Iron Studies Flashcards
In normal physiology, where is Fe absorbed and also lost?
Gut - absorbs app 1-2mg/day
as the epithelial cells turn over 1-2mg/day is lost
Is Fe stored in after absorption through gut lumen to the blood?
It is not stored after reabsorption, rather it is stored in the enterocyte and can be sloughed off if in excess. There is no absorption in the rest of the body
What is the normal saturation level of transferrin?
40%
How is transferrin and transferring receptor produced? Compare situations between low and high iron.
Fe controls the transferrin and transferring receptor proteins that it needs:
Low Fe in enterocyte: IRE BP (iron responsive binding protein) binds to IRE on mRNA, therefore transferrin receptor produced
High Fe in enterocyte: IRE-BP cannot bind to IRE on transferrin mRNA, therefore transferrin mRNA is destabilised and less production
How is transferrin and transferring receptor produced? Compare situations between low and high iron.
Fe controls the transferrin and transferring receptor proteins that it needs:
Low Fe in enterocyte: IRE BP (iron responsive binding protein) binds to IRE on mRNA, therefore transferrin receptor produced
High Fe in enterocyte: IRE-BP cannot bind to IRE on transferrin mRNA, therefore transferrin mRNA is destabilised and less production
What are the complications of haemochromatosis?
Fe causing damage directly:
- Liver disease
- DM: Fe damage pancreatic islets
- Cardiac dysfunction
- Skin pigmentation
- Athropathy: Fe oxidizes joint tissue and destroys it
- Gonadal Dysfunction
- FHx
Prevalence of haemachromatosis?
1/400 people
even though gene is 1/200 people the gene is only 50% penetrance
How many grams of body Fe required until organ damage?
0-20g asymptomatic, non-specific symptoms
20g signs of organ damage (liver)
>20g early death
What mutations are associated with haemochromatosis?
H63D
C282Y
What level of ferritin leads to an increase in ALT?
1000 - i.e. liver damage
Effect of pregnancy on Fe studies
Transferrin will high (even in anaemia), as estrogen increases production.
Why? As you want to send Fe to baby
What are the physiological Fe losses?
Sweat, skin, gut (mostly) = 1mg/day
Menses leads to additional 1-2 mg/day
Pregnancy, breast feeding, delivery (give to baby)
Sx of Fe deficiency
Weakness, fatigue, headache, irritability, sore tongue, angular chelitis, nail changes
‘Too little in’ causes of Fe deficiency?
a. Dietary deficiency
b. Malabsorption: coeliac, achlorhydria (PPI not associated) as low pH needed in reabsorption of Fe, bowel resection
‘Too much out’ causes of FE deficiency?
a. Gut ulceration - reflux, peptic ulceration, Crohn’s
b. Tumours - GIT, kidney, uterus
c. Infection - hookworm, malaria
d. Rare: intravascular haemolysis, dialysis
How do bacteria attempt to take our body Fe?
Bacteria require Fe for their own growth and use haemolysins and siderophores
What form of iron is absorbed from gut lumen -> enterocyte, enterocyte -> blood?
gut lumen -> enterocyte: ferric Fe3+ becomes ferrous Fe2+ and is STORED in enterocyte as FERRITIN (can then be sloughed off)
enterocyte -> blood: Fe2+ via ferroportin to blood stream becomes Fe3+ then transported around blood with TRANSFERRIN (that relies on transferrin R)
Is Fe stored after absorption through gut lumen to the blood?
No, it is not stored after reabsorption, rather it is stored in the enterocyte as ferritin and is then sloughed off if in excess or released if deficient in Fe. There is no absorption in the rest of the body
How many grams of body Fe is needed until it causes organ damage?
0-20g asymptomatic, non-specific symptoms
20g signs of organ damage (liver)
>20g early death
What are the markers of Fe studies?
*important
- Serum Fe: Fe in blood
- TIBC (total binding capacity): amount of Fe that can be bound to Fe protein
- % Transferrin Saturation: extent which Fe binding sites on transferrin are occupied by Fe
- Serum ferritin: iron stores in body
What is the normal serum transferrin level
Normal serum transferrin: 2-3.5
What are the effects of pregnancy of Fe studies?
Transferrin will high (even in anaemia), as estrogen increases production.
Why? As you want to send Fe to baby
What are the mechanisms in which bacteria attempt to take our body Fe?
Bacteria require Fe for their own growth; they use haemolysins and siderophores
Fe study of inflammation:
Serum Fe: low
Transferrin: low
Saturation % transferrin: low
Serum Ferritin: high
What is the role of haptoglobin?
Haptoglobin is an acute phase protein that binds to Hb in attempt to conserve it in the bloodstream (away from bacteria) during inflammation.
Therefore with no inflammation, Haptoglobin is low; inflammation, haptoglobin is high
What is the effect of inflammation on Fe studies?
Inflammation leads to the body attempting to retain and protect its Fe from bacteria. Therefore cytokines signal the liver to produce: haemopexin and haptoglobin.
Fe: Low (decrease release) Transferrin: Low (acute phase response) Saturation: Low Ferritin: high (increase storage) MCV: does not change (anaemia of chronic disease
Fe study of iron excess:
Fe: high
Transferrin: low
Saturation: high
Ferritin: high
Fe study of iron deficiency:
Fe: low
Transferrin: high
Saturation: low
Ferritin: low
Fe study of inflammation:
Fe: low
Transferrin: low
Saturation: low
Ferritin: high
