Iron Metabolism and Microcytic Anaemias

Question 1

What are microcytic anaemias

Answer 1

Anaemias whereby erythrocytes are smaller than normal and often paler (hypochromic)

Question 2

Causes of microcytic anaemias

Answer 2

T halassaemias (globin chains affected)
A naemia of chronic disease
I ron deficiency
L ead poisoning 
S ideroblastic anaemia

Question 3

What are the two main oxidation states of iron?

Answer 3

Ferrous (reduced) = Fe 2+

Ferric (oxidised) = Fe 3+ (can’t be absorbed)

Question 4

What are the two dietary iron groups referred as and what are good sources?

Answer 4

1) Haem (only Fe 2+) = chicken, duck, salmon, beef steak, beef burger
2) Non-haem (mix of Fe 2+ and Fe 3+) = rice, fortified cereals, oats, potatoes

Question 5

Describe the absorption of iron

Answer 5

• in duodenum and upper jejunum
  1) Fe 3+ in chyme reduced to Fe 2+ by REDUCTASE (vitamin C cofactor)
  2) Fe 2+ enter Enterocytes via DMT1 while haem can just diffuse in
  3) hame degraded by haem oxygenase
  4) Fe 2+ can be converted to Fe 3+ to be stored (FERRITIN = protein storage)
  5) Fe 2+ leaves by FERROPORTIN to enter blood
  6) Fe 2+ oxidised by HEPHAESTIN so it can bind to TRANSFERIN to travel the body

Question 6

What are positive factors affecting absorption of non-haem?

Answer 6

Vitamin C and citrate -prevent formation of insoluble iron compound

Question 7

Negative factors affecting absorption of non-haem

Answer 7

• Tannins (in tea)
• Phytates (e.g. chapattis)
• Fibre
• Antacids

They bind to non-haem iron to intestine to reduce absorption

Question 8

Describe the cellular uptake of iron

Answer 8

1) Fe 3+ transferrin enter via receptor mediated endocytosis
2) Fe 3+ within endosmose released from transferrin by acidic condition and reduced to Fe 2+
3) Fe 2+ transported to cytoplasm by DMT1
4) Fe 2+ can be storred in ferritin/exported by ferroportin/taken up by mt for cytochrome enzymes

Question 9

How is iron recycled in the body?

Answer 9

Old RBCs phagocytosis by macrophages (splenic and kupffer in liver) which catabolises haem
Iron is then exported to blood (transferrin) or storred in macrophage (ferritin)

Question 10

List the control mechanisms for regulation of iron absorption

Answer 10

• regulation of transporters i.e ferroportin
• regulation of receptors e.g. transferrin
• hepcidin and cytokines
• cross talk between epithelial cells and other cells like macrophages

Question 11

What does Hepcidin do?

Answer 11

Induces internalisation and degradation of ferroportin = decrease iron overload in the blood

Question 12

How does anaemia of chronic disease arise?

Answer 12

1) Inflammatory condition
2) Cytokines production from immune cells (IL6)
3) Increased production of hepcidin (as well as inhibition of erythropoietin production)
4) Inhibition of ferroportin (decreased iron release)
5) Plasma iron reduction leads to inhibition erythropoiesis

Question 13

How can small doses (~1-2mg) of iron lost from the body?

Answer 13

• desquamation of epithelial
• menstrual bleeding
• sweat
• pregnancy

NO MECHANISMS TO REGULATE EXCRETION OF IRON

Question 14

Causes of iron deficiency

Answer 14

• insufficiency in diet e.g. vegans
• malabsorption
• bleeding e.g. menstruation
• increased requirement e.g. pregnancy
• anaemia of chronic disease

Question 15

Signs and symptoms of iron deficiency

Answer 15

• physiological effects of anaemia e.g. tiredness, pallor
• pica (unusual craving for non-nutrive substances e.g. dirt)
• cold hands + feet
• epithelial changes (angular cheilitis, koilonychia, glossitis)

Question 16

How if iron deficiency tested?

Answer 16

Reduced plasma ferritin indicates iron deficiency
-normal or increased DOESNT exclude iron deficiency as it can increase because of cancer, infection alcoholism etc.

CHr (reticulocyte haemoglobin content) remains low even in infection

Question 17

Treatment of iron deficiency

Answer 17

• dietary advice
• oral iron supplements
• intramuscular iron injections
• intravenous iron
• blood transfusion

Question 18

How is iron excess dangerous?

Answer 18

Excess iron deposited in organs as haemosiderin (insoluble) which promotes free radical formation

Question 19

What is transfusion associated haemosiderosis?

Answer 19

• gradual accumulation of iron from repeated blood transfusions
• big problem for transfusion dependent anaemia e.g. sickle cell, thalassaemia

-iron chelating agents (desferioxamine) delays but can’t stop it

Question 20

What is hereditary haemochromatosis

Answer 20

Autosomal recessive disorder of HFE gene

• no HFE protein that can reduce affinity of transferrin receptor and it has a negative effect on hepcidin production
• too much iron enters cell
• treated with venesection