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Micronutrients :
(intake does not exceed 100 mg daily)
Daily intake Body stores
10 mg 2.5 mg 1-2 mg
2.5 grams of total body iron exist as haemoglobin Only 1-2 mg of iron is taken up daily from the diet (which contains 10-20mg iron)
Only 1 mg of iron is lost daily from the body (about 0.025% of total body iron) nonspecific pathways (sloughing of dead cells, iron excretion in bile)
In women, additional 30 mg of iron is lost monthly by menstruation (about 1% of total body iron)
There is no special pathway for iron excretion The amount of total body iron is determined only at the level of iron uptake from the duodenum
1) Haemoproteins
Porphyrins:
They are intensely red Under ultraviolet light, they display very strong red fluorescence Accumulation of porphyrins is harmful, and results in rare inherited diseases called porphyrias Porphyrin plus iron gives Haem Heme is an exceptional porphyrin compound: HAEM IS NOT FLUORESCENT
Porphyrin
Haem
Iron in Haemoproteins
Cytochromes of the mitochondrial respiratory chain (100 mg of iron) Haemoglobin: more than one half of total body iron (2.5 grams) Myoglobin: about 0.3 grams Fe, muscle oxygen storage protein
Cytochrome P450: most abundant haemoprotein of the liver (about 1 mg) detoxifies foreign compounds
Ferritin:
iron storage protein. In men, contains up to 1 gram of iron
450 kDa protein consisting of 24 subunits Inside the ferritin shell, iron ions form crystallites together with phosphate and hydroxide ions. The resulting particle is similar to the mineral ferrihydrite. Each ferritin complex can store about 4500 iron (Fe3+) ions.
Transferrin
Transferrin saturation: Normal about 30-50 % Transferrin saturation under 15 %= Iron deficiency
therefore
Total body iron level is regulated only at the level of iron absorption from the small intestine
Primary Haemochromatosis
Iron accumulates in the liver, heart and pancreas, excess iron damages these organs by free radical production
Transferrin saturation increases, serum ferritin increases
Therapy: Phlebotomy (removal of 0.5 l of blood): a decrease of iron in the circulation leads to iron mobilisation from stores
Secondary Haemochromatosis
Hypochromic microcytic erythrocytes Serum ferritin decreases (iron stores are depleted) transferrin saturation decreases (15 % or less)
Most common cause of iron-deficiency anemia in women: simply lack of iron in the diet.
If iron deficiency anemia is seen in a male patient, the patient should always be checked for blood loss from the gastrointestinal tract
Anemia of chronic disease Mild anemia combined with increased iron stores mild anemia + increased ferritin
Transferrin
Transferrin receptor
Cells which need iron express high number of transferrin receptors on their surface
Transferrin receptor expression is regulated posttranscriptionally at the level of transferrin receptor mRNA stability:
Recent (2001) look at iron metabolism: Iron metabolism is regulated mainly at the level of IRON EXPORT FROM THE CELL
Enterocytes (endothelial cells in small intestine): daily uptake and export of about 1 mg of iron from the diet Hepatocytes:
Able to mobilise stored iron from ferritin if needed
MACROPHAGES
2001-2002:
Hepcidin demonstrates the strong connection between iron metabolism and defence against pathogens
Bacteria need iron for their ribonucleotide reductase (DNA synthesis) Host needs iron for his antibacterial enzymes (Nitric oxide synthase and others)
Pathophysiology of both hemochromatosis and anemia of chronic disease can be easily explained by the action of hepcidin.
Hepcidin summary: Hepcidin is released from the liver according to body iron status: iron overload increases hepcidin, iron deficiency decreases hepcidin expression. Hepcidin blocks iron export from macrophages and enterocytes. Inflammation increases hepcidin production.