Iron in health and disease

Question 1

what is iron used for in the body? (2)

-what is iron present in?

Answer 1

Oxygen transport
(reversible O2 binding by Hb)
Electron transport
(in both ferrous and ferric forms)

-Hb, myoglobin, Enzymes

Question 2

Why can iron be dangerous? (2)

Answer 2

chemical reactivity- causes oxidative stress

No mechanism for excretion

Question 3

Where is iron in Hb?

Answer 3

in the globin chain, the Fe ion sits in the porphyrin ring

Question 4

Explain iron exchange within the body

-see diagram on slide 7

Answer 4

More than 1/2 the iron in the body is stored in Hb
Iron is recycled within the body
Iron is absorbed (1mg/day) and then circulates briefly in the plasma bound to transferrin.
It is then transported to BM and is then incorporated int o RBCs.
When these are broken down the Iron is stored in Macrophages (+body tissues) until it is needed.

Question 5

How do you asses iron status:

-name the 3 compartments of iron within the body & how these are measured?

Answer 5

-functional iron
(Hb conc)

Transport iron
(% saturation of transferrin with iron)

Storage iron
(serum ferritin & tissue biopsy BM or Liver)

Question 6

Transferrin

• what is it?
• function?
• what does transferrin saturation measure?
• how is ^ calculated?
• what is a normal level?
• what will be seen in iron overload and iron deficiency?

Answer 6

• protein with 2 binding sites for iron atoms
• transports iron FROM donor tissues (macrophages, intestinal cells and hepatocytes) TO tissues expressing transferrin receptors especially erythroid marrow
• iron supply
• serum iron/total iron binding capacity X 100%
• about 20-50%

-overload= transferrin saturation elevated 
deficiency= transferrin saturation decreased

Question 7

Ferritin

• what is it?
• function & capacity?
• what does serum ferritin measure?
• what effects serum ferritin levels?

Answer 7

• Large intracellular protein
• spherical and stores up to 4000 ferric ions in Fe3+ form
• tiny amounts of serum ferritin reflects intracellular ferritin synthesis in response to iron- indirect measure of storage iron
• acute phase protein so inc in infection/malignancy

Question 8

How is iron absorption regulated:

• intraluminal factors (3)
• Mucosal factors (2)
• Systemic factors (3)

Answer 8

-solubility of inorganic ions
haem iron easier to absorb
Reduction of ferric (Fe3+) to ferrous (Fe2+)

-expression of iron transporters
DMT-1 at mucosal surface
Ferroportin at serial tissue

-Hepcidin
major negative regulator of iron uptake
produced in liver in response to iron overload & inflammation
Down regulates ferroportin)

Question 9

explain iron absorption in the duodenum?

Answer 9

DMT-1
transports iron into the duodenal enterocyte

Ferroportin
facilitates iron export from the enterocyte
then passed on to transferrin

Hepcidin
Down regulates ferroportin so iron stored in enterocytes

Question 10

Name the 3 categories of iron metabolism disorders?

Answer 10

iron deficiency
Iron malutilisation
Iron overload

Question 11

Give the consequences of a negative iron balance:

• to erythrocytes?
• causes what kind of anaemia?
• epithelial changes? (3)

Answer 11

• iron def erythrocytes and falling red cell MCV
• microcytic anaemia

-Epithelial changes
skin, koilonychia, angular stomatitis

Question 12

give causes of hypochromic, microcytic anaemias? (2-2,1)

Answer 12

Haem deficiency
Lack of Iron (iron def, anaemia of chronic disease)
Congenital sideroblastic anaemia

Globin def
e.g. thalassaemias

Question 13

Causes of iron deficiency? (3)

INVESTIGATE THE CAUSE

Answer 13

insufficient dietary intake to meet physiological requirements

Loss of iron though bleeding
(Menorrhagia, GI, tumours, ulcers, NSAIDs, parasitic infection)
Haematuria

malabsorption

Question 14

Iron malutilisation

• occurs in what?
• briefly describe the pathophysiology (3)

Answer 14

-anaemia of chronic disease

-increased transcription of ferritin RNA stimulated by inflammatory cytokines, ferritin synthesis increases
Increased plasma Hepcidin blocks ferroportin-mediated release of iron
results in impaired iron supply to marrow erythroblasts and eventually hypo chromic red cells

Question 15

Primary iron overload

-describe the mechanism by who this occurs?

Answer 15

Long term excess iron absorption with parenchymal rather than ,macrophage iron loading
= eventual organ damage

Question 16

Hereditary Haemochromatosis

• what is it?
• clinical features? (7)
• investigation for diagnosis? -what gene is involved- name the mutation? inheritance? effect on body? penetrance?
• treatment?
• patients at greater risk from that conditions?
• screening?

Answer 16

-herediatary disease characterised by excessive intestinal absorption of iron

-weakness/fatigue
joint pains
impotence
Arthritis
Cirrhosis
Diabetes
Cardiomyopathy

-Transferrin saturation, will be >50%
liver biopsy if unsure

-mutation of the HFE gene 
C282Y or H63D mutations 
Recessive so need to be homozygous for one or heterozygous for both 
Reduced hepcidin synthesis 
Incomplete penetrance 

-weekly phlebotomy 450-500ml
initial aim to exhaust iron stores then keep ferritin below 50ug/l

-DM, infections, Cardiac failure, hepatic bleeding/varices
hepatoma

-of first degree relatives

Question 17

Secondary iron overload

• causes? (6)
• course of disease?
• treatment?

Answer 17

-repeated RBC transfusion 
excessive iron absorption relating to over-active erythropoiesis
(+thalassaemia syndromes
Sideroblastic anaemias
Red cell aplasia
Myelodysplasia)

-occurs a lot more quickly than haemochromatosis, in thalassaemia can get transfusions every 2 wks

-venesection not an option
iron chelating agents:
Desferrioxamine
Deferiprone
Deferasirox