Iron in Health and Disease

Question 1

which 2 iron transporters are involved in absorbing it from the gut?

Answer 1

DMT-1 (divalent metal transporter) at mucosal surface

Ferroportin at serosal surface

Question 2

what is the major negative regulator of iron uptake?

when is it released?

what does it do?

Answer 2

hepcidin

released in response to iron overload or inflammation

down regulates ferroportin

Question 3

How can iron deficiency be confirmed?

Answer 3

Iron deficiency can be confirmed by a combination of anaemia (decreased haemoglobin iron) and reduced storage iron (low serum ferritin)

Question 4

how do chronic disorders cause anaemia?

Answer 4

Red calls are broken down by inflammatory macrophages where it is blocked.

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

Question 5

what are the clinical features of iron overload?

Answer 5

Presentation usually in middle age or later
Iron overload > 5g
 arthritis
 cirrhosis
 diabetes
cardiomyopathy
impotence 
fatigue

Question 6

what is the pathophysiology and inheritance of haemochromcytosis?

Answer 6

Mutations of HFE gene
1 in 8 of population carry C282Y mutation; 1 in 4 the H63D mutation
Patients are usually C282Y homozygotes; occasionally C282Y/H63D double heterozygotes
Main effect likely to be via reduced hepcidin synthesis
Account for 95% of hereditary haemochromatosis
Incomplete penetrance

Question 7

what is the diagnosis of haemochromatosis

Answer 7

Risk of iron loading: transferrin saturation >50% (sustained on repeat fasting sample)‏
Iron load: 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

Question 8

what is the chance of a sibling of a patient with hemochromatosis being affected?

Answer 8

1 in 4

Question 9

what are causes of iron overload?

Answer 9

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)

Question 10

what is the treatment of iron overload?

Answer 10

Iron chelating agents:
Desferrioxamine (s.c. or IV infusion)‏
New oral agents 	
Deferiprone
Deferasirox