6. Erythropoiesis

Question 1

What are the different sites of erythropoiesis prior to birth?

Answer 1

3rd week of development - yolk sac and mesothelial layers of the placenta

6th week - liver and spleen - this is where they are being

3rd month onwards - bone marrow now becomes the principle source of erythrocytes

Question 2

What are the different sites of erythropoiesis after birth?

Answer 2

Up to 5 years old - bone marrow in all bones

5-25 years - bone marrow of long bones

Over 25 years - Produced in the bone marrow of membranous bones i.e. vertebrae, sternum, ribs, cranial bones, ilium

Question 3

Briefly describe red and yellow bone marrow and what is meant by ‘myeloid tissue’

Answer 3

Red bone marrow is the site of erythropoiesis

Yellow bone marrow contains large amounts of fat droplets and cells

Myeloid tissue is another term for bone marrow

Question 4

Give the stages of erythropoiesis

Answer 4

Haemocytoplast (haematopoietic stem cell) in the bone marrow

This differentiates into a common myeloid progenitor cell (proerythroblast) and is committed at this stage

Many transformations then occur to become an erythroblast with a condensed nucleus

The cytoplasm then becomes filled with Hb. and a reticulocyte is formed (immature erythrocyte) once the nucleus is expelled and released into the blood

Question 5

What is a normoblast?

Answer 5

This is a late late erythroblast?

SO haemocytoplast to proerythroblast to normoblast to reticulocyte to erythrocyte

Question 6

How does a proerythroblast appear histologically?

Answer 6

Large, round cell

Large staining nucleus

Bright blue rim of cytoplasm surrounds the large staining nucleus

IMAGE ON THE MILLAR PP

Question 7

How does a normoblast appear histologically?

Answer 7

From the image of the proerythroblast:

The nucleus becomes very condensed (is then finally ejected and the cell becomes a reticulocyte)

Question 8

How can you differentiate reticuloytes from erythrocytes histologically?

Answer 8

There are obvious dark markings visible in reticulocytes

These are ribosomes/ribosomal RNA

Question 9

“Diapedesis”

Answer 9

The passing of erythrocytes through the pores in the capillary membranes into the blood capillaries from the bone marrow

Question 10

What is the RBC in a healthy adult?

Answer 10

Men - 5.2 million per microlitre
Women - 4.7 million per microlitre

Just need to remember that it is around 5 million per microlitre

Question 11

What is the lifespan of an erythrocyte and why?

Answer 11

120+/-30 days - this remains remarkably constant in healthy adults

These wear out quickly due to a developed reduced oxygen carrying capacity - they become rigid and cannot pass through capillaries

Question 12

What is the MCV in normal RBCs and in macro and microcytic anaemia?

Answer 12

Normal RBC - 90 fl

Microcytic anaemia - <80 fl

Macrocytic - >100 fl

Question 13

Describe how the process of erythropoeisis is controlled

Answer 13

Controlled via EPO - erythroprotien

EPO is produced in the kidney via fibroblasts in the proximal tubule of the cortex of the kidney

EPO has an effect once the cell has committed i.e. on myeloid progenitor cells/proerythroblasts - it acts to speed up the maturation of the erythroblasts and increases their release into the circulation

Question 14

Why is erythropoiesis be controlled by EPO?

Answer 14

Because oxygen levels around the proximal tubule of the cortex of the kidney are constant and changes due to e.g. exercise do not have an impact

The EPO releasing cells themselves are sensitive to hypoxia - these can then cause an increased/decreased release of EPO

Question 15

What is the link between kidney damage and anaemia?

Answer 15

Kidney damage can lead to microcytic anaemia

This is because kidney damage will result in reduced EPO production

Question 16

How do erythrocytes produce ATP and why do they require ATP?

Answer 16

Erythrocytes do not have mitochondria so cannot use oxidative metabolism to make ATP

SO produce it via anaerobic glycolysis and also use the pentose phosphate pathway for NADPH

Require ATP for sodium pumps in the membrane and also for GLUT1 transporters which take up glucose

Question 17

What else can a common myeloid progenitor cell differentiate into?

Answer 17

Can differentiate into any of the myeloid red cell family

Megakaryotes
Erythrocytes
Mast cells
Myeloblasts

Question 18

Name the different myeloblasts

Answer 18

Basophil
Neutrophil
Eosinophil
Monocyte which can then differentiate into a macrophage

Question 19

What other cell lineage is there other than myeloid?

Answer 19

Lymphoid - haemoblasts can differentiate into lymphocytes

Question 20

State the different lymphoid cells

Answer 20

Common lymphoid progenitor cell can differentiate into a natural killer cell or a small lymphocyte

A small lymphocyte can then differentiate into T lymphocyte or B lymphocyte

B lymphocyte can then differentiate into a plasma cell

Question 21

How are erythrocytes removed from the body?

Answer 21

Erythrocytes are disposed of as they pass through the spleen

Believed that antigens of old erythrocytes differ to the antigens of young erythrocytes and hence allows their detection by splenic macrophages

OR may be due to increased levels of methaemoglobin in the cell

OR detected by their increased rigidity - become trapped in the splenic capillaries - when trapped, can be engulfed by splenic macrophages

Question 22

Describe the mechanism of action of splenic macrophages

Answer 22

Haem and globin are separated
Globin is broken down into amino acids
Haem prosthetic groups are broken open by haemoxygenase enzyme
The iron atom is removed for reuse
Biliverdin is left as a result - this is green in colour

Question 23

How is biliverdin converted to bilirubin?

Answer 23

Via biliverdin reductase

This process occurs in the macrophage

Question 24

What happens to the bilirubin formed from the biliverdin?

Answer 24

Binds to albubin in splenic macrophages and is released in the blood - is unconjugated

Then reaches the liver and is attached to glucaronic acid which is more soluble
The bilirubin is now conjugated

The conjugated bilirubin passes to the small intestine in bile and is converted to urobilinogen via bacteria

Most urobilinogen passes out of the body in the faeces and about 10% is passed back in the portal vein to the spleen and is passed to the to the kidney and excreted in the urine (provides yellow colour)

Question 25

What is the ESR?

Answer 25

Erythrocyte sedimentation rate

Question 26

What is the charge on an erythrocyte and what does this mean?

Answer 26

Negative surface charge - means that they normally repel one another

Question 27

What alters the ESR?

Answer 27

Inflammation - causes the negative charge to be reduced - erythrocytes can clump together - the ESR is increased

Question 28

What is a raised ESR indicative of?

Answer 28

Raised ESR is a specific marker for infection/inflammation in the blood

Question 29

What is a rouleux?

Answer 29

This is a clump of erythrocytes due to a loss of negative charge - occurs during inflammation