IRON Flashcards
1
Q
What is the chemical symbol for Iron?
A
Fe
2
Q
What is the atomic number of Iron?
A
26
3
Q
What is the molecular weight of Iron?
A
56
4
Q
In which oxidation states can Iron exist?
A
• 2+ • 3+
5
Q
What is Ferrous iron and what does it indicate?
A
• Ferrous (2+) “reduced” - gained an electron
6
Q
What is Ferric iron and what does it indicate?
A
• Ferric (3+) “oxidized” - lost an electron
7
Q
Why is a redox change required for Iron metabolism?
A
• Redox change is required for iron metabolism
8
Q
What is the total body iron content?
A
• Body iron content: 3-4 g
9
Q
What percentage of the body’s iron is found in hemoglobin?
A
• Hb iron: 70%
10
Q
What percentage of the body’s iron is stored iron?
A
• Storage iron: 25%
11
Q
What forms of storage iron exist in the body?
A
- Ferritin
- Hemosiderin
12
Q
What percentage of iron is found in myoglobin?
A
• Myoglobin iron: 5%
13
Q
What percentage of iron comes from other sources in the body?
A
• Other sources: <1%
14
Q
What are the other sources of iron in the body?
A
- Peroxidase
- Catalase
- Cytochromes
- Fiboflavin enzymes
- Transferrin
15
Q
What percentage of body iron is found in serum?
A
• Serum: 0.1%
16
Q
What are the oxygen-related functions of iron?
A
• Oxygen carriers • Hemoglobin • Oxygen storage • Myoglobin
17
Q
What role does iron play in energy production?
A
- Cytochromes (oxidative phosphorylation)
- Krebs cycle enzymes
18
Q
What is the role of iron in liver detoxification?
A
• Liver detoxification (cytochrome p450)
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
20
Q
What health issues can result from iron excess?
A
- Iron excess (overload) possibly related to cancers
- Cardiac toxicity
21
Q
What are the possible causes of iron deficiency?
A
- Excessive bleeding
- Inadequate intake
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
23
Q
What enzyme releases free ferrous iron from the protoporphyrin ring in hemin?
A
• Heme Oxygenase
24
Q
How is heme transported into cells?
A
• Receptor-mediated endocytosis via Heme transporter
25
What is the role of Duodenal Cytochrome B (DCYTB) in iron metabolism?
• Reduce ferric iron to ferrous iron
26
What does Divalent Metal Transporter-1 (DMT-1) do?
• Ferrous iron enters enterocytes
27
What is the function of Ferroportin?
• Gateway from enterocyte to blood (ferrous)
28
How does Hepcidin regulate Ferroportin?
• Hepcidin regulates ferroportin
29
What is the role of Hephaestin in iron metabolism?
• Oxidizes ferrous to ferric iron
30
What are the mechanisms of iron scavenging in the body?
* 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
31
Why has the body evolved to avoid iron deficiency?
• Historically iron deficiency is the disease we have evolved to avoid.
32
Is iron loss a regulated process?
• No, iron loss is an unregulated process
33
How does the body regulate iron loss?
* 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
34
How is iron homeostasis maintained in the body?
• Iron homeostasis is regulated by adjusting iron intake
35
What are the physiological mechanisms of iron loss?
* Cell loss: gut, desquamation
* Menstruation (1mg/day)
* Pregnancy
* Lactation
36
What are the pathological mechanisms of iron loss?
* Bleeding
* Gut diseases
* Menorrhagia
* Surgery
* Gross hematuria
37
What is required for iron homeostasis in a steady state?
• Intake of any element equals loss of that element (nitrogen, water, salt, iron)
38
How much iron is absorbed each day through the diet?
• 10 – 20 mg iron are absorbed each day
39
What percentage of dietary iron is absorbed?
• Only 10% of dietary iron absorbed
40
How much iron leaves the body each day in iron balance?
• 1 – 2 mg iron leaves the body each day
41
Where does iron absorption primarily occur in the digestive system?
• Occurs in the duodenum & upper jejunum
42
What are the two forms of dietary iron?
• Heme iron • Non-heme iron
43
What is Hepcidin and where is it synthesized?
* 25 amino acid peptide
* Chromosome 19
* Hepatic bacteriocidal protein
* Master iron regulatory hormone
44
What is the primary function of Hepcidin?
* Inactivates ferroportin
* Stops iron getting out of gut cells
* Leads to decreased gut iron absorption
45
How does Hepcidin affect iron absorption?
* Inactivates ferroportin
* Stops iron getting out of gut cells
* Leads to decreased gut iron absorption
46
What enzymes are required to oxidize iron for binding to transferrin during iron release from cells?
* Hephaestin in gut
* Ceruloplasmin in other cells
47
How does Hepcidin block iron release from cells?
• Hepcidin blocks iron release from all cells
48
What is the function of Transferrin?
* 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
49
What is the molecular weight of Transferrin?
• Protein MW 77,000
50
Where is Transferrin synthesized?
• Synthesized in the liver.
51
How many Fe3+ molecules can each Transferrin molecule bind?
• Each molecule can bind two Fe3+ molecules (oxidized)
52
What percentage of serum iron is bound to Transferrin?
• Contains 95% of serum Fe
53
What is the typical saturation percentage of Transferrin with iron?
• Usually about 33% saturated with Fe
54
How does iron overload affect Transferrin production?
• Production decreased in iron overload
55
How does iron deficiency affect Transferrin production?
• Production increased in iron deficiency
56
What is the role of Transferrin Receptors in iron metabolism?
* 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
What happens to Transferrin Receptors after binding Transferrin?
* Receptor + transferrin endocytosed * Iron released into the cell via Iron transporter (DMT1)
* Receptor + transferrin return to the cell surface
* Transferrin released
58
What are Soluble Transferrin Receptors?
* Truncated form of cell surface receptors
* Found in the circulation
* High levels with iron deficiency
* Low levels with iron overload
59
When are Soluble Transferrin Receptor levels high?
• High levels with iron deficiency
60
When are Soluble Transferrin Receptor levels low?
• Low levels with iron overload
61
What is Ferritin and its molecular weight?
• Ferritin is an iron storage protein • Molecular weight: 460,000 Da
62
Where is Ferritin primarily stored in the body?
• In the liver and nearly all other cells
63
What percentage of body iron is stored in Ferritin?
• 20% iron by weight
64
What is Hemosiderin?
• Partially degraded ferritin • Found intravascularly
65
What laboratory tests are used to assess iron status?
* 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
What does the serum iron concentration test measure?
* 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
What conditions can cause low serum iron levels?
* Iron deficiency
* Other: random variation
* Acute or chronic inflammation
* Pre-menstrual
68
What conditions can cause high serum iron levels?
* Iron overload
* Other: random variation
* Pregnancy
* Recent iron ingestion
69
What is Transferrin Testing also known as?
• TIBC (Total Iron Binding Capacity)
70
What does Transferrin Testing measure?
* Total number of transferrin sites for iron binding
* Also known as TIBC (Total Iron Binding Capacity)
71
When are Transferrin levels high?
* Low body iron stores
* High estrogen states (pregnancy, oral contraceptive pills)
72
When are Transferrin levels low?
* 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
What does Percent Transferrin Saturation measure?
* Percent of transferrin iron-binding sites filled with iron
* % saturation = (serum iron/TIBC) x 100
74
What does a high Percent Transferrin Saturation indicate?
• Iron overload
75
What does the Ferritin blood test reflect?
* Reflects iron stores
* Low serum levels indicate iron deficiency
* High serum levels indicate iron overload
76
What conditions can cause high Ferritin levels besides iron overload?
* Tissue release (hepatitis, leukemia, lymphoma)
* Acute phase response (tissue damage, infection, cancer)
77
What methods are used to measure serum iron concentration?
• Spectrophotometric method
78
What methods are used to measure Unsaturated iron-binding capacity?
• Spectrophotometric method
79
What methods are used to measure TIBC?
* Chemical test (indirect)
* Immunologic method (direct)
80
What method is used to measure Ferritin?
• Immunologic method
81
What method is used to measure Serum transferrin receptors?
• Immunologic method
82
What does the RBC protoporphyrin test measure?
* Measures excess protoporphyrin (Pp)
* Uses Zn to react with free Pp * Uses hematofluorometer
83
What is the Prussian Blue Stain used for in iron studies?
• To stain hemosiderin, siderocytes, and sideroblasts with blue coloration
84
What do low hemoglobin levels indicate?
* Low with iron deficiency
* Anemia of chronic disease
85
What is Iron Deficiency and what causes it?
* Extremely common
* Due to reduced intake
* Increased loss
* Increased demands
86
What laboratory changes indicate iron deficiency?
* Low iron
* Low ferritin
* Elevated Transferrin (TIBC)
* Low transferrin saturation
* Hypochromia
* Microcytosis
* Anemia
87
What are the stages of Iron Deficiency?
* Reduced iron stores
* Iron deficient erythropoiesis
* Iron deficient anemia
88
What are common causes of Iron Deficiency?
* Reduced intake
* Increased loss
* Increased demands such as obstetric causes
* Malabsorption
* Bowel cancer
* Hemorrhoids
* Inflammatory bowel disease
89
What characterizes Anemia of Chronic Disease (ACD)?
* 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
How does Hepcidin affect iron metabolism in Anemia of Chronic Disease?
* Increased hepcidin blocks iron release from gut cells
* Traps iron in macrophages and liver cells
91
How does Ferritin behave in Pure Iron Deficiency versus Acute Phase Response?
* Low in Pure Iron Deficiency
* Increased or normal in Acute Phase Response
92
What are the differences between Pure Iron Deficiency and Acute Phase Response in terms of TIBC?
* High TIBC in Pure Iron Deficiency
* Normal or low TIBC in Acute Phase Response
93
What laboratory markers are elevated in Acute Phase Response?
* C-reactive protein (CRP)
* Erythrocyte sedimentation rate (ESR)
94
What is Genetic Hemochromatosis?
• An iron overload disease caused by increased iron absorption due to genetic mutations, primarily in the HFE gene
95
What is the penetrance range of Genetic Hemochromatosis?
• 1 – 50%
96
Why does Genetic Hemochromatosis have limited penetrance?
• It may require other genes to be involved along with environmental factors
97
What is the most common genetic mutation associated with Genetic Hemochromatosis?
• C282Y mutation in the HFE gene
98
How does Hepcidin relate to Genetic Hemochromatosis?
* Genetic Hemochromatosis is associated with low hepcidin levels
* Leads to overactivity of ferroportin
* Increased iron absorption
99
What are the types of Genetic Hemochromatosis based on genetic defects?
* Type 1 – HFE defects
* Type 2a – Haemojuvelin defects
* Type 2b – Hepcidin defects
* Type 3 – Transferrin receptor defects
* Type 4 – Ferroportin defects
100
What are the future treatment possibilities for iron-related disorders?
* Treatment with hepcidin for iron overload
* Blocking hepcidin for anemia of chronic disease
* Diagnostic tests based on hepcidin
101
What is the primary focus of managing Anemia of Chronic Disease?
* Addressing the underlying chronic condition
* Managing anemia, potentially with erythropoiesis-stimulating agents
102
What is the primary focus of managing Genetic Hemochromatosis?
• Reducing iron overload, typically through phlebotomy or chelation therapy
103
What are common symptoms of iron overload in Genetic Hemochromatosis?
* Liver cirrhosis
* Heart disease
* Diabetes (bronze diabetes)
* Joint pain
104
What laboratory tests are used to diagnose Genetic Hemochromatosis?
* Serum ferritin
* Transferrin saturation
* Genetic testing for HFE mutations
105
How does the body conserve iron during intravascular hemolysis?
* Free hemoglobin binds to haptoglobins
* Free heme binds to hemopexin
* Both are taken up by the liver
106
What is the role of Cytochromes in iron metabolism?
* Involved in oxidative phosphorylation
* Essential for energy production
107
What enzyme is involved in the conversion of hydrogen peroxide to free radicals in iron toxicity?
• Iron catalyzes the conversion, often involving peroxidase enzymes
108
What is the relationship between Iron Absorption and Iron Loss?
* Iron homeostasis is maintained by balancing iron intake with iron loss
* There are no regulated mechanisms to directly control iron loss
109
What is the main cause of increased mortality in Genetic Hemochromatosis?
• Cirrhosis and liver disease
110
What are some other sources of iron besides hemoglobin, myoglobin, and serum?
* Peroxidase
* Catalase
* Cytochromes
* Fiboflavin enzymes
* Transferrin
111
What is the role of Hemojuvelin in iron metabolism?
• Involved in the regulation of hepcidin production
112
What happens to iron when hepcidin levels are increased?
* Iron is trapped in macrophages and liver cells
* Iron absorption from the gut is decreased
113
What is the role of Hephaestin in iron metabolism?
• Oxidizes ferrous iron to ferric iron, allowing it to bind to transferrin
114
How does Ferroportin function in iron transport?
• Exports ferrous iron from cells into the bloodstream
115
What is the function of Transferrin Receptors on cell surfaces?
* Bind transferrin-iron complexes
* Mediate their uptake into cells
116
What distinguishes Soluble Transferrin Receptors from membrane-bound Transferrin Receptors?
* Soluble Transferrin Receptors are truncated forms found in circulation
* Can indicate iron status
117
What is the significance of a high level of Soluble Transferrin Receptors?
• Indicates iron deficiency
118
What is the significance of a low level of Soluble Transferrin Receptors?
• Indicates iron overload
119
What method is used to measure Serum Ferritin?
• Immunologic method
120
What is Prussian Blue Stain used for in iron studies?
• To stain hemosiderin, siderocytes, and sideroblasts with blue coloration
121
What does a bone marrow biopsy show in iron deficiency?
• Low bone marrow iron
122
What is the relationship between Mean Cell Volume and iron status?
• Low Mean Cell Volume is seen in iron deficiency and thalassemia
123
What are the common laboratory changes in Anemia of Chronic Disease?
* Low hemoglobin
* Low serum iron
* Increased ferritin
* Low TIBC
* Low transferrin saturation
124
How does Anemia of Chronic Disease differ from Pure Iron Deficiency?
* ACD has increased ferritin and decreased TIBC due to inflammation
* Pure Iron Deficiency has low ferritin and increased TIBC
