Iron Flashcards
what are the 2 forms of iron
ferric Fe3+ and ferrous Fe 2+
what is iron present in
haemoglobin
myoglobin
enzymes eg cytochromes
what makes up haem
porphyrin ring and Fe3+ makes haem
where is iron absorbed
in the duodenum
what absorbs iron
DMT-1 in the duodenum
what does ferroportin do
facilitates iron export from the enterocyte, passed on from transferring for transport elsewhere
what does hepcidin do
down-regulates ferroportin
how is iron absorption regulated
intraluminal factors
mucosal factors
systemic factors
what are the intraluminal factors that affect iron absorption
solubility of inorganic iron
haem iron easier to absorb
reduction of ferric (Fe3+) to ferrous Fe2+
what are the mucosal factors that affect iron absorption
DMT-1 at mucosal surface
ferroportin at serosal surface
what are systemic factors
these are the major negative regulator of iron uptake
produced in liver in response to iron load and inflammation
down regulated ferroportin
iron ‘trapped’ in duodenal cells and macrophages
What 3 ways can you assess iron
functional iron-haemoglobin concentration
transport iron/iron supply to tissues
storage iron
how is functional iron measured
haemoglobin
how is transport iron measured
% saturation of transferring with iron
how is storage iron measured
serum ferritin or tissue biopsy (rarely needed)
what is ferritin
spherical intracellular protein
stores up to 4000 ferric ions
what is an indirect way of measuring storage of iron
serum ferritin
in inflammation eg sepsis malignancy, liver injury how would you expect serum ferritin levels to be
increased
what are the main disorders of iron metabolism
iron deficiency
iron malutlisation-anameia of chronic disease
iron overload
what are the consequences of negative iron balance
exhaustion of iron stores
iron deficient erythropoiesis-falling red cell MCV
microcytic anaemia
epithelial changes-skin, koilonychias, angular stomatitis
hypochromaic microcytic anaemias are caused by
deficient haemoglobin synthesis
haem deficiency or globin deficiency
how can iron deficiency be confirmed
anaemia (decreased haemoglobin iron) and reduced storage iron (low serum ferritin)
what are the causes of iron deficiency
insufficient intake-more likely in women and children due to greater requirements, dietary factors
losing too much-bleeding
malabsorption-relatively uncommon
what are the causes of chronic blood loss
menorrhagia
gi
hamaturia
what is occult blood loss
GI blood loss of 8-10ml per day (4-5mg iron)can occur without any symptoms or signs of bleeding
therefore a negative iron balance can occur
what happens in anaemia of chronic disease
increased transcription of ferritin mRNA stimulated by inflammatory cytokines so ferritin synthesis increased
increased plasma hepcidin blocks ferroportin-mediated release of iron
results in impaired iron supply to marrow erythroblasts and eventually hypochromic red cells
what are the causes of iron overload
primary-hereditary haemochromatosis
secondary-transfusional, iron loading anaemias
describe primary iron overload
long term excess iron absorption with parenchymal rather than macrophage iron loading
describe the genetic problem in hereditary haematochromatosis
commonest form is due to mutations in HFE gene
decreases synthesis of hepcidin
increased iron absorption
what are the clinical features of hereditary haemochromatosis
weakness/fatigue, joint pains, impotence, arthritis, cirrhosis, diabetes, cardiomyopathy
when do clinical features tend to present
in middle age or later when iron overload >5g
describe the mutations in the HFE gene
1 in 8 of population carry C282Y mutation; 1 in 4 the H63D mutation
Patients are usually C282Y homozygotes; occasionally C282Y/H63D compound heterozygotes
how is hereditary haemochormatosis diagnosed
Risk of iron loading: transferrin saturation >50% (sustained on repeat fasting sample)
Increased iron stores: serum ferritin >300 g/l in men or >200 g/l in pre-menopausal women
Liver biopsy: only if uncertain about iron loading or to assess tissue damage
treatment of hh
Weekly venesection
- 450-500ml - 200-250mg iron
Initial aim to exhaust
iron stores (ferritin
<20 µg/l)
Thereafter keep ferritin
below 50 µg/l
examples of iron-loading anaemias
Sources
Repeated red cell transfusions
Excessive iron absorption related to over-active erythropoiesis
Disorders
Massive ineffective erythropoiesis
Thalassaemia syndromes
Sideroblastic anaemias
Refractory hypoplastic anaemias
Red cell aplasia
Myelodysplasia (MDS)
each unit of blood has how much iron
250mg iron
what is less predictable with regular red cell transfusions and iron overload
excess intestinal iron absorption may be hidden until tissue damage become symptomatic
name some iron chelating agents
Desferrioxamine (subcut or IV infusion)
Newer oral agents
Deferiprone
Deferasirox
