partially degraded ferritin • Found intravascularly

65
Q

What laboratory tests are used to assess iron status?

A
  • Serum ferritin
  • Serum iron concentration
  • Total Iron Binding Capacity (TIBC)
  • Percent Iron Saturation
  • Bone Marrow/Liver biopsy
  • Serum transferrin receptor assay
  • Erythrocyte protoporphyrin test
66
Q

What does the serum iron concentration test measure?

A
  • Number of transferrin sites bound with iron
  • Over 95% of iron in serum bound to transferrin
  • Measures all serum iron (not in red cells)
67
Q

What conditions can cause low serum iron levels?

A
  • Iron deficiency
  • Other: random variation
  • Acute or chronic inflammation
  • Pre-menstrual
68
Q

What conditions can cause high serum iron levels?

A
  • Iron overload
  • Other: random variation
  • Pregnancy
  • Recent iron ingestion
69
Q

What is Transferrin Testing also known as?

A

• TIBC (Total Iron Binding Capacity)

70
Q

What does Transferrin Testing measure?

A
  • Total number of transferrin sites for iron binding
  • Also known as TIBC (Total Iron Binding Capacity)
71
Q

When are Transferrin levels high?

A
  • Low body iron stores
  • High estrogen states (pregnancy, oral contraceptive pills)
72
Q

When are Transferrin levels low?

A
  • High body iron stores
  • Malnutrition
  • Chronic liver disease
  • Chronic disease (e.g., malignancy)
  • Protein-losing states
  • Congenital deficiency
  • Neonates
  • Acute phase response (negative reactant)
73
Q

What does Percent Transferrin Saturation measure?

A
  • Percent of transferrin iron-binding sites filled with iron
  • % saturation = (serum iron/TIBC) x 100
74
Q

What does a high Percent Transferrin Saturation indicate?

A

• Iron overload

75
Q

What does the Ferritin blood test reflect?

A
  • Reflects iron stores
  • Low serum levels indicate iron deficiency
  • High serum levels indicate iron overload
76
Q

What conditions can cause high Ferritin levels besides iron overload?

A
  • Tissue release (hepatitis, leukemia, lymphoma)
  • Acute phase response (tissue damage, infection, cancer)
77
Q

What methods are used to measure serum iron concentration?

A

• Spectrophotometric method

78
Q

What methods are used to measure Unsaturated iron-binding capacity?

A

• Spectrophotometric method

79
Q

What methods are used to measure TIBC?

A
  • Chemical test (indirect)
  • Immunologic method (direct)
80
Q

What method is used to measure Ferritin?

A

• Immunologic method

81
Q

What method is used to measure Serum transferrin receptors?

A

• Immunologic method

82
Q

What does the RBC protoporphyrin test measure?

A
  • Measures excess protoporphyrin (Pp)
  • Uses Zn to react with free Pp * Uses hematofluorometer
83
Q

What is the Prussian Blue Stain used for in iron studies?

A

• To stain hemosiderin, siderocytes, and sideroblasts with blue coloration

84
Q

What do low hemoglobin levels indicate?

A
  • Low with iron deficiency
  • Anemia of chronic disease
85
Q

What is Iron Deficiency and what causes it?

A
  • Extremely common
  • Due to reduced intake
  • Increased loss
  • Increased demands
86
Q

What laboratory changes indicate iron deficiency?

A
  • Low iron
  • Low ferritin
  • Elevated Transferrin (TIBC)
  • Low transferrin saturation
  • Hypochromia
  • Microcytosis
  • Anemia
87
Q

What are the stages of Iron Deficiency?

A
  • Reduced iron stores
  • Iron deficient erythropoiesis
  • Iron deficient anemia
88
Q

What are common causes of Iron Deficiency?

A
  • Reduced intake
  • Increased loss
  • Increased demands such as obstetric causes
  • Malabsorption
  • Bowel cancer
  • Hemorrhoids
  • Inflammatory bowel disease
89
Q

What characterizes Anemia of Chronic Disease (ACD)?

A
  • Infection
  • Inflammation
  • Malignancy
  • Low iron absorption
  • Low serum iron
  • Stainable iron stores in RE cells
  • Increased hepcidin
  • Blocks iron in gut cells
  • Traps iron in macrophages and liver cells
  • Functional iron deficiency
  • Not responsive to iron therapy
  • Hard to separate from iron deficiency anemia
  • May co-exist
90
Q

How does Hepcidin affect iron metabolism in Anemia of Chronic Disease?

A
  • Increased hepcidin blocks iron release from gut cells
  • Traps iron in macrophages and liver cells
91
Q

How does Ferritin behave in Pure Iron Deficiency versus Acute Phase Response?

A
  • Low in Pure Iron Deficiency
  • Increased or normal in Acute Phase Response
92
Q

What are the differences between Pure Iron Deficiency and Acute Phase Response in terms of TIBC?

A
  • High TIBC in Pure Iron Deficiency
  • Normal or low TIBC in Acute Phase Response
93
Q

What laboratory markers are elevated in Acute Phase Response?

A
  • C-reactive protein (CRP)
  • Erythrocyte sedimentation rate (ESR)
94
Q

What is Genetic Hemochromatosis?

A

• An iron overload disease caused by increased iron absorption due to genetic mutations, primarily in the HFE gene

95
Q

What is the penetrance range of Genetic Hemochromatosis?

A

• 1 – 50%

96
Q

Why does Genetic Hemochromatosis have limited penetrance?

A

• It may require other genes to be involved along with environmental factors

97
Q

What is the most common genetic mutation associated with Genetic Hemochromatosis?

A

• C282Y mutation in the HFE gene

98
Q

How does Hepcidin relate to Genetic Hemochromatosis?

A
  • Genetic Hemochromatosis is associated with low hepcidin levels
  • Leads to overactivity of ferroportin
  • Increased iron absorption
99
Q

What are the types of Genetic Hemochromatosis based on genetic defects?

A
  • Type 1 – HFE defects
  • Type 2a – Haemojuvelin defects
  • Type 2b – Hepcidin defects
  • Type 3 – Transferrin receptor defects
  • Type 4 – Ferroportin defects
100
Q

What are the future treatment possibilities for iron-related disorders?

A
  • Treatment with hepcidin for iron overload
  • Blocking hepcidin for anemia of chronic disease
  • Diagnostic tests based on hepcidin
101
Q

What is the primary focus of managing Anemia of Chronic Disease?

A
  • Addressing the underlying chronic condition
  • Managing anemia, potentially with erythropoiesis-stimulating agents
102
Q

What is the primary focus of managing Genetic Hemochromatosis?

A

• Reducing iron overload, typically through phlebotomy or chelation therapy

103
Q

What are common symptoms of iron overload in Genetic Hemochromatosis?

A
  • Liver cirrhosis
  • Heart disease
  • Diabetes (bronze diabetes)
  • Joint pain
104
Q

What laboratory tests are used to diagnose Genetic Hemochromatosis?

A
  • Serum ferritin
  • Transferrin saturation
  • Genetic testing for HFE mutations
105
Q

How does the body conserve iron during intravascular hemolysis?

A
  • Free hemoglobin binds to haptoglobins
  • Free heme binds to hemopexin
  • Both are taken up by the liver
106
Q

What is the role of Cytochromes in iron metabolism?

A
  • Involved in oxidative phosphorylation
  • Essential for energy production
107
Q

What enzyme is involved in the conversion of hydrogen peroxide to free radicals in iron toxicity?

A

• Iron catalyzes the conversion, often involving peroxidase enzymes

108
Q

What is the relationship between Iron Absorption and Iron Loss?

A
  • Iron homeostasis is maintained by balancing iron intake with iron loss
  • There are no regulated mechanisms to directly control iron loss
109
Q

What is the main cause of increased mortality in Genetic Hemochromatosis?

A

• Cirrhosis and liver disease

110
Q

What are some other sources of iron besides hemoglobin, myoglobin, and serum?

A
  • Peroxidase
  • Catalase
  • Cytochromes
  • Fiboflavin enzymes
  • Transferrin
111
Q

What is the role of Hemojuvelin in iron metabolism?

A

• Involved in the regulation of hepcidin production

112
Q

What happens to iron when hepcidin levels are increased?

A
  • Iron is trapped in macrophages and liver cells
  • Iron absorption from the gut is decreased
113
Q

What is the role of Hephaestin in iron metabolism?

A

• Oxidizes ferrous iron to ferric iron, allowing it to bind to transferrin

114
Q

How does Ferroportin function in iron transport?

A

• Exports ferrous iron from cells into the bloodstream

115
Q

What is the function of Transferrin Receptors on cell surfaces?

A
  • Bind transferrin-iron complexes
  • Mediate their uptake into cells
116
Q

What distinguishes Soluble Transferrin Receptors from membrane-bound Transferrin Receptors?

A
  • Soluble Transferrin Receptors are truncated forms found in circulation
  • Can indicate iron status
117
Q

What is the significance of a high level of Soluble Transferrin Receptors?

A

• Indicates iron deficiency

118
Q

What is the significance of a low level of Soluble Transferrin Receptors?

A

• Indicates iron overload

119
Q

What method is used to measure Serum Ferritin?

A

• Immunologic method

120
Q

What is Prussian Blue Stain used for in iron studies?

A

• To stain hemosiderin, siderocytes, and sideroblasts with blue coloration

121
Q

What does a bone marrow biopsy show in iron deficiency?

A

• Low bone marrow iron

122
Q

What is the relationship between Mean Cell Volume and iron status?

A

• Low Mean Cell Volume is seen in iron deficiency and thalassemia

123
Q

What are the common laboratory changes in Anemia of Chronic Disease?

A
  • Low hemoglobin
  • Low serum iron
  • Increased ferritin
  • Low TIBC
  • Low transferrin saturation
124
Q

How does Anemia of Chronic Disease differ from Pure Iron Deficiency?

A
  • ACD has increased ferritin and decreased TIBC due to inflammation
  • Pure Iron Deficiency has low ferritin and increased TIBC