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Haematology Lectures > L.6 Iron Metabolism > Flashcards

L.6 Iron Metabolism Flashcards

1
Q

What is the site in the Hb molecule to which oxygen reversibly binds?

A

Iron held at the centre of the porphyrin ring

This is crucial for oxygen transport in the blood.

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2
Q

What are the two forms of iron supplied in the diet?

A
  • Haem iron
  • Non-Haem iron

These forms differ in their sources and absorption characteristics.

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3
Q

What is Haem iron derived from?

A

Hb and myoglobin from food of animal origin

Haem iron is in the Ferrous (Fe++) form.

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4
Q

What is the form of Non-Haem iron?

A

Ferric (Fe+++) form

It must be converted to the ferrous form before absorption.

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5
Q

How is Non-Haem iron reduced for absorption?

A

It is reduced in the stomach due to its acid environment

This reduction is necessary for its conversion to the absorbable ferrous form.

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6
Q

What is the approximate daily iron intake recommended for a healthy diet?

A

15mg iron/day

This amount is necessary to meet the body’s requirements.

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7
Q

How much iron does the body need to absorb daily?

A

1-2 mg/day

This is to compensate for daily losses.

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8
Q

List sources of dietary iron.

A
  • Red meat
  • Liver
  • Green vegetables
  • Poultry
  • Dried fruit

These foods contribute to the dietary iron intake.

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9
Q

What type of iron is absorbed more rapidly?

A

Organic iron in haem form (Fe2+)

This form is found in red meat and liver.

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10
Q

What type of iron is found in vegetable matter?

A

Inorganic iron (Fe3+ form)

This form is less easily absorbed compared to organic iron.

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11
Q

What substances increase iron absorption?

A
  • Ascorbic acid
  • Muscle protein

They increase absorption by reducing ferric iron to ferrous iron.

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12
Q

What substance can inhibit iron absorption?

A

Caffeine

This can negatively affect the amount of iron the body can take in.

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13
Q

How much iron does the typical adult human body contain?

A

About 3-5 grams of iron

This iron is crucial for various bodily functions.

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14
Q

What are the vital functions of iron in the body?

A
  • Synthesis of haem
  • Synthesis of myoglobin
  • Synthesis of cytochromes
  • Co-factor in DNA synthesis
  • Connective tissue production

Iron plays multiple essential roles in biological processes.

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15
Q

What happens when there is excessive iron in the body?

A

It is toxic to the body

This toxicity can lead to various health issues.

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16
Q

Where is iron primarily found in the body?

A
  • Red blood cells (RCs)
  • Macrophages
  • Hepatocytes
  • Enterocytes

These cells are key sites for iron storage and utilization.

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17
Q

How much iron is lost from the body per day?

A

1-2 mg of iron

Loss occurs through blood loss, urine, feces, or sloughed mucosal epithelial cells.

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18
Q

What must be done to replace lost iron?

A

It must be replaced through the diet

This is essential to maintain healthy iron levels.

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19
Q

What increases the efficiency of intestinal absorption of iron?

A

Accelerated erythropoietic activity and depletion of body iron stores

This is a physiological response to increased demand for red blood cell production.

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20
Q

What factors result in accelerated erythrocyte production?

A

Bleeding, hypoxia, and haemolysis

These conditions signal the body to produce more red blood cells to compensate for loss or low oxygen levels.

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21
Q

What can lead to excess iron in various organs?

A

Increased iron uptake in extravascular haemolysis and anaemias with ineffective erythropoiesis

The body does not lose iron from erythrocytes that are haemolyzed in vivo, leading to accumulation.

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22
Q

What is the primary determinant of total body iron homeostasis?

A

Balancing and linking the absorption of iron by the enterocytes of the duodenum with total body requirements

This ensures that iron levels meet the physiological needs of the body.

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23
Q

What are the components of positive iron balance?

A

Iron intake = heme iron + non-heme iron; Iron supplementation = oral iron, IV iron

Positive iron balance occurs when intake meets or exceeds the body’s needs.

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24
Q

What factors contribute to negative iron balance?

A
  • Iron losses: menstruation, surgery, trauma, bleeding, GI bleeding
  • Increased iron requirements: athletes, pregnancy, growth + development
  • Poor absorption: consumption of tannins/calcium, low stomach acid, small intestinal bacteria

Negative iron balance occurs when iron losses or requirements exceed intake.

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25
How is iron balance controlled in the body?
At the level of iron absorption in the duodenum and jejunum ## Footnote There is no physiological mechanism for excretion of iron, making absorption regulation critical.
26
What modifies the control of iron balance?
* Availability of iron in the body * Blood oxygen content/hypoxia * Blood haemoglobin concentration * EPO activity in bone marrow/rate of erythropoiesis * Inflammation can minimise iron availability ## Footnote These factors influence how much iron is absorbed based on the body's needs.
27
What can cause iron excess in the body?
* Dietary excess (over supplementation) * Inherited protein defect (haemochromatosis) * Anaemia (ineffective erythropoiesis) * Iatrogenic (Red Cell Transfusions) ## Footnote Excess iron can result from both external factors and internal dysfunctions.
28
What is the master iron regulating protein?
Hepcidin ## Footnote Regulates iron recycling and balance via interaction with ferroportin-1.
29
What protein transports iron across the enterocyte apical plasma membrane?
DMT1 ## Footnote Divalent metal transporter-1 is responsible for this transport.
30
What is the function of DCytB in iron absorption?
Reduces Fe3+ to Fe2+ at enterocyte border ## Footnote This is crucial for iron absorption.
31
What is Ferroportin-1's role in iron homeostasis?
Transports iron across the basolateral membrane of the enterocyte ## Footnote Ferroportin-1 is the only known cellular exporter of iron.
32
What does Hephaestin do?
Facilitates cellular export of iron & oxidizes Fe2+ to Fe3+ for binding to apotransferrin ## Footnote This process is essential for iron transport in the bloodstream.
33
What is the role of the Transferrin Receptor (TfR)?
Binds transferrin to cell for internalization of iron ## Footnote This process is vital for cellular iron uptake.
34
What does HFE interact with to regulate iron uptake?
TfR ## Footnote This interaction regulates the receptor's affinity for transferrin.
35
What is the primary function of Transferrin?
Transports iron around the blood ## Footnote Transferrin is a key protein in iron transport.
36
What regulates hepcidin expression?
Hemojuvelin ## Footnote Hemojuvelin is important for iron homeostasis.
37
What are the two forms of dietary iron?
Non-heme and Heme iron ## Footnote Non-heme is found in vegetables, while heme is present in red meats.
38
What role does gastric acid play in iron absorption?
Solubilizes ferric (Fe3+) form of iron ## Footnote Provides an acidic environment that facilitates transport across the enterocyte membrane.
39
How is ferric iron (Fe3+) reduced to ferrous iron (Fe2+)?
By the action of DcytB at the brush border ## Footnote DcytB is a ferric reductase on the surface of enterocytes.
40
What happens to iron in the enterocyte after it is transported across the plasma membrane?
It can be stored as ferritin or transported into the plasma ## Footnote This storage or transport is crucial for maintaining iron levels in the body.
41
What happens to the iron stored as ferritin when the enterocyte is sloughed off?
It is lost into the intestinal tract ## Footnote This is a natural process in the lifecycle of enterocytes.
42
What enzyme releases haem iron from haem?
Haemoxygenase-1 ## Footnote This enzyme is crucial for the availability of haem iron for absorption.
43
How is the movement of iron into plasma regulated?
By Hepcidin ## Footnote Hepcidin controls the expression of ferroportin, regulating iron export from various cells.
44
What is the ferrous form of iron exported from enterocytes by?
Ferroportin
45
What converts ferrous iron (Fe2+) into ferric iron (Fe3+)?
Hephaestin and caeruloplasmin
46
What is the primary carrier protein for transporting iron in plasma?
Transferrin
47
When free of iron, transferrin is called _______.
Apotransferrin
48
What is transferrin bound to iron termed?
Transferrin
49
Iron is best transported as _______ iron (Fe3+).
Ferric
50
What proteins convert ferrous iron (Fe2+) to ferric iron (Fe3+)?
Ferroxidases (Ceruloplasmin and Hephaestin)
51
Where does transferrin deliver iron?
Bone marrow
52
What is the function of transferrin in the plasma?
Mediates iron exchange between tissues
53
Is transferrin lost in delivering iron to cells?
No, it returns to plasma and is reused
54
What percentage of iron from degraded hemoglobin is recycled to the plasma?
Approx 85%
55
Transferrin can be used as an indication of _______ status.
Body iron
56
Transferrin is also termed the _______.
Total iron binding capacity (TIBC)
57
What does the saturation of transferrin with high levels of iron stimulate?
Hepcidin release
58
What effect does hepcidin release have on iron levels?
Reduces iron passing from intestines to blood
59
What percentage of serum iron is complexed with transferrin?
95%
60
What is the transferrin saturation formula?
Serum iron/TIBC x 100%
61
What is the saturation level of transferrin with iron?
One third
62
How does the Iron-Transferrin complex enter developing RBCs?
By receptor mediated endocytosis attaching to TfR on the RC membrane
63
Where is iron incorporated into the haem molecule?
In the mitochondria
64
What percentage of iron taken into developing erythroblasts is converted to haem within 1 hour?
80 – 90%
65
What happens to excess iron taken up by developing erythroblasts?
Stored as Ferritin
66
What is the function of Apotransferrin after releasing its iron?
Exits RBC and returns to plasma to collect more iron
67
How does TfR expression respond to changes in iron status?
Down-regulated by high iron conditions and up-regulated on iron depletion
68
What are soluble TFR (sTfR) and their significance?
Transferrin receptors shed from red cell membrane indicating increased erythropoiesis
69
Where is iron stored when not immediately required by developing RC?
In the BM, liver, pancreas, and spleen
70
What is the primary storage depot for iron?
The liver
71
What are the storage forms of iron?
* Ferritin * Haemosiderin
72
How is Haemosiderin formed?
From aggregates of ferritin
73
Where is Hemosiderin primarily found?
In macrophages
74
How can storage iron in the form of haemosiderin be estimated?
In bone marrow sections
75
What is the release rate of iron from Haemosiderin?
Slow, considered long term storage of iron
76
What is Ferritin?
The primary iron storage protein
77
Where is Ferritin found?
In the bone marrow, liver, spleen within vesicles called siderosomes
78
What do plasma levels of ferritin indicate?
Iron status
79
Can Ferritin be visualized by unstained light microscopy?
No, but can be seen using iron stains
80
What is the relationship between Ferritin and inflammation?
Ferritin is an acute phase protein and may be increased in inflammation
81
Why is Ferritin not a reliable indicator of iron status in the presence of inflammation?
Because levels rise in response to inflammatory states
82
What other conditions can increase Ferritin levels?
* Kidney disease * Liver disease * Malignancy
83
What is hepcidin?
A 25 AA peptide coded by the HAMP gene on Ch19
84
Where is hepcidin produced?
In the liver
85
What does hepcidin control?
The expression of ferroportin, which controls the export of iron
86
What happens when iron stores are adequate?
Hepcidin decreases absorption and/or transfer of iron by inhibiting ferroportin-1
87
What effect does hepcidin have on macrophages?
It blocks the export of iron stored in macrophages
88
What occurs when total body iron is low?
Downregulation of hepcidin permits increased iron absorption
89
What induces hepcidin synthesis?
An excess of iron
90
What inhibits hepcidin synthesis?
Lack of iron
91
What additional factors control hepcidin synthesis?
Anaemia and hypoxia
92
How can infection and inflammation affect hepcidin?
They can affect hepcidin synthesis
93
How does hepcidin decrease iron absorption?
By inhibiting the expression of genes involved in the uptake or transfer of iron (e.g., DMT1, DcytB)
94
What happens during dietary iron deficiency?
Hepcidin release is blocked; DMT1, DcytB, and ferroportin are upregulated
95
List factors resulting in high hepcidin.
* Chronic kidney disease * Dialysis * Genetic factors * Infectious/inflammatory disease * Intravenous/oral iron administration * Red blood cell transfusions * Reduced glomerulofiltration rate * Replete iron stores
96
List factors leading to low hepcidin.
* Alcohol abuse * Anaemia * Chronic hepatitis C virus infection * Chronic liver disease * Erythropoiesis stimulating agents * Epo * Hypoxia * Ineffective/expanded erythropoiesis * Genetic factors * Oestrogens * Testosterone
97
What is the first step of hepcidin action when iron levels are adequate?
Liver stores full of iron
98
What happens after hepcidin is produced when iron levels are adequate?
Hepcidin binds ferroportin
99
What occurs to membrane ferroportin when hepcidin binds it?
It is internalized back into enterocyte and digested by lysosomes
100
What is the result of ferroportin inactivation?
Decreased iron absorption
101
What is the first step of hepcidin action when iron levels are low?
Increased demand for iron (e.g., IDA, hypoxia, increased erythropoietic activity)
102
What happens to hepcidin production when iron levels are low?
Hepcidin production is decreased
103
How is the rate of iron absorption related to erythropoiesis?
Directly related to demands of erythropoiesis
104
What increases when hepcidin production is low?
Increased absorption of iron into plasma and increased activity of ferroportin

Haematology Lectures (14 decks)

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