Extra Haem

Question 1

Where abouts is iron absorbed in the small intestine?

Answer 1

Duodenum.

Question 2

What’s the difference between haem iron and non haem iron?

Answer 2

Haem iron is from animal products and is in ferrous form, Fe2+, and is much better absorbed.

Non haem iron is mainly in Ferric form, Fe3+, and requires the action of reducing substances such as ascorbic acid, vitamin C, for absorption and is much less efficiently absorbed.

Question 3

What does non haem iron often contain which reduces absorption?

Answer 3

Non haem iron sources such as soy beans often contain phytates which reduce absorption.

Question 4

What is the name of the physiological mechanism for the removal of iron?

Answer 4

Trick question! There is no physiological mechanism for the excretion of iron. Iron is also potentially toxic to organs such as the heart and liver, so iron absorption is tightly controlled.

Question 5

How much iron is absorbed from the diet each day?

Answer 5

1-2mg per day

Question 6

What is erythropoietin and what does it do?

Answer 6

It is a glycoprotein synthesised in the kidney in response to hypoxia. It stimulates the bone marrow to produce more red blood cells.

Question 7

What does hepcidin do and how does it work?

Answer 7

Blocks the absorption and release of storage iron be degrading ferroportin, causing iron absorbed to bind to ferritin in the enterocytes which is lost to the body when the enterocyte dies and is shed into the lumen.

Question 8

How is hepcidin synthesis related to erythropoietic activity and what does this allow?

Answer 8

Hepcidin synthesis is suppressed by erythropoietic synthesis, ensuring iron supply (for the production of haem) by increasing the amount of ferroportin available in the duodenum enterocyte, increasing iron absorption.

Question 9

Hepcidin production can be increased in inflammatory states. How can this cause anaemia and what is the resultant anaemia called?

Answer 9

Reduction in iron absorption causes anaemia, this is known as anaemia of chronic disease.

Question 10

How do pro-inflammatory cytokines cause anaemia?

Answer 10

Interferon causes a reduction of erythropoiesis.

Interleukin and tumour necrosis factor increase levels of hepcidin and reduce the production of erythropoiesis.

Question 11

Vitamin B12 and folate deficiency affect what cells in particular?

Answer 11

All rapidly dividing cells.
Bone marrow cells can grow but are unable to divide normally, known as megoloplastic erythropoiesis.
Epithelial cells such as those lining the mouth and gut
Gonads.

Question 12

Name some sources of vitamin B12.

Answer 12

(All animal derived products except fortified cereals)
Meat
Liver & kidney
Fish
Oysters and clams
Eggs
Milk and cheese
Fortified cereals

Question 13

Name some sources of folate/folic acid.

Answer 13

Green leafy vegetables
Cauliflower
Brussel sprouts
Liver and kidney
Whole grain cereals
Yeast
Fruit

Question 14

What may vitamin B12 deficiency result from (4)?

Answer 14

Inadequate intake e.g. vegan IM’s
Lack of stomach acid - achlorhydria - can occur when part of the stomach is removed.
Inadequate secretion of IF - pernicious anaemia
Malabsorption e.g. coeliac disease.

Question 15

Why may a lack of stomach acid reduce Vitamin B12 absorption?

Answer 15

Vitamin B12 requires both the intrinsic factor to bind to but also hydrochloride acid to cleave it from the proteins.

Question 16

Each erythrocytes contains around how much haemoglobin?

Answer 16

300 million molecules.

Question 17

What is haemoglobin A in adults made of?

Answer 17

It is a tetramer; it’s made of 4 subunits, each composed of a globin chain (2 alpha, 2 beta) bound to a haem group.

Question 18

What does a haem group consist of and how much does oxygen does the iron ion bind to?

Answer 18

Each haem group consists of a ferrous iron ion (Fe2+) held in a ring known as porphyrin.
Each Fe2+ can bind to 1 oxygen molecule.

Question 19

How does haemoglobin differ at birth?

Answer 19

Fetal haemoglobin (haemoglobin F) has 2 beta and 2 GAMMA globin chains.

Question 20

What 4 factors contribute to the easy oxygen delivery/oxygen having less affinity for haemoglobin.

Answer 20

Lower pH
Higher CO2 levels
Higher 2,3 DPG levels
Higher temperature

Question 21

What causes haemoglobin to have a higher affinity for oxygen/give up oxygen less readily?

Answer 21

Higher levels of Fetal Haemoglobin

Higher levels of CO

Question 22

What type of effector is 2,3-DPG and what does it do?

Answer 22

Allosteric effector and it modulates haemoglobin affinity.

Question 23

How does 2,3-DPG work?

Answer 23

Binds to beta globin chain in the central cavity of haemoglobin molecule.

Question 24

What does 2,3-DPG help respond to?

Answer 24

It plays a role in the adaptive response to anaemia, hypoxia and high altitude.

Question 25

What is G6PD and what metabolism is it tightly coupled with?

Answer 25

G6PD is an important enzyme in the hexose monophosphate (HMP) shunt.

The HMP shunt is tightly coupled with the metabolism of Glutathione, which protects red cells from oxidant damage.

Question 26

What does a deficiency in G6PD cause?

Answer 26

Causes red cells to be more vulnerable to oxidative damage.

Causes severe, intravascular haemolysis as a result of infection or exposure to an exogenous oxidant.

Question 27

GP6D is the most prevalent enzyme disorder affecting about 400 million people worldwide. How has this gene managed to survive through natural selection?

Answer 27

The deficiency also confers a selective advantage to falciparum malaria.

Question 28

What are episodes of intravascular haemolysis usually associated with and why (in terms of cell shape)? (What happens to the cell membrane and haemoglobin)

Answer 28

The appearance of considerable numbers of irregularly contracted cells. These cells are irregular in outline, are smaller than normal cells and have lost their central pallor. They usually result from oxidant damage to the cell membrane and haemoglobin. Haemoglobin is denatured and forms round inclusions called Heinz bodies, which can be detected by a specific test.

Question 29

What are reticulocytes?

Answer 29

Young red blood cells

Question 30

How can we detect reticulocytes?

Answer 30

Staining with new methylene blue which stains for their higher RNA content.

Question 31

What is reticulocytosis and why may it occur?

Answer 31

Reticulocytosis is the presence of increased number of reticulocytes.

It may occur as a response to bleeding or haemolysis (red cell destruction).

Question 32

What is the difference between anisocytosis and poikilocytosis?

Answer 32

Anisocytosis - red cells show more variation in SIZE than usual.
Poikilocytosis - red cells show more variation in SHAPE than usual.

Question 33

What are target cells and what are they the result of?

Answer 33

Target cells are red cells with an accumulation of haemoglobin in the centre of the area of central pallor.

It is the result of many different conditions including:
Obstructive jaundice 
Liver disease
Haemoglobinopathies
Hyposplenism

Question 34

What are sickle cells the result of?

Answer 34

Polymerisation of haemoglobin S, which when deoxygenated is much less soluble than haemoglobin A.

Question 35

Why does Haemoglobin S occur?

Answer 35

When someone has one or two copies of an abnormal beta globin gene (beta^S).

Question 36

What are schistocytes and what are they the result of?

Answer 36

They are fragments of red blood cells, often the result of a shearing process caused but the platelet rich blood clots in the small blood vessels e.g disseminated intravascular coagulation.