Iron Studies Flashcards
What is the charge on ferrous iron?
2+ (reduced)
What is the charge on ferric iron?
3+ (oxidised)
What are the 4 main functions of iron?
Oxygen carriers
Oxygen storage
Energy production (cytochromes for ox phos, Krebs cycle enzymes)
Liver detoxification (cytochrome p450)
How much iron is ingested daily on average? How much is absorbed?
10-20 mg
1-2 mg
How is iron absorbed?
Reduced to ferrous form in low pH of stomach and separates from ligand
Converted back to ferric form in high pH of intestine and is absorbed
Reduced as it is absorbed
How is iron stored?
In ferritin as the ferrous form In haemosiderin (slow release form)
How is iron transferred?
Transferrin
What is the normal saturation of transferrin?
40%
What are the roles of HFE?
Controls the rate at which transferrin can be absorbed into the body
Also has effects on hepcidin and therefore the release of iron from cells
What is the classical mutation in haemochromatosis?
C282Y mutation in HFE
Can also have C282Y and H63D heterozygote
Describe the role of the iron response element (IRE)
High iron
Iron binds to and represses action of IRE
IRE does not bind to the mRNA transcript for transferrin
mRNA is degraded
Less transferrin is produced
Opposite occurs with low iron, opposite is true for ferritin production
List 7 morbidities associated with haemochromatosis
Liver disease DM Cardiac dysfunction Skin pigmentation Arthropathy Gonadal dysfunction FHx (can be passed on)
When does iron start to accumulate in haemochromatosis?
After child (turnover is reduced) Same is true in normal population (ferritin is higher in males than pre-menopausal females due to menstruation in both diseased and normal populations)
What is the threshold for organ damage (esp liver) in iron excess?
20g
What are the findings on iron studies in iron excess?
High ferritin
High iron saturation
Low transferrin (due to binding of IRE)
Why is ferritin not a good test for haemochromatosis?
Level varies depending on type of mutation and whether pt is heterozygous or homozygous
In what population is ferritin a good test for haemochromatosis?
In women
Above what ferritin level does ALT start to rise?
1000
What is the effect of oestrogen on transferrin?
Increases
What is the cut-off for what is considered a “high transferrin” in a pregnant woman?
~6
What is the difference between iron depletion and iron deficiency?
Iron depletion refers to low ferritin in a non-anaemic person
Iron deficiency is a clinical syndrome with symptoms and signs of microcytic anaemia
List 7 signs of IDA
Weakness Fatigue Headache Irritability Sore tongue Angular chelitis Nail changes
How is iron lost and how much is lost this way?
Sweat, skin, gut: 1 mg/day
Menses: additional 1-2 mg/day
+ more if pregnant, breast-feeding or antenatally
List 8 causes of iron deficiency
Dietary deficiency Malabsorption Gut ulceration Tumours Infection Menorrhagia Other rarer causes
What 3 malabsorption states are often associated with iron deficiency?
Coeliac disease
Achlorhydria (not associated with PPI)
Bowel resection
When might gut ulceration occur?
Reflux
PUD
Crohn’s
List 3 sites for tumours which can cause iron deficiency
Gut
Kidney
Uterus
List 2 infections which can cause iron deficiency
Hookworm
Malaria
List 4 other rarer causes of iron deficiency
Intravascular haemolysis
Pulmonary haemosiderosis
EPO therapy
Dialysis
What are the findings on iron studies in IDA?
Low ferritin Low iron saturation High transferrin Anaemia (low Hb) Low MCV
What ferritin level causes low Hb?
<10
What ferritin level causes low MCV?
<10 to see microcytosis)
What ferritin level causes high RDW?
<40
Why can iron be normal in certain inflammatory conditions (e.g. UC)?
mm
What can siderophore infusion be used to treat?
Iron overload
What is the effect of fever on siderophore production?
Decreases
How does the immune system respond to the detection of bacteria to prevent their access to iron?
White cell releases lactoferrin, which binds iron in acid environment (environment of inflammation)
Cytokines induce APP production
Caeruloplasmin oxidises iron
Haemopexin removes heme from circulation
Haptoglobin removes Hb from blood
Hepcidin and ferroportin decrease iron release
What is the effect of inflammation on iron studies results?
Decreased transferrin Decreased iron saturation Decreased iron Increased ferritin Reduced Hb Normal MCV
