Iron in Health and Disease

Question 1

what is iron used for

Answer 1

oxygen transport
electron transport - mitochondrial production of ATP

present in:
Hb
myoglobin
enzymes

Question 2

what makes iron dangerous

Answer 2

chemical reactivity
-can take part in oxidative reactions and free radical production

requirements are:

• safe transport
• safe storage
• regulation of iron absorption

Question 3

where is the majority of iron in the body found

Answer 3

haemolytic

Fe2 sits in a porphyrin ring to form Haem

1 Haem group per globulin

Question 4

what happens to iron in Hb after RBCs are broken down

Answer 4

binds to transferrin and re-enters the plasma

Question 5

how much iron to be absorb/loose per day

Answer 5

absorb 1mg/day

lose 1mg/day (bleeding, worn out skin cells etc, cannot be controlled)

iron in Hb is constantly recycled

Question 6

where is iron absorbed

Answer 6

duodenum - uptake into cells of duodenal mucosa

influenced by dietary factors

Question 7

what enhances iron absorption

Answer 7

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

Question 8

what inhibits iron absorption

Answer 8

tannins eg. tea
phytates eg. cereals, bran, nuts and seeds
calcium eg. dairy products

Question 9

what is the mechanism of iron absorption

Answer 9

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

Question 10

what regulated iron absorption

Answer 10

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

Question 11

what happens to heptocidin levels in iron deficiency

Answer 11

decreases to facilitate absorption of more iron

Question 12

how do you asses iron status

Answer 12

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)

Question 13

what is transferrin

Answer 13

protein which binds two iron atoms

transports irons from donor tissues (macrophages, intestinal cells, hepatocytes)
to tissue expressing transferrin receptors (erythroid marrow)

Question 14

what does transferrin saturation measure

Answer 14

iron supply
-serum iron/total iron binding capacity

reflects proportion of diferric transferrin

transferrin saturation - 20-50%

Question 15

what is ferritin

Answer 15

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

Question 16

what causes increased ferritin

Answer 16

iron overload

inflammation
sepsis
malignancy
liver injury

Question 17

what are the disorders of iron metabolism

Answer 17

iron deficiency
iron malutilisation ‘anaemia of chronic disease’
iron overload

Question 18

what are the consequences of iron deficiency

Answer 18

exhaustion of iron stores

iron deficiency erythropoiesis
-falling red cell MCV

microcytic hypochromic anaemia

epithelial changes

• skin
• koilonychia
• angular stomatitis

Question 19

what causes microcytic anaemias

Answer 19

deficient haemoglobin synthesis

Haem deficiency

• lack of iron
• anaemia of chronic disease
• congenital sideroblastic anaemia

globing deficiency
-thalassaemias

Question 20

how can iron deficiency be confirmed

Answer 20

anaemia (decreased Hb iron)

reduced iron storage (low serum ferritin)

Question 21

causes of iron deficiency

Answer 21

insufficient intake

• women and children
• diet

loosing too much
-bleeding

not absorbing
-coeliac disease

Question 22

causes of chronic blood loss

Answer 22

menorrhagia 
GI 
-tumours
-ulcers
-NSAIDS 
-parasitic infection 
haematuria

Question 23

what is Iron Malutilisation (anaemia of chronic disease)

Answer 23

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

Question 24

why does anaemia of chronic disease occur

Answer 24

protective mechanism to reduce iron supply to pathogens

Question 25

causes of iron overload

Answer 25

primary
-herreditary haemochromatosis

secondary

• transfusional
• iron loading anaemias

Question 26

what is hereditary haemochromatosis

Answer 26

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

Question 27

clinical features of hereditary haemochromatosis

Answer 27

weakness/fatigue
joint pains 
impotence 
arthritis 
cirrhosis 
diabetes 
cardiomyopathy 

usually presents in middle age or later

iron overload >5g

Question 28

treatment of hereditary haemochromatosis

Answer 28

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

Question 29

causes of death in hereditary haemochromatosis

Answer 29

diabetes 
infection 
cardiac failure
hepatic failure 
hepatoma

Question 30

who else do you test in hereditary haemochromatosis

Answer 30

family screening
first degree relative 1/4 risk

HFE genotype and iron status

may be undetectable until irreversible organ damage occurs

Question 31

what causes secondary iron overload

Answer 31

Repeated red cell transfusion

Excessive iron absorption related to over-active erythropoiesis

Question 32

disorders causing iron overload

Answer 32

massive ineffective erythropoiesis

• thalasaemia
• sideroblastic anaemias
• bone marrow not working
  - red cell aplasia
  - myelodysplasia

Question 33

what is the treatment of secondary iron overload

Answer 33

ironchelating drugs as venesection is not an option in already anaemic patients

Question 34

what iron chelating agents are used

Answer 34

desferrioxamine subcutaneous or IV