Iron Metabolism Flashcards
What is iron used for in the body?
– Transports and stores oxygen
– Integral part of many enzymes
including energy metabolism, neurotransmitter production, collagen formation and immune system function
Why is iron content in the body carefully controlled?
Have no mechanism for excreting iron – must maintain a fine balance between absorption and loss
Name the sites containing active iron in the body
��-- Haemoglobin �-- Myoglobin: oxygen reserve in muscles ��--Tissue Iron: enzyme systems, cytochromes ��-- Transported iron-’serum iron’
Give two inactive stores of iron
�Ferritin – soluble
��Haemosiderin – Macrophage iron, Insoluble
Where do you find the majority of iron in the body?
Most in haemoglobin
Stores of iron (liver)
Less in myoglobin
Where is haem iron and non-heam iron found in the diet?
Haem iron – meat
Non-haem iron – cereal and vegetables
What are the two form of iron and which is the correct form to be absorbed by the body?
Fe2+ – ferrous form in meat, easier to absorb
Fe3+ – ferric form in veg and cereals must be reduced by stomach acid to be absorbed
Where does the majority of iron absorption take place?
What facilitates this in the apical surface?
Duodenum and upper jejunum by enterocytes (epithelial cells in jejunum and duodenum)
Transferrin brings two Fe molecules in per transferrin
What protein exports iron out of the blood?
ferrroportin
Describe the process of iron absorption into enterocytes
Stomach acid reduces Fe3+ to Fe2+
Transferrin transports two Fe2+ into enterocytes by endocytosis. Can be stored in RBC as ferritin.
Then enters blood by ferroportin, where it is transported to the liver for storage or used by Hb
What affect does vitamin C have on iron absorption?
Enhances iron absorption
How is iron taken into red blood cells?
by binding of Iron-transferrin complex to transferrin receptor (TfR)
Erythroid cells contain the highest number of TfRs
What can be used as a good level of functional iron levels?
soluble TfR (sTfR) is a good indicator of functional iron levels
What does the regulation of iron absorption depend on?
dietary factors, body iron stores and erythropoiesis
What are the major mechanisms for the control of iron absorption?
Transporter regulation (can be up or down regulated)
Receptor expression
Crosstalk between epithelial cells and macrophages (other cells)
Hepcidin – tissue derived factor
What does hepcidin do?
– negative regulator of iron absorption
by degrading ferroportin, a protein involved in moving iron out of cells
This prevents iron absorption from gut ane iron release from macrophages
Describe hepcidin synthesis
– Secreted by the liver and excreted by the kidneys
�– Synthesis increased in iron overload
��– Transgenic mice constructed to over-express hepcidin died shortly after birth with iron deficiency (negative regulator)
��– Hepcidin production is decreased by high erythropoietic activity
Where dose the majority of the iron in the body come from?
Recycling of iron in body (RBC) accounts for about 80%
How do macrophages acquire iron?
Macrophages ‘eat’ old senescent RBCs
Why are iron deficiencies important to recognise?
Most common nutritional disorder worldwide Is a symptom of: 1. Insufficient intake/poor absorption 2. Increased use -- physiological eg pregnancy -- pathological eg bleeding
What are some physiological affects of anaemia?
tiredness reduced oxygen carrying capacity (pallour, reduced exercise tolerance) CCF shortness of breath palpitations
How can you confirm iron deficiency?
– Low Hb
– Small RBC and low MCV (mean cell volume)
��– Pencil cells, hypchromia, microcytosis, target cells
��– Low serum ferritin, serum iron (transferrin bound iron) and %transferrin saturation, raised TIBC (total iron binding capacity, measures transferrin levels)
Why is serum ferritin important to look at?
Correlates with stores of iron in the body
What is the most important thing to measure in iron deficiency?
Ferritin is the single most important measure of iron status
Reduced levels –> iron deficiency
High/normal levels –> don’t rule out iron deficiency
When can ferritin levels be increased?
ferritin increased with acute or chronic
inflammation, malignancy, liver disease, and
alcoholism
What are the main methods of iron replacement?
– Oral, Diet
– Supplements……
Iron replacement
����– Intravenous – anaphylaxis
����– Intramuscular
Describe the pathology of iron excess
Exceeds binding capacity of transferrin
– increased free iron in the blood which is dangerous as it can produce free radical which damage lipid, protein, DNA etc
Define haemachromotosis
– Disorder of iron excess resulting in end organ damage
Causes c��irrhosis, diabetes mellitus, hypogonadism, cardiomyopathy, and arthropathy and skin pigmentation
��– Normal body iron 2-3g; damage when reaches 10-15g
Describe hereditary haemochromotosis
Autosomal recessive
Four genes can cause it while three interact normally
Treat with venesection (remove blood to remove iron then retransfuse in)
What is transfusion associated aemosiderosis?
Transfusion dependent anaemias such as
thalassaemia, myelodysplasia
There is a gradual accumulation of iron
Treat with iron chelating agents eg desferrioxamine which delay but don’t stop inevitable effects of iron overload
Give some tests which can confirm iron overload
– Raised serumferritin
��– Increased % transferrin saturation
����– Genetic testing for mutations of HFE gene
��– Evidence parenchymal iron overload on liver biopsy
��– Amount of iron removed by venesection
