Iron in Health and Disease Flashcards
what is iron used for
oxygen transport
electron transport - mitochondrial production of ATP
present in:
Hb
myoglobin
enzymes
what makes iron dangerous
chemical reactivity
-can take part in oxidative reactions and free radical production
requirements are:
- safe transport
- safe storage
- regulation of iron absorption
where is the majority of iron in the body found
haemolytic
Fe2 sits in a porphyrin ring to form Haem
1 Haem group per globulin
what happens to iron in Hb after RBCs are broken down
binds to transferrin and re-enters the plasma
how much iron to be absorb/loose per day
absorb 1mg/day
lose 1mg/day (bleeding, worn out skin cells etc, cannot be controlled)
iron in Hb is constantly recycled
where is iron absorbed
duodenum - uptake into cells of duodenal mucosa
influenced by dietary factors
what enhances iron absorption
Haem-vs non-harm iron
-haem iron from animal products absorbed better
ascorbic acid (vit C) helps reduced iron to Fe2+ to make it absorbed more easily
alcohol
what inhibits iron absorption
tannins eg. tea
phytates eg. cereals, bran, nuts and seeds
calcium eg. dairy products
what is the mechanism of iron absorption
Duodenal cytochrome B
- found in luminal surface
- reduced Fe3+ (ferric) to Fe2+ (ferrous)
DMT (divalent metal transporter)
-transports ferrous iron into the duodenal enterocyte
OR
Haem transporter
-transfers Haem into the duodenal enterocyte
Ferroportin
- facilitates iron export from enterocyte
- passed on to transferrin
what regulated iron absorption
Hepcidin
-hepcidin production in the liver increases due to increased iron load or inflammation
binds to ferroportin and causes its degradation
iron therefore ‘trapped’ in the duodenal cells
what happens to heptocidin levels in iron deficiency
decreases to facilitate absorption of more iron
how do you asses iron status
functional iron
- Hb concentration
- where iron in use is
transport iron/supply to tissues
-% saturation of transferrin with iron
storage iron
- serum ferritin
- tissue biopsy (rarely needed)
what is transferrin
protein which binds two iron atoms
transports irons from donor tissues (macrophages, intestinal cells, hepatocytes)
to tissue expressing transferrin receptors (erythroid marrow)
what does transferrin saturation measure
iron supply
-serum iron/total iron binding capacity
reflects proportion of diferric transferrin
transferrin saturation - 20-50%
what is ferritin
spherical intracellular protein - stores up to 4000 ferric irons
tiny amounts of serum ferritin reflects intracellular ferritin synthesis
therefore serum ferritin is a surrogate marker to tissue ferritin
what causes increased ferritin
iron overload
inflammation
sepsis
malignancy
liver injury
what are the disorders of iron metabolism
iron deficiency
iron malutilisation ‘anaemia of chronic disease’
iron overload
what are the consequences of iron deficiency
exhaustion of iron stores
iron deficiency erythropoiesis
-falling red cell MCV
microcytic hypochromic anaemia
epithelial changes
- skin
- koilonychia
- angular stomatitis
what causes microcytic anaemias
deficient haemoglobin synthesis
Haem deficiency
- lack of iron
- anaemia of chronic disease
- congenital sideroblastic anaemia
globing deficiency
-thalassaemias
how can iron deficiency be confirmed
anaemia (decreased Hb iron)
reduced iron storage (low serum ferritin)
causes of iron deficiency
insufficient intake
- women and children
- diet
loosing too much
-bleeding
not absorbing
-coeliac disease
causes of chronic blood loss
menorrhagia GI -tumours -ulcers -NSAIDS -parasitic infection haematuria
what is Iron Malutilisation (anaemia of chronic disease)
up regulating of ferritin production stimulated by inflammation -
iron stores increase
hepcidin increases
iron becomes stuck in duodenal enterocyte as transferrin
leads to microcytic hypochromic red cells
why does anaemia of chronic disease occur
protective mechanism to reduce iron supply to pathogens
causes of iron overload
primary
-herreditary haemochromatosis
secondary
- transfusional
- iron loading anaemias
what is hereditary haemochromatosis
long-term excess iron absorption with parenchymal iron loading
HFE gene mutation
decreased hepcidin synthesis
increased iron absorption
gradual iron accumulation with risk of end organ damage
clinical features of hereditary haemochromatosis
weakness/fatigue joint pains impotence arthritis cirrhosis diabetes cardiomyopathy
usually presents in middle age or later
iron overload >5g
treatment of hereditary haemochromatosis
weekly venesection
450-500ml
200-250mg of iron
initial aim to exhaust iron stores then once its norm just do it when ferritin comes back up
thereafter keep ferritin below 50
causes of death in hereditary haemochromatosis
diabetes infection cardiac failure hepatic failure hepatoma
who else do you test in hereditary haemochromatosis
family screening
first degree relative 1/4 risk
HFE genotype and iron status
may be undetectable until irreversible organ damage occurs
what causes secondary iron overload
Repeated red cell transfusion
Excessive iron absorption related to over-active erythropoiesis
disorders causing iron overload
massive ineffective erythropoiesis
- thalasaemia
- sideroblastic anaemias
- bone marrow not working
- red cell aplasia
- myelodysplasia
what is the treatment of secondary iron overload
ironchelating drugs as venesection is not an option in already anaemic patients
what iron chelating agents are used
desferrioxamine subcutaneous or IV
