82-85. Iron metabolism Flashcards
What is the total body content of iron?
4g
What two intracellular proteins are responsible for the storage of iron?
Ferritin (soluble)
- readily available from RES
- tiny amount in serum in proportion to amounts in RES
Haemosiderin (insoluble conglomerates of ferritin)
- iron only slowly available
In what conditions would serum ferritin:
a) Decrease
b) increase
a) Iron deficiency anaemia
b) iron overload
Ferritin is also an acute phase protein which is raised in response to damage/infection/inflammation
What is responsible for the transport of iron?
Transferrin (Tf) - a glycoprotein synthesised by hepatocytes with two iron binding domains
- is 30% saturated with Fe
Synthesis of transferrin increases with lowered iron levels
How many mg of iron are lost during menstruation?
1-2mg/day
What is the daily need of iron?
What is the average intake of iron in the Western diet?
1-2mg/d
15-20mg/d
Therefore iron deficiency anaemia is very rare in adults
What are the dietary sources for:
a) Haem iron
b) non-haem iron
a) Red meat
b) White meat, green vegetables, cereal
Why is regulation of iron absorption important?
It’s the single physical mechanism for maintaining our iron balance - there is no excretory mechanism
Where is most iron absorbed?
Duodenum (duodenal enterocytes)
How is non-haem iron released from food?
By acid digestion and proteolytic enzymes in stomach
What is the role of duodenal cytochrome b1 (dCytb1)?
What is the process influenced by?
Reduced non-haem iron from the ferric to the ferrous form
Vitamin C
What is the role of divalent metal transporter 1 (DMT1)?
Allows iron (Fe2+) to be taken up into the cell
What is DMT1 and what causes it’s expression to be upregulated?
Divalent metal transporter 1 is an electrogenic pump. It’s expression is upregulated by iron deficiency
Iron is transported from the enterocyte to the circulating plasma through _______ and _______
ferroportin; hepcidin
What is ferroportin?
A transmembrane protien which is also responsible for the release of iron from macrophages
What is the most important regulator or GI absorption and RES release?
the interaction between ferroportin and hepcidin
Describe RES iron uptake, storage and release and then recycled
RES macrophages acquire iron from effete RBCs with the breakdown of haem into iron and bilirubin
Iron is stored in RES macrophages as ferritin (stores around 500mg)
Iron release from RES macrophages is regulated by ferroportin and hepcidin
RES released iron to transferrin in plasma - iron in plasma transported by transferrin
Tf-iron taken up via Tf receptors on erythroblasts (80% of Tf receptors), hepatocytes etc
Where is transferrin synthesised? How many binding sites does it have for iron?
Liver; 2
How much iron is bound to transferrin per day? How much iron can be transported by transferrin at any one time?
50mg/day; 4mg at any one time
When Tf-iron enters an erythroblast, what are it’s two possible fates?
Enters mitochondria to be a component of haem (by ALA-S2)
OR
Stored in erythroblast as ferrin
True or false: Hb can reversibly bind to O2 without being oxidised or reduced.
True
What is the golden rule with patients who have iron deficiency anaemia?
In males and post-menopausal women, IDA is caused by GI blood loss until proven otherwise
In young women; caused by menstrual blood loss and/or pregnancy
(GI investigations should only be carried out with GI symptoms or blood in stool)
Define haematinic
The general term for the nutrients required for the production of RBCs in bone marrow (iron, bit B12, folic acid)
What are the three haematinic deficiencies possible in coeliac disease (list from most likely to least likely)
- Folate deficiency (in green veg, orange juice, liver)
- Iron deficiency (in haem and non-haem)
- Vitamin B12 deficiency (meat & dairy)
What are the signs of hyposplenism in coeliac disease on a blood film?
Target cells, Howell-Jolly bodies (nucleated RBC), irregular RBC count
Hepcidin is the most important influence on iron metabolism. Where is it produced, and what is it’s role?
Produced in the liver.
Role is to reduce the iron content in the circulation
Does this by binding to and degrading ferroportin to reduce the GI absorption of iron and reducing macrophage release of iron from RES
What is required for the synthesis of hepcidin?
HFE (human haemochromatosis protein)/ High iron Fe
Hepcidin loss causes…..
Increased GI absorption of iron and increased RES iron release
Increased Tf% saturation parenchymal overload (HH)
What is hereditary haemochromatosis and what causes it?
An autosomal recessive disorder causing iron overload
Caused by abnormalities of the HFE gene (most cases)
What is the most common mutation of the HFE gene?
homozygous C282Y
How does a mutation of the HFE gene cause HH?
Reduction in the production of hepcidin
How does iron overload affect the:
a) liver
b) pancreas
c) joints
d) skin
a) Cirrhosis
b) Diabetes
c) arthritis (of the 3rd metacarpophalangeal joint)
d) Bronzing
What is restrictive cardiomyopathy?
Walls of ventricles become stiff but not necessarily thickened
How can HHC be treated?
Venesection - initially up to weekly (500ml whole blood gives 250mg iron)
Monitor ferritin and transferrin saturation
Prevent/limit organ damage
What is the total body iron in someone with HHC?
20g
