Session 5-Haemopoiesis, Erythropoiesis And Iron

Question 1

Where are RBCs, platelets and most WBCs produced?

Answer 1

Bone marrow

Question 2

What is bone marrow aspirate?

Answer 2

Liquid marrow with some solid particles

Question 3

What is haematopoiesis controlled by?

Answer 3

Hormones

Question 4

Which system is responsible for the control and removal of blood cells?

Answer 4

Reticuloendothelial system (RES)

Question 5

Which cells are part of the reticuloendothelial system?

Answer 5

Monocytes
Macrophages 
Kupffer cells
Tissue histiocytes 
Microglial cells in CNS

Question 6

What are the main organs of the reticuloendothelial system?

Answer 6

Spleen

Liver

Question 7

What do reticuloendothelial cells in the spleen do?

Answer 7

Dispose of blood cells

Question 8

In a full blood count, what information do the following give about blood cells:

1) haemoglobin
2) red blood count
3) mean cell volume

Answer 8

1) how effective they are
2) how many there are
3) how large they are

Question 9

What are the functions of RBCs?

Answer 9

1) carry Hb
2) maintain Hb in its reduced (ferrous) state
3) generate energy
4) maintain osmotic equilibrium
5) deliver oxygen to tissues

Question 10

Why do RBCs have a high SA:volume ratio?

Answer 10

More efficient gas exchange and increases flexibility as it moves through capillaries

Question 11

What can a change in the shape of a RBC result in?

Answer 11

Cells can become more fragile and can burst and not be functional -> anaemia

Question 12

Describe the structure of haemoglobin

Answer 12

Tetramer of 2 pairs of globin chains each with own haem group

Question 13

What are the two configurations that haemoglobin can exist as?

Answer 13

Oxyhaemoglobin

Deoxyhaemoglobin

Question 14

Which chromosomes are the globin gene clustered on?

Answer 14

11 and 16

Question 15

When does foetal Hb switch to adult Hb?

Answer 15

3-6 months of age

Question 16

What is the function of Hb?

Answer 16

Carriage of O2 from lungs to tissues and CO2 between tissues and lungs

Question 17

True or false: haem molecule combines reversibly with O2 and CO2

Answer 17

TRUE

Question 18

What do globin chains allow?

Answer 18

1) protect haem molecule from oxidation
2) confer solubility
3) permits variation in oxygen affinity

Question 19

What shape is an oxygen dissociation curve?

Answer 19

Sigmoid

Question 20

Complete the sentences:

Reduced pO2 is detected in interstitial ____________ cells in kidney. This leads to increased production of ________________ hormone. This hormone stimulates maturation and release of ____ cells from marrow. Hb then rises, pO2 rises and _________________ production falls.

Answer 20

Peritubular
Erythropoietin
Red
Erythropoietin

Question 21

What are the two main metabolic pathways in red cells?

Answer 21

1) glycolysis

2) pentose phosphate pathway

Question 22

What are the two forms of iron?

Answer 22

Available (functional)

Stored

Question 23

What are the functional forms of iron?

Answer 23

Haemoglobin
Myoglobin
Tissue iron
Transported iron

Question 24

What are the types of stored iron?

Answer 24

Ferritin

Haemosiderin

Question 25

True or false: iron requirement increases with age

Answer 25

FALSE - decreases with age

Question 26

Which cells 'eat' old senescent RBCs?

Answer 26

Macrophages

Question 27

Where is 95% of stored iron found?

Answer 27

Liver tissue-hepatocytes as ferritin

Question 28

Where is haemosiderin found?

Answer 28

In Kupffer cells

Question 29

True or false: humans don't have a developed pathway for excretion of iron

Answer 29

TRUE

Question 30

Where can haem iron be obtained from?

Answer 30

Meat

Question 31

Where can non-haem iron be obtained from?

Answer 31

Pulses, nuts, grains etc

Question 32

Why is haem iron a better source of iron than non-haem iron?

Answer 32

Iron in haem iron is present in ferrous form, which is used by us. Non-haem iron is ferric form and this needs to be converted to ferrous form

Question 33

How does non-haem iron exist?

Answer 33

Fe3+ (ferric)

Question 34

On which surface does Fe2+ bind transferrin?

Answer 34

Apical surface of duodenum and upper jejunum

Question 35

How is iron exported out of an enterocyte?

Answer 35

Ferroportin

Question 36

What do foetal enterocytes have receptors for?

Answer 36

Lactoferrin

Question 37

Iron is taken into cells by the binding of iron-transferrin complex to what?

Answer 37

Transferrin receptor (TfR)

Question 38

Which cells contain the highest number of transferrin receptors?

Answer 38

Erythroid cells

Question 39

Which vitamin enhances iron absorption?

Answer 39

Vitamin C (ascorbic acid)

Question 40

What inhibits iron absorption?

Answer 40

Precipitation/chelation of iron eg tea, chapatis, antacids

Question 41

What are the control mechanisms of iron absorption? (4)

Answer 41

1) regulation of transporters 2) expression of receptors 3) hepcidin and cytokines 4) crosstalk between epithelial cells and other cells like macrophages

Question 42

What is hepcidin?

Answer 42

Negative regulator of iron absorption

Question 43

Where is hepcidin: 1) secreted? 2) excreted?

Answer 43

1) liver | 2) kidneys

Question 44

When is hepcidin synthesis increased?

Answer 44

Iron overload

Question 45

When is hepcidin production decreased?

Answer 45

High erythropoietic activity

Question 46

What is hepcidin production regulated by? (3)

Answer 46

1) HFE 2) transferrin receptor 3) inflammatory cytokines

Question 47

How does hepcidin inhibit iron?

Answer 47

Degrades ferroportin (protein involved in moving iron out of cells) and this prevents: 1) iron absorption from gut 2) iron release from macrophages

Question 48

What are the reasons for iron deficiency? (2)

Answer 48

1) insufficient intake/poor absorption | 2) increased use (pregnancy, bleeding)

Question 49

What are the symptoms of anaemia?

Answer 49

1) tiredness 2) reduced oxygen carrying capacity (pallor, reduced exercise tolerance) 3) cardiac symptoms-angina, palpitations, development of heart failure

Question 50

What are the signs of anaemia? (4)

Answer 50

1) pallor 2) tachycardia 3) increased respiratory rate 4) epithelial changes

Question 51

True or false: iron deficiency leads to hypochromic and microcytic cells

Answer 51

TRUE

Question 52

What is the most commonly used measure of iron status?

Answer 52

Ferritin (acute phase protein)

Question 53

When is CHR used to test for iron deficiency?

Answer 53

If a patient has an infection

Question 54

What are the possible treatments of iron deficiency? (5)

Answer 54

1) dietary advice 2) oral iron supplements (with orange juice) 3) intramuscular iron injections 4) intravenous iron 5) transfusion (not unless there is severe anaemia)

Question 55

What can reduced iron produce?

Answer 55

Highly reactive hydroxyl and lipid radicals

Question 56

What is excess iron deposited as in tissues?

Answer 56

Haemosiderin

Question 57

What is haemochromatosis?

Answer 57

Disorder of iron excess resulting in end organ damage due to iron deposition

Question 58

What does haemochromatosis cause?

Answer 58

``` Liver cirrhosis Diabetes mellitus Hypogonadism Cardiomyopathy Arthropathy Skin pigmentation ```

Question 59

True or false: hereditary haemochromatosis is autosomal dominant

Answer 59

FALSE - recessive

Question 60

What is hereditary haemochromatosis a mutation in?

Answer 60

HFE gene

Question 61

What does HFE protein usually do?

Answer 61

Competes with transferrin for binding to transferrin receptor

Question 62

What happens to HFE in hereditary haemochromatosis?

Answer 62

Mutated HFE cannot bind so transferrin has no competition, too much iron enters cells

Question 63

How is hereditary haemochromatosis treated?

Answer 63

With venesection

Question 64

What is used to treat transfusion associated haemosiderosis?

Answer 64

Iron chelating agents