Iron metabolism and homeostasis Flashcards
(30 cards)
What is iron needed for?
Formation of haemoglobin, and other metabolic processes in the body
What is the total body content of iron?
Where is this distributed?
4g
3g is in bone marrow and RBCs.
The rest is in RES, myoglobin, and enzymes e.g. cytochromes, peroxidases.
What happens to serum ferritin levels in IDA and in iron overload?
In IDA, ferritin levels decrease.
In iron overload, ferritin levels increase.
What kind of molecule is transferrin?
A glycoprotein made in hepatocytes. More is made in low iron levels, and vice versa.
What happens when serum iron levels drop?
Iron from the ferritin pool is then removed and taken via transferrin in the plasma to where its needed.
What do transferrin molecules have high affinity for?
How does transferrin get iron into RBCs to become haem?
Transferrin receptors on RBC precursor membranes in bone marrow.
Ingested by endocytosis, and transferrin delivers iron to the mitochondria where haem is synthesised.
Why is regulating iron absorption so important?
There’s no physiological mechanism for iron excretion, so absorption has to be tightly regulated to maintain iron balance
Where does iron absorption principally occur?
Duodenum
What type of iron is more easily absorbed?
Haem iron, rather than non-haem iron.
How is non-haem iron released from food?
By acid digestion and proteolytic enzymes in the stomach. It has to be reduces from ferric to ferrous form by duodenal cytochrome B1, which is enhanced by vitamin C and alcohol.
What receptor mediates non-haem iron absorption into enterocytes?
Divalent metal transporter 1 (DMT1). DMT1 is an electrogenic pump and it’s expression is upregulated in iron deficiency.
How is iron exported from the enterocyte to the plasma?
Why is this important
Via ferroportin (transmembrane protein) and hepcidin (hormone). The interaction between the 2 is the single most important regulator of iron absorption and of RES iron release.
Describe the difference in haem iron and non-haem iron absorption from the small intestine.
Haem iron is taken into the cells by endocytosis.
Non-haem iron has to be converted from ferric (Fe3) to ferrous (Fe2) by duodenal cytochrome B1, and then binds to the DMT1 receptor and is taken into enterocytes.
What does iron do once it’s in the cell?
Either is stored as ferritin for when it’s needed, or is taken via ferroportin into the blood.
What happens to iron once in the blood?
Iron is converted back into ferric form by hepcidin, which is upregulated in response to increased body iron stores.
Iron then binds back to transferrin.
How is iron stored in the RES?
Once RBCs become effete after 120 days, RES macrophages turn haem into iron (and bilirubin) and iron is stored as ferritin or haemosiderin.
How is RBC iron recycled?
The iron from effete RBCs is released from the RES to transferrin in the plasma, which is then taken up by transferrin receptors on RBC precursors.
What are the main causes of IDA?
Menorrhagia, pregnancy, GI tract malignancy, oesophagitis, GORD, coeliac disease.
What kind of anaemia is IDA?
Microcytic and hypochromic
What are the symptoms of IDA?
Fatigue, headache, dyspnoea, palpitations, koilonychia, angular chelitis, glossitis
What investigations should be carried out in IDA?
Bloods: decreased ferritin, decreased iron, increased iron binding capacity
What treatment is available for IDA?
Treat the cause; iron supplement e.g. ferrous sulphate
What haematinic (things which increase haemoglobin) deficiencies are seen in coeliac disease?
- Folate deficiency (most likely)
- Iron deficiency
- Vitamin B12 deficiency (unlikely)
How does hepcidin help to regulate plasma iron concentrations?
Hepcidin binds to ferroportin and degrades it, meaning that iron is sequestered in cells instead of absorbed into blood. This occurs in enterocytes and in macrophages (RES).
