Iron Flashcards
what are the roles of iron
oxygen transport (reversible binding to Hb) electron transport (for ATP production in mitochondria)
what is iron present in
haemoglobin (majority) myoglobin enzymes: cytochromes macrophage liver stores (parenchymal tissue) erythroid marrow plasma
why is iron dangerous
causes oxidative stress
no mechanism for excretion
what is the structure of Hb
haem (Fe2+ in porphyrin ring) group in each globin chain
how much iron is absorbed per day
1mg
where is most iron stores
red cell Hb
how much iron is lost per day
1mg (e.g. shedding of skin)
where does iron absorption occur
mainly in the duodenum - into mucosa cells
what enhances iron absorption
ascorbic acid (vit C -> reduces Fe2+ to form DMTI protein) alcohol haem iron (iron from meat, has specific transporter compared to veggie iron)
what inhibits iron absorption
tannins (tea)
phytates (cereals, bran, nuts and seeds)
calcium
how is iron absorbed
duodenal cytochrome B (found in luminal surface, reduces ferric acid (Fe3+) to ferrous (Fe2+))
DMT (divalent metal transporter, transports into duodenal enterocyte)
ferroportin (facilitates export from enterocyte, passed onto transferrin)
what regulates iron absorption
hepcidin
(negative regulator, produced in liver in response to increased iron load and inflammation. binds to ferroportin and degrades it making iron trapped in duodenal cells and macrophages)
how do you assess functional iron
Hb conc (most iron present in Hb)
how do you asses transport iron/ iron supply to tissues
% saturation of transferrin with iron
how do you assess iron stores
serum ferritin tissue biopsy (rarely needed)
what is transferrin
protein with two binding sites for iron atoms that transports it from donor tissues (macrophages, intestinal cells, hepatocytes) to tissues expressing transferrin receptors e.g erythroid marrow
what does transferrin saturation measure
iron supply
how do you calculate transferrin saturation
serum iron / total iron binding capacity x 100%
what is normal transferrin saturation
20-50%
what happens to transferrin in iron overload
saturation is elevated (max 100%)
what happens to transferrin in iron deficiency
saturation is decreased
what is ferritin
intracellular protein that store
what does serum ferritin indicate
intracellular ferritin synthesis= INdirect measure of storage iron
what else can raise ferritin
acts as an acute phase protein- malignancy, infection, liver disease etc
what happens to ferritin in iron overload and deficiency
deficiency- decreased
overload- increased
what can cause iron malutilisation
anaemia of chronic disease
what are the consequences of a negative iron balance (low intake/ malutilisation)
exhaustion of iron stores
iron deficient erythropoiesis: falling red
cell MCV
microcytic anaemia
epithelial changes: skin, koilonychia, angular stomatitis
what causes hypochromic microcytic anaemia
deficient Hb synthesis:
- haem deficiency= lack of iron for erythropoiesis (deficiency, anaemia of chronic disease (normal body iron))
- congenital sideroblastic anaemia (rare)
-globin deficiency (thalassaemias)
how is iron deficiency confirmed
combination of anaemia (decreased Hb iron) and reduced storage iron (low serum ferritin)
what can cause iron deficiency
insufficient intake to meet physiological need (more likely in women and children as greater need)
- diet
- chornic bleeding: menorrhagia, haematuria (kidney tumour), GI: tumours, ulcers, NSAIDs, parasitic infections, occult
- malabsorption: coeliac disease
what is occult blood loss
GI blood loss of 8-10ml per day (4-5ml iron) without any signs or symptoms
(def can occur as max dietary intake is 4-5mg/day)
is iron def anaemia a symptom or a diagnosis
symptoms (replacement therapy may relive symptoms without treating underlying cause)
Ix essential
early surgery for GI tumours curative
what is the pathophysiology of anaemia of chronic disease
inflammatory macrophage iron block:
increased ferritin mRNA due to inflammatory cytokines
increased ferritin synthesis
increased plasma hepcidin blocks ferroportin mediated release of iron
=impaired iron supply to marrow erythroblasts
=hypochromic red cells
• Iron stores in macrophages and duodenal cells increase due to:
- Raised inflammatory cytokines upregulate ferritin
- Raised hepcidin blocks the ferroportin-mediated release of iron from cells
• Total iron is not changing but it is just stuck in placed that you can’t use it
• This is done to prevent bacterial from using iron in blood to grow
what are the causes of iron overload
primary: heriditary haemochromatosis
secondary: transfusional, iron loading anaemias
what causes primary ion overload
long term excess iron absorption with parenchymal rather than marcophage iron loading
(hereditary haemochromatosis= HH)
what causes HH
most commonly caused by mutations in HFE gene (AR)
decreased synthesis of hepcidin
=increased iron absorption
=gradual iron accumulation with risk to end organ damage
what are the clinical features of HH
weakness/ fatigue joint pains impotence arthritis cirrhosis diabetes cardiomyopathy
present in middle age or later
can be asymptomatic untill end organ damage has occurred
iron overload >5g
how is HH diagnosed
> 50% transferrin saturation that is sustained on repeated samples
increased serum ferritin >300 (men), >200 (pre menopausal women)
(liver biopsy hardly used, fibroscan for cirrhosis)
what is the treatment for HH
weekly venesection (450-500mls = 200-250mg iron) want ferritin <20 initially then aim to keep it below 50 by venesection 2/3 times a year
siblings have 1 in 4 chance- test children
(screening= genetic test (HFE genotype) + iron status (ferritin and transferrin saturation)
what are the most common causes of death in HH
hepatoma hepatic failure/bleedinf varices cardiac dailure infections diabetes
what can cause iron loading anaemias
- repeated red cell transfusions
- excessive iron absorption due to overactive erythropoiesis
disorders: massive but ineffective erythropoiesis: -thalassaemia -sideroblastic anaemias (cant incorperate iron into haem) refractory hypoplastic anaemias: -red cell aplasia -myelodysplasia
how much iron does each unit of blood contain
250mg
how often do you need transfusions in thalassaemias
2-3 weekly lifelong
what is the treatment for secondary iron overload
cant vensect if patient already anaemic use iron chelating agents: -desferrioxamine (s/c or IV) -deferipone oral -deferasirox oral (often compliance problems)
