Iron

Question 1

what are the 2 forms of iron

Answer 1

ferric Fe3+ and ferrous Fe 2+

Question 2

what is iron present in

Answer 2

haemoglobin
myoglobin
enzymes eg cytochromes

Question 3

what makes up haem

Answer 3

porphyrin ring and Fe3+ makes haem

Question 4

where is iron absorbed

Answer 4

in the duodenum

Question 5

what absorbs iron

Answer 5

DMT-1 in the duodenum

Question 6

what does ferroportin do

Answer 6

facilitates iron export from the enterocyte, passed on from transferring for transport elsewhere

Question 7

what does hepcidin do

Answer 7

down-regulates ferroportin

Question 8

how is iron absorption regulated

Answer 8

intraluminal factors
mucosal factors
systemic factors

Question 9

what are the intraluminal factors that affect iron absorption

Answer 9

solubility of inorganic iron
haem iron easier to absorb
reduction of ferric (Fe3+) to ferrous Fe2+

Question 10

what are the mucosal factors that affect iron absorption

Answer 10

DMT-1 at mucosal surface

ferroportin at serosal surface

Question 11

what are systemic factors

Answer 11

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

Question 12

What 3 ways can you assess iron

Answer 12

functional iron-haemoglobin concentration
transport iron/iron supply to tissues
storage iron

Question 13

how is functional iron measured

Answer 13

haemoglobin

Question 14

how is transport iron measured

Answer 14

% saturation of transferring with iron

Question 15

how is storage iron measured

Answer 15

serum ferritin or tissue biopsy (rarely needed)

Question 16

what is ferritin

Answer 16

spherical intracellular protein

stores up to 4000 ferric ions

Question 17

what is an indirect way of measuring storage of iron

Answer 17

serum ferritin

Question 18

in inflammation eg sepsis malignancy, liver injury how would you expect serum ferritin levels to be

Answer 18

increased

Question 19

what are the main disorders of iron metabolism

Answer 19

iron deficiency
iron malutlisation-anameia of chronic disease
iron overload

Question 20

what are the consequences of negative iron balance

Answer 20

exhaustion of iron stores
iron deficient erythropoiesis-falling red cell MCV
microcytic anaemia
epithelial changes-skin, koilonychias, angular stomatitis

Question 21

hypochromaic microcytic anaemias are caused by

Answer 21

deficient haemoglobin synthesis

haem deficiency or globin deficiency

Question 22

how can iron deficiency be confirmed

Answer 22

anaemia (decreased haemoglobin iron) and reduced storage iron (low serum ferritin)

Question 23

what are the causes of iron deficiency

Answer 23

insufficient intake-more likely in women and children due to greater requirements, dietary factors
losing too much-bleeding
malabsorption-relatively uncommon

Question 24

what are the causes of chronic blood loss

Answer 24

menorrhagia
gi
hamaturia

Question 25

what is occult blood loss

Answer 25

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

Question 26

what happens in anaemia of chronic disease

Answer 26

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 27

what are the causes of iron overload

Answer 27

primary-hereditary haemochromatosis | secondary-transfusional, iron loading anaemias

Question 28

describe primary iron overload

Answer 28

long term excess iron absorption with parenchymal rather than macrophage iron loading

Question 29

describe the genetic problem in hereditary haematochromatosis

Answer 29

commonest form is due to mutations in HFE gene decreases synthesis of hepcidin increased iron absorption

Question 30

what are the clinical features of hereditary haemochromatosis

Answer 30

weakness/fatigue, joint pains, impotence, arthritis, cirrhosis, diabetes, cardiomyopathy

Question 31

when do clinical features tend to present

Answer 31

in middle age or later when iron overload >5g

Question 32

describe the mutations in the HFE gene

Answer 32

1 in 8 of population carry C282Y mutation; 1 in 4 the H63D mutation Patients are usually C282Y homozygotes; occasionally C282Y/H63D compound heterozygotes

Question 33

how is hereditary haemochormatosis diagnosed

Answer 33

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

Question 34

treatment of hh

Answer 34

Weekly venesection - 450-500ml - 200-250mg iron Initial aim to exhaust iron stores (ferritin <20 µg/l)‏ Thereafter keep ferritin below 50 µg/l

Question 35

examples of iron-loading anaemias

Answer 35

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 36

each unit of blood has how much iron

Answer 36

250mg iron

Question 37

what is less predictable with regular red cell transfusions and iron overload

Answer 37

excess intestinal iron absorption may be hidden until tissue damage become symptomatic

Question 38

name some iron chelating agents

Answer 38

Desferrioxamine (subcut or IV infusion)‏ Newer oral agents Deferiprone Deferasirox